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Prevalence of resistance to antiseptics and mupirocin among invasive coagulase-negative staphylococci from very preterm neonates in NICU: the creeping threat?

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Summary

In neonatal intensive care units, topical agents represent an increasing part of the infection control armamentarium. Fifty-one coagulase-negative staphylococci (CNS) isolated from catheter-associated bloodstream infections in very preterm neonates were investigated in this study: 41.2% exhibited decreased susceptibility to at least one antiseptic (chlorhexidine 12%, benzalkonium 24%, acriflavine 33%) and 61% were resistant to mupirocin. QacA/B, mupA and both genes were detected by polymerase chain reaction in 59%, 63% and 49% of CNS, respectively. Seventy-six percent of Staphylococcus epidermidis (5/5 pulsed-field-gel electrophoresis subgroups) and 11% of Staphylococcus capitis (1/3 subgroups) were multi-resistant. Skin antisepsis using low-concentration aqueous formulations and off-label mupirocin indications should benefit from a stewardship programme.

Introduction

In neonatal intensive care units (NICU), catheter-associated bloodstream infections (CABSI) due to coagulase-negative staphylococci (CNS) are the main healthcare-associated infections (HAI), occurring in 11% of patients. HAI increase morbidity, mortality and risk of long-term disabilities.1 Preventive measures include the use of chlorhexidine (CHX) for skin antisepsis, gauze dressing and catheter injection hub-site disinfection.1 Combination therapy with CHX skin disinfection and mupirocin nasal decolonization can be effective in managing outbreaks of Staphylococcus aureus infections.2

Unfortunately, the use of topical agents can select resistant strains of staphylococci. MupA is the major resistance gene responsible for high-level mupirocin resistance.3 Quaternary ammonium compound (QAC)-resistant determinants, encoded by qac family genes, are multi-drug efflux pumps that decrease bacterial susceptibility to cationic antiseptic agents.4 Mainly located on mobile genetic elements as plasmids, these genes could be transferred between staphylococcal species.4

Beyond failure of CABSI preventive strategies, CNS that are resistant to topical agents could act as a reservoir of mupA and qac genes that could be transferred to S. aureus.3, 4 This paper reports a phenotypic and molecular study evaluating the prevalence of antiseptic- and mupirocin-resistant strains among CNS responsible for CABSI in a French referral NICU.

Section snippets

Methods

This study was performed in a level 3, 28-bedded NICU at the university-affiliated Antoine Béclère Hospital (Assistance Publique–Hôpitaux de Paris network). During the study period, 1799 neonates were admitted to the NICU (total 21,796 patient-days).

All non-duplicate CNS from clinically relevant CABSI diagnosed among preterm neonates (<32 completed weeks of gestation) between January 2009 and September 2011 were included. CABSI was defined according to international consensus criteria: one or

Results

Over the study period, 51 strains were collected from extremely preterm (67.4%) or very preterm (32.6%) neonates (all weighing <1500 g). The species distribution was: S. epidermidis (N = 25), S. capitis (N = 18), Staphylococcus haemolyticus (N = 2) and other species (N = 6).

All but one strain was resistant to meticillin, and 88% and 30% were resistant to gentamicin and ofloxacin, respectively. All strains were susceptible to vancomycin, and all but two strains were susceptible to teicoplanin.

Discussion

The burden of HAI in NICU has led physicians to use preventive strategies including antiseptics and topical antimicrobial compounds. The present study found a high prevalence of phenotypic and genotypic antiseptic and mupirocin resistance among a sample of clinically relevant CNS isolated from preterm neonates. Reports concerning mupirocin and antiseptic susceptibility of CNS are scarce, and to the best of the authors' knowledge, this work provides the first data from an NICU. In the present

Acknowledgments

The authors wish to thank the staff from the NICU and the pharmacy.

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