trimethoprim--sulfamethoxazole-drug-combination and Leukopenia

Decrease of blood cells may be induced by either components of co-trimoxazole. Side effects of the trimethoprim component are much more frequent, particularly in risk groups. They are dose dependent, usually not severe, only rarely of clinical significance and easily treated or prevented by folate supplementation. In contrast, side effects of the sulfamethoxazole component seem to be extremely rare. They are similar to the hematological side effects of other sulfonamide drugs. They are idiosyncratic, nonpredictable and mostly mediated by the immune-system. They may be of life-threatening severity and no therapy is known except termination of exposure and supportive measures such as substitution of blood cells and antiinfectious therapy by non-related antibiotics.

Topics: Anemia; Anti-Infective Agents; Blood Cells; Drug Combinations; Humans; Leukopenia; Risk; Sulfamethoxazole; Thrombocytopenia; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

The efficacy of the prophylactic administration of sulfamethoxazole/trimethoprim (ST) plus norfloxacin (NFLX) versus ST alone to prevent the development of bacterial infection during chemotherapy-induced leukopenia was compared in patients with lung cancer. Patients who underwent systemic chemotherapy were randomized into one of the prophylactic regimens when grade 3 or 4 leukopenia occurred. Prophylactic treatment was performed on 133 courses of leukopenia in 75 patients and the efficacy was evaluated on 127 of those courses after excluding those patients who demonstrated a fever within 24 h from the start of the prophylaxis. The number of patients who had leukopenia associated fever was two out of 63 (3.2%) with the ST plus NFLX regimen and 10 out of 64 (15.6%) with ST alone; the difference was statistically significant. The prophylactic use of ST plus NFLX was thus found to be more useful than ST alone for the treatment of chemotherapy-induced leukopenia in patients with lung cancer.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cisplatin; Drug Therapy, Combination; Female; Granulocyte Colony-Stimulating Factor; Humans; Leukopenia; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Norfloxacin; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the safety and efficacy of 100 mg dapsone three times weekly for Pneumocystis carinii pneumonia (PCP) prophylaxis in HIV-infected, trimethoprim-sulfamethoxazole (TMP-SMX)-intolerant patients.. Retrospective chart review of patients followed-up to 22 May 1992.. Infectious diseases outpatient clinic of a tertiary care center in suburban New York City.. Twenty-three HIV-infected patients requiring PCP prophylaxis with documented intolerance to TMP-SMX.. Patients were followed clinically and with laboratory testing at approximately monthly intervals.. Dapsone was discontinued in nine (39%) patients because of adverse reactions. All reactions occurred within the first 2 months of treatment. Two (14%) of the remaining 14 patients developed histologically proven PCP over 126 patient-months of follow-up.. Approximately 40% of TMP-SMX-intolerant HIV-infected individuals are also intolerant of dapsone. Prophylaxis failures may be expected on a dose regimen of 100 mg dapsone three times weekly. More experience with other dose regimens and alternative agents is needed.

Topics: Adult; AIDS-Related Opportunistic Infections; Contraindications; Dapsone; Drug Eruptions; Female; Fever; Glutathione; HIV Infections; Humans; Leukopenia; Male; Pneumonia, Pneumocystis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Twenty-four consecutive HIV-positive patients affected by Toxoplasma gondii encephalitis received trimethoprim-sulfamethoxazole (cotrimoxazole) as acute-phase treatment. Two dosage regimens of cotrimoxazole were used: 40 mg/kg/day (12 patients) or 120 mg/kg/day (12 patients) of total compound (trimethoprim plus sulfamethoxazole). Clinical and radiological responses to treatment were evaluated, and the product-limit method for survival data analysis was used. Eighteen of 24 patients showed both a clinical and radiological response (75% response rate). There were no differences in response rates between patients receiving the two dosage regimens of cotrimoxazole. Adverse reaction consisted of leukopenia (two cases) and skin rash (three cases) which led to the discontinuation of the drug in one case. These results suggest that a randomized, controlled clinical trial should be carried out comparing cotrimoxazole versus sulfadiazine-pyrimethamine in AIDS patients with Toxoplasma gondii encephalitis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Drug Eruptions; Encephalitis; Female; Humans; Leukopenia; Male; Middle Aged; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

We report the hematologic changes in 90 black children who were randomized to receive a 10-day course of either trimethoprim-sulfamethoxazole (TMP-SMZ) or amoxicillin as therapy for acute otitis media. Absolute neutrophil counts less than 1500/mm3 developed at least once during the 23-day evaluation in 28 (57%) of the 49 children given TMP-SMZ and in 22 (54%) of the 41 who received amoxicillin. Incidence of leukopenia, thrombocytopenia, and anemia was negligible in both groups. Pancytopenia did not occur in any child. Absolute neutrophil counts had increased to greater than 1500/mm3 by the end of the study period in all of the patients but six, whose recovery required an additional 1 to 63 days. Decreased neutrophil counts in antibiotic-treated subjects remained within the range of findings for healthy black children, suggesting that a count less than 1500/mm3 may be an inappropriate criterion for an adverse drug effect. Neither TMP-SMZ nor amoxicillin produced hematologic effects that would detract from their continued use in children with infections caused by antibiotic-susceptible organisms.

Topics: Amoxicillin; Clinical Trials as Topic; Drug Combinations; Female; Humans; Infant; Leukocyte Count; Leukopenia; Male; Neutrophils; Otitis Media; Random Allocation; Sulfamethoxazole; Time Factors; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Adult; Autoimmune Diseases; Contraindications, Drug; Drug Therapy, Combination; Female; Humans; Leukopenia; Liver; Male; Methotrexate; Middle Aged; Pneumonia, Pneumocystis; Transaminases; Trimethoprim, Sulfamethoxazole Drug Combination

The objective of this study was to quantify the risk of serious blood and skin disorders associated with co-trimoxazole.. We conducted a population-based cohort study of serious blood and skin disorders requiring hospitalization among otherwise healthy users of co-trimoxazole at Group Health Cooperative and Puget Sound (GHC).. During the years 1987 to 1993 we found six cases of co-trimoxazole-associated blood disorders and three cases of co-trimoxazole-associated skin disorders yielding risks of 5.6/100,000 (95% CI 2.6-12.2) and 2.8/100,000 (95% CI 0.9-8.2) respectively. In all cases found there was prompt recovery after discontinuation of co-trimoxazole. We found no cases of toxic epidermal necrolysis.. We conclude that the risk of blood and skin disorders associated with the use of co-trimoxazole leading to hospitalization is low.

Topics: Adult; Aged; Anti-Infective Agents; Child, Preschool; Cohort Studies; Erythema Multiforme; Female; Hematologic Diseases; Hospitalization; Humans; Leukopenia; Longitudinal Studies; Male; Middle Aged; Neutropenia; Pancytopenia; Risk Assessment; Skin Diseases; Stevens-Johnson Syndrome; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination

To quantify the risk of serious blood and skin disorders requiring hospitalization among otherwise healthy users of co-trimoxazole.. We conducted a population-based cohort study at Group Health Cooperative of Puget Sound (GHC).. During the years 1987 to 1993 we found six cases of co-trimoxazole-associated blood disorders and three cases of co-trimoxazole-associated skin disorders yielding risks of 5.6/100,000 (95% CI 2.6-12.2) and 2.8/100,000 (95% CI 0.9-8.2) respectively. In all cases found there was prompt recovery after discontinuation of co-trimoxazole. We found no cases of toxic epidermal necrolysis.. We conclude that the risk of blood and skin disorders associated with the use of co-trimoxazole leading to hospitalization is low.

Topics: Adult; Aged; Anti-Infective Agents; Child, Preschool; Cohort Studies; Erythema Multiforme; Female; Hematologic Diseases; Hospitalization; Humans; Leukopenia; Longitudinal Studies; Male; Middle Aged; Neutropenia; Pancytopenia; Product Surveillance, Postmarketing; Risk Assessment; Skin Diseases; Stevens-Johnson Syndrome; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Drug Eruptions; Female; Fever; Humans; Leukopenia; Liver Function Tests; Middle Aged; Pruritus; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Agranulocytosis; Decision Making; Diagnosis, Differential; Dyspnea; Edema; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Infant, Newborn; Leukopenia; Lung Diseases; Lupus Erythematosus, Systemic; Pregnancy; Pregnancy Complications; Puerperal Disorders; Trimethoprim, Sulfamethoxazole Drug Combination

During the 10-year period 1976-1985, a total of 154 cases of blood dyscrasia were reported in Sweden which were evaluated as having a probable or possible causal relationship with trimethoprim-sulphamethoxazole (T-SM). There were 61 cases of leucopenia (of which 16 had agranulocytosis), 28 cases of thrombocytopenia, and two of non-haemolytic anaemia. There were also 32 cases of bicytopenia and 31 cases of tricytopenia. The median age varied from 38 years in the leucopenia group to 81 years in those with tricytopenia. The overall fatality rate was 17%, ranging from 2% in the group with mild leucopenia to 52% in the group with tricytopenia. In relation to sales and prescription data, the overall incidence of reported T-SM blood dyscrasias was 5.3 per million defined daily doses, and among out-patients the incidence was one case per 18,000 prescriptions. Thus the overall incidence of any blood reaction to T-SM appears to be low. In relation to prescription data, elderly people were overrepresented among the serious reactions.

Topics: Adult; Aged; Aged, 80 and over; Agranulocytosis; Female; Hematologic Diseases; Humans; Incidence; Leukopenia; Male; Middle Aged; Registries; Sweden; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination

12 AIDS/ARC patients with or suspected of Pneumocystis carinii pneumonia were treated with co-trimoxazole and received supplementary folic or folinic acid to avoid peripheral blood cytopenia. Most patients developed decreased numbers of neutrophils and hemoglobin while receiving co-trimoxazole. Supplementary folate/folinate could not abolish the drug-induced cytopenia. Routine prescription of folinic acid is not recommended. Folic acid is cheap and may be beneficial and should be prescribed.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Anemia; Drug Combinations; Folic Acid; Hematologic Diseases; Humans; Leucovorin; Leukopenia; Pneumonia, Pneumocystis; Prospective Studies; Sulfamethoxazole; Thrombocytopenia; Time Factors; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Daily administration of 1 mg of folinic acid to immunosuppressed rats with incipient or established Pneumocystis carinii pneumonia did not impair the capacity of trimethoprim-sulfamethoxazole to either prevent or treat this disease. These observations constitute the first experimental support for the use of folinic acid to prevent or control cytopenias that occur in patients with Pneumocystis carinii pneumonia who are under trimethoprim-sulfamethoxazole treatment.

Topics: Animals; Dexamethasone; Drug Combinations; Drug Interactions; Immunosuppression Therapy; Leucovorin; Leukopenia; Male; Pneumocystis; Pneumonia, Pneumocystis; Random Allocation; Rats; Rats, Inbred Strains; Sulfamethoxazole; Tetracycline; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Drug Combinations; Humans; Leucovorin; Leukopenia; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

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

We reviewed the charts of 38 patients with the acquired immunodeficiency syndrome who were treated for Pneumocystis carinii pneumonia. Only 5 of 37 patients started on trimethoprim-sulfamethoxazole were able to complete treatment; in 29 patients drug toxicity occurred and in 19 treatment was changed due to adverse reactions that included rash, fever, neutropenia, thrombocytopenia, and transaminase elevation. Pentamidine was given to 30 patients (1 as initial treatment); toxicity occurred in 13 but only 4 required a change in drug. Adverse reactions from pentamidine included fever, rash, neutropenia, transaminase elevation, azotemia, and hypoglycemia. Patients received trimethoprim-sulfamethoxazole a median of 9.5 days, and pentamidine, a median of 12.5 days. Toxicity from trimethoprim-sulfamethoxazole appeared earlier than toxicity associated with pentamidine (7.5 versus 9.5 days of treatment). In patients with the acquired immunodeficiency syndrome, trimethoprim-sulfamethoxazole has a higher incidence of adverse reactions than pentamidine (p less than 0.005).

Topics: Acquired Immunodeficiency Syndrome; Adult; Drug Combinations; Drug Eruptions; Drug Hypersensitivity; Fever; Humans; Leukopenia; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Clinical features of 49 episodes of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome were compared with those of 39 episodes in patients with other immunosuppressive diseases. At presentation patients with the syndrome were found to have a longer median duration of symptoms (28 days versus 5 days, p = 0.0001), lower mean respiratory rate (23.4 versus 30, p = 0.005), and higher median room air arterial oxygen tension (69 mm Hg versus 52 mm Hg, p = 0.0002). The survival rate from 1979 to 1983 was similar for the two groups (57% and 50% respectively). Patients with the syndrome had a higher incidence of adverse reactions to trimethoprim-sulfamethoxazole (22 of 34 versus 2 of 17, p = 0.0007). Survivors with the syndrome at initial presentation had a significantly lower respiratory rate, and higher room air arterial oxygen tension, lymphocyte count, and serum albumin level compared to nonsurvivors. Pneumocystis carinii pneumonia presents as a more insidious disease process in patients with the syndrome, and drug therapy in these patients is complicated by frequent adverse reactions.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; Child; Drug Combinations; Drug Eruptions; Drug Hypersensitivity; Female; Humans; Immunologic Deficiency Syndromes; Leukocyte Count; Leukopenia; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Respiration; Retrospective Studies; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination