Treatment of infections due to coagulase-negative staphylococci

INTRODUCTION

Coagulase-negative staphylococci (CoNS) are part of the normal flora of human skin [1]. These organisms have relatively low virulence but are increasingly recognized as agents of clinically significant infection of the bloodstream and other sites. Risk factors for CoNS infection include foreign bodies (such as indwelling prosthetic devices or intravascular catheters) and immune compromise. Treatment of CoNS infections can be challenging given limitations of antimicrobial resistance and the frequent presence of foreign material.

Issues related to antimicrobial resistance and treatment of CoNS infections will be reviewed here. The microbiology, pathogenesis, epidemiology of CoNS are discussed separately, as are the clinical features, diagnosis, and treatment of specific infections caused by these organisms. (See "Microbiology, pathogenesis, and epidemiology of coagulase-negative staphylococci".)

ANTIMICROBIAL RESISTANCE

Methicillin

Microbiology — Resistant to methicillin and semisynthetic penicillins has been observed in more than 80 percent of coagulase-negative staphylococcal isolates [2]. Such isolates are often resistant to multiple classes of antibiotics in addition to beta-lactams. The genes responsible for resistance are often found on plasmids, facilitating the horizontal exchange of resistance genes among strains. The mecA gene encoding a low-affinity penicillin-binding protein (PBP 2a) is responsible for mediating methicillin or oxacillin resistance in CoNS, as in S. aureus [3]. This resistance is heterotypic since only a minority of the bacterial population (as few as one in 10(3) or 10(6) organisms) expresses the resistant phenotype; this makes detection of resistance especially challenging [4]. (See "Microbiology of methicillin-resistant Staphylococcus aureus".)

Epidemiology — Studies describing the acquisition and spread of resistant organisms have been performed in patients undergoing cardiac surgery [5-9]. Preoperatively, cardiac surgery patients generally have CoNS skin isolates that are susceptible to methicillin; resistant clones appear to emerge with selective pressure of perioperative antibiotic prophylaxis [5]. In one study including 29 patients who underwent preoperative sampling of the nares, subclavian and inguinal areas, methicillin-resistant CoNS were detected in rare numbers from at least one site in 75 percent of patients [6]. Following surgery, more than half of the clinical sites with baseline evidence of colonization contained high levels of methicillin-resistant staphylococci. Antibiograms and plasmid profile patterns suggested that these resistant organisms were derived from the small number of resistant organisms present preoperatively.

Other studies have also demonstrated that patients undergoing cardiac surgery have postoperative skin flora composed primarily of methicillin-resistant CoNS [7,8]. In one report of 69 patients, colonization with methicillin resistant organisms 10 days postoperatively (a resistance pattern not present preoperatively) was observed in 91 percent of patients [7]. The preoperative and postoperative isolates were distinct on plasmid analysis. Some of the nurses in the cardiothoracic intensive care unit were observed to be colonized with CoNS resistant to methicillin of the matching plasmid type [7].