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

Abstract

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.

FIG 1

Trends in PSSA during the study period. The frequency of PSSA across all sites increased during the study period, linear regression P = 0.002, R² = 0.778.

FIG 2

β-lactam MICs in PSSA. MICs to penicillin, ampicillin, oxacillin, cefazolin, and cephalexin were determined by broth dilution for all PSSA.

FIG 3

Cefazolin and oxacillin MICs in PSSA versus PR-MSSA. Cefazolin and oxacillin broth dilution MICs were conducted for PSSA and PR-MSSA. (A) Cefazolin MICs in PSSA were lower than PR-MSSA, P = 0.001. (B) Oxacillin MICs were lower in PSSA than PR-MSSA, P = 0.001.

FIG 4

eBurst of PSSA and select matched PR-MSSA. PSSA are depicted in blue and PR-MSSA in gray. Numbered nodes correspond to individual sequence types (ST); the size of individual nodes corresponds to the relative abundance of isolates of a given ST. Nodes connected by a single line represent single locus variants (SLV).