title: TDM-guided therapy with daptomycin and meropenem in a morbidly obese, critically ill patient.
abstract: OBJECTIVE
  To describe a case of severe cellulitis, successfully treated with high-dose daptomycin plus continuous infusion meropenem, in a patient with morbid obesity and renal failure, in whom drug exposure over time was optimized by means of real-time therapeutic drug monitoring (TDM).
  
  
  METHODS
  A 63-year-old man with morbid obesity (body mass index 81.6 kg/m²) and renal failure was admitted to the emergency department because of severe cellulitis. The patient had an admission Laboratory Risk Indicator for Necrotizing Fasciitis score of 9, and broad-spectrum antimicrobial therapy with daptomycin and meropenem was started. Because of rapidly changing renal function, dosage adjustments were guided by an intensive program of TDM (daptomycin ranging from 1200 mg every 48 hours over 30 minutes to 1200 mg every 36 hours over 30 minutes; meropenem ranging from 0.25 g every 8 hours over 6 hours to 500 mg every 4 hours by continuous infusion). Clinical response was observed within 72 hours. However, a sudden increase of serum creatine kinase (SCK) raised questions about the need for discontinuation of daptomycin. The drug concentrations were not toxic; therefore, we decided to continue therapy. Significant clinical improvement, with SCK normalization, was observed within a few days. Antimicrobial therapy was switched on day 29 to amoxicillin/clavulanate plus levofloxacin, and then discontinued at discharge on day 53.
  
  
  CONCLUSIONS
  High-dose daptomycin plus continuous infusion meropenem may ensure adequate empiric antimicrobial coverage in patients with possible early necrotizing fasciitis. However, in patients with morbid obesity and changing renal function, significant challenges may arise because of the hydrophilic nature of these drugs and the inaccuracy of standard methods of estimating renal function.
  
  
  CONCLUSIONS
  Real-time TDM may represent an invaluable approach in optimizing drug exposure with high-dose daptomycin plus continuous infusion meropenem in patients with severe cellulitis, morbid obesity, and changing renal function.
authors.affiliation: Institute of Clinical Pharmacology & Toxicology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Udine, Italy. pea.federico@aoud.sanita.fvg.it
authors.forename: Federico
authors.initials: F
authors.lastname: Pea
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Cojutti
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Sbrojavacca
authors.forename: Barbara
authors.initials: B
authors.lastname: Cadeo
authors.forename: Francesco
authors.initials: F
authors.lastname: Cristini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bulfoni
authors.forename: Mario
authors.initials: M
authors.lastname: Furlanut
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D002481:Cellulitis / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003402:Creatine Kinase / Q000097:blood; D017576:Daptomycin / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D016903:Drug Monitoring; D004359:Drug Therapy, Combination / Q000009:adverse effects; D019115:Fasciitis, Necrotizing / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D009767:Obesity, Morbid / Q000150:complications*; D051437:Renal Insufficiency / Q000150:complications*; D012720:Severity of Illness Index; D013845:Thienamycins / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D003402:Creatine Kinase; D000077731:Meropenem; D017576:Daptomycin