A 62-year-old man who underwent mitral valve replacement 1 month ago is being evaluated in the emergency department for low-grade fevers. He has some malaise and dyspnea. Multiple sets of blood cultures are drawn and, within hours, all bottles grow gram-positive cocci in clusters that are catalase-positive and coagulase-negative. The decision is made to begin empiric antibiotic therapy. Initial empiric treatment should include which of the following antibiotics?
This patient who was recently hospitalized for mitral valve replacement now has fevers and bacteremia with catalase-positive, coagulase-negative, gram-positive cocci in clusters. This is consistent with infection due to coagulase-negative staphylococci (CoNS). These organisms produce a polysaccharide slime facilitating prosthetic device adherence. As a result, CoNS are a major cause of infection in patients with indwelling catheters or implanted foreign bodies (eg, peritoneal dialysis catheters, vascular grafts) and a common cause of prosthetic valve endocarditis (PVE). For example, Staphylococcus epidermidis (a type of CoNS) can cause an indolent endocarditis following valve replacement; if left untreated, it can lead to intracardiac abscess, prosthetic valve dehiscence, and septic embolization. As CoNS are a component of normal skin flora, it may be difficult initially to distinguish blood culture contamination from true infection; however, recovery of the same organism from several blood culture bottles indicates infection.
Most (>80%) CoNS strains are methicillin-resistant. Therefore, particularly with nosocomial infection (as is likely in this patient), CoNS should be assumed to be methicillin-resistant until proven otherwise. Vancomycin should be a component of initial therapy. Additional antimicrobial agents (eg, gentamicin and/or rifampin, which kills bacteria on foreign material) are administered in some cases of deep-seated methicillin-resistant CoNS infection or staphylococcal PVE. If susceptibility results later demonstrate a methicillin-susceptible isolate, vancomycin can be switched to a semi-synthetic β-lactamase-resistant penicillin such as nafcillin or oxacillin. Native valve endocarditis due to methicillin-sensitive staphylococci is best treated with nafcillin or oxacillin (Choice D). Very few strains of S epidermidis are susceptible to penicillin G (Choice E).
(Choice A) A methicillin-resistant strain of S epidermidis will likely be cephalosporin-resistant, as the mechanism of methicillin resistance (mecA chromosomal gene) involves alterations in the penicillin-binding protein PBP 2a, which is used by both penicillins and cephalosporins.
(Choice B) Ciprofloxacin is a fluoroquinolone antibiotic. Ciprofloxacin resistance appears to accompany methicillin resistance in staphylococci due to the simultaneous presence of multiple antibiotic resistance genes.
(Choice C) Although clindamycin can be used for the treatment of certain infections caused by oxacillin-resistant Staphylococcus, it is not appropriate initial therapy for CoNS bacteremia. Inducible clindamycin resistance exists in some S aureus strains, resulting in treatment failure.
Educational objective:
Initial empiric treatment of coagulase-negative staphylococcal infection should include vancomycin due to widespread methicillin resistance, especially in nosocomial infections. If susceptibility results indicate a methicillin-susceptible isolate, vancomycin can be switched to nafcillin or oxacillin.