June 19, 2018
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Cefazolin inoculum effect associated with higher mortality in patients with MSSA

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The cefazolin inoculum effect is associated with an increase in 30-day all-cause mortality in patients with methicillin-susceptible Staphylococcus aureus bacteremia, or MSSA, where cephalosporins are used as first-line therapy, according to study findings published in Open Forum Infectious Diseases.

Recent studies have favored using cefazolin — a first-generation cephalosporin — over nafcillin to treat MSSA bacteremia, but research has not evaluated the clinical influence of the cefazolin inoculum effect (CzIE) on the effectiveness of cephalosporins for severe MSSA infections, said William R. Miller, MD, assistant professor in the division of infectious diseases and member of the Center for Antimicrobial Resistance and Microbial Genomics at the UTHealth McGovern Medical School in Houston, and colleagues.

“The cephalosporin inoculum effect is defined as a prominent rise in the antibiotic minimum inhibitory concentration ... when the susceptibility test is performed with an inoculum higher than the standard recommended bacterial inoculum,” they wrote.

For their study, they prospectively evaluated 77 patients with MSSA bacteremia seen at three Argentinian hospitals and determined cefazolin MICs at both standard (approximately 105 CFU/mL) and high (approximately 107 CFU/mL) inoculum. They defined CziE as an increase of MIC of at least 16 g/mL when tested at high inoculum.

Miller and colleagues observed the CzIE in 54.5% of patients and an 85.3-fold average increase in the cefazolin MIC for isolates that demonstrated the CzIE when tested at high inoculum. Patients with isolates exhibiting the CzIE were more likely to have a primary bacteremia associated with a catheter or an unknown source (P = .03) and significantly higher baseline creatinine levels vs. those without the CzIE (0.9 vs. 1.4; P = .005). Patients from the two groups had no statistically significant differences in age, clinical illness severity, place of acquisition or presence of endocarditis, Miller and colleagues reported.

There was no difference in 7-day all-cause mortality between the groups, but CzIE was associated with significantly increased mortality at 30 days (39.5% vs. 15.2%; P=.034), they reported. Adjusting for confounders, the researchers found that MSSA patients with the CzIE still had significantly higher 30-day mortality (RR = 2.65; 95% CI, 1.10-6.42; P = 0.03). An association was also seen between higher 30-day, all-cause mortality and a secondary source of bacteremia (RR = 2.15; 95% CI, 1.01-4.57; P = .047).

In addition, they identified a trend toward increased 30-day mortality in patients older than age 81 years.

“In patients with MSSA bacteremia where cephalosporins are used as first-line therapy, the CzIE was associated with increased 30-day mortality,” the researchers wrote. “Clinicians should be cautious when using cefazolin as first-line therapy for these infections.” – by Jennifer Byrne

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Disclosures: Miller reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.