Comparative evaluation of the tolerability of cefazolin and nafcillin for treatment of methicillin-susceptible Staphylococcus aureus infections in the outpatient setting.
BACKGROUND
Nafcillin and cefazolin are considered first-line therapy for most infections with methicillin-susceptible Staphylococcus aureus (MSSA), and recent studies have suggested similar clinical efficacy. Limited data are available on the comparative tolerability of these agents.


METHODS
In this retrospective cohort analysis of patients treated with either nafcillin or cefazolin for MSSA infection in the outpatient parenteral antimicrobial therapy clinic at Massachusetts General Hospital from 2007 to 2011, the frequency of premature antimicrobial discontinuation (PAD) and drug-emergent events (DEEs) was calculated.


RESULTS
Three hundred sixty-six and 119 patients were treated with nafcillin or cefazolin, respectively. The median anticipated duration of therapy was comparable at 28 (interquartile range [IQR], 16-37) and 29 (IQR, 24-39) days, respectively, for those treated with nafcillin and cefazolin. Fewer patients completed the prespecified treatment course with nafcillin than with cefazolin (PAD rate, 33.8% vs 6.7%; P < .0001). The hazard ratio for PAD in the nafcillin vs cefazolin groups was 2.81 (95% confidence interval [CI], 1.26-3.68). More patients in the nafcillin group developed rash (13.9% vs 4.2%; P = .002), renal dysfunction (11.4% vs 3.3%; P = .006), and liver function abnormalities (8.1% vs 1.6%; P = .01). Overall rates of DEEs per 1000 patient-days were 16.9 (95% CI, 10.4-27.3) and 4.8 (95% CI, 1.1-10.2), respectively. In 9 cases of nafcillin discontinuation, treatment was changed to cefazolin; all 9 completed treatment with no further observed DEEs.


CONCLUSIONS
Nafcillin treatment was associated with higher rates of both PAD as well as DEEs compared with cefazolin treatment. This difference in tolerability, in addition to efficacy and cost, should be considered when decisions for outpatient parenteral MSSA treatment are made.
Division of Infectious Diseases, Massachusetts General Hospital Harvard Medical School Division of Infectious Diseases, Boston Children's Hospital.
Ilan
I
Youngster
Division of Infectious Diseases, Massachusetts General Hospital Harvard Medical School Infection Control Unit, Massachusetts General Hospital, Boston, Massachusetts.
Erica S
ES
Shenoy
Division of Infectious Diseases, Massachusetts General Hospital Harvard Medical School Infection Control Unit, Massachusetts General Hospital, Boston, Massachusetts.
David C
DC
Hooper
Division of Infectious Diseases, Massachusetts General Hospital Harvard Medical School.
Sandra B
SB
Nelson
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002437:Cefazolin / Q000031:analogs & derivatives*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008404:Massachusetts; D008712:Methicillin / Q000627:therapeutic use; D008875:Middle Aged; D009254:Nafcillin / Q000627:therapeutic use*; D010045:Outpatients; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D009254:Nafcillin; D002437:Cefazolin; D008712:Methicillin
MSSA; OPAT; cefazolin; nafcillin; tolerability