title: Antifungal wound penetration of amphotericin and voriconazole in combat-related injuries: case report.
abstract: BACKGROUND
  Survivors of combat trauma can have long and challenging recoveries, which may be complicated by infection. Invasive fungal infections are a rare but serious complication with limited treatment options. Currently, aggressive surgical debridement is the standard of care, with antifungal agents used adjunctively with uncertain efficacy. Anecdotal evidence suggests that antifungal agents may be ineffective in the absence of surgical debridement, and studies have yet to correlate antifungal concentrations in plasma and wounds.
  
  
  METHODS
  Here we report the systemic pharmacokinetics and wound effluent antifungal concentrations of five wounds from two male patients, aged 28 and 30 years old who sustained combat-related blast injuries in southern Afghanistan, with proven or possible invasive fungal infection. Our data demonstrate that while voriconazole sufficiently penetrated the wound resulting in detectable effluent levels, free amphotericin B (unbound to plasma) was not present in wound effluent despite sufficient concentrations in circulating plasma. In addition, considerable between-patient and within-patient variability was observed in antifungal pharmacokinetic parameters.
  
  
  CONCLUSIONS
  These data highlight the need for further studies evaluating wound penetration of commonly used antifungals and the role for therapeutic drug monitoring in providing optimal care for critically ill and injured war fighters.
authors.affiliation: United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, TX, 78234, USA. kevin.s.akers.mil@mail.mil.|Department of Medicine, Infectious Disease Service, San Antonio Military Medical Center, 3698 Chambers Pass, JBSA Fort Sam Houston, TX, 78234, USA. kevin.s.akers.mil@mail.mil.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Akers
authors.affiliation: United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, TX, 78234, USA. matthew.p.rowan.vol@mail.mil.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Rowan
authors.affiliation: United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, TX, 78234, USA. krista.l.niece.ctr@mail.mil.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Niece
authors.affiliation: United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, TX, 78234, USA. john.c.graybill.mil@mail.mil.
authors.forename: John C
authors.initials: JC
authors.lastname: Graybill
authors.affiliation: Department of Medicine, Infectious Disease Service, San Antonio Military Medical Center, 3698 Chambers Pass, JBSA Fort Sam Houston, TX, 78234, USA. katrin.mende.ctr@mail.mil.|Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA. katrin.mende.ctr@mail.mil.
authors.forename: Katrin
authors.initials: K
authors.lastname: Mende
authors.affiliation: United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, TX, 78234, USA. kevin.k.chung.mil@mail.mil.|Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA. kevin.k.chung.mil@mail.mil.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Chung
authors.affiliation: Department of Medicine, Infectious Disease Service, San Antonio Military Medical Center, 3698 Chambers Pass, JBSA Fort Sam Houston, TX, 78234, USA. clinton.k.murray.mil@mail.mil.|Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA. clinton.k.murray.mil@mail.mil.
authors.forename: Clinton K
authors.initials: CK
authors.lastname: Murray
mesh_terms: D000328:Adult; D000666:Amphotericin B / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000671:Amputation, Surgical; D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001228:Aspergillosis / Q000628:therapy; D001753:Blast Injuries / Q000382:microbiology / Q000628:therapy; D002056:Burns / Q000382:microbiology / Q000628:therapy*; D016638:Critical Illness; D003646:Debridement; D016903:Drug Monitoring; D060585:Fusariosis / Q000628:therapy; D006801:Humans; D008297:Male; D009091:Mucormycosis / Q000628:therapy; D009181:Mycoses / Q000628:therapy*; D065819:Voriconazole / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000067398:War-Related Injuries / Q000382:microbiology / Q000628:therapy*; D014950:Wounds, Penetrating / Q000382:microbiology / Q000628:therapy*
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B; D065819:Voriconazole