trimethoprim--sulfamethoxazole-drug-combination and Protein-Energy-Malnutrition

Pneumocystis jirovecii is an opportunistic pathogen causing life-threatening pneumonia in immunosuppressed patients. The number of non-HIV immunosuppressed patients at risk for Pneumocystis pneumonia is rapidly growing. In contrast to HIV patients, there are no guidelines for Pneumocystis prophylaxis in other immunocompromised hosts. A detailed analysis of current literature data allowed us hereby to define the type of immunocompromised patients for whom evidence suggests a benefit for PCP prophylaxis.

Topics: Anti-Infective Agents; Connective Tissue Diseases; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; HIV Infections; Humans; Immunocompromised Host; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Protein-Energy Malnutrition; Randomized Controlled Trials as Topic; Risk Factors; Transplantation; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vasculitis

Antibiotic therapy for infection with Shiga-toxin-producing Escherichia coli O157:H7 is controversial because of the possibility of its inducing hemolytic uremic syndrome and acute encephalopathy. In a previous study, mice with protein-calorie malnutrition were found to be highly susceptible to this pathogen. The efficacy of oral antibiotic therapy in malnourished mice infected with O157 organisms was assessed. Mice fed a low-protein calorie diet were infected intragastrically with 2 x 10(6) colony-forming units of a Shiga-toxin-producing strain of Escherichia coli O157:H7. Infected mice were orally given a therapeutic dose of an antibiotic, including norfloxacin, fosfomycin, kanamycin, ampicillin, clarithromycin or trimethoprim-sulfamethoxazole for 3 days: mice on protocol A received the antibiotic on days 1-3, starting on the day after infection, and mice on protocol B received the antibiotic on days 3-5. The duration of fecal pathogen excretion was shorter and the toxin level in the stool and blood lower in the mice that received protocol A than in untreated mice; all of the mice treated on protocol A survived the lethal infection. All antibiotics except trimethoprim-sulfamethoxazole, administered on protocol B, exhibited the same effect as that exhibited by the respective antibiotic administered on protocol A. Only the mice treated with protocol B of trimethoprim-sulfamethoxazole had a higher toxin level in the blood than untreated controls, resulting in 95% mortality. These results suggest that the antibiotics used in this study, except for trimethoprim-sulfamethoxazole, could reduce the risk of hemolytic uremic syndrome and acute encephalopathy following Escherichia coli O157:H7 infection in humans, and that fosfomycin, in particular, may be relevant for testing in humans.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Bacterial Toxins; Brain Chemistry; Disease Models, Animal; Disease Progression; Escherichia coli Infections; Escherichia coli O157; Feces; Fosfomycin; Kanamycin; Mice; Mice, Inbred C57BL; Norfloxacin; Protein-Energy Malnutrition; Reference Values; Sensitivity and Specificity; Shiga Toxins; Statistics, Nonparametric; Survival Rate; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The pharmacokinetics of trimethoprim-sulphamethoxazole was examined in seven malnourished (marasmic) infants receiving cotrimoxazole (CMZ) for treatment of urinary tract infection. Comparisons were made with the SMZ level of ten nutritionally normal infants, hospitalized for first and second degree burns, receiving CMZ for treatment of bronchitis. CMZ was administered as an oral suspension (20 mg TMP and 100 mg SMZ, 5 ml), patients receiving 22 mg SMZ/kg body weight. Capillary blood samples, 0.05 ml were taken at prescribed intervals. Elimination half-life of SMZ in the marasmic infants was prolonged, 9.6 vs 4.9 hr, in their eutrophic counterparts. In addition, greater area under the curve (AUC), 573 vs 328 micrograms/ml/h, was noted in the malnourished group. This disparity may be due to differences in body fluid distribution between the two groups.

Topics: Drug Combinations; Female; Humans; Infant; Kinetics; Male; Protein-Energy Malnutrition; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination