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Antimicrobial prescription patterns in tertiary care centres in India: a multicentric point prevalence survey
Authors: Bhattacharjee S, et al.
Abstract
Background: Antimicrobial resistance (AMR) poses a global health threat, emphasizing the need for Point Prevalence Surveys (PPS) to understand antibiotic use and resistance. This study assesses antibiotic use patterns and resistance in tertiary care hospitals across India to inform AMR interventions.
Methods: This cross-sectional survey was conducted over two weeks between May and August 2023 in eight Indian tertiary care hospitals. The survey comprised two parts: the ward form, which captured ward details (name, specialty, bed count, and antibiotic use), and the patient form, which documented demographics, antimicrobial therapy, and microbiological data, including redundant coverage and designated antibiotics. Rationality was assessed using 50 forms from each site. Data were collected digitally by trained team of surveyors. The study included hospitalized patients on systemic antimicrobials, excluding outpatient, day-care dialysis patients, and those on topical antibiotics.
Findings: Among 3974 patients in eight hospitals, adult surgical and pediatric medical wards had the highest antibiotic usage. Of 4248 prescriptions, the most common antibiotics were ceftriaxone (14.9%, 95% CI: 10.4%, 18.4%), metronidazole (10.2%, 95% CI: 6.0%–11.2%), amikacin (8.7%, 95% CI: 6.3%–11.3%), piperacillin/tazobactam (8.7%, 95% CI: 9.1%–10.5%), and meropenem (7.1%, 95% CI: 5.2%–9.5%). Antibiotics were categorized as ‘Watch’ (57.03%), ‘Access’ (32.67%), and ‘Reserve’ (5.08%). Primary indications were community-acquired infections (30.6%, 95% CI: 25.1%–32.5%) and surgical prophylaxis (31%, 95% CI: 29.8%–36.9%). HAIs prevalence was 13.3% (95% CI: 9.3%–15.4%), with majority of use being empiric (48.96%, 95% CI: 35.1%–58.8%). Common isolates included Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. Assessment of rationale of antibiotic use was assessor dependent and variable (0–50% irrational prescriptions, majority due to prolonged duration of prophylaxis/treatment) across sites.
Interpretation: The SASPI (Society of Antimicrobial Stewardship Practices in India)-led survey underscores the high use of antibiotics in the included tertiary care centers emphasizing the need for point prevalence surveys to guide antimicrobial stewardship programs. It highlights the importance of ongoing AMR surveillance, improved stewardship, and education to refine prescribing practices, targeting hospital-acquired infections, and reducing unnecessary treatments.
Funding: None.
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Blood culture collection and administration of intravenous ceftriaxone by paramedics in patients with suspected sepsis (the pass trial)
Authors: Daniel Cudini
Abstract
Objective: To evaluate the feasibility of pre-hospital blood culture (BC) collection and intravenous (IV) antibiotic administration in patients with suspected sepsis.
Methods: In this open-label trial, BCs were collected in all participants, who were then randomised to ongoing care (control) or ongoing care plus 2 g IV ceftriaxone (intervention). Time to antibiotic administration was the primary outcome.
Results: Thirty-five patients were enrolled and randomised (21 control, 14 intervention). BCs were obtained in 89% (n = 31/35) and grew a pathogen in 42% (n = 13/31). Intervention patients received antibiotics a median of 108 (95% CI 34 to 170) minutes earlier (P < 0.01).
Conclusion: BCs were successfully obtained by paramedics, and pre-hospital IV ceftriaxone resulted in expedited antibiotic administration. Clinical trial registration: ACTRN12618000199213.
Keywords: EMS; antibotics; blood culture; ceftriaxone; out of hospital; paramedic; pre hospital; sepsis.
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Implementation of an antimicrobial stewardship program for urinary tract infections in long-term care facilities: a cluster-controlled intervention study
Authors: Elisabeth König
Abstract
Background: Widespread inappropriate use of antimicrobial substances drives resistance development worldwide. In long-term care facilities (LTCF), antibiotics are among the most frequently prescribed medications. More than one third of antimicrobial agents prescribed in LTCFs are for urinary tract infections (UTI). We aimed to increase the number of appropriate antimicrobial treatments for UTIs in LTCFs using a multi-faceted antimicrobial stewardship intervention.
Methods: We performed a non-randomized cluster-controlled intervention study. Four LTCFs of the Geriatric Health Centers Graz were the intervention group, four LTCFs served as control group. The main components of the intervention were: voluntary continuing medical education for primary care physicians, distribution of a written guideline, implementation of the project homepage to distribute guidelines and videos and onsite training for nursing staff. Local nursing staff recorded data on UTI episodes in an online case report platform. Two blinded reviewers assessed whether treatments were adequate.
Results: 326 UTI episodes were recorded, 161 in the intervention group and 165 in the control group. During the intervention period, risk ratio for inadequate indication for treatment was 0.41 (95% CI 0.19-0.90), p = 0.025. In theintervention group, the proportion of adequate antibiotic choices increased from 42.1% in the pre-intervention period, to 45.9% during the intervention and to 51% in the post-intervention period (absolute increase of 8.9%). In the control group, the proportion was 36.4%, 33.3% and 33.3%, respectively. The numerical difference between intervention group and control group in the post-intervention period was 17.7% (difference did not reach statistical significance). There were no significant differences between the control group and intervention group in the safety outcomes (proportion of clinical failure, number of hospital admissions due to UTI and adverse events due to antimicrobial treatment).
Conclusions: An antimicrobial stewardship program consisting of practice guidelines, local and web-based education for nursing staff and general practitioners resulted in a significant increase in adequate treatments (in terms of decision to treat the UTI) during the intervention period. However, this difference was not maintained in the post-intervention phase. Continued efforts to improve the quality of prescriptions further are necessary.
Trial registration: The trial was registered at ClinicalTrials.gov NCT04798365.
Keywords: Antibiotic stewardship; Healthcare associated infection; Nursing home; Urinary tract infections.
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Efficacy of aqueous olanexidine compared with alcohol-based chlorhexidine for surgical skin antisepsis regarding the incidence of surgical-site infections in clean-contaminated surgery: a randomized superiority trial
DOI: 10.1093/bjs/znaf065
Authors: Masashi Takeuchi
Abstract
Background: Surgical-site antisepsis is used to prevent surgical-site infections (SSIs). Although several guidelines have indicated the efficacy of antiseptics, such as chlorhexidine, povidone-iodine, and olanexidine, in reducing the SSI rate, an optimal recommendation is still not established. The aim of this study was to evaluate the efficacy of aqueous olanexidine compared with chlorhexidine-alcohol as the optimal antiseptic for preventing SSI in clean-contaminated surgery.
Methods: This multicentre randomized trial for surgical skin antisepsis in clean-contaminated gastrointestinal and hepatobiliary-pancreatic surgeries in five hospitals evaluated the efficacy of olanexidine and chlorhexidine-alcohol. The primary endpoint was 30-day SSI. Secondary outcomes included the occurrence of SSI types, intervention-related toxicity, and reoperation caused by SSI.
Results: Overall, 700 patients from five institutions underwent randomization; 347 received olanexidine and 345 received chlorhexidine-alcohol in the full analysis set. The 30-day SSI rate was 12.4% (43 of 347) in the olanexidine group and 13.6% (47 of 345) in the chlorhexidine-alcohol group (adjusted risk ratio (aRR) 0.911 (95% c.i. 0.625 to 1.327); P = 0.626). No significant differences were observed between the groups regarding the secondary outcomes, including the occurrence of superficial incisional SSI, deep incisional SSI, organ/space SSI, and reoperation caused by SSI. Overall adverse effects were seen in two patients (0.58%) in the olanexidine group and in three patients (0.87%) in the chlorhexidine-alcohol group (aRR 0.663 (95% c.i. 0.111 to 3.951)).
Conclusion: Olanexidine did not significantly reduce the occurrence of overall SSI compared with chlorhexidine-alcohol. Nevertheless, these findings provide valuable insights for developing novel surgical SSI management protocols.
Registration number: UMIN 000049712 (University Hospital Medical Information Network Clinical Trials Registry).
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Effectiveness of intrapartum azithromycin to prevent infections in planned vaginal births in low-income and middle-income countries: a post-hoc analysis of data from a multicentre, randomised, double-blind, placebo-controlled trial
Authors: Waldemar A Carlo
Abstract
Background: In 2023, the Azithromycin Prevention in Labor Use (A-PLUS) trial showed intrapartum azithromycin reduces maternal sepsis or death in women with planned vaginal delivery in low-resource settings, but whether it reduces maternal infection is unknown. We aimed to evaluate the effectiveness of intrapartum azithromycin in reducing maternal infection.
Methods: We performed a post-hoc analysis of the multicentre, facility-based, randomised, double-blind, placebo-controlled A-PLUS trial. This trial compared prophylactic intrapartum single oral dose of 2 g azithromycin versus placebo on maternal morbidity and mortality in low-resource settings in southeast Asia and Africa from Sept 9, 2020, to Aug 18, 2022. The trial enrolled women in labour at 28 weeks’ gestation (or later) at eight sites in the Democratic Republic of the Congo, Kenya, Zambia, Bangladesh, India, Pakistan, and Guatemala and found that azithromycin reduced the incidence of maternal sepsis or death. The primary outcome of the present analysis was the incidence of any maternal infection in the azithromycin versus placebo groups, which was defined as one or more of these infections after randomisation: chorioamnionitis, endometritis, perineal or caesarean wound infection, abdominopelvic abscess, mastitis or breast abscess, and other infections. Any neonatal infection was also analysed. All analyses were by intention to treat in all those with data available for that outcome. Relative risks (RRs) and 95% CIs were estimated with a Poisson model adjusted for treatment group and site. Subgroup analyses included a two-way interaction test between intervention group and subgroup. A-PLUS was registered at ClinicalTrials.gov, number NCT03871491.
Findings: 29 278 women were randomly assigned to groups: 14 590 to receive azithromycin, 14 688 to receive placebo. Baseline characteristics were similar between the azithromycin and placebo groups (43·3% vs 43·4% primiparous, 8·5% vs 8·7% high risk for infection). The presence of any maternal infection occurred less often in the azithromycin group (580 [4·0%] of 14 558) compared with the placebo group (824 [5·6%] of 14 661 women; RR 0·71, 95% CI 0·64-0·79, p<0·0001). Any neonatal infection did not differ between treatment groups. Adverse events were not detected.
Interpretation: Among women planning vaginal delivery, this analysis provides evidence indicating that intrapartum azithromycin is associated with a lower incidence of maternal infections than placebo.
Funding: The Eunice Kennedy Shriver National Institute of Child Health and Human Development and Bill and Melinda Gates Foundation via Foundation of National Institutes of Health.
Translations: For the French and Spanish translations of the abstract see Supplementary Materials section.
Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
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Cost-effectiveness of intrapartum azithromycin to prevent maternal infection, sepsis, or death in low-income and middle-income countries: a modelling analysis of data from a randomised, multicentre, placebo-controlled trial
Authors: Jackie K Patterson
Abstract
Background: Sepsis is one of the leading causes of maternal mortality globally. In 2023, the Azithromycin Prevention in Labor Use (A-PLUS) trial showed intrapartum azithromycin for women planning a vaginal birth reduced the risk of maternal sepsis or death and infection. We aimed to evaluate the cost-effectiveness of intrapartum azithromycin for pregnant people planning a vaginal birth in low-income and middle-income countries (LMICs) using A-PLUS trial data.
Methods: We compared the benefits and costs of intrapartum azithromycin versus standard care across 100 000 model simulations using data from the A-PLUS trial and a probabilistic decision tree model that included 24 mutually exclusive scenarios. A-PLUS was a randomised, double-blind, placebo-controlled trial that enrolled 29 278 women in labour at 28 weeks’ gestation or more at eight sites in the Democratic Republic of the Congo, Kenya, Zambia, Bangladesh, India, Pakistan, and Guatemala. Women randomly assigned to azithromycin received a single intrapartum 2 g oral dose. In this cost-effectiveness analysis, we considered the cost of azithromycin treatment and its effects on a composite outcome of maternal infection, sepsis, or death and its individual components, and health-care use. Our analysis had a health-care sector perspective. We summarised results as an average and 95% CI of the model simulations. We also conducted sensitivity analyses. A-PLUS was registered at ClinicalTrials.gov, number NCT03871491.
Findings: In model simulations, intrapartum azithromycin resulted in 1592·0 (95% CI 1139·7 to 2024·1) cases of maternal infection, sepsis, or death averted per 100 000 pregnancies, yielding 248·5 (95·3 to 403·7) facility readmissions averted, 866·8 (537·8 to 1193·2) unplanned clinic visits averted, and 1816·2 (1324·5 to 2299·7) antibiotic regimens averted. Using mean health-care costs across the A-PLUS sites, intrapartum azithromycin resulted in net savings of US$32 661 (-52 218 to 118 210) per 100 000 pregnancies and 13·2 (8·3 to 17·9) disability-adjusted life-years averted. The cost of facility readmission, cost of azithromycin, and probability of infection had the greatest impact on the incremental cost.
Interpretation: In most cases, intrapartum azithromycin is a cost-saving intervention for the prevention of maternal infection, sepsis, or death in LMICs. This evidence supports global consideration of intrapartum azithromycin as an economically efficient preventive therapy to reduce infection, sepsis, or death among women planning a vaginal birth in LMICs.
Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Foundation for the National Institutes of Health through the Maternal, Newborn, and Child Health Discovery and Tools Initiative of the Bill & Melinda Gates Foundation TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.
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Efficacy of Low-Dose Fluconazole for Primary Prophylaxis of Invasive Candida Infections in Patients With Acute Leukemia: A Double-Blind Randomized Clinical Trial
DOI: 10.1002/cam4.70837
Authors: Roghayeh Savary-Kouzehkonan
Abstract
Background: Invasive fungal infections (IFIs), particularly Candida infections, are a significant cause of morbidity and mortality in patients with acute leukemia. While fluconazole is widely used for prophylaxis, the optimal dosing regimen remains uncertain. This study aimed to evaluate the efficacy of low-dose fluconazole for primary prophylaxis against invasive Candida infections in patients with acute leukemia receiving intensive chemotherapy.
Methods: A double-blind, randomized clinical trial was conducted with patients diagnosed with acute leukemia. Patients were assigned to receive either low-dose (150 mg/day) or standard high-dose (400 mg/day) fluconazole for primary prophylaxis against invasive Candida infections during intensive chemotherapy. The primary outcomes were the efficacy of antifungal prophylaxis and the safety profile.
Results: A total of 120 patients (60 per group) were enrolled. The overall incidence of Candida infections was similar between the groups (p = 0.615). Candida colonization was higher in the low-dose fluconazole group during the first week, particularly with non-albicans Candida at oral and subaxillary sites (p < 0.001). However, by the third week, both groups showed a significant decline in colonization, with the reduction in the oral cavity being statistically significant (p = 0.03). Aspergillosis occurred in 38.3% of patients, with no significant difference between groups (p > 0.99). Adverse events were similar in both groups (p > 0.05).
Conclusion: Low-dose fluconazole is an effective alternative to high-dose regimens for preventing Candida infections in acute leukemia patients, with similar efficacy and safety. The rising threat of aspergillosis highlights the need for targeted prophylaxis. Further research is needed to refine strategies for high-risk patients.
Trial registration: Iranian Registry of Clinical Trials (IRCT) number: IRCT20140818018842N37.
Keywords: Candida; acute leukemia; antifungal prophylaxis; fluconazole; hematological malignancy; invasive fungal infection.
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Chlorhexidine solutions are more effective than povidone-iodine solutions as skin disinfectants for the prevention of intravascular catheter-related infections: A meta-analysis
Authors: Aiping Deng
Abstract
Catheter-related infections pose a significant risk to critically ill patients, making it crucial to select an appropriate sterilization solution. However, there is currently no consensus on the use of chlorhexidine-containing solutions or povidone-iodine (PVI) and the auxiliary ingredients in solutions. Meta-analysis. PubMed, EMBASE, OVID, Web of Science, and Cochrane Library databases. Two reviewers independently performed study screening and data extraction and used the Cochrane risk-of-bias tool 2.0 (RoB 2.0) for quality assessment. We included 10 fully published RCTs with 12 pairs of comparisons, which included a total of 9,689 catheters. The analysis revealed that chlorhexidine gluconate (CHG)-containing solutions were significantly more effective than PVI in preventing CRBSI (RR = 0.460, 95% CI 0.323-0.654, P < 0.001), catheter-related sepsis (RR = 0.419, 95% CI 0.206-0.853, P = 0.016), and catheter colonization (RR = 0.409, 95% CI 0.266-0.630, P < 0.001). Further subgroup analysis demonstrated that, regardless of the concentration of CHG (≤ 1% or > 1%), it was superior to PVI in preventing CRBSI and catheter colonization (RR = 0.271 ~ 0.585, 95% CI 0.110 ~ 0.400‒0.590‒0.926). CHG-alcohol is most effective at preventing catheter-related infections, especially those caused by 70% alcohol. Compared to PVI, CHG-70% alcohol is the most effective disinfectant for preventing catheter-related infections, as it combines the rapid disinfection and evaporation properties of alcohol with the prolonged antimicrobial effects of chlorhexidine.PROSPERO registration number: CRD42024507163.
Keywords: Catheter-related bloodstream infections; Chlorhexidine; Povidone-iodine.
© 2025. The Author(s).
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Mass distribution of azithromycin and child mortality among underweight infants in rural Niger: a subgroup analysis of the AVENIR cluster-randomised trial
Authors: Brittany Peterson
Abstract
Objective: Azithromycin has been shown to reduce all-cause child mortality. This subgroup analysis investigates azithromycin’s mortality impact by underweight status using Azithromycine pour la Vie des Enfants au Niger: Implementation et Recherche (AVENIR) trial data.
Design: The AVENIR trial randomised communities into three arms: azithromycin for children aged 1-59 months, azithromycin for infants aged 1-11 months or placebo. Weight-for-age z-score was used to categorise children into subgroups of either moderate to severe underweight or not and severe underweight or not.
Setting: 2880 communities with a population of less than 2500 people in the Dosso and Tahoua regions of Niger that participated in the AVENIR trial were included.
Participants: 97 572 children aged 1-59 months who had weight captured during at least one census participated.
Results: Underweight subgroups had higher overall mortality compared with non-underweight subgroups. IRDs of deaths in children aged 1-11 months comparing communities receiving azithromycin to children 1-59 months of age to placebo were -6.2 deaths per 1000 person-years (95% CI -9.3 to -2.6) overall, -8.0 (95% CI -15.9 to -0.4) in the moderate to severe subgroup and -11.2 (95% CI -26.0 to -2.1) in the severe subgroup. Similar trends were noted in the azithromycin 1-11 month comparison. Malnutrition was not a statistically significant effect modifier for either comparison.
Conclusions: Although analyses suggest the potential for stronger effects in more severe underweight subgroups, we were unable to demonstrate underweight status as an effect modifier. In fact, azithromycin mass drug administration to children 1-59 months old reduced mortality in all subgroups, and, especially as the number of lives saved would be the highest by treating all subgroups, our results do not support restricting eligibility for this intervention.
Trial registration number: clinicaltrials.gov NCT04224987.
Keywords: Community child health; Mass Drug Administration; Mortality.
© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.
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Cefazolin versus placebo for surgical antibiotic prophylaxis in low-risk cesarean delivery: a feasibility blinded randomized controlled trial
Authors: Victoria A Eley
Abstract
Background: Pre-incisional antibiotics are recommended for all patients having cesarean delivery, despite emerging concerns regarding effects on the infant. In this feasibility blinded randomized controlled trial we aimed to test research processes in low-risk women receiving cefazolin or placebo prior to elective cesarean delivery.
Methods: The trial was prospectively registered (ACTRN12619001705178). Eligible women were aged ≥ 18 and < 40 years, ≥ 37 weeks gestation, at low risk of surgical site infection (SSI) and recruited from a single tertiary centre. We reported proportions of women eligible and consenting; adherence to perioperative infection prevention; blinding adequacy of staff using Bang’s blinding index; SSI surveillance and diagnosis according to the Centre for Disease Control definitions and patient reported outcome measures using validated questionnaires up to 90 days.
Results: We screened 1651 women, with 1245 (75%) ineligible based on body mass index or presence of diabetes. Of 287 eligible women, 30 were randomized (11%) with 15 in each group. Reasons for non-participation included “wanting antibiotics” (68, 27%), “no reason” (62, 25%) and lack of research staff (33, 13%). Compliance with perioperative infection prevention occurred in 5 of 7 steps. Spontaneous placental separation occurred in 25 (83%) and Comfeel dressing in 29 (97%). Blinding was adequate for all staff groups. SSI surveillance occurred in 156 of 210 (74%) timepoints. SSI occurred in two patients who received pre-incisional cefazolin and were successfully treated as outpatients. Patient reported outcome questionnaires were completed at 136 of 180 (76%) timepoints. There was no difference in maternal health-related quality of life between the groups.
Conclusions: Feasibility was impacted by the high-risk population and patient desire for antibiotics. Adherence to perioperative infection prevention practices were high but incomplete. These study processes could be effectively applied in a larger population, targeting low risk maternity patients.
Trial registration: Prospectively registered 4/12/2019 with the Australian New Zealand Clinical Trials Registry (ACTRN12619001705178).
Keywords: Allergy; Antibiotics; Atopy; Cesarean delivery; Surgical prophylaxis; Surgical site infection; Wound infection.
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Collateral benefits of ivermectin mass drug administration designed for malaria against headlice in Mopeia, Mozambique: a cluster randomised controlled trial
Authors: Joanna Furnival-Adams
Abstract
Background: Headlice are prevalent worldwide, with a higher burden in rural, lower-middle income settings. They can cause intense itchiness, discomfort, and secondary bacterial infections with potentially serious consequences. Ivermectin is efficacious against headlice, and is also being evaluated as a malaria vector control tool. In this study, we explored risk factors for headlice, and assessed the efficacy of ivermectin mass drug administration (MDA) designed for malaria against headlice.
Methods: We conducted an open-label, assessor-blind, cluster-randomized controlled trial in Mopeia, Mozambique. A single dose of ivermectin was given monthly to eligible humans or humans and livestock (humans: 400 μg/kg, livestock: 1% injectable 200 μg/kg) in 3 consecutive months during the rainy season. The control group received albendazole (humans only). Thirty-nine clusters (13 per arm) were randomly selected for the nested assessment of headlice prevalence. 1341 treated participants were followed up at least once, 1, 2 and 3 months and 382 untreated (ineligible) participants at 3 and 6 months after the first MDA round. Headlice diagnosis was determined by scalp examination. Logistic regression was used to identify risk factors for headlice at baseline, and to estimate the treatment effect at each time point.
Results: A total of 1309 participants were included in the main analysis assessing ivermectin MDA efficacy, and 1332 in the risk factor analysis. The baseline headlice prevalence was 11%. Risk factors included living with a household member with head itch [adjusted odds ratio (aOR) = 48.63, 95% confidence interval (CI): 28.7-82.3, P-value < 0.0001], being female (aOR = 2.25, 95% CI: 1.33-3.80, P-value < 0.01), and using surface water as the main water (aOR = 2.37, 95% CI: 1.12-5.33, P-value = 0.04). The treated population receiving ivermectin had significantly lower odds of having headlice at 3 months compared to those receiving albendazole (aOR = 0.19, 95% CI: 0.04-0.91, P-value = 0.04). There was no indirect effect on headlice among children ineligible for treatment.
Conclusions: In a highly endemic setting, mass drug administration with ivermectin significantly reduces headlice infestation prevalence among those who receive the drug for three sequential months. The lack of effect among untreated, ineligible children implies that additional interventions would be needed to interrupt local transmission.
Trial registration: This study is registered with ClinicalTrials.gov (NCT04966702).
Keywords: Ectoparasites; Headlice; Ivermectin; Malaria; Mass drug administration.
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Does hydroxychloroquine reduce the risk of infection in patients with systemic lupus erythematosus? a systematic review and meta-analysis
Authors: Shangtian Wang
Abstract
Objectives: This study aimed to investigate the anti-infective utility of hydroxychloroquine in patients with systemic lupus erythematosus (SLE) by analyzing published case-control and cohort studies.
Methods: A systematic literature review was conducted on January 28, 2024, using PubMed, Cochrane, Embase, and Web of Science Core Collection databases. Odds ratios (OR) were used for statistical analysis.
Results: Hydroxychloroquine exhibits a propensity to diminish infection risk in systemic lupus erythematosus patients, albeit without statistical significance (OR = 0.77, 95%CI 0.51-1.18, p = 0.23). Subgroup analyses revealed a significant prevention of serious infections (OR = 0.40, 95%CI 0.25-0.64, p = 0.0001). Interestingly, a potential causal relationship between hydroxychloroquine use and lower infection risk was observed in the cohort studies subgroup (OR = 0.66, 95%CI 0.44-0.99, p = 0.04), but not in the case-control studies subgroup (OR = 1.06, 95%CI 0.63-1.79, p = 0.83). It is important to note the risks associated with high-dose use, such as retinopathy.
Conclusions: Although hydroxychloroquine tends to reduce infection risk in SLE patients, the evidence is not strong. It can decrease severe infections, but high doses should be used cautiously and selectively in patients with impaired renal function. Further studies are required to establish optimal dosing and efficacy for specific diseases, considering the potential influence of study design on the observed associations between hydroxychloroquine use and infection risk in SLE patients.
Copyright: © 2025 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Seven vs Fourteen Days of Antibiotics for Gram-Negative Bloodstream Infection: A Systematic Review and Noninferiority Meta-Analysis
Authors: Todd C Lee
Abstract
Importance: Gram-negative bloodstream infections are a common cause of hospitalization. A 2-week duration of antibiotic therapy has been commonly used, but shorter durations may have similar outcomes.
Objectives: To assess whether 7 days of antibiotic therapy was noninferior to 14 days.
Data sources: Starting with a 2022 individual patient data meta-analysis, PubMed, Cochrane Central Register of Controlled Trials, and Web of Science were searched to identify additional eligible randomized clinical trials (RCTs) conducted from May 1, 2022, until November 30, 2024.
Study selection: RCTs involving primarily adults who were hospitalized at the time of Gram-negative bloodstream infection and were allocated to 7 or 14 days of antibiotic therapy. Studies were independently reviewed by 2 investigators.
Data extraction and synthesis: PRISMA guidelines were followed. Data were extracted by 2 investigators. Any unpublished data were obtained directly from study authors. Risk of bias and certainty of the evidence were assessed in duplicate using the Cochrane Risk of Bias Tool, version 2, and the Grading of Recommendations Assessment, Development and Evaluation approach. Data were pooled by separate random-effects meta-analyses for the intention-to-treat (ITT) and per-protocol (PP) populations. A noninformative prior probability was used for the effect, and an evidence-based weakly informative prior probability was used for heterogeneity. Risk ratios (RRs), 95% credible intervals (CrIs), and probability of noninferiority were calculated using a prespecified upper bound of 1.25 or less.
Main outcomes and measures: Ninety-day all-cause mortality.
Results: Four eligible RCTs contributed 3729 patients in the ITT population (1912 women [51.3%]; median age range, 67-79 years) and 3126 in the PP population. In the ITT analysis, within 90 days, 226 patients (12.8%) receiving 7 days of antibiotics died compared with 253 (13.7%) receiving 14 days, corresponding to an RR for 90-day mortality of 0.91 (95% CrI, 0.69-1.22) and a 97.8% probability of noninferiority. In the PP analysis, the RR was 0.93 (95% CrI, 0.68-1.32), corresponding to a 95.1% probability of noninferiority.
Conclusions and relevance: In this systematic review and meta-analysis of patients with Gram-negative bloodstream infections and adequate source control, 7 days of antibiotic therapy had a high probability of being noninferior to 14 days. These findings support a shorter duration of antibiotic therapy for appropriately selected patients like those in the included RCTs.
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Invasive Aspergillosis in the Current Era.
Authors: Herrera S et al
Abstract
Despite significant advances, aspergillosis remains a critical health concern, with an evolving epidemiology and expanding populations of at-risk patients. Historically, fewer than 10 Aspergillus species were considered clinically significant. However, advancements in diagnostic technologies, such as DNA sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, have identified previously unrecognized “cryptic” Aspergillus species. This clinical review highlights the current epidemiology, risk factors, pathogenesis, clinical presentation, diagnosis, and invasive aspergillosis (IA) treatment. Diagnosing IA necessitates a multifaceted approach, integrating clinical evaluation, imaging studies, microbiological culture, serologic tests, and advanced molecular techniques.
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In Vitro Elimination of Highly Multidrug-Resistant Bacteria by the Lactic Acid Bacterial Drug Candidate ILP100.
Authors: Lofton Tomenius H et al
Abstract
Introduction: Multidrug resistance (MDR) has been identified in wound bacterial isolates from Ukrainian war victims treated in Ukraine and across Europe. ILP100, a drug candidate for the treatment of skin wounds, is composed of a Limosilactobacillus reuteri expressing human chemokine CXCL12. In this study, the antimicrobial effects of ILP100 were tested on MDR bacteria isolated from wounds of Ukrainian war victims.
Methods: ILP100 was co-cultured with one of the wound pathogens (Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus; 12 non-MDR and 12 MDR isolates) in broth media for 12 h with subsequent survival recovery on agar plates. Additionally, agar plates were precoated with ILP100 at clinical doses (3 vs. 24 h, 1 × 107 CFU/cm2) followed by co-culture with pathogens inoculated in soft agar (1 × 104 CFU/cm2). To compare ILP100 with relevant antibiotics, MDR-inoculated soft agar was applied to plates with standardized ILP100 drops and antibiotic-loaded discs, followed by 18-20 h aerobic incubation at 37 °C.
Results: Dose-dependent growth inhibition of all pathogens was demonstrated, as 1000:1 and 100:1 (ILP100/isolate) inhibited pathogenic growth up to log 6.4 and log 4.3 CFU/ml, respectively. Potent antimicrobial effects were demonstrated after precoating with ILP100, as pathogen recovery was only demonstrated after 3 h of precoating, only for 10/18 isolates and then only partially. Benchmarking to relevant antibiotic discs resulted in large cleared zones surrounding the ILP100 spots but not the antibiotic discs, demonstrating potent bacterial killing by ILP100-secreted factors. Interestingly, the MDR pathogens were significantly more sensitive to the ILP100 released factors than the non-MDR isolates.
Conclusion: ILP100 effectively eliminates MDR wound pathogens, which reveals a promising strategy for the development of new classes of urgently needed antimicrobials.
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Whole genome analysis and biocontrol potential of endophytic Bacillus cereus EMS1 against Fusarium wilt in banana.
Authors: Singh S et al
Abstract
Endophytic bacteria are essential for promoting plant growth and increasing plant resilience to various environmental stresses. Although it is well-documented that several endophytic Bacillus species exhibit plant growth-promoting properties, this is the first report on the genome study of Bacillus cereus EMS1, isolated from Musa acuminata G9 in India. This study analyzed the genomics, plant growth traits, and fusarium wilt mitigation potential of Bacillus cereus EMS1. This analysis identified specific genomic features, including potential mechanisms contributing to plant growth promotion, which were also submitted to NCBI (Bioproject ID: PRJNA784269). The in vivo study showed that EMS1 mitigated the impact of Fusarium oxysporum f. sp. cubense on banana plants. Although it did not affect the number of leaves, other parameters influenced by pathogen infection and EMS1 treatment showed notable differences, including fresh weight (Fusarium oxysporum only: 15 g; EMS1 + Fusarium oxysporum: 21 g), dry weight (Fusarium oxysporum only: 1 g; EMS1 + Fusarium oxysporum: 4.7 g), and root length (Fusarium oxysporum only: 6.5 cm; EMS1 + Fusarium oxysporum: 9 cm). Additionally, genomic analysis revealed that the EMS1 genome contains distinctive genes linked to plant growth and antimicrobial activity. Overall, the findings highlight the potential of endophytic Bacillus cereus EMS1 in promoting plant growth and enhancing banana plant resistance against Fusarium oxysporum.
Other specific DSP article suggested by Editorial Board
Luteolin: a Novel Approach to Fight Bacterial Infection.
Authors: Chagas MDSDS et al
Abstract
Diseases caused by bacteria significantly impact public health, causing both acute and chronic issues, sequelae, and death. The problems get even more significant, considering the antimicrobial resistance. Bacterial resistance occurs when antibacterial drugs fail to kill the microbes, leading to the persistence of infection and pathogen spread in the host. Thus, the search for new molecules with antibacterial activity dramatically impacts human health. Natural products have proven to be a prosperous source of these agents. Among them, the flavonoids deserve to be highlighted. They are secondary metabolites, primarily involved in plant signaling and protection. Thus, they play an essential role in plant adaptation to the environment. Herein, we will focus on luteolin because it is commonly found in edible plants and has diverse pharmacological properties such as anti-inflammatory, anticancer, antioxidant, and antimicrobial. We will further explore the luteolin antibacterial activity, mechanisms of action, structure-activity relationship, and toxicity of luteolin. Thus, we have included reports of luteolin with antibacterial activity recently published, as well as focused on nanotechnology as a pivotal and helpful approach for the clinical use of luteolin. This review aims to foster future research on luteolin as a therapeutic agent for treating bacterial infection.
Other specific DSP article suggested by Editorial Board
Effects of preoperative topical levofloxacin on conjunctival microbiome in patients undergoing intravitreal injections.
Authors: Juhong J et al
Abstract
Purpose: Endophthalmitis is a serious eye infection that can occur after intravitreal injections. Topical antibiotics are frequently used as a preventative measure, but their impact on the conjunctival microbiome is not fully understood.
Methods: Conjunctival swabs were collected from 33 eyes of 33 patients undergoing intravitreal injections, both before and after a 3-day course of prophylactic topical levofloxacin 0.5%. Conjunctival microbiome analysis was conducted using 16S rRNA sequencing on the Illumina MiSeq platform. Bioinformatics processing identified unique amplicon sequence variants (ASVs) to evaluate microbial diversity and community composition. Alpha and beta diversity indices were analyzed.
Results: Topical levofloxacin treatment resulted in no significant change in alpha diversity indices, including Shannon index, Chao1, Shannon, PD whole tree, and observed ASVs, indicating stable microbial richness and evenness. In contrast, beta diversity analysis, assessed through Bray-Curtis dissimilarity, revealed significant differences in microbial composition between pre- and post-treatment samples. These changes included a decrease in the abundance of Staphylococcus and Bacillus species and an increase in the abundance of Streptococcus, Haemophilus, and Neisseria.
Conclusion: Although prophylactic topical levofloxacin was found to alter the conjunctival microbiome and showed inconsistent effects on the abundance of pathogenic bacteria, its clinical effectiveness as a preventative measure against endophthalmitis remains inconclusive. Further studies are needed to clarify its role in infection prevention.
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Prevalence of pilus islets and association with clonal complex in Streptococcus pneumoniae isolated from children in Suzhou, China.
Authors: Shen J et al
Abstract
Pilus islets (PIs) in Streptococcus pneumoniae play a crucial role in bacterial adhesion and virulence. This study aims to investigate the prevalence of PIs and explore their associations with serotypes, clones, and antibiotic susceptibility in S. pneumoniae isolated from children in Suzhou, China. A total of 341 S. pneumoniae isolates from aseptic specimens, ear secretions, and sputum between 2018 and 2021 were analyzed. Serotyping was conducted using latex and Quellung reactions. Antimicrobial susceptibility testing was performed using E-test methods. Multi-locus sequence typing (MLST) was conducted to identify the sequence types and clonal complex (CC). PI-1 and PI-2 were detected by PCR assays for the rlrA and sipA genes, respectively. A total of 63.6% of the included S. pneumoniae isolates expressed at least one type of PI, with strains of PCV13 vaccine serotypes showing a significantly higher positive rate of PIs than non-vaccine serotype strains (71.6% vs. 24.5%). PI prevalence varied across sample sources and clonal complexes. While a stronger association of PIs with clones than with serotypes was identified, most of the piliated isolates belonged to prevalent CCs, such as CC271. In addition, piliated isolates tended to be resistant to antibiotics compared to the non-piliated isolates. Our study highlights the high prevalence of PIs and the implications on antibiotic resistance and clonal dissemination of S. pneumoniae among children in Suzhou, China.IMPORTANCEThis study reveals a high prevalence of PIs in Streptococcus pneumoniae among children in China, which differs from isolates in other countries and highlights their implications for antibiotic resistance and clonal dissemination. To our knowledge, we are the first to report PI prevalence across different clinical samples within the same population, suggesting a potential link between PIs and acute otitis media (AOM) in Chinese children. These findings contribute valuable insights into the role of PIs in clinical settings and underline the need for targeted interventions, including vaccine strategies and antimicrobial stewardship protocols. By advancing our knowledge of PI epidemiology, this research enriches the existing literature and aims to inform public health initiatives, ultimately improving health outcomes for vulnerable pediatric populations.