PROSPECTIVE RANDOMIZED COMPARISON OF IMIPENEM MONOTHERAPY WITH IMIPENEM PLUS NETILMICIN FOR TREATMENT OF SEVERE INFECTIONS IN NONNEUTROPENIC PATIENTS

Nosocomial pneumonia and sepsis, as well as severe diffuse peritonitis , must be treated early in order to prevent complications such as sept ic shock and organ dysfunctions. With the availability of new broad-sp ectrum and highly bactericidal antibiotics, the need of combining beta -lactams with aminoglycosides for the treatment of severe infections s hould be reassessed. A prospective randomized controlled study was per formed to compare imipenem monotherapy with a combination of imipenem plus netilmicin in the empiric treatment of nosocomial pneumonia, noso comial sepsis, and severe diffuse peritonitis. A total of 313 patients were enrolled, and 280 were assessable. The antibiotic treatment was successful in 113 of 142 patients (80%) given the monotherapy and in 1 19 of 138 patients (86%) given the combination (P = 0.19). The failure rates for the most important type of infection, i.e., pneumonia, were similar in the two groups, as well as the number of superinfections. While creatinine increase was associated with factors not related to a ntibiotic therapy for all eight patients of the monotherapy group, no factor other than the antibiotics could be found for 6 of the 14 cases of nephrotoxicity observed in the combination group (P = 0.014). Fina lly, the emergence of Pseudomonas aeruginosa resistant to imipenem occ urred in 8 monotherapy patients and in 13 combination therapy patients . In conclusion, imipenem monotherapy appeared as effective as the com bination of imipenem plus netilmicin for the treatment of severe infec tion. The addition of netilmicin increased nephrotoxicity, and it did not prevent the emergence of P. aeruginosa resistant to imipenem.