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Keywords:

  • bacteriuria;
  • urological procedures

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Study Type – Therapy (case series)

Level of Evidence 4

What's known on the subject? and What does the study add?

Urine culture and antibiotics are usually given before outpatient urological procedures, namely cystoscopy or intravesical BCG therapy. Injudicious use of antibiotics promotes multidrug bacterial resistance.

Pretreatment antibacterial therapy may not be necessary before outpatient urological procedures in patients with bladder cancer. Such strategy facilitates timely intervention and avoids antibiotic resistance.

OBJECTIVES

  • • 
    To investigate the frequency of infectious complications after intravesical BCG therapy or cystoscopy in antibiotic-naive patients with bladder tumours who have asymptomatic bacteriuria.
  • • 
    The aim was to avoid antibiotics in infected patients undergoing these common outpatient urological procedures.

METHODS

  • • 
    A total of 354 patients received induction BCG therapy and another 663 patients underwent cystoscopy after submitting a voided urine sample for culture. They received no antibiotics before or after the procedure.
  • • 
    Significant bacteriuria was defined as >104 or >105 colony-forming units per millilitre with a single organism.
  • • 
    The patients were followed for 3 months for onset of febrile UTI, defined as dysuria and fever >38 °C requiring antibiotics.

RESULTS

  • • 
    Ninety BCG-treated patients (25%) and 114 cystoscopy patients (17%) had bacteriuria.
  • • 
    After BCG therapy, two patients with infected urine (2.2%) and three with sterile cultures (1.1%) had febrile UTIs (P= 0.17).
  • • 
    After cystoscopy, four infected patients (3.5%) and five uninfected patients (1%) had febrile UTIs (P= 0.08).
  • • 
    All UTIs resolved within 24 h with oral antibiotics, and none of the patients was admitted for bacterial sepsis.

CONCLUSIONS

  • • 
    Antibacterial prophylaxis before intravesical BCG therapy or outpatient cystoscopy does not appear to be necessary in patients with asymptomatic bacteriuria.
  • • 
    Such strategy avoids overuse of antibiotics, reducing drug-resistant bacterial infections.

INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Asymptomatic bacteriuria is common in adults and does not normally require treatment [1]. An exception is if patients undergo urological procedures. Practice guidelines recommend antibiotics to sterilize the urine before invasive procedures, especially in patients at risk for UTI [2]. Risk factors include advanced age, anatomical anomalies of the urinary tract, diabetes, poor nutrition, smoking status, chronic steroid use, immune deficiency or catheters [3]. Since patients with bladder cancer commonly have one or more of these risk factors, urologists usually give prophylactic antibiotics before cystoscopy or intravesical BCG therapy, aiming to prevent urinary infection or bacterial sepsis.

Unnecessary antibiotics to treat subclinical infection cause multidrug bacterial resistance, which is now a major health concern [4]. Intravesical therapy and flexible cystoscopy entail minimal trauma to the bladder and may not induce symptomatic UTI in infected patients. This pattern of care prospective study investigates the frequency of infectious complications after BCG therapy and surveillance cystoscopy in antibiotic-naive patients with bladder tumour who have asymptomatic bacteriuria. Such strategy facilitates timely interventions and avoids overuse of antibiotics.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Consecutive patients with bladder cancer seen as outpatients to receive induction BCG therapy or to undergo surveillance cystoscopy were eligible. All agreed to participate in this institutional review board approved study and provided informed consent. No patient was febrile or had symptoms of a UTI, and they were not receiving antibiotics. Patients with prosthetic joints or heart valves were not excluded. Immediately before starting BCG therapy or undergoing cystoscopy, each patient submitted a clean-catch voided urine sample for bacteriological studies. Urine cultures were classified as negative or positive. A negative culture yielded no growth. Significant bacteriuria was defined as a positive culture of >104 or >105 colony-forming units per millilitre with a single organism.

Patients underwent instillations of BCG through a small urethral catheter once a week for 6 weeks and did not receive antibiotics. They were monitored each week during treatments and then weekly by phone. Flexible digital surveillance cystoscopy used a sterile technique. Small papillary tumours were fulgurated. The procedure averaged 5–10 min. After BCG therapy and cystoscopy, patients were given a fact card with instructions to call if they had dysuria or a temperature of 38 °C. A nurse phoned patients weekly for a month after the interventions, and then monthly for 3 months, to inquire as to their status.

Endpoint was frequency of febrile UTI, defined as a fever of 38 °C or higher and a positive urine culture within 3 months after cystoscopy or last BCG treatment. Antibiotics prescribed for any reason by other physicians was considered an adverse event. Sample size was based on a projected proportion of 20% of patients with bacteriuria [5] and less than 5% developing a UTI, with no difference between infected and uninfected patients. The chi-squared test was used to test the correlation of bacteriuria with frequency of UTI, with a two-sided significance level of 0.05.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

In all, 1017 patients with bladder tumours were evaluated – 354 received BCG therapy and another cohort of 663 patients underwent surveillance cystoscopy. None received antibiotics before the procedure. Patient characteristics and results by urological procedure are shown in Table 1. The median age of the patients was 68 years (range 24–100 years), and the majority were males (77%). The groups were balanced for patients at risk for urinary infection, including prior or current smokers, diabetics, symptomatic prostatic obstruction requiring medication, age older than 65 years, or chronic steroid use for transplants, lupus, cirrhosis or rheumatoid arthritis.

Table 1. Patient characteristics and results by urological procedure
VariableBCG therapyCystoscopy
  • CFU, colony-forming unit.

  • *

    Positive for pyuria, nitrites or microscopy.

  • **

    P= 0.17; +P= 0.08 (Pearson chi-squared test).

No. of patients354663
Age, median (range)67 (36–99)69 (24–100)
Sex, males269 (76%)507 (77%)
Prior/current smoker275 (78%)490 (74%)
Increased risk of urine infection  
 Diabetes28 (8%)46 (7%)
 Prostatic obstruction62 (23%)127 (25%)
 Age 65 years or older240 (68%)463 (70%)
 Steroids18 (5%)40 (6%)
 Paraplegic (condom catheter)10
Tumours fulgurated at cystoscopyNA70 (11%)
Abnormal urinalysis*155 (44%)194 (29%)
Positive urine culture  
 Yes (>104 or >105 CFU/mL)90 (25%)114 (17%)
 No (no growth)264 (75%)549 (83%)
Febrile UTI  
 Positive urine culture2 (2.2%)**4 (3.5%)+
 Negative urine culture3 (1.1%)5 (1%)

Of the BCG-treated patients, 25% had significant bacteriuria compared with 17% of the cystoscopy patients. Infecting organisms included Escherichia coli in 78 patients, Enterococcus in 73, Staphylococcus in 30, Gardnerella in eight, Streptococcus in six, Klebsiella in four, and one each of Pseudomonas, Proteus, Mycobacteria, Enterobacter or Bacteroides species.

Two patients (2.2%) with positive urine cultures developed a febrile UTI after completing induction BCG therapy compared with three patients (1.1%) with negative cultures (P= 0.17); after undergoing cystoscopy, four infected patients (3.5%) and five uninfected patients (1%) had a symptomatic UTI (P= 0.01). All resolved with culture-sensitive antibiotics within 12–24 h. No patient was admitted for bacterial or BCG sepsis.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

The major finding of this study is that patients with bladder tumour with bacteriuria were able to safely undergo two common urological interventions, intravesical BCG and cystoscopy, and not require pretreatment antimicrobial therapy to sterilize the urine. Infectious complications occurred in less than 4% of infected and uninfected patients, and none developed bacterial sepsis. Although febrile UTIs were more frequent in infected patients, the difference, limited by few adverse events, was insignificant. A multivariable analysis of risk factors for infection, including age, sex, smoking status, comorbidity and abnormal urinalysis or positive urine culture, was unable to identify which patients were more likely to develop a febrile UTI. None of the patients who had tumours fulgurated developed a UTI.

This is the only study investigating intravesical BCG in patients with infected bladder tumour [6], and further studies are warranted. Prophylactic antibiotics have been evaluated before cystoscopy in randomized controlled trials. However, they investigated only patients who started with sterile urine, and the results are mixed; some studies show antibiotics reduce the frequency of febrile UTIs over placebo [7,8] and others show no benefit [9,10]. One study was truncated because of an unanticipated infection rate of only 0.85% in control patients, making it impossible to detect a benefit for prophylactic antibiotics [10]. The largest randomized trial enrolling 2481 patients showed that the rate of bacteriuria after cystoscopy was reduced from 9% in a placebo group to 3% in patients receiving ciprofloxacin prophylaxis [8]. Clinically significant urinary infections were infrequent (five patients) and similar among the two groups, indicating that bacteriuria rarely portends serious infection. Such data further indicate that a randomized trial to test reduction in clinically significant UTIs using routine antimicrobial therapy is not feasible because it would expose the majority of patients to unnecessary antibiotics when fewer than 4% eventually require such treatment.

Antibiotic prophylaxis is common in urology patients and ciprofloxacin is the most frequently given antibiotic before outpatient urological procedures. As a result, drug-resistant infections are becoming more frequent, now approaching 30% for ciprofloxacin [11]. The Centers for Disease Control and Infection has launched an infectious awareness initiative for patients with cancer, asking oncologists to practise ‘antibiotic stewardship’, i.e. to avoid the indiscriminate use of antibiotics [12].

Asymptomatic bacteriuria is common in patients with bladder cancer undergoing induction BCG therapy and outpatient flexible surveillance cystoscopy. Routine antimicrobial prophylaxis seems unnecessary, even in infected patients, because clinically significant UTIs are rare and easily treated. Avoiding indiscriminant use of antibiotics in such cases facilitates timely interventions and reduces bacterial resistance.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES