title: Treatment of methicillin-resistant Staphylococcus aureus infections with a minimal inhibitory concentration of 2 μg/mL to vancomycin: old (trimethoprim/sulfamethoxazole) versus new (daptomycin or linezolid) agents.
abstract: BACKGROUND
  Guidelines recommend that agents other than vancomycin be considered for some types of infection due to methicillin-resistant Staphylococcus aureus (MRSA) when the minimum inhibitory concentration (MIC) to vancomycin is 2 μg/mL or more. Alternative therapeutic options include daptomycin and linezolid, 2 relatively new and expensive drugs, and trimethoprim/sulfamethoxazole (TMP/SMX), an old and inexpensive agent.
  
  
  OBJECTIVE
  To compare the clinical efficacy and potential cost savings associated with use of TMP/SMX compared to linezolid and daptomycin.
  
  
  METHODS
  A retrospective study was conducted at Detroit Medical Center. For calendar year 2009, unique adults (age >18 years) with infections due to MRSA with an MIC to vancomycin of 2 μg/mL were included if they received 2 or more doses of TMP/SMX and/or daptomycin and/or linezolid. Data were abstracted from patient charts and pharmacy records.
  
  
  RESULTS
  There were 328 patients included in the study cohort: 143 received TMP/SMX alone, 89 received daptomycin alone, 75 received linezolid alone, and 21 patients received a combination of 2 or more of these agents. In univariate analysis, patients who received TMP/SMX alone had significantly better outcomes, including in-hospital (p = 0.003) and 90-day mortality (p < 0.001) compared to patients treated with daptomycin or linezolid. Patients receiving TMP/SMX were also younger (p < 0.001), had fewer comorbid conditions (p < 0.001), had less severe acute severity of illness (p < 0.001), and received appropriate therapy more rapidly (p = 0.001). In multivariate models the association between TMP/SMX treatment and mortality was no longer significant. Antimicrobial cost savings associated with using TMP/SMX averaged $2067.40 per patient.
  
  
  CONCLUSIONS
  TMP/SMX monotherapy compared favorably to linezolid and daptomycin in terms of treatment efficacy and mortality. Use of TMP/SMX instead of linezolid or daptomycin could potentially significantly reduce antibiotic costs. TMP/SMX should be considered for the treatment of MRSA infection with MIC of 2 μg/mL to vancomycin.
authors.affiliation: Division of Infectious Diseases, Detroit Medical Center, Wayne State University, Harper University Hospital, Detroit, MI, USA.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Campbell
authors.forename: Dror
authors.initials: D
authors.lastname: Marchaim
authors.forename: Jason M
authors.initials: JM
authors.lastname: Pogue
authors.forename: Bharath
authors.initials: B
authors.lastname: Sunkara
authors.forename: Suchitha
authors.initials: S
authors.lastname: Bheemreddy
authors.forename: Pradeep
authors.initials: P
authors.lastname: Bathina
authors.forename: Harish
authors.initials: H
authors.lastname: Pulluru
authors.forename: Neelu
authors.initials: N
authors.lastname: Chugh
authors.forename: Melanie N
authors.initials: MN
authors.lastname: Wilson
authors.forename: Judy
authors.initials: J
authors.lastname: Moshos
authors.forename: Kimberley
authors.initials: K
authors.lastname: Ku
authors.forename: Kayoko
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Emily T
authors.initials: ET
authors.lastname: Martin
authors.forename: Paul R
authors.initials: PR
authors.lastname: Lephart
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rybak
authors.forename: Keith S
authors.initials: KS
authors.lastname: Kaye
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D000328:Adult; D000367:Age Factors; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*; D015331:Cohort Studies; D017046:Cost Savings; D017576:Daptomycin / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D016527:Drug Costs; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015999:Multivariate Analysis; D023303:Oxazolidinones / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000191:economics / Q000382:microbiology; D013997:Time Factors; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D014640:Vancomycin / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D014640:Vancomycin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D000069349:Linezolid; D017576:Daptomycin