Dataset Information

Trimethoprim+Sulfamethoxazole Reduces Rates of Melioidosis in High-Risk Hemodialysis Patients.

ABSTRACT:

Introduction

Melioidosis causes sepsis and death in the Top End of Northern Australia during the monsoonal wet season. Dialysis-dependent adults suffer higher melioidosis rates compared to low rates among renal transplant patients who routinely receive trimethoprim+sulfamethoxazole prophylaxis.

Methods

We performed a prospective interventional study to determine the efficacy and safety of daily trimethoprim+sulfamethoxazole prophylaxis in hemodialysis patients during the wet season, from 1 November 2014 to 30 April 2015. Hemodialysis (for ≥ 3 months) patients ≥ 18 years of age were offered treatment. A total of 269 patients on hemodialysis were eligible. Eight of the 269 patients (3%) were excluded from the analysis for being on melioidosis treatment. In all, 169 of 261 patients (64.8%) received the prophylaxis, and 92 of 261 patients (35.2%) did not, because of allergy history (n = 10), remoteness and logistical reasons (n = 60), poor dialysis attendance (n = 11), and refusal (n = 11). We monitored for clinical side effects 3 times weekly and neutropenia, thrombocytopenia, and liver function monthly throughout treatment and for 2 months posttreatment.

Results

In all, 169 of 261 patients (64.8%) received the prophylaxis. There was no age (years) difference by group (prophylaxis vs. nonprophylaxis, 54.7 [11.3] vs. 54.3 [11.2] [P = 0.751]). Sixteen of 261 patients (6%) had melioidosis. The event frequency was 0% (0/169, prophylaxis, vs. 17.4% [16/92, nonprophylaxis], P < 0.001). Higher thrombocytopenia and neutropenia rates were noted in the prophylaxis group. These did not warrant treatment stoppage. There was no difference in liver function. Three patients (1.8%) withdrew from the treatment because of side effects.

Conclusion

Daily dosing was effective and safe. Posthemodialysis dosing in the subsequent seasons was effective and safer. We recommend this approach in melioidosis-prevalent regions.

SUBMITTER: Majoni SW

PROVIDER: S-EPMC5762962 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Trimethoprim+Sulfamethoxazole Reduces Rates of Melioidosis in High-Risk Hemodialysis Patients.

Majoni Sandawana William SW Hughes Jaquelyne T JT Heron Bianca B Currie Bart J BJ

Kidney international reports 20170920 1

<h4>Introduction</h4>Melioidosis causes sepsis and death in the Top End of Northern Australia during the monsoonal wet season. Dialysis-dependent adults suffer higher melioidosis rates compared to low rates among renal transplant patients who routinely receive trimethoprim+sulfamethoxazole prophylaxis.<h4>Methods</h4>We performed a prospective interventional study to determine the efficacy and safety of daily trimethoprim+sulfamethoxazole prophylaxis in hemodialysis patients during the wet seaso ...[more]

PMID: 29340327

Similar Datasets

Project description:BackgroundMelioidosis, an infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei, is difficult to cure. Antimicrobial treatment comprises intravenous drugs for at least 10 days, followed by oral drugs for at least 12 weeks. The standard oral regimen based on trial evidence is trimethoprim-sulfamethoxaxole (TMP-SMX) plus doxycycline. This regimen is used in Thailand but is associated with side-effects and poor adherence by patients, and TMP-SMX alone is recommended in Australia. We compared the efficacy and side-effects of TMP-SMX with TMP-SMX plus doxycycline for the oral phase of melioidosis treatment.MethodsFor this multi-centre, double-blind, non-inferiority, randomised placebo-controlled trial, we enrolled patients (aged ≥15 years) from five centres in northeast Thailand with culture-confirmed melioidosis who had received a course of parenteral antimicrobial drugs. Using a computer-generated sequence, we randomly assigned patients to receive TMP-SMX plus placebo or TMP-SMX plus doxycycline for 20 weeks (1:1; block size of ten, stratified by study site). We followed patients up every 4 months for 1 year and annually thereafter to the end of the study. The primary endpoint was culture-confirmed recurrent melioidosis, and the non-inferiority margin was a hazard ratio (HR) of 1.7. This study is registered with www.controlled-trials.com, number ISRCTN86140460.FindingsWe enrolled and randomly assigned 626 patients: 311 to TMP-SMX plus placebo and 315 to TMP-SMX plus doxycycline. 16 patients (5%) in the TMP-SMX plus placebo group and 21 patients (7%) in the TMP-SMX plus doxycycline group developed culture-confirmed recurrent melioidosis (HR 0.81; 95% CI 0.42-1.55). The criterion for non-inferiority was met (p=0.01). Adverse drug reactions were less common in the TMP-SMX plus placebo group than in the TMP-SMX plus doxycycline group (122 [39%] vs 167 [53%]).InterpretationOur findings suggest that TMP-SMX is not inferior to TMP-SMX plus doxycycline for the oral phase of melioidosis treatment, and is preferable on the basis of safety and tolerance by patients.FundingThailand Research Fund, the Melioidosis Research Center, the Center of Excellence in Specific Health Problems in Greater Mekong Sub-region cluster, and the Wellcome Trust.

Project description:BackgroundTrimethoprim-sulfamethoxazole (TMP-SMX) is a commonly used antibiotic. While cutaneous adverse drug reactions associated with TMP-SMX are commonly recognized, lung toxicity induced by TMP-SMX is an unusual condition, with scattered reports of hypersensitivity pneumonitis, acute fibrinous organizing pneumonia, interstitial lung disease and acute respiratory distress syndrome. Reports of TMP-SMX-associated drug-induced lung injury (DLI) are rare in the pediatric population and its pathogenesis is not well understood. Diagnosis of DLI remains a challenge, given the wide range of clinical presentations that overlap with other conditions and the lack of diagnostic tests. In this report, we describe a case of TMP-SMX-induced lung injury in an eight-year-old child.Case descriptionAn eight-year-old girl presented in respiratory failure with acute symptoms of shortness of breath, fever, maculopapular rash and vomiting. This was associated with pneumonitis, pneumothorax, pneumomediastinum and subcutaneous emphysema on imaging. She had been on 25 days of TMP-SMX for treatment of Group D Salmonella bacteremia and osteomyelitis that was diagnosed prior to this current presentation. TMP-SMX was discontinued on admission due to concerns of possible drug reaction. Extensive infective, autoimmune and immunologic workup did not reveal the cause of the respiratory failure. Considering the absence of an alternative explanation for her clinical presentation and similarities in clinical courses to other reported cases, she was eventually diagnosed with TMP-SMX-associated DLI. She received a course of corticosteroids with subsequent clinical improvement and was weaned off home oxygen therapy a few months after her discharge from the hospital.ConclusionsDiagnosis of DLI can be challenging. The early identification of DLI and discontinuation of culprit drug is essential in its management. Further understanding of the underlying pathophysiology and risk factors for TMP-SMX-associated DLI is required.

Project description:BackgroundU.S. emergency department visits for cutaneous abscess have increased with the emergence of methicillin-resistant Staphylococcus aureus (MRSA). The role of antibiotics for patients with a drained abscess is unclear.MethodsWe conducted a randomized trial at five U.S. emergency departments to determine whether trimethoprim-sulfamethoxazole (at doses of 320 mg and 1600 mg, respectively, twice daily, for 7 days) would be superior to placebo in outpatients older than 12 years of age who had an uncomplicated abscess that was being treated with drainage. The primary outcome was clinical cure of the abscess, assessed 7 to 14 days after the end of the treatment period.ResultsThe median age of the participants was 35 years (range, 14 to 73); 45.3% of the participants had wound cultures that were positive for MRSA. In the modified intention-to-treat population, clinical cure of the abscess occurred in 507 of 630 participants (80.5%) in the trimethoprim-sulfamethoxazole group versus 454 of 617 participants (73.6%) in the placebo group (difference, 6.9 percentage points; 95% confidence interval [CI], 2.1 to 11.7; P=0.005). In the per-protocol population, clinical cure occurred in 487 of 524 participants (92.9%) in the trimethoprim-sulfamethoxazole group versus 457 of 533 participants (85.7%) in the placebo group (difference, 7.2 percentage points; 95% CI, 3.2 to 11.2; P<0.001). Trimethoprim-sulfamethoxazole was superior to placebo with respect to most secondary outcomes in the per-protocol population, resulting in lower rates of subsequent surgical drainage procedures (3.4% vs. 8.6%; difference, -5.2 percentage points; 95% CI, -8.2 to -2.2), skin infections at new sites (3.1% vs. 10.3%; difference, -7.2 percentage points; 95% CI, -10.4 to -4.1), and infections in household members (1.7% vs. 4.1%; difference, -2.4 percentage points; 95% CI, -4.6 to -0.2) 7 to 14 days after the treatment period. Trimethoprim-sulfamethoxazole was associated with slightly more gastrointestinal side effects (mostly mild) than placebo. At 7 to 14 days after the treatment period, invasive infections had developed in 2 of 524 participants (0.4%) in the trimethoprim-sulfamethoxazole group and in 2 of 533 participants (0.4%) in the placebo group; at 42 to 56 days after the treatment period, an invasive infection had developed in 1 participant (0.2%) in the trimethoprim-sulfamethoxazole group.ConclusionsIn settings in which MRSA was prevalent, trimethoprim-sulfamethoxazole treatment resulted in a higher cure rate among patients with a drained cutaneous abscess than placebo. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00729937.).

Project description:BackgroundSkin and skin-structure infections are common in ambulatory settings. However, the efficacy of various antibiotic regimens in the era of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is unclear.MethodsWe enrolled outpatients with uncomplicated skin infections who had cellulitis, abscesses larger than 5 cm in diameter (smaller for younger children), or both. Patients were enrolled at four study sites. All abscesses underwent incision and drainage. Patients were randomly assigned in a 1:1 ratio to receive either clindamycin or trimethoprim-sulfamethoxazole (TMP-SMX) for 10 days. Patients and investigators were unaware of the treatment assignments and microbiologic test results. The primary outcome was clinical cure 7 to 10 days after the end of treatment.ResultsA total of 524 patients were enrolled (264 in the clindamycin group and 260 in the TMP-SMX group), including 155 children (29.6%). One hundred sixty patients (30.5%) had an abscess, 280 (53.4%) had cellulitis, and 82 (15.6%) had mixed infection, defined as at least one abscess lesion and one cellulitis lesion. S. aureus was isolated from the lesions of 217 patients (41.4%); the isolates in 167 (77.0%) of these patients were MRSA. The proportion of patients cured was similar in the two treatment groups in the intention-to-treat population (80.3% in the clindamycin group and 77.7% in the TMP-SMX group; difference, -2.6 percentage points; 95% confidence interval [CI], -10.2 to 4.9; P=0.52) and in the populations of patients who could be evaluated (466 patients; 89.5% in the clindamycin group and 88.2% in the TMP-SMX group; difference, -1.2 percentage points; 95% CI, -7.6 to 5.1; P=0.77). Cure rates did not differ significantly between the two treatments in the subgroups of children, adults, and patients with abscess versus cellulitis. The proportion of patients with adverse events was similar in the two groups.ConclusionsWe found no significant difference between clindamycin and TMP-SMX, with respect to either efficacy or side-effect profile, for the treatment of uncomplicated skin infections, including both cellulitis and abscesses. (Funded by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, National Institutes of Health; ClinicalTrials.gov number, NCT00730028.).

Project description:ObjectivesTo characterise the risk of admission to hospital for hyperkalaemia in elderly patients treated with trimethoprim-sulfamethoxazole in combination with spironolactone.DesignPopulation based nested case-control study.SettingOntario, Canada, from 1 April 1992 to 1 March 2010.ParticipantsCases were residents of Ontario aged 66 years or above receiving chronic treatment with spironolactone and admitted to hospital with hyperkalaemia within 14 days of receiving a prescription for either trimethoprim-sulfamethoxazole, amoxicillin, norfloxacin, or nitrofurantoin. Up to four controls for each case were identified from the same cohort, matched on age, sex, and presence or absence of chronic kidney disease and diabetes, and required to have received one of the study antibiotics within 14 days before the case's index date.Main outcome measuresOdds ratio for association between admission to hospital with hyperkalaemia and receipt of a study antibiotic in the preceding 14 days, adjusted for conditions and drugs that may influence risk of hyperkalaemia.ResultsDuring the 18 year study period, 6903 admissions for hyperkalaemia were identified, 306 of which occurred within 14 days of antibiotic use. Of these, 248 (81%) cases were matched to 783 controls. 10.8% (17,859/165,754) of spironolactone users received at least one prescription for trimethoprim-sulfamethoxazole. Compared with amoxicillin, prescription of trimethoprim-sulfamethoxazole was associated with a marked increase in the risk of admission to hospital for hyperkalaemia (adjusted odds ratio 12.4, 95% confidence interval 7.1 to 21.6). The population attributable fraction was 59.7%, suggesting that approximately 60% of all cases of hyperkalaemia in older patients taking spironolactone and treated with an antibiotic for a urinary tract infection could be avoided if trimethoprim-sulfamethoxazole was not prescribed. Treatment with nitrofurantoin was also associated with an increase in the risk of hyperkalaemia (adjusted odds ratio 2.4, 1.3 to 4.6), but no such risk was found with norfloxacin (adjusted odds ratio 1.6, 0.8 to 3.4)ConclusionsAmong older patients receiving spironolactone, treatment with trimethoprim-sulfamethoxazole was associated with a major increase in the risk of admission to hospital for hyperkalaemia. This drug combination should be avoided when possible.

Dataset Information

Trimethoprim+Sulfamethoxazole Reduces Rates of Melioidosis in High-Risk Hemodialysis Patients.

Introduction

Methods

Results

Conclusion

Publications

Trimethoprim+Sulfamethoxazole Reduces Rates of Melioidosis in High-Risk Hemodialysis Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets