By Mais Faraj
October 11, 2015

Cefazolin Trumps Nafcillin for MSSA Infection

SAN DIEGO — For patients infected with methicillin-susceptible Staphyl ococcus aureus  (MSSA), outcomes with cefazolin are similar to those with nafcillin, the recommended first-line therapy, according to a new study.
However, cefazolin is less expensive, more convenient, and leads to fewer adverse events.
"The reason nafcillin is usually preferred over cefazolin is the concern for the inoculum effect, which is seen when you have infections with a high bacterial burden, such as endocarditis and osteomyelitis," said investigator Maggie Monogue, PharmD, from the Parkland Health and Hospital System in Dallas.
The inoculum effect refers to the decreasing effectiveness of an antibiotic with increasing bacterial density, she explained. It is related to the beta-lactamase enzymes that are produced by the bacteria, which have been shown to deactivate cefazolin in vitro.
"From our findings, it looks as if the inoculum effect is not a concern," Dr Monogue told Medscape Medical News. "We recommend using cefazolin over nafcillin regardless of severity of illness."
The study results were presented here at the Interscience Conference of Antimicrobial Agents and Chemotherapy 2015.
From our findings, it looks as if the inoculum effect is not a concern.
In their single-center, retrospective, noninferiority study, Dr Monogue and her colleagues assessed 142 patients infected with MSSA. Half were treated with cefazolin and half with nafcillin.
The primary source of infection was an intravenous catheter in 24% of the patients and skin or wound infection in 16%.
The primary outcome was the rate of treatment failure, defined as a switch in antibiotics because of lack of clinical improvement or adverse reaction, recurrent MSSA infection within 90 days, persistent bacteremia for at least 72 hours, or MSSA-associated death within 30 days.
There was no significant difference in the primary outcome between the cefazolin and nafcillin groups (8.4% vs 14.0%).
However, the rate of adverse events was significantly lower in the cefazolin group than in the nafcillin group (7.0% vs 19.7%; P = .027).
Event Cefazolin, % Nafcillin, % P Value
Nephrotoxicity 2.8 16.9 ≤0.05
Neutropenia 2.8 0.0 0.77
Thrombocytopenia 4.2 1.4 0.77
Drug-induced fever 1.4 0.0 0.89
Other 0.0 1.4 0.89

For patients with endocarditis, pneumonia, deep abscesses, or osteomyelitis, there were no treatment failures in the cefazolin group; however, Dr Monogue acknowledged, the study did not specifically investigate the inoculum effect.
"We don't want to assume there was not an inoculum effect, although we did have a fair number of high-burden patients with osteomyelitis, deep abscesses, endocarditis," she explained. "We'd need a larger sample size to really make that solid conclusion."
In this study, there were 16 patients with osteomyelitis (six in the cefazolin group and 10 in the nafcillin group), eight with infective endocarditis (three in the cefazolin group and five in the nafcillin group), 14 with deep abscesses (six in the cefazolin group and eight in the nafcillin group), and seven with pneumonia (three in the cefazolin group and four in the nafcillin group).
"It's just great to see that we're now getting more and more support for using cefazolin instead of some of these more expensive agents," said Athena Hobbs, PharmD, from Baptist Memorial Hospital in Memphis, Tennessee, who stopped to discuss the poster.

"Using a more cost-effective agent makes sense, and actually seeing the clinical outcomes from that is great," she told Medscape Medical News.
Dr Monogue and Dr Hobbs have disclosed no relevant financial relationships.
Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC) 2015: Abstract S912. Presented September 19, 2015.

Author Description

Mais Faraj

Mais is a clinical pharmacist at Superior Care Pharmacy.

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