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There are limited data on the role of antimicrobials in the treatment of skin abscesses. In this trial, clindamycin or trimethoprim–sulfamethoxazole was found to facilitate more rapid resolution than placebo in the management of skin abscess under 5 cm in diameter. More than 4 in 100 people seek treatment for skin infections annually in the United States. 1 Abscesses are the most common of these infections, and the majority of patients are treated as outpatients. 1 Serious complications, such as bacteremia, occur in rare cases. 1 , 2 Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) strains, causes most skin infections, 3 , 4 but the appropriate strategy for the treatment of these infections has not been defined. Clindamycin and trimethoprim–sulfamethoxazole (TMP-SMX) are recommended for outpatient treatment of abscesses because of their low cost and in vitro activity against community-associated MRSA and methicillin-susceptible strains, 5 but data on their . . .

The cornerstone of malaria prevention in pregnancy, intermittent preventive treatment (IPTp) with sulfadoxine–pyrimethamine, is contraindicated in women with HIV who are receiving co-trimoxazole prophylaxis. We assessed whether IPTp with dihydroartemisinin–piperaquine is safe and effective in reducing the risk of malaria infection in women with HIV receiving co-trimoxazole prophylaxis and antiretroviral drugs. For this randomised, double-blind, placebo-controlled clinical trial, women with HIV attending the first antenatal care clinic visit, resident in the study area, and with a gestational age up to 28 weeks were enrolled at five sites in Gabon and Mozambique. Participants were randomly assigned (1:1) to receive either IPTp with dihydroartemisinin–piperaquine at each scheduled antenatal care visit plus daily co-trimoxazole (intervention group) or placebo at each scheduled antenatal care visit plus daily co-trimoxazole (control group). Randomisation was done centrally via block randomisation (block sizes of eight), stratified by country. IPTp was given over 3 days under direct observation by masked study personnel. The number of daily IPTp tablets was based on bodyweight and according to the treatment guidelines set by WHO (target dose of 4 mg/kg per day [range 2–10 mg/kg per day] of dihydroartemisinin and 18 mg/kg per day [range 16–27 mg/kg per day] of piperaquine given once a day for 3 days). At enrolment, all participants received co-trimoxazole (fixed combination drug containing 800 mg trimethoprim and 160 mg sulfamethoxazole) for daily intake. The primary study outcome was prevalence of peripheral parasitaemia detected by microscopy at delivery. The modified intention-to-treat population included all randomly assigned women who had data for the primary outcome. Secondary outcomes included frequency of adverse events, incidence of clinical malaria during pregnancy, and frequency of poor pregnancy outcomes. All study personnel, investigators, outcome assessors, data analysts, and participants were masked to treatment assignment. This study is registered with ClinicalTrials.gov, NCT03671109. From Sept 18, 2019, to Nov 26, 2021, 666 women (mean age 28·5 years [SD 6·4]) were enrolled and randomly assigned to the intervention (n=332) and control (n=334) groups. 294 women in the intervention group and 308 women in the control group had peripheral blood samples taken at delivery and were included in the primary analysis. Peripheral parasitaemia at delivery was detected in one (<1%) of 294 women in the intervention group and none of 308 women in the control group. The incidence of clinical malaria during pregnancy was lower in the intervention group than in the control group (one episode in the intervention group vs six in the control group; relative risk [RR] 0·12, 95% CI 0·03–0·52, p=0·045). In a post-hoc analysis, the composite outcome of overall malaria infection (detected by any diagnostic test during pregnancy or delivery) was lower in the intervention group than in the control group (14 [5%] of 311 women vs 31 [10%] of 320 women; RR 0·48, 95% CI 0·27–0·84, p=0·010). The frequency of serious adverse events and poor pregnancy outcomes (such as miscarriages, stillbirths, premature births, and congenital malformations) did not differ between groups. The most frequently reported drug-related adverse events were gastrointestinal disorder (reported in less than 4% of participants) and headache (reported in less than 2% of participants), with no differences between study groups. In the context of low malaria transmission, the addition of IPTp with dihydroartemisinin–piperaquine to co-trimoxazole prophylaxis in pregnant women with HIV did not reduce peripheral parasitaemia at delivery. However, the intervention was safe and associated with a decreased risk of clinical malaria and overall Plasmodium falciparum infection, so it should be considered as a strategy to protect pregnant women with HIV from malaria. European and Developing Countries Clinical Trials Partnership 2 (EDCTP2) and Medicines for Malaria Venture. For the Portuguese and French translations of the abstract see Supplementary Materials section.

In this randomized clinical trial in patients presenting to U.S. emergency departments with an acute uncomplicated cutaneous abscess, drainage plus trimethoprim–sulfamethoxazole therapy for a week was associated with modest clinical benefits as compared with drainage alone. Between 1993 and 2005, annual emergency department visits for skin and soft-tissue infections in the United States increased from 1.2 million to 3.4 million, primarily because of an increased incidence of abscesses. 1 , 2 During this period, community-associated methicillin-resistant Staphylococcus aureus (MRSA) emerged as the most common cause of purulent skin and soft-tissue infections in many parts of the world. 3 Trimethoprim–sulfamethoxazole, which has retained in vitro activity against community-associated MRSA, is among the most commonly prescribed antibiotics to treat these infections. 4 The primary treatment of a cutaneous abscess is drainage. 5 Whether adjunctive antibiotics lead to improved outcomes in patients with uncomplicated . . .

Uncomplicated skin infections are a common outpatient clinical problem. In this randomized, controlled trial, clindamycin and trimethoprim–sulfamethoxazole (TMP-SMX) were compared as outpatient therapy for uncomplicated cellulitis or abscess. Skin and skin-structure infections (hereafter referred to as skin infections) are common conditions among patients seeking medical care in the United States, 1 , 2 accounting for approximately 14.2 million outpatient visits in 2005 1 and more than 850,000 hospital admissions. 3 Skin infections are associated with considerable complications, including bacteremia, the need for hospitalization and surgical procedures, and death. 4 , 5 Results of cultures of skin-infection lesions in the United States have shown that most of the infections are caused by methicillin-resistant Staphylococcus aureus (MRSA), 6 , 7 but the efficacy of various antibiotic regimens in areas where community-associated MRSA is endemic has not been defined. . . .

ObjectivesTo investigate the efficacy and safety of trimethoprim/sulfamethoxazole (TMP-SMX) as primary prophylaxis for pneumocystis pneumonia (PCP) in patients with rheumatic diseases receiving high-dose steroids.MethodsThe study included 1522 treatment episodes with prolonged (≥4 weeks) high-dose (≥30 mg/day prednisone) steroids in 1092 patients over a 12-year period. Of these, 262 treatment episodes involved TMP-SMX (prophylaxis group) while other episodes involved no prophylaxis (control group). Differences in 1-year PCP incidence and its mortality between the two groups were estimated using Cox regression. To minimise baseline imbalance, propensity score matching was performed and efficacy outcome was mainly assessed in the postmatched population (n=235 in both groups).ResultsDuring a total of 1474.4 person-years, 30 PCP cases occurred with a mortality rate of 36.7%. One non-fatal case occurred in the prophylaxis group. TMP-SMX significantly reduced the 1-year PCP incidence (adjusted HR=0.07(95% CI 0.01 to 0.53)) and related mortality (adjusted HR=0.08 (95% CI 0.0006 to 0.71)) in the postmatched population. The result of the same analysis performed in the whole population was consistent with that of the primary analysis. Incidence rate of adverse drug reactions (ADR) related to TMP-SMX was 21.2 (14.8–29.3)/100 person-years. Only two serious ADRs (including one Stevens-Johnson syndrome case) occurred. The number needed to treat for preventing one PCP (52 (33–124)) was lower than the number needed to harm for serious ADR (131 (55–∞)).ConclusionTMP-SMX prophylaxis significantly reduces the PCP incidence with a favourable safety profile in patients with rheumatic disease receiving prolonged, high-dose steroids.

This study from four Australian centers examined whether low-dose, continuous oral antibiotic therapy would prevent urinary tract infection in children (under the age of 18 years) who had already had one or more microbiologically proven urinary tract infections. Long-term, low-dose trimethoprim–sulfamethoxazole was associated with a modest decrease in the number of urinary tract infections in predisposed children. Long-term, low-dose trimethoprim–sulfamethoxazole was associated with a modest decrease in the number of urinary tract infections in predisposed children. Urinary tract infection is a very common illness in children, affecting 2% of boys and 8% of girls by the age of 7 years. 1 Urinary tract infection is associated with long-term morbidity, with renal damage reported in about 5% of affected children. 2 The observation that urinary tract infection and vesicoureteral reflux are associated with renal damage 3 – 5 led to the standard clinical practice of assessment with voiding cystourethrography for the presence of vesicoureteral reflux in children who had had urinary tract infection 6 , 7 and the administration of daily low-dose antibiotics for many years 8 to prevent further urinary tract infections and . . .

High mortality is associated with initiation of antiretroviral therapy for HIV. In this report from sub-Saharan Africa, enhanced prophylaxis with isoniazid, fluconazole, azithromycin, and albendazole was associated with decreased mortality at 24 and 48 weeks.

Previous studies have shown that intravenous ceftriaxone or meropenem for 14 days, followed by oral trimethoprim–sulfamethoxazole for 1 year, cures 98% of people with Whipple's disease. However, intravenous therapy requires hospitalisation and carries risks for treatment-associated complications. The aim of this study was to investigate whether oral-only treatment for Whipple's disease is non-inferior to intravenous therapy. This phase 2/3, prospective, open-label, randomised, controlled, non-inferiority trial enrolled individuals aged 18 years or older with confirmed Whipple's disease from across Germany who had received treatment for less than 1 month at Charité–Universitätsmedizin Berlin. Participants were randomly assigned (1:1) with block randomisation to receive either intravenous ceftriaxone (2 g once per day) for 14 days, followed by oral trimethoprim–sulfamethoxazole (960 mg twice per day) for 12 months, or oral doxycycline (100 mg twice per day) plus hydroxychloroquine (200 mg twice per day) for 12 months. Ten participants who had already received intravenous ceftriaxone were non-randomly assigned to the intravenous treatment group. Participants in the oral-only treatment group were PCR-positive for Tropheryma whipplei in cerebrospinal fluid received trimethoprim–sulfamethoxazole (960 mg five times per day) until clearance. The primary outcome was complete clinical remission without recurrence during the observation period of 24 months, assessed in the intention-to-treat (ITT) population. The prespecified non-inferiority margin was –18%. Safety was a secondary endpoint, assessed in the ITT population. The study was registered with the EU Clinical Trials Register, EudraCT 2008–003951–54, and is completed. Between May 26, 2010, and Oct 30, 2018, we screened 310 individuals and enrolled 64 participants in the study. After exclusion of four individuals whose diagnosis was not confirmed, 31 participants were assigned to the intravenous treatment group and 29 to the oral-only treatment group. By ITT, 25 (81%) of 31 participants in the intravenous treatment group and 28 (97%) of 29 participants in the oral-only treatment group had complete clinical remission without recurrence. The risk difference was 15·9 percentage points (95% CI –1·2 to 33·1), with the lower bound of the 95% CI above our non-inferiority margin of –18%. A post-hoc per-protocol analysis confirmed the non-inferiority of oral-only treatment. No participant relapsed, but two participants in the intravenous treatment group died from nosocomial infections. Serious adverse events occurred in 13 (42%) of 31 participants in the intravenous treatment group and eight (28%) of 29 participants in the oral-only treatment group, but this difference was not statistically significant (p=0·244). Oral-only treatment of Whipple's disease was safe and non-inferior to sequential intravenous–oral treatment. Oral treatment facilitates patient management and might reduce hospital-acquired treatment complications and costs. German Research Foundation and the Robert Koch Institute. For the German translation of the abstract see Supplementary Materials section.

ObjectivesSevere infections contribute to morbidity and mortality in antineutrophil cytoplasm antibody-associated vasculitis (AAV). This study aimed to identify risk factors associated with severe infections in participants of the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial.MethodsData on 197 patients recruited into the RAVE trial were analysed. Participants received either rituximab (RTX) or cyclophosphamide (CYC), followed by azathioprine (AZA). Clinical and laboratory data of patients with and without severe infections (≥grade 3, according to the Common Terminology Criteria for Adverse Events version 3.0) were compared. Risk factors for severe infections were investigated using Cox-regression models.ResultsEighteen of 22 (82%) severe infections occurred within 6 months after trial entry, most commonly respiratory tract infections (15/22, 68%). At baseline, lower absolute numbers of CD19+ cells were observed in patients with severe infections either receiving RTX or CYC/AZA at baseline, while CD5+B and CD3+T cells did not differ between groups. In Cox-regression analysis, higher baseline serum immunoglobulin M levels were associated with the risk of severe infections, whereby a higher baseline total CD19+B cell number and prophylaxis against Pneumocystis jirovecii with trimethoprim-sulfamethoxazole (TMP/SMX) with decreased risk of severe infections. Use of TMP/SMX was associated with lower risk of severe infections in both groups, receiving either RTX or CYC/AZA.ConclusionsThe use of low-dose TMP/SMX is associated with reduced risk of severe infections in patients with AAV treated with either RTX or CYC/AZA. Reduced B cell subpopulations at start of treatment might be a useful correlate of reduced immunocompetence.

Background Sulfamethoxazole-trimethoprim (SMX/TMP) is a standard drug for the prophylaxis of Pneumocystis pneumonia (PJP) in immunosuppressed patients with systemic rheumatic diseases, but is sometimes discontinued due to adverse events (AEs). The objective of this non-blinded, randomized, 52-week non-inferiority trial was to quest an effective chemoprophylaxis regimen for PJP with a low drug discontinuation rate. Results at week 24 were reported. Methods Adult patients with systemic rheumatic diseases who started prednisolone ≥0.6 mg/kg/day were randomized into three dosage groups: a single-strength group (SS, SMX/TMP of 400/80 mg daily), half-strength group (HS, 200/40 mg daily), and escalation group (ES, started with 40/8 mg daily, increasing incrementally to 200/40 mg daily). The primary endpoint was non-incidence rates (non-IR) of PJP at week 24. Results Of 183 patients randomly allocated at a 1:1:1 ratio into the three groups, 58 patients in SS, 59 in HS, and 55 in ES started SMX/TMP. A total of 172 patients were included in the analysis. No cases of PJP were reported up to week 24. Estimated non-IR of PJP in patients who received daily SMX/TMP of 200/40 mg, either starting at this dose or increasing incrementally, was 96.8–100% using the exact confidence interval as a post-hoc analysis. The overall discontinuation rate was significantly lower with HS compared to SS ( p  = 0.007). The discontinuation rates due to AEs were significantly lower with HS ( p  = 0.006) and ES ( p  = 0.004) compared to SS. The IR of AEs requiring reduction in the dose of SMX/TMP ( p  = 0.009) and AEs of special interest ( p  = 0.003) were different among the three groups with significantly higher IR in SS compared to HS and ES. Conclusions Although there were no PJP cases, the combined group of HS and ES had an excellent estimated non-IR of PJP and both were superior in safety to SS. From the perspective of feasibility and drug discontinuation rates, the daily half-strength regimen was suggested to be optimal for prophylaxis of PJP in patients with systemic rheumatic diseases. Trial registration The University Hospital Medical Information Network Clinical Trials Registry number is UMIN000007727 , registered 10 April 2012.