trimethoprim--sulfamethoxazole-drug-combination and Nausea

Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and limited treatment options. Patients with IPF have altered lung microbiota, with bacterial burden within the lungs associated with mortality; previous studies have suggested benefit with co-trimoxazole (trimethoprim-sulfamethoxazole).. To determine the efficacy of co-trimoxazole in patients with moderate and severe IPF.. Double-blind, placebo-controlled, parallel randomized trial of 342 patients with IPF, breathlessness (Medical Research Council dyspnea scale score >1), and impaired lung function (forced vital capacity ≤75% predicted) conducted in 39 UK specialist interstitial lung disease centers between April 2015 (first patient visit) and April 2019 (last patient follow-up).. Study participants were randomized to receive 960 mg of oral co-trimoxazole twice daily (n = 170) or matched placebo (n = 172) for between 12 and 42 months. All patients received 5 mg of folic acid orally once daily.. The primary outcome was time to death (all causes), lung transplant, or first nonelective hospital admission. There were 15 secondary outcomes, including the individual components of the primary end point respiratory-related events, lung function (forced vital capacity and gas transfer), and patient-reported outcomes (Medical Research Council dyspnea scale, 5-level EuroQol 5-dimension questionnaire, cough severity, Leicester Cough Questionnaire, and King's Brief Interstitial Lung Disease questionnaire scores).. Among 342 individuals who were randomized (mean age, 71.3 years; 46 [13%] women), 283 (83%) completed the trial. The median (interquartile range) duration of follow-up was 1.02 (0.35-1.73) years. Events per person-year of follow-up among participants randomized to the co-trimoxazole and placebo groups were 0.45 (84/186) and 0.38 (80/209), respectively, with a hazard ratio of 1.2 ([95% CI, 0.9-1.6]; P = .32). There were no statistically significant differences in other event outcomes, lung function, or patient-reported outcomes. Patients in the co-trimoxazole group had 696 adverse events (nausea [n = 89], diarrhea [n = 52], vomiting [n = 28], and rash [n = 31]) and patients in the placebo group had 640 adverse events (nausea [n = 67], diarrhea [n = 84], vomiting [n = 20], and rash [n = 20]).. Among patients with moderate or severe IPF, treatment with oral co-trimoxazole did not reduce a composite outcome of time to death, transplant, or nonelective hospitalization compared with placebo.. ISRCTN Identifier: ISRCTN17464641.

Topics: Administration, Oral; Aged; Cough; Double-Blind Method; Female; Hospitalization; Humans; Idiopathic Pulmonary Fibrosis; Lung Transplantation; Male; Nausea; Patient Acuity; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP/SMX) is recognized as the superior agent for Pneumocystis carinii pneumonia (PCP) prophylaxis but a high incidence of adverse drug reactions, which may be due to toxic drug metabolites, limits its use. AIDS Clinical Trials Group protocol 268 was a randomized, double-blind, controlled two-arm trial designed to determine whether gradual initiation of TMP/SMX suspension reduced the incidence of treatment-limiting adverse drug reactions compared with routine initiation of double-strength (DS; 160 mg/800 mg) tablets. In all, 372 HIV-1-infected study subjects with a CD4+ cell count <250 x 10 cells/mm3 who had not previously received TMP/SMX for PCP prophylaxis were randomized to receive either daily TMP/SMX DS tablets or a gradually increasing dose of TMP/SMX suspension. The suspension dose was increased to reach the equivalent of a DS tablet by study day 13. During the first 2 weeks, study subjects also received a matching placebo tablet/suspension. After week 2, all study subjects received TMP/SMX tablets for the next 10 weeks. There were significantly fewer study subjects who discontinued prophylaxis during the first 12 weeks when TMP/SMX therapy was initiated gradually (17%) than when initiated in DS tablet formulation (33%) (p =.0002). Gradual initiation was also associated with significantly fewer adverse drug reactions. Gradual initiation of TMP/SMX for primary PCP prophylaxis reduces the incidence of its treatment-limiting adverse effects.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Double-Blind Method; Drug Eruptions; Female; Fever; HIV Infections; HIV-1; Humans; Male; Nausea; Pneumonia, Pneumocystis; Pruritus; Trimethoprim, Sulfamethoxazole Drug Combination

In 103 patients with small-cell lung cancer, we compared four courses of standard doses of Adriamycin (A) (Adria Laboratories, Columbus, Ohio), vincristine (V), and cyclophosphamide (C) with a regimen of increased doses of cyclophosphamide and to a lesser extent, Adriamycin. We found no significant difference in rate (22% v 21%) or median duration (seven v nine months) of complete remission. Patients not in complete remission after the four cycles of AVC received two courses of VP-16 (etoposide) and cisplatin: the complete remission rate increased to 49% and 48% respectively. Patients on the high-dose arm received co-trimoxazole prophylaxis; those on the standard arm did not. Patients on the high-dose arm had a higher incidence of neutropenia (nadir less than 500 cells/microL) but a lower incidence of infection for similar degrees of neutropenia. However, they also suffered more severe side effects of a different kind. Cotrimoxazole thus allowed for the administration of higher doses of chemotherapy to outpatients by protecting them from infection. However, the higher doses of cyclophosphamide and Adriamycin, did not improve treatment results, produced more severe side effects, and is not recommended.

Topics: Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cats; Cisplatin; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Combinations; Etoposide; Female; Humans; Infection Control; Lung Neoplasms; Male; Middle Aged; Nausea; Neutropenia; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine; Vomiting

A randomised single-blind clinical trial compared cinoxacin (500 mg every 12 hours) to co-trimoxazole (160 mg trimethoprim, 800 mg sulphamethoxazole every 12 hours) in the treatment of 63 patients with urinary tract infections. The symptomatic response was 73% for both drugs. Bacterial eradication was achieved in 81% and 100% of patients receiving cinoxacin and co-trimoxazole respectively. Three patients receiving co-trimoxazole stopped treatment because of adverse reactions. We conclude that cinoxacin is an effective and safe antibacterial agent in the treatment of urinary tract infections.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents, Urinary; Bacteriuria; Cinoxacin; Clinical Trials as Topic; Cystitis; Drug Combinations; Drug Hypersensitivity; Escherichia coli Infections; Female; Humans; Male; Middle Aged; Nausea; Pyelonephritis; Pyridazines; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

The introduction of sulfa drugs for the chemotherapy of bacterial infections in 1935 revolutionized medicine. Although their mechanism of action is understood, the molecular bases for most of their side effects remain obscure. Here, we report that sulfamethoxazole and other sulfa drugs interfere with tetrahydrobiopterin biosynthesis through inhibition of sepiapterin reductase. Crystal structures of sepiapterin reductase with bound sulfa drugs reveal how structurally diverse sulfa drugs achieve specific inhibition of the enzyme. The effect of sulfa drugs on tetrahydrobiopterin-dependent neurotransmitter biosynthesis in cell-based assays provides a rationale for some of their central nervous system-related side effects, particularly in high-dose sulfamethoxazole therapy of Pneumocystis pneumonia. Our findings reveal an unexpected aspect of the pharmacology of sulfa drugs and might translate into their improved medical use.

Topics: 5-Hydroxytryptophan; Adult; Alcohol Oxidoreductases; Anti-Infective Agents; Biopterins; Cell Line; Central Nervous System; Crystallography, X-Ray; Fibroblasts; Humans; Levodopa; NADP; Nausea; Pneumonia, Pneumocystis; Protein Conformation; Structure-Activity Relationship; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination; Vomiting

Cyclospora spp. which are coccidian parasites are rare gastroenteritis pathogens. The first cyclosporiasis case in Turkey was reported in 1998 in a patient with AIDS. In this paper we report a case of Cyclospora gastroenteritis, in a patient who was admitted to our hospital and who had had diarrhea, abdominal pain and nausea for ten days. In the anamnesis it was learned that he had travelled to the Black Sea region and had drunk muddy and cloudy water. His physical examination was normal except for increased bowel sounds. There were no leukocytes or erythrocytes in the direct microscopy of the stool and bacteriologic culture did not yield any enteropathogen. Cylospora oocyysts were seen in the parasitologic exmination. The patient was treated with cotrimaxasole (2x1,160/800 mg tablet). There was no pathogen in the repeated stool examination. Our case suggests that parasitologic examination should not be neglected in longlasting diarrhea cases and occasionally Cyclospora may be the causative agent.

Topics: Abdominal Pain; Adult; Anti-Infective Agents; Cyclospora; Cyclosporiasis; Diarrhea; Female; Gastroenteritis; Humans; Nausea; Trimethoprim, Sulfamethoxazole Drug Combination

The authors describe the case of a fifty-nine-year-old white man, previously in good health, who initiated his present illness with acute episode of enterocolitis characterized by mild fever and, in the next eight hours, twenty-four episodes of watery diarrhea, nausea and vomiting, as well as generalized sweating and severe weakness secondary to hypovolemia and electrolyte disorder. These complications were corrected in seventy-two hours in the intensive care unit. Two days later, when the patient was stable hemodynamically, under cardiac monitoring and with normal laboratory studies including serum electrolytes, he developed electrocardiographic changes characterized by trifascicular block (prolonged P-R interval, complete right bundle branch block [CRBBB] and left posterior hemiblock [LPH]) with a cardiac rate of thirty beats per minute, for which a temporary pacemaker was inserted. Endomyocardial biopsy showed histopathologic signs of myocarditis and the immunologic study of the cardiac tissue revealed positive polymerize chain reaction (PCR+) with the presence of antitoxine choleric antibodies (AcTCA). After three weeks, the same conduction disturbances remained, for which a permanent pacemaker was inserted. On top of intravenous fluid replacement and electrolyte supplements, the patient was managed with tetracycline 2 g a day for one week and sulfamethoxazole-trimethoprim 800/160 mg a day for two weeks. The purpose of this study is to present a rare and very well-documented myocarditis by cholera in a patient with enteric disease, in whom several cardiac complications occurred.

Topics: Anti-Bacterial Agents; Antibodies, Bacterial; Bradycardia; Bundle-Branch Block; Cholera; Diarrhea; Electrocardiography; Enterocolitis; Humans; Male; Middle Aged; Myocarditis; Nausea; Pacemaker, Artificial; Polymerase Chain Reaction; Sweating; Tetracycline; Trimethoprim, Sulfamethoxazole Drug Combination; Vibrio cholerae; Vomiting

We reviewed hospital records of women on the obstetrics and gynecologic services with a diagnosis of antibiotic-associated diarrhea, pseudomembranous colitis, or Clostridium difficile infection to better characterize the incidence and course of women with C difficile infection. Cases were included if there was identification of C difficile by culture or toxin or endoscopic verification of pseudomembranous colitis. Between January 1985 and June 1995, there were 74,120 admissions to the obstetrics and gynecology services at two tertiary level hospitals. Eighteen women were found to have documented C difficile infection (0.02%)--3 from the obstetric services, 10 from the benign gynecologic services, and 5 from the gynecologic/oncology services. Diarrhea developed from 2 days to 30 days after antibiotics had been given (mean, 10 days). Nine patients had fever, six had nausea and vomiting, and five had abdominal pain. Antimicrobial agents given before infection included cephalexin, cefoxitin, imipenem, ciprofloxacin, trimethoprim/sulfamethoxazole, ampicillin, gentamicin, and clindamycin. All patients were treated successfully with inpatient antimicrobial agents-15 with metronidazole and 3 with vancomycin. There was one possible recurrence.

Topics: Abdominal Pain; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Bacterial Toxins; Cefoxitin; Cephalexin; Cephalosporins; Cephamycins; Ciprofloxacin; Clindamycin; Clostridioides difficile; Colonoscopy; Diarrhea; Enterocolitis, Pseudomembranous; Female; Fever; Gentamicins; Humans; Imipenem; Incidence; Middle Aged; Nausea; Penicillins; Pregnancy; Pregnancy Complications, Infectious; Retrospective Studies; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination; Vomiting