A 12-year-old boy is brought to the emergency department due to a skin infection. Temperature is 38.4 C (101.1 F). Physical examination shows an area of erythema, warmth, and tenderness on his right distal leg. Laboratory results are notable for leukocytosis. The patient is started on intravenous nafcillin. Two days later, he shows limited response to antibiotic therapy. Light microscopy of pus obtained from the site shows gram-positive cocci in clusters, and sensitivity testing demonstrates little response to nafcillin but good response to vancomycin. Which of the following is the most likely explanation for nafcillin treatment failure in this patient?

Question

A 12-year-old boy is brought to the emergency department due to a skin infection.  Temperature is 38.4 C (101.1 F).  Physical examination shows an area of erythema, warmth, and tenderness on his right distal leg.  Laboratory results are notable for leukocytosis.  The patient is started on intravenous nafcillin.  Two days later, he shows limited response to antibiotic therapy.  Light microscopy of pus obtained from the site shows gram-positive cocci in clusters, and sensitivity testing demonstrates little response to nafcillin but good response to vancomycin.  Which of the following is the most likely explanation for nafcillin treatment failure in this patient?

Quizplus · Accepted Answer

11ec160b_3bf0_a280_9249_712de980edfa_MD0001_00 The presence of gram-positive cocci in clusters that do not respond to nafcillin but show sensitivity to vancomycin suggests infection with methicillin-resistant Staphylococcus aureus (MRSA). S aureus is a common cause of skin infections in the United States. Most skin infections are minor, but S aureus can cause serious infections (eg, surgical wound infections, bloodstream infections in the presence of central intravenous catheters, pneumonia). S aureus strains that are resistant to oxacillin, nafcillin, and methicillin have been historically termed MRSA, but they are also resistant to all β-lactam agents, including penicillin, cephalosporins (except ceftaroline, a fifth-generation cephalosporin), and carbapenems. Methicillin (nafcillin) resistance is typically mediated by alterations in the structure of penicillin-binding proteins (PBP), the enzymes involved in cell wall synthesis. Altered PBPs, especially PBP2a, have greatly reduced affinity for β-lactam antimicrobial agents (except ceftaroline). (Choice A) Resistance to tetracycline and sulfonamides is due at least in part to a decrease in the levels of drug accumulation due to decreased uptake and/or increased efflux. (Choice B) Approximately 95% of S aureus isolates in the United States produce penicillinase, which causes penicillin resistance by breaking penicillin's β-lactam ring. However, nafcillin is penicillinase-stable (along with oxacillin and methicillin). (Choices C and D) Mutations in DNA gyrase cause resistance to quinolone antibiotics. Mutations in RNA polymerase cause resistance to rifampin. Educational objective: Methicillin-resistant Staphylococcus aureus is resistant to all β-lactam antibiotics, including beta-lactamase-resistant antibiotics, as it has an altered penicillin-binding protein that does not bind β-lactams effectively.

A 12-Year-Old Boy Is Brought to the Emergency Department Due