Preventie van postoperatieve wondinfecties

Initiatief: NVVH / SRI Aantal modules: 26

Prolongatie van antimicrobiële profylaxe

Uitgangsvraag

Wat is het effect van postoperatieve profylactische toediening van antibiotica bij patiënten die een operatie ondergaan op de preventie van postoperatieve wondinfecties?

Aanbeveling

Ter preventie van postoperatieve wondinfecties is het niet noodzakelijk of wenselijk de perioperatieve intraveneuze antibiotische profylaxe te continueren na de operatie.

 

De toediening van perioperatieve intraveneuze antibiotische profylaxe (ter voorkoming van postoperatieve wondinfecties) dient te voldoen aan de volgende voorwaarden:

  • Eerste dosering <60 min voor incisie of aanleggen bloedleegte gegeven
  • Direct postoperatief staken

Voor herdosering verwijst de werkgroep naar de SWAB-richtlijn Peri-operatieve profylaxe (2019). (paragraaf Organisatie, timing en duur van de profylaxe)

Overwegingen

Voor- en nadelen van de interventie en de kwaliteit van het bewijs

Als matig beoordeeld bewijs uit een meta-analyse van 58 gerandomiseerde gecontroleerde onderzoeken (RCT's) met 20.918 deelnemers toonde geen doorslaggevend bewijs voor het voordeel van het voortzetten van antibiotische profylaxe na de operatie voor het verminderen van de incidentie van postoperatieve wondinfecties (POWI’s) in vergelijking met onmiddellijke stopzetting. Vergelijkingen van postoperatieve regimes van verschillende duur toonde eveneens geen doorslaggevend bewijs in het voordeel van langdurige regimes.

 

Subgroep analyse toonde aan dat de effectiviteit van het stopzetten van antibiotische profylaxe na de operatie afhankelijk is of de chirurgische antibiotische profylaxe in de praktijk juist is toegepast. Wanneer de profylaxe juist is toegepast (d.w.z. tijdige toediening van de eerste dosis en herhaalde toediening indien aangewezen volgens de duur van de ingreep), toonde de studies met matige bewijskracht aan dat er geen voordeel is in het voortzetten van antibiotische profylaxe na de operatie voor het verminderen van POWI in vergelijking met het stopzetten ervan. Studies met matige bewijskracht toonden aan dat het voortzetten van antibiotische profylaxe na de operatie alleen effectief was wanneer de chirurgische antibiotische profylaxe niet juist was toegepast.  

 

Enig bewijs uit verkennende analyse geeft aan dat het voortzetten van antibiotische profylaxe na de operatie het risico op POWI geassocieerd met maxillofaciale en cardiale chirurgie zou kunnen verminderen; echter, er waren heel weinig studies beschikbaar voor de subgroep maxillofaciale chirurgie en hartchirurgie.

 

Wanneer kosten en bijwerkingen werden gerapporteerd, leek het voortzetten na de operatie de kosten te verhogen en leidde het tot meer bijwerkingen. Antibioticagebruik is geassocieerd met belangrijke bijwerkingen op een tijdsafhankelijke manier (Branch-Elliman 2019, Hartbarth 2000, Stevens 2011). Op hun beurt zijn deze bijwerkingen geassocieerd met een aanzienlijke economische last die bijdraagt aan aanvullende verwervings- en administratiekosten in verband met het voortzetten van antibiotische profylaxe na de operatie (Cunha 2018, Dubbekerke 2012, OECD 2018).

 

Internationale richtlijnen

Deze bevindingen zijn in lijn met de aanbevelingen van de CDC (Berrios-Torres 2017) en de WHO (WHO 2018) over dit onderwerp. Beide richtlijnen raden niet aan om extra antimicrobiële profylaxe na de operatie toe te dienen ter voorkoming van POWI. De NICE-richtlijn heeft geen aanbeveling gedaan.

 

Waarden en voorkeuren van patiënten (en evt. hun verzorgers)

Voor de individuele patiënt kan een kortere duur van antibiotica leiden tot een korter ziekenhuisverblijf en minder gebruik van antibiotica, met de bijbehorende bijwerkingen. Bijwerkingen van de gebruikte antibiotica zijn vaak gastro-intestinale klachten zoals misselijkheid, braken, diarree en buikpijn. Minder antibiotica zullen waarschijnlijk leiden tot minder bijwerkingen. Bovendien is er meer onderzoek gedaan naar de negatieve impact van antibiotica op de darmmicrobiota met zowel korte- als langetermijngevolgen voor de gezondheid (Patangia, 2022; Ramirez 2020). Bovendien kan minder antibiotica leiden tot minder antimicrobiële resistentie tegen bepaalde antibiotica.

Het is belangrijk om patiënten te informeren over het nut en de noodzaak van de behandeling. Voor de rol van de patiënt bij het herkennen van een infectie verwijst de werkgroep naar de module Patiëntbetrokkenheid van deze richtlijn.

 

Kosten (middelenbeslag)

Kosten werden matig gerapporteerd, zo niet volledig, en er konden geen zinvolle meta-analyses worden uitgevoerd om deze resultaten te beoordelen. Wanneer kosten werden gerapporteerd, leek het voortzetten van profylaxe na de operatie de kosten te verhogen.

 

Aanvaardbaarheid, haalbaarheid en implementatie

Er zijn geen problemen te verwachten met betrekking tot de haalbaarheid van de verlenging van antimicrobiële profylaxe voor implementatie in de klinische praktijk.

 

Rationale van de aanbeveling: weging van argumenten voor en tegen de interventies

We hebben geen bewijs gevonden voor het voordeel van het voortzetten van antibiotische profylaxe na de operatie in vergelijking met het stopzetten op het verminderen van de incidentie van POWI. Opmerkelijk genoeg bood het voortzetten na de operatie geen extra voordeel bij het voorkomen van POWI, vooral wanneer chirurgische antibiotische profylaxe juist werd toegepast. Onze bevindingen ondersteunen de aanbevelingen van de WHO tegen het voortzetten van chirurgische antibiotische profylaxe na de operatie. Gezien de bijbehorende nadelige effecten, met name antimicrobiële resistentie, heeft deze veelvoorkomende toepassing in de praktijk geen basis. Toegenomen bewustzijn en educatie zijn vereist onder zowel zorgprofessionals als patiënten, vooral door inspanningen voor stewardship te prioriteren onder chirurgen en anesthesisten en te blijven aandringen op andere preventiemaatregelen naast chirurgische antibiotische profylaxe. Toekomstig onderzoek om het voordeel van het voortzetten van antibiotische profylaxe na de operatie te verduidelijken, indien aanwezig, zou vooraf de monitoring van bijwerkingen moeten specificeren, gedetailleerde gegevens verstrekken over kosten en het tijdstip van toediening voorafgaand aan de operatie en herhaalde toediening van antibiotica tijdens de operatie moeten standaardiseren.

Onderbouwing

Het gebruik van antibiotica staat momenteel onder toezicht vanwege zorgen over de opkomst van antimicrobiële resistentie en andere schadelijke bijwerkingen. Wereldwijd is ongeveer één op de zes voorschriften voor antibiotica in het ziekenhuis bedoeld voor chirurgische antibiotische profylaxe, die vaak gedurende meerdere dagen na de operatie wordt voortgezet. Hoewel de effectiviteit van een juiste antibiotische profylaxe bij het voorkomen van postoperatieve wondinfecties (POWIs) bij aangewezen procedures algemeen erkend is, suggereren toenemende bewijzen dat een enkele preoperatieve dosis antibiotica, met extra intra-operatieve toediening indien nodig, mogelijk even effectief is als een langdurig postoperatief regime bij verschillende procedures.

Moderate GRADE

 

Postoperative continuation of surgical prophylactic intravenous antibiotics is unlikely to reduce the number of postoperative surgical site infections, if the prophylactic intravenous antibiotics have been correctly administered (first dose less than 60 minutes before incision, perioperative re-dosing four hours after the previous dose and in case of excessive peroperative bleeding).

 

Bronnen: De Jonge + update (Aberg, 1993; Abro, 2014; Abubakar, 2001; Adaji, 2020; Ahmed, 2019; Balbo, 1991; Baquin, 2004; Bates, 1992; Becker, 2008; Becker, 1991; Bentley, 1999; Berry, 2019; Bidkar, 2014; ; Bozorgzadeh, 1999; Buckley, 1990; Campos, 2015; Cartana, 1994; Carroll, 2003; Chang, 2005; Chauhan, 2018; Cioca, 2002; Crist, 2018; Danda, 2010; Davis, 2016; Eshghpour, 2014; Fujita, 2015; Fujita, 2007; Fridrich, 1994; Garcia, 2020; Gargotta, 1991; Gupta, 2010; Haga, 2012; Hall, 1998; Hanif, 2015; Hellbusch, 2008; Hussain, 2012; Imamura, 2012; Irato, 1997; Ishibashi, 2014; Ishibashi, 2009; Jansisyanont, 2008; Jiang, 2004; Kang, 2009; Karren, 1993; Kim, 2017; Kow, 1995; Lau, 1990; Liberman, 1995; Lin, 2011; Lindeboom, 2003; Liu, 2008; Loozen, 2017; Lyimo, 2013; Madadi, 2019; Maier, 1992; Mann, 1990; McArdle, 1995; Meijer, 1993; Mohri, 2007; Mui, 2005; Niederhauser, 1997; Nooyen, 1994; Nusrath, 2020; Olak, 1991; Orjuela, 2020; Orlando, 2015; Otani, 2004; Rajabi, 2012; Rajan, 2005; Regimbeau, 2014; Righi, 1996; Sadraei-Moosavi, 2017; Salih, 2018; Santibañes, 2018; Sawyer, 1990; Scher, 1997; Sgroi, 1990; Shaheen, 2014; Su, 2005; Sugawara, 2016; Suzuki, 2011; Takayama, 2019; Takemoto, 2015; Tamayo, 2008; Tan, 2020; Togo, 2007; Tsang, 1992; Turano, 1992; Unemura, 2000; Urquhart, 2019; Wahab, 2013; Westen, 2015; Yamamoto, 2018; Yang, 2001).

Description of studies

Ninety-eight studies were included in the analysis of the literature, in which 10,227 patients were involved.

 

Fifty-eight RCTs compared postoperative continuation of antibiotic prophylaxis of any duration with direct postoperative discontinuation (Aberg, 1993; Abro, 2014; Balbo, 1991; Bates, 1992; Becker, 2008; Berry, 2019; Buckley, 1990; Campos, 2015; Cartana, 1994; Chauhan, 2018; Cioca, 2002; Crist, 2018; Danda, 2010; Fujita, 2007; Gargotta, 1991; Haga, 2012; Hall, 1998; Hellbusch, 2008; Hussain, 2012; Imamura, 2012; Irato, 1997; Jiang, 2004; Kang, 2009; Kim, 2017; Kow, 1995; Liberman, 1995; Lindeboom, 2003; Loozen, 2017; Lyimo, 2013; Madadi, 2019; Maier, 1992; Mann, 1990; Meijer, 1993; Mohri, 2007; Mui, 2005; Nooyen, 1994; Nusrath, 2020; Olak, 1991; Orjuela, 2020; Orlando, 2015; Rajabi, 2012; Rajan, 2005; Regimbeau, 2014; Sadraei-Moosavi, 2017; Salih, 2018; Santibañes, 2018; Scher, 1997; Sgroi, 1990; Shaheen, 2014; Su, 2005; Suzuki, 2011; Tamayo, 2008; Tan, 2020; Tsang, 1992; Turano, 1992; Unemura, 2000; Wahab, 2013; Westen, 2015).

 

One RCT compared postoperative continuation of antibiotic prophylaxis (multiple doses) for less than 24 hours with a single postoperative dose (Karren, 1993).

 

Thirty-one RCTs compared postoperative continuation of antibiotic prophylaxis for more than 24 hours with postoperative continuation equal or less than 24 hours (Abubakar, 2001; Ahmed, 2019; Baquin, 2004; Becker, 1991; Bentley, 1999; Bidkar, 2014; Bozorgzadeh, 1999; Carroll, 2003; Chang, 2005; Eshghpour, 2014; Fujita, 2015; Fridrich, 1994; Garcia, 2020; Hanif, 2015; Ishibashi, 2014; Ishibashi, 2009; Jansisyanont, 2008; Lau, 1990; Lin, 2011; Liu, 2008; Madadi, 2019; McArdle, 1995; Mui, 2005; Niederhauser, 1997; Rajabi, 2012; Righi, 1996; Takayama, 2019; Takemoto, 2015; Urquhart, 2019; Yamamoto, 2018; Yang, 2001).

 

Seven RCTs compared postoperative continuation of antibiotic prophylaxis for more than 48 hours with postoperative continuation equal or less than 48 hours (Adaji, 2020; Davis, 2016; Gupta, 2010; Otani, 2004; Sawyer, 1990; Sugawara, 2016; Togo, 2007).

 

One RCT compared postoperative continuation of antibiotic prophylaxis for more than 72 hours with postoperative continuation equal or less than 72 hours (Park, 2010).

 

Results

 

1. Surgical site infections

 

A. Postoperative continuation versus immediate discontinuation

SSI for postoperative continuation versus immediate discontinuation were reported in 58 studies (Aberg, 1993; Abro, 2014; Balbo, 1991; Bates, 1992; Becker, 2008; Berry, 2019; Buckley, 1990; Campos, 2015; Cartana, 1994; Chauhan, 2018; Cioca, 2002; Crist, 2018; Danda, 2010; Fujita, 2007; Gargotta, 1991; Haga, 2012; Hall, 1998; Hellbusch, 2008; Hussain, 2012; Imamura, 2012; Irato, 1997; Jiang, 2004; Kang, 2009; Kim, 2017; Kow, 1995; Liberman, 1995; Lindeboom, 2003; Loozen, 2017; Lyimo, 2013; Madadi, 2019; Maier, 1992; Mann, 1990; Meijer, 1993; Mohri, 2007; Mui, 2005; Nooyen, 1994; Nusrath, 2020; Olak, 1991; Orjuela, 2020; Orlando, 2015; Rajabi, 2012; Rajan, 2005; Regimbeau, 2014; Sadraei-Moosavi, 2017; Salih, 2018; Santibañes, 2018; Scher, 1997; Sgroi, 1990; Shaheen, 2014; Su, 2005; Suzuki, 2011; Tamayo, 2008; Tan, 2020; Tsang, 1992; Turano, 1992; Unemura, 2000; Wahab, 2013; Westen, 2015).

 

The results were pooled in a meta-analysis. The pooled number of SSI in the postoperative continuation group was 543/10691 (5.1%), compared to 588/10227 (5.7%) in the immediate discontinuation group. This resulted in a pooled relative risk ratio (RR) of 0.91 (95% CI 0.81 to 1.02), in favour of the postoperative continuation group (figure 1). This was not considered as a clinically relevant difference.

 

The studies were divided in three different categories:

(I) studies that adhered to the best standard of practice versus studies that did not adhere to the best standard of practice;

(II) studies that timed the first dose within 60 minutes before surgery versus studies that did not time the first dose within 60 minutes before surgery; and

(III) studies that specified intraoperative repeated administration when indicated versus studies that did not specify intraoperative repeated administration when indicated.

 

Analysis

N

SSI in longer regimen

SSI shorter regimen

Relative risk (95%CI)

Overall analysis

58

543 of 10.691

588 of 10.227

0.91 (0.81 - 1.02)

 

Adherence to current best practice standards of SAP (repeat dose + timing correct)

Yes

29

234 of 5.564

215 of 5.184

1.06 (0.88 - 1.28)

No

29

543 of 10.691

588 of 10.227

0.81 (0.68 - 0.96)

 

Timing of first dose specified and within 60 min before surgery

Yes

39

354 of 7.214

352 of 6.831

0.99 (0.86 - 1.15)

No

19

189 of 3.477

236 of 3.396

0.77 (0.61 - 0.96)

 

Intraoperative repeat administration specified when indicated

Yes

39

303 of 7.042

317 of 6.576

0.92 (0.79 - 1.08)

No

19

240 of 3.649

271 of 3.651

0.88 (0.72 - 1.08)

 

Table 1. Meta-analysis and subgroup analyses of incidence of SSI associated with postoperative continuation versus postoperative discontinuation of antibiotic prophylaxis.

 

I. Adherent to best standards of practice versus not adherent to best standards of practice

Current best practice standards for surgical antibiotic prophylaxis are described in the American Society of Health-System Pharmacists clinical practice guidelines on antimicrobial prophylaxis in surgery (Bratzler 2013): 

 

1) timing of the first preoperative dose within 60 min before incision;

2) repeat administration when the procedure duration exceeded two times the half-life of the antibiotic used.

 

The subgroup analyses indicates that compliance with best practice standards for surgical antibiotic prophylaxis significantly modified the association between postoperative continuation of antibiotic prophylaxis and the incidence of SSI (Figure 1).

 

In the subgroup analysis of 29 trials that were not compliant with abovementioned best practice standards of surgical antibiotic prophylaxis, continuation of antibiotic prophylaxis after surgery resulted in significant less SSI, compared with its immediate discontinuation (RR 0.81 [0.68-0.96]; corresponding heterogeneity was moderate (I² = 13%).

 

When the analysis was restricted to 29 trials that were compliant with abovementioned best practice standards of surgical antibiotic prophylaxis, there was no benefit of postoperative continuation of antibiotic prophylaxis (1.06 [0.89-1.28]). The corresponding heterogeneity in effect size was low (I² < 0.1%).

 

Figure 1. Forest plot showing the comparison between postoperative continuation of antibiotic prophylaxis to immediate discontinuation of antibiotic prophylaxis for surgical site infections (SSI) - Adherent to best standards of practice versus not adherent to best standards of practice. Pooled relative risk ratio (RR), random effects model. Z: p-value of overall effect; df: degrees of freedom; I2; SD: standard deviation; statistical heterogeneity; CI: confidence interval.

 

II. Timing of first dose within 60 minutes before surgery versus timing of first dose not within 60 minutes before surgery

Adequate timing alone did affect the effect estimate (Figure 2). In 19 trials where the first preoperative dose given >60 min before incision, continuation of antibiotic prophylaxis after surgery prevented SSI compared with its immediate discontinuation, RR 0.77 (95% CI 0.61 – 0.96). In the 39 studies with adequate timing of the first dose of antibiotic prophylaxis (<60 min prior to incision) there was no benefit found for continuation of antibiotic prophylaxis after surgery, RR 0.99 (0.86 - 1.15).

Figure 2. Forest plot showing the comparison between postoperative continuation of antibiotic prophylaxis to immediate discontinuation of antibiotic prophylaxis for surgical site infections (SSI) - Timing of first dose within 60 minutes before surgery versus timing of first dose not within 60 minutes before surgery. Pooled relative risk ratio (RR), random effects model. Z: p-value of overall effect; df: degrees of freedom; I2; SD: standard deviation; statistical heterogeneity; CI: confidence interval.

 

III. Intraoperative repeat administration specified when indicated versus intraoperative repeat administration not specified when indicated

Adequate repeat administration alone did not affect the effect estimate (Figure 3). In the 39 studies with adequate repeat administration antibiotic prophylaxis the pooled relative risk was 0.92 (95% CI 0.79 – 1.08), versus no adequate timing RR 0.88 (95% CI 0.72 – 1.08) in 19 studies.

Figure 3. Forest plot showing the comparison between postoperative continuation of antibiotic prophylaxis to immediate discontinuation of antibiotic prophylaxis for surgical site infections (SSI) - Intraoperative repeat administration specified when indicated versus intraoperative repeat administration not specified when indicated. Pooled relative risk ratio (RR), random effects model. Z: p-value of overall effect; df: degrees of freedom; I2; SD: standard deviation; statistical heterogeneity; CI: confidence interval.

 

B. Postoperative postoperative continuations of antibiotic prophylaxis (multiple doses) for <24h versus a single postoperative dose   

One study (Karran, 1993) compared postoperative continuation (multiple doses) for <24h versus a single dose after surgery. The number of SSI was 44/113 (38.9%) in the group with longer antibiotic prophylaxis, versus 39/114 (34.2%) in the group with a single postoperative dose. This resulted in a RR of 0.82 (0·57–1·40). This was not considered as a clinically relevant difference.

 

C. Postoperative continuation of surgical antibiotic prophylaxis for more than 24 hours versus postoperative continuation of surgical antibiotic prophylaxis equal or less than 24 hours

SSI for postoperative continuation for more than 24 hours versus postoperative continuation of surgical antibiotic prophylaxis equal or less than 24 hours were reported in 31 studies (Abubakar, 2001; Ahmed, 2019; Baquin, 2004; Becker, 1991; Bentley, 1999; Bidkar, 2014; Bozorgzadeh, 1999; Carroll, 2003; Chang, 2005; Eshghpour, 2014; Fujita, 2015; Fridrich, 1994; Garcia, 2020; Hanif, 2015; Ishibashi, 2014; Ishibashi, 2009; Jansisyanont, 2008; Lau, 1990; Lin, 2011; Liu, 2008; Madadi, 2019; McArdle, 1995; Mui, 2005; Niederhauser, 1997; Rajabi, 2012; Righi, 1996; Takayama, 2019; Takemoto, 2015; Urquhart, 2019; Yamamoto, 2018; Yang, 2001). The results were pooled in a meta-analysis. The pooled number of SSI in the postoperative continuation for more than 24 hours group was 244/2920 (8.4%), compared to 275/2944 (9.3%) in the postoperative continuation equal or less than 24 hours group. This resulted in a pooled relative risk ratio (RR) of 0.88 (95% CI 0.66 to 1.17), in favour of the postoperative continuation for more than 24 hours group (figure 4). This was not considered as a clinically relevant difference.

 

Figure 4. Forest plot showing the comparison between postoperative continuation of antibiotic prophylaxis for more than 24 hours to postoperative continuation of antibiotic prophylaxis equal or less than 24 hours for surgical site infections (SSI). Pooled relative risk ratio (RR), random effects model. Z: p-value of overall effect; df: degrees of freedom; I2; SD: standard deviation; statistical heterogeneity; CI: confidence interval.

 

D. Postoperative continuation of surgical antibiotic prophylaxis for more than 48 hours versus postoperative continuation of surgical antibiotic prophylaxis equal or less than 48 hours

SSI for postoperative continuation for more than 48 hours versus postoperative continuation of surgical antibiotic prophylaxis equal or less than 48 hours were reported in seven studies (Adaji, 2020; Davis, 2016; Gupta, 2010; Otani, 2004; Sawyer, 1990; Sugawara, 2016; Togo, 2007). The results were pooled in a meta-analysis. The pooled number of SSI in the postoperative continuation for more than 48 hours group was 56/493 (11.4%), compared to 38/504 (7.5%) in the postoperative continuation equal or less than 48 hours group. This resulted in a pooled relative risk (RR) of 1.44 (95% CI 0.90 to 2.31), in favor of the postoperative continuation equal or less than 48 hours group (Figure 5). This was considered as a clinically relevant difference.

 

Figure 5. Forest plot showing the comparison between postoperative continuation of antibiotic prophylaxis for more than 48 hours to postoperative continuation of antibiotic prophylaxis equal or less than 48 hours for surgical site infections (SSI). Pooled relative risk ratio (RR), random effects model. Z: p-value of overall effect; df: degrees of freedom; I2; SD: standard deviation; statistical heterogeneity; CI: confidence interval.

 

E. Postoperative continuation of surgical antibiotic prophylaxis for more than 72 hours versus postoperative continuation of surgical antibiotic prophylaxis equal or less than 72 hours

SSI for postoperative continuation for more than 72 hours versus postoperative continuation of surgical antibiotic prophylaxis equal or less than 72 hours was reported in one study (Park, 2020).

The number of SSI for more than 72 hours antibiotics prophylaxis was 3/125 (2.4%), versus 4/130 (3.1%) in the postoperative continuation equal or less than 72 hours. This resulted in a RR of 0.61 (0.14 – 2.63). This was not considered as a clinically relevant difference.

 

2. Exploratory subgroup analysis

 

To investigate potential procedure-specific effects, we also did post-hoc exploratory subgroup analyses by procedure type.

 

Analysis

SG

N

SSI in longer regimen

SSI shorter regimen

Relative risk (95%CI)

Overall analysis

 

 

58

543 of 10.691

588 of 10.227

0.91 (0.81 - 1.02)

 

Subgroup analyses

Maxillofacial surgery

A

6

9 of 268

27 of 279

0.38 (0.18 - 0.80)

B

3

4 of 95

11 of 105

0.44 (0.14 - 1.39)

Cardiac surgery

A

3

21 of 1.144

48 of 988

0.43 (0.26 - 0.71)

B

1

0 of 300

1 of 150

0.17 (0.01- 4.08)

Vascular Surgery

A

1

15 of 149

28 of 153

0.55 (0.31 - 0.99)

B

0

NA

NA

NA

Appendectomy

A

7

35 of 798

34 of 604

0.75 (0.47 - 1.20)

B

4

22 of 473

24 of 383

0.76 (0.43 - 1.37)

Colorectal surgery

A

2

32 of 368

48 of 269

0.68 (0.40 - 1.15)

B

1

15 of 181

16 of 179

0.93 (0.47 - 1.82)

Upper GI surgery

A

4

51 of 647

51 of 636

0.98 (0.62 - 1.54)

B

3

41 of 486

36 of 472

1.11 (0.63 - 1.97)

Cholecystectomy

A

6

39 of 693

37 of 712

1.06 (0.69 – 1.64)

B

2

6 of 170

5 of 168

1.19 (0.37 - 3.86)

Hepatobiliary Surgery

A

1

64 of 503

64 of 501

1.00 (0.72 - 1.38)

B

0

NA

NA

NA

Mixed general surgery

A

9

187 of 3.773

170 of 3.817

1.11 (0.91 - 1.35)

B

4

83 of 2.328

65 of 2.364

1.30 (0.95 - 1.78)

Caesarean section

A

4

37 of 549

27 of 551

1.38 (0.85 - 2.22)

B

4

37 of 549

27 of 551

1.38 (0.85 - 2.22)

Gynaecological surgery

A

3

4 of 336

11 of 337

0.37 (0.12 - 1.17)

B

1

1 of 264

1 of 267

1.01 (0.06 -16.08)

Ortho/Trauma surgery

A

4

12 of 633

19 of 578

0.57 (0.28 - 1.18)

B

3

9 of 320

17 of 277

0.48 (0.22 - 1.06)

Thoracic surgery

A

2

5 of 230

3 of 233

1.44 (0.36 - 5.87)

B

0

NA

NA

NA

Head and neck surgery

A

2*

13 of 159

8 of 156

1.60 (0.43 - 5.95)

B

1

10 of 58

8 of 55

1.19 (0.50 - 2.78)

Transplantation surgery

A

2

14 of 151

11 of 151

1.29 (0.63 - 2.64)

B

1

1 of 102

2 of 203

0.50 (0.05 - 5.48)

SG: Subgroup, A: Overall analysis, B: Adherence to current standards of practice subgroup, N: Number of studies, SSI: Surgical site infection, 95%CI: 95% confidence interval, NA: Not available, tau2: Tau-squared, MR: Meta-regression, MA: Meta-analysis, % of heterogeneity variance explained: 

* One study excluded from analysis because of no events in both arms

Table 2. Results of the subgroup analysis by surgical subspecialty

 

3. Adverse events

24 studies (17 included in the primary analysis) described possible harmful effects or adverse events related to surgical antibiotic prophylaxis (Table 2). Of these, 18 studies could not attribute adverse events to antibiotic use in both the intervention and control groups (Becker 2008, Carrol 2003, Cartana 1994, Danda 2010, Eshghpour 2014, Fujita 2015, Imamura 2012, Kang 2009, Lindeboom 2003, Liu 2008, Loozen 2017, Maier 1992, Mohri 2007, Rajabi 2012, Regimbeau 2007, Righi 1996, Sawyer 1990, Suzuki 2011). The remaining six studies reported increased adverse events in the groups with prolonged regimens (Bidkar 2014, Karran 1993, Mui 2005, Rajan 2005, de Santibañes 2018, Turano 1992). Of these, one study reported increased cases of C difficile infection in the prolonged postoperative continuation group (Mui 2005). The other studies reported an increased frequency of rash and pruritus, erythema, phlebitis, hypotension, gastrointestinal disturbance (including nausea and diarrhoea), and unspecified local and systemic side-effects with postoperative continuation of antibiotic prophylaxis. No study reported on antimicrobial resistance. Owing to heterogeneity between studies in the comparisons made and the outcomes measured, no meta-analysis could be done of adverse effects.

 

Study

Adverse event definition

Longer postoperative regimens

Shorter postoperative regimens

Mui 2005¶

Clostridium difficile confirmed by fecal clostridium toxin

5 of 177

0 of 92

Karran 1993 †

Hypotension, phlebitis, rash, erythema

5 of 114

1 of 113

Turano 1992 *

Thrombophlebitis, allergic reaction and gastrointestinal disturbances

40 of 1517

10 of 1700

Bidkar 2014 ‡

Gastrointestinal disturbances

19 of 39

1 of 39

Rajan 2005 *

Nausea, diarrhea, skin rash, pruritus

29 of 100

2 of 100

de Santibañes 2018 *

Unspecified

4 of 96

3 of 105

Liu 2008 ‡

No adverse events attributable to antibiotic use in both the intervention and control group.

Carrol 2003 ‡

No adverse events attributable to antibiotic use in both the intervention and control group.

Righi 1996 ‡

No adverse events attributable to antibiotic use in both the intervention and control group.

Maier 1992 *

No adverse events attributable to antibiotic use in both the intervention and control group.

Sawyer 1990 §

No adverse events attributable to antibiotic use in both the intervention and control group.

Kang 2009 *

No adverse events attributable to antibiotic use in both the intervention and control group.

Lindeboom 2003 *

No adverse events attributable to antibiotic use in both the intervention and control group.

Suzuki 2011 *

No adverse events attributable to antibiotic use in both the intervention and control group.

Fujita 2015 *

No adverse events attributable to antibiotic use in both the intervention and control group.

Imamura 2012 *

No adverse events attributable to antibiotic use in both the intervention and control group.

Mohri 2007 *

No adverse events attributable to antibiotic use in both the intervention and control group.

Regimbeau 2007 *

No adverse events attributable to antibiotic use in both the intervention and control group.

Becker 2008 *

No adverse events attributable to antibiotic use in both the intervention and control group.

Cartana 1994 *

No adverse events attributable to antibiotic use in both the intervention and control group.

Eshghpour 2014 ‡

No adverse events attributable to antibiotic use in both the intervention and control group.

Loozen 2017 *

No adverse events attributable to antibiotic use in both the intervention and control group.

Rajabi 2012 ¶

No adverse events attributable to antibiotic use in both the intervention and control group.

Danda 2010 *

No adverse events attributable to antibiotic use in both the intervention and control group.

* Postoperative continuation vs immediate discontinuation of SAP; † Postoperative continuation for 24h vs a single dose after surgery; ‡ Postoperative continuation for >24h vs ≤ 24h; § Postoperative continuation for >48h vs ≤ 48h;

¶ Postoperative continuation vs immediate discontinuation of SAP and Postoperative continuation for >24h vs ≤ 24h

Table 3. Studies reporting adverse events related to SAP

 

4. Studies reporting costs of SAP continuation

Five studies (Chang 2005, Liberman 1995, Orlando 2015, Rajan 2005, Su 2005) addressed cost-effectiveness and reported a cost increase associated with longer antibiotic prophylaxis regimens, in some cases as a result of treatment for side-effects and hospitalisation time in addition to prophylaxis treatment, which varied from US$36.90 to $78.95 (Table 4). None of these studies calculated costs associated with the emergence of antimicrobial resistance. All five studies were done in high-income countries (Australia, Italy, Taiwan, and the USA).

 

Study

Cost included

Cost postoperative continuation

Cost postoperative discontinuation

Absolute difference

Relative difference

Liberman 1995*

Antibiotics

$ 54.80

$ 17.90

+ $ 36.90

3.06

Chang 2005†

Total costs

$ 1,768.00

$ 1,728.00

+ $ 40.00

1.02

Rajan 2005*

Total costs

$ 93.45

$ 14.50

+ $ 78.95

6.44

Su 2005*

Antibiotics

$ 48.00

$ 3.50

+ $ 44.50

13.71

Orlando 2015

Antibiotics

$ 38.80

$ 3.88

+ $ 34.92

10.00

* Postoperative continuation vs immediate discontinuation of SAP;

† Postoperative continuation for>24 h vs ≤ 24 h

Table 4: Studies reporting costs of SAP continuation

 

Level of evidence of the literature

 

Surgical site infections

The level of evidence regarding the outcome SSI was derived from randomized controlled trials and therefore started high. The level of evidence was downgraded by one level because of risk of bias. The level of evidence was considered as moderate.

A systematic review of the literature was performed to answer the following question: What is the effect of postoperative continuation of antibiotic prophylaxis on the incidence of SSI compared with its postoperative discontinuation in adult patients undergoing surgical procedures?

 

P: Adult patients undergoing any surgical procedure.

I: Postoperative continuation of antibiotic prophylaxis.

C: Postoperative discontinuation of antibiotic prophylaxis.

O: Surgical site infections (SSI).

 

Relevant outcome measures

The guideline development group considered surgical site infections as a critical outcome for decision making.

 

The working group defined a threshold of 10% for continuous outcomes and a relative risk (RR) for dichotomous outcomes of <0.80 and >1.25 as a minimal clinically (patient) important difference.

 

Search and select (Methods)

The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms, based on the literature search of de Jonge (2020) from the 24th of July 2018 up to the 28th of January 2021. The detailed search strategy is available on request via https://richtlijnendatabase.nl/. The systematic literature search resulted in 992 hits. Studies were selected based on the following criteria: systematic reviews and randomized controlled trials on the postoperative administration of antibiotics to prevent postoperative wound infections. One hundred eighty-eight studies were initially selected based on title and abstract screening. After reading the full text, 90 studies were excluded (see the table with reasons for exclusion in the table of excluded studies under the tab 'Evidence tabellen'), and 98 studies were included.

 

Results

Ninety-eight studies were included in the analysis of the literature under the tab 'Samenvatting literatuur'. Important study characteristics and results and quality assessments are summarized in the evidence tables and risk of bias tables under the 'evidence tabellen' tab.

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Author, Year

Scope, participants

Type of surgery

Wound class.

CDC SSI definition, Follow-up

Intervention

Control

 

Postoperative continuation of surgical antibiotic prophylaxis vs. postoperative discontinuation of surgical antibiotic prophylaxis

1

Sadraei-Moosavi 2018

Single centre 152*

Appendectomy (open, uncomplicated)

II-III

No

1g Ceftriaxone & 0.5g Metronidazole IV preoperatively + 24h postoperatively

1g Ceftriaxone & 0.5g Metronidazole IV preoperatively

No

Yes

2

Hussain 2012

Single centre 377

Appendectomy (open, uncomplicated)

II-III

Noa, 30 days

Cefuroxime & Metronidazole IV preoperatively + 1x postoperatively

Cefuroxime & Metronidazole IV preoperatively

Yes

Yes

3

Liberman 1995

Single centre 99*

Appendectomy (open uncomplicated)

II-III

Noa, 3 weeks

2g Cefoxitin IV preoperatively + 3x q 6h postoperatively

2g Cefoxitin IV preoperatively

Yes

Yes

4

Tsang 1992

Single centre 103**

Appendectomy (open, uncomplicated)

II-III

Noa, 4 weeks

1.5 mg/kg Gentamicin IV & 7.5 mg/kg Metronidazole IV preoperatively +2x q 8h postoperatively

1.5 mg/kg Gentamicin IV & 7.5 mg/kg Metronidazole IV preoperatively

No

Yes

5

Salih

2018

Single centre 111*

Appendectomy (open, uncomplicated)

II-III

CDC, 10 days

0.5 mg metronidazole IV preoperatively + 9x q 8h postoperatively

0.5 mg metronidazole IV preoperatively

Yes

Yes

6

Suzuki 2011

Single centre 370

Colorectal surgery

II-III

Nof, 30 days

1g Flomoxef IV preoperatively + 4x q 12h

1g Flomoxef IV preoperatively

Yes

Yes

7

Fujita 2007

Multi centre 377

Colorectal surgery

II-III

Nod, NR

1g Cefmetazole IV preoperatively + 2x q 8h

1g Cefmetazole IV preoperatively

Yes

No

8

Imamura 2012

Multi centre 355

Upper GI surgery

II

CDC, 30 days

1g of Cefazolin IV preoperatively +1 x direct postoperative & 4x q 12h postoperative

1g of Cefazolin IV preoperatively

No

Yes

9

Haga 2012

Single centre 325

Upper GI surgery

II

CDC, 30 days

1g of Cefazolin IV preoperatively + 5x q 12h postoperatively

1g of Cefazolin IV preoperatively

No

Yes

10

Balbo 1991

Multi centre 117

Upper GI surgery

II-III

Nov, 30 days

2g Mezlocillin IV preoperatively + 2x q 6h postoperatively

2g Mezlocillin iv preoperatively

Yes

Yes

11

Mohri 2007

Multi centre 486

Upper GI surgery

II

CDC, 6 weeks

1g Cefazolin IV or 1.5 g Ampicillin sulbactam IV preoperatively + 7x q 12h postoperatively

1g Cefazolin IV or 1.5 g Ampicillin sulbactam IV preoperatively

Yes

Yes

12

Chauhan 2018

Single centre 210*

Laparoscopic Cholecystectomy

II-III

Nod, 30 days

1g Ceftriaxone IV preoperatively + 4x q 12h postoperatively

1g Ceftriaxone IV preoperatively

No

No

13

Santibañes 2018

Single centre 201

Laparoscopic Cholecystectomy

II-III

Nod, 30 days

Ampicillin sulbactam IV q 6h preoperatively (admission – surgery, < 5 days) + 1g Amoxicillin/Clavulanic acid PO 15x q 8h

Ampicillin sulbactam IV q 6h preoperatively (admission until surgery, < 5 days) + 1g Placebo PO 15x q 8h

No

No

14

Kim 2017

Multi centre 188

Laparoscopic Cholecystectomy

II-III

Yes, 30 days

1g Cefoxitin IV preoperatively + q 8h IV or PO if tolerated until POD 3

1g Cefoxitin IV preoperatively + placebo q 8h IV or PO if tolerated until POD 3

Yes

Yes

15

Loozen 2017

Single centre 150

Laparoscopic Cholecystectomy

II-III

Nou

2g Cefazolin IV preoperatively + 0.75g Cefazoline IV & 0.5g Metronidazole IV 9x q 8h

2g Cefazolin IV preoperatively

Yes

Yes

16

Regimbeau 2014

Multi centre 414

Open or laparoscopic Cholecystectomy

II-III

CDC, 30 days

2g Amoxiclav IV 3dd before surgery & preoperatively + 15x q 8h IV or PO if tolerated

2g Amoxiclav IV 3dd before surgery & preoperatively

Yes

No

17

Unemura 2000

Multi centre 242

Laparoscopic cholecystectomy

II-III

Noa, NR

2g Cephalosporin IV preoperatively + 4x q 12h postoperatively

2g Cephalosporin IV preoperatively

No

Yes

18

Meijer 1993

Multi centre 1004

Hepatobiliary surgery

II

Noi, 4-6 weeks

1.5g Cefuroxime IV preoperatively + 0.75g Cefuroxime IV 2x q 8h postoperatively

1.5g Cefuroxime IV preoperatively

No

No

19

Abro 2014

Single centre 208

Mixed general surgery

I-III

Noj, 35 days

2g Ceftriaxone IV preoperatively + 1g Ceftriaxone IV 2x q 8h postoperatively (& 0.25g Gentamicin & 0.5g Metronidazole when indicated)

2g Ceftriaxone IV preoperatively (& 0.25g Gentamicin & 0.5g Metronidazole when indicated)

No

Yes

20

Becker 2008

Single centre 44

Mixed general surgery

I

CDC, 30 days

1g Cefazoline IV preoperatively + 3dd postoperatively until drains were removed

1g Cefazoline IV preoperatively

Yes

Yes

21

Scher 1997

Single centre 768

Mixed general surgery

II

Nod, NR

1g of Cefazolin IV preoperatively + 1g Cefazolin IV 3x q 8h postoperatively

1g of Cefazolin IV preoperatively

Yes

Yes

22

Kow 1995

Single centre 1010*

Mixed general surgery

II-III

Nob, 4-6 weeks

2g Cefoxitin IV & 0.5 Metronidazole IV preoperatively + 2x q 6h postoperatively

2g Cefoxitin IV & 0.5g Metronidazole IV preoperatively

No

No

1g Cefotaxime IV & 0.5g metronidazole IV preoperatively + 2x q 6h postoperatively

1g Cefotaxime IV & 0.5g metronidazole IV preoperatively

23

Nusrath 2020

Single centre 312

Mixed oncological surgery

II

CDC, 30 days

1.5g Cefuroxime IV preoperatively + 12x q 8h 1.5g Cefuroxime IV postoperatively

1.5g Cefuroxime IV preoperatively

Yes

No

24

Turano 1992

Single centre 3567*

Abdominal, Gynaecological and Urological surgery

II-III

Noa, 7 days

1g Cefotaxime IV preoperatively + 2x q 6h after the first dose

1g Cefotaxime IV preoperatively

Yes

Yes

25

Bates 1992

Multi centre 900*

Mixed general surgery

II-IV

Nob, 30 days

0.25g/0.125g Amoxicillin/clavulanic acid IV preoperatively + 2x q 8h postoperatively

0.25g/0.125g Amoxicillin/clavulanic acid IV preoperatively

Yes

No

26

Aberg 1991

Single centre 428*

Mixed general surgery

II-III

Noa, 30 days

1.5g Cefuroxime IV preoperatively + 2x q 8h (& 0.5g metronidazole when indicated)

1.5g Cefuroxime IV preoperatively (& 0.5g metronidazole when indicated)

No

No

27

Sgroi 1990

Single centre 352

Mixed general

II-III

Noa, NR

1 x Cephalosporin preoperatively + 2x q 8h postoperatively

1 x Cephalosporin preoperatively

Yes

No

28

Westen 2015

Multi centre 176

C-section

II

Nok, 30 days

1g Ampicillin IV & 0.5g Metronidazole IV preoperatively + 0.5 Amoxicillin & 0.5g Metronidazole IV 2x q 8h postoperatively followed by 0.5g Amoxicillin PO and 0.4g metronidazole PO 9x q 8h

1g Ampicillin IV & 0.5g Metronidazole IV preoperatively

Yes

Yes

29

Shaheen 2014

Single centre 100

C-section

II

Nol, 6 weeks

1g Cefotaxime IV preoperatively + 2 x q 12h postoperatively followed by 0.4g Cefuroxime PO for 5 days

1g Cefotaxime IV preoperatively

Yes

Yes

30

Lyimo 2013

Single centre 500

C-section

II

CDC, 30 days

3 mg/kg Gentamicin IV & 0.5g Metronidazole I +

preoperatively Metronidazole 0.5g 3x q 8h postoperatively

3 mg/kg Gentamicin IV & 0.5g Metronidazole IV preoperatively

Yes

Yes

31

Tan 2020

Single centre 486

C-section

II

Noae, NI

2 g Cefuroxime IV preoperatively + 3 days postoperatively

2 g Cefuroxime IV preoperatively

Yes

Yes

32

Su 2005

Single centre 532

Gynaecological surgery

II

Nom, 90 days

1g Cefazolin preoperatively + 3x q 6h postoperatively

1g Cefazolin IV preoperatively

Yes

Yes

33

Irato 1997

Single centre 84

Gynaecological surgery

II-III

Now, NR

2g cefotetan IV preoperatively + 10x q 12h

2g cefotetan IV preoperatively

Yes

No

34

Cartaña 1994

Single centre 58

Gynaecological surgery

II

Nod, 4 days

4g Piperacillin preoperatively + 2x q 6h postoperatively

4g Piperacillin IV preoperatively

Yes

No

35

Buckley 1990

Single centre 204

Orthopaedic / trauma surgery

I

Noa, 6 weeks

2g Cefazolin IV preoperatively + 1g Cefazolin 3x q 6h postoperatively

2g Cefazolin IV preoperatively

Yes

Yes

36

Garotta 1991

Multi centre 614

Orthopaedic / trauma surgery

I

Noc, 1 year

2g Ceftizoxime IV preoperatively + 1x q 12h postoperatively

2g Ceftizoxime IV preoperatively

Yes

No

37

Hellbusch 2008

Multi centre 233

Orthopaedic / trauma surgery

I

Noo, >21 days

1g<100kg<2g Cefazolin IV preoperatively + 9x q 8h postoperatively followed by 0.5g Cephalexin PO 28x q 6h

1g<100kg<2g Cefazolin IV preoperatively

Yes

Yes

38

Crist 2018

Single centre 227

Orthopaedic / trauma surgery

I

Nox

1g<100kg<2g Cefazolin IV preoperatively + 2x q 8h postoperatively

1g<100kg<2g Cefazolin IV preoperatively + 2x q 8h Saline

Yes

Yes

39

Nooyen 1994

Single centre 844

Cardiothoracic surgery

I

Noc, NR

20mg/kg Cefuroxime IV preoperatively + 0.75g Cefuroxime IV 9x q 8h postoperatively

20mg/kg Cefuroxime IV preoperatively

Yes

No

40

Tamayo 2008

Single centre 838

Cardiothoracic surgery

I

CDC, 12 months

2g Cefazolin IV preoperativel + 1g Cefazolin IV 2x q 8h postoperatively

2g Cefazolin IV preoperatively

No

Yes

41

Olak 1991

Single centre 199

Cardiothoracic surgery

II

Noa, 6 weeks

2g Cefazolin IV preoperatively + 1g Cefazolin IV 5x q 8h postoperatively

2g Cefazolin IV preoperatively

No

Yes

42

Orjuela 2020

Single centre 360

Cardiac surgery

I

Noaf, 2 years

1g Cefazolin IV preoperatively + 1g Cefazolin IV 3x q 8h postoperatively

1g Cefazolin IV preoperatively

Yes

Yes

 

43

Madadi 2019

Single centre 300

Cardiothoracic surgery

I

Noaa, 30 days

1-2 g Cephazolin IV preoperatively + Cephazolin IV 3x q 8h

1-2 g Cephazolin IV preoperatively

Yes

Yes

1-2 g Cephazolin IV preoperatively + Cephazolin IV 3x q 8h & Ciprofloxacin PO 14x q 12h

1-2 g Cephazolin IV preoperatively

Yes

Yes

44

Jiang 2004

Multi centre 264

Thoracic surgery

II-III

CDC, 30 days

1.5g cefuroxime IV preoperatively + 15x 0.75g q 8h postoperatively

1.5g cefuroxime IV preoperatively

No

No

45

Hall 1998

Single centre 302

Vascular surgery

I

Noc, 42 days

3.0g/0.1g Ticarcillin Clavulanic acid IV preoperatively + q 6h postoperatively until lines were removed

3.0g/0.1g Ticarcillin Clavulanic acid IV preoperatively

No

Yes

46

Orlando 2015

Multi centre 205

Transplant surgery

I

CDC, 30 days

2g Cefazolin IV or 1g Cefotaxime IV preoperatively + q 12h postoperatively until removal of Foley catheter

2g Cefazolin IV or 1g Cefotaxime IV preoperatively

Yes

Yes

47

Berry 2019

Single centre 97

 

Liver transplant surgery

II

CDC, 30 days

3.375 g  Piperacillin/Tazobactam IV OR 2g Cefepime IV & 0.5 mg Metronidazole IV OR 1g Vancomycin IV & 0.4 mg Ciprofloxacin IV preoperatively

+ 8x q 8h 3.375 g Piperacillin/Tazobactam IV OR 2g Cefepime IV & 0.5 mg Metronidazole IV OR 1g Vancomycin IV & 0.4 mg Ciprofloxacin IV

postoperatively

3.375 g  Piperacillin/Tazobactam IV OR 2g Cefepime IV & 0.5 mg Metronidazole IV OR 1g Vancomycin IV & 0.4 mg Ciprofloxacin IV preoperatively

 

Yes

No

48

Maier 1992

Single centre 106

Head and neck surgery

I-II

Nod, NR

1.5 g Cefuroxime IV preoperatively + 2x q 8h postoperatively

1.5 g Cefuroxime IV preoperatively

Yes

No

49

Mann 1990

Single centre 113

Head and neck surgery

II

Noa, NR

2g Cefotiam IV & 0.5g Metronidazole IV preoperatively + 2x q 8h postoperatively

2g Cefotiam IV & 0.5g Metronidazole IV preoperatively

Yes

Yes

50

Rajan 2005

Single centre 200

Head and neck surgery

II

Nod, 30 days

2.2g Amoxicillin / clavulanic acid IV preoperatively + 1g Amoxicillin/ clavulanic acid PO 14x q 12h postoperatively

2.2g Amoxicillin / clavulanic acid IV preoperatively

Yes

No

51

Campos 2015

Single centre 74

Maxillofacial surgery

I-II

Noe, 6 weeks

2g Cefazolin IV preoperatively + 1g Cefazolin IV 4x q 6h postoperatively

2g Cefazolin IV preoperatively

Yes

Yes

 

52

Lindeboom 2003

Single centre 70

Maxillofacial surgery

II

Nos, 3 months

0.4g Clindamycin IV preoperatively + Clindamycin IV 4x q 6h postoperatively

0.4g Clindamycin IV preoperatively

Yes

Yes

 

53

Cioaca 2002

Single centre 140*

Maxillofacial surgery

II

Noa, 14 days

2.4 mg Amoxicillin/ Clavulanic acid IV preoperatively + 15x q 8h postoperatively

2.4 mg Amoxicillin/ Clavulanic acid IV preoperatively

No

No

2g Cefazolin IV preoperatively + 15x q 8h postoperatively

2g Cefazolin IV preoperatively

54

Wahab 2013

Single centre 60*

Maxillofacial surgery

II

CDC, 2 months

1g Amoxicillin IV preoperatively + 0.5g Amoxicillin IV 2x q 4h postoperatively

1g Amoxicillin IV preoperatively

No

No

55

Danda 2010

Single centre 150*

Maxillofacial surgery

II

Nob, 4 weeks

1g Ampicillin IV preoperatively + Ampicillin 0.5g IV  4x q 6h postoperatively

1g Ampicillin IV preoperatively

No

No

56

Kang 2009

Single centre 56

Maxillofacial surgery

II

CDC, 2 weeks

1g Cefpiramide IV preoperatively + 6x q 12h postoperatively

1g Cefpiramide IV preoperatively

Yes

Yes

57

Rajabi 2012

Single centre 291*

Appendectomy (open, uncomplicated)

II-III

Noa, 10 days after discharge

1g Ceftriaxone IV & 0.5g Metronidazole IV preoperatively + 1g Ceftriaxone IV q 12h & 0.5g Metronidazole IV q 8h For 1 OR 3 days postoperatively

1g Ceftriaxone IV & 0.5g Metronidazole IV preoperatively

No

Yes

58

Mui 2005

Single centre 269*

Appendectomy (open, uncomplicated)

II-III

Noa, 30 days

1.5g Cefuroxime IV & 0.5 g Metronidazole IV preoperatively + 2x postoperatively OR a 5-day course IV until PO was tolerated (Cefuroxime 0.25g 2dd + metronidazole 0.4g 3dd)

1.5g Cefuroxime IV & 0.5 g Metronidazole IV preoperatively

Yes

Yes

 

Postoperative continuation of surgical antibiotic prophylaxis for multiple postoperative doses <24h vs. postoperative continuation of surgical antibiotic prophylaxis for one postoperative dose

59

Karran 1993

Single centre 227

Colorectal surgery

II-III

Nog, 6-8 weeks

1g Imipenem IV preoperatively + 1x 3h postoperatively followed by 0.5 Imipenem IV 2x q 8 h

1g Imipenem IV preoperatively + 1x 3h postoperatively

No

No

 

Postoperative continuation of surgical antibiotic prophylaxis > 24h vs postoperative continuation of surgical antibiotic prophylaxis <= 24h

60

Rajabi 2012

Single centre 194*

Appendectomy (open, uncomplicated)

II-III

Noa, 10 days after discharge

1.5g Cefuroxime IV & 0.5 g Metronidazole IV preoperatively + 1g Ceftriaxone 6x q 12h & 0.5g Metronidazole IV q 9x q 8h postoperatively

1.5g Cefuroxime IV & 0.5 g Metronidazole IV preoperatively + 1g Ceftriaxone 2x q 12h & 0.5g Metronidazole IV 3x q 8h postoperatively

No

Yes

61

Mui 2005

Single centre177*

Appendectomy (open, uncomplicated)

II-III

Noa, 30 days

1.5g Cefuroxime IV & 0.5 g Metronidazole IV preoperatively + 5-day course IV until PO was tolerated (Cefuroxime 250mg 2dd + metronidazole 400mg 3dd)

1.5g Cefuroxime IV & 0.5 g Metronidazole IV preoperatively + 2x for 1 day postoperatively

Yes

Yes

62

Ishibashi 2014

Single centre 297

Colorectal surgery

II-III

CDC, 30 days

1g Flomoxef IV + 1x 1h postoperatively followed by 4x q 12h

1g Flomoxef IV + 1x 1h postoperatively

No

Yes

63

Ishibashi 2009

Single centre 275

Colorectal surgery

II-III

CDC, 30 days

1g Cefotiam IV or Cefmetazole IV + 1x 1h postoperatively followed by 4 x q 12h

1g Cefotiam IV or 1g Cefmetazole IV + 1x 1h postoperatively

No

Yes

64

McArdle 1995

Single centre 169

Colorectal surgery

II-III

Noa, 4 weeks after discharge

0.5g Metronidazole IV & 0.12g Gentamicin IV + 0.5g Metronidazole IV & 0.08g Gentamicin 9x q 8h

0.5g Metronidazole IV & 0.12g Gentamicin IV+ 0.5g Metronidazole IV & 0.08g gentamicin IV 2x q 8h

Yes

Yes

65

Becker 1991

Single centre 40

Colorectal surgery

II-III

Nob, 56 days

2g Cefoxitin IV preoperatively + 2x q 6h after the initial dose followed by  1g Cefoxitin IV 20x q 6h postoperatively

2g Cefoxitin IV preoperatively + 2x q 6h after the initial dose

Yes

No

66

Fujita 2015

Single centre 257

Upper GI surgery

II

CDC, 30d

1g Cefmetazole IV 4x q 3h starting preoperatively + 4x q 12h postoperatively

1g Cefmetazole IV 4x q 3h starting preoperatively

Yes

Yes

67

Lau 1990

Single centre 203

Open cholecystectomy

II-III

Noh, 1 year

2g Cefamandole IV preoperatively + 0.5g Cefamandole IV 30x q 6h after the initial dose

2g Cefamandole IV preoperatively + 0.5g Cefamandole IV 2x q 6h after the initial dose

Yes

No

68

Yang 2001

Multi centre 731

Mixed general

II-III

Nod, NR

0.3g Nefibromycin IV & 0.5g metronidazole IV when needed + 9x q 8h postoperatively

0.3g Nefibromycin IV & 0.5g metronidazole IV when needed + 2x q 8h postoperatively

Yes

No

69

Bozorgzadeh 1999

Single centre 300*

Mixed general surgery

II-III

CDC, 30 days

1g Cefoxitin IV for 24 with the first dose given in the emergency department after determination of the requirement for laparotomy + 20x q 6h

1g Cefoxitin IV for 24 with the first dose given in the emergency department after determination of the requirement for laparotomy + 4x q 6h

No

No

70

Hanif 2015

Single centre 220*

Mixed general surgery

II-III

Nod, NR

1g Sulbactam IV & 0.5 g Cephaperazone IV preoperatively + 14x q 8h

1g Sulbactam IV & 0.5 g Cephaperazone IV preoperatively + 2x q 8h

Yes

No

71

Chang 2005

Single centre 156

Gynaecological surgery

II

Noo, 7 days after discharge

2g Cephalothin IV & 0.08g Gentamicin IV preoperatively + 1g Cephalothin IV  5-10x q 6h & 0.06-0.08g Gentamicin IV 4-8x q 8h postoperatively

2g Cephalothin IV & 0.08g Gentamicin IV preoperatively + 1g Cephalothin IV 4x q 6h & 0.06-0.08g Gentamicin IV 3x q 8h postoperatively

Yes

No

72

Takemoto 2015

Single centre 314

Orthopaedic / trauma surgery

I

CDC, 1 year

Cefazolin for drain duration starting preoperatively (average of 3.2 days)

Cefazolin for 24h starting preoperatively

Yes

Yes

73

Lin 2011

Single centre 231

Cardiothoracic surgery

I

CDC, 30 days

1 gr Cefazolin preoperatively + 9x q 8h postoperatively

1 gr Cefazolin preoperatively + 3x q 8h postoperatively

No

Yes

74

Niederhauser 1997

Single centre 53

Cardiothoracic surgery

I

CDC, 3-540 days

1g of cefazolin preoperatively +  2x q 8h postoperatively followed by Ticarcillin/clavunate 5.2g 6x q 8h & 0.5g Vancomycin q 12h until removal of IABP

1g of cefazolin preoperatively + 2x q 8h postoperatively

Yes

Yes

75

Liu 2008

Single centre 53

Head and neck surgery

II

CDC, 30 days

0.3g Clindamycin IV preoperatively +12x q 6h postoperatively

0.3g Clindamycin IV preoperatively +

4x q 6h postoperatively

Yes

Yes

76

Carroll 2003

Single centre 74

Head and neck surgery

II

Nop, 7 days

0.9g Clindamycin IV preoperatively +15x q 8h after the initial dose

0.9g Clindamycin IV preoperatively +

3x q 8h after the initial dose

Yes

Yes

77

Righi 1996

Single centre 162

Head and neck surgery

II

Nos, 20 days

0.6g Clindamycin IV & Cefonicid 1g IV preoperatively + 0.6g Clindamycin IV 9x q 8h & Cefonicid 1g 3x q 12h postoperatively

0.6g Clindamycin IV & Cefonicid 1g IV preoperatively + 0.6g Clindamycin IV 3x q 8h & Cefonicid 1g 1x q 12h postoperatively

Yes

No

78

Bidkar 2014

Single centre 78*

Head and neck surgery

I-III

Nod, 3 weeks

1.5g Cefuroxime preoperatively + 0.75g Cefuroxime 2x q 12h postoperatively followed by 0.2g Cefixime PO 16x q 12h

1.5g Cefuroxime Preoperatively + 0.75g Cefuroxime 2x q 12h postoperatively

Yes

Yes

79

 

Abubaker 2001

Single centre 30

Maxillofacial surgery

II

Noe, 6 weeks

2m U aqueous Penicillin-G IV q 4h from admission trough the preoperative and intraoperative phase and for 12h postoperatively followed by 0.5g penicillin PO 20x q 6h

2m U aqueous Penicillin-G IV q 4h from admission trough the preoperative and intraoperative phase and for 12h postoperatively

Yes

Yes

80

Eshghpour 2014

Single centre 50*

Maxillofacial surgery

II

Nod, 6 weeks

1g Cefazolin IV preoperatively + 1x q 4h after the initial dose followed by 0.5g Amoxicillin PO 21x q 8h

1g Cefazolin IV preoperatively + 1x q 4h after the initial dose

Yes

Yes

 

81

Jansisyanont 2008

Multi centre 122*

Maxillofacial surgery

II

CDC, 6 weeks

1.2g Amoxicillin / Clavulanic acid + 0.625g Amoxicillin / clavulanic acid PO 15x q 8h postoperatively

1.2g Amoxicillin / Clavulanic acid preoperatively + 1x q 8h postoperatively

Yes

Yes

2 million units of aqueous Penicillin IV + 0.5g Amoxicillin PO 15x q 8h postoperatively

2m U of aqueous Penicillin IV preoperatively + 1x q 4h postoperatively

82

Baqain 2004

Single centre 34

Maxillofacial surgery

II

Not, 6 weeks

1g Amoxicillin IV + 0.5g Amoxicillin IV 1x q 3h postoperatively followed by 0.5g Amoxicillin 15x q 8h

1g Amoxicillin IV + 0.5g Amoxicillin IV 1x q 3h postoperatively

No

No

83

Bentley 1999

Single centre 30

Maxillofacial surgery

II

CDC, 30 days

2m U aqueous Penicillin-G IV preoperatively + 1x q 3h postoperatively after the last intraoperative dose followed by 1m U Penicillin-G IV 8x q 6h followed by 0.3g penicillin-V PO 8x q 6h

2m U aqueous Penicillin-G IV preoperatively + 1x q 3h postoperatively after the last intraoperative dose

No

Yes

84

Fridrich 1994

Single centre 30*

Maxillofacial surgery

II

Nod, 8 weeks

2m U Penicillin IV preoperatively + q 4h until IV discontinuation on postoperative day 1 followed by 0.5g Penicillin VK 28x q 6h

2m U Penicillin IV preoperatively + a 2h until participants reached the recovery room, where the final dose was given

Yes

Yes

85

Garcia 2020

Single centre 124

Mammaplasty

I

CDC, 30 days

1g cephalothin IV preoperatively + 3x postoperatively q 6h

followed by 500mg oral cephalexin 28x q 6h

1g cephalothin IV preoperatively + 3x postoperatively q 6h followed by oral placebo 28x q 6h

Yes

No

86

Ahmed 2019

Single centre 159

Hollow viscus injury

III

CDC, unknown

1g sulbactam + cefoperazone and 0.5g metronidazole IV preoperatively + 16x postoperatively q 8h

1g sulbactam + cefoperazone and 0.5g metronidazole IV preoperatively + 3x q 8h postoperatively

Yes

No

87

Urquhart 2019

Single centre 282

Spinal surgery

I

CDC, 1 year

2g cefazolin IV preoperatively + 12x q 8h postoperatively

OR 1g vancomycin IV preoperatively + 6x q 12h

2g cefazolin IV preoperatively + 3x q 8h postoperatively

OR 1g vancomycin IV preoperatively + 2x q 12h

Yes

Yes

88

Takayama 2019

Multi centre 480

Hepatobiliary surgery

II

CDC, 30 days

1g flomoxef IV preoperatively + q 3h intra-operatively + 6x q 12h post-operatively

1g flomoxef IV preoperatively + q 3h intra-operatively + 1x q 6h post-operatively

Yes

Yes

89

Madadi 2019

Single centre 300

Cardiac surgery 

I

Noag, 2 years

1-2g cephazolin IV preoperatively + 3x q 8h postoperatively

1-2g cephazolin IV preoperatively

Yes

Yes

1-2g cephazolin IV preoperatively + 3x q 8h postoperatively followed by 250-500mg ciprofloxacin14x q12h oral

90

Yamamoto 2018

Single centre 82

Hepatobiliary surgery

II

Noad, unknown

1g cefozopran IV preoperatively + 9x q 12h postoperatively

 1g cefozopran IV preoperatively + 1x postoperatively

Yes

Yes

 

Postoperative continuation of surgical antibiotic prophylaxis > 48h vs postoperative continuation of surgical antibiotic prophylaxis <= 48h

91

Togo 2007

Single centre 180

Hepatobiliary surgery

II

CDC, 30 days

1g Flomoxef IV preoperatively + 1x postoperatively followed by 2g Flomoxef IV 10x q 12h

1g Flomoxef IV preoperatively + 1x postoperatively followed by 2g Flomoxef IV 4x q 12h

Yes

Yes

92

Sugawara 2018

Single centre 86

Hepatobiliary surgery

II-III

CDC, 30 days

Cefazoline IV  (or in case of a positive culture, as culture indicated) preoperatively + 12x q8h

Cefazoline IV (or in case of a positive culture, as culture indicated) preoperatively + 6x q8h

Yes

Yes

93

Gupta 2010

Single centre 227

Cardiothoracic surgery

I

CDC, 30 days

Ceftazidime Pentahydrate IV & Amikacin IV preoperatively + for 72h postoperatively

Ceftazidime Pentahydrate IV & Amikacin IV preoperatively + for 48h postoperatively

Yes

Yes

94

Otani 2004

Single centre 40

Thoracic surgery

II-III

Nod, 14 days

1g Cefmetazole IV preoperatively + 1x directly postoperatively followed by 12 x q 12h

1g Cefmetazole IV preoperatively + 1x directly followed by 2 x q 12h

No

No

95

Sawyer 1990

Multi centre 50

Head and neck surgery

II

Nos, NR

1g Cefazolin IV & 0.5g Metronidazole IV preoperatively + 1g Cefazolin IV 21x q 8h & 0.5g Metronidazole IV 28x q 6 h postoperatively

1g Cefazolin IV & 0.5g Metronidazole IV preoperatively + 1g Cefazolin IV 6x q 8h & 0.5g Metronidazole IV  8x q 6 h postoperatively

No

Yes

96

Davis 2017

Single centre 171*

Maxillofacial surgery

II

CDC, 30 days / 1 year

2g Cefazolin IV preoperatively + 3x q 8h postoperatively followed by 0.5g Cephalexin PO & 0.3g Clindamycin PO 8x q 6h

2g Cefazolin IV preoperatively + 3x q 8h postoperatively

Yes

Yes

97

Adaji 2020

Single centre 243

C-section

III

Noab, 14 days / 6 weeks

0.75g Cefuroxime IV & 0.4g Metronidazole IV preoperatively +

0.75g cefuroxime IV

4x q 12h & 6x q 8h Metronidazole IV postoperatively followed by 0.5g Cefuroxime PO 10x q 12h & 0.4g Metronidazole PO 5x q 24h

0.75g Cefuroxime IV & 0.4g Metronidazole IV preoperatively +

0.75g cefuroxime IV

4x q 12h & 6x q 8h Metronidazole IV postoperatively

Yes

No

 

Postoperative continuation of surgical antibiotic prophylaxis > 72h vs postoperative continuation of surgical antibiotic prophylaxis <= 72h

98

Park 2010

Multi centre 255

Colorectal surgery

II-III

CDC, 21 days

1g Cefotetan IV preoperatively + 15x q 8h postoperatively

1g Cefotetan IV preoperatively + 9x q 8h postoperatively

Yes

Yes

CDC: Center for Disease Control and Prevention; SSI: Surgical Site infection; Wound class.: CDC Wound Classification; : Timing of preoperative intravenous antibiotic specified and within 60 min prior to incision; : Repeat of surgical antibiotic prophylaxis administration specified when Indicated; *: Included paediatric patients; **: exclusively paediatric patients; No[letter]: SSI definition deviating from CDC classification. Letter refers to specification in appendix 3; IV: intravenous; H: Hour; x: times/frequency; q: per/interval; g: gram; NR: not recorded; SSI: surgical site infection; IABP: intra-aortic balloon pumping; <: less than; >: more than; <= less than or equal to; >=more than or equal to; POD: Postoperative day

 

a. Purulent discharge with or without culture

b. Purulent discharge, or serous with a positive culture

c. Discharge with a positive culture

d. Wound infection, not otherwise specified

e. Pus drainage at the fracture site or in the vicinity of the surgical intervention site; b) increased swelling 7 days after the operation; c) presence of a fistula in the area of the surgical intervention or at the site of the fracture, with active drainage; d) other clinical features observed by the evaluator, including typical signs of infection such as fever, oedema and localized redness.

f. Purulent discharge or abscess

g. Purulent discharge, positive bacteriological culture, abscess, peritonitis, septicaemia

h. Purulent discharge, serous discharge + positive bacteriological cultures, serous discharge after the patient had returned home. Intra-peritoneal abscess was diagnosed by ultrasonic evidence of an abscess and by laparotomy

i. 0: No sign of infection., 1: Minor infection (erythema, stitch abscess or skin edge necrosis)., 2: Major infection (purulent discharge or wound dehiscence).

j. Pain at the operative site, persistent fever >38°C wound erythema, tenderness, wound discharge and dehiscence.

k. Presence of erythema, purulent discharge, cellulitis or wound abscess, peritonitis,

pelvic abscess or wound dehiscence.

l. Superficial or deep infection, pus discharge, abscess formation, wound dehiscence, and hematoma formation

m. Abdominal wound infection or trocar wound infection (including wound discharge or abscess). Pelvic abscess or tuba-ovarian abscess. Vaginal cuff abscess. Postoperative septicaemia.

n. Pelvic cellulitis, vaginal cuff abscess, pelvic abscess, wound infection

o. If the wound appeared red or oedematous or if there was drainage.

p. A wound was considered infected if the colour became red or the wound was swollen. A pink wound that developed purulent discharge was also considered infected.

q. Purulent drainage (either spontaneously or by incision) or muco-cutaneous fistula interpreted as wound infection.

r. Major wound infection was defined as wound breakdown and undermining of tissues sufficient to allow packing of the wound. Lesser complications, such as cellulitis or a tiny fistula, allowing only entry of a cotton-tipped applicator were considered as minor.

s. Presence of purulent drainage (either spontaneously or by incision), accompanied by pain or tenderness, localized swelling, redness, and heat or fever (>38.5° C) or an increase in localized swelling after an initial postoperative decrease of oedema, together with pain, discomfort, induration, and an increase in body temperature (>38.5° C).

t. The need for additional antibiotics

u. Wound infection Erythema of incision(s), pus and/or turbid fluid. Intra-abdominal abscess

v. Purulent discharge, endoperitoneal abscess or diffuse peritonitis but not secondary to anastomotic leakage

w. Infiltrate, dehiscence or Purulent secretion of the wound.

x. Purulent drainage at the operative site with the presence of one or more of the classic signs and symptoms of inflammation (rubor, calor, tumor, dolor)

z. Pus discharge from the wound, redness, tenderness and oedema. Intra-abdominal collection was defined as fluid collection inside the peritoneal cavity confirmed by ultrasound or CT

aa. Pocket infection with localized inflammation without evidence of systemic infection. Pocket infection with positive blood culture but without evidence of infective endocarditis. Device-related endo- carditis according to the Duke modified criteria.

ab. Partial or total dehiscence with the presence of purulent or serous wound discharge.

ac. Postoperative body temperature of> 38 °C; with incision bleeding, redness and pain, inflammatory exudate, or possible dehiscence of incision.

ad. Postoperative infectious complications were defined as: clinically relevant postoperative pancreatic fistula (CR-POPF) which was defined according to International Study Group (ISGPF) criteria, intra-abdominal abscess, postoperative cholangitis and wound infection.

ae. Diagnosis of abdominal incision infection: Postoperative maternal body temperature of > 38 °C; with incision bleeding, redness and pain, inflammatory exudate, or possible dehiscence of incision.

af. Infectious complications were defined as infection of the wound, presence of pus from the surgical wound requiring open drainage, bacteremia, or endocarditis.

ag. Infections were classified in one of the following categories: (1) pocket infection with localized inflammation without evidence of systemic infection; (2) pocket infection with positive blood culture but without evidence of infective endocarditis; (3) device-related endocarditis according to the Duke modified criteria.11

 

Criteria for risk of bias assessment

 

 

Risk of bias domain

 

Criteria for judgment

Selection bias

Low risk of bias: A random component was used in the sequence generation process and allocation was concealed

High risk of bias: A non-random component was used or allocation was inadequately concealed. Unclear: Sequence generation or allocation concealment was insufficiently described for judgement.

Performance bias

Low risk of bias: Blinding of patients and investigators was described (e.g. with a placebo control group)

 

Hight risk of bias: There was no blinding of patients and investigators.

 

Unclear: Blinding of participants and investigators was insufficiently described for judgement

Detection bias

Low risk of bias: Outcome assessor blinding was ensured High risk of bias: Outcome assessors were not blinded

Unclear: Blinding of outcome assessors was insufficiently described.

Attrition bias

Low risk of bias: An intention to treat analysis was conducted or attrition was low or balanced and unlikely to have affected the outcome

 

High risk of bias: Attrition was unbalanced or high relative to the event incidence and could have affected the outcome.

 

Unclear: Attrition was insufficiently described

Reporting bias

Low risk of bias: No outcomes mentioned in the study registration or protocol where omitted or altered.

High risk of bias: Outcomes mentioned in the study registration or protocol where omitted or altered. Unclear: No registration or protocol was available

Other bias

Low risk of bias, unless other concerns existed on the validity of the study

 

Risk of bias evaluation of the included studies

Author, Year

Random sequence generation (selection bias)

Allocation concealment (selection bias)

Blinding of participants and personnel (performance bias)

Blinding of outcome assessment (detection bias)

Incomplete outcome data (attrition bias)

Selective reporting (reporting bias)

Other bias

Sadraei-Moosavi 2018

Unclear

Unclear

Unclear

Unclear

Unclear

Low

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

All predefined outcomes reported

 No concerns

Hussain 2012

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Liberman 1995

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Tsang 1992

High

High

High

Unclear

Unclear

Unclear

Low

 

Randomized according to hospital numbers (even –odd)

Randomized according to hospital numbers (even –odd)

No blinding described and no allocation concealment

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Suzuki 2011

Low

Unclear

Unclear

Unclear

Low

Unclear

Low

 

Random number table

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Missing data balanced in numbers across intervention groups for similar reasons

No protocol or registration

No concerns

Fujita 2007

Low

Low

High

High

Low

Unclear

Low

 

Central computer randomisation

Central computer randomisation

Not blinded

Not blinded

Low attrition, unlikely to influence outcome

No protocol or registration

No concerns

Imamura 2012

Low

Low

High

High

Low

Low

Low

 

Mersenne twister randomisation

Central randomisation

Not blinded

Not blinded

Intention to treat analysis

All predefined outcomes reported

No concerns

Haga 2012

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Balbo 1991

Unclear

High

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Based on a randomisation list

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Mohri 2007

Low

Low

Low

Low

Low

Unclear

Low

 

Central computer randomisation

Central computer randomisation

Blinded investigators and patients

Independent outcome assessor

Balanced in reason and groups, unlikely to affect outcome

No protocol or registration

No concerns

Chauhan 2018

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Santibañes 2018

Low

Low

Low

Low

Low

Low

Low

 

Not (sufficiently) described

Not (sufficiently) described

Blinded investigators and patients

Blinded investigators and patients

Intention to treat analysis

All predefined outcomes reported

No concerns

Kim 2017

Low

Low

Low

Low

Low

Low

Low

 

Computer randomisation

Central allocation by independent investigator

Blinded investigators and patients

Blinded investigators and patients

Missing outcomes balanced in reason and groups

All predefined outcomes reported

No concerns

Loozen 2017

Low

Low

High

Unclear

Low

Low

Low

 

Central computer randomisation

Central computer randomisation

Not blinded

Not (sufficiently) described

Missing outcomes balanced in reason and groups

All predefined outcomes reported

No concerns

Regimbeau 2014

Low

Low

Unclear

Low

Low

Unclear

Low

 

Central computer randomisation

Central computer randomisation based

Not (sufficiently) described

Blinded outcome assessor

Intention to treat analysis

No protocol or registration

No concerns

Unemura 2000

High

High

Unclear

Unclear

Unclear

Unclear

Low

 

Randomized by alternately selecting treatment allocation

Randomized by alternately selecting treatment allocation

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Meijer 1993

Low

Low

Low

Low

Low

Unclear

Low

 

Central computer randomisation

Central computer randomisation

Blinded investigators and patients

Blinded outcome assessor

Intention to treat analysis

No protocol or registration

No concerns

Abro 2014

Unclear

Unclear

Unclear

Unclear

High

Unclear

Low

 

Not (sufficiently) described)

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

High attrition relative to events. Could have affected outcome

No protocol or registration

No concerns

Becker 2008

Low

Unclear

Low

Unclear

Unclear

Unclear

Low

 

Drawing of envelopes

Not (sufficiently) described

Randomisation after procedure

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Scher 1997

Low

Low

Unclear

Unclear

Unclear

Unclear

Low

 

Central randomisation by random number chart*

Central randomisation by random number chart *

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Kow 1995

Unclear

Unclear

High

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not blinded

 

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Turano 1992

Unclear

High

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Open randomisation

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Bates 1992

Low

Unclear

Unclear

Low

Low

Unclear

Low

 

Randomized by random number table

Not (sufficiently) described

Not (sufficiently) described

Blinded outcome assessor

Attrition low and balanced. Unlikely to affect outcome

No protocol or registration

No concerns

Aberg 1991

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Sgroi 1990

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Westen 2015

Unclear

Low

Unclear

Low

Low

Low

Low

 

Not (sufficiently) described

Sequentially numbered, opaque, sealed envelopes

Not (sufficiently) described

Blinded outcome assessor

Intention to treat analysis

All predefined outcomes reported

No concerns

Shaheen 2014

Low

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Shuffled cards

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Lyimo 2013

Low

Unclear

High

High

Low

Unclear

Low

 

Drawing of envelopes

Not (sufficiently) described

Not blinded

Not blinded

Intention to treat analysis

No protocol or registration

No concerns

Su 2005

Low

Unclear

Unclear

Unclear

High

Unclear

Low

 

Computer randomisation

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Unbalanced attrition. Could have affected outcome

No protocol or registration

No concerns

Irato 1997

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Cartaña 1994

Low

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Random number table

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Buckley 1990

Unclear

Unclear

Low

Low

High

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Blinded investigators and patients

Blinded outcome assessors

Unbalanced attrition. Could have affected outcome

No protocol or registration

No concerns

Garotta 1991

Low

Low

Unclear

Unclear

Unclear

Unclear

Low

 

Central computer randomisation

Central computer randomisation

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Hellbusch 2008

Unclear

Unclear

Unclear

Unclear

High

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

High attrition relative to events. Could have affected outcome

No protocol or registration

No concerns

Crist 2018

Unclear

Low

Low

Low

High

Unclear

Low

 

Not (sufficiently) described

Pharmacy controlled randomisation

Blinded investigators and patients

Blinded investigators and patients

High attrition relative to events. Could have affected outcome

No protocol or registration

No concerns

Nooyen 1994

Low

Low

Unclear

Unclear

High

Unclear

Low

 

Central computer randomisation

Central computer randomisation

Not (sufficiently) described

Not (sufficiently) described

Unbalanced attrition. Could have affected outcome

No protocol or registration

No concerns

Tamayo 2008

Low

Unclear

Unclear

Low

High

Unclear

Low

 

Computerized randomisation

Not (sufficiently) described

Not (sufficiently) described

Blinded outcome assessor

High attrition relative to events. Could have affected outcome

No protocol or registration

No concerns

Olak 1991

Low

Low

Low

Low

Unclear

Unclear

Low

 

Central random number generation

Central random number generation

Blinded investigators and patients

Blinded outcome assessor

Not (sufficiently) described

No protocol or registration

No concerns

Jiang 2004

Low

High

Unclear

Unclear

Unclear

Unclear

Low

 

Random number list

Open list

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Hall 1998

Low

Low

Unclear

Unclear

Unclear

Unclear

Low

 

Computer randomisation

Sequentially numbered, opaque, sealed envelopes

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Orlando 2015

Low

Low

Unclear

Unclear

Low

Low

Low

 

Central computer randomisation

Central computer randomisation

Not (sufficiently) described

Not (sufficiently) described

All patients complied with the study protocol

All predefined outcomes reported

No concerns

Maier 1992

High

High

High

Unclear

Unclear

Unclear

Low

 

Randomisation by even and uneven days

Randomisation by even and uneven days

No blinding described and no allocation concealment

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Mann 1990

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Rajan 2005

Low

Unclear

Low

Unclear

Unclear

Unclear

Low

 

Drawing of envelopes

Not (sufficiently) described

Blinded investigators

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Campos 2015

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Lindeboom 2003

Low

High

Unclear

Low

Unclear

Unclear

Low

 

Random number list

Open list

Not (sufficiently) described

Blinded outcome assessor

Not (sufficiently) described

No protocol or registration

No concerns

Cioaca 2002

Unclear

Unclear

Unclear

Low

Low

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Blinded outcome assessor

Attrition low and balanced. Unlikely to affect outcome

No protocol or registration

No concerns

Wahab 2013

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Danda 2010

Unclear

Unclear

Low

Low

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Blinded investigators and patients

Blinded outcome assessor

Not (sufficiently) described

No protocol or registration

No concerns

Kang 2009

Low

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Computer randomisation

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Rajabi 2012

Unclear

Unclear

Low

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Mui 2005

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Karran 1993

Unclear

Unclear

Unclear

Unclear

High

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

High attrition relative to events. Could have affected outcome

No protocol or registration

No concerns

Ishibashi 2014

Unclear

Unclear

Low

Unclear

Low

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Randomisation after procedure

Not (sufficiently) described

Attrition low and balanced. Unlikely to affect outcome

No protocol or registration

No concerns

Ishibashi 2009

Unclear

Unclear

Low

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Randomisation after procedure

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

McArdle 1995

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Becker 1991

Unclear

Unclear

Low

Low

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Blinded investigators and patients

Blinded outcome assessor

Not (sufficiently) described

No protocol or registration

No concerns

Fujita 2015

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Lau 1990

Unclear

Unclear

Low

Low

High

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Randomisation after procedure

Blinded outcome assessor

High attrition relative to events. Could have affected outcome

No protocol or registration

No concerns

Yang 2001

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Bozorgzadeh 1999

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Hanif 2015

High

High

Unclear

Unclear

Unclear

Unclear

Low

 

Randomisation by alternating assignment

Randomisation by alternating assignment

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Chang 2005

Low

Low

Unclear

Unclear

Unclear

Unclear

Low

 

Central computer randomisation

Central computer randomisation

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No concerns

Takemoto 2015

Low

Unclear

Low

Low

High

Low

Low

 

Computer randomisation

Not (sufficiently) described

Investigators blinded

Outcome assessors blinded

High attrition relative to events. Could have affected outcome

All predefined outcomes reported

No concerns

Lin 2011

Low

unclear

Unclear

Low

low

Unclear

Low

 

Computer randomisation

Not (sufficiently) described

Not (sufficiently) described

Blinded outcome assessor

Intent-to-treat analysis

No protocol or registration

No concerns

Niederhauser 1997

Low

Unclear

Low

Unclear

Low

Unclear

Low

 

Randomisation list

Not (sufficiently) described

Randomisation after procedure

Not (sufficiently) described

All participants were analysed

No protocol or registration

 

No concerns

Liu 2008

Low

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Computer randomisation

Not (sufficiently) described

Randomisation after procedure

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Carroll 2003

unclear

unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Righi 1996

unclear

unclear

Unclear

Unclear

High

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

High attrition relative to events. Could have affected outcome

No protocol or registration

No concerns

Bidkar 2014

Low

Unclear

Low

Low

Low

Unclear

Low

 

Computer randomisation

Not (sufficiently) described

Blinded investigators

Blinded outcome assessors

All participants were analysed

No protocol or registration

No concerns

Abubaker 2001

Unclear

Low

Low

Low

High

Unclear

Low

 

Not (sufficiently) described

Central randomisation

Blinded investigators and participants

Blinded outcome assessors

High attrition relative to events. Could have affected outcome

No protocol or registration

No concerns

Eshghpour 2014

Unclear

Unclear

Unclear

Unclear

Low

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

All participants were analysed

No protocol or registration

No concerns

Jansisyanont 2008

Unclear

Unclear

Unclear

Unclear

High

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

High attrition relative to events. Could have affected outcome

No protocol or registration

No concerns

Baqain 2004

Low

Low

Low

low

Low

Unclear

Low

 

Central randomisation by random list

Central randomisation by random list

Blinded investigators and patients

Blinded outcome assessors

All participants were analysed

No protocol or registration

No concerns

Bentley 1999

Unclear

Unclear

Low

Low

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Blinded investigators and patients

Blinded outcome assessors

Not (sufficiently) described

No protocol or registration

No concerns

Fridrich 1994

Unclear

Unclear

Unclear

Unclear

Low

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

All participants were analysed

No protocol or registration

No concerns

Togo 2007

Low

Low

Unclear

Unclear

low

unclear

Low

 

Central computer randomisation

Central computer randomisation

Not (sufficiently) described

Not (sufficiently) described

All participants were analysed

No protocol or registration

No concerns

Sugawara 2018

Low

Low

Low

Unclear

Low

Low

Low

 

Central computer randomisation

Central computer randomisation

Randomisation after procedure

Not (sufficiently) described outcome

All participants were analysed

All predefined outcomes reported

No concerns

Gupta 2010

Low

Low

Low

Low

Low

Unclear

Low

 

Randomisation by random number table

Allocation concealed throughout the study

Blinded investigators and patients

Blinded outcome assessors

Attrition low. Unlikely to affect outcome.

No protocol or registration

No concerns

Otani 2004

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Sawyer 1990

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

Davis 2017

Low

Unclear

Low

Low

High

Low

Low

 

Randomisation by drawing envelopes

Not (sufficiently) described

Blinded investigators and patients

Blinded outcome assessors

High attrition relative to events. Could have affected outcome

All predefined outcomes reported

No concerns

Park 2010

Unclear

Unclear

Unclear

Unclear

Unclear

Unclear

Low

 

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

Not (sufficiently) described

No protocol or registration

No concerns

* Information obtained through correspondence with author

 

Studies excluded after full text review

Author and year

Reason for exclusion

Kumar 20131

Incomparable regimen

Ahn 20132

Not an RCT

Fonseca 20063

Incomparable regimen

Sevin 20074

Not an RCT

Han 20145

Not an RCT

Farran 20086

Did not address study question

Schardey 19977

Did not address study question

Vu 20148

Not an RCT

Basoli 20089

Did not address study question

Safdar 199210

Incomparable regimen

Gidiri 201411

Incomparable regimen

Kato 200712

Incomparable regimen

Dahl A 200613

Not an RCT

Kakimaru 201014

Not an RCT

Kato 200615

Not an RCT

Pedrini 200516

Not an RCT

Righi 199517

Duplicate of Righi 1996

Adde 201218

Incomparable regimen

Luaces 201019

Incomparable regimen

Lacasa 200720

Incomparable regimen

Jensen 199021

Incomparable regimen

Boffi 199222

Duplicate of Gazzaniga 1992

Gazzaniga 199223

Incomparable regimen

Mathur 201324

Incomparable regimen

Kaczmarzyk 200725

Did not address study question

Vargas-Mena 201226

Not an RCT

Wu 199827

Did not address study question

Ahmadi 200528

Did not address study question

Morimoto 199829

Did not address study question

Morimoto 199330

Not retrievable

Hashizume 200431

Incomparable regimen

Bonzanini 199332

Did not address study question

Fukushima 201433

Congress abstract

Badia 201134

Congress abstract

Hashimoto 201435

Congress abstract

Ijarotimi 201336

Not retrievable

Shakya 201037

Not retrievable

Ko 201038

Not retrievable

Rajshekhar 200939

Congress abstract

Patacchiola 200040

Did not address study question

Urbanetz 199441

Not retrievable

Cartana 199042

Not retrievable

Ali 200643

Congress abstract

Ricart-Hoffiz 201144

Congress abstract

Rolle 199045

Not retrievable

Orlando 201046

Congress abstract

Navarro 199547

Did not address study question

Lee 201248

Not retrievable

Cheshani 201549

Not retrievable

Ali 201250

Not retrievable

Seker 201151

Not retrievable

Bencini 199452

Not retrievable

Lindeboom 200553

Did not address study question

Marcucci 199054

Not retrievable

Shahid 200755

Did not address study question

Cuthbertson 199156

Did not address study question

Akgur 199257

Did not address study question

Garcia 201758

Did not address study question

Ghosh 201759

Congress abstract

Habibi 201660

Congress abstract

Phillips 201661

Congress abstract

Samson 201762

Congress abstract

Chen 201863

Not retrievable

Yalagachin 201864

Did not address study question

Kate 202065

Congress abstract

Mohammed 202066

Incomparable regimen

Sabbagh 202067

Study protocol

Togo 202068

Did not address study question

Guler 201969

Incomparable regimen

Han-Gyu 201970

Incomparable regimen

Kirby 201971

Incomparable regimen

Knight72

No surgery

Nagata 201973

Study protocol

Nitrushwa 201974

Congress abstract

Omar 201975

Did not address study question

Posillico 201976

Not an RCT

Shigemura 201977

Study protocol

Speich 201978

Study protocol

Shah 201679

Conference abstract

Griffiths 201880

Study protocol

Knight 201881

Study protocol

Montravers 201882

Did not address study question

Yang 201783

Not an RCT

Chen 201884

Not retrievable

Shkedy 201885

Did not address study question

Sittirai86

Did not address study question

Van Oostveen87

Study protocol

Yates 201888

Not an RCT

Backes 201789

Did not address study question

Vathul 201790

Conference abstract

 

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83. Yang S, Liu G, Tang D, Cai D. Evaluation Intravenous Drip Cephazolin Prophylaxis of Breast Cancer Surgery Site Infection. J Craniofac Surg. 2017;28(6):e527-e531.

84. Chen J, Huang LG, Hu XJ. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2018;32(13):998-1001.

85.Shkedy Y, Stern S, Nachalon Y, et al. Antibiotic prophylaxis in clean head and neck surgery: A prospective randomised controlled trial. Clin Otolaryngol. 2018;43(6):1508-1512.

86. Sittitrai P, Siriwittayakorn C. Perioperative antibiotic prophylaxis in open tracheostomy: A preliminary randomized controlled trial. Int J Surg. 2018;54(Pt A):170-175.

87. van Oostveen RB, Romero-Palacios A, Whitlock R, et al. Prevention of Infections in Cardiac Surgery study (PICS): study protocol for a pragmatic cluster-randomized factorial crossover pilot trial [published correction appears in Trials. 2019 Oct 16;20(1):595]. Trials. 2018;19(1):688.

88. Yates AJ Jr; American Association of Hip and Knee Surgeons Evidence-Based Medicine Committee. Postoperative prophylactic antibiotics in total joint arthroplasty. Arthroplast Today. 2018;4(1):130-131.

89. Backes M, Dingemans SA, Dijkgraaf MGW, et al. Effect of Antibiotic Prophylaxis on Surgical Site Infections Following Removal of Orthopedic Implants Used for Treatment of Foot, Ankle, and Lower Leg Fractures: A Randomized Clinical Trial [published correction appears in JAMA. 2018 Mar 13;319(10 ):1051]. JAMA. 2017;318(24):2438-2445.

90. Vathul B, Pari M. Is antibiotic prophylaxis for open thyroidectomies necessary? a randomized trial in south indian population. Clujul Med. 2017;90;S88.

 

Autorisatiedatum en geldigheid

Laatst beoordeeld  : 01-12-2024

Laatst geautoriseerd  : 01-12-2024

Geplande herbeoordeling  : 01-12-2026

Initiatief en autorisatie

Initiatief:
  • Nederlandse Vereniging voor Heelkunde
  • Samenwerkingsverband Richtlijnen Infectiepreventie
Geautoriseerd door:
  • Nederlands Oogheelkundig Gezelschap
  • Nederlandse Internisten Vereniging
  • Nederlandse Orthopaedische Vereniging
  • Nederlandse Vereniging voor Anesthesiologie
  • Nederlandse Vereniging voor Dermatologie en Venereologie
  • Nederlandse Vereniging voor Heelkunde
  • Nederlandse Vereniging voor Keel-Neus-Oorheelkunde en Heelkunde van het Hoofd-Halsgebied
  • Nederlandse Vereniging voor Kindergeneeskunde
  • Nederlandse Vereniging voor Medische Microbiologie
  • Nederlandse Vereniging voor Neurochirurgie
  • Nederlandse Vereniging voor Obstetrie en Gynaecologie
  • Nederlandse Vereniging voor Plastische Chirurgie
  • Nederlandse Vereniging voor Thoraxchirurgie
  • Verpleegkundigen en Verzorgenden Nederland
  • Vereniging voor Hygiëne en Infectiepreventie in de Gezondheidszorg
  • Patiëntenfederatie Nederland
  • Landelijke Vereniging van Operatieassistenten
  • Nederlandse Vereniging van Anesthesiemedewerkers

Algemene gegevens

De ontwikkeling/herziening van deze richtlijnmodule werd ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten (www.demedischspecialist.nl/kennisinstituut) en werd gefinancierd uit de Kwaliteitsgelden Medisch Specialisten (SKMS). De financier heeft geen enkele invloed gehad op de inhoud van de richtlijnmodule.

Samenstelling werkgroep

Voor het ontwikkelen van de richtlijnmodules 2 tot 16 is in 2020 op initiatief van de NVvH een multidisciplinaire werkgroep ingesteld, bestaande uit vertegenwoordigers van alle relevante specialismen (zie hiervoor de Samenstelling van de werkgroep) die betrokken zijn bij de zorg voor preventie van postoperatieve wondinfecties. Daarnaast is in 2022 op initiatief van het Samenwerkingsverband Richtlijnen Infectiepreventie (SRI) een separate multidisciplinaire werkgroep samengesteld voor de herziening van de WIP-richtlijn over postoperatieve wondinfecties: module 17-22. De ontwikkelde modules van beide werkgroepen zijn in deze richtlijn samengevoegd.

Belangenverklaringen

De Code ter voorkoming van oneigenlijke beïnvloeding door belangenverstrengeling is gevolgd. Alle werkgroepleden hebben schriftelijk verklaard of zij in de laatste drie jaar directe financiële belangen (betrekking bij een commercieel bedrijf, persoonlijke financiële belangen, onderzoek financiering) of indirecte belangen (persoonlijke relaties, reputatiemanagement) hebben gehad. Gedurende de ontwikkeling of herziening van een module worden wijzigingen in belangen aan de voorzitter doorgegeven. De belangenverklaring wordt opnieuw bevestigd tijdens de commentaarfase.

Een overzicht van de belangen van werkgroepleden en het oordeel over het omgaan met eventuele belangen vindt u in onderstaande tabel. De ondertekende belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van de Federatie Medisch Specialisten.

 

Werkgroeplid

Functie

Nevenfuncties

Gemelde belangen

Ondernomen actie

Mevr. prof. dr. M.A. Boermeester

Chirurg

* Medisch Ethische Commissie, Amsterdam UMC, locatie AMC

* Antibiotica Commissie, Amsterdam UMC

Persoonlijke financiële belangen

Hieronder staan de beroepsmatige relaties met bedrijfsleven vermeld waarbij eventuele financiële belangen via de AMC Research B.V. lopen, dus institutionele en geen persoonlijke gelden zijn: Skillslab instructeur en/of spreker (consultant) voor KCI/3M, Smith&Nephew, Johnson&Johnson, Gore, BD/Bard, TELABio, GDM, Medtronic, Molnlycke.

 

Persoonlijke relaties

Geen.

 

Extern gefinancierd onderzoek

Institutionele grants van KCI/3M, Johnson&Johnson en New Compliance.

 

Intellectuele belangen en reputatie

Ik maak me sterk voor een 100% evidence-based benadering van maken van aanbevelingen, volledig transparant en reproduceerbaar. Dat is mijn enige belang in deze, geen persoonlijk gewin.

 

Overige belangen

Geen.

 

Extra kritische commentaarronde.

Dhr. dr. M.J. van der Laan

Vaatchirurg

Vice voorzitter Consortium Kwaliteit van Zorg NFU, onbetaald

 

Persoonlijke financiële belangen

Geen.

 

Persoonlijke relaties

Geen.

 

Extern gefinancierd onderzoek

Geen.

 

Intellectuele belangen en reputatie

Geen.

 

Overige belangen

Geen.

 

Geen.

 

Dhr. dr. W.C. van der Zwet

Arts-microbioloog

Lid Regionaal Coördinatie Team, Limburgs infectiepreventie & ABR Zorgnetwerk (onbetaald)

Dhr. dr. D.R. Buis

Neurochirurg

Lid Hoofdredactieraad Tijdschrift voor Neurologie & Neurochirurgie - onbetaald

Dhr. dr. J.H.M. Goosen

Orthopaedisch Chirurg

Inhoudelijke presentaties voor Smith&Nephew en Zimmer Biomet. Deze worden vergoed per uur.

Mw. drs. H. Jalalzadeh

Arts-onderzoeker

Geen.

Persoonlijke financiële belangen

Geen.

 

Persoonlijke relaties

Geen.

 

Extern gefinancierd onderzoek

Geen.

 

Intellectuele belangen en reputatie

Geen.

 

Overige belangen

Geen.

Geen.

 

Dhr. dr. N. Wolfhagen

AIOS chirurgie

Mw. drs. H.  Groenen

Arts-onderzoeker

Dhr. dr. F.F.A. Ijpma

Traumachirurg

Dhr. dr. P. Segers

Cardiothoracaal chirurg

Mw. Y.E.M. Dreissen

AIOS neurochirurgie

Dhr. R.R. Schaad

Anesthesioloog

 

Inbreng patiëntenperspectief

Er werd aandacht besteed aan het patiëntenperspectief door uitnodigen van de Patiëntenfederatie Nederland voor de invitational conference. De verkregen input is meegenomen bij het opstellen van de uitgangsvragen, de keuze voor de uitkomstmaten en bij het opstellen van de overwegingen. De conceptmodules zijn tevens voor commentaar voorgelegd aan de Patiëntenfederatie Nederland en de eventueel aangeleverde commentaren zijn bekeken en verwerkt. Voor de modules 17-22 was de patiëntfederatie vertegenwoordigd in de werkgroep.

 

Wkkgz & Kwalitatieve raming van mogelijke substantiële financiële gevolgen

Bij de richtlijn is conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uitgevoerd of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling zijn richtlijnmodules op verschillende domeinen getoetst (zie het stroomschema op de Richtlijnendatabase).

 

Uit de kwalitatieve raming blijkt dat er waarschijnlijk geen substantiële financiële gevolgen zijn.

 

Voor module 8 (Negatieve druktherapie) geldt dat uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (5.000 - 40.000 patiënten). Tevens volgt uit de toetsing dat het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft. Er worden daarom geen substantiële financiële gevolgen verwacht.

 

Voor de overige modules en aanbevelingen geldt dat uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (>40.000 patiënten). Tevens volgt uit de toetsing dat het overgrote deel (±90%) van de zorgaanbieders en zorgverleners al aan de norm voldoet en het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft. Ook wordt geen toename in het aantal in te zetten voltijdsequivalenten aan zorgverleners verwacht of een wijziging in het opleidingsniveau van zorgpersoneel. Er worden daarom geen substantiële financiële gevolgen verwacht.

Methode ontwikkeling

Evidence based

Implementatie

Zie voor de implementatie het implementatieplan in het tabblad 'Bijlagen'. 

Werkwijze

AGREE

Deze richtlijnmodule is opgesteld conform de eisen vermeld in het rapport Medisch Specialistische Richtlijnen 2.0 van de adviescommissie Richtlijnen van de Raad Kwaliteit. Dit rapport is gebaseerd op het AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II; Brouwers, 2010).

 

Knelpuntenanalyse en uitgangsvragen

Tijdens de voorbereidende fase inventariseerde de werkgroepen de knelpunten in de zorg voor patiënten die chirurgie ondergaan. Tevens zijn er knelpunten aangedragen door middel van een invitational conference. De verslagen hiervan zijn opgenomen onder aanverwante producten.

Op basis van de uitkomsten van de knelpuntenanalyse zijn door de werkgroep concept-uitgangsvragen opgesteld en definitief vastgesteld.

 

Uitkomstmaten

Na het opstellen van de zoekvraag behorende bij de uitgangsvraag inventariseerde de werkgroep welke uitkomstmaten voor de patiënt relevant zijn, waarbij zowel naar gewenste als ongewenste effecten werd gekeken. Hierbij werd een maximum van acht uitkomstmaten gehanteerd. De werkgroep waardeerde deze uitkomstmaten volgens hun relatieve belang bij de besluitvorming rondom aanbevelingen, als cruciaal (kritiek voor de besluitvorming), belangrijk (maar niet cruciaal) en onbelangrijk. Tevens definieerde de werkgroep tenminste voor de cruciale uitkomstmaten welke verschillen zij klinisch (patiënt) relevant vonden.

 

Methode literatuursamenvatting

Een uitgebreide beschrijving van de strategie voor zoeken en selecteren van literatuur is te vinden onder ‘Zoeken en selecteren’ onder Onderbouwing. Indien mogelijk werd de data uit verschillende studies gepoold in een random-effects model. De beoordeling van de kracht van het wetenschappelijke bewijs wordt hieronder toegelicht.

 

Beoordelen van de kracht van het wetenschappelijke bewijs

De kracht van het wetenschappelijke bewijs werd bepaald volgens de GRADE-methode. GRADE staat voor ‘Grading Recommendations Assessment, Development and Evaluation’ (zie http://www.gradeworkinggroup.org/). De basisprincipes van de GRADE-methodiek zijn: het benoemen en prioriteren van de klinisch (patiënt) relevante uitkomstmaten, een systematische review per uitkomstmaat, en een beoordeling van de bewijskracht per uitkomstmaat op basis van de acht GRADE-domeinen (domeinen voor downgraden: risk of bias, inconsistentie, indirectheid, imprecisie, en publicatiebias; domeinen voor upgraden: dosis-effect relatie, groot effect, en residuele plausibele confounding).

GRADE onderscheidt vier gradaties voor de kwaliteit van het wetenschappelijk bewijs: hoog, redelijk, laag en zeer laag. Deze gradaties verwijzen naar de mate van zekerheid die er bestaat over de literatuurconclusie, in het bijzonder de mate van zekerheid dat de literatuurconclusie de aanbeveling adequaat ondersteunt (Schünemann, 2013; Hultcrantz, 2017).

 

GRADE

Definitie

Hoog

  • er is hoge zekerheid dat het ware effect van behandeling dichtbij het geschatte effect van behandeling ligt;
  • het is zeer onwaarschijnlijk dat de literatuurconclusie klinisch relevant verandert wanneer er resultaten van nieuw grootschalig onderzoek aan de literatuuranalyse worden toegevoegd.

Redelijk

  • er is redelijke zekerheid dat het ware effect van behandeling dichtbij het geschatte effect van behandeling ligt;
  • het is mogelijk dat de conclusie klinisch relevant verandert wanneer er resultaten van nieuw grootschalig onderzoek aan de literatuuranalyse worden toegevoegd.

Laag

  • er is lage zekerheid dat het ware effect van behandeling dichtbij het geschatte effect van behandeling ligt;
  • er is een reële kans dat de conclusie klinisch relevant verandert wanneer er resultaten van nieuw grootschalig onderzoek aan de literatuuranalyse worden toegevoegd.

Zeer laag

  • er is zeer lage zekerheid dat het ware effect van behandeling dichtbij het geschatte effect van behandeling ligt;
  • de literatuurconclusie is zeer onzeker.

 

Bij het beoordelen (graderen) van de kracht van het wetenschappelijk bewijs in richtlijnen volgens de GRADE-methodiek spelen grenzen voor klinische besluitvorming een belangrijke rol (Hultcrantz, 2017). Dit zijn de grenzen die bij overschrijding aanleiding zouden geven tot een aanpassing van de aanbeveling. Om de grenzen voor klinische besluitvorming te bepalen moeten alle relevante uitkomstmaten en overwegingen worden meegewogen. De grenzen voor klinische besluitvorming zijn daarmee niet één op één vergelijkbaar met het minimaal klinisch relevant verschil (Minimal Clinically Important Difference, MCID). Met name in situaties waarin een interventie geen belangrijke nadelen heeft en de kosten relatief laag zijn, kan de grens voor klinische besluitvorming met betrekking tot de effectiviteit van de interventie bij een lagere waarde (dichter bij het nuleffect) liggen dan de MCID (Hultcrantz, 2017).

 

Overwegingen (van bewijs naar aanbeveling)

Om te komen tot een aanbeveling zijn naast (de kwaliteit van) het wetenschappelijke bewijs ook andere aspecten belangrijk en worden meegewogen, zoals aanvullende argumenten uit bijvoorbeeld de biomechanica of fysiologie, waarden en voorkeuren van patiënten, kosten (middelenbeslag), aanvaardbaarheid, haalbaarheid en implementatie. Deze aspecten zijn systematisch vermeld en beoordeeld (gewogen) onder het kopje ‘Overwegingen’ en kunnen (mede) gebaseerd zijn op expert opinion. Hierbij is gebruik gemaakt van een gestructureerd format gebaseerd op het evidence-to-decision framework van de internationale GRADE Working Group (Alonso-Coello, 2016a; Alonso-Coello 2016b). Dit evidence-to-decision framework is een integraal onderdeel van de GRADE methodiek.

 

Formuleren van aanbevelingen

De aanbevelingen geven antwoord op de uitgangsvraag en zijn gebaseerd op het beschikbare wetenschappelijke bewijs en de belangrijkste overwegingen, en een weging van de gunstige en ongunstige effecten van de relevante interventies. De kracht van het wetenschappelijk bewijs en het gewicht dat door de werkgroep wordt toegekend aan de overwegingen, bepalen samen de sterkte van de aanbeveling. Conform de GRADE-methodiek sluit een lage bewijskracht van conclusies in de systematische literatuuranalyse een sterke aanbeveling niet a priori uit, en zijn bij een hoge bewijskracht ook zwakke aanbevelingen mogelijk (Agoritsas, 2017; Neumann, 2016). De sterkte van de aanbeveling wordt altijd bepaald door weging van alle relevante argumenten tezamen. De werkgroep heeft bij elke aanbeveling opgenomen hoe zij tot de richting en sterkte van de aanbeveling zijn gekomen.

In de GRADE-methodiek wordt onderscheid gemaakt tussen sterke en zwakke (of conditionele) aanbevelingen. De sterkte van een aanbeveling verwijst naar de mate van zekerheid dat de voordelen van de interventie opwegen tegen de nadelen (of vice versa), gezien over het hele spectrum van patiënten waarvoor de aanbeveling is bedoeld. De sterkte van een aanbeveling heeft duidelijke implicaties voor patiënten, behandelaars en beleidsmakers (zie onderstaande tabel). Een aanbeveling is geen dictaat, zelfs een sterke aanbeveling gebaseerd op bewijs van hoge kwaliteit (GRADE gradering HOOG) zal niet altijd van toepassing zijn, onder alle mogelijke omstandigheden en voor elke individuele patiënt.

 

Implicaties van sterke en zwakke aanbevelingen voor verschillende richtlijngebruikers

 

Sterke aanbeveling

Zwakke (conditionele) aanbeveling

Voor patiënten

De meeste patiënten zouden de aanbevolen interventie of aanpak kiezen en slechts een klein aantal niet.

Een aanzienlijk deel van de patiënten zouden de aanbevolen interventie of aanpak kiezen, maar veel patiënten ook niet. 

Voor behandelaars

De meeste patiënten zouden de aanbevolen interventie of aanpak moeten ontvangen.

Er zijn meerdere geschikte interventies of aanpakken. De patiënt moet worden ondersteund bij de keuze voor de interventie of aanpak die het beste aansluit bij zijn of haar waarden en voorkeuren.

Voor beleidsmakers

De aanbevolen interventie of aanpak kan worden gezien als standaardbeleid.

Beleidsbepaling vereist uitvoerige discussie met betrokkenheid van veel stakeholders. Er is een grotere kans op lokale beleidsverschillen. 

 

Organisatie van zorg

In de knelpuntenanalyse en bij de ontwikkeling van de richtlijnmodule is expliciet aandacht geweest voor de organisatie van zorg: alle aspecten die randvoorwaardelijk zijn voor het verlenen van zorg (zoals coördinatie, communicatie, (financiële) middelen, mankracht en infrastructuur). Randvoorwaarden die relevant zijn voor het beantwoorden van deze specifieke uitgangsvraag zijn genoemd bij de overwegingen. Meer algemene, overkoepelende, of bijkomende aspecten van de organisatie van zorg worden behandeld in de module Organisatie van zorg.

 

Commentaar- en autorisatiefase

De conceptrichtlijnmodule werd aan de betrokken (wetenschappelijke) verenigingen en (patiënt) organisaties voorgelegd ter commentaar. De commentaren werden verzameld en besproken met de werkgroep. Naar aanleiding van de commentaren werd de conceptrichtlijnmodule aangepast en definitief vastgesteld door de werkgroep. De definitieve richtlijnmodule werd aan de deelnemende (wetenschappelijke) verenigingen en (patiënt) organisaties voorgelegd voor autorisatie en door hen geautoriseerd dan wel geaccordeerd.

 

Adaptatie

Een aantal modules van deze richtlijn betreft een adaptatie van modules van de World Health Organization (WHO)-richtlijn ‘Global guidelines for the prevention of surgical site infection’ (WHO, 2018), te weten:

  • Module Normothermie
  • Module Immunosuppressive middelen
  • Module Glykemische controle
  • Module Antimicrobiële afdichtingsmiddelen
  • Module Wondbeschermers bij laparotomie
  • Module Preoperatief douchen
  • Module Preoperatief verwijderen van haar
  • Module Chirurgische handschoenen: Vervangen en type handschoenen
  • Module Afdekmaterialen en operatiejassen

Methode

  • Uitgangsvragen zijn opgesteld in overeenstemming met de standaardprocedures van het Kennisinstituut van de Federatie Medisch Specialisten.
  • De inleiding van iedere module betreft een korte uiteenzetting van het knelpunt, waarbij eventuele onduidelijkheid en praktijkvariatie voor de Nederlandse setting wordt beschreven.
  • Het literatuuronderzoek is overgenomen uit de WHO-richtlijn. Afhankelijk van de beoordeling van de actualiteit van de richtlijn is een update van het literatuuronderzoek uitgevoerd.
  • De samenvatting van de literatuur is overgenomen van de WHO-richtlijn, waarbij door de werkgroep onderscheid is gemaakt tussen ‘cruciale’ en ‘belangrijke’ uitkomsten. Daarnaast zijn door de werkgroep grenzen voor klinische besluitvorming gedefinieerd in overeenstemming met de standaardprocedures van het Kennisinstituut van de Federatie Medisch Specialisten, en is de interpretatie van de bevindingen primair gebaseerd op klinische relevantie van het gevonden effect, niet op statistische significantie. In de meta-analyses zijn naast odds-ratio’s ook relatief risico’s en risicoverschillen gerapporteerd.
  • De beoordeling van de mate van bewijskracht is overgnomen van de WHO-richtlijn, waarbij de beoordeling is gecontroleerd op consistentie met de standaardprocedures van het Kennisinstituut van de Federatie Medisch Specialisten (GRADE-methode; http://www.gradeworkinggroup.org/). Eventueel door de WHO gerapporteerde bewijskracht voor observationele studies is niet overgenomen indien ook gerandomiseerde gecontroleerde studies beschikbaar waren.
  • De conclusies van de literatuuranalyse zijn geformuleerd in overeenstemming met de standaardprocedures van het Kennisinstituut van de Federatie Medisch Specialisten.
  • In de overwegingen heeft de werkgroep voor iedere aanbeveling het bewijs waarop de aanbeveling is gebaseerd en de aanvaardbaarheid en toepasbaarheid van de aanbeveling voor de Nederlandse klinische praktijk beoordeeld. Op basis van deze beoordeling is door de werkgroep besloten welke aanbevelingen ongewijzigd zijn overgenomen, welke aanbevelingen niet zijn overgenomen, en welke aanbevelingen (mits in overeenstemming met het bewijs) zijn aangepast naar de Nederlandse context. ‘De novo’ aanbevelingen zijn gedaan in situaties waarin de werkgroep van mening was dat een aanbeveling nodig was, maar deze niet als zodanig in de WHO-richtlijn was opgenomen. Voor elke aanbeveling is vermeld hoe deze tot stand is gekomen, te weten: ‘WHO’, ‘aangepast van WHO’ of ‘de novo’.

Voor een verdere toelichting op de procedure van adapteren wordt verwezen naar de Bijlage Adapteren.

 

Literatuur

Agoritsas T, Merglen A, Heen AF, Kristiansen A, Neumann I, Brito JP, Brignardello-Petersen R, Alexander PE, Rind DM, Vandvik PO, Guyatt GH. UpToDate adherence to GRADE criteria for strong recommendations: an analytical survey. BMJ Open. 2017 Nov 16;7(11):e018593. doi: 10.1136/bmjopen-2017-018593. PubMed PMID: 29150475; PubMed Central PMCID: PMC5701989.

 

Alonso-Coello P, Schünemann HJ, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Rada G, Rosenbaum S, Morelli A, Guyatt GH, Oxman AD; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction. BMJ. 2016 Jun 28;353:i2016. doi: 10.1136/bmj.i2016. PubMed PMID: 27353417.

 

Alonso-Coello P, Oxman AD, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Vandvik PO, Meerpohl J, Guyatt GH, Schünemann HJ; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines. BMJ. 2016 Jun 30;353:i2089. doi: 10.1136/bmj.i2089. PubMed PMID: 27365494.

 

Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, Fervers B, Graham ID, Grimshaw J, Hanna SE, Littlejohns P, Makarski J, Zitzelsberger L; AGREE Next Steps Consortium. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ. 2010 Dec 14;182(18):E839-42. doi: 10.1503/cmaj.090449. Epub 2010 Jul 5. Review. PubMed PMID: 20603348; PubMed Central PMCID: PMC3001530.

 

Hultcrantz M, Rind D, Akl EA, Treweek S, Mustafa RA, Iorio A, Alper BS, Meerpohl JJ, Murad MH, Ansari MT, Katikireddi SV, Östlund P, Tranæus S, Christensen R, Gartlehner G, Brozek J, Izcovich A, Schünemann H, Guyatt G. The GRADE Working Group clarifies the construct of certainty of evidence. J Clin Epidemiol. 2017 Jul;87:4-13. doi: 10.1016/j.jclinepi.2017.05.006. Epub 2017 May 18. PubMed PMID: 28529184; PubMed Central PMCID: PMC6542664.

 

Medisch Specialistische Richtlijnen 2.0 (2012). Adviescommissie Richtlijnen van de Raad Kwalitieit. http://richtlijnendatabase.nl/over_deze_site/over_richtlijnontwikkeling.html

 

Neumann I, Santesso N, Akl EA, Rind DM, Vandvik PO, Alonso-Coello P, Agoritsas T, Mustafa RA, Alexander PE, Schünemann H, Guyatt GH. A guide for health professionals to interpret and use recommendations in guidelines developed with the GRADE approach. J Clin Epidemiol. 2016 Apr;72:45-55. doi: 10.1016/j.jclinepi.2015.11.017. Epub 2016 Jan 6. Review. PubMed PMID: 26772609.

 

Schünemann H, Brożek J, Guyatt G, et al. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available from http://gdt.guidelinedevelopment.org/central_prod/_design/client/handbook/handbook.html.

 

World Health Organization. Global guidelines for the prevention of surgical site infection,

second edition. Geneva: World Health Organization; 2018. (https://www.who.int/publications/i/item/9789241550475, accessed 12 June 2023).

 

Zoekverantwoording

Zoekacties zijn opvraagbaar. Neem hiervoor contact op met de Richtlijnendatabase.

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