trimethoprim--sulfamethoxazole-drug-combination and Chemical-and-Drug-Induced-Liver-Injury

Drug-induced liver injury (DILI) is a rare but known adverse event associated with trimethoprim-sulfamethoxazole (TMP-SMX) in adults. No studies to date have looked at the risk of this association in children. We systematically reviewed the evidence for a potential association between TMP-SMX and DILI in the pediatric population.. PubMed, Medline, Embase, Cochrane Database of Systematic Reviews, Scopus and Web of Science was searched using a combination of terms to identify reports of TMP-SMX exposure, liver injury and pediatrics (≤18 years old). We included any studies with hepatic adverse events occurring after exposure to TMP-SMX. Bibliographies were reviewed for additional relevant references. The Narajno scale was used to assess causality in case studies.. A total of 22 studies were identified: 3 randomized trials, 1 prospective observational study, 8 retrospective observational studies and 10 case reports. Among the randomized trials and prospective studies, only mild, transient hepatic function abnormalities were reported. Retrospective observational studies reported 1 fatal DILI and statistically significant increased odds of DILI with TMP-SMX use compared with nonuse. Among the 10 case reports, severe liver outcomes and mild hepatic function abnormalities were both reported. Naranjo scores suggested reported hepatic adverse events were probably because of exposure in 5, possible in 4, and doubtful in 1 case report.. Evidence regarding DILI associated with TMP-SMX exposure in pediatrics is limited. Observational population studies show mild hepatic abnormalities. Case reports suggest more severe manifestations of DILI. Additional studies may reveal the association between TMP-SMX and DILI in pediatrics.

Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Child; Humans; Liver; Observational Studies as Topic; Pediatrics; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

A 22-year-old woman was given trimethoprim plus sulphamethoxazole for a urinary infection (160 and 800 mg, respectively, daily), drugs she had not previously taken. After 2 weeks she noticed a rash of small spots on her trunk. In addition she had nausea and vomiting. The rash faded within 2 days of stopping the drug, but progressive jaundice developed.. SGPT and SGOT concentrations rose to maximally 328 and 83 U/l, total bilirubin to maximally 5.9 mg/dl. There was no evidence for viral hepatitis (B or C, cytomegalovirus, Epstein-Barr), autoimmune hepatitis or primary biliary hepatitis. Liver biopsy showed central acinar cholestasis, which suggested drug-induced liver damage.. The patient's symptoms regressed over several weeks without any specific treatment and 8 weeks after onset of the rash the laboratory tests also became normal. The allergic cause of the cholestatic hepatitis was confirmed by a lymphocyte transformation test.. Clinical suspicion of drug allergy as cause of a cholestatic hepatitis can be confirmed reliably and without any risk to the patient with the lymphocyte transformation test.

Topics: Adult; Anti-Infective Agents, Urinary; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Diagnosis, Differential; Drug Hypersensitivity; Female; Humans; Lymphocyte Activation; Remission, Spontaneous; Time Factors; 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

Antimicrobial drugs that can be taken orally are needed for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Preliminary data indicate that dapsone with trimethoprim may be an effective alternative to trimethoprim-sulfamethoxazole, which is frequently toxic.. In a double-blind trial, 60 patients with AIDS and mild-to-moderately-severe first episodes of P. carinii pneumonia (partial pressure of oxygen in arterial blood, greater than 60 mm Hg while breathing room air) were randomly assigned to 21 days of treatment with either trimethoprim-sulfamethoxazole (20 and 100 mg per kilogram of body weight per day, respectively) or trimethoprim-dapsone (20 mg per kilogram per day and 100 mg per day).. The orally administered treatment failed because of progressive pneumonitis in 3 of the 30 patients assigned to trimethoprim-sulfamethoxazole and in 2 of the 30 assigned to trimethoprim-dapsone (P greater than 0.3). Major toxic effects required a switch to intravenous pentamidine for 17 patients (57 percent) in the trimethoprim-sulfamethoxazole group, as compared with 9 (30 percent) in the trimethoprim-dapsone group (P less than 0.025). With trimethoprim-sulfamethoxazole, there were more instances of severe chemical hepatitis (six, as compared with one in the trimethoprim-dapsone group) and marked neutropenia (five vs. one). Intolerable rash (three in each treatment group) and severe nausea and vomiting (two in each group) occurred with equal frequency with both drug combinations. Methemoglobinemia occurred in most of the patients treated with trimethoprim-dapsone, but it was asymptomatic and the level exceeded 20 percent in only one patient. Mild hyperkalemia (serum potassium level, 5.1 to 6.1 mmol per liter) also occurred in 53 percent of the patients treated with trimethoprim-dapsone.. In patients with AIDS, oral therapy with trimethoprim-sulfamethoxazole and with trimethoprim-dapsone are equally effective for mild-to-moderate first episodes of P. carinii pneumonia, but with trimethoprim-dapsone there are fewer serious adverse reactions than with trimethoprim-sulfamethoxazole.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Chemical and Drug Induced Liver Injury; Dapsone; Double-Blind Method; Drug Combinations; Female; Humans; Male; Neutropenia; Pentamidine; Pneumonia, Pneumocystis; Random Allocation; Survival Rate; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Sulfonamides are widely used to treat and prevent various bacterial and opportunistic infections. The aim of this study was to describe the clinical presentation and outcomes of a large cohort of patients with sulfonamide hepatotoxicity.. Between 2004 and 2020, 105 patients with hepatotoxicity attributed to trimethoprim/sulfamethoxazole (TMP-SMZ) (n = 93) or other sulfonamides (n = 12) were enrolled. Available liver biopsies were reviewed by a single hepatopathologist.. Among the 93 TMP-SMZ cases, 52% were female, 7.5% younger than 20 years, and the median time to drug-induced liver injury (DILI) onset was 22 days (range: 3-157). Younger patients were significantly more likely to have rash, fever, eosinophilia, and a hepatocellular injury pattern at onset that persisted at the peak of liver injury compared with older patients ( P < 0.05). The 18 (19%) TMP-SMZ patients treated with corticosteroids had more severe liver injury and a higher mortality but a trend toward more rapid normalization of their laboratory abnormalities compared with untreated patients. During follow-up, 6.2% of the TMP-SMZ patients died or underwent liver transplantation. Chronic DILI developed in 20% and was associated with cholestatic injury at onset and higher peak total bilirubin levels.. Sulfonamide hepatotoxicity is characterized by a short drug latency with frequent hypersensitivity features at onset. Subject age is an important determinant of the laboratory profile at presentation, and patients with cholestasis and higher total bilirubin levels were at increased risk of developing chronic DILI. Corticosteroids may benefit a subgroup of patients with severe injury, but further studies are needed.

Topics: Adrenal Cortex Hormones; Bilirubin; Chemical and Drug Induced Liver Injury; Cholestasis; Female; Humans; Male; Sulfanilamide; Trimethoprim, Sulfamethoxazole Drug Combination

Taiwanese patients frequently experience severe hepatotoxicity associated with high-dose methotrexate (HD-MTX) treatment, which interferes with subsequent treatment. Drug-drug interactions occur when MTX is used in combination with proton pump inhibitors (PPIs), trimethoprim-sulfamethoxazole (TMP-SMX), or non-steroidal anti-inflammatory drugs (NSAIDs). In East Asia, real-world analyses on the effects of co-medication and other potential risk factors on the clinical course of HD-MTX-mediated acute hepatotoxicity in patients with osteogenic sarcoma (OGS) are limited.. This cohort study included patients with newly diagnosed OGS who were treated with HD-MTX between 2009 and 2017 at Taipei Veterans General Hospital. We collected data on the clinical course of HD-MTX-mediated acute hepatotoxicity, co-medications, and other potential risk factors, and analyzed the effects of these factors on the clinical course of HD-MTX-mediated acute hepatotoxicity.. Almost all patients with OGS treated with HD-MTX developed acute hepatotoxicity with elevated alanine aminotransferase (ALT) levels. Most patients with Grade 3-4 ALT elevation failed to recover to Grade 2 within 7 days. Women and children are high-risk subgroups for HD-MTX-mediated elevation of ALT levels. Age is a factor that contributes to the pharmacokinetic differences of HD-MTX. However, the concurrent use of PPIs, TMP-SMX, or NSAIDs did not affect the elimination of MTX when administered with adequate supportive therapy.. Co-administration of PPIs, TMP-SMX, or NSAIDs may have limited effects on acute hepatotoxicity in well-monitored and adequately pre-medicated patients with OGS undergoing chemotherapy with HD-MTX. Clinicians should pay particular attention to ALT levels when prescribing HD-MTX to children and women.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Bone Neoplasms; Chemical and Drug Induced Liver Injury; Child; Cohort Studies; Disease Progression; Female; Humans; Methotrexate; Osteosarcoma; Proton Pump Inhibitors; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim (TMP)-sulfamethoxazole (SMX) is an important cause of idiosyncratic drug-induced liver injury (DILI), but its genetic risk factors are not well understood. This study investigated the relationship between variants in the human leukocyte antigen (HLA) class 1 and 2 genes and well-characterized cases of TMP-SMX DILI.. European American and African American persons with TMP-SMX DILI were compared with respective population controls. HLA sequencing was performed by Illumina MiSeq (Illumina, San Diego, CA) for cases. The HLA genotype imputation with attribute bagging program was used to impute HLA alleles for controls. The allele frequency difference between case patients and controls was tested by Fisher's exact tests for each ethnic group. For European Americans, multivariable logistic regression with Firth penalization was used to test the HLA allelic effect after adjusting for age and the top two principal components. Molecular docking was performed to assess HLA binding with TMP and SMX. The European American subset had 51 case patients and 12,156 controls, whereas the African American subset had 10 case patients and 5,439 controls. Four HLA alleles were significantly associated in the European American subset, with HLA-B*14:01 ranking at the top (odds ratio, 9.20; 95% confidence interval, 3.16, 22.35; P = 0.0003) after covariate adjustment. All carriers of HLA-B*14:01 with TMP-SMX DILI possessed HLA-C*08:02, another significant allele (P = 0.0026). This pattern was supported by HLA-B*14:01-HLA-C*08:02 haplotype association (P = 1.33 × 10. HLA-B*14:01 is associated with TMP-SMX DILI in European Americans, and HLA-B*35:01 may be a potential genetic risk factor for African Americans.

Topics: Adult; Aged; Alleles; Black or African American; Chemical and Drug Induced Liver Injury; Female; Genome-Wide Association Study; Haplotypes; HLA-B Antigens; Humans; Logistic Models; Male; Middle Aged; Molecular Docking Simulation; Multivariate Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; White People

Trimethoprim-sulfamethoxazole (TMP-SMX) is a broad-spectrum antibiotic. However, its use is associated with toxic reactions. Virgin coconut oil (VCO), derived from coconut, has been widely used throughout history for its medicinal value. The aim of this study was to investigate the beneficial actions of VCO against TMP-SMX-induced alterations in serum biochemical end points.. Twenty rats were divided into four groups. Group 1 (control) received no drug, whereas group 2 received TMP-SMX (8/40 mg/kg) twice daily for 7 days. Group 3 was administered coconut oil at a dose of 600 mg/kg body weight per day. The last group was treated with TMP-SMX (8/40 mg/kg) and coconut oil (600 mg/kg) simultaneously. Blood samples were collected from all groups on the 8th day of the experiment for measurement of serum biochemical parameters. Organ weights and coefficients were also evaluated.. TMP-SMX caused a significant (p<0.05) increase in the levels of serum total bilirubin, lactate dehydrogenase, and alkaline phosphatase by 192%, 67%, and 41%, respectively, relative to controls. This was followed by a significant reduction in triglyceride and relative kidney weight by 40% and 7%, respectively. There were no significant differences (p>0.05) in the activities of serum aminotransferases, total acid phosphatase, γ-glutamyl transferase, uric acid, cholesterol, albumin, and urea levels. Supplementation of VCO ameliorated TMP-SMX-induced effects by restoring the levels of total bilirubin, alkaline phospahatase, and lactate dehydrogenase.. The results of this study demonstrate that the active components of coconut oil had protective effects against the toxic effects induced by TMP-SMX administration, especially in the liver of rats.

Topics: Animals; Anti-Infective Agents; Biomarkers; Chemical and Drug Induced Liver Injury; Coconut Oil; Folic Acid Antagonists; Kidney; Kidney Function Tests; Liver Function Tests; Male; Organ Size; Plant Oils; Rats, Wistar; Trimethoprim, Sulfamethoxazole Drug Combination

The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for Pneumocystis jirovecii pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of P. jirovecii pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. NAT1 and NAT2 acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145-0.957), while serostatus of hepatitis B or C virus, NAT1 and NAT2 acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV-infected Taiwanese patients who received TMP/SMX for pneumocystosis. Concomitant use of fluconazole was associated with decreased risk for TMP/SMX-related hepatotoxicity.

Topics: Adult; Aged; Aged, 80 and over; Anti-HIV Agents; Anti-Infective Agents; Arylamine N-Acetyltransferase; Chemical and Drug Induced Liver Injury; Drug Interactions; Female; Fluconazole; Gene Expression; HIV; HIV Infections; Humans; Isoenzymes; Liver; Male; Middle Aged; Multivariate Analysis; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymorphism, Single Nucleotide; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Chemical and Drug Induced Liver Injury; Humans; Hyponatremia; Jaundice; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

Reactivation of certain latent viruses has been linked with a more severe course of drug-induced hypersensitivity reaction (HSR). For example, reactivation of human herpes virus (HHV)-6 is associated with severe organ involvement and a prolonged course of disease. The present study discusses an HSR developed in a previously healthy male exposed to ceftriaxone, doxycycline, vancomycin, and trimethoprim/sulfamethoxazole (co-trimoxazole; TMP/SMX). Initially, the patient presented clinical manifestations of HSR, as well as clinical and laboratory measurements compatible with liver and renal failure. Moreover, the patient presented skin desquamation compatible with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis. During the reaction, it was observed HHV-6 reactivation. The severity of clinical symptoms is correlated with HHV-6 titer, as well as with results of the in vitro lymphocyte toxicity assay (LTA). Serum levels of a large panel of cytokines are compared between the patient, a large population of SJS patients, and a cohort of healthy controls, using data collected by our laboratory over the years. HHV-6 was measured in the cell culture media from lymphocytes incubated with each of the 4 drugs. Moreover, we describe a new assay using cytokines released by patient lymphocytes following in vitro exposure to the incriminated drugs as biomarkers of HSR. Based on LTA results, HHV-6 reactivation and cytokine measurements, we establish that only doxycycline and TMP/SMX were involved in the HSR. As result of this analysis, the patient could continue to use the other 2 antibiotics safely.

Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Cytokines; Doxycycline; Drug Eruptions; Drug Hypersensitivity; Herpesvirus 6, Human; Humans; Lymphocytes; Male; Roseolovirus Infections; Stevens-Johnson Syndrome; Translational Research, Biomedical; Trimethoprim, Sulfamethoxazole Drug Combination; Virus Activation; Young Adult

An association between herpes virus reactivations and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is accepted. We report six cases of DRESS with viral reactivation occurring within a single 1-month period. We attempted to find a common factor for these six cases and carried out clinical and virological examinations. Before and after this "epidemic", the mean number of cases of DRESS seen at the same centre was one per quarter, making the occurrence of six cases within a single month all the more remarkable and prompting us to seek an explanation.. All six patients had taken a partly causative medication from different drug classes three to six weeks prior to the start of symptoms and herpes virus was detected in the blood of all of these subjects at the time of DRESS onset (four reactivations and two primary infections), and one patient subsequently displayed herpetic meningoencephalitis 95 days after the initial episode, associated with recurrence of DRESS.. There was no common denominator among these six DRESS patients in terms of either drug class or reactivation of a particular type of herpes virus, which raises the possibility of a single unidentified environmental agent. DRESS does not appear fully explainable in terms of a cellular response to drug antigens but seems rather to result from complex interactions between the drug-induced immune response, viral reactivation and antiviral immune response. Several investigators have reported sequential reactivation of herpes viruses in DRESS. A viral epidemic could thus cause a "DRESS epidemic" in patients on medication.. These cases point to the possible existence of a shared initial environmental factor (infectious or not) that favours reactivation of herpes viruses and induces DRESS in patients on medication. Before and after this "DRESS epidemic", about one patient each quarter was admitted to hospital for DRESS.

Topics: Acute Kidney Injury; Adult; Aged; Allopurinol; Amoxicillin; Anti-Bacterial Agents; Carbamazepine; Chemical and Drug Induced Liver Injury; Cytomegalovirus; Cytomegalovirus Infections; Disease Outbreaks; Drug Eruptions; Epstein-Barr Virus Infections; Female; France; Herpesvirus 4, Human; Herpesvirus 6, Human; Herpesvirus 7, Human; Humans; Hypereosinophilic Syndrome; Imidazoles; Immunocompromised Host; Male; Middle Aged; Models, Biological; Roseolovirus Infections; Seasons; Trimethoprim, Sulfamethoxazole Drug Combination; Virus Activation

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

Due to the escalating rates of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection, trimethoprim-sulfamethoxazole (TMP-SMX) is being used increasingly in the pediatric population for skin and soft tissue infections. Although this combination agent has been associated with a hypersensitivity syndrome involving cutaneous skin eruptions, pediatric cases of TMP-SMX-induced hepatotoxicity are rare. We describe a relatively healthy, 9-year-old boy who developed a CA-MRSA skin and soft tissue infection and was treated with TMP-SMX. After 14 days of therapy, he was taken to the emergency department with a 3-day history of fever, headache, and neck pain. He was diagnosed with a viral syndrome, acetaminophen was prescribed, and he was sent home. Three days later, the patient returned to the emergency department with fever, vomiting, decreased energy and appetitie, and suprapubic abdominal pain, and he was hospitalized. Laboratory test results revealed elevated liver function test values. After other potential causes of liver toxicity were excluded, TMP-SMX was determined to be the cause of his acute liver toxicity. The drug was discontinued, his symptoms resolved, and his liver function tests returned to normal. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient's development of hepatotoxicity and the TMP-SMX therapy. This rare adverse reaction to TMP-SMX has been reported in adults; however, to our knowledge, it has been reported in only five other children. Due to the increasing use of TMP-SMX in children, clinicians should be aware of this potentially life-threatening, immunemediated hypersensitivity reaction. Fortunately, however, the hepatotoxicity appears to resolve after discontinuation of the TMP-SMX therapy in most reported cases. This case report illustrates the importance of early detection of drug-induced hepatotoxicity and timely drug discontinuation to prevent the need for liver transplantation.

Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Child; Drug Hypersensitivity; Early Diagnosis; Eosinophilia; Humans; Liver; Male; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Chemical and Drug Induced Liver Injury; Child, Preschool; Diagnosis, Differential; Drug Hypersensitivity; Exanthema; Humans; Male; Mucocutaneous Lymph Node Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

A 34-yr-old woman developed simultaneous pancreatitis and hepatitis following exposure to trimethoprim-sulfamethoxazole (TMP/SMX). The episode occurred 4 yr after a previous episode of hepatitis associated with TMP/SMX. This patient represents the second case of concurrent TMP/SMX-induced pancreatitis and hepatitis reported in the literature. However, it is the first in which the adverse reaction was documented following an inadvertent rechallenge with the drug.

Topics: Adult; Chemical and Drug Induced Liver Injury; Female; Humans; Pancreatitis; Trimethoprim, Sulfamethoxazole Drug Combination

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

Topics: Adult; AIDS-Related Opportunistic Infections; Chemical and Drug Induced Liver Injury; Diagnosis, Differential; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Liver Function Tests; Pneumonia, Pneumocystis; Sinusitis; Transaminases; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Animals; Anti-Infective Agents; Chemical and Drug Induced Liver Injury; Colitis; Dog Diseases; Dogs; Soft Tissue Infections; Sulfasalazine; 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: Cephalexin; Chemical and Drug Induced Liver Injury; Follow-Up Studies; Hematologic Diseases; Humans; Kidney Diseases; Skin Diseases; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

To report a patient with 2 consecutive reversible drug-induced liver disorders and the application of International Consensus Meeting Criteria for the screening and diagnosis of drug-induced liver disorders.. An 88-year-old man in a chronic care institution developed abdominal discomfort and jaundice after finishing a 10-day course of trimethoprim/sulfamethoxazole therapy for a urinary tract infection (UTI). The jaundice and the symptoms resolved spontaneously and the final diagnosis was symptomatic drug-induced liver injury, mixed type. After 1 month, the same patient received a course of cefadroxil therapy for another UTI. He developed an asymptomatic drug-induced liver injury, mixed type. Six months later, the patient received oral penicillin therapy and then ciprofloxacin, with no change in his liver function test results.. To our knowledge, there are only a few other reports in the literature of a drug-induced liver injury with cefadroxil therapy; more cases are reported with trimethoprim/sulfamethoxazole than with cefadroxil. The criteria of an International Consensus Meeting were helpful to evaluate both incidences of liver injury in this patient with the aim of establishing the diagnosis and causality assessment. Additionally, the criteria were used to show that the patient had 2 separate liver injuries.. Screening and diagnosis of drug-induced liver disorders depend on careful history taking and 5 specific biochemical liver tests. The evolution of the liver disorder induced by cefadroxil therapy probably was interrupted because of its early detection. Appropriate screening was done with the subsequent administration of new potentially hepatotoxic drugs.

Topics: Aged; Aged, 80 and over; Anti-Infective Agents, Urinary; Cefadroxil; Cephalosporins; Chemical and Drug Induced Liver Injury; Humans; Male; Penicillins; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Candidiasis, Oral; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Drug Interactions; Fluconazole; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

We report the case of a 26-yr-old patient with fulminant liver failure and acute hemorrhagic pancreatitis secondary to the use of trimethoprim-sulfamethoxazole (Bactrim DS). Our patient presented with skin rash and decreased C3 and C4 levels, which we believed was due to a hypersensitivity reaction secondary to the sulfonamide component (sulfamethoxazole). To our knowledge, this is the first case reported in which sulfamethoxazole-trimethoprim has been implicated as a cause of fulminant liver failure and acute hemorrhagic pancreatitis simultaneously, and emphasizes the need of discontinuing this medication as soon as there is evidence of liver and pancreatic dysfunction.

Topics: Adult; Chemical and Drug Induced Liver Injury; Complement C3; Complement C4; Drug Hypersensitivity; Erythema; Hemorrhage; Humans; Male; Pancreatitis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Drug Combinations; Humans; Male; Recurrence; Respiratory Tract Infections; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Cyclophosphamide has proved to be the most effective therapy for Wegener's granulomatosis, but mortality remains high at many medical centers, and the necessity for giving this toxic agent for many years to prevent relapses remains a major problem. Successful treatment of this disease with sulfamethoxazole-trimethoprim has been reported by DeRemee et al, and experience in a series of ten patients at Thomas Jefferson University Hospital, Philadelphia, confirms its effectiveness. Nine patients are in remission, and the condition of one patient improved. Relapses occurred in four patients after intervals of remission ranging from four to 30 months, but responded to increased doses of trimethoprim in two patients, while two patients required resumption of therapy with cytotoxic agents. Although the effects of sulfamethoxazole-trimethoprim are suppressive rather than curative, its use represents a major advance in treatment of Wegener's granulomatosis, permitting successful treatment of many patients without high toxic doses of cyclophosphamide and prednisone.

Topics: Adolescent; Adult; Aged; Chemical and Drug Induced Liver Injury; Drug Combinations; Female; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Recurrence; Sulfamethoxazole; Thrombocytopenia; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (co-trimoxazole) is used extensively for treatment of pulmonary and urinary tract infections. Side effects may affect skin, blood, bone marrow, kidney and the liver. Although a number of sulfonamides have been reported to have produced hepatic lesions, hepatitis following therapy with trimethoprim-sulfamethoxazole is a rather rare event. While trimethoprim has not yet been reported as a cause of hepatic disorders, sulfamethoxazole has occasionally been described as inducing hepatic injury. In some cases, these reactions are accompanied by symptoms indicative for allergic reactions such as fever, rash and eosinophilia. Seven well documented cases are analyzed and discussed with respect to the nature of side effects caused by co-trimoxazole.

Topics: Adult; Aged; Anti-Infective Agents; Chemical and Drug Induced Liver Injury; Drug Combinations; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Chemical and Drug Induced Liver Injury; Drug Combinations; Humans; In Vitro Techniques; Lymphocyte Activation; Male; Prostaglandin Antagonists; Stimulation, Chemical; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Infective Agents; Chemical and Drug Induced Liver Injury; Drug Combinations; Fever; Humans; Jaundice; Male; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urination Disorders

Topics: Adult; Chemical and Drug Induced Liver Injury; Cholestasis; Drug Combinations; Female; Hepatic Encephalopathy; Humans; Male; Middle Aged; Sulfamethoxazole; Sulfonamides; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Infective Agents, Urinary; Chemical and Drug Induced Liver Injury; Drug Combinations; Humans; Liver; Male; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Drug Combinations; Drug Hypersensitivity; Female; Humans; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Trimethoprim-sulfamethoxazole is known to produce hepatitis. We report a case involving the inadvertent rechallenge with trimethoprim-sulfamethoxazole (Bactrim) in a patient with a previous episode of drug-induced hepatitis. A liver biopsy specimen showed both cholestatic and cytotoxic changes consistent with drug-induced damage. Comparison with existing cases is presented and an immunologic cause is considered.

Topics: Biopsy; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Drug Combinations; Humans; Liver; Male; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Chemical and Drug Induced Liver Injury; Drug Combinations; Humans; Male; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Two cases of severe sulfonamide liver injury are described. In one patient, fulminant liver failure developed after two days of taking sulfamethoxazole-trimethoprim. The patient was treated with resin hemoperfusion and recovered completely. Another patient became jaundiced after using sulfamethoxydiazine for ten days. Very severe intrahepatic cholestasis developed and cleared up only after high-dose prednison treatment. Marked hyperbilirubinemia persisted for four months and aminotransferase activity had not normalized ten months after the onset of the disease.

Topics: Adult; Anti-Infective Agents, Urinary; Chemical and Drug Induced Liver Injury; Drug Combinations; Female; Humans; Male; Middle Aged; Sulfameter; Sulfanilamides; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

During the decade 1968-1978 the Danish Board of Adverse Reactions to Drugs received 572 (6% of the total number) reports on hepatotoxicity. Halothane amounted to one fourth of the reported cases. Among the 94 psychotropic-induced adverse drug reactions 54 cases were attributed to chlorpromazine, 10 to tricyclic antidepressants, and only 2 to benzodiazepines. Considering the drug consumption data, the combination trimethoprim-sulfamethoxazole is nearly five times more frequently associated with hepatotoxicity than administration of sulfamethizole. Almost two thirds of the hepatotoxic reactions were classified as cytotoxic. Halothane, oxyphenisatin, rifampicin, alfa-methyldopa, papaverine, phenytoin, and ajmaline were almost exclusively related to cytotoxic reactions. Excluding the halothane-induced hepatotoxic reactions, the relative mortality of the cytotoxic (6%) reactions is not significantly different from that of the cholestatic (3%) ones. Thirteen percent of the patients with halothane-induced hepatotoxicity died.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents, Urinary; Antidepressive Agents, Tricyclic; Antitubercular Agents; Benzodiazepines; Chemical and Drug Induced Liver Injury; Child; Chlorpromazine; Contraceptives, Oral; Denmark; Drug Combinations; Female; Halothane; Humans; Male; Middle Aged; Oxyphenisatin Acetate; Risk Management; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination