trimethoprim--sulfamethoxazole-drug-combination and Hemolysis

Topics: Abnormalities, Drug-Induced; Anti-Infective Agents; Anticoagulants; Biomedical Research; Cytochrome P-450 Enzyme System; Drug Eruptions; Drug Interactions; Female; Folic Acid Deficiency; Hematologic Diseases; Hemolysis; Humans; Hyperkalemia; Hypoglycemia; Hypoglycemic Agents; Immunocompromised Host; Infant, Newborn; Infant, Small for Gestational Age; Kidney; Nervous System Diseases; Pregnancy; Trimethoprim, Sulfamethoxazole Drug Combination; Warfarin

Dapsone may be used for Pneumocystis jirovecii pneumonia (PJP) prophylaxis in hematology patients receiving immunosuppressive therapy or after hematopoietic stem cell transplant (HSCT) in the setting of trimethoprim-sulfamethoxazole (TMP-SMX) adverse drug reaction (ADR) history. Dapsone-induced hematological toxicities such as oxidative hemolysis may limit use in these patients and modern assessments of dapsone allergy cross-reactivity in non-HIV patients with a sulfonamide allergy are largely absent. The aim of this single-centre, retrospective study was to describe dapsone usage in hematology patients requiring PJP prophylaxis, including HSCT recipients, over a 12-month period in terms of indications, incidence of dapsone-attributed oxidative hemolysis, and immune cross-reactivity in those previously labeled with a sulfonamide allergy, as well as describing potential opportunities for first-line TMP-SMX PJP prophylaxis reintroduction. Of 24 patients meeting the study inclusion criteria, 12 (50%) were receiving dapsone PJP prophylaxis post-HSCT. No cases of breakthrough PJP infection were noted. Sixteen patients (67%) were initiated on dapsone to avoid the perceived risk of further myelosuppression with TMP-SMX and five patients (21%) because of prior delayed immune-mediated allergy to TMP-SMX. None experienced rash with dapsone therapy. Six patients (25%) were successfully rechallenged on TMP-SMX, including one patient with prior TMP-SMX-associated rash. Four (17%) patients had confirmed oxidative hemolysis, all resulting in dapsone cessation. Dapsone PJP prophylaxis in hematology patients was effective and safe, with nonlife threatening dapsone-related hemolysis noted in a small number. An absence of sulfonamide allergy cross-reactivity was noted, suggesting greater TMP-SMX rechallenges or desensitization could be considered in those receiving dapsone.

Topics: Aged; Anemia, Hemolytic; Anti-Infective Agents; Antibiotic Prophylaxis; Dapsone; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Hemolysis; Humans; Immunosuppression Therapy; Male; Middle Aged; Oxidative Stress; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Dapsone (4-4'-diaminodiphenylsulfone) is commonly used for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in immunocompromised patients. Oxidant hemolysis is a known complication of dapsone, but its frequency in adult patients who have undergone a SCT for hematological malignancies is not well established. We studied the presence of oxidant hemolysis, by combining examination of RBC morphology and laboratory data, in 30 patients who underwent a SCT and received dapsone for PCP prophylaxis, and compared this group with 26 patients who underwent a SCT and received trimethoprim-sulfamethoxazole (TMP-SMX) for PCP prophylaxis. All patients had normal glucose-6-phosphate dehydrogenase (G6PDH) enzymatic activity. In SCT patients, dapsone compared with TMP-SMX for PCP prophylaxis was associated with a high incidence of oxidant hemolysis (87 vs 0%, P<0.001), and the morphological evaluation of oxidant hemolysis correlated well with laboratory evidence of hemolysis. Dapsone-induced oxidant hemolysis in SCT patients is 20-fold higher than the reported rate in the population of HIV-infected patients, and thus much higher than the prevalence of G6PDH variants in the general population. In our patients, it manifested clinically as a lower Hb that was not significant enough to result in increased packed RBC transfusions.

Topics: Adult; Anti-Infective Agents; Dapsone; Female; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Hemoglobins; Hemolysis; Humans; Male; Middle Aged; North America; Oxidants; Prevalence; Retrospective Studies; Stem Cell Transplantation; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Aerococcus urinae has been described as resistant to trimethoprim-sulfamethoxazole (SXT), but the test medium may affect this observation. Twenty-seven clinical isolates of A. urinae tested susceptible to SXT in cation-adjusted Mueller-Hinton broth (CAMHB) plus lysed horse blood and resistant in CAMHB plus lysed sheep blood.

Topics: Aerococcus; Animals; Anti-Bacterial Agents; Culture Media; Drug Combinations; Gram-Positive Bacterial Infections; Hemolysis; Horses; Humans; Microbial Sensitivity Tests; Sheep; Trimethoprim, Sulfamethoxazole Drug Combination

The case of a patient who developed aseptic meningitis, hemolytic anemia, hepatitis, and orthostatic hypotension simultaneously during treatment with trimethoprim-sulfamethoxazole is described.. A healthy 37-year-old African- American man was receiving treatment with trimethoprim-sulfamethoxazole double strength. This was the patient's first experience with trimethoprim- sulfamethoxazole, and he was not taking any other medications during the treatment period. He had been taking trimethoprim-sulfamethoxazole for approximately eight days when he revisited his family physician, complaining of headaches, dizziness, difficulty with speech, weakness, and itching on the trunk of his body and legs, where a maculopapular rash was noted. Orthostatic hypotension was also noted at that visit, with a standing blood pressure measurement of 95/80 mm Hg. Based on these findings and since the patient had no signs of infection, his physician instructed him to discontinue the drug. The patient was admitted to the emergency department of a local hospital within two days due to ongoing headache, elevated temperature, and nuchal rigidity, symptoms suggestive of meningitis. Because of the presence of hemolysis, the patient underwent testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency, for which he tested positive. The patient was discharged five days after admission and referred to a hematology clinic for follow-up. The patient has since returned to his routines of daily living and has reported no fatigue or other lingering adverse symptoms.. A 37-year-old African- American man with G6PD deficiency developed hemolytic anemia, hepatitis, orthostatic hypotension, and aseptic meningitis simultaneously after using trimethoprim-sulfamethoxazole.

Topics: Adult; Anemia, Hemolytic; Anti-Infective Agents, Urinary; Chemical and Drug Induced Liver Injury; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Hypotension, Orthostatic; Liver Function Tests; Male; Meningitis, Aseptic; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Vibrio cholerae O139 Bengal emerged as a second aetiologic agent of cholera in South Asia in late 1992. This new serogroup arose from a Vibrio cholerae O1 strain by deletion of the chromosomal region encoding O1 specificity and acquisition of a novel 35-kb region encoding the O139 specificity. Previous studies indicated significant phenotypic and genotypic changes in O139 isolates over the years since its first appearance. This prompted us to study possible polymorphism in the 35-kb novel region encoding the O139 specificity. A total of 17 V. cholerae O139 isolates originating from different countries and years in South Asia and China, and a single unrelated V. cholerae O139 isolate from Argentina were studied. The 35-kb chromosomal region was amplified as two fragments of 12 and 23 kb in an extended PCR from all isolates. These amplicons were then treated separately with seven different restriction enzymes and separated by agarose gel electrophoresis. The South Asian and Chinese isolates gave identical patterns for the same enzymes, but different patterns for different enzymes, thus exhibiting no polymorphism in the 35-kb region. However, the Argentine isolate gave distinct patterns for most of the enzymes confirming its different origin. This data indicated that the portion of the chromosome encoding the O139 antigen specificity is highly conserved. As found in previous studies, the early O139 isolates were resistant to trimethoprim-sulfamethoxazole (TMP-SMX) and vibriostatic compound, O/129, and CAMP- haemolysin positive. The isolates of later years diverged exhibiting different patterns by pulsed-field gel electrophoresis (PFGE), and becoming susceptible to TMP-SMX and O/129, and CAMP-haemolysin negative.

Topics: Anti-Bacterial Agents; Argentina; Asia; China; Cholera; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Hemolysis; Humans; O Antigens; Polymorphism, Genetic; Pteridines; Trimethoprim, Sulfamethoxazole Drug Combination; Vibrio cholerae O139

The synthesis and biological properties of a novel water-soluble echinocandin-like lipopeptide, FR131535, are described. This compound displayed potent in vitro and in vivo antifungal activities. The hemolytic activity of FR901379 was reduced by replacing the acyl side chain. This compound showed good water-solubility, comparable to the natural product FR901379.

Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Bronchogenic Cyst; Candida albicans; Candidiasis; Disease Models, Animal; Echinocandins; Female; Fungal Proteins; Glucosyltransferases; Hemolysis; Membrane Proteins; Mice; Mice, Nude; Peptides; Peptides, Cyclic; Pneumonia, Pneumocystis; Schizosaccharomyces pombe Proteins; Solubility

The photochemical reactions in vitro of sulfamethoxazole alone and in combination with trimethoprim were studied to obtain information on the photosensitization mechanism. Sulfamethoxazole in aqueous solution, on exposure to UVB radiation, generates free radicals and singlet oxygen, with the neutral molecule being at least twice as active as the sulfamethoxazole anion. Photoexcited sulfamethoxazole can participate in electron transfer to cytochrome-c and nitro blue tetrazolium, and sensitizes the peroxidation of linoleic acid and the hemolysis of human erythrocytes, predominantly by a free radical mechanism. Trimethoprim is relatively inactive in the same photochemical systems.

Topics: Anti-Infective Agents; Electron Transport; Erythrocytes; Free Radicals; Hemolysis; Humans; Lipid Peroxidation; Molecular Structure; Oxygen; Photosensitizing Agents; Spectrophotometry, Ultraviolet; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anemia, Hemolytic; Ethnicity; Favism; Female; France; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Infant; Italy; Jaundice; Male; Metabolic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination; X Chromosome

Despite some similarities, L-streptococci could be clearly differentiated from A-streptococci. Formamide, autoclaved and nitrous acid extracts of all L-streptococcal cultures studied reacted only with their specific antisera and did not cross-react with any other group specific streptococcal antigens. All 33 L-streptococcal cultures, in contrast to A-streptococci, produced beta-D-glucuronidase and beta-D-galactosidase, hydrolyzed Na-hippurate, grew on 10% and 40% bile blood agar and were agglutinated by the lectin of Arachis hypogaea. Some differences between A- and L-streptococci were also observed in their sensitivity patterns to bacitracin and sulfamethoxazole-trimethoprim.

Topics: Agglutination; Bacitracin; Drug Combinations; Hemolysis; Streptococcus; Streptococcus pyogenes; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antimalarials; Drug Combinations; Hemolysis; Humans; Infant; Infant, Newborn; Malaria; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination