ARC Journal of Urology

AUTHOR DETAILS

Thuchchai Pipitpanpipit, M.D.

Division of Urology, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
[email protected]

Assoc. Prof. Pitak Santanirand, Ph.D.

Clinical Microbiology Unit, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
[email protected]

Assoc. Prof. Wisoot Kongchareonsombat, M.D.

Division of Urology, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
[email protected]

KEYWORDS

Antibiotic prophylaxis; trans-rectal prostatic biopsy; ciprofloxacin; cefixime; transient bacterae-mia

INTRODUCTION

Prostate cancer incidence rates have increased in recent years. In the United States of America (USA), accounting for the most common of all new cases of cancer in males, prostate cancer is the second leading cause of cancer death in American men, behind only lung cancer (1). In Thailand, prostate cancer is the eighth commonly diagnosed cancer (2), and the numbers of cases have gradually in-creased.

Trans-rectal prostatic biopsy is the mainstay method used for the diagnosis of prostate cancer (3). Al-though it is generally considered a safe procedure, complications secondary to biopsy have been some of the most common adverse events encountered in practice. Trans-rectal prostatic biopsy related to sepsis and septicaemia around 13% to 20% (4). Bacteria that cause these infections are Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterococcus (5, 6).

Pre-procedural antibiotic prophylaxis is recommended for all patients. This concept is based on the fact that 16% to 100% of cases of biopsy with no prophylaxis presented either asymptomatic bacteri-uria or transient bacteremia, increasing the risk for infectious complications, such as urinary tract in-fection (UTI), sepsis and Fournier’s syndrome (7). Currently, many urologists use prophylactic anti-biotic therapy to minimize infective complications after trans-rectal prostatic biopsy, but such therapy does not completely eliminate infection. The reported infection rate varies considerably in studies us-ing different antibiotic regimens (8-13). Nowadays, we prescribe the oral form of ciprofloxacin be-cause the drug, also called fluoroquinolone, is broad spectrum and penetrates the prostate gland well. Patients took the drug one day before undergoing biopsy, and they were then given ciprofloxacin for four days, but we found an infectious complication does not decrease. Moreover, the prevalence of the antibiotic resistance rate in E. coli is rapidly rising in Thailand (14) and also across the world (15-16).

The objective of this study is to compare the efficacy of antibiotic prophylaxis with ciprofloxacin ver-sus cefixime (both oral administration) to determine effective regulation in the future.

MATERIALS AND METHODS

Between June 2014 and June 2015, at the urologic clinic, Ramathibodi Hospital, 100 patients entered the study after giving informed consent. The inclusion criteria were: (i) digital rectal examination pos-itive; (ii) prostatic specific antigen (PSA) level>4 ng/ mL; (iii) from 55-85 years old; and (iv) accep-tance or informed consent form. The exclusion criteria were: (i) immunodeficiency; (ii) coagulopathy; (iii) UTI; (iv) took an antibiotic within one week before biopsy; (v) on urinary catheter; (vi) heart in-tervention history; (vii) refused informed consent form; and (viii) allergy to ciprofloxacin or cefixime.

The 100 patients were randomized into two groups, using computer-generated random numbers. The enema was administered on the day before biopsy was required. Oral prophylactic antibiotics were administered to all patients 30-60 minutes before the procedure. Patients in group 1 (50, mean age 67.7 years) received ciprofloxacin. In group 2, 50 patients (mean age 69.7 years) were given cefixime. During biopsy, sterile technique and local anaesthetic were applied. We used extended 12-core biopsy technique and collected blood culture within 24 hours. The volunteers were informed that complica-tions are especially serious events, and they were instructed to take medicine continuously for four days after the procedure. The volunteers were also told to make appointments 14 days later for the biopsy results and were followed up on for complications.

Descriptive statistics were used to analyze the data. Data analysis comparing the two treatment groups was assessed from an unpaired t-test and Fisher's exact test. The threshold for statistical significance was set at p<0.05.

RESULTS

For males with suspected prostate cancer, 50 patients were classified as group 1 (ciprofloxacin), and 50 patients were classified as group 2 (cefixime). The mean age of the patients was 67.70 +/- 7.3 and 69.70 +/- 7.9 years, respectively. No statistical significance was found between the two groups as shown in Table 1.

Transient bacteraemia was recorded for one patient (2%, Enterococcus) in group 2; the patient did not develop true bacteraemia. No significant difference was found between the two groups as shown in Table 2.

Dysuria was significantly higher in the cefixime group; there were no cases in group 1, and there were seven cases (14%) in group 2 as shown in Table 3. In terms of other complications, including acute urinary retention, hematuria, rectal bleeding, vasovagal syncope and hematospermia, no significant difference was found between the groups (p>0.05).

In both groups, the most common pathology was benign prostatic hyperplasia (BPH) (48.8% and 53.6%, respectively) as shown in Table 4.

DISCUSSION

Transient, usually asymptomatic bacteraemia occurs in a wide variety of procedures and manipula-tions, particularly those associated with mucous membrane trauma, thus increasing the risk for infec-tious complications, such as UTI, sepsis and Fournier’s syndrome (17). Therefore, trans-rectal prostat-ic biopsy is considered to be a harmful procedure.

Fluoroquinolone antibiotics, such as ciprofloxacin, are the most popular prophylactic agents used in trans-rectal prostatic biopsy (18). Ciprofloxacin has a broad spectrum of activity especially against most gram-negative organisms that cause UTIs (19). In recent years, there has been increasing micro-bial resistance to ciprofloxacin and other quinolones worldwide. For this reason, clinicians have been under increasing pressure to shift away from the use of quinolones to that of alternative antibiotics in recent years. In the present study, we evaluated whether oral cefixime could be used as an effective alternative antibiotic prophylaxis for men undergoing trans-rectal prostatic biopsy. Cefixime is a third-generation cephalosporin and is commonly used to treat bacterial infections of the ear, urinary tract, and upper respiratory tract (20). It can also be administered easily in an oral form, and our local resistance data in 2015 showed that ≈65% of coliforms that were isolated from urine samples were resistant to ciprofloxacin, whereas only 25% of coliforms were resistant to cefixime (14).

The present results show that the dysuria rates among men undergoing trans-rectal prostatic biopsy were significantly higher in the group receiving cefixime prophylaxis compared with those who received ciprofloxacin prophylaxis. No difference was found in the transient bacteraemia rate between these two regimes. This suggests that prophylaxis with cefixime failed to be better either because there was poor absorption of the antibiotic via the gastrointestinal tract or there was a low serum con-centration.

Based on the present results, we feel that cefixime is not an effective antimicrobial agent compared with ciprofloxacin in preventing post-trans-rectal prostatic biopsy transient bacteraemia, and it appears to show high rate of dysuria after trans-rectal prostatic biopsy. Until a more suitable, effective oral prophylactic agent is found, quinolone-based antibiotics should remain the antibiotic of choice for men undergoing trans-rectal prostatic biopsy, but this needs to be judged on a case-by-case basis.

CONCLUSION

Ciprofloxacin appears to be a superior prophylactic agent to cefixime in men undergoing trans-rectal prostatic biopsy. Changing antibiotic prophylaxis from a quinolone-based regime may therefore be putting our patients at an increased risk for serious infectious complications after trans-rectal prostatic biopsy.