Inoculum Effect with Cefazolin among Clinical Isolates of Methicillin-Susceptible
            <i>Staphylococcus aureus</i>
            : Frequency and Possible Cause of Cefazolin Treatment Failure

Nannini, Esteban C.; Stryjewski, Martín E.; Singh, Kavindra V.; Bourgogne, Agathe; Rude, Tom H.; Corey, G. Ralph; Fowler, Vance G.; Murray, Barbara E.

doi:10.1128/aac.00317-09

Cited by 112 publications

(146 citation statements)

References 29 publications

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“…First of all, the number of patients in each group was limited in order to have better matching between the groups; thus, the number of patients may have been too small to detect differences in treatment outcomes between cefazolin and nafcillin, especially considering that approximately 20% of isolates showed an inoculum effect on cefazolin (10). A sample size of 110 in each group was needed to detect a 10% difference in mortality with 80% power and a 5% alpha error.…”

Section: Discussionmentioning

confidence: 99%

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Is Cefazolin Inferior to Nafcillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia?

Lee

Choe

Song

et al. 2011

Antimicrob Agents Chemother

109

100

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Section: Discussionmentioning

confidence: 99%

“…Among 4 identified Blas, type A Bla most efficiently hydrolyzes cefazolin (14). Recently, a study demonstrated that about 20% of MSSA isolates showed a substantial inoculum effect and suggested that cefazolin treatment might be associated with clinical failure for serious MSSA infections (10).…”

mentioning

confidence: 99%

Is Cefazolin Inferior to Nafcillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia?

Lee

Choe

Song

et al. 2011

Antimicrob Agents Chemother

109

100

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“…The role of this agent was questioned, however, following case reports of treatment failures, suggesting a reduced efficacy compared to the efficacy of antistaphylococcal penicillins (23,234). Potential explanations for this included an increased susceptibility of cefazolin to the inoculum effect (208) and to staphylococcal ␤-lactamases (248). No randomized control trial comparing these agents has been performed to definitively answer questions regarding relative efficacies.…”

Section: Antibiotic Choicementioning

confidence: 99%

Predictors of Mortality in Staphylococcus aureus Bacteremia

et al. 2012

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SUMMARY Staphylococcus aureus bacteremia (SAB) is an important infection with an incidence rate ranging from 20 to 50 cases/100,000 population per year. Between 10% and 30% of these patients will die from SAB. Comparatively, this accounts for a greater number of deaths than for AIDS, tuberculosis, and viral hepatitis combined. Multiple factors influence outcomes for SAB patients. The most consistent predictor of mortality is age, with older patients being twice as likely to die. Except for the presence of comorbidities, the impacts of other host factors, including gender, ethnicity, socioeconomic status, and immune status, are unclear. Pathogen-host interactions, especially the presence of shock and the source of SAB, are strong predictors of outcomes. Although antibiotic resistance may be associated with increased mortality, questions remain as to whether this reflects pathogen-specific factors or poorer responses to antibiotic therapy, namely, vancomycin. Optimal management relies on starting appropriate antibiotics in a timely fashion, resulting in improved outcomes for certain patient subgroups. The roles of surgery and infectious disease consultations require further study. Although the rate of mortality from SAB is declining, it remains high. Future international collaborative studies are required to tease out the relative contributions of various factors to mortality, which would enable the optimization of SAB management and patient outcomes.

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“…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.…”

mentioning

confidence: 99%

“…The distribution was similar for isolates with higher penicillin MICs (Table 3). 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).…”

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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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Inoculum Effect with Cefazolin among Clinical Isolates of Methicillin-Susceptible Staphylococcus aureus : Frequency and Possible Cause of Cefazolin Treatment Failure

Cited by 112 publications

References 29 publications

Is Cefazolin Inferior to Nafcillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia?

Is Cefazolin Inferior to Nafcillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia?

Predictors of Mortality in Staphylococcus aureus Bacteremia

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

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