Going Back in Time: Increasing Penicillin Susceptibility among Methicillin-Susceptible Staphylococcus aureus Osteoarticular Infections in Children

Antimicrob Agents Chemother. 2023 Jan 24;67(1):e0119622. doi: 10.1128/aac.01196-22. Epub 2023 Jan 4.


In the late 1940s to 1950s, Staphylococcus aureus isolates first-gained resistance to penicillin. Recently, some centers have described an increase in the proportion of methicillin susceptible S. aureus (MSSA) which are also susceptible to penicillin (PSSA). There are little data on the frequency of PSSA infections in children. We investigated the prevalence of penicillin susceptibility among pediatric MSSA acute hematogenous osteoarticular infection (OAI) isolates. MSSA OAI isolates were obtained through surveillance studies at Texas Children's and St. Louis Children's Hospitals from January 2011 to December 2019. All isolates underwent PCR for blaZ β-lactamase, PVL genes and agr group. All blaZ negative isolates then underwent penicillin MIC determination. blaZ negative isolates with penicillin MIC ≤ 0.125 μg/mL were considered PSSA. Multilocus sequence typing (MLST) was conducted on a subset of isolates. A total of 329 unique isolates were included in the study. The median patient age was 9.2 years (IQR:5.1 to 12.2). Overall, 6.7% of isolates were penicillin susceptible. No PSSA were detected prior to 2015 but increased yearly thereafter. By the final study year, 20.4% of isolates were PSSA (P = 0.001). PSSA were similar to penicillin-resistant MSSA (PR-MSSA) isolates in terms agr group and PVL carriage as well as clinical presentation and outcomes. PSSA were of distinct sequence types compared to PR-MSSA. PSSA appears to be increasing among OAI in U.S. children. Overall, PSSA isolates are associated with a similar clinical presentation as penicillin-resistant isolates. The potential for use of penicillin treatment in PSSA OAI warrants further study.

Keywords: MSSA; children; osteomyelitis; pediatrics; penicillin.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Child
  • Child, Preschool
  • Humans
  • Methicillin / pharmacology
  • Methicillin / therapeutic use
  • Methicillin-Resistant Staphylococcus aureus* / genetics
  • Microbial Sensitivity Tests
  • Multilocus Sequence Typing
  • Penicillins / pharmacology
  • Penicillins / therapeutic use
  • Staphylococcal Infections* / drug therapy
  • Staphylococcal Infections* / epidemiology
  • Staphylococcus aureus / genetics


  • Methicillin
  • Penicillins
  • Anti-Bacterial Agents