DON’T SHOOT YOURSELF IN THE FOOT ICAAC/IDSA Conference, Washington DC, October 2008 – Poster presentation K1370 email: christopher.a.green@uhl-tr.nhs.uk, tel: 0044 116 258 6544, fax: 0044 116 258 7784 DON’T SHOOT YOURSELF IN THE FOOT C A GREEN1, S S BUKHARI1, J A STEPHENSON2, T R L GRIFFITHS2 1Department of Medical Microbiology, University Hospitals of Leicester NHS Trust, Leicester LE1 5WW, United Kingdom 2Department of Urology, University Hospitals of Leicester NHS Trust, Leicester LE1 5WW, United Kingdom ABSTRACT Background: As a measure to reduce the high incidence of Clostridium difficile in our hospitals, surgical antibiotic prophylaxis was modified to lower-risk agents. Prophylaxis for trans-rectal ultrasound guided (TRUS) biopsies of prostate was changed from ciprofloxacin (cip) 500mg PO plus gentamicin (gen) 120mg IM to co-amoxiclav (co-amx) 625mg PO plus gen 120mg IM. Prior to this change two consecutive annual audits had demonstrated a 1% rate of post-operative infective complications requiring admission that was within accepted standards of the British Association of Urological Surgeons. 48 TRUS biopsies were performed in three weeks following this change. A cluster of 7 (14.5%) patients were re-admitted with gram-negative bacteraemia, two requiring Intensive Care admission for septic shock. A comprehensive practice review identified no changes in any critical control points except the antibiotic prophylaxis. This was then changed back to cip plus gen and data showed that the infection admission rate returned to pre-existing levels. We evaluated plausible explanations for this cluster. Method: Microorganisms were identified from blood cultures and antibiotic susceptibilities determined using standard methods. Results: R = Resistant, S = Sensitive Conclusions: (1) Pre-existing resistance to co-amx explains 3 of 7(43%) of the break-through bacteraemias, suggesting that gen alone was insufficient for effective prophylaxis. (2) In 4 of 7(57%) the isolates were co-amx susceptible which implies that breakthrough bacteraemias occurred due to poor prostatic penetration. (3) Use of ciprofloxacin provided superior protection against post-TRUS biopsy bacteraemias regardless of the unquantifiable risk of C. difficile infection. Introduction As a measure to reduce the high incidence of Clostridium difficile in our hospitals, surgical antibiotic prophylaxis was modified to lower risk agents. Prophylaxis for trans-rectal ultrasound guided (TRUS) biopsies of prostate was changed from ciprofloxacin 500mg PO plus gentamycin 120mg IM to co-amoxiclav 625mg PO plus gentamycin 120mg IM1. An illustration of the procedure is presented in Figure 1. Prior to this change two consecutive annual audits had demonstrated only two documented cases of post operative septicaemia in one year, and none in the other. The average was a 1% rate of post-operative infective complications requiring admission that was within accepted standards of the British Association of Urological Surgeons2. 48 TRUS biopsies were performed in three weeks following this change. From this population a cluster of 7 (14.5%) patients were re-admitted with gram-negative bacteraemia, with two requiring Intensive Care Unit (ICU) admission for septic shock. All patients eventually made a full recovery. In addition to the clinical problems these cases presented, the management of these problems incurred additional cost. For example, the extended inpatient stay approximates to £3000 for seven days on an ICU for each of the two ICU admissions, plus the costs of managing the other five cases on urology wards. A comprehensive practice review identified no changes in any critical control points except the antibiotic prophylaxis. This was then changed back to ciprofloxacin plus gentamycin and data showed that the post-operative infection admission rate returned to pre-existing levels. We evaluated plausible explanations for this cluster. Results Table 1. Results of isolate susceptibility testing R = Resistant, S = Susceptible Microorganism Antibiotic susceptibilities Co-Amoxiclav Gentamycin Ciprofloxacin (1) Escherichia coli S R (2) Escherichia coli (3) Escherichia coli (4) Escherichia coli (5) Escherichia coli (6) Escherichia coli (7) Enterococcus faecalis Microorganism Antibiotic susceptibilities Co-Amx Gen Cip (1) Escherichia coli S R (2) Escherichia coli (3) Escherichia coli (4) Escherichia coli (5) Escherichia coli (6) Escherichia coli (7) Enterococcus faecalis Conclusions Pre-existing resistance to co-amoxiclav was demonstrated andexplains 3 (43%) of the break-through bacteraemias, suggesting gentamycin alone was insufficient for effective prophylaxis. In 4 of 7 (57%) the isolates were co-amoxiclav susceptible which implies that breakthrough bacteraemias occurred due to sub-therapeutic concentrations of co-amoxiclav owing to poor prostatic tissue penetration. Use of ciprofloxacin provided superior protection against post-TRUS biopsy bacteraemias regardless of the low but unquantifiable risk of C. difficle infection. Methods Patient isolates from blood cultures were identified according to Health Protection Agency3 (HPA) Standard Operating Procedure methods, and the microorganisms antibiotic susceptibilities were determined using standard British Society for Antimicrobial Chemotherapy (BSAC)4 methods (see Figure 1). The result are presented in Table 1, and photographs of isolate susceptibility testing is presented in Figure 2. Figure 2. Photographs of E. coli isolates (left) and E. faecalis isolates (right) undergoing antibiotic suscepibility testing by BSAC methodology against ciprofloxacin (CIP), gentamycin (CN) and co-amoxiclav (AMC). Discussion Informal review of patients undergoing this procedure shows an extremely low risk of acquiring C. difficile in this population in the post-operative follow-up period after having used ciprofloxacin perioperatively. It would therefore appear that it was unnecessary to alter our antibiotic prophylaxis guidance in this cohort of patients and in line with the principle of “do no harm”. However our enthusiasm for a radical change in practice to the “less risky” co-amoxiclav backfired with a result that we had a significant cluster of serious TURP-related blood stream infections. In our zeal for reducing a hypothesised risk of C. difficile we inadvertently increased a real risk of another serious complication and thus shot ourselves in the foot. Figure 1. An illustration of TRUS-biopsies of prostate procedure (taken from imagesMD website) References 1 University Hospitals of Leicester NHS Trust Antimicrobial Website (www.uhl-tr.nhs.uk) 2 British Association of Urological Surgeons (www.baus.org.uk) 3 Health Protection Agency (www.hpa.org.uk) 4 British Society for Antimicrobial Chemotherapy (www.bsac.org.uk)