Active Surveillance, Drug Resistance, and Genotypic Profiling of Staphylococcus aureus Among School-Age Children in China

Abstract

Methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization predisposes individuals for endogenous infections and is a major threat to children. Recently, oxacillin/cefoxitin-susceptible mecA-positive S. aureus (OS-MRSA) has been reported worldwide. Herein, a prospective, cross-sectional study was conducted across five schools, representing three educational stages, in Guangzhou, China. Nasal swabs from 2,375 students were cultured for S. aureus and all isolates were subjected to antibiotic susceptibility testing phenotypically and confirmed by femB and mecA genetic detection; all the isolates were classified as MSSA, MRSA, or OS-MRSA. All strains were also analyzed by multi-locus sequence typing. Among the 2,375 swabs, S. aureus was detected in 744 children (31.3%, 95% CI: 25.9-36.7%), of whom 72 had MRSA (3.0%, 95% CI: 0.6-5.4%) and 4 had OS-MRSA (0.2%, 95% CI: 0.1-0.3%), of which an oxacillin- and cefoxitin-susceptible MRSA strain was identified. The prevalence of S. aureus and MRSA was higher in younger children. The highest percentage of drug resistance of the S. aureus isolates (n = 744) was to penicillin (85.5%), followed by erythromycin (43.3%) and clidamycin (41.0%). The most prevalent sequence types (STs) were ST30, ST45, and ST188 in MSSA, accounting for 38.7% of the total isolates, whereas ST45, ST59, and ST338 accounted for 74.6% of the MRSA isolates and ST338 accounted for 50.0% of the OS-MRSA isolates. The MRSA and OS-MRSA isolates (n = 76) were grouped into three clades and one singleton, with clonal complex (CC) 45 as the most predominant linkage. The top nine multi-locus sequence typing-based CCs (CC30, CC45, CC5, CC1, CC15, CC944, CC398, CC59, CC7) represented 86.7% of all S. aureus isolates. All CC30 isolates were resistant to erythromycin and clidamycin, and almost all these isolates were also resistant to penicillin (99.2%). The CC45 and CC59 isolates exhibited high resistance rates to oxacillin at 31.5 and 59.0%, respectively. This study provides updated data valuable for designing effective control strategies to mitigate the burden of disease and to improve the adequacy of empirical antimicrobial treatments for potentially harmful infections.

Keywords: Staphylococcus aureus; antibiotic resistance; methicillin-resistant Staphylococcus aureus; molecular epidemiology; nasal colonization; oxacillin-susceptible MRSA.

Figure 1

Minimum spanning tree based on the genotypic structure of all Staphylococcus aureus isolates. Each sequence type is represented by a node. The size of each node represents the number of S. aureus strains with this genotype. The length of two nodes indicates the genetic distance between the two genotypes. Labeled nodes are the top nine clonal complexes. Red, green, and blue circles represent clonal complexes that were methicillin-resistant (MRSA), cefoxitin/oxacillin-susceptible mecA-positive (OS-MRSA), and methicillin-susceptible S. aureus (MSSA), respectively.

Figure 2

Dendrogram and antibiogram of 72 methicillin-resistant (MRSA) and four cefoxitin/oxacillin-susceptible mecA-positive (OS-MRSA) Staphylococcus aureus isolates were generated based on multi-locus sequence typing data. All isolates (n = 76) were grouped into three clades and one singleton. I, intermediate resistant; R, resistant. CIP, ciprofloxacin; CLI, clindamycin; ERY, erythromycin; GEN, gentamicin; RIF, rifampicin; SXT, sulfamethoxazole-trimethoprim; TCY, tetracycline.

Figure 3

Heatmap of the antibiotic resistance patterns among the top nine clonal complexes. *rifampicin resistance or intermediate resistance. Antibiotics: PEN, penicillin; OXA, oxacillin; ERY, erythromycin; CLI, clindamycin; D test, inducible clindamycin resistance; RIF, rifampicin; TCY, tetracycline; SXT, sulfamethoxazole-trimethoprim; CIP, ciprofloxacin; LVX, levofloxacin; MFX, moxifloxacin; GEN, gentamicin; NIT, nitrofurantoin; LZD, linezolid; TGC, tigecycline; VAN, vancomycin; QDA, quinupristin/dalfopristin.