Clinical outcome of cephalothin versus vancomycin therapy in the treatment of 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 causative agents in neonatal nosocomial septicemia. Because of widespread methicillin resistance among CONS, empiric therapy with vancomycin is recommended as the primary antibiotic regimen for these infections. In our unit, empiric treatment of nosocomially acquired septicemia consists of cephalothin and gentamicin, which are adjusted subsequently according to the determined bacterial susceptibility profile. Vancomycin is initiated only when the patient has been treated recently with cephalothin or when intravascular lines or endotracheal tube are colonized with oxacillin/cephalothin-resistant CONS strains. The aim of the present study was to evaluate the efficacy of our antibiotic regimen for CONS septicemia, in relation to methicillin-resistance 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 by the attending neonatologist and was defined by clinical symptoms of septicemia in the presence of a positive finding of a blood culture test, which was performed using a defined protocol. All CONS blood isolates were included 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 patients, 23%); and primary treatment with cephalothin, switched subsequently to vancomycin (26 patients, 39%). It was found that 92% of all CONS blood isolates (61/66) were mec A-positive. Concordance of mec A gene carriage with methicillin/oxacillin resistance was found in 56 of 66 isolates (85%); 10 of 61 (16%) isolates that were mec A-positive were determined as oxacillin-susceptible. Although 22 of the 25 blood isolates of the cephalothin-treated patients were mec A-positive, clinical recovery was uneventful. In the 26 patients in whom antibiotic therapy was switched from cephalothin to vancomycin, two strains were cephalothin-susceptible and 8 patients already had recovered clinically before the switch, which was based solely on susceptibility test results.


CONCLUSIONS
Cephalothin was found to be clinically efficacious in the treatment 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 remained 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 during or after recent cephalothin treatment. By applying this approach in our unit, we were able to reduce vancomycin use from 62% in 1994 to 1995 to 21% in 1997. This shows that such a policy may result in an important reduction of vancomycin use, which may aid in postponing the threatening emergence of vancomycin resistance among Gram-positive cocci.
Krediet
T G
TG
Department of Neonatology, Wilhelmina Children's Hospital, Utrecht University, The Netherlands.
Jones
M E
ME
Gerards
L J
LJ
Fleer
A
A
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002511:Cephalosporins / Q000627:therapeutic use*; D002512:Cephalothin / Q000627:therapeutic use*; D003030:Coagulase; D005798:Genes, Bacterial; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016106:Methicillin Resistance / Q000235:genetics*; D012189:Retrospective Studies; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013210:Staphylococcus / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D014640:Vancomycin / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D003030:Coagulase; D014640:Vancomycin; D002512:Cephalothin