trimethoprim--sulfamethoxazole-drug-combination and Cholestasis

Topics: Adult; Alkaline Phosphatase; Anti-Infective Agents; Bilirubin; Biomarkers; Cholestasis; Female; gamma-Glutamyltransferase; Humans; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

The main disadvantage of endoscopic insertion of an endoprosthesis is the tendency of the stent to clog after a few months. In this study we determined the role of bile viscosity in stent clogging.. Sixty patients were stented with 10 Fr 11-cm stents. The stents were electively removed after 2 months, and a bile sample was obtained simultaneously. Bile viscosity was measured with a coaxial rotation viscometer. The influence of treatment with antibiotics and a mucolytic agent on viscosity was assessed in a randomized trial.. Bile viscosity correlated significantly with DNA and total protein concentration. After treatment with either N-acetylcysteine or co-trimoxazole a lower mean value of the viscosity was observed, but this was not statistically significant. There was no correlation between bile viscosity and the amount of sludge adhering to the stents.. In most patients bile viscosity plays a limited role in stent clogging. Only in patients with excessively high viscosity do mucolytic agents or treatment with antibiotics seem to have a role.

Topics: Acetylcysteine; Aged; Bile; Cholestasis; Drainage; Female; Humans; Male; Palliative Care; Prospective Studies; Stents; Trimethoprim, Sulfamethoxazole Drug Combination; Viscosity

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

Drug-induced aseptic meningitis is a rare, but challenging diagnosis, most commonly reported with nonsteoroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Trimethoprim/sulfamethoxazole (TMP/SMX) is a sulfonamide that is widely used in clinical practice for the treatment and prophylaxis of various infections. The most common side effects associated with TMP/SMX are generally mild and self-limited, but serious side effects have been reported, including liver injury and aseptic meningitis.. We report a 2,5 year old Dutch girl with both drug-induced aseptic meningitis and drug-induced liver injury while using TMP/SMX prophylaxis. Ursodeoxycholic acid was started because of cholestatic injury. After cessation of TMP/SMX, full convalescence was reached within weeks.. This is the first report of a young patient with both aseptic meningitis and drug-induced liver injury caused by TMP/SMX. Drug-induced aseptic meningitis and cholestatic hepatitis constitute a considerable diagnostic challenge to clinicians. In addition to a thorough evaluation for infectious causes, clinicians should be aware of drug-induced aseptic meningitis and cholestatic hepatitis.

Topics: Anti-Infective Agents; Child, Preschool; Cholestasis; Female; Hepatitis; Humans; Meningitis, Aseptic; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Cholestasis; Diagnosis, Differential; Female; Fever; Headache; Humans; Transaminases; Trimethoprim, Sulfamethoxazole Drug Combination

Oncocytic changes seen in hepatocytes in patients receiving highly active antiretroviral therapy (HAART) are a result of mitochondrial damage. This is the first report that provides the electron microscopy illustration of mitochondrial proliferation as a result of the HAART drug Stavudine (Zerit) hepatotoxicity. The drug's effect on mitochondrial DNA replication leads to depleted mitochondrial-encoded proteins and configurational defects of the mitochondrial inner membrane leading to reduced and abnormal cristae, which house the electron transport chain and elementary bodies. This results in a decrease in the NAD/NADH ratio and reduces oxidative phosphorylation. The shift in the NAD/NADH ratio decreases the rate of fatty acid beta oxidation and oxidation of pyruvate by the Krebs cycle. Decreased oxidation of pyruvate drives it into an alternative pathway to form lactate leading to lactic acidosis. This mitochondrial dysfunction results in a compensatory increase in mitochondrial biogenesis, which results in oncocytic changes of the hepatocytes.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Biopsy; Cholestasis; DNA Replication; DNA, Mitochondrial; Female; Hepatocytes; Humans; Microscopy, Electron, Transmission; Mitochondria, Liver; Mitochondrial Proteins; Stavudine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Cholestasis; Female; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Aged, 80 and over; Cholestasis; Female; Humans; Respiratory Tract Infections; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Aged; Cholestasis; Female; Humans; Liver; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

A distinct clinical syndrome of cholestasis and hepatitis occurred during early infancy in seven infants with perinatally acquired human immunodeficiency virus 1 infection. In five infants hepatitis was the first manifestation of human immunodeficiency virus 1 infection. The median age of onset of hepatitis was 7 months (range, 5 to 10 months). The mean total bilirubin concentration at presentation was 7.4 mg/dl (range, 3.9 to 11 mg/dl), the mean aspartate aminotransferase was 1512 IU/liter (range, 782 to 2960 IU/liter) and the mean alanine amino-transferase 512 IU/liter (range, 92 to 1247 IU/liter). The absolute CD4 count at the time of onset of hepatitis ranged from 191 to 2298 cells/mm3 (mean, 766 cells/mm3). Six of the seven children died within 12 weeks of onset of hepatitis, three as a result of complications of Pneumocystis carinii pneumonia, and two died of complications secondary to cytomegalovirus. In only one infant was the cause of death the direct consequence of liver failure. The seventh infant died 17 months after the onset of hepatitis of dilated cardiomyopathy. No specific etiologic agent has been identified as the cause of cholestatic hepatitis in these infants. In situ hybridization studies to detect human immunodeficiency virus 1 messenger RNA was negative in the liver tissue obtained at biopsy and autopsy in five of the samples tested.

Topics: Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bilirubin; CD4-Positive T-Lymphocytes; Cholestasis; Female; Hepatitis; HIV Infections; HIV-1; Humans; Immunoglobulins; Infant; Jaundice; Leukocyte Count; Liver; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Alanine Transaminase; Aspartate Aminotransferases; Bilirubin; Cholestasis; Giant Cells; Hepatitis, Viral, Human; Hepatomegaly; HIV Infections; HIV Seropositivity; Humans; Infant; Liver; Pentamidine; Pneumonia, Pneumocystis; Splenomegaly; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Drug-induced liver injury due to trimethoprim sulfamethoxazole is rare and classified as an unpredictable or idiosyncratic type of hepatotoxic reaction. Early reports suggested that the pattern of liver injury in the majority of cases is mixed hepatocellular-cholestatic. The current report describes two cases of severe, prolonged cholestasis after treatment with trimethoprim sulfamethoxazole; intractable pruritus and abnormal liver test results lasted for 1-2 years after discontinuation of the drug. Liver biopsy specimens showed a cholestatic pattern of liver injury and only minimal hepatocellular necrosis or inflammation. Recent case reports suggest that cholestasis alone may occur after the use of trimethoprim sulfamethoxazole; these two additional cases show that cholestasis may be quite prolonged.

Topics: Adult; Cholestasis; Female; Humans; Middle Aged; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

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