trimethoprim--sulfamethoxazole-drug-combination and Critical-Illness

Stenotrophomonas maltophilia is a life-threatening nosocomial pathogen with profound multidrug-resistant attributes. It is associated with high mortality, particularly in immunocompromised patients. Data on therapy for S. maltophilia infections are scarce, especially in children hospitalized in intensive care settings (pediatric intensive care unit).. A retrospective chart review of pediatric patients with isolates of S. maltophilia hospitalized over a 5-year period in 2 pediatric intensive care units.. Thirty-one patients and 91 isolates from blood, respiratory secretions and soft tissues were identified and reviewed. The overall incidence of S. maltophilia infections increased during the study period (P = 0.003). The all-cause crude mortality was 61%, and the attributed mortality was approximately 16%. Risk factors associated with mortality included longer hospitalization before infection (P = 0.002), septic shock (P = 0.003), mechanical ventilation (P = 0.004), an indwelling central vein catheter (P = 0.03) and prior use of steroids (P = 0.04) and carbapenems (P = 0.004). On multivariate analysis, mortality was associated with mechanical ventilation (P = 0.02) and preinfection hospitalization days (P = 0.01). Combination treatment of trimethoprim and sulfamethoxazole, ciprofloxacin and/or minocycline significantly extended survival time (P < 0.001). The method of treatment did not significantly affect the interval between S. maltophilia isolation to resolution of infection (P = 0.200).. Combinations of trimethoprim and sulfamethoxazole, ciprofloxacin and minocycline are proposed for pediatric intensive care unit patients harboring S. maltophilia. Meticulous evaluation of central vascular access and prior treatment with carbapenems are indicated, especially for mechanically ventilated and septic children.

Topics: Anti-Bacterial Agents; Child; Child, Preschool; Critical Illness; Cross Infection; Disease Management; Female; Gram-Negative Bacterial Infections; Hospitalization; Humans; Incidence; Infant; Intensive Care Units, Pediatric; Israel; Male; Medical Records; Microbial Sensitivity Tests; Retrospective Studies; Risk Factors; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the extent of elimination of trimethoprim (TMP) and sulfamethoxazole (SMX) via continuous venovenous hemodiafiltration (CVVHDF) in 2 critically ill patients with renal failure.. A 62-year-old woman with Pneumocystis jirovecii pneumonia (PCP) was admitted to our intensive care unit for severe acute respiratory distress syndrome. A 77-year-old man was admitted for aortic root replacement and developed septic shock and nosocomial pneumonia due to Stenotrophomonas maltophilia. Both patients developed acute renal failure, necessitating CVVHDF. They were treated with intravenous TMP/SMX adapted to renal function. The first patient received TMP 6.4 mg/kg/day and SMX 32 mg/kg/day, corresponding to 50% of the recommended high-dose TMP/SMX regimen in PCP patients. The second patient received TMP 1.7 mg/kg/day and SMX 8.6 mg/kg/day, corresponding to 50% of the usual dose in bacterial infections. We determined peak and trough serum TMP and SMX concentrations and the extent of TMP/SMX CVVHDF clearance at steady-state while the patients were still anuric and oliguric.. Data on TMP and SMX pharmacokinetics in CVVHDF are lacking and dosing recommendations are inconclusive. In both patients, CVVHDF clearance of TMP ranged from 21.5 to 28.9 mL/min, corresponding with normal renal clearance (20-80 mL/min). SMX clearance in CVVHDF showed high variability (18.7, 26.7, and 42.6 mL/min) and exceeded renal clearance values in normal renal function (1-5 mL/min). Accordingly, peak TMP serum concentrations were within the recommended range in the patient treated with a reduced TMP/SMX dose for PCP, whereas her SMX peak concentrations were only one third of recommended target concentrations.. Our data indicate that both TMP and SMX are removed by CVVHDF to a significant degree, and dose reduction of TMP/SMX in CVVHDF bears the risk of underdosing. Given variability in drug exposure in critically ill patients, therapeutic drug monitoring is advisable in anuric or oliguric patients undergoing continuous renal replacement therapy to ensure optimal TMP/SMX dosing.

Topics: Acute Kidney Injury; Aged; Anti-Infective Agents; Critical Illness; Cross Infection; Female; Gram-Negative Bacterial Infections; Hemodiafiltration; Humans; Infusions, Intravenous; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of our study was to describe the characteristics of Xanthomonas infections in a population of critically ill surgical patients. The clinical records and microbiological data on 93 patients in a surgical intensive care unit (SICU) developing Xanthomonas infections were reviewed. Xanthomonas was isolated in 125 sites in the 93 patients. Their average age was 48 years (range, 14-94). Mortality occurred in 25 patients (26.9%) versus 10.3 per cent of SICU patients in general (P < 0.05). Patients were in the SICU for an average of 11.9 days before developing a positive Xanthomonas culture, and 87 per cent (81/93) of patients developed an infection at some other site before isolation of Xanthomonas. Trimethoprim sulfamethoxazole was the only drug to which the isolates were commonly sensitive (123/125 = 98.4%). We conclude that Xanthomonas 1) is associated with increased mortality; 2) is resistant to many of the drugs that usually cover Gram-negative infections; and 3) commonly complicates a prolonged intensive care stay, thus serving as a marker for severity of illness.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Critical Care; Critical Illness; Drug Resistance, Microbial; Female; Gram-Negative Bacterial Infections; Humans; Length of Stay; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Surgical Procedures, Operative; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination; Xanthomonas

Current dosage regimens of trimethoprim-sulfamethoxazole used to treat Pneumocystis carinii pneumonia in AIDS patients have been based on data from healthy subjects or patients without AIDS. The clearance and absorption characteristics of the drugs may potentially be different between patients with and without AIDS. This study was conducted to assess the pharmacokinetics of trimethoprim-sulfamethoxazole in critically ill and non-critically ill AIDS patients treated for P. carinii pneumonia. Patients received trimethoprim at 15 mg/kg of body weight and sulfamethoxazole at 75 mg/kg of body weight daily intravenously in three to four divided doses and were switched to the oral route when the regimen was tolerated. Serum samples for determination of drug concentrations were obtained over 12 h after intravenous and oral dosing. The pharmacokinetics of trimethoprim and sulfamethoxazole were compared in eight critically ill versus nine non-critically ill male patients and were as follows, respectively: clearance, 1.88 +/- 0.44 versus 1.73 +/- 0.64 ml/min/kg for trimethoprim and 0.40 +/- 0.12 versus 0.34 +/- 0.11 ml/min/kg for sulfamethoxazole; volume of distribution, 1.6 +/- 0.5 versus 1.5 +/- 0.5 liters/kg for trimethoprim and 0.5 +/- 0.3 versus 0.4 +/- 0.1 liters/kg for sulfamethoxazole; and half-life, 10.9 +/- 7.4 versus 11.3 +/- 4.0 h for trimethoprim, and 15.5 +/- 9.5 versus 14.3 +/- 4.7 h for sulfamethoxazole. No significant differences (P > 0.05) were observed between patient groups, although there was wide intersubject variability. Absorption appeared to be similar between the critically ill and non-critically patients: bioavailability was 97.5% +/- 22.4% versus 101.8% +/- 22.7% for trimethoprim and 86.2% +/- 17.9% versus 99.1% +/- 20.5% for sulfamethoxazole, respectively. Because of the similar pharmacokinetics of trimethoprim-sulfamethoxazole in critically ill and non-critically ill AIDS patients, the two groups of patients may receive similar dosages. Dosage adjustment does not appear to be required when switching from the intravenous to the oral route.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; APACHE; Biological Availability; Critical Illness; Half-Life; Humans; Injections, Intravenous; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination