SAN FRANCISCOCA—Significantly high rates of premature treatment discontinuation was observed in patients treated with either nafcillin or cefazolin, with high rates of drug-related adverse events (DRAE) occurring with nafcillin treatment, as presented at IDWeek 2013.

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Methicillin-sensitive Staphylococcus aureus (MSSA), a major pathogen found in community-acquired and healthcare-associated infections, is the most common cause for prolonged antimicrobial administration. Ilan Youngster, MD, from Boston Children’s Hospital and Massachusetts General Hospital, Boston, MA, and colleagues explained that first-line therapy for most MSSA infections is nafcillin and cefazolin but limited data exists on the safety and tolerability of these agents.

This retrospective cohort analysis consisted of patients treated with either nafcillin or cefazolin for MSSA infection in the outpatient parenteral antimicrobial therapy (OPAT) clinic at Massachusetts General Hospital from 2007–2011. Researchers reviewed laboratory and clinical data including demographics, source of infection, baseline disease, treatment length, co-medications, DRAE, and all-cause medication discontinuation rates. Patients were treated with nafcillin (n=366) or cefazolin (n=119) for a median of 28 days (16–37) and 29 days (24–39) respectively.

Analyses showed that significantly fewer patients completed the prespecified treatment course with nafcillin (34% overall discontinuation rate of nafcillin vs. 7% in the cefazolin group, P<0.0001). In nine cases of nafcillin discontinuation, treatment was changed to cefazolin. All patients completed treatment with no further DRAE.  

Rash occurred in 51 (13.9%) patients in the nafcillin group compared to 5 (4.2%) in the cefazolin group (P=0.002). Similarly, renal dysfunction [42 (11.4%) vs. 4 (3.3%); P=0.006] and transaminitis [30 (8.1%) vs. 2 (1.6%); P=0.01] were more commonly observed in nafcillin-treated patients than cefazolin-treated patients. Neutropenia developed in 31 (8.4%) patients on nafcillin and in 4 (3.3%) patients on cefazolin (P=0.06). In addition, C. difficile colitis developed in 9 (2.4%) patients on nafcillin therapy and one patient (0.8%) on cefazolin (P=0.46). 

Nafcillin treatment was associated with higher rates of DRAE than cefazolin treatment, researchers concluded. Treatment discontinuation was significantly higher in patients in the nafcillin group vs. cefazolin group.

“Difference in tolerability, in addition to efficacy and cost, should be taken into account when deciding on long term IV treatment for MSSA in the OPAT setting,” noted Dr. Youngster.