Abstract
Background
In the United States, approximately 30,000 invasive group B Streptococcus (iGBS) infections occur annually; beta-lactam antibiotics (BL) are the first choice for prevention in young infants and treatment in all age groups. We obtained phenotypic and genotypic data for iGBS isolates from U.S. population-based surveillance sites to describe the emergence and characteristics of strains with reduced beta-lactam susceptibility (RS) over a 20-year period.
Methods
We analyzed RS iGBS isolates from eight Active Bacterial Core surveillance sites from 1998–2017. Through 2014, minimum inhibitory concentrations (MIC) for six BL were determined by broth microdilution, followed by whole genome sequencing (WGS) of RS isolates exceeding pre-defined breakpoints (Table 1). In 2015, WGS and MIC testing were performed for all isolates. After 2015, all isolates underwent WGS. MIC testing was continued on approximately 25% of isolates; otherwise, only those with modified penicillin binding protein (PBP) 2x transpeptidase amino acid sequence types or suboptimal WGS (< 1 % of isolates) underwent MIC testing. Clinical information on RS cases was abstracted from medical charts.
Results
Of 26,058 out of 27,269 iGBS isolates (95.6%) tested to date, 107 (0.4%) exhibited RS, increasing from 0% in 1998 to a peak of 1.1% in 2016 (P< 0.05 for trend) (Figure 1). Seven (6.5%) RS strains were from infants aged < 90 days; the rest were from adults aged ≥30 years (Table 2). RS strains consisted of 52 PBP2x types with diverse susceptibility patterns (Table 1). Seven RS strains (6.5%) had wild-type (non-modified) PBP2x; all met the RS criteria based on a single cephalosporin with a confirmed (repeated) MIC value at the break point (Table 1). Compared to non-RS strains, RS strains were more common in patients who presented with cellulitis and osteomyelitis and with underlying conditions such as diabetes or chronic skin breakdown (Table 2). Of 82 (85.4%) patients with RS strains and additional clinical information, 8.3% had known prior GBS infection; 26.8% had known BL exposure in the preceding year.
Conclusion
Preliminary results show that RS increased in recent years; strains RS to penicillin and ampicillin remain low. Variable pbp2x mutations have emerged and predominant strains have not yet been identified.
Disclosures
Nisha B. Alden, MPH, CDC (Grant/Research Support) Lee Harrison, MD, Dynavax (Consultant)GSK (Consultant)Merck (Consultant)OMVax (Consultant)Pfizer (Consultant)Sanofi Pasteur (Consultant)
Susceptibility of group B streptococci to 16 beta-lactam antibiotics, including new penicillin and cephalosporin derivatives.