Coagulase-negative staphylococcal infections in a neonatal intensive care unit: In vivo response to cloxacillin

Abstract

Following the introduction of cloxacillin and gentamicin as the first line of treatment for possible late-onset sepsis (LOS) in the authors' neonatal intensive care unit (NICU), it was subsequently noted that very low birth weight (VLBW) infants improved clinically, despite subsequently positive blood cultures for oxacillin-resistant, coagulase-negative Staphylococcus (CONS). The results of the management of VLBW infants with CONS sepsis during one calendar year, based on clinical rather than laboratory findings, are presented. VLBW infants with LOS were identified through the neonatal database, and the charts of those with CONS were reviewed for antibiotic usage, antibiotic resistance pattern, clearance of CONS from the blood and NICU discharge status. Oxacillin sensitivity was determined by the presence of the mecA gene. From January 1 to December 31, 2002, 27 VLBW infants, treated in the authors' NICU for LOS due to CONS, were identified. The mean age of LOS infants with CONS was 15 days (median 12 days; range three to 54 days), the mean birth weight (+/- SD) was 904+/-247 g, and the mean gestational age at birth (+/- SD) was 27+/-2 weeks. All infants were started on cloxacillin and gentamicin, and improved clinically over the first 48 h. Six isolates were sensitive to cloxacillin. Twenty-three infants grew oxacillin-resistant CONS, eight of whom had persistence of CONS on repeat culture secondary to central lines. Two infants grew two strains of CONS. Eighteen of 22 infants (82%) with in vitro oxacillin-resistant CONS had clearance of bacteremia with cloxacillin and gentamicin. Ten infants (37%) received vancomycin, based on the authors' guidelines. There were no cases of prolonged bacteremia requiring rifampicin. Three infants died, but none of the deaths could be attributed to CONS. The authors describe clinical improvement with clearance of CONS using cloxacillin and gentamicin, despite laboratory results suggesting oxacillin resistance. The authors' unit policy was based on clinical response and permitted the continuation of cloxacillin, provided that a repeat blood culture was negative. Vancomycin use was suggested for clinical deterioration or persistence of CONS. These results question the in vitro tests of resistance. Clearance of oxacillin-resistant CONS from the blood points to in vivo sensitivity, while the laboratory testing suggests in vitro resistance. The absence of subsequent positive blood cultures for CONS confirms clearance of this organism. It was demonstrated that cloxacillin (150 mg/kg/day dose), along with gentamicin, can clear CONS from the blood within 48 h. The relationship between in vivo and in vitro sensitivities also needs to be further studied both in the laboratory and in a prospective trial.