rifampin and Stevens-Johnson-Syndrome

Topics: Anti-Bacterial Agents; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Toxins; Blood; Carrier State; Drug Resistance, Microbial; Humans; Nose; Rifampin; Sepsis; Shock, Septic; Staphylococcal Infections; Staphylococcus aureus; Stevens-Johnson Syndrome; Teichoic Acids

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Desensitization, Immunologic; Dose-Response Relationship, Drug; Ethambutol; Female; Humans; Isoniazid; Male; Pyrazinamide; Rifampin; Stevens-Johnson Syndrome; Treatment Outcome; Tuberculosis

Prospective randomised clinical trial comparing the safety and efficacy of rifampicin- and thiacetazone-containing regimens in human immunodeficiency virus (HIV)-infected adults with pulmonary tuberculosis (TB) at the National Tuberculosis Treatment Centre, Kampala, Uganda.. To assess demographic, clinical and laboratory risk factors associated with toxicity during treatment with streptomycin, thiacetazone and isoniazid (STH) of HIV-1 infected adults with pulmonary TB.. Nested case-control study of all subjects randomized to the STH treatment arm. Baseline demographic, clinical, microbiological, hematological and radiographic characteristics were compared between subjects who developed and those who did not develop adverse drug reactions (ADR).. Of the 90 subjects randomized to STH, 13 developed ADR yielding an incidence rate of 19.6 events per 100 person years of observation (PYO). Eleven of the 13 ADR were cutaneous hypersensitivity reactions, including one fatal case of Stevens-Johnson syndrome. Eight of 13 patients who developed ADR were tuberculin anergic, compared to 12 of 77 patients who did not develop ADR (P < 0.001). An absolute lymphocyte count below 2000 cells/mm3 was also associated with ADR (P = 0.02).. Initial anergy to tuberculin and lymphocytopenia, markers of advanced HIV infection and immunosuppression, were associated with increased risk for adverse drug reactions during STH chemotherapy.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Case-Control Studies; Clonal Anergy; Confidence Intervals; Developing Countries; Drug Eruptions; Drug Therapy, Combination; Female; HIV-1; Humans; Incidence; Jaundice; Lymphopenia; Male; Middle Aged; Odds Ratio; Prospective Studies; Rifampin; Risk Factors; Stevens-Johnson Syndrome; Survival Rate; Thioacetazone; Tuberculosis, Pulmonary; Uganda

Severe cutaneous adverse reactions related to first-line antituberculosis drugs are associated with high mortality and long-term morbidity. Oral sequential drug challenge, as a form of drug provocation testing, helps to salvage therapy by identifying culprit drugs but is associated with risk and is costly. IFN-γ enzyme-linked immune absorbent spot (ELISpot), an adjunctive in vitro diagnostic tool, may help to guide risk-stratification approaches. To determine the diagnostic accuracy of IFN-γ ELISpot against full-dose sequential drug challenge, we analyzed samples collected prospectively at multiple time points in 32 patients with first-line antituberculosis drug‒associated severe cutaneous adverse reaction (81% HIV infected, 25 with drug reaction with eosinophilia and systemic symptoms, and 7 with Stevens‒Johnson syndrome/toxic epidermal necrolysis). Sensitivity of IFN-γ ELISpot was 33% (4 of 12), 13% (1 of 8), 11% (1 of 9), and 0% (0 of 4) for rifampicin, isoniazid, pyrazinamide, and ethambutol, respectively (positivity threshold ≥50 spot forming units/million cells). Specificity was 100% for all the four drugs. Rifampicin IFN-γ ELISpot sensitivity increased to 58% (7 of 12) if a threshold of 20 spot forming units was used and to 75% (3 of 4) when restricted to samples <12 weeks after acute severe cutaneous adverse reaction event; specificity remained 100% for both. IFN-γ ELISpot offers adequate risk stratification of rifampicin severe cutaneous adverse reaction using acute samples and lowered threshold for positivity. Given the low sensitivity of IFN-γ ELISpot for other first-line antituberculosis drugs, additional optimization is needed to improve risk-stratification potential.

Topics: Antitubercular Agents; Ethambutol; HIV Infections; Humans; Interferon-gamma; Isoniazid; Pyrazinamide; Rifampin; Stevens-Johnson Syndrome

Topics: Antibiotics, Antitubercular; Cross Reactions; Humans; Immunoglobulin E; Male; Middle Aged; Rifabutin; Rifampin; Stevens-Johnson Syndrome; Treatment Outcome

A 58-year-old female with a history of dermatomyositis was receiving large oral doses of steroids. She had pulmonary tuberculosis and developed a fever, systemic exudative erythema, exanthema, and epidermolysis covering 30% of her body surface area while being treated with four agents, including isoniazid (INH) and rifampicin (RFP). Histopathologically, eosinophilic necrosis was observed in all layers of the epidermis and a diagnosis of Stevens-Johnson syndrome (SJS) progressive toxic epidermal necrolysis (TEN) was made. The drugs suspected in the drug-induced lymphocyte stimulation test (DLST) re-testing were INH and RFP, and the DLST was considered to be important during the recovery period as well as in the acute phase. Early treatment with plasma exchange therapy and large quantities of intravenous immunoglobulin (IVIG) was successful. Plasma exchange therapy and IVIG are extremely effective when SJS and TEN occur in a patient already on high-dose steroid therapy. Note that the incidence of SJS and TEN is believed to be higher in patients with collagen disease, such as in our case, as compared to the general population.

Topics: Dermatomyositis; Desensitization, Immunologic; Exanthema; Female; Humans; Immunoglobulins, Intravenous; Isoniazid; Middle Aged; Plasma Exchange; Rifampin; Stevens-Johnson Syndrome; Treatment Outcome; Tuberculosis, Pulmonary

Dermatological reactions are frequent drug-related complications in patients with HIV infection. The most serious disorders are Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), a.k.a. Lyell's syndrome, that are potentially fatal. The purpose of this report is to describe 8 cases of SJS/TEN observed in Lomé teaching hospital (Togo) after intake of a combination of rifampicin-isoniazid by HIV-infected patients. There were 5 men and 3 women with a mean age of 28 years. All patients presented AIDS. The disorder was SJS in 3 cases and TEN in 5. In 6 cases, manifestations occurred during initiation of treatment (mean delay for onset, 16 days). In the remaining two cases, manifestations occurred 6 days and 8 days respectively after beginning treatment for recurrent tuberculosis. Mean skin detachment was 8% in patients with SJS and 55.7% in patients with TEN. Five patients including 4 with TEN and 1 with SJS died. This study documents incrimination of combined rifampin-isoniazid treatment in the occurrence of SJS/TEN in patients with HIV infection and confirms the severity and poor prognosis of these disorders. The presence of opportunistic infections such as pulmonary tuberculosis may be an unfavourable prognostic factor in immunocompromised patients with these severe dermatological disorders.

Topics: Adult; Antibiotics, Antitubercular; Antitubercular Agents; Drug Therapy, Combination; Female; HIV Infections; Humans; Isoniazid; Male; Rifampin; Stevens-Johnson Syndrome; Togo; Tuberculosis, Miliary; Tuberculosis, Pulmonary

Topics: Acquired Immunodeficiency Syndrome; Adult; Humans; Male; Rifampin; Stevens-Johnson Syndrome; Tuberculosis, Pulmonary

Topics: Adult; Female; Humans; Rifampin; Stevens-Johnson Syndrome; Tuberculosis, Pulmonary

Topics: Adult; Drug Interactions; Ethambutol; Humans; Male; Rifampin; Stevens-Johnson Syndrome