132 Phenotypic and Genotypic Aminoglycoside Resistance in Blood Culture Isolates of Coagulase Negative Staphylococci from A Single Neonatal Intensive Care Unit, 1989–2000

Abstract

Background/aims: Coagulase-negative staphylococci (CONS) are the most prevalent pathogen causing late onset sepsis in neonates. A combination therapy including aminoglycosides is often used for empiric treatment of this condition. The aims of the study were to determine the susceptibility of neonatal CONS blood culture isolates to different aminoglycosides and to correlate the presence of genes encoding aminoglycoside modifying enzymes (AME) to amino-glycoside susceptibility pattern and methicillin resistance.Methods: Over a 12 years period 180 CONS blood culture isolates from one single neonatal unit were collected. According to standard definitions 95 isolates were classified as contaminants and 85 as invasive isolates. Susceptibility testing with Etest or the paper disk diffusion method was done for gentamicin, amikacin, netilmicin, tobramycin, arbekacin and oxacillin. Three different genes encoding AME [aac(6′)-Ie- aph(2“)-Ia, ant(4′)-I and aph(3′)-IIIa] and the methicillin resistance gene, mecA, were detected with PCR.Results: For tobramycin, gentamicin, netilmicin and amikacin 57 (32 %), 61 (34 %), 85 (47 %) and 110 (61 %) of all isolates, respectively, remained susceptible. No increase in aminoglycoside resistance rate was detected during the study period. The susceptibility rates were significant lower among invasive isolates versus contaminants. aac(6′)-Ieaph(2“)-Ia was encountered in 125 isolates (69 %), and 22 isolates (12 %) carried this gene in combination with the ant(4′)-Ia gene. Only 10 of 125 aac(6′)-Ieaph(2”)-Ia positive strains had gentamicin MIC≤2 mg/L, but 124 strains remained susceptible to arbekacin. However, 57 isolates highly resistant to gentamicin (MIC ≥128 mg/L) showed smaller arbekacin zone diameter (p < 0,001) than other isolates. Only 9 % of methicillin resistant strains were susceptible to gentamicin compared to 79 % of methicillin susceptible strains. Methicillin resistant strains remained susceptible to netilmicin (28 %), amikacin (48 %) and arbekacin (99 %).Conclusion: A high prevalence of aminoglycoside resistance was detected. Among the traditional aminoglycosides netilmicin or amikacin seems a better choice compared to gentamicin in the treatment of neonatal CONS infections. An optimal dosing regimen with high peak concentration will ensure best coverage for borderline resistant CONS strains. Arbekacin showed superior performance with antibacterial activity to 99.4 % of all isolates. We advocate including arbekacin in future clinical trials of empiric therapy of late onset neonatal sepsis.