Absence of patient-to-patient intrahospital transmission of Staphylococcus aureus as determined by whole-genome sequencing

Abstract

Nosocomial transmission of pathogens is a major health care challenge. The increasing spread of antibiotic-resistant strains represents an ongoing threat to public health. Previous Staphylococcus aureus transmission studies have focused on transmission of S. aureus between asymptomatic carriers or used low-resolution typing methods such as multilocus sequence typing (MLST) or spa typing. To identify patient-to-patient intrahospital transmission using high-resolution genetic analysis, we sequenced the genomes of a consecutive set of 398 S. aureus isolates from sterile-site infections. The S. aureus strains were collected from four hospitals in the Houston Methodist Hospital System over a 6-month period. Importantly, we discovered no evidence of transmission of S. aureus between patients with sterile-site infections. The lack of intrahospital transmission may reflect a fundamental difference between day-to-day transmission events in the hospital setting and the more frequently studied outbreak scenarios. Importance: Previous studies have suggested that nosocomial transmission of S. aureus is common. Our data revealed an unexpected lack of evidence for intrahospital transmission of S. aureus between patients with invasive infections. This finding has important implications for hospital infection control and public health efforts. In addition, our data demonstrate that highly related pools of S. aureus strains exist in the community which may complicate outbreak investigations.

FIG 1

Radial phylogenetic tree mapping the 398 isolates of the HMHS-SA collection based on SNP distance to reference strain FPR3757. Isolates are represented by red filled circles, and numbers correspond to 4 general groupings identified through whole-genome sequencing. Group 1 (green circle) is primarily ST8 organisms that group very tightly with the ST8 reference strain. Group 2 (blue circles) encompasses two groups, both approximately equidistant from the reference strain. One is primarily ST5 isolates, and the other is ST15 strains and others. Group 3 is predominantly ST30 and ST45, and group 4 is rare members of CC75, not previously isolated in the United States. The tree is truncated to enhance detail. (Inset) To-scale version of tree; bar, 0.800.

FIG 2

Circular cladogram colored by MLST. All MLST STs of a given clonal complex are colored shades of the same color. MLST was determined using a combination of SRST2 software and manual sequence review. Strains with a novel MLST allele type are labeled in gray (“Novel”).

FIG 3

Flow diagram demonstrating the process of screening the 398 S. aureus isolates for potential intrahospital transmission. First, the ST8 and ST5 isolates were selected, and any isolate pair with a pairwise distance of 40 SNPs or less was selected for review. If the pair of isolates were from the same patient, no further investigation was performed. If the isolates were from two individual patients, the medical record was reviewed individually to identify if the infections were present on admission, had differences in antimicrobial susceptibility, or were from different hospitals without a shared caregiver. No intrahospital transmission events were identified in these isolates.

FIG 4

Comparison of the evolutionary rates of ST8 and ST5 clones in the HMHS-SA collection. For patients with multiple ST8 or ST5 S. aureus isolates collected over time, the evolutionary rate was calculated. The mean and quartile ranges are indicated for each MLST type. The increased evolutionary rate in ST5 isolates collected over time from the same patient can be observed. The evolutionary rates between the two groups are significantly different with a P value of 0.031 using an unpaired t test with Welch’s correction.

FIG 5

Radial phylogenetic tree of the 3 CC75 HMHS-SA isolates. A clear relationship is evident between HMHS-SA-57 and HMHS-SA-328, which were isolated from the same patient several months apart, compared to HMHS-SA-153. Isolate HMHS-SA-153 was typed as ST1223 by SRST2. HMHS-SA-57 and HMHS-SA-328 share a novel MLST type, which is a single locus variant of ST2793.

FIG 6

Cladogram showing no significant clustering based on hospital of origin. Small clusters of isolates from hospital B, C, or D represent multiple isolates collected from the same patient at that hospital.