trimethoprim--sulfamethoxazole-drug-combination and Drug-Related-Side-Effects-and-Adverse-Reactions

This systematic review and network meta-analysis (NMA) aimed to compare the efficacy of all available treatments for severe melioidosis in decreasing hospital mortality and to identify eradication therapies with low disease recurrence rates and minimal risk of adverse drug events (AEs).. Relevant randomized controlled trials (RCT) were searched from Medline and Scopus databases from their inception until July 31, 2022. RCTs that compared the efficacy between treatment regimens for severe melioidosis or eradication therapy of melioidosis, measured outcomes of in-hospital mortality, disease recurrence, drug discontinuation, or AEs, were included for review. A two-stage NMA with the surface under the cumulative ranking curve (SUCRA) was used to estimate the comparative efficacy of treatment regimens.. Fourteen RCTs were included in the review. Ceftazidime plus granulocyte colony-stimulating factor (G-CSF), ceftazidime plus trimethoprim-sulfamethoxazole (TMP-SMX), and cefoperazone-sulbactam plus TMP-SMX had a lower mortality rate than other treatments and were ranked as the top three most appropriate treatments for severe melioidosis with the SUCRA of 79.7%, 66.6%, and 55.7%, respectively. However, these results were not statistically significant. For eradication therapy, treatment with doxycycline monotherapy for 20 weeks was associated with a significantly higher risk of disease recurrence than regimens containing TMP-SMX (i.e.,TMP-SMX for 20 weeks, TMP-SMX plus doxycycline plus chloramphenicol for more than 12 weeks, and TMP-SMX plus doxycycline for more than 12 weeks). According to the SUCRA, TMP-SMX for 20 weeks was ranked as the most efficacious eradication treatment (87.7%) with the lowest chance of drug discontinuation (86.4%), while TMP-SMX for 12 weeks had the lowest risk of AEs (95.6%).. Our results found a non-significant benefit of ceftazidime plus G-CSF and ceftazidime plus TMP-SMX over other treatments for severe melioidosis. TMP-SMX for 20 weeks was associated with a lower recurrence rate and minimal risk of adverse drug events compared to other eradication treatments. However, the validity of our NMA may be compromised by the limited number of included studies and discrepancies in certain study parameters. Thus, additional well-designed RCTs are needed to improve the therapy of melioidosis.

Topics: Ceftazidime; Doxycycline; Drug-Related Side Effects and Adverse Reactions; Granulocyte Colony-Stimulating Factor; Humans; Melioidosis; Network Meta-Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei. The two stages of melioidosis treatment are the intense intravenous phase and the oral eradication phase. Although co-trimoxazole has been in use for several years, the literature does not demonstrate uniformity of the drug doses, combinations, or durations suitable for the eradication phase of melioidosis. The safety profile of co-trimoxazole was not documented in the literature, nor have systematic studies of its effectiveness been done. This systematic review sought to study on the dose, duration and combination of co-trimoxazole therapy in view of clinical efficacy and safety in the eradication phase of melioidosis.. This systematic review included all of the published articles that employed co-trimoxazole in the eradication phase after 1989, including, randomized clinical trials, case-control studies, cohorts, case reports, and case series. Throughout the eradication (maintenance) phase, co-trimoxazole usage was permissible in any dose for any period. A total of 40 results were included in the analysis which contained six clinical trials, one cohort study, one Cochrane review, and thirty-two case series/case reports. Clinical and microbial relapse rates are low when co-trimoxazole is used in single therapy than in combination. There were several adverse events of co-trimoxazole, however, a quantitative analysis was not conducted as the data did not include quantitative values in most studies.. The dose of co-trimoxazole, duration of the eradication phase, and other combinations used in the treatment was varying between studies. Compared to combined therapy patients treated with co-trimoxazole alone the mortality and relapse rates were low. The lowest relapse rate and lowest mortality rate occur when using co-trimoxazole 1920 mg twice daily. The duration of therapy varies on the focus of melioidosis and it is ranged from 2 months to one year and minimum treatment duration associated with low relapse rate is 3 months. The use of co-trimoxazole over the maintenance phase of melioidosis is associated with clinical cure but has adverse effects.

Topics: Administration, Intravenous; Case-Control Studies; Cohort Studies; Drug-Related Side Effects and Adverse Reactions; Humans; Melioidosis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii is an opportunistic pathogen causing life-threatening pneumonia in immunosuppressed patients. The number of non-HIV immunosuppressed patients at risk for Pneumocystis pneumonia is rapidly growing. In contrast to HIV patients, there are no guidelines for Pneumocystis prophylaxis in other immunocompromised hosts. A detailed analysis of current literature data allowed us hereby to define the type of immunocompromised patients for whom evidence suggests a benefit for PCP prophylaxis.

Topics: Anti-Infective Agents; Connective Tissue Diseases; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; HIV Infections; Humans; Immunocompromised Host; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Protein-Energy Malnutrition; Randomized Controlled Trials as Topic; Risk Factors; Transplantation; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vasculitis

Topics: Adult; Breast Feeding; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; Family Practice; Female; Humans; Middle Aged; Milk, Human; Postpartum Period; Pregnancy; Quinolones; Risk Assessment; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Human immunodeficiency virus (HIV) carrier patients experience several secondary effects with drugs, being mainly skin reactions and myelosuppression. Owing to this, close observation of patients is necessary with regard to therapeutic and prophylactic schedules. In this paper, we describe the secondary effects of zidovudine in 60 patients of groups III and IV from CDC. The main toxicity was found in bone marrow; with anemia in 50% and leukopenia in 53% of patients. Finally, the more frequent secondary effects of therapy for opportunist infections are analysed. A guide for identifying the drugs' secondary effects is also included, based on our experience and on a wide range of literature reviews.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antitubercular Agents; Drug-Related Side Effects and Adverse Reactions; Ganciclovir; HIV Infections; Humans; Opportunistic Infections; Pentamidine; Product Surveillance, Postmarketing; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

The therapeutic arsenal for MRSA infections is limited. The aim of this study was to assess the non-inferiority of a combination of trimethoprim/sulfamethoxazole plus rifampicin versus linezolid alone for the treatment of MRSA infection.. We conducted a randomized, open-label, single-centre, non-inferiority trial comparing trimethoprim/sulfamethoxazole (160 mg/800 mg three times daily) plus rifampicin (600 mg once a day) versus linezolid (600 mg twice a day) alone in adult patients with various types of MRSA infection. Patients were allocated 1:1 to either regimen. The primary outcome was clinical cure at 6 weeks after the end of treatment (non-inferiority margin 20%) assessed by both ITT and PP analyses. Secondary outcomes included the microbiologically documented persistence of MRSA in clinical cultures, mortality and adverse events. The study protocol has been registered with ClinicalTrials.gov (NCT00711854).. Overall, 150 patients were randomized to one of the two treatment arms between January 2009 and December 2013 and were included in the ITT analysis. Of these 56/75 (74.7%) in the linezolid group and 59/75 (78.7%) in the trimethoprim/sulfamethoxazole and rifampicin group experienced clinical success (risk difference 4%, 95% CI -9.7% to 17.6%). The results were confirmed by the PP analysis, with 54/66 (81.8%) cured patients in the linezolid group versus 52/59 (88.1%) in the trimethoprim/sulfamethoxazole and rifampicin group (risk difference 6.3%, 95% CI -6.8% to 19.2%). There were no statistically significant differences between the two groups in any of the secondary outcomes, including microbiologically documented failure. Four adverse drug reactions attributed to the study medication occurred in the linezolid group versus nine in the trimethoprim/sulfamethoxazole and rifampicin group.. Compared with linezolid, trimethoprim/sulfamethoxazole and rifampicin seems to be non-inferior in the treatment of MRSA infection.

Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Oxazolidinones; Rifampin; Staphylococcal Infections; Survival Analysis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Malaria during pregnancy has serious consequences that are worsened by HIV infection. Malaria preventive measures for HIV-infected pregnant women include cotrimoxazole (CTX) prophylaxis given to prevent HIV-related opportunistic infections and also protective against malaria, or intermittent preventive treatment (IPTp) with an antimalarial drug. Here, we present the first study evaluating CTX efficacy versus mefloquine (MQ)-IPTp, alone and in combination, in HIV-infected pregnant women.. We conducted 2 randomized, open-label, noninferiority trials in Benin. In the CTX-mandatory trial, HIV-infected women with CD4 counts of <350 per cubic millimeter received CTX either alone or with MQ-IPTp (N = 292). In the CTX-not-mandatory trial (CD4 count >350/mm), CTX was compared with MQ-IPTp (N = 140). In both the trials, the primary end point was microscopic placental parasitemia.. At delivery, 1 woman in each CTX-alone treatment group exhibited placental parasitemia, versus no women in the groups receiving MQ. CTX alone demonstrated noninferiority in the CTX-mandatory trial. However, polymerase chain reaction-detected placental parasitemia was markedly reduced in the CTX + MQ group compared with CTX alone (0/105 vs. 5/103, P = 0.03). Because of insufficient recruitment in the CTX-not-mandatory trial, noninferiority could not be conclusively assessed. Dizziness and vomiting of moderate intensity were reported by 34%-37% of women receiving MQ in both the trials, versus 0%-3% in CTX groups (P < 0.0001). No serious adverse events related to these drugs were found.. CTX alone provided adequate protection against malaria in HIV-infected pregnant women, although MQ-IPTp showed higher efficacy against placental infection. Although more frequently associated with dizziness and vomiting, MQ-IPTp may be an effective alternative given concerns about parasite resistance to CTX.

Topics: Adult; Antimalarials; Benin; Chemoprevention; Dizziness; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; HIV Infections; Humans; Infant; Infant, Newborn; Malaria; Mefloquine; Parasitemia; Pregnancy; Pregnancy Complications, Parasitic; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

There are no published reports on studies comparing itraconazole (ITC), sulfamethoxazole-trimethoprim (cotrimoxazole, CMX), and ITC followed by CMX (ITC/CMX) in the treatment of paracoccidiodomycosis. This study aimed to compare the efficacy, effectiveness, safety and time to clinical and serologic cure in paracoccidioidomycosis patients treated with ITC or CMX, the antifungal agents most widely used.. A quasi-experimental study was performed in 177 patients with a confirmed or probable diagnosis of paracoccidioidomycosis. Treatment was divided into two stages: 1) initial, which was continued until clinical cure was achieved and the erythrocyte sedimentation rate decreased to normal values; 2) complementary, which was continued until serologic cure was achieved. Medians were compared via the Mann-Whitney test, and frequencies were compared via the chi-squared test. The assessment of variables as a function of time was performed using Kaplan-Meier curves and Cox regression. The significance level was established as p≤0.05.. No difference was found in the efficacy and effectiveness of the initial treatment of 47 individuals given ITC and 130 individuals given CMX; however, the time to clinical cure was shorter in the former compared with the latter group (105 vs. 159 days; p = 0.001), specifically in patients with the chronic form. Efficacy and effectiveness of the three regimens were similar in the complementary treatment; however, the time to serologic cure was shorter when ITC (161 days) or CMX (495 days) was used compared with ITC/CMX (881 days) [p = 0.02]. The independent predictors of a shorter time to serologic cure were treatment with ITC [risk ratio = 6.61 (2.01-21.75)] or with CMX [risk ratio = 5.11 (1.91-13.67)]). The prevalence of side effects was lower with ITC (6.4%) than with CMX (20.0%; p = 0.03).. Since ITC induced earlier clinical cure and was better tolerated than CMX, such triazole should be considered the first-choice for PCM treatment.

Topics: Adult; Antifungal Agents; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Itraconazole; Male; Middle Aged; Paracoccidioidomycosis; Prevalence; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Owing to a broad spectrum and low cost antimicrobial, cotrimoxazole is largely prescribed. However, its use is associated with various adverse drug reactions (ADRs) that warrant to ensure rational prescribing. This study aimed to describe spontaneous reports of cotrimoxazole ADRs and to evaluate the quality of prescription in patients who had ADRs. Suspected cotrimoxazole-induced ADRs cases reported to the Bordeaux regional pharmacovigilance center (France) during a 5-year period were described. Seriousness was assessed according to international criteria. Quality of prescription was assessed by compliance with the Summary of Product Characteristics (SPC) and relevance of cotrimoxazole indication. Then, an ADR was considered as preventable if the cotrimoxazole indication was not relevant, or potentially preventable if indication was relevant but the prescription was not compliant with the SPC. A total of 96 cases were analyzed: median age was 60.5 years (range: 4-94); 59.4% of patients were male. ADRs were mostly cutaneous disorders (n = 46) and hematological disorders (n = 25). A total of 60 serious ADRs occurred in 55 patients. Prescribers complied with all SPC recommendations in 21.9% of cases. Indication of cotrimoxazole was relevant or highly relevant in 41 cases. In 58% of cases, the occurrence of a cotrimoxazole-induced ADR would have been preventable or potentially preventable. In a context of increasing interest for this antibiotic to treat infections due to resistant bacteria, physicians should be more aware of the potential consequences of inappropriate prescribing cotrimoxazole and reserve its use when there is no alternative and under suitable monitoring.

Topics: Adverse Drug Reaction Reporting Systems; Drug-Related Side Effects and Adverse Reactions; Humans; Inappropriate Prescribing; Male; Middle Aged; Pharmacovigilance; Trimethoprim, Sulfamethoxazole Drug Combination

Although there is a lack of data in trimethoprim-sulfamethoxazole (TMP-SMX) serum monitoring utility for invasive nocardial infections, therapeutic drug monitoring is widely used to optimize dosing and avoid adverse reactions that may cause treatment interruption.We retrospectively reviewed all adults who received TMP-SMX to treat nocardial brain abscess and had SMX serum level testing from 2010 to 2020.Twenty-two patients received treatment with TMP-SMX for Nocardia species brain abscess and 16 (72.7%) had a reported SMX level, with a median patient age of 65.5 years (interquartile range, IQR 59.5-72.5). Compared to those who did not have a documented SMX serum level, patients with SMX levels had a shorter median course of TMP-SMX treatment (322 days [IQR 188-365] vs. 365 [IQR 224-365]; P = .31) and higher therapeutic induction dose (10 [62.5%] vs. 3 [50%]; P = .92). Similarly, they were more frequently on hemodialysis (3 [13.6%] vs. 1 [4.5%]; P = > .99). The median peak level was 158.5 (IQR 120-218) μg/mL, collected at 2 hours (75%) post-administration in the induction phase (81.3%). Patients with documented SMX levels had fewer reported drug toxicity (5 [31.3%] vs. 4 [66.7%]; P = .1) than those without SMX levels. Among the five patients who reported TMP-SMX-related toxicity, 4 (80%) had an SMX peak level >150 μg/mL. There was no difference in the cure, relapse, and death rates among the two groups.While SMX level was not associated with Nocardia species brain abscess cure rates and mortality, most patients with SMX peak >150 μg/mL experienced drug toxicity.

Topics: Brain Abscess; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Nocardia; Retrospective Studies; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

Cutaneous adverse drug reactions (cADRs) among people living with HIV (PLWH) are common. Data on drug eruptions among PLWH in Malaysia are limited. Thus, our study aimed to determine the clinical patterns of cADRs among PLWH and the risk factors associated with severe cutaneous adverse reactions (SCAR).. A cross-sectional study was conducted among PLWH who developed cADRs presenting to our dermatology clinic from June 2020 to December 2020. The Naranjo scale was used for drug causality assessment.. A total of 78 PLWH were recruited with a male-to-female ratio of 12:1. The maculopapular eruption was the commonest type of cADRs (75.6%), followed by drug reaction with eosinophilia and systemic symptoms (DRESS) (15.4%). SCAR is defined as a potentially life-threatening, immunologically mediated, drug-induced disease, accounting for 17.9% of the cases. Most of the patients were on antiretroviral therapy (ART) (85.9%), with efavirenz + tenofovir/emtricitabine being the most common combination (80.6%). Efavirenz (51.3%) was the main culprit drug implicated, followed by trimethoprim/sulfamethoxazole (23.1%) and nevirapine (11.5%). CD4 T-cell count <100 cells/μL (. The commonest cADR seen in PLWH was maculopapular eruption, while efavirenz, trimethoprim/sulfamethoxazole, and nevirapine were the three main implicated drugs. Most of the cases had probable drug causality and were not preventable. PLWH with CD4 count <100 cells/μL were particularly at risk of developing SCAR. Overall, this study showed that immune suppression and polypharmacy as a consequence of opportunistic infection prophylaxis are important factors contributing to the increased risk of ADRs among PLWH.

Topics: Cross-Sectional Studies; Drug-Related Side Effects and Adverse Reactions; Female; HIV; HIV Infections; Humans; Malaysia; Male; Nevirapine; Tertiary Care Centers; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of this study was to determine the rates of trimethoprim/sulfamethoxazole (TMP/SMX)-associated pseudo-elevation and true nephrotoxicity by comparison of creatinine-estimated and cystatin C-estimated GFRs (glomerular filtration rates) before and after TMP/SMX administrations.. Patients in whom serum creatinine and cystatin C were simultaneously measured are the cohort of this study. A decreasing of creatinine-estimated GFR posterior to TMP/SMX by ≥ 20% and a decreasing of cystatine C-estimated GFR posterior to TMP/SMX by ≥ 20% were defined as true nephrotoxicity. A decreasing of creatinine-estimated GFR posterior to TMP/SMX by ≥ 20% and a decreasing of cystatine C-estimated GFR posterior to TMP/SMX by < 20% were defined as pseudo-elevation.. A total of 66 patients were enrolled. Within the 19 patients in whom serum creatinine and cystatin C were measured simultaneously both before and after TMP/SMX administrations, 10 patients (52.6%) had nephrotoxicity. Fewer random error and systematic bias between creatinine- and cystatine C-estimated GFR were observed after TMP/SMX than before TMP/SMX by Bland-Altman analysis.. Using cystatin C, we reveled TMP/SMX-associated nephrotoxicity is not uncommon. We should equally pay attention to TMP/SMX-associated nephrotoxicity and pseudo-elevation. In spite of pseudo-elevation, creatinine-estimated GFR after receiving TMP/SMX is ironically reliable as surrogate maker for renal clearance.

Topics: Creatinine; Drug-Related Side Effects and Adverse Reactions; Glomerular Filtration Rate; Humans; Renal Insufficiency; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX), a prophylactic agent against pneumocystis pneumonia (PCP), can cause adverse drug reactions (ADRs), particularly in patients with systemic lupus erythematosus (SLE). However, the risk factors for ADRs remain unclear. Thus, we sought to examine the prevalence of TMP-SMX-related ADRs in patients with SLE and identify specific risk factors for ADR development in these patients.. We retrospectively reviewed data from patients with connective tissue disease (CTD) who were administered TMP-SMX as a PCP prophylactic. The prevalence of ADRs was compared between patients with SLE and those with other CTDs. Univariate and multivariate analyses were conducted to identify risk factors for ADRs in patients with SLE.. Of the 424 patients with CTD included in our study (SLE, n = 162; other CTDs, n = 262), 22 with SLE (13.6%) developed ADRs, and this rate was significantly higher than that observed in patients with non-SLE CTDs (n = 18 [6.9%], p = 0.033). In patients with SLE, univariate analyses revealed direct associations of ADRs with anti-Sm (p < 0.001), anti-RNP (p = 0.02), and anti-Ro/SS-A antibodies (p = 0.042). Multivariate analysis identified a significant association between anti-Sm antibody levels and the development of ADRs (adjusted odds ratio 5.27, 95% confidence interval 1.80-15.40, p = 0.002).. Patients with SLE who are prophylactically administered TMP-SMX are at high risk of ADRs. Among these patients, those who display a positive anti-Sm antibody should be carefully monitored for ADRs.

Topics: Connective Tissue Diseases; Drug-Related Side Effects and Adverse Reactions; Humans; Lupus Erythematosus, Systemic; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

There are several isolated reports of systemic medications or medical conditions that can cause acute transient myopic shifts along with other ocular sequelae, but rarely has this been reported for the combination antibiotic sulfamethoxazole-trimethoprim.. This case illustrates a rarely seen condition that may result from treatment with sulfamethoxazole-trimethoprim and result in serious, vision-threatening conditions. These can be treated by immediate discontinuation of the drug, steroids, ocular hypertensive medication, and cycloplegia, depending on the circumstances.. A 20-year-old woman presented complaining of blindness upon waking. She had been experiencing fever, malaise, and significant abdominal pain for weeks. Blood culture revealed infection with Staphylococcus aureus and Escherichia coli for which she was prescribed sulfamethoxazole (800 mg) and trimethoprim (160 mg) twice daily. After a week of treatment, she awoke unable to see. Examination revealed narrowed angles, bilateral 6-D myopic shift, macular folding with scattered microaneurysms, and intraretinal hemorrhages with mild macular edema and field defects. The condition resolved with discontinuation of the drug and use of steroids, ocular hypertensive, and cycloplegic agents. Her visual acuity returned to near normal within 3 days. Resolution of macular edema, field defects, and hemorrhages followed.. An adverse reaction possibly caused by sulfamethoxazole-trimethoprim is described causing ciliochoroidal effusion resulting in acute myopic shift and other sequelae. Successful treatment is demonstrated, and implications are discussed.

Topics: Anti-Bacterial Agents; Bacteremia; Disease Progression; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Macular Edema; Myopia; Retinal Hemorrhage; Trimethoprim, Sulfamethoxazole Drug Combination; Vision Disorders; Visual Acuity; Visual Fields; Young Adult

Stenotrophomonas maltophilia-induced pulmonary haemorrhage is considered a fatal infection among haematological patients. The outcome can be explained by the patients' immunity status and late diagnosis and treatment.. We present the rare case of successful outcome in a 61-year-old female who developed alveolar haemorrhage and acute respiratory distress syndrome 8 days after a chemotherapy session for her acute lymphoblastic leukaemia, in the context of secondary bone marrow aplasia. Stenotrophomonas maltophilia was isolated in sputum culture. The patient benefitted from early empirical treatment with colistin followed by trimethoprim/sulfamethoxazole, according to the antibiogram. Despite a severe initial clinical presentation in need of mechanical ventilation, neuromuscular blocking agents infusion, and ventilation in prone position, the patient had a favourable outcome and was discharged from intensive care after 26 days.. Stenotrophomonas maltophilia severe pneumonia complicated with pulmonary haemorrhage is not always fatal in haematological patients. Empirical treatment of multidrug-resistant Stenotrophomonas maltophilia in an immunocompromised haematological patient presenting with hemoptysis should be taken into consideration.

Topics: Anti-Bacterial Agents; Colistin; Drug-Related Side Effects and Adverse Reactions; Female; Gram-Negative Bacterial Infections; Hemorrhage; Humans; Immunocompromised Host; Middle Aged; Pneumonia, Bacterial; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pulmonary Alveoli; Respiratory Distress Syndrome; Sputum; Stenotrophomonas maltophilia; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Abdominal Pain; Administration, Oral; Amylases; Cells, Cultured; Child; Drug-Related Side Effects and Adverse Reactions; Edema; Enzyme-Linked Immunospot Assay; Female; Humans; Immunization; Lipase; Lymphocyte Activation; Pancreatitis; T-Lymphocytes, Cytotoxic; Trimethoprim, Sulfamethoxazole Drug Combination; Vomiting; Withholding Treatment

Both co-trimoxazole and pentamidine are used for the treatment of pneumocystis pneumonia (PCP) and are known to cause hypoglycemia as an adverse drug reaction. Here, we describe a rare case of a late-diagnosed female patient with acquired immunodeficiency syndrome (AIDS) who developed the first hypoglycemic attack as an adverse effect of co-trimoxazole, followed by a second hypoglycemic attack as an adverse effect of pentamidine. Physicians caring for patients with AIDS and PCP should be aware of possible hypoglycemia in patients with many risk factors.

Topics: Acquired Immunodeficiency Syndrome; Aged; Anti-Infective Agents; Atovaquone; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hypoglycemia; Pentamidine; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Although the frequency of bone and joint infections caused by Enterobacter spp. is increasing, studies regarding the optimal antibiotic therapy are scarce. The objective of this retrospective study was to assess the clinical outcomes and safety of a fluoroquinolone-cotrimoxazole combination for the treatment of bone and joint infections caused by Enterobacter cloacae. Between 2010 and 2017, 30 patients with bone and joint infections caused by E. cloacae were treated with a fluoroquinolone-cotrimoxazole combination for 8-12 weeks. There were 26 cases (87%) of infection of an internal fixation device, two cases (6.6%) of pseudarthrosis with chronic osteomyelitis, and two cases (6.6%) of infection of knee and ankle prosthetic devices. The cure rate of the fluoroquinolone-cotrimoxazole combination was 80% by intention-to-treat analysis, with a mean follow-up of 29.3 ± 19.1 months. The fluoroquinolone-cotrimoxazole combination for 8-12 weeks is effective for the treatment of bone and joint infections caused by E. cloacae.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Arthritis; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Enterobacter cloacae; Enterobacteriaceae Infections; Female; Fluoroquinolones; Humans; Male; Middle Aged; Osteomyelitis; Prosthesis-Related Infections; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Adult; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Protein Binding; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

The objective of the study was to evaluate the efficacy and tolerability of trimethoprim-sulfamethoxazole (also known as co-trimoxazole, TMPS) to treat Klebsiella pneumoniae (Kp)-K. pneumoniae carbapenemase (KPC) infections.. Clinical data of patients with a TMPS-susceptible Kp-KPC infection were collected as a case series.. We report clinical outcomes and tolerability for 14 patients infected by Kp-KPC strains susceptible to TMPS, including three bloodstream infections. In ten cases (71.4%), TMPS was administered as monotherapy. In all but one case, Kp-KPC infection was cured. In the remaining patient, therapy was discontinued because of an adverse event.. The use of TMPS to treat TMPS-susceptible Kp-KPC infections seems promising.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP/SMX) is effective as prophylaxis against many infections in immunocompromised patients. However, it is not commonly prescribed for patients with systemic lupus erythematous (SLE) due to the risk of adverse reactions (ADRs). An upfront graded administration protocol for TMP/SMX was adopted, and its safety and efficacy were assessed.. Data from 59 patients with SLE patients who received prophylactic TMP/SMX were retrospectively analyzed. The incidence and risk factors for ADRs in patients who received TMP/SMX before and after the introduction of graded administration were assessed.. The incidence of ADRs was 41.9% in the non-graded administration group, vs. 10.7% in the graded administration group (p = 0.009). The rate of high fever, liver function test (LFT) abnormality, shortness of breath, and hospitalization were reduced in upfront graded administration group. In addition, a higher rate of anti-Ro/SS-A positivity was found in patients experienced ADRs (46.2% in reactors vs. 5.6% in non-reactors; p = 0.012) in the non-graded administration group.. Upfront graded administration of TMP/SMX reduces the incidence and severity of ADRs in SLE patients. The high incidence of TMP/SMX ADRs in SLE patients was also confirmed, especially when anti-Ro/SS-A antibody is present.

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Cohort Studies; Drug-Related Side Effects and Adverse Reactions; Female; Hospitalization; Humans; Immunocompromised Host; Incidence; Japan; Lupus Erythematosus, Systemic; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Information on antiretroviral therapy (ART) use in HIV-infected children with severe malnutrition (SM) is lacking. We investigated long-term ART outcomes in this population.. Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or body mass index-for-age Z score less than -3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age Z score less than -3) and poor CD4% recovery (CD4% <25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification.. Three hundred fifty-five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age Z score increased from -5.6 at ART initiation to -2.3 after 36 months. Not using trimethoprim-sulfamethoxazole prophylaxis at baseline was associated with poor weight recovery [odds ratio: 2.49 vs. using; 95% confidence interval (CI): 1.66-3.74; P < 0.001]. Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (odds ratio: 1.78 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.08-2.92; P = 0.023) and mortality (hazard ratio: 2.57 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.24-5.33; P = 0.011). Twenty-two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient-years, and rates did not differ by malnutrition severity.. Trimethoprim-sulfamethoxazole prophylaxis is important for the recovery of weight-for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability, but CD4% response is compromised in children with a very low weight-for-height/body mass index-for-age Z score, which may contribute to their high rate of mortality.

Topics: Adolescent; Anti-Bacterial Agents; Anti-Retroviral Agents; Antibiotic Prophylaxis; Antiretroviral Therapy, Highly Active; Asia; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Female; HIV Infections; Humans; Infant; Male; Malnutrition; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Anti-Infective Agents; Child; Drug-Related Side Effects and Adverse Reactions; Female; Flow Cytometry; Humans; Infant; Male; Prognosis; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Anti-HIV Agents; Bacterial Infections; Darunavir; Drug Hypersensitivity; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; HIV Infections; Humans; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Ambulatory Care; Child; Drug-Related Side Effects and Adverse Reactions; Extracorporeal Membrane Oxygenation; Humans; Patient Safety; Pediatrics; Respiratory Distress Syndrome; Risk Assessment; Tracheostomy; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Walking

Hyperkalemia is commonly seen in the elderly and is occasionally fatal. Inadvertently combining potassium sparing medications can result in profound hyperkalemia which may result in cardiac dysrhythmias, especially in the setting of chronic kidney disease. An 85 year-old woman on a drug regimen of sotalol, valsartan, spironolactone, and trimethoprim-sulfamethoxazole presented to the emergency department with hypotension and bradycardia. Presumptive treatment for hyperkalemia was started based on her initial electrocardiogram. This diagnosis was later confirmed with a serum potassium value of 10.1 mmol/L. Following pharmacologic treatment, emergency hemodialysis was performed and the patient subsequently recovered. It is known that several drug classes can cause hyperkalemia, with elderly patients at a higher risk of developing this side effect. It is believed that this was a major contributor to the degree of hyperkalemia seen in this patient.

Topics: Aged, 80 and over; Anti-Arrhythmia Agents; Diuretics; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Female; Humans; Hyperkalemia; Renal Dialysis; Sotalol; Spironolactone; Trimethoprim, Sulfamethoxazole Drug Combination

Little is known about the characteristic features of oral mucosal fixed drug eruption (FDE).. To present the clinical highlights and the differential diagnosis of oral mucosal FDE in a relatively large group of patients from Turkey.. This was a methodological, retrospective, cross-sectional study of 61 patients with oral mucosal FDE. The causative drug was established mainly by oral provocation test.. The age range of 61 patients (38 females, 23 males) was 7 to 62 years. Naproxen and cotrimoxazole were the main inducers. Fourteen patients (23%) had a solitary oral lesion predominantly located on the dorsum of the tongue, or on the hard palate, the former statistically significantly associated with cotrimoxazole. Bullous/erosive (n = 47), aphthous (n = 12), and erythematous (n = 2) morphology were observed. A considerable number of patients were referred with a prior clinical diagnosis of herpes simplex and Behçet's disease; some of them were already receiving long-term treatment with acyclovir and colchicine, respectively.. The main limitation of the present study resides in its retrospective design.. Isolated oral lesions, aphthous lesions, severe bullous/erosive lesions, and the absence of residual pigmentation are the main features that may cause difficulties in the differential diagnosis. It is important to differentiate dysmenorrhea-related monthly attacks of oral FDE in female patients caused by nonsteroidal anti-inflammatory drugs from menstruation-triggered attacks of herpes simplex infection, and isolated orogenital aphthous FDE from Behçet's disease, especially in countries with a high frequency of the disease in order to prevent irrelevant therapies.

Topics: Adolescent; Adult; Age Distribution; Behcet Syndrome; Child; Cross-Sectional Studies; Diagnosis, Differential; Drug Eruptions; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Herpes Simplex; Humans; Incidence; Male; Middle Aged; Mouth Mucosa; Naproxen; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sex Distribution; Stomatitis, Aphthous; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Drug-induced immune haemolytic anaemia is a rare but serious condition. This study investigated the possibility of drug aetiology of immune haemolytic anaemia (IHA) in 134 patients with new onset of IHA who were identified in the Berlin Case-Control Surveillance Study between 2000 and 2009. Single drugs related to IHA in three or more patients and assessed more than once as a certain or probable cause of IHA in a standardized causality assessment included diclofenac, fludarabine, oxaliplatin, ceftriaxone and piperacillin. In a case-control study including all 124 IHA cases developed in outpatient care and 731 controls, significantly increased odds ratios (OR) were observed for beta-lactam antibiotics (OR=8·8; 95% confidence interval [CI] 3·2-25·2), cotrimoxazole (OR=6·5; CI 1·1-37·9), ciprofloxacin (OR=6·9, CI 1·3-38·5), fludarabine (OR=22·2; CI: 2·8-454·5) and lorazepam (OR=5·3; CI: 1·2-21·2). Excluding new onset cases with a chronic IHA disease course, an increased risk became also apparent for diclofenac with an OR of 3·1 (CI 1·3-7·0). This is the first case-control study investigating drugs as risk factors for IHA. It corroborates an increased risk for several drugs that have been implicated as a cause of IHA in the standardized causality assessment of individual cases.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Hemolytic, Autoimmune; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Berlin; beta-Lactams; Case-Control Studies; Ciprofloxacin; Diclofenac; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Lorazepam; Male; Middle Aged; Odds Ratio; Piperacillin; Population Surveillance; Trimethoprim, Sulfamethoxazole Drug Combination; Vidarabine; Young Adult

Chronic neurotoxicity is a recognized long-term complication following chemotherapy in a range of diseases. Neurotoxicity adversely affects patients' quality of life. The objective of this study is to examine whether there is evidence of acute neurotoxicity.. This prospective study included patients with secondary progressive multiple sclerosis (SPMS-BMT, n = 14) and hematological malignancies (HM-BMT, n = 17) receiving chemotherapy as preconditioning for bone marrow transplant. The control groups included SPMS patients matched for demographic and clinical data (SPMS-PL, n = 14) and healthy controls (n = 14). Neurodegeneration was assessed at baseline and longitudinally (months 1, 2, 3, 6, 9, 12, 24, and 36), combining a clinical scale for disability (Expanded Disability Status Scale [EDSS]), a serum protein biomarker for neurodegeneration (neurofilaments, NfH-SMI35), and brain atrophy measures (magnetic resonance imaging).. Disability progression was significantly more acute and severe following chemotherapy compared to placebo. Immediately after starting chemotherapy, serum NfH-SMI35 levels increased in 79% (p < 0.0001) of SPMS-BMT patients and 41% (p < 0.01) of HM-BMT patients compared to 0% of SPMS-PL patients or healthy controls. In SPMS-BMT serum NfH-SMI35 levels were > 100-fold higher 1 month after chemotherapy (29.73ng/ml) compared to baseline (0.28ng/ml, p < 0.0001). High serum NfH-SMI35 levels persisting for at least 3 months were associated with sustained disability progression on the EDSS (p < 0.05). Brain atrophy rates increased acutely in SPMS-BMT (-2.09) compared to SPMS-PL (-1.18, p < 0.05).. Neurotoxicity is an unwanted acute side effect of aggressive chemotherapy.

Topics: Acute Disease; Adult; Anti-Infective Agents; Bone Marrow Transplantation; Brain; Case-Control Studies; Disability Evaluation; Drug-Related Side Effects and Adverse Reactions; Female; Hematologic Neoplasms; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Multiple Sclerosis, Chronic Progressive; Neurofilament Proteins; Neurotoxicity Syndromes; Prednisolone; Single-Blind Method; Statistics, Nonparametric; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

The clarity of prescription drug instructions is a health literacy and medication safety concern.. To assess the variability of pharmacy interpretations of physician prescriptions.. Identically written prescriptions for 4 common medications (atorvastatin, alendronate, trimethoprim/sulfamethoxazole, ibuprofen) were filled in 6 pharmacies (2 largest chains, 2 grocery stores, 2 independents) in 4 cities (Boston, Chicago, Los Angeles, Austin).. Components of the instruction were coded as dose, frequency, administration route, timing, indication, and auxiliary instructions.. In all, 85 labels were evaluated. Dose frequency was omitted on 6% of instructions ("take 1 tablet for cholesterol"). Timing was explicitly stated on 2% of instructions ("in the morning"). All prescriptions included indications; pharmacies transcribed these onto 38% of labels. The prescription for alendronate stated not to lie down for at least 30 minutes after taking; this was transcribed with 50% of instructions. Reading difficulty was above recommended levels for 46% of instructions; with 14% greater than a high school level.. Efforts are needed to ensure patients receive clear, consistent information supporting safe medication use.

Topics: Alendronate; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Atorvastatin; Bone Density Conservation Agents; Comprehension; Contraindications; Drug Information Services; Drug Labeling; Drug Prescriptions; Drug-Related Side Effects and Adverse Reactions; Education, Pharmacy; Educational Status; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ibuprofen; Patient Education as Topic; Pharmaceutical Preparations; Pharmacies; Professional Competence; Pyrroles; Trimethoprim, Sulfamethoxazole Drug Combination; Urban Health Services; Writing

To examine prescription Food and Drug Administration (FDA) C, D and X drugs in general obstetric population.. Historical cohort study.. A total of 18 575 women who gave a birth in Saskatchewan between January 1997 and December 2000 were included. Among them, 3604 (19.4%) received FDA C, D or X drugs at least once during pregnancy. The pregnancy exposure rates were 15.8, 5.2 and 3.9%, respectively, for category C, D and X drugs, and were 11.2, 7.3 and 8.2%, respectively, in the first, second and third trimesters. Salbutamol (albuterol), trimethoprim/sulfamethoxazole (co-trimoxazole), ibuprofen, naproxen and oral contraceptives were the most common C, D, X drugs used during pregnancy.. About one in every five women uses FDA C, D and X drugs at least once during pregnancy, and the most common prescription drugs in pregnancy are antiasthmatic, antibiotics, nonsteroid anti-inflammation drugs, antianxiety or antidepressants and oral contraceptives.

Topics: Adult; Albuterol; Contraceptives, Oral; Cross-Sectional Studies; Drug Prescriptions; Drug-Related Side Effects and Adverse Reactions; Female; Gestational Age; Humans; Ibuprofen; Infant, Newborn; Naproxen; Population Surveillance; Pregnancy; Prenatal Exposure Delayed Effects; Saskatchewan; Trimethoprim, Sulfamethoxazole Drug Combination; United States; United States Food and Drug Administration

Topics: Chronic Disease; Drug-Related Side Effects and Adverse Reactions; Humans; Purpura, Thrombocytopenic; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Drug-induced immune thrombocytopenia, excluding heparin-induced thrombocytopenia, is a rare adverse drug reaction for which the evidence about frequency, relative risk and risk factors mainly originates from case reports and case studies. This study aims to quantify the risk for thrombocytopenia following exposure to drugs that are most often reported to cause thrombocytopenia in the general population.. A retrospective, case-control study was conducted within the PHARMO record linkage system. Cases were defined as patients hospitalised for thrombocytopenia in the period 1 January 1990 to 31 December 2002. For each case, up to four controls were matched based on age, sex and geographical area. Exposure on the index date to anticonvulsants, beta-lactam antibacterials, cinchona alkaloids, disease modifying antirheumatic drugs (DMARDs), diuretics, NSAIDs, sulfonamide antibacterials and tuberculostatics was assessed and categorised into mutually exclusive groups of current, recent, past and non-use. The risk was quantified with multivariate conditional logistic regression analysis.. The study population comprised 705 cases and 2658 controls. Current use of beta-lactam antibacterials was associated with an increased risk for thrombocytopenia (adjusted odds ratio 7.4, 95% CI 1.8, 29.6). Increased risk estimates, although not significant, were found for current exposure to DMARDs and the sulfonamide antibacterial cotrimoxazole (trimethoprim/sulfamethoxazole). No increased risk was found for anticonvulsants, cinchona alkaloids, diuretics, NSAIDs or tuberculostatics.. More evidence for an increased risk for thrombocytopenia in current use of beta-lactam antibacterials in the general population was provided. The expected increase in risk could not be confirmed for the other drugs investigated, which is possibly a result of the limited statistical power. Future studies including more patients and with laboratory data should confirm our findings before drawing definite conclusions.

Topics: Anti-Infective Agents; Antirheumatic Agents; beta-Lactams; Case-Control Studies; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Medical Records Systems, Computerized; Middle Aged; Netherlands; Odds Ratio; Retrospective Studies; Risk Factors; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination

Drug-drug interactions are a preventable cause of morbidity and mortality, yet their consequences in the community are not well characterized.. To determine whether elderly patients admitted to hospital with specific drug toxicities were likely to have been prescribed an interacting drug in the week prior to admission.. Three population-based, nested case-control studies.. Ontario, Canada, from January 1, 1994, to December 31, 2000.. All Ontario residents aged 66 years or older treated with glyburide, digoxin, or an angiotensin-converting enzyme (ACE) inhibitor. Case patients were those admitted to hospital for drug-related toxicity. Prescription records of cases were compared with those of controls (matched on age, sex, use of the same medication, and presence or absence of renal disease) for receipt of interacting medications (co-trimoxazole with glyburide, clarithromycin with digoxin, and potassium-sparing diuretics with ACE inhibitors).. Odds ratio for association between hospital admission for drug toxicity (hypoglycemia, digoxin toxicity, or hyperkalemia, respectively) and use of an interacting medication in the preceding week, adjusted for diagnoses, receipt of other medications, the number of prescription drugs, and the number of hospital admissions in the year preceding the index date.. During the 7-year study period, 909 elderly patients receiving glyburide were admitted with a diagnosis of hypoglycemia. In the primary analysis, those patients admitted for hypoglycemia were more than 6 times as likely to have been treated with co-trimoxazole in the previous week (adjusted odds ratio, 6.6; 95% confidence interval, 4.5-9.7). Patients admitted with digoxin toxicity (n = 1051) were about 12 times more likely to have been treated with clarithromycin (adjusted odds ratio, 11.7; 95% confidence interval, 7.5-18.2) in the previous week, and patients treated with ACE inhibitors admitted with a diagnosis of hyperkalemia (n = 523) were about 20 times more likely to have been treated with a potassium-sparing diuretic (adjusted odds ratio, 20.3; 95% confidence interval, 13.4-30.7) in the previous week. No increased risk of drug toxicity was found for drugs with similar indications but no known interactions (amoxicillin, cefuroxime, and indapamide, respectively).. Many hospital admissions of elderly patients for drug toxicity occur after administration of a drug known to cause drug-drug interactions. Many of these interactions could have been avoided.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Asthmatic Agents; Anti-Infective Agents; Antihypertensive Agents; Case-Control Studies; Clarithromycin; Contraindications; Digoxin; Diuretics; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Female; Glyburide; Hospitalization; Humans; Hyperkalemia; Hypoglycemia; Male; Ontario; Trimethoprim, Sulfamethoxazole Drug Combination

The frequency of multimorbidity in elderly patients may mislead the physician into practicing polypragmasy (polypharmacy), resulting in unpredictable drug interactions. Such interactions are a quite common cause of hospitalization in geriatric patients. Pharmacokinetics are often altered in the aged, and individualized medication should take into consideration not only the patient's age, liver and kidney function, but also the individual variability of hepatic metabolism and drug absorption from the gastrointestinal tract dictated by genetic polymorphism. Drug treatment in the elderly should always be carefully assessed as to its risks and benefits, and, where indicated, certain medications should be replaced by or omitted.

Topics: Age Factors; Aged; Aged, 80 and over; Algorithms; Anti-Infective Agents; Anti-Infective Agents, Urinary; Ciprofloxacin; Creatinine; Diphenhydramine; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hypnotics and Sedatives; Male; Models, Theoretical; Pharmaceutical Preparations; Pharmacogenetics; Polymorphism, Genetic; Polypharmacy; Trimethoprim, Sulfamethoxazole Drug Combination

Drug eruptions are among the most common cutaneous disorders encountered by the dermatologist. Some drug eruptions, although trivial, may cause cosmetic embarrassment and fixed drug eruption (FDE) is one of them. The diagnostic hallmark is its recurrence at previously affected sites.. We evaluated 450 FDE patients to determine the causative drugs.. The ratio of men to women was 1:1.1. The main presentation of FDE was circular hyperpigmented lesion. Less commonly FDE presented as: nonpigmenting erythema, urticaria, dermatitis, periorbital or generalized hypermelanosis. Occasionally FDE mimicked lichen planus, erythema multiforme, Stevens-Johnson syndrome, paronychia, cheilitis, psoriasis, housewife's dermatitis, melasma, lichen planus actinicus, discoid lupus erythematosus, erythema annulare centrifugum, pemphigus vulgaris, chilblains, pityriasis rosea and vulval or perianal hypermelanosis. Cotrimoxazole was the most common cause of FDE. Other drugs incriminated were tetracycline, metamizole, phenylbutazone, paracetamol, acetylsalicylic acid, mefenamic acid, metronidazole, tinidazole, chlormezanone, amoxycillin, ampicillin, erythromycin, belladonna, griseofulvin, phenobarbitone, diclofenac sodium, indomethacin, ibuprofen, diflunisal, pyrantel pamoate, clindamycin, allopurinol, orphenadrine, and albendazole.. Cotrimoxazole was the most common cause of FDE, whereas FDE with diclofenac sodium, pyrantel pamoate, clindamycin, and albendazole were reported for the first time. FDE may have multiform presentations.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Child; Child, Preschool; Drug Eruptions; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Infant; Male; Middle Aged; Pakistan; Skin; Trimethoprim, Sulfamethoxazole Drug Combination

To determine whether patients should participate directly in detecting adverse reactions to drugs their ability to provide written reports of symptoms experienced during treatment with amoxycillin or trimethoprim-sulphamethoxazole was investigated. When compared with telephone interviews forms on which patients reported events were reliable (the observed agreement with the same statements posed during telephone calls was 85%, kappa = 0.56) and valid (sensitivity = 54%, specificity = 94%). Patients were also supplied with forms that invited them to report adverse reactions, and their perceptions were compared with those of a panel of experts, who were informed of all clinical events that had been reported during the detailed telephone interviews. Patients were more conservative than the experts in attributing clinical events to drug treatment. The extent of agreement varied and was notably poor for skin and bowel complaints (kappa = 0.13 in each case). The performance of event report forms and reaction report forms as instruments of detection was compared in a hypothetical situation in which the experts' views represented the "truth" about adverse reactions to a new drug. Event reporting had a higher sensitivity than reaction reporting (42% v 24%) but a lower specificity (58% v 98%). National centres monitoring adverse drug reactions should probably resist pressure to accept reports of reactions directly from the public, but a system based on large scale reporting of events might be valuable in aiding the early detection of symptomatic reactions to new drugs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin; Anti-Infective Agents; Australia; Child; Child, Preschool; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Patient Participation; Pharmacies; Product Surveillance, Postmarketing; Sulfamethoxazole; Surveys and Questionnaires; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

A total of 167 264 symptoms were recorded in numerical shorthand during a ten years period in a general practice. Computer analysis yielded 1535 adverse reactions with the drug prescribed. Especially prominent were reactions from three antibiotics (13% of all reported reactions), most of which were alimentary symptoms. Ampicillin also induced rashes reported at a rate of 5.2 per thousand prescriptions. Reactions to an oral contraceptive (Minovlar) were the most frequent to a single named drug, being 25.9% of prescriptions for that drug. A worldwide total of around one trillion symptoms seems likely before AD 2000. Computers could be used to detect the unpredictable side effects, as with practolol. Various 'costs' involved are noted, together with wider questions.

Topics: Ampicillin; Computers; Contraceptives, Oral; Contraceptives, Oral, Combined; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Family Practice; Humans; Oxytetracycline; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Age Factors; Aged; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Hematologic Diseases; Humans; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination