Sulfamethoxazole-induced sulfamethoxazole urolithiasis: a case report.

BACKGROUND: Drug-induced urolithiasis falls into two categories: drug-induced and metabolically-induced. Certain antimicrobials are associated with each; sulfonamides are associated with drug- or metabolite-containing calculi when taken in large doses over a long period of time. Trimethoprim-sulfamethoxazole, a member of the sulfonamide family, is a rare cause of drug-induced calculi. Cases of sulfonamide urolithiasis occurring in patients with known stone disease have rarely been reported. CASE PRESENTATION: We report a case of a patient with a brief history of recurrent calcium oxalate nephrolithiasis requiring 2 ureteroscopic procedures whose existing 6 mm lower pole renal stone more than quadrupled in size to form a 4 cm renal staghorn after 4 months of high-dose treatment for Nocardia pneumonia with trimethoprim-sulfamethoxazole. After ureteroscopy with laser lithotripsy and basketing of fragments, the stone was found to be predominantly composed of N4-acetyl-sulfamethoxazole, a metabolite of sulfamethoxazole. CONCLUSION: Stones composed of sulfamethoxazole or its metabolites are rare but have known associated risk factors that should be considered when prescribing this antibiotic. This case report illustrates additional risk factors for consideration, including pre-existing urinary calculi that may serve as a nidus for sulfamethoxazole deposition, and reviews treatment and prevention methods.

In Vitro Protective Effect of Ascorbic Acid Against Antibiotic-Induced Hepatotoxicity.

BACKGROUND: Although antibiotic-induced hepatotoxicity is recoverable with mild impairment, and some cases were reported to cause morbidity. However, an adjuvant is essential in reducing such incidences. OBJECTIVE: The aim of this study is to evaluate the protective effect of ascorbic acid on antibiotic induced liver toxicity using liver slices. METHOD: Fresh liver slices were incubated with different concentrations of sulfamethoxazole tetracycline and clavulanic acid along with ascorbic acid (200µg/ml) for 2 hours. The liver homogenate was assessed for markers like ALT, AST, MDA and CAT levels. Cytotoxicity assessment was performed using MTT assay. RESULTS: Incubating liver slices with all three antibiotics shows elevated levels of aminotransferases, MDA and CAT enzyme when compared to the control groups which indicates the level of hepatotoxicity. In the presence of ascorbic acid, the elevated levels of TBARS, ALT and AST were significantly reduced which showcases the protective effect of ascorbic acid. The percentage survival of cell was also shown to have improved while accessed using cell viability assay. CONCLUSION: Obtained data suggests that consuming vitamin C or vitamin C containing food like citrus fruits or green leafy vegetables equivalent to 3g/day during antibiotic treatment, perhaps put down the risk of liver toxicity to a greater extent.

[Drug exanthema in connection with trimethoprim and sulfamethoxazole treatment, triggered by leech therapy]. / Arzneimittelexanthem in Zusammenhang mit Trimethoprim- und Sulfamethoxazol-Medikation -- Blutegeltherapie als triggernder Faktor.

In a 58-year-old hospitalized woman with gonarthrosis a leech therapy was applied to both knee joints. In the evening of the following day she observed strong pruritus in the area of the leech bites; in addition a maculopapular exanthema appeared on the torso and her lower extremities. The allergic reaction lasted four days. Administration of antihistamines only led to a slight improvement of the symptoms. A full restitution could only be achieved after a systemic dose of glucocorticoids on the fourth day after leech therapy. Eight days before beginning of the leech therapy a five-day antibiotic therapy with trimethoprim and sulfamethoxazole (Cotrim forte) had been administered to treat an uncomplicated urinary infection. Allergic reactions are well-known complications of these antibiotics and of leech therapy. The four-day duration of the allergic reaction after leech therapy, however, was untypical. In order to explain these symptoms, a prick test and an epicutaneous test for the antibiotic components were executed five weeks after the leech therapy. Furthermore, a second leech therapy was administered and a lymphocyte transformation test (LTT) was carried out. The results of the LTT showed a sensitization for sulfamethoxazole and a possible sensitization for trimethoprim, the results of the epicutaneous test showed a positive reaction to sodium lauryl sulfate, a component of the antibiotic. In the area of the leech bites a clear local skin reaction was observed. These results suggest a drug exanthema, in all probability triggered by the leech therapy.

Drug-induced pneumonitis caused by sulfamethoxazole, trimethoprim during treatment of Pneumocystis carinii pneumonia in a patient with refractory ulcerative colitis.

We recently treated a patient with intractable ulcerative colitis complicated with Pneumocystis carinii pneumonia in whom sulfamethoxazole/trimethoprim caused pneumonitis. The pneumonitis was difficult to differentiate from worsening of the infection or the appearance of another opportunistic infection. The patient's history of sulfasalazine (sulfonamide)-induced pneumonitis made diagnosis possible. The CD4/CD8 ratio of lymphocyte subsets in bronchoalveolar lavage fluid was decreased at the diagnosis of Pneumocystis carinii pneumonia and this ratio had increased when drug-induced pneumonitis was diagnosed. Topical administration of beclomethasone dipropionate by enema was a safe and effective for the treatment of such a compromised patient with active colitis.

Immune response to sulfamethoxazole in patients with AIDS.

Antibody- and cell-mediated responses to sulfamethoxazole (SMX) were analyzed in AIDS patients with or without a history of hypersensitivity and in negative controls. In 20 of 20 (P < 0.01) human immunodeficiency virus (HIV)-seropositive patients with skin reactions to cotrimoxazole, we found SMX-specific antibodies, while only 9 of 20 and 17 of 20 HIV-seropositive patients without a history of hypersensitivity to cotrimoxazole had SMX-specific immunoglobulin M (IgM) and IgG, respectively. The levels of specific IgM and IgG were higher in patients with skin reactions than in patients without reactions (IgM, 1.0 +/- 0.19 versus 0.47 +/- 0.23 [P < 0.001]; IgG, 0.68 +/- 0.15 versus 0.47 +/- 0.14 [P < 0.001] [mean optical density values +/- standard deviations]). Seronegative controls with no history of exposure to sulfa compounds did not have SMX-specific IgG or IgM antibodies, and controls with a history of intake of SMX with or without reactions had low levels of IgG and IgM. The SMX-specific IgG subclasses were exclusively IgG1 and IgG3. None of the patients had detectable SMX-specific IgE or IgA antibodies nor did they exhibit a cell-mediated response as measured by a lymphocyte proliferation assay. Antibodies to SMX recognized N-acetyl-sulfonamide, N-(2-thiazolyl)-sulfanilamide, sulfadiazine, and sulfisoxazole but did not recognize sulfanilamide or 3-amino-5-methyl isoxazole in an inhibition assay. It is not known whether the SMX-specific antibodies associated with hypersensitivity reactions to SMX in HIV-seropositive patients have a pathogenic role in these reactions. Sulfanilamide or 3-amino-5-methyl isoxazole, on the other hand, could be potential alternative therapies in HIV-seropositive patients with a history of skin reactions to SMX.

Tratamiento farmacológico del paciente con fiebre tifoidea: estudio comparativo entre ciprofloxacina y trimetoprim-sulfametoxazol / Pharmacological treatment of typhoid fever: A comparative study of Ciprofloxacin vs. Trimetoprim-sulfametoxasol

En un estudio abierto, prospectivo, longitudinal y comparativo se incluyeron 30 pacientes de uno u otro sexo, seleccionados del Hospital "José Ma. Rodríguez", de Ecatepec, Morelos, con diagnóstico de fiebre tifoidea, a los cuales se les administró ciprofloxacina o trimetoprim-sulfametoxasol y se comparó la eficacia y tolerancia entre ambos medicamentos. Las bacterias aisladas se obtuvieron por mielocultivo y/o hemocultivo; asimismo, se practicaron reacciones serológicas, siendo la reacción de Widal positiva en todos los casos estudiados. La dosis empleada fue de 500 mg de ciprofloxacina cada 12 h por vía oral en 16 pacientes y trimetoprim-sulfametoxazol, 800 mg por vía oral cada 12 h en los 14 pacientes restantes. Se logró la erradicación bacteriológica al final del tratamiento en la totalidad de los pacientes de ambos grupos, siendo importante señalar que el grupo de ciprofloxacina se obtuvieron cultivos negativos al sexto día de tratamiento en 10 casos (62.5%) y en nueve (64.3%) de los del grupo trimetoprim-sulfametoxasol. El número de días promedio para que la fiebre desapareciera fue de 5.6 para los pacientes del grupo ciprofloxacina y de 6.8 para los del grupo de trimetoprim-sulfametoxazol. Se concluye que la ciprofloxacina es una buena apción para el tratamiento del paciente adulto con fiebre tifoidea, mostrando niveles de eficacia y seguridad similares a los de trimetoprim-sulfametoxazol con la ventaja de que el síndrome febril se abatió más rápido en el grupo de ciprofloxacina.

Effect of folic and folinic acid on cytopenia occurring during co-trimoxazole treatment of Pneumocystis carinii pneumonia.

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.

Use of norfloxacin in the treatment of acute diarrheal disease.

In studies conducted in seven countries, 392 persons with acute diarrhea were enrolled and randomly assigned to one of three regimens. In order to compare the effectiveness of various therapies for acute gastroenteritis, patients were treated for five days with either norfloxacin, 400 mg twice daily, norfloxacin, 400 mg three times a day, or trimethoprim/sulfamethoxazole, (160 mg/800 mg) twice daily. Clinical cure occurred in 89 percent (lower dose) and 91 percent (higher dose) of those treated with norfloxacin, compared with 78 percent of those receiving trimethoprim/sulfamethoxazole; cure rates in each treatment group were greater when the patient's stool contained fecal leukocytes. In 105 of 106 (99 percent) patients treated with either dose of norfloxacin and in 49 of 52 (94 percent) trimethoprim/sulfamethoxazole-treated subjects, the bacterial enteropathogen identified in the pretreatment stool was eradicated on the posttreatment specimen. Two percent (two patients) of those receiving the lower dose of norfloxacin, 3 percent (two patients) of those receiving trimethoprim/sulfamethoxazole, and 4 percent (three patients) of those receiving the higher dose of norfloxacin experienced minor and transient adverse hematologic or blood chemistry reactions. In addition, mild cutaneous reactions that were attributed to the study medications developed in two patients receiving the higher dose of norfloxacin and in three patients who received trimethoprim/sulfamethoxazole. These studies indicate that norfloxacin is safe and effective therapy for bacterial diarrhea.

Ofloxacin versus trimethoprim-sulphamethoxazole in acute cystitis.

The clinical and bacteriological efficacy and adverse reactions of ofloxacin vs trimethoprim-sulphamethoxazole were investigated in a double-blind, randomised study in 250 female patients (125 in each group) with acute, uncomplicated lower urinary tract infections. The dosages of ofloxacin and trimethoprim-sulphamethoxazole were 100mg and 160mg + 800mg twice daily, respectively. The duration of therapy was 3 days. 81% of the patients had significant bacteriuria. Escherichia coli was isolated in 76% and Staphylococcus saprophyticus in 11% of the infections. The bacteriological elimination, clinical cure and improvement rates of the evaluable patients on ofloxacin treatment were 92 and 95%, respectively. The corresponding figures on trimethoprim-sulphamethoxazole therapy were 88 and 90%. Adverse reactions were clinically unimportant, and none of the patients had to stop treatment. Mild and transient side effects, mainly from the gastrointestinal tract, central nervous system and skin, were reported by 19 and 22% of the patients in the ofloxacin and trimethoprim-sulphamethoxazole groups, respectively. None of the differences in clinical and bacteriological efficacy and side effects of ofloxacin vs trimethoprim-sulphamethoxazole were statistically significant. Ofloxacin appears to be an appropriate antibiotic for short term therapy of acute, uncomplicated, lower urinary tract infections, comparing favourably with trimethoprim-sulphamethoxazole treatment in this study.

Clinical experience with ofloxacin in upper and lower urinary tract infections. A comparison with co-trimoxazole and nitrofurantoin.

The efficacy and tolerance of ofloxacin were compared with those of co-trimoxazole in upper urinary tract infections (UTIs) and nitrofurantoin in lower UTIs in a prospective, controlled, randomised, observer-blind study. Ofloxacin proved to be an effective and well-tolerated substance. The clinical cure rate was more pronounced than that of both comparative drugs and ofloxacin was also superior to co-trimoxazole and nitrofurantoin in terms of bacterial elimination. A second, controlled study showed that single doses of ofloxacin 100mg were clinically and bacteriologically as effective as a 3-day course of ofloxacin 100mg twice daily in women with uncomplicated lower UTIs.

A comparative study of cefadroxil and co-trimoxazole in patients with lower respiratory tract infections.

The most common causative pathogens in lower respiratory disease are S. pneumoniae, H. influenzae and S. pyogenes. Cefadroxil and co-trimoxazole, both orally administered broad spectrum antibiotics, are effective against these organisms when given in a twice-daily regimen. In this open randomised study, 42 patients with lower respiratory tract infections received cefadroxil 1 g or co-trimoxazole 1 double-strength tablet every 12 hours for a mean duration of 11 and 13 days, respectively. Pathogens were isolated in the pre-treatment sputum of 51% of patients given cefadroxil and in 25% of those who received co-trimoxazole. Similar overall cure rates were observed after treatment with cefadroxil (67%) and co-trimoxazole (60%); sputum purulence was similarly diminished by both drugs (91% and 85%, respectively). Neither antibiotic caused serious side effects. Thus, in a convenient twice-daily regimen, cefadroxil and co-trimoxazole are comparably effective in treating lower respiratory tract infections.

Oral trimethoprim/sulfamethoxazole for prevention of bacterial infection during the induction phase of cancer chemotherapy in children.

We conducted a randomized, double-blind, placebo-controlled study to evaluate the efficacy of oral trimethoprim/sulfamethoxazole (TMP/SMX) in the prevention of bacterial infections in children with cancer. Sixty-three patients with acute leukemia were studied during the induction phase of chemotherapy; 28 patients with solid tumors who were starting intensive chemotherapy were also enrolled and treated for 2 months. There was no significant difference in the frequency of febrile episodes between the 43 children receiving trimethoprim/sulfamethoxazole and the 48 receiving placebo. However, when the group of 74 children who experienced granulocytopenia (absolute granulocyte count less than 500/microL) was analyzed separately, significant reductions in the frequencies of confirmed bacteremia (2.6% v 20.0%, P = .02) and febrile episodes (35.9% v 65.7%, P = .01) were observed in the trimethoprim/sulfamethoxazole group. Furthermore, life table analysis showed that children with leukemia receiving trimethoprim/sulfamethoxazole had significantly more days without fever and without bacteremia. No benefits from prophylaxis were recognized in the subgroup with solid tumors. Although the frequency of oral thrush was greater (P = .02) in the trimethoprim/sulfamethoxazole group (25.6%) than in the placebo group (6.3%), invasive fungal infection did not occur. Although the mean duration of granulocytopenia was greater among those receiving trimethoprim/sulfamethoxazole (13.7 v 9.0 days, P = .05), this did not appear to increase the overall risk for bacterial infection. These data suggest that trimethoprim/sulfamethoxazole reduces the frequency of bacteremia and febrile episodes in granulocytopenic children undergoing induction chemotherapy for acute leukemia.

Multiclinic comparative study of norfloxacin and trimethoprim-sulfamethoxazole for treatment of urinary tract infections.

Three hundred seventy patients with upper or lower urinary tract infections were entered into a multicenter, open comparative study. A total of 190 patients were treated with norfloxacin, and 180 patients were treated with trimethoprim-sulfamethoxazole. The percentage of strains susceptible to norfloxacin (99%) was significantly greater (P less than 0.001) than the percentage of strains susceptible to trimethoprim-sulfamethoxazole (90%). The percentages of patients with bacteriological outcomes of eradication were greater in the norfloxacin group (97%) than in the trimethoprim-sulfamethoxazole group (90%). The difference was significant (P less than 0.05). Seven patients (three treated with norfloxacin, four treated with trimethoprim-sulfamethoxazole) experienced early reinfection. Of 370 patients entered into the study, 20 patients experienced clinical adverse effects that were probably or definitely related to the study drug; 6 patients were in the group that received norfloxacin, and 14 were in the group that received trimethoprim-sulfamethoxazole. Study antimicrobial agents were discontinued because of clinical adverse effects in eight patients (norfloxacin, one patient; trimethoprim-sulfamethoxazole, seven patients). Three patients receiving norfloxacin and four patients receiving trimethoprim-sulfamethoxazole had laboratory adverse effects which were classified as probably or definitely drug related. None of the clinical or laboratory adverse effects was serious.