Introducing Fosfomycin for Surgical Prophylaxis-Emergence of Resistance in Aerobic Faecal Gram-negative Bacteria of In-patients, but Not Among Strains Causing Infection after Elective Colorectal Procedures

Abstract

Fosfomycin was introduced for prophylaxis of surgical infection at 6 centres in a randomized study of elective colorectal operations (fosfomycin/metronidazole, n = 251 vs doxycycline/metronidazole, n = 237). Preoperative faecal specimens from the patients showed a relatively high prevalence rate of doxycycline-resistant bacteria (aerobic Gram-negative isolates 38%, enterococci 24%, overall 35%) with constant rates over time during the 15-month study period. The resistance rates for fosfomycin were lower (overall 12%), and remained constant for enterococci (average 10%), but increased for aerobic Gram-negative isolates from 9% during the initial part to 17% during the final part of the study (p = 0.007). Most aerobic strains in wound secretions from infected patients (20/26) could not be recovered from a preoperative faecal swab of the same patient. Isolates from infection after doxycycline prophylaxis had twice as high doxycycline resistance rates (overall 63%, 82% for Gram-negative isolates) as wound isolates from infection after fosfomycin prophylaxis (30%) and preoperative faecal flora isolates (35%, p = 0.02), indicating that bacterial resistance contributed to failure of doxycycline prophylaxis. In contrast, no increase in fosfomycin resistance rates was found among aerobic isolates from infection after fosfomycin prophylaxis (10%). This suggested that the emerging fosfomycin resistance was associated with reduced bacterial virulence and thus was of less clinical significance than doxycycline resistance.