title: Poor outcomes of empiric ceftriaxone ± azithromycin for community-acquired pneumonia caused by methicillin-susceptible Staphylococcus aureus.
abstract: While ceftriaxone 1 g q24h is commonly used for hospitalized patients with community-acquired pneumonia (CAP), the prescribing information recommends 2-4 g a day to treat methicillin-susceptible Staphylococcus aureus (MSSA). Similarly, recent pharmacodynamic analyses suggest shortcomings of 1 g q24h against the bulk of the MSSA. We evaluated the outcomes of empiric ceftriaxone 1 g q24h ± azithromycin in patients with MSSA pneumonia, as compared with Streptococcus pneumoniae. Adult patients admitted to Hartford Hospital from 1/2005 to 12/2014 with respiratory culture for MSSA or S. pneumoniae were considered for inclusion. Non-ICU, CAP patients were included. Early clinical failure (ECF) was defined as persistent signs/symptoms or change of antibiotic due to poor response at 72-96 h. A multivariate analysis was performed to evaluate predictors of ECF. Over the study period, 403 MSSA and 227 S. pneumoniae positive respiratory cultures were identified. The majority of patients were excluded due to the following: no signs/symptoms of pneumonia, hospital-acquired pneumonia, alternative antibiotics, and polymicrobial infection. Thirty-nine patients met inclusion/exclusion criteria. All but three patients in the S. pneumoniae group received ceftriaxone + azithromycin. ECF was greater in the MSSA group (53 vs. 4 %, P = 0.003), as was length of stay (7.5 ± 5.4 vs. 4.6 ± 3.3 days, P = 0.006). When controlling for disease severity and macrolide non-susceptibility in a multivariate analysis, MSSA was significantly correlated with ECF (OR 12.3, 95 % CI 0.8-188.8). Poor clinical outcomes were observed in patients empirically treated with ceftriaxone ± azithromycin for MSSA CAP. Despite the popularity of ceftriaxone 1 g q24h, these data suggest this dose or compound may be inadequate for CAP caused by MSSA.
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour St, Hartford, CT, 06102, USA.
authors.forename: Wonhee
authors.initials: W
authors.lastname: So
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour St, Hartford, CT, 06102, USA.
authors.forename: Jared L
authors.initials: JL
authors.lastname: Crandon
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour St, Hartford, CT, 06102, USA. david.nicolau@hhchealth.org.|Division of Infectious Diseases, Hartford Hospital, 80 Seymour St, Hartford, CT, 06102, USA. david.nicolau@hhchealth.org.
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D000368:Aged; D017963:Azithromycin / Q000627:therapeutic use*; D002443:Ceftriaxone / Q000627:therapeutic use*; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology*; D004359:Drug Therapy, Combination; D005260:Female; D006760:Hospitalization; D006801:Humans; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000188:drug therapy* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013296:Streptococcus pneumoniae / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D002443:Ceftriaxone; D017963:Azithromycin
keywords: Ceftriaxone; MSSA; Outcomes; Pneumonia