Comparative Effectiveness of Cefazolin Versus Nafcillin or Oxacillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections Complicated by Bacteremia: A Nationwide Cohort Study

McDanel, Jennifer S.; Roghmann, Mary-Claire; Perencevich, Eli N.; Ohl, Michael; Goto, Michihiko; Livorsi, Daniel J; Jones, Makoto; Albertson, Justin; Nair, Rajeshwari; O'Shea, Amy; Schweizer, Marin L.

doi:10.1093/cid/cix287

Cited by 115 publications

(95 citation statements)

References 19 publications

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“…Similar to the results of our study, several other retrospective studies have suggested that cefazolin and antistaphylococcal penicillin agents may have similar efficacy in the treatment of MSSA BSI [6-9]. Others have even suggested a treatment benefit with cefazolin over antistaphylococcal penicillins [17, 24]. Several comprehensive reviews of these data have been published elsewhere [12, 25, 26].…”

Section: Discussionsupporting

confidence: 88%

“…Cefazolin patients in our cohort also had a significantly higher incidence of diabetes than nafcillin patients. McDanel et al [24] reported a similar difference in patients with diabetes being more likely to receive cefazolin (incidence of diabetes: 40 vs. 33%; p < 0.001). The clinical implication of this finding remains unclear.…”

Section: Discussionmentioning

confidence: 90%

“…Rates of adverse drug effects were also higher in the oxacillin arm (30 vs. 3%; p = 0.0006). In a large, retrospective, multicenter cohort study of 1,163 patients receiving cefazolin and 2,004 patients receiving nafcillin or oxacillin at 119 Veterans Affairs hospitals, 90-day mortality rates were 20% in the cefazolin group and 25% in the antistaphylococcal penicillin group ( p = 0.001) [24]. Rates of MSSA infection recurrence at 90 days were similar among groups (2 vs. 1%; p = 0.474).…”

Section: Discussionmentioning

confidence: 99%

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Does the Beta-Lactam Matter? Nafcillin versus Cefazolin for Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections

et al. 2018

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Background: Antistaphylococcal penicillins have historically been regarded as the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI). However, recent outcomes data compared to cefazolin treatment are conflicting. Objective: This study compared treatment failure and adverse effects associated with nafcillin and cefazolin for MSSA BSI. Methods: Adult inpatients with MSSA BSI between January 1, 2009 and August 31, 2015 were included in this retrospective cohort study if they received ≥72 h of nafcillin or cefazolin as directed therapy after no more than 72 h of any empiric therapy. The primary composite endpoint was treatment failure defined by clinician documentation, 30-day recurrence of infection, all-cause 30-day in-hospital mortality, or loss to follow-up. Secondary outcomes included antibiotic-related acute kidney injury (AKI), acute interstitial nephritis (AIN), hepatotoxicity, and rash. Results: Among 157 patients, 116 (73.9%) received nafcillin and 41 (26.1%) received cefazolin. The baseline characteristics were similar except cefazolin-treated patients had higher APACHE II scores and more frequent renal dysfunction. No difference in the composite treatment failure outcome (28.4 vs. 31.7%; p = 0.69) was detected between the nafcillin and cefazolin groups, respectively. In a sensitivity analysis excluding patients without known follow-up, there was no significant difference of treatment failure. AKI, AIN, hepatotoxicity, and rash were all numerically more frequent among nafcillin-treated patients. Conclusions: Among nafcillin- or cefazolin-treated patients with MSSA BSI, there was no significant difference in treatment failure. Observing more frequent presumptive adverse effects associated with nafcillin receipt, future prospective studies evaluating cefazolin appear warranted.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Does the Beta-Lactam Matter? Nafcillin versus Cefazolin for Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections

et al. 2018

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“…Unlike previous reports, our study directly addresses the question of whether the presence of the CzIE negatively affects patient survival. Prior studies of cefazolin vs nafcillin for MSSA bacteremia have largely focused on retrospective clinical data, with limited or no microbiologic information, including evaluation of the presence of the CzIE [23–25, 29]. One retrospective study analyzed 113 patients with MSSA bacteremia whose isolates were available for testing.…”

Section: Discussionmentioning

confidence: 99%

The Cefazolin Inoculum Effect Is Associated With Increased Mortality in Methicillin-Susceptible Staphylococcus aureus Bacteremia

Miller

Seas

Carvajal

et al. 2018

Open Forum Infectious Diseases

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BackgroundRecent studies have favored the use of cefazolin over nafcillin for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. The clinical influence of the cefazolin inoculum effect (CzIE) in the effectiveness of cephalosporins for severe MSSA infections has not been evaluated.MethodsWe prospectively included patients from 3 Argentinian hospitals with S. aureus bacteremia. Cefazolin minimum inhibitory concentrations (MICs) were determined at standard (105 colony-forming units [CFU]/mL) and high (107 CFU/mL) inoculum. The CzIE was defined as an increase of MIC to ≥16 µg/mL when tested at high inoculum. Whole-genome sequencing was performed in all isolates.ResultsA total of 77 patients, contributing 89 MSSA isolates, were included in the study; 42 patients (54.5%) had isolates with the CzIE. In univariate analysis, patients with MSSA exhibiting the CzIE had increased 30-day mortality (P = .034) and were more likely to have catheter-associated or unknown source of bacteremia (P = .033) compared with patients infected with MSSA isolates without the CzIE. No statistically significant difference between the groups was observed in age, clinical illness severity, place of acquisition (community vs hospital), or presence of endocarditis. The CzIE remained associated with increased 30-day mortality in multivariate analysis (risk ratio, 2.65; 95% confidence interval, 1.10–6.42; P = .03). MSSA genomes displayed a high degree of heterogeneity, and the CzIE was not associated with a specific lineage.ConclusionsIn patients with MSSA bacteremia where cephalosporins are used as firstline therapy, the CzIE was associated with increased 30-day mortality. Clinicians should be cautious when using cefazolin as firstline therapy for these infections.

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“…This approach assumes that any other antibiotics received, for any duration, are equal in terms of beneficial and harmful effects. Operational definitions of definitive therapy also differ by study, where periods of empiric and definitive therapy may vary between patients or be set equal for all patients . A solution to this misclassification has been to include those without changes in therapy, treated with monotherapy or simple combinations.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity in the treatment of bloodstream infections identified from antibiotic exposure mapping

Caffrey

Babcock

Lopes

et al. 2019

Pharmacoepidemiology and Drug

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Purpose As changes in antibiotic therapy are common, intent‐to‐treat and definitive therapy exposure definitions in infectious disease clinical trials and observational studies may not accurately reflect all antibiotics received over the course of the infection. Therefore, we sought to describe changes in antibiotic therapy and unique treatment patterns among patients with bacteremia. Methods We conducted a retrospective cohort study of hospitalizations from Veterans Affairs (VA) Medical Centers (January 2002‐September 2015) and community hospitals (de‐identified Optum Clinformatics DataMart with matched Premier Hospital data; October 2009‐March 2013). In the VA population, antibiotic exposures were mapped from the culture collection date among those with positive Staphylococcus aureus cultures. In the Optum‐Premier population, exposures were mapped from the admission date among those with a primary diagnosis of bacteremia. Results Our study included 50 467 bacteremia admissions, with only 14% of admissions having the same treatment pattern as another admission. For every 100 bacteremia admissions, 89 had changes in antibiotic therapy. For every 100 bacteremia admissions with changes in therapy, 95 had unique antibiotic treatment patterns. These findings were consistent in both populations, over time, and among different facilities within study populations. The median time to first therapy change was 2 days after initial therapy, with a median of three changes. Conclusions Changes in antibiotic therapy for bloodstream infections were nearly universal regardless of hospital setting. Based on our findings, common antibiotic exposure definitions of intent‐to‐treat and definitive therapy would misclassify exposure in 86% of admissions, which highlights the need for better operational definitions of exposure in infectious diseases research.

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Comparative Effectiveness of Cefazolin Versus Nafcillin or Oxacillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections Complicated by Bacteremia: A Nationwide Cohort Study

Cited by 115 publications

References 19 publications

Does the Beta-Lactam Matter? Nafcillin versus Cefazolin for Methicillin-Susceptible <b><i>Staphylococcus aureus</i></b> Bloodstream Infections

Does the Beta-Lactam Matter? Nafcillin versus Cefazolin for Methicillin-Susceptible <b><i>Staphylococcus aureus</i></b> Bloodstream Infections

The Cefazolin Inoculum Effect Is Associated With Increased Mortality in Methicillin-Susceptible Staphylococcus aureus Bacteremia

Heterogeneity in the treatment of bloodstream infections identified from antibiotic exposure mapping

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