Abstract
The optimum dosage regimen for cotrimoxazole in the treatment of life threatening infections due to susceptible organisms encountered in critically ill patients is unclear despite decades of the drug’s use. Therapeutic drug monitoring to determine the appropriate dosing for successful infection eradication is not widely available. The clinician must utilize published pharmacokinetic, pharmacodynamic, and effective inhibitory concentration information to determine potential dosing regimens for individual patients when treating specific pathogens. Using minimum inhibitory concentrations known to successfully block growth for target pathogens, the pharmacokinetics of both trimethoprim and sulfamethoxazole can be utilized to establish empiric dosing regimens for critically ill patients while considering organ of clearance impairment. The author’s recommendations for appropriate dosing regimens are forwarded based on these parameters.
Highlights
The optimum dosage regimen for cotrimoxazole in the treatment of life threatening infections due to susceptible organisms encountered in critically ill patients is unclear despite decades of the drug’s use
Review Cotrimoxazole, the combination of trimethoprim (TMP) and sulfamethoxazole (SMX), is frequently required for the treatment of critically ill patients with infections caused by sensitive pathogens, such as Pneumocystis jovenii or Stenotrophomonas maltophilia
This paper will review the available pharmacodynamic and pharmacokinetic data necessary for the clinician to determine the optimum dosage of TMP/SMX for selected infections in the critically ill
Summary
Limited documentation of appropriate concentrations for treatment of critically ill patients forces the clinician to use available pharmacodynamic, toxicologic, and pharmacokinetics of both TMP and SMX in determining dosing regimens for critically ill patients considering organ of clearance impairment. Abbreviations APACHE II: Acute Physiology and Chronic Health Evaluation II; CAPD: Continuous Ambulatory Peritoneal Dialysis; CLSI: Clinical and Laboratory Standards Institute; Cmax: maximum concentration within the dosing interval; Cmin: minimum concentration within dosing interval; CrCl: creatinine clearance; CVVHDF: Continuous Veno-venous Hemodiafiltration; ESBL: extended-spectrum β-lactamase-producing; IV: intravenous; MIC90: minimum inhibitory concentration adequate to inhibit 90%; MRSA: methicillin-resistant Staphylococcus aureus; NAT2: N-acetyltransferase 2; PCP: Pneumocystis pneumonitis; PO: oral; SMX: sulfamethoxazole; T1/2: half-life; Tmax: time to reach maximum concentration; TMP: trimethoprim; Vd: volume of distribution. Authors’ information The author is a clinical pharmacist at St. Paul’s Hospital in Vancouver, British Columbia where he has practiced for 25 years. The author is a Clinical Professor, Faculty of Pharmaceutical Sciences, University of British Columbia
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