Cotrimoxazole - optimal dosing in the critically ill

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.

A Four-Center Retrospective Study of the Efficacy and Toxicity of Low-Dose Trimethoprim-Sulfamethoxazole for the Treatment of Pneumocystis Pneumonia in Patients without HIV Infection

“…Particularly, the incidences of vomiting and decreased platelet count were higher in this group. Increased serum creatinine levels, hyponatremia, hyperkalemia, anemia, and neutropenia are considered concentration-dependent adverse reactions of TMP-SMX, whereas rash, fever, gastrointestinal disorders, liver function abnormalities, and thrombocytopenia are considered concentration-independent reactions (21,22). TMP-SMX-induced thrombocytopenia appears to be an immunemediated process resulting in platelet destruction by drug-dependent platelet antibodies (23).…”

Stenotrophomonas, Achromobacter, and Nonmelioid Burkholderia Species: Antimicrobial Resistance and Therapeutic Strategies

“…Trimethoprim-sulfamethoxazole remains the first-line therapy for S. maltophilia. On the basis of in vitro pharmacodynamics modelling and the bacteriostatic action of trimethoprim-sulfamethoxazole, it is recommended that a higher dose be used (daily dose of 15 mg per kg of the trimethoprim component, split 6 to 8 hourly), 51,52 which is more similar to the dose chosen for the treatment of Pneumocystis jirovecii pneumonia. In the setting of trimethoprimsulfamethoxazole resistance, second line agents are available and are often used in combination (see ►Table 6).…”

“…Trimethoprim-sulfamethoxazole remains a recommended first-line therapy. Higher dosing schedules (15 mg per kg of the trimethoprim component, split 6 to 8 hourly) has again been recommended based on pharmacokinetic and pharmacodynamics data in the critically ill, 52 as well as extrapolated data from B. pseudomallei, the pathogen causing melioidosis. 62 In contrast to S. maltophilia, B. cepacia complex are often sensitive to meropenem, which is another first-line therapy, but are inherently resistant to polymyxin and colistin.…”

Role of Therapeutic Drug Monitoring in Pulmonary Infections: Use and Potential for Expanded Use of Dried Blood Spot Samples

“…Also, when aminoglycosides are administered together with drugs that influence 318 their renal clearance, the kinetics of the aminoglycosides will change and the plasma concentration 319 of the drugs needs to be monitored [32]. Aminoglycosides do not undergo hepatic metabolism and 320 therefore dose adjustment in patients with hepatic impairment is not required [44,45]. Sometimes, 321 patients can be treated at home with an aminoglycoside, for example patients with cystic fibrosis or 322 patients that need long term treatment with aminoglycosides.…”

“…Dose adjustments for aminoglycosides are required in patients with impaired 317 renal function [44]. Also, when aminoglycosides are administered together with drugs that influence 318 their renal clearance, the kinetics of the aminoglycosides will change and the plasma concentration 319 of the drugs needs to be monitored [32].…”