Clinical outcome of cephalothin versus vancomycin therapy in the treatmentof coagulase-negative staphylococcal septicemia in neonates: Relation to methicillin resistance and mec A gene carriage of blood isolates

Objective. Coagulase-negative staphylococci (CONS) are the most common caus ative agents in neonatal nosocomial septicemia. Because of widespread methi cillin resistance among CONS, empiric therapy with vancomycin is recommende d as the primary antibiotic regimen for these infections. In our unit, empi ric treatment of nosocomially acquired septicemia consists of cephalothin a nd gentamicin, which are adjusted subsequently according to the determined bacterial susceptibility profile. Vancomycin is initiated only when the pat ient has been treated recently with cephalothin or when intravascular lines or endotracheal tube are colonized with oxacillin/cephalothin-resistant CO NS strains. The aim of the present study was to evaluate the efficacy of ou r antibiotic regimen for CONS septicemia, in relation to methicillin-resist ance and the carriage of mec A gene, encoding methicillin resistance, among CONS blood isolates from our unit. Methods. Clinical symptoms of septicemia, clinical outcome, and laboratory parameters of septicemia (C-reactive protein) were studied retrospectively in 66 patients with CONS septicemia. The diagnosis of septicemia was made b y the attending neonatologist and was defined by clinical symptoms of septi cemia in the presence of a positive finding of a blood culture test, which was performed using a defined protocol. All CONS blood isolates were includ ed to determine mec A gene carriage. Results. In the 66 patients, three treatment categories were distinguished: treatment with cephalothin (25 patients, 38%); with vancomycin (15 patient s, 23%); and primary treatment with cephalothin, switched subsequently to v ancomycin (26 patients, 39%). It was found that 92% of all CONS blood isola tes (61/66) were mec A-positive. Concordance of mec A gene carriage with me thicillin/oxacillin resistance was found in 56 of 66 isolates (85%); 10 of 61 (16%) isolates that were mec A-positive were determined as oxacillin-sus ceptible. Although 22 of the 25 blood isolates of the cephalothin-treated p atients were mec A-positive, clinical recovery was uneventful. In the 26 pa tients in whom antibiotic therapy was switched from cephalothin to vancomyc in, two strains were cephalothin-susceptible and 8 patients already had rec overed clinically before the switch, which was based solely on susceptibili ty test results. Conclusions. Cephalothin was found to be clinically efficacious in the trea tment of neonatal CONS septicemia, despite a steadily increasing mec A gene carriage of CONS blood isolates in our neonatal intensive care unit and a corresponding high methicillin/oxacillin resistance. Hence, cephalothin rem ained the antibiotic of first choice in the treatment of CONS septicemia in our unit with vancomycin selected exclusively for cases not responding to initial cephalothin treatment, or for patients developing CONS septicemia d uring or after recent cephalothin treatment By applying this approach in ou r unit, we were able to reduce vancomycin use from 62% in 1994 to 1995 to 2 1% in 1997. This shows that such a policy may result in an important reduct ion of vancomycin use, which may aid in postponing the threatening emergenc e of vancomycin resistance among Gram-positive cocci.