Detection and Prevalence of Penicillin-Susceptible Staphylococcus aureus in the United States in 2013

Abstract

bUsing blaZ PCR as the "gold standard," the sensitivities of CLSI penicillin zone edge and nitrocefin-based tests for ␤-lactamase production in Staphylococcus aureus were 64.5% and 35.5%, respectively, with specificity of 99.8% for both methods. In 2013, 13.5% of 3,083 S. aureus isolates from 31 U.S. centers were penicillin susceptible. P enicillinase-producing strains of Staphylococcus aureus emerged in the 1940s and by the 1970s represented 70 to 85% of the S. aureus population (1). Four types of blaZ genes (A to D) have been associated with penicillinase production in S. aureus (2). A study conducted in Germany demonstrated the sensitivity of nitrocefinbased testing was unacceptably low (36%) for penicillinase detection compared to blaZ PCR (3). Since 2012, the Clinical and Laboratory Standards Institute (CLSI) has recommended the penicillin zone edge test (4) to screen S. aureus isolates with a susceptible penicillin MIC (Յ0.12 g/ml) or disk zone (Ն29 mm) for ␤-lactamase production (5).There are limited data regarding the detection and prevalence of penicillin-susceptible S. aureus using a molecular method as the reference standard. The objectives of this national study were (i) to evaluate multiple phenotypic methods for ␤-lactamase detection in S. aureus using blaZ PCR as the "gold standard" and (ii) to determine the prevalence of penicillin-susceptible S. aureus in the United States.As part of a national surveillance program, laboratories were asked to send 100 clinically significant S. aureus isolates to the University of Iowa. Isolates were recovered from specimens received during June to December 2013. Susceptibility testing using the CLSI broth microdilution method (5, 6) and mecA PCR were performed as previously described (7) on the 3,083 isolates received from 31 centers. The predominant specimen sources were 61% wound, 18% blood, 10% lower respiratory tract, 4% tissue, and 2% sterile body fluid. Classification as methicillin-susceptible S. aureus (MSSA) was based on a negative mecA PCR result. All isolates with a susceptible penicillin MIC (Յ0.12 g/ml) were assessed for ␤-lactamase production using blaZ PCR, penicillin zone edge, and induced nitrocefin-based testing. PCR to amplify a 355-bp region of the blaZ gene was followed by sequencing to classify positive strains as type A, B, C, or D as previously described (8). The blaZ type was also determined for a subset of penicillinresistant isolates (n ϭ 51). The penicillin zone edge test was performed on Mueller-Hinton agar using a 10-U penicillin disk following CLSI guidelines (5). After 16 to 18 h of incubation in ambient air, a sharp zone edge was interpreted as positive and a fuzzy zone as negative for ␤-lactamase production. Nitrocefinbased testing was performed on induced growth taken from the zone margin surrounding a 10-U penicillin disk.As expected, all 1,387 mecA-positive strains had penicillin MICs in the resistant range (Ն0.5 g/ml; 80% at Ͼ16 g/ml). There were 448 isolates (14.5% of all isolates, 26.4% of MSSA isolates) with a susceptible...

Molecular epidemiology of β-lactamase production in penicillin-susceptible Staphylococcus aureus under high-susceptibility conditions

“…First, this is the first report demonstrating a lack of blaZ gene expression in S. aureus isolates with high susceptibility to penicillin G (specifically, MIC 0.03 mg/ml). Consistent with our results, previous studies in the U.S [7]. and Germany [12] found that blaZ positivity rates differed markedly (MIC 0.03 mg/ml, 0%; MIC ¼ 0.06 mg/m, 3.8e6.2%; and MIC ¼ 0.12 mg/ml, 23.2e32.1%).…”

“…At the National Center for Global Health and Medicine (NCGM; Tokyo, Japan), S. aureus isolates with penicillin G minimum inhibitory concentration (MIC) 0.12 mg/ml accounted for 31% of isolates (733/2387) [45% of methicillinsusceptible S. aureus (733/1638), ( Fig. S1)] collected between 2013 and 2015; this is higher than the prevalence of penicillinsusceptible isolates reported in previous studies [7,8]. Therefore, although penicillin G is an option for the treatment of S. aureus infection, careful interpretation of susceptibility results is warranted.…”

“…Penicillinase-producing S. aureus isolates emerged in the 1940s [5], and penicillin susceptibility in S. aureus had decreased to 15%e 30% of isolates by the 1970s [6]. Penicillin-susceptible S. aureus was recently found to constitute 13.5% and 14% of isolates in the U.S. and Australia, respectively [7,8]. At the National Center for Global Health and Medicine (NCGM; Tokyo, Japan), S. aureus isolates with penicillin G minimum inhibitory concentration (MIC) 0.12 mg/ml accounted for 31% of isolates (733/2387) [45% of methicillinsusceptible S. aureus (733/1638), ( Fig.…”

Non-microbial Natural Products That Inhibit Drug-Resistant Staphylococcus aureus

“…However, few years after its introduction, penicillin resistance including penicillin-resistant S. aureus was isolated from hospitals. Penicillin resistance of S. aureus is highly prevalent with up to 86% of clinical S. aureus isolates being resistant to the antibiotic in the US [47]. Meantime, far way in Australia, a similar observation was made as 80% of S. aureus isolates were resistant to penicillin [48].…”

Clinical Outcomes with Penicillin Versus Alternative β‐Lactams in the Treatment of Penicillin‐Susceptible Staphylococcus aureus Bacteremia

“…Interestingly, in recent years, an increasing prevalence of penicillin‐susceptible S. aureus (PSSA) has been observed. In 2013, penicillin susceptibility among S. aureus isolates in the United States was 13.5%, and the prevalence in other places was reported to be even higher . However, vancomycin and extended‐spectrum penicillins were most commonly used for treatment, despite penicillin having a narrow spectrum of activity, minimal adverse drug events (ADEs), and ease of administration as a continuous infusion .…”