Prevalence and Characterization of the Cefazolin Inoculum Effect in North American Methicillin-Susceptible Staphylococcus aureus Isolates

Dingle, Tanis C.; Gamage, Dulini; Gómez-Villegas, Sara I; Hanson, Blake; Reyes, Jinnethe; Abbott, April N.; Burnham, Carey‐Ann D.; Bard, Jennifer Dien; Fritz, Stephanie A.; Miller, William R.; Westblade, Lars F.; Zimmer, Barbara; Arias, César A.; Butler-Wu, Susan M.

doi:10.1128/jcm.02495-21

Cited by 13 publications

(9 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This treatment distinction was based on the potential that the cefazolin inoculum effect (CzIE) may render cefazolin less effective than ASPs based on in vitro findings, demonstrating cefazolin is more susceptible to beta-lactamase degradation than ASPs [ 26 ]. Specifically, isolates are determined to display CzIE if there is an increase in MIC to >16 mcg/mL when susceptibility testing is performed with higher bacterial inoculums of ~5 × 10 7 colony-forming units (CFU)/mL, as opposed to the standard density of ~5 × 10 5 CFU/mL [ 27 ]. This testing is not routinely performed in clinical laboratories, given the laborious nature of the methodologies.…”

Section: Beta-lactam Selection In Methicillin-susceptible S...mentioning

confidence: 99%

“…This testing is not routinely performed in clinical laboratories, given the laborious nature of the methodologies. An epidemiologic study of S. aureus isolates from North America identified the CzIE to be displayed in 18.6% (57/305), with some geographical variability in prevalence [ 27 ]. However, data pertaining to the impact of CzIE on patient outcomes are limited.…”

Section: Beta-lactam Selection In Methicillin-susceptible S...mentioning

confidence: 99%

See 1 more Smart Citation

Heartbreaking Decisions: The Dogma and Uncertainties of Antimicrobial Therapy in Infective Endocarditis

et al. 2023

View full text Add to dashboard Cite

Infective endocarditis (IE) is a rare but increasingly prevalent disease with high morbidity and mortality, requiring antimicrobials and at times surgical intervention. Through the decades of healthcare professionals’ experience with managing IE, certain dogmas and uncertainties have arisen around its pharmacotherapy. The introduction of new antimicrobials and novel combinations are exciting developments but also further complicate IE treatment choices. In this review, we provide and evaluate the relevant evidence focused around contemporary debates in IE treatment pharmacotherapy, including beta-lactam choice in MSSA IE, combination therapies (aminoglycosides, ceftaroline), the use of oral antimicrobials, the role of rifamycins, and long-acting lipoglycopeptides.

show abstract

Section: Beta-lactam Selection In Methicillin-susceptible S...mentioning

confidence: 99%

Section: Beta-lactam Selection In Methicillin-susceptible S...mentioning

confidence: 99%

Heartbreaking Decisions: The Dogma and Uncertainties of Antimicrobial Therapy in Infective Endocarditis

et al. 2023

View full text Add to dashboard Cite

show abstract

“…45,46 In 2018, Wang and colleagues 47 noted that 23% of the 45 isolates collected from 4 major medical centers in Chicago exhibited CzIE, while 24% of the blaZ -positive isolates had ≥4-fold elevation in cefazolin MIC between standard and high inoculum. In 2022, Dingle and colleagues 48 evaluated clinical MSSA isolates from 6 laboratories across North America noting the overall CzIE prevalence was 18.6% but ranged from 0% to 27.9%.…”

Section: Study Selection/data Extractionmentioning

confidence: 99%

Therapeutic Options for Adult Patients With Persistent Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Narrative Review

Chastain

Covert

et al. 2023

Ann Pharmacother

View full text Add to dashboard Cite

Objective: To compare the efficacy of antimicrobial therapies used in the management of persistent methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Data Sources: A literature search using the PubMed database (inception to December 2022) was conducted using the search terms “ Staphylococcus aureus bacteremia,” “methicillin-susceptible Staphylococcus aureus bacteremia,” “persistent methicillin-susceptible Staphylococcus aureus bacteremia,” and “refractory methicillin-susceptible Staphylococcus aureus bacteremia .” In addition, therapeutic agents which could be used as treatment for MSSA including “nafcillin,” “oxacillin,” “cefazolin,” “ceftaroline,” “gentamicin,” “rifampin,” and “daptomycin” were also combined with the aforementioned search terms to capture data using these agents. Study Selection/Data Extraction: Clinical data were limited to those published in the English language. Articles and abstracts were considered for inclusion in addition to ongoing trials identified through ClinicalTrials.gov. Data Synthesis: A total of 78 articles were reviewed including 17 in vitro or animal model studies and 39 studies including patient data. The remaining 22 articles included guidelines, review articles, and editorials. Recent data evaluating use of dual β-lactam regimens for persistent MSSA bacteremia were limited to 8 case reports or case series. Relevance to Patient Care and Clinical Practice: At present, there is little guidance on how to best manage patients with persistent MSSA bacteremia. This narrative review collates the available data to assist clinicians in selecting the best possible antimicrobial regimen when facing this clinical conundrum. Conclusions: Modification of antimicrobial therapy, in conjunction with source control and infectious diseases consultation, may all be necessary to sterilize blood cultures in patients with persistent MSSA bacteremia.

show abstract

“…the effect is proportionate to the bacterial inoculum present at site of infection). 6 The CzIE phenomenon is potentially mediated by the β-lactamase enzyme ( blaZ) gene encoding type A and C β-lactamases in MSSA isolates. 7 Reportedly, up to 25% of MSSA isolates exhibit CzIE, based on a North American study of 305 blood culture isolates.…”

Section: Introductionmentioning

confidence: 99%

“… 7 Reportedly, up to 25% of MSSA isolates exhibit CzIE, based on a North American study of 305 blood culture isolates. 6 The reference standard for detecting CzIE is broth microdilution, which requires technical expertise beyond that available in routine microbiology laboratories. 8 In routine practice, cefazolin susceptibility is inferred from oxacillin or cefoxitin susceptibility testing, molecular detection of mecA or mecC , or PBP2a assay as per CLSI guidelines.…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of cefazolin inoculum effect in serious MSSA infections: a systematic review

Lo,

Sritharan,

Zhang

et al. 2024

JAC-Antimicrobial Resistance

View full text Add to dashboard Cite

Background The cefazolin inoculum effect (CzIE) is a phenomenon whereby some MSSA isolates demonstrate resistance to cefazolin when a high bacterial inoculum is used for susceptibility testing. The clinical significance of this phenotypic phenomenon remains unclear. We conducted a systematic review to answer the following question: In patients with serious MSSA infection treated with cefazolin, does infection due to CzIE-positive MSSA isolates result in worse clinical outcomes than infection due to CzIE-negative MSSA isolates? Methods Ovid MEDLINE, Embase, Cochrane CENTRAL, medRxiv and bioRxiv were searched from inception until 12 April 2023. Studies were included if they tested for CzIE in clinical isolates from MSSA infections in humans. Two independent reviewers extracted data and conducted risk-of-bias assessment. Main outcomes were treatment failure and mortality. Pooling of study estimates was not performed given the heterogeneity of patient populations and outcome definitions. Results Twenty-three observational studies were included. CzIE presence amidst MSSA isolates ranged from 0% to 55%. There was no statistically significant mortality difference in two studies that compared MSSA infections with and without CzIE, with ORs ranging from 0.72 to 19.78. Of four studies comparing treatment failure, ORs ranged from 0.26 to 13.00. One study showed a significantly higher treatment failure for the CzIE group, but it did not adjust for potential confounders. Conclusions The evidence on CzIE is limited by small observational studies. In these studies, CzIE did not predict higher mortality in MSSA infections treated with cefazolin. Our findings do not support CzIE testing in clinical practice currently.

show abstract

Prevalence and Characterization of the Cefazolin Inoculum Effect in North American Methicillin-Susceptible Staphylococcus aureus Isolates

Abstract: Antistaphylococcal penicillins and cefazolin remain the primary treatments for infections with methicillin-susceptible Staphylococcus aureus (MSSA). The cefazolin inoculum effect (CzIE) causes the cefazolin MIC to be elevated in proportion to the number of bacteria in the inoculum.

Cited by 13 publications

References 27 publications

Heartbreaking Decisions: The Dogma and Uncertainties of Antimicrobial Therapy in Infective Endocarditis

Heartbreaking Decisions: The Dogma and Uncertainties of Antimicrobial Therapy in Infective Endocarditis

Therapeutic Options for Adult Patients With Persistent Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Narrative Review

Clinical significance of cefazolin inoculum effect in serious MSSA infections: a systematic review

Contact Info

Product

Resources

About