Guidelines for the perioperative prophylaxis in urological interventions of the urinary and male genital tract

Transcription

1 International Journal of Antimicrobial Agents 17 (2001) Guidelines for the perioperative prophylaxis in urological interventions of the urinary and male genital tract Kurt G. Naber a, *, Alfons G. Hofstetter b, Peter Brühl c, Karl-Horst Bichler d, Cordula Lebert e, Working Group Urinary Tract Infections of the Paul Ehrlich Society for Chemotherapy 1, Working Group Urological Infections of the German Society for Urology 2 a Urologic Clinic, Hospital St. Elisabeth, St. Elisabethstrasse 23, D Straubing, Germany b Department of Urology, Uni ersity of Munich, Munich, Germany c Department of Urology, Uni ersity of Bonn, Bonn, Germany d Department of Urology, Uni ersity of Tübingen, Tubingen, Germany e Hospital of Nürnberg, Nurnberg, Germany 1. Introduction Almost 50 years after its introduction, perioperative prophylaxis is still controversial. Whereas a clear benefit was established for certain surgical operations especially for those of the categories clean-contaminated and contaminated, e.g. elective colonic surgery [1], there was no general consensus on the use of antibacterial prophylaxis for elective operations of the category clean. This is because studies including sufficient number of patients for meaningful statistical analysis are absent. Moreover, the traditional classification of surgical procedures according to Cruse [2] into clean, clean-contaminated, contaminated and dirty does not adequately describe the risk of infection. Numerous patients and surgical conditions, such as duration of operation, blood loss etc. have been demonstrated to correlate with risk of infection [3]. Such risk factors can also lead to infectious complications even in clean operations [4]. The significance of each factor, however, is not yet quantified. This is especially true for open operations and endoscopic procedures in urology [5]. Prospective randomised studies are absent. Currently, most studies are poorly designed. The differentiation Translated into English by permission, from a paper in German published in Chemotherapie Journal 2000; 9: * Corresponding author. Tel.: ; fax: address: naberk@klinikum-straubing.de (K.G. Naber). 1 Chairman: Kurt G. Naber. 2 Chairman: Alfons G. Hofstetter. between therapy and prophylaxis is not clear. Evaluation of risk factors is unsatisfactory, and the terms bacteriuria and infection are not critically used [6]. In addition, many of these studies lack knowledge of pharmacokinetics and pharmacodynamics of the antimicrobial agents, bacterial pathogenicity and resistance, and the role of nosocomial infections [6,7]. It is thus not surprising that the literature is inconclusive in regard to prophylaxis, showing negative, as well as positive results for every type of urological intervention. A survey of 320 German urologists revealed controversial opinions about perioperative antibiotic prophylaxis [8]. Antibiotic prophylaxis was administered in more than half of the procedures involving the urinary tract, and most urologists used prophylaxis, when opening the intestine. There was, however, little agreement on the choice of antibiotics and the duration of prophylaxis. Consequently, guidelines for the indication of perioperative prophylaxis in urology are certainly necessary. In this paper, we present practical recommendations. These recommendations are based on clinical studies, expert opinion, and professional consensus. The common principles for perioperative prophylaxis (Table 1), a result of a consensus conference of the Paul Ehrlich Society for Chemotherapy [9], were also considered. 2. Goals of perioperative antibacterial prophylaxis The aim of perioperative prophylaxis is to limit infection related to intervention. However, it can not compensate for poor hygiene and operative technique /01/$ - $ Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved. PII: S (00)

2 322 K.G. Naber et al. / International Journal of Antimicrobial Agents 17 (2001) Antibiotic prophylaxis is only one component of infection prevention management. Other important factors should not be neglected, e.g. catheter care and closed drainage system [6,10 12]. The end points of perioperative prophylaxis in urology are debatable. It is generally agreed that its main aim in urology is to prevent symptomatic or febrile genito-urinary infections, such as acute pyelonephritis, prostatitis, epididymitis and urosepsis, as well as serious wound infections. Should this be extended to include postoperative asymptomatic bacteriuria or even a small wound infection, which could easily be treated on an outpatient basis? On the other hand, is prevention of postoperative pneumonia and sepsis also an issue of perioperative prophylaxis? Perioperative antibacterial prophylaxis in urology certainly has to go beyond the traditional aim of prophylaxis, which is the prevention of wound infections [6,13,14]. In TUR of the prostate, several controlled studies have shown that the rate of postoperative bacteriuria can be reduced by perioperative prophylaxis. In some studies, this translates into reduction of symptomatic urinary tract infections or prevention of febrile episodes [15 18]. Since the rate of septic complications is generally below 1%, a prospective study will require large numbers of patients to be recruited to reach statistical significance. Until now, most of our knowledge on the prevention of urosepsis has been derived from retrospective studies only [19]. 3. Indications for perioperative antibacterial prophylaxis The need for prophylaxis depends not only on the type of intervention but also on the risk for each individual patient. Patient s risk factors, such as chronic debility, diabetes mellitus, immunosuppression, and increased risk for endocarditis in-patients with artificial cardiac valves have to be considered. Increased exposure to endogenous bacteria can be expected in procedures that include bowel segments, transrectal biopsy of the prostate and in contaminated tissue. Furthermore, bacterial contamination in the urinary tract is often associated with long-term drainage (catheter, splints, nephrostoma etc.) or with obstruction due to urolithiasis and tumors (Table 2). In infected stones pretreated with antibiotics, persistence of pathogens within the stone must be considered even if the preoperative urine is sterile. In the absence of risk factors and with sterile urine, prophylaxis may not be necessary. However, if the anticipated risk changes during operation, (e.g. high blood loss, duration of operation longer than 2 3 h, accidental perforation of the intestine or the urinary tract), intraoperative administration of antibiotics Table 1 General aspects of perioperative antibacterial prophylaxis [9] 1 Perioperative antibacterial prophylaxis is an important factor for quality control of operative procedures. 2 The primary aim of perioperative prophylaxis is to limit postoperative infectious complications. This includes local, e.g. wound infection, as well as systemic infections, e.g. deep respiratory and urinary tract infections. 3 Perioperative antibacterial prophylaxis should be adapted to the risk of the individual patient. 4 The risk for infection starts at the beginning of the operation. Considering the pharmacokinetics of the substance, an effective antibacterial concentration has to be maintained throughout the whole period at risk. 5 A too early administration of the antibiotic is not useful, probably even harmful. 6 An antibacterial substance is selected according to the risk for infection (expected pathogens and individual patient s risk) and the regional epidemiology. Of specific interest are secondary infections due to Gram-negative bacteria. 7 For perioperative antibacterial prophylaxis only substances should be selected which turned out to be effective in controlled clinical studies. 8 For the individual patient, emergence of resistant pathogens may be of minimal risk, but this is not true for the entire hospital. should be considered. In the preoperative work-up of the patient, any infection, especially of the urinary tract, should be identified. If an infection is present and the intervention cannot be delayed, antibiotic therapy should be given on an empirical basis before surgery and continued afterwards, preferably according to sensitivity testing, when it becomes available. From a microbiological point of view, any perioperative antibiotic prophylaxis represents a compromise. The desired effect of reducing the bacterial load has to be balanced against the negative consequences, e.g. drug induced adverse events and possible selection of resistant strains (Fig. 1). Table 2 General risk factors Risk factors due to Patient s condition Reduced general condition Metabolic dysfunction, e.g. diabetes mellitus Immunosuppression Special risk, e.g. artificial cardiac valve Reoperation Increased bacterial load OP using bowel segments Transrectal biopsy of the prostate Longterm urinary drainage Urinary obstruction

3 K.G. Naber et al. / International Journal of Antimicrobial Agents 17 (2001) Choice of antibiotics Fig. 1. Perioperative antibacterial prophylaxis has to be balanced between reduction of bacterial load and increase of adverse events and selection of resistant strains. 4. Timing and duration of perioperative antibacterial prophylaxis Studies have shown that wound infections are usually prevented by administration of an antibiotic before contamination takes place [20 22]. High blood levels are needed at the start of the surgical procedure and, therefore, timing and dosing are important factors [23]. In clinical practice, the best time for administration is min prior to start of operation, when anaesthesia is initiated, if the antibiotic is given intravenously. If intra-operative complications occur, the antibiotic should be given immediately. This approach has been particularly effective in emergency general surgery [24]. Clinical studies have shown a significant increase of postoperative infections if the single prophylactic dose of antibiotic is not given within but more than 1 h before or after the start of the operation [21]. Any antibiotic given after wound closure will not alter the rate of wound infection. The rate of adverse events and the selection pressure for antibiotic resistance will increase. There are, however, no studies demonstrating specifically such a correlation in endoscopic procedures. Extrapolation of these results seems, however, reasonable. Generally, a single full dose of a suitable antibiotic will not be less effective than multiple dosing. Only in the case of prolonged intervention ( h) is an additional dose required, whose size and timing are dictated by the pharmacokinetics. Antibiotic prophylaxis should not be continued for more than 24 h [10,25 27]. The administration of antibiotics for more than 1 day is not considered to be prophylaxis, but therapy. This may become necessary in case of severe contamination. Interventional therapy becomes necessary. A suitable antibiotic should be highly effective, well tolerated and cheap. Its antibacterial spectrum should include the expected range of normal flora and pathogens usually found at the site of operation and on the surrounding skin and mucous membranes. In-patients with preceding antibiotic therapy account should be taken of the altered bacterial spectrum and its resistance pattern (Table 2). Broad-spectrum antibiotics such as the third generation cephalosporins, acylaminopenicillins plus beta-lactamase inhibitors and carbapenems, should only be used sparingly, i.e if the site of operation is contaminated with multi-resistant bacteria. Their administration should usually be restricted to the treatment of severe infections [10,25,27]. This applies also to the routine use of vancomycin in prophylaxis, e.g. patients on dialysis or with suspected infections caused by venous catheters. Such usage may select vancomyin-resistant enterococci. The choice of the antibiotic also depends on its pharmacokinetic properties, and dosage should secure effective tissue levels during the operation. Depending on the antibiotic s half-life and the duration of the intervention, an additional dose may be indicated. For urological indications, it is advisable to choose a drug with high urinary concentrations. 6. Mode of application Parenteral and preferably intravenous administration of the antibiotic is primarily recommended to reach sufficient tissue concentrations, particularly in an emergency. Oral administration of a fluoroquinolone in patients undergoing transurethral resection and transrectal biopsy of the prostate had been successful [18,28]. Oral antibiotics with high bioavailability should only be administered if intestinal reabsorption is secured. Fluoroquinolones of group 2 or 3, according to the classification of the Paul Ehrlich Society for Chemotherapy [29] are suitable, which can also be used for systemic therapy; they are highly excreted by the kidneys. From pharmaco-economic aspect, oral application 1 2 h before the procedure is an attractive alternative. 7. Recommendations according to type of urological interventions For perioperative antibacterial prophylaxis, the urological interventions are categorised into open and endoscopic-instrumental operations (including extracorporal shock wave lithotripsy [ESWL]) and di-

4 324 K.G. Naber et al. / International Journal of Antimicrobial Agents 17 (2001) Table 3 Most common pathogens causing nosocomial urinary tract infections Escherichia coli Proteus mirabilis Enterococci Pseudomonas spp. Staphylococci (Candida spp.) agnostic procedures (Tables 3 and 4). The recommended antibiotics are shown in Table Urological operations including bowel segments Intestinal microorganisms are usually responsible for the development of postoperative infections, which include intestinal segments. The most frequent are Escherichia coli and other Enterobacteriaceae, enterococci, anaerobes and streptococci, as well as staphylococci in wound infections. Aminopenicillins combined with a beta-lactamase inhibitor (BLI) and second generation cephalosporins in combination with metronidazole, are recommended; correspondingly in high risk patients acylaminopenicillins combined with BLI and third generation cephalosporins could be used. It is a matter of discussion but not proven by clinical studies, whether continent pouches or bladder replacements require prolonged preventive antibiotic therapy. Indwelling catheters and regular irrigation of the Table 4 Classification of urological operations and interventions Open operations Urinary tract including bowel segments Urinary tract without bowel segments Outside the urinary tract Special operations Using implants, e.g. penis and sphincter prosthesis Reconstructive genital operations Acute operation Secondary operation Endoscopic-instrumental operations Prostate Bladder Ureter and kidney Percutaneous litholapaxy Laparascopic operations Extracorporal shock wave lithotripsy (ESWL) Diagnostic inter entions Prostate biopsy: transrectal and perineal Urethrocystoscopy Ureterorenoscopy Percutaneous pyeloscopy Laparoscopic procedures colonised intestinal segment (neobladder) with increase of pressure could result in postoperative bacteraemia. Local antibiotic irrigation is, however, not recommended. 9. Urological operations without bowel segments General antibiotic prophylaxis is not required in open operations without bowel segments. It is necessary only in patients with an increased risk of infections (Table 2). The most frequent infecting organism is E. coli followed by enterococci, Proteus spp. and Klebsiella spp. in the urinary tract and staphylococci for wound infections. In cases of preceding antibiotic therapy even for remote infections, selection of resistant bacterial strains and if, the patient is hospitalised for a longer period, the bacterial spectrum of nosocomial pathogens must be taken into consideration (Table 3). A perioperative antibiotic regime recommended for prophylaxis according to the expected range of pathogens includes fluoroquinolones with sufficient renal excretion, aminopenicillins with BLI or the second generation cephalosporins. Third generation cephalosporins or acylaminopenicillins with BLI are available as alternatives for patients with an increased risk of infection, patients treated earlier with an antibiotic or those with permanent catheter or nephrostomy drainage. 10. Urological operations outside of the urinary tract Perioperative antibiotic prophylaxis is not generally recommended except in long reconstructive operations on the genital area or with implant surgery (prosthesis of sphincter or penis). It can be achieved with first or second generation cephalosporins, since staphylococcal infection predominates. In elective operations, in which any wound infection may become a serious event, e.g. loss of implant, the patient might be screened preoperatively for methicillin- resistant Staphylococcus aureus (MRSA) by a nasal swab. 11. Endo-urological operations (including extracorporal shock wave lithotripsy) Perioperative prophylaxis is only recommended in cases of increased risk of infection (Table 1). Appropriate antibiotic regimens are fluoroquinolones with sufficient renal excretion, aminopenicillins with BLI, second generation cephalosporins and cotrimoxazole. Comparative studies of short-term prophylaxis using fluoroquinolones versus co-trimoxazole are not available. Perioperative prophylaxis in patient without risk factors is questionable.

5 K.G. Naber et al. / International Journal of Antimicrobial Agents 17 (2001) Table 5 Recommendations for perioperative antibacterial prophylaxis in urological interventions Procedure Most common Antibiotic(s) of choice Alternative antibiotic(s) Remarks pathogen(s) Open operations Urinary tract including Enterobacteriaceae, Aminopenicillin+BLI a In high risk patients: In all patients bowel segments enterococci, anaerobes cephalosporin 2 cephalosporin 3, Urinary tract without streptococci, wound infection: staphylococci Enterobacteriaceae, +metronidazole Fluoroquinolone b, acylaminopenicillin+bli In high risk patients: In patients with increased bowel segments enterococci; wound cephalosporin 2, cephalosporin 3, risk of infection infection: staphylococci aminopenicillin+bli acylaminopenicillin+bli Implant/prosthesis; Staphylococci Cephalosporin 1 /2 In all patients penis sphincter Reconstructive genital Staphylococci Cephalosporin 1 /2 In secondary operations operation and in patients with increased risk of infection Other interventions Staphylococci Cephalosporin 1 /2 In patients with increased outside of the urinary tract risk of infection Endoscopic-instrumental operations Prostate, bladder, ureter, Enterobacteriaceae Fluoroquinolone b, Cotrimoxazole In patients with increased kidney, incl. staphylococci enterococci aminopenicillin+bli, risk of infection Percutaneous cephalosporin 2, litholapaxy and ESWL c fosfomycin trometamol Diagnostic inter entions Transrectal biopsy of the Enterobacteriaceae, Fluoroquinolone b, Aminoglycoside In all patients prostate (with thick enterococci, anaerobes, aminopenicillin+bli, needle) streptococci cephalosporin 2 +metranidazole Perineal biopsy of the Enterobacteriaceae, Fluoroquinolone b, Cotrimoxazole In patients with increased prostate, enterococci, staphylococci aminopenicillin+bli, risk of infection urethrocystoscopy, ureterorenoscopy, percutaneous pyeloscopy, laparoscopic procedures cephalosporin 2 a BLI, beta-lactamase inhibitor. b Fluoroquinolone with sufficient renal excretion. c ESWL-extracorporal shock wave lithotripsy. 12. Diagnostic urological intervention Perioperative antibacterial prophylaxis, e.g. with an aminopenicillin plus a BLI, a fluoroquinolone with sufficient renal excretion [28,29], or an aminoglycoside [30], is generally recommended only in transrectal prostate biopsy. In other diagnostic procedures of the urinary tract, prophylaxis is only suggested in high risk patients. A fluoroquinolone or cotrimoxazole is appropriate. 13. Postoperative drainage of the urinary tract When continuous urinary drainage is left in place after an operation, prolonged perioperative antibacterial prophylaxis is not indicated [31]. Asymptomatic bacteriuria has to be treated before any urinary tract intervention or when the drainage tube is removed. In case of short-term catheterisation and persistent asymptomatic bacteriuria in female patients, a short-term antibacterial regimen is sufficient [32]. 14. Pharmaco-economics The results of the largest study performed world-wide in the control of nosocomial infections (SENIC) have shown that urinary tract infections (42%), followed by wound infections (24%), are the most frequent cause of infective postoperative complications [33]. If these infections can be prevented, there is obviously great potential for cost-reduction in surgery. However, cost benefit considerations of perioperative antibacterial

6 326 K.G. Naber et al. / International Journal of Antimicrobial Agents 17 (2001) prophylaxis have not been fully addressed. One exception is a meta-analysis of eight prospective, randomised, controlled trials in ESWL, where there was a 50% reduction of median risk of UTI in-patients treated with prophylaxis (2.1% vs. a median risk of 5.7%). This difference was statistically significant (P=0.0005). The authors also calculated a cost-benefit for those patients having received prophylaxis [34]. Similar studies e.g. for TUR of the prostate and for bladder tumors are missing. Nevertheless, an appreciation of cost-saving by perioperative prophylaxis can only be evaluated by suitable studies. References [1] Clarke IS, Condon RE, et al. Preoperative oral antibiotics reduce septic complications of colon operations: results of a prospective, double-blind clinical study. Ann Surg 1979;186: [2] Cruse PJE, Foord R. The epidemiology of wound infection: A 10-year old prospective study of wounds. 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