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Antimicrobial therapy of complicated urinary

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Initiative: SWAB Number of modules: 14
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UTI in patients with ADPKD

Last review: 3/1/13

Question

What is the optimal treatment in patients with Polycystic Kidney Disease?

 

Recommendation

PET scan can be useful to identify a cyst infection. PET scan is considered positive when increased Fludeoxyglucose (FDG) uptake is demonstrated in at least one cyst.

 

For the diagnosis of a cyst infection the following criteria should be used:

  • Cyst infection is considered as definite in the presence of a cyst aspiration showing evidence of infection (neutrophils debris and/or micro-organism).
  • Cyst infection is considered likely in the presence of all of the following features: fever (temperature >38.5°C for >3 days), abdominal pain (particularly a palpable area of renal or liver tenderness), increased C-reactive protein (CRP; >50 mg/L), and the absence of any significant recent intracystic bleeding or other causes of fever.

 

Duration of treatment in case of a pyelonephritis in patients with autosomal dominant polycystic kidney disease is not different from that in other patients with a complicated UTI.

 

In case of a cyst infection, it is recommended to start initially with ciprofloxacin, but to use the culture results to tailor treatment.

 

A period of 4-6 weeks is recommended for the treatment of an infected cyst.

 

In case of large (> 5 cm) infected cysts, early drainage is advised in combination with antibiotic treatment

 

Considerations

No data are available on a comparison of antimicrobial regimens for this group of patients.

For the above-mentioned reasons and the known resistance patterns of the causative uropathogens, it is recommended to start initially with ciprofloxacin, but to use the culture results to tailor treatment.

Duration of treatment in case of a pyelonephritis is not different from that in other patients with a complicated UTI. The optimal duration for treatment of infected cysts is unknown. Usually a longer period of 4-6 weeks is recommended.

 

Evidence

This guideline does not include individual introductions to each module. A general introduction can be found in the attachments under the heading 'related'.

Level 3 

The incidence of lower and upper UTI and cyst infections is high in patients with autosomal dominant polycystic kidney disease [(150) C, (144) C, (145) D].

Level 3

Eschericha coli is the most common causative organism, accounting for 75% of cases [(144) C; (150) C].

Level 3 

Urinary cultures are often negative, since the cysts may not be in communication with the collecting system [(150), C].

Level 3 

Ultrasound, CT scan and MRI failed to detect the infected cyst in the majority of patients [(144) C].

Level 3

PET scan can be useful to identify a cyst infection  [(144) C; (151) D; (148) D; (152) D].

 

 

 

 

Level 4

PET scan is considered positive when increased Fludeoxyglucose (FDG) uptake is demonstrated in at least one cyst and the following criteria can be used for the diagnosis of a cyst infection [(144) D]:

- Cyst infection is considered as definite in the presence of a cyst aspiration showing evidence of infection (neutrophils debris and/or micro-organism).

- Cyst infection is considered likely in the presence of all of the following features: fever (temperature >38.5°C for >3 days), abdominal pain (particularly a palpable area of renal or liver tenderness), increased C-reactive protein (CRP; >50 mg/L), and the absence of any significant recent intracystic bleeding or other causes of fever.

Level 3

To treat a cyst infection fluoroquinolones or TMP-SMX must be used. Penicillins and aminoglycosides often do not penetrate cysts [(144) C].

Level 4

In case of large (> 5 cm) infected cysts, early drainage is advised in combination with antibiotic treatment [(144) D].

Level 4

Efficacy of antibiotic treatment and infection eradication are defined by a good clinical response and at least two negative blood and/or urine cultures [(144) D].

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder, with a prevalence of 1:500-1000, and accounting for 4-10% of dialysis patients (144), (145). Approximately 50-75% of patients with ADPKD will have a UTI during their lifetime, most of them presenting as an uncomplicated lower UTI (Gibson, 1998 222 /id}. The incidence of complicated upper UTI has not been well evaluated, but ranged from 32% in a retrospective cohort and up to 56% in an autopsy study (146), (147). Discrimination between an upper UTI caused by a pyelonephritis or by a cyst infection can be difficult (145), (148).

Although cyst infection is reported as one of the most frequent complications of ADPKD (149), published data on this topic are relatively scarce and all data are retrospective.

 

In one of the largest studies in this field, a retrospective French cohort study of 389 patients with ADPKD (144), incidence rates of cyst infections were 0.01 episode per patient per year, accounting for hospitalization in 8.4% of the ADPKD patients  E. coli was the most common causing organism, accounting for 75% of cases, which suggests an ascending mechanism for cyst infection.

A more recent retrospective study from Albania (150) demonstrated in 180 ADPKD patients that 60% had a UTI during a 1-year follow-up period. UTI were more frequent in women than in men, 43% had a cyst infection, 38% a pyelonephritis and 19% a lower UTI. Again, E. coli was found in 75% of the patients. Blood culture was positive in only 10% of the patients, and urine culture was negative in 40%. Urinary cultures are often negative, since the cysts may not be in communication with the collecting system.

 

Radiological imaging for the diagnosis of infected cysts is often of little help because the cyst changes, induced by an infection, are not very specific. PET scan can be useful to identify the infected cysts (151), although PET scan has not been evaluated in intracystic bleeding, which is the main differential diagnosis of cyst infections in these patients. In the above-mentioned study from Sallee et al. (144), ultrasound, CT scan and magnetic resonance imaging (MRI) failed to detect a likely or definite cyst infection (for definitions, see below) in 94%, 82% and 60%, respectively, and yielded negative results in more than half of the patients with a definite diagnosis of cyst infections. In contrast, PET scan proved to be helpful for the detection of cyst infection in 100% of the cases, which was also shown is smaller case series (148), (152). PET scan was considered positive when increased Fludeoxyglucose (FDG) uptake was demonstrated in at least one cyst, and the diagnosis was based on the following criteria (144):

  • Cyst infection is considered as definite in the presence of a cyst aspiration showing evidence of infection (neutrophils debris and/or micro-organism).
  • Cyst infection is considered likely in the presence of all of the following features: fever (temperature >38.5°C for >3 days), abdominal pain (particularly a palpable area of renal or liver tenderness), increased C-reactive protein (CRP; >50 mg/L), and the absence of any significant recent intracystic bleeding (based on the results of an abdominal CT scan), or other causes of fever.

The Guideline committee recommends to use these criteria in clinical practice.

 

Treatment

As far as possible, a distinction should be made between cyst infection and pyelonephritis, since most cysts are not in communication with a filtering glomerulus. As a consequence, in case of a cyst infection, the antibiotics must enter the cyst by diffusion, which is more efficient for lipid soluble drugs like fluoroquinolones and TMP-SMX. Penicillins and aminoglycosides often do not penetrate cysts. In case of large (> 5 cm) infected cysts, early drainage in combination with antibiotic treatment is advised (144).  Efficacy of antibiotic treatment and infection eradication are defined by a good clinical response and at least two negative blood and/or urine cultures (144).

Polycystic Kidney Disease AND Urinary Tract Infections

Pubmed: 160 hits, all abstracts screened, 11 articles included

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This guideline does not include evidence tables.

Authorization date and validity

Last review  : 01-03-2013

Last authorization  : 01-03-2013

Planned reassessment  :

This guideline was developed and approved by representatives of the professional medical societies, mentioned in the introduction and methods sections and therefore represents the current professional standard in 2013. The guideline contains general recommendations. It is possible that, in individual cases, these recommendations do not apply. Applicability of the guideline in clinical practice resorts to the responsibility of every individual practitioner. Facts or circumstances may occur, in which deviation of the guideline is justified, in order to provide optimal quality of care for the patient.

Initiative and authorization

Initiative:
  • Stichting Werkgroep Antibioticabeleid
Authorized by:
  • Nederlands Huisartsen Genootschap
  • Nederlandse Internisten Vereniging
  • Nederlandse Vereniging voor Medische Microbiologie
  • Nederlandse Vereniging voor Obstetrie en Gynaecologie
  • Nederlandse Vereniging voor Urologie
  • Stichting Werkgroep Antibioticabeleid

General details

Development of this guideline was supported and financed by the SKMS (Kwaliteitsgelden Medisch Specialisten).

Scope and target group

The objective of these guidelines is to update clinicians with regard to important advances and controversies in the antibiotic treatment of patients with complicated urinary tract infections (UTIs).

 

The guidelines described here cover the empirical antimicrobial therapy of adult patients (for this guideline 12 years or older) with a complicated UTI admitted to a hospital (emergency room or ward) in the Netherlands. Uncomplicated UTIs are treated predominantly by the general practitioner. For the relevant guidelines, see the recently updated Standard for Urinary Tract Infections of the Dutch Society of General Practitioners (NHG). We have tried to adhere to this standard insofar as possible. Urethritis and epididymitis are not included in this guideline.

The Guidelines give a general therapy advice for all UTI with systemic symptoms because, at first presentation of a patient, it is not always possible to differentiate between an acute prostatitis, pyelonephritis or urosepsis. In addition, this differentiation has no consequences for the choice of empirical antimicrobial therapy. Apart from these general guidelines, we give specific advice for certain groups of patients separately.

Samenstelling werkgroep

Preparation of the guideline text was carried out by a multidisciplinary committee consisting of experts, delegated from the professional societies for infectious diseases (VIZ), medical microbiology (NVMM), hospital pharmacists (NVZA), urology (NVU), gynaecology (NVO), nephrology (NFN) and general practice (NHG). After consultation with the members of these professional societies, the definitive guideline was drawn up by the delegates and approved by the board of SWAB.

 

  • Dr. S.E. Geerlings (coordinator, SWAB), Internal Medicine/Infectious Diseases specialist, Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam
  • Dr. C. van Nieuwkoop (VIZ, NIV), Internal Medicine, Emergency Medicine and Infectious Diseases specialist, Department of Internal Medicine, Hagaziekenhuis, the Hague
  • E. van Haarst (NVU), Urologist, Department of Urology, St. Lucas Andreas Hospital, Amsterdam
  • Dr. M. van Buren (NFN), Internal Medicine and Nephrology specialist, Department of Internal Medicine, Hagaziekenhuis, the Hague
  • Dr. B.J. Knottnerus (NHG), General Practitioner, Department General Practice, Academic Medical Center, Amsterdam
  • Dr. E. E. Stobberingh (NVMM), Medical microbiologist, Lab Medical Microbiology, Maastricht Univerisity Medical Center, Maastricht
  • Prof. dr. C.J. de Groot (NVOG), Gynaecologist, Department of Obstetrics and Gynaecology, Vrije Universiteit Medical Center, Amsterdam
  • Prof. dr. J.M. Prins (SWAB), Internal Medicine/Infectious Diseases specialist, Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam

 

The Guideline committee would also like to thank Frederique Bemelman (nephrologist) for her comments on the chapter about renal transplantation and Albert Vollaard (infectious disease specialist) for his comments on the subchapter about methenamine.

Declaration of interest

The SWAB employs strict guidelines with regard to potential conflicts of interests as described in the SWAB Format for Guideline Development (www.swab.nl). Members of the preparatory committee reported the following potential conflicts of interest:

 

SE Geerlings: for the RCTs mentioned in the reference numbers 84 en 168 (Beerepoot et al.): Ref 84: Cranberry capsules and placebo capsules for this trial were delivered by Springfield Nutraceuticals, Oud Beijerland, The Netherlands. Ref 168: Chr Hansen A/S, Denmark has the patents for Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 and donated the placebo capsules for this trial.

E v Haarst: has received speaker fees on a national urological symposium from GlaxoSmithKline, the manufacturer of amoxicillin-clavulanic acid.

Other authors: no potential conflicts of interest declared.

Patient involvement

This guideline does not include patient involvement.

Method of development

evidence based

Implementation

This guideline does not include an implementation strategy.

Methods and proces

This guideline was drawn up according to the recommendations for evidence-based development of guidelines (6), (Evidence-Based Richtlijn-Ontwikkeling (EBRO) and Appraisal of Guidelines Research and Evaluation (AGREE), www.agreecollaboration.org). The guidelines are derived from a review of literature based on the 9 key questions concerning the treatment of UTI. Studies were assigned a degree of evidential value according to the handbook of the Dutch Institute for Healthcare Improvement (Centraal Begeleidingsorgaan/Kwaliteitsinstituut voor de gezondheidszorg, CBO) (CBO. Evidence-based Richtlijnontwikkeling, handleiding voor werkgroepleden. Utrecht: CBO; 2007). Conclusions were drawn, completed with the specific level of evidence, according to the grading system adopted by SWAB (Table 1 and 2). The only exception concerns Nethmap, an annual report from which the resistance surveillance data were used. The Guideline committee cannot give Nethmap a level of evidence and decided to use an asterix (*), but is of the opinion that the results can be given substantial weight, since the surveillance data described in Nethmap cover 30% of the Dutch population. Subsequently, specific recommendations were formulated.

In order to develop recommendations for the optimal treatment of UTI, the literature was searched for the key questions. For each question a literature search was performed in the PubMed database (January 1966 to January 2012) as well as in the Cochrane Register of Controlled Trials (CENTRAL). For resistance surveillance data NethMap 2011 was used, and for the interpretation of susceptibility test results, in addition, reports of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) were used. When scientific verification could not be found, the guideline text was formulated on the basis of the opinions and experiences of the members of the Guideline committee.

Search strategy

Searches are available upon request. Please contact the Richtlijnendatabase.

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Prevention in patients with recurrent UTI