trimethoprim--sulfamethoxazole-drug-combination and Liver-Diseases

Paracoccidioidomycosis (PCM) is a neglected systemic mycosis endemic to Latin America caused by dimorphic fungi of the genus Paracoccidioides. The acute juvenile PCM is a severe type of presentation that usually affects young vulnerable patients and rarely progresses to portal hypertension. Here, two cases of liver disease and portal hypertension as complications of acute juvenile PCM are reported. Diagnosis of PCM was performed by isolation of the fungus and molecular identification of the strains provided through partial sequencing of two protein encoding genes, arf and gp43. Genotypic analysis revealed that Paracoccidioides brasiliensis S1 was the phylogenic species involved in both cases. Patients presented a good clinical response to amphotericin B and sulfamethoxazole-trimethoprim. These results highlight the importance of the interdisciplinary approach in patients with severe forms of PCM to avoid and treat complications, and the necessity of further investigations focusing on host-pathogen interaction in order to explain the broad clinical spectrum in PCM as well as the severity and poor outcome in some clinical cases.

Topics: Adolescent; Adult; Amphotericin B; Female; Fungal Proteins; Humans; Hypertension, Portal; Latin America; Liver Diseases; Male; Paracoccidioides; Paracoccidioidomycosis; Phylogeny; Sequence Analysis, DNA; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acetylation; Adolescent; Chemical and Drug Induced Liver Injury; Cytotoxicity Tests, Immunologic; Hematologic Diseases; Humans; Kidney Diseases; Liver Diseases; Lymphocytes; Male; Phenotype; Skin Diseases; Thyroid Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

We report on a case of massive bleeding into the liver parenchyma during treatment with a combination of warfarin sodium and trimethoprim-sulfamethoxazole. A fifty-five-year-old woman was put on long-term anticoagulant therapy with warfarin sodium. Two years later a course of trimethoprim-sulfamethoxazole was given to treat bronchitis. Following a bout of severe epigastric pain, ultrasonography and computed tomography (CT) then showed an enlarged liver containing several large hematomas. Subsequent CT scans, after tentative treatment only, showed regression of the liver hematomas, with almost complete disappearance after eight months. Bleeding complications and drug interactions related to this case are discussed, together with a review of the only six previous reports in the world literature of liver hematomas following anticoagulant therapy. Also mentioned are five patients in whom thrombolytic therapy gave rise to the same adverse reaction.

Topics: Chemical and Drug Induced Liver Injury; Drug Interactions; Drug Therapy, Combination; Female; Hematoma; Humans; Liver; Liver Diseases; Middle Aged; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Warfarin

The proportion of patients with antituberculosis drug-induced hepatotoxicity (ATDH) was unexpectedly low during a trial on cotrimoxazole prophylaxis in Malawian HIV-positive pulmonary tuberculosis patients. About 2% of the patients developed grade 2 or 3 hepatotoxicity during tuberculosis (TB) treatment, according to WHO definitions. Data on ATDH in sub-Saharan Africa are limited. Although the numbers are not very strong, our trial and other papers suggest that ATDH is uncommon in this region. These findings are encouraging in that hepatotoxicity may cause less problem than expected, especially in the light of combined HIV/TB treatment, where drug toxicity is a major cause of treatment interruption.

Topics: Adolescent; Adult; Age Distribution; Anti-Infective Agents; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Drug Administration Schedule; Female; HIV Infections; Humans; Liver Diseases; Malawi; Male; Middle Aged; Sex Distribution; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Topics: Adult; Anti-Infective Agents; Chemical and Drug Induced Liver Injury; Granuloma, Plasma Cell; HIV Infections; Humans; Liver Diseases; Magnetic Resonance Imaging; Male; Trimethoprim, Sulfamethoxazole Drug Combination

To monitor trimethoprim and sulfamethoxazole plasma levels in patients with AIDS-associated Pneumocystis carinii pneumonia.. Trimethoprim-sulfamethoxazole steady-state plasma concentrations were measured by high-pressure liquid chromatography during 37 episodes of Pneumocystis carinii pneumonia in patients with AIDS. Initially, 15-23 mg/kg/day trimethoprim and 75-115 mg/kg/day sulfamethoxazole were given i.v. Assuming a therapeutic range for trimethoprim from 4 to 10 microg/ml, the doses were adjusted if trimethoprim levels were found to be outside this range.. Mean concentrations were 6.7+/-3.3 g/ml for trimethoprim and 187+/-56 microg/ml for sulfamethoxazole. A widespread inter-patient range was found and could be decreased after dose adjustment. Enzyme inducing co-medication did not influence plasma concentrations. In patients with coexisting chronic liver disease, significantly increased sulfamethoxazole plasma levels were observed. A correlation could be demonstrated between serum creatinine and trimethoprim plasma levels. Adverse reactions associated with co-trimoxazole occurred during 65% of treatment periods and increased with increasing trimethoprim-sulfamethoxazole levels, as well as increasing length of treatment. Therapy only had to be prematurely discontinued in one patient. Overall mortality was 2.7%. Monitoring of co-trimoxazole levels during the treatment of P. carinii pneumonia in AIDS may help in reducing the high variability of plasma-concentrations and in avoiding severe side-effects especially associated in patients with chronic liver disease or renal failure.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Chromatography, High Pressure Liquid; Chronic Disease; Drug Monitoring; Female; Humans; Kidney; Liver Diseases; Male; Middle Aged; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adult; Antiviral Agents; Chemical and Drug Induced Liver Injury; Diagnosis, Differential; Humans; Liver Diseases; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Alanine Transaminase; Aspartate Aminotransferases; Ethanol; Humans; Liver Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Aerosols; AIDS-Related Opportunistic Infections; Drug Resistance, Microbial; Homosexuality, Male; Humans; Liver Diseases; Male; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Splenic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

A case is presented of bilateral intraocular nocardial infection associated with lung and liver foci and responding to treatment. Difficulties in diagnosis and treatment are discussed. It is suggested that unusual infections such as this should be considered in the differential diagnosis of chorioretinitis, and should be carefully sought, especially in immunocompromised patients. However, our patient is unusual in having no evidence of immunosuppression predisposing to ocular involvement in his nocardial infection.

Topics: Biopsy; Chorioretinitis; Diagnosis, Differential; Endophthalmitis; Humans; Liver Diseases; Lung Diseases; Male; Middle Aged; Nocardia Infections; Radiography; Sulfamethazine; Trimethoprim, Sulfamethoxazole Drug Combination; Ultrasonography; Visual Acuity

Forty-four episodes of Pneumocystis carinii pneumonia (PCP) occurred in 36 of 70 patients with the acquired immunodeficiency syndrome. Thirty-four patients with 40 episodes of PCP were treated with trimethoprim-sulfamethoxazole. Therapy was successful in 18 episodes (45%), but was unsuccessful in 15 episodes (37.5%). In the latter cases, two patients died within 72 hours; 13, of whom nine died, had therapy changed to pentamidine. In seven additional episodes (17.5%), trimethoprim-sulfamethoxazole was changed to pentamidine due to adverse reactions; all patients survived. Seven patients (26% of survivors) developed recurrent PCP. Twenty-two patients (65%) developed adverse reactions to trimethoprim-sulfamethoxazole, including leukopenia (20), hepatotoxicity (12), fever (eight), rash (six), and immediate reactions (two). Reactions were most common during the second week of therapy. Patients with the acquired immunodeficiency syndrome who have PCP have a high trimethoprim-sulfamethoxazole failure rate, due either to adverse reactions or unresponsive infection. Late recurrence is common.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amidines; Drug Combinations; Drug Therapy, Combination; Humans; Leukopenia; Liver Diseases; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Recurrence; Retrospective Studies; Sulfamethoxazole; Time Factors; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination