Prevalence of blaZ gene types and the cefazolin inoculum effect among methicillin-susceptible Staphylococcus aureus blood isolates and their association with multilocus sequence types and clinical outcome

Chong, Yong Pil; Park, S.‐J.; Kim, E. S.; Bang, Kyung Mi; Kim, M.-N.; Kim, S.-H.; Lee, S.-O.; Choi, Sang‐Ho; Jeong, Jin‐Yong; Woo, Jun Hee; Kim, Y. S.

doi:10.1007/s10096-014-2241-5

Cited by 39 publications

(47 citation statements)

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“…There are published reports (including from our group) that correlate the CFZ inoculum effect with clinical failure (4,5,7,14,16). These reports have shown that, in the majority of the strains, an increase in the CFZ MICs (tested at high inoculum) was associated with the presence of type A ␤-lactamase (4, 5, 7).…”

Section: Discussionmentioning

confidence: 91%

“…This review states that, in addition, limited by small sample size and possible selection bias, the only comparative study to date examining the clinical impact of the cefazolin InE (i.e., the study referred to above from Asia [South Korea] [7]) did not show any significant differences in outcomes when comparing isolates with and without cefazolin InE. However, it is not clear what percentage of the patients had endocarditis or deep-seated and/or undrained infections, which would be more likely to have a large inoculum present.…”

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confidence: 99%

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Efficacy of Ceftaroline against Methicillin-Susceptible Staphylococcus aureus Exhibiting the Cefazolin High-Inoculum Effect in a Rat Model of Endocarditis

Singh

Tran

Nannini

et al. 2017

Antimicrob Agents Chemother

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Certain Staphylococcus aureus strains exhibit an inoculum effect (InE) with cefazolin (CFZ) that has been associated with therapeutic failures in highinoculum infections. We assessed the in vitro activities of ceftaroline (CPT), CFZ, and nafcillin (NAF) against 17 type A ␤-lactamase (␤la)-producing, methicillin-susceptible S. aureus (MSSA) strains, including the previously reported TX0117, which exhibits the CFZ InE, and its ␤la-cured derivative, TX0117c. Additionally, we determined the pharmacokinetics of CPT in rats after single intramuscular doses of 20 and 40 mg/kg of body weight and evaluated the activities of CPT (40 mg/kg every 8 h [q8h]), CFZ, and NAF against TX0117 and TX0117c in a rat model of infective endocarditis. No InE was observed for CPT or NAF, whereas a marked InE was detected for CFZ (MIC, 8 to Ն128 g/ml). CPT and NAF treatment against TX0117 resulted in mean bacterial counts of 2.3 and 2.1 log 10 CFU/g in vegetations, respectively, compared to a mean of 5.9 log 10 CFU/g in the CFZ-treated group (CPT and NAF versus CFZ, P ϭ 0.001; CPT versus NAF, P ϭ 0.9830). Both CFZ and CPT were efficacious against the ␤la-cured derivative, TX0117c, compared to time zero (t 0 ) (P ϭ Ͻ0.0001 and 0.0015, respectively). Our data reiterate the in vivo consequences of the CFZ InE and show that CPT is not affected by this phenomenon. CPT might be considered for highinoculum infections caused by MSSA exhibiting the CFZ InE.KEYWORDS ␤-lactamase, Staphylococcus aureus, ceftaroline, endocarditis S taphylococcus aureus continues to be a leading cause of bacterial infections worldwide, including skin and soft tissue infections, bacteremia, pneumonia, endocarditis, septic arthritis, and osteomyelitis (1-3). The prevalence of methicillin-susceptible S. aureus (MSSA) isolates exhibiting the cefazolin (CFZ) inoculum effect (InE) in the United States has been reported to range from 19% to 27% (4, 5). Besides the United States, the overall prevalence of the cefazolin InE was reported to be 36% in South America (Colombia, Ecuador, Peru, and Venezuela), where MSSA ␤-lactamase (␤la) type A and type C were 66% and 31%, respectively (6). In South Korea, the blaZ gene was detected in 92% of 220 MSSA isolates studied, and a pronounced cefazolin InE was observed in 13%, most of which (79%) expressed type A ␤-lactamase (7). More recently, a study

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Section: Discussionmentioning

confidence: 91%

mentioning

confidence: 99%

Efficacy of Ceftaroline against Methicillin-Susceptible Staphylococcus aureus Exhibiting the Cefazolin High-Inoculum Effect in a Rat Model of Endocarditis

Singh

Tran

Nannini

et al. 2017

Antimicrob Agents Chemother

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“…A 2009 study analyzing 98 MSSA isolates reported no blaZ for 13%, type A ␤-lactamase for 26%, type B for 15%, and type C for 46% (8). A South Korean study found type A blaZ in 17%, type B in 20%, type C in 53%, and type D in 1% of 220 MSSA isolates (12). Cefazolin failures have been reported for MSSA infections caused by type A blaZ isolate demonstrating an inoculum effect (8), but other retrospective studies have only found treatment success (12).…”

mentioning

confidence: 99%

“…A South Korean study found type A blaZ in 17%, type B in 20%, type C in 53%, and type D in 1% of 220 MSSA isolates (12). Cefazolin failures have been reported for MSSA infections caused by type A blaZ isolate demonstrating an inoculum effect (8), but other retrospective studies have only found treatment success (12). Prospective studies are needed to determine if screening MSSA isolates for a cefazolin inoculum effect has clinical utility.…”

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confidence: 99%

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

et al. 2016

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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...

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“…However, there are concerns about cefazolin therapeutic failures and relapses in the treatment of MSSA strains that demonstrate the CIE (2,3,20,21). Previous studies have demonstrated that the CIE in MSSA is closely associated with the blaZ type, and type A blaZ-positive MSSA can present a CIE (3,11,12,22,23). However, the prevalence of CIE positivity among MSSA strains positive for type A blaZ is variable, and approximately 15 to 65% of these strains exhibited no CIE (3,11,12,22,23).…”

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confidence: 99%

Association between Type A blaZ Gene Polymorphism and Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus

Lee

Park

Lee

et al. 2016

Antimicrob Agents Chemother

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Prevalence of blaZ gene types and the cefazolin inoculum effect among methicillin-susceptible Staphylococcus aureus blood isolates and their association with multilocus sequence types and clinical outcome

Cited by 39 publications

References 21 publications

Efficacy of Ceftaroline against Methicillin-Susceptible Staphylococcus aureus Exhibiting the Cefazolin High-Inoculum Effect in a Rat Model of Endocarditis

Efficacy of Ceftaroline against Methicillin-Susceptible Staphylococcus aureus Exhibiting the Cefazolin High-Inoculum Effect in a Rat Model of Endocarditis

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

Association between Type A blaZ Gene Polymorphism and Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus

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