Coagulase-negative staphylococcal sepsis in neonates. Association between antibiotic resistance, biofilm formation and the host inflammatory response.
BACKGROUND
Coagulase-negative staphylococci (CoNS) are the most prevalent pathogens causing late onset sepsis in neonates. They are often multiresistant to antibiotics, and the ability to form biofilm is considered their main virulence determinant.


METHODS
During a 12-year period, we identified 150 neonates having 164 suspected septic episodes with growth of CoNS in blood culture. We examined the relationship between antibiotic resistance, phenotypic biofilm production and genetic determinants for biofilm formation in different CoNS species and their correlation with neonatal inflammatory response.


RESULTS
Eighty-five episodes were classified as true sepsis, and 79 episodes of CoNS growth in blood culture were considered contaminations. Sixty-one percent of Staphylococcus epidermidis isolates produced biofilm compared with 26% of CoNS non-epidermidis (P < 0.001). We observed no difference in phenotypic biofilm production or genetic determinants for biofilm formation between invasive isolates and contaminants. C-reactive protein levels as a marker of inflammatory response were higher in CoNS sepsis caused by methicillin and aminoglycoside resistant versus susceptible isolates (P = 0.031). In contrast, there was a significant association between a lower C-reactive protein response and biofilm-positive isolates (P = 0.018). Antibiotic resistance was significantly correlated with biofilm production in S. epidermidis, but not in other CoNS species.


CONCLUSIONS
CoNS sepsis with biofilm-forming strains was associated with a decreased host inflammatory response, potentially limiting the immune system to counteract the infection. The impact of antibiotic resistance and virulence determinants on clinical outcome of neonatal CoNS sepsis warrants additional clinical studies.
Klingenberg
Claus
C
Department of Pediatrics, University Hospital of North Norway. klingenberg@unn.no
Aarag
Elizabeth
E
Rønnestad
Arild
A
Sollid
Johanna Ericson
JE
Abrahamsen
Tore Gunnar
TG
Kjeldsen
Gry
G
Flaegstad
Trond
T
D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D018441:Biofilms; D003030:Coagulase / Q000378:metabolism; D015331:Cohort Studies; D024881:Drug Resistance, Bacterial; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000032:analysis; D007363:Intensive Care Units, Neonatal; D016014:Linear Models; D008297:Male; D008826:Microbial Sensitivity Tests; D015999:Multivariate Analysis; D011336:Probability; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D013203:Staphylococcal Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology* / Q000453:epidemiology; D013210:Staphylococcus / Q000145:classification* / Q000187:drug effects; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D003030:Coagulase; D018836:Inflammation Mediators