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Systematic Review: Shorter Antibiotic Courses Often Prove Non-Inferior for Common Bacterial Infections

3 Feb, 2025 | 10:00h | UTC

Background: The overuse of antibiotics contributes significantly to the global rise in antimicrobial resistance (AMR). Shorter antibiotic treatment courses have gained traction as an important antimicrobial stewardship intervention. They can potentially reduce drug-related side effects, healthcare costs, and selection pressure favoring resistant pathogens. This review synthesizes findings from randomized controlled trials (RCTs) on antibiotic duration across various common bacterial infections—including respiratory tract, genitourinary, skin and soft tissue, bone/joint, and intra-abdominal infections—to inform practical, day-to-day clinical decision-making.

Objective:

To assess the comparative efficacy of short- versus long-course antibiotic therapy for frequent bacterial infections.
To highlight key evidence gaps, particularly for severe infections, critically ill populations, and low- to middle-income settings.
To propose practical treatment durations in light of current guidelines and study outcomes.

Methods:

Comprehensive search of MEDLINE and Embase through July 2024 (PROSPERO 2021, CRD42021276209).
Inclusion: RCTs that compared differing antibiotic durations for bacterial infections or perioperative prophylaxis, reporting clinical cure, relapse, or mortality.
Exclusion: Non-bacterial infections (viral/fungal), pilot studies, non-randomized designs.
Data extraction: Patient demographics, infection type, interventions, outcomes, adherence, and risk-of-bias assessment per the RoB 2 tool.
Guideline review: Major international guidelines (e.g., IDSA, NICE, WHO) were examined to contextualize trial findings.

Results:

A total of 315 RCTs were included; 85% concluded no difference, non-inferiority, or equivalence of shorter compared with longer antibiotic courses.
Shorter therapy (often 5–7 days) is well-supported for uncomplicated bacterial sinusitis, community-acquired pneumonia (CAP), simple urinary tract infections (UTIs), cellulitis, and intra-abdominal infections with adequate surgical source control.
Evidence for reducing duration in severe infections (e.g., bloodstream infections, ventilator-associated pneumonia caused by non-fermenting Gram-negative bacilli) or in critically ill populations remains limited.
Only 7% of RCTs involved intensive care unit (ICU) patients, and 14% were conducted in low- or middle-income countries.
Methodologically, 15% of trials posed a low risk of bias; however, non-adherence to assigned durations was common (median 11% per study). Very few trials tracked emergence of resistant organisms through follow-up cultures.

Key findings:

Acute GAS Pharyngotonsillitis:
10 days of penicillin V or amoxicillin remains the conventional standard to ensure microbiological eradication and minimize rheumatic fever risk. While 5 days of azithromycin may be used in macrolide-responsive settings, it is not preferred as first-line therapy due to broader-spectrum activity and limited evidence for preventing complications, particularly in high-risk populations.
Community-Acquired Pneumonia (CAP):
- Outpatient adults with mild to moderate CAP typically improve with 5 days of appropriate therapy (e.g., amoxicillin, doxycycline, or a macrolide), provided patients show clinical stability.
- Severe CAP or complicated presentations (e.g., MRSA, Pseudomonas, multi-lobar involvement) may need 7–10 days or until clinical stability is achieved.
Acute Bacterial Sinusitis (Adults):
- 5–7 days of amoxicillin/clavulanate or other first-line agents usually suffice if the diagnosis is certain.
Genitourinary Infections:
- Uncomplicated Cystitis (Non-Pregnant Women):
  - 3–5 days of nitrofurantoin or trimethoprim/sulfamethoxazole is often adequate, reflecting strong RCT support.
- Pyelonephritis or Complicated UTIs (e.g., in men, catheter-associated):
  - While some RCTs show 7 days can be as effective as 14 days in afebrile males with mild UTI, a trial in febrile males demonstrated inferior outcomes with shorter courses. Clinicians should exercise caution in febrile or higher-risk cases.
Skin and Soft Tissue Infections (e.g., Cellulitis):
- 5–6 days of effective oral therapy is sufficient for uncomplicated cellulitis if there is marked clinical improvement by Day 5.
- For recurrent abscesses or complicated scenarios, duration may need to be extended or individualized.
Bone and Joint Infections:
- 6 weeks is often sufficient for vertebral osteomyelitis in stable patients.
- For prosthetic joint infections with retained hardware, 6 weeks of therapy was inferior to 12 weeks in a key trial, necessitating individualized duration based on surgical management.
Intra-Abdominal Infections:
- With adequate source control, 4–5 days of antibiotics commonly yields outcomes on par with extended courses.
- Longer therapy (≥7 days) may be needed when abscesses are not fully drained or in immunocompromised patients.
Perioperative Prophylaxis:
- A single preoperative dose (possibly repeated if surgery is prolonged or blood loss is excessive) is sufficient in most procedures.
- Continuing prophylaxis beyond 24 hours rarely provides additional benefit and may increase adverse events.

Conclusions: Numerous well-conducted RCTs support shorter antibiotic courses for many common bacterial infections. Nonetheless, high-quality data are sparse for severe or complex infections, pediatric populations with significant comorbidities, and low-resource settings. Clinicians should tailor antibiotic duration to the infection type, disease severity, patient factors, and local resistance patterns—while remaining cognizant that shorter courses can safely balance efficacy, safety, and stewardship aims in many cases.

Study Strengths and Limitations:

Strengths: Large volume of RCTs, broad infection scope, and inclusion of diverse study designs. Substantial evidence supports shortening antibiotic regimens for multiple common infections.
Limitations: Underrepresentation of severe, ICU-level infections, children with serious comorbidities, and low-resource settings. High variation in diagnostic criteria, antibiotic choices, and adherence monitoring. Many trials reported low event rates, posing potential non-inferiority bias.

Future Research:

Well-powered RCTs focusing on severe infections (e.g., MDR Gram-negative bloodstream infections, staphylococcal bacteremia, ventilator-associated pneumonia with resistant pathogens).
Trials in low- and middle-income countries with robust microbiological and economic assessments.
Studies using adaptive designs and validated biomarkers to refine duration–response relationships and detect shifts in AMR at the population level.

Reference: Mo Y, Tan WC, Cooper BS. Antibiotic duration for common bacterial infections—a systematic review. JAC-Antimicrobial Resistance. 2025;7(1):dlae215. DOI: https://doi.org/10.1093/jacamr/dlae215

RCT: Albendazole–Ivermectin Co-Formulation Achieves Higher Cure Rates for T. trichiura and Hookworms

22 Jan, 2025 | 12:41h | UTC

Background: Soil-transmitted helminthiases (STH) affect an estimated 1.5 billion people worldwide, with Trichuris trichiura and hookworms remaining particularly challenging to treat. Although single-dose albendazole or mebendazole is standard in mass deworming programs, these agents show limited efficacy against T. trichiura and often leave Strongyloides stercoralis under-treated. Ivermectin has demonstrated broad activity against multiple parasites, suggesting that a combined albendazole–ivermectin regimen might enhance treatment outcomes, simplify protocols, and potentially curb emerging drug resistance.

Objective: This trial aimed to evaluate the safety, efficacy, and acceptability of a novel fixed-dose co-formulation (FDC) tablet containing albendazole (400 mg) plus a higher-than-standard, fixed dose of ivermectin (9 mg or 18 mg), administered once daily (FDC×1) or for three consecutive days (FDC×3). Investigators compared these regimens against single-dose albendazole alone for the treatment of T. trichiura, hookworms, and S. stercoralis in children and adolescents.

Methods: In this adaptive, randomized, parallel-group, phase 2/3 trial, 1001 participants aged 5–18 years were recruited from schools in Ethiopia, Kenya, and Mozambique. All were infected with at least one of T. trichiura, hookworms, or S. stercoralis. Eligible participants were allocated (by computer-generated block randomization) to either a single dose of albendazole 400 mg (control), a single-dose FDC of albendazole–ivermectin (FDC×1), or a three-day FDC regimen (FDC×3). Primary endpoints included safety (phase 2) and efficacy (phase 3), determined by cure rates at day 21 using the Kato–Katz and Baermann methods. Laboratory staff were blinded to treatment assignment.

Results: No serious adverse events were reported; mild-to-moderate gastrointestinal symptoms were the most frequent treatment-related events, resolving spontaneously within 48 hours. Cure rates for T. trichiura were 35.9% (95% CI 27.7–44.1) in the albendazole group, 82.9% (78.2–87.5) in FDC×1, and 97.2% (95.2–99.3) in FDC×3. For hookworms, cure rates were 65.1% (56.0–74.2) with albendazole, 79.8% (72.8–86.9) with FDC×1, and 95.0% (91.1–98.9) with FDC×3. Egg reduction rates in FDC arms consistently surpassed those of albendazole alone, especially for multi-day dosing. The sample size for S. stercoralis was insufficient to power a definitive efficacy conclusion, though ivermectin-containing arms trended toward favorable results. Palatability questionnaires indicated the orodispersible FDC was well accepted in taste, texture, and overall ease of administration.

Conclusions: A new co-formulation of albendazole plus ivermectin delivered at higher, fixed doses demonstrated an excellent safety profile and superior efficacy against T. trichiura and hookworms compared with albendazole monotherapy. This approach may streamline programmatic control of multiple STH species, including S. stercoralis, while contributing to reduced transmission in endemic communities.

Implications for Practice: For mass deworming initiatives, a single-dose FDC offers improved cure rates over albendazole alone while preserving simplicity. Where higher efficacy is critical—such as programs targeting near-elimination goals or in clinical settings—the three-day regimen may be preferable. Nonetheless, implementation feasibility, cost considerations, and further confirmation of efficacy against S. stercoralis and other co-endemic parasites remain important next steps.

Study Strengths and Limitations: Strengths include a multicenter design across three countries and a rigorous adaptive protocol that assessed both safety and efficacy. Limitations include the lack of blinding for participants and care providers (though outcome assessors were blinded), the underpowered sample size for S. stercoralis, and reliance on single-stool diagnostics, which may underestimate residual infections.

Future Research: Additional large-scale studies should confirm these findings in varied geographic regions and evaluate the cost-effectiveness of both single-dose and multi-day FDC strategies. Integrating albendazole–ivermectin with treatment programs for other neglected tropical diseases (e.g., onchocerciasis) could further amplify public health benefits. Genomic and pharmacokinetic analyses will clarify resistance patterns and optimize dosing regimens for broader implementation.

Reference: Krolewiecki A, Kepha S, Fleitas PE, van Lieshout L, Gelaye W, Messa A Jr, et al. “Albendazole–ivermectin co-formulation for the treatment of Trichuris trichiura and other soil-transmitted helminths: a randomised phase 2/3 trial.” The Lancet Infectious Diseases. Published January 10, 2025. DOI: https://doi.org/10.1016/S1473-3099(24)00669-8

Network Meta-analysis: Oseltamivir Fails to Improve Key Outcomes in Nonsevere Influenza

20 Jan, 2025 | 11:17h | UTC

Background: Influenza causes significant respiratory morbidity and can lead to severe complications, especially in high-risk individuals. Current guidelines endorse antiviral therapy, yet the evidence for reducing mortality, hospital admission, and symptom duration in nonsevere cases remains controversial. Recent recommendations have often focused on neuraminidase inhibitors (e.g., oseltamivir), despite uncertainties regarding clinical impact and adverse effects. An editorial accompanying this study underscores the need to reexamine routine antiviral use, especially oseltamivir, given minimal benefit observed in outpatient populations.

Objective: To assess and compare the efficacy and safety of direct-acting antiviral medications (baloxavir, oseltamivir, laninamivir, zanamivir, peramivir, umifenovir, favipiravir, and amantadine) in treating patients with nonsevere influenza.

Methods: This systematic review and network meta-analysis included 73 randomized clinical trials (N=34,332) that evaluated antivirals vs placebo, standard care, or another antiviral. Eligible studies enrolled nonhospitalized patients with confirmed or suspected influenza. Outcomes included mortality, hospital admission, time to symptom alleviation, adverse events, and emergence of antiviral resistance. Risk of bias was assessed with a modified Cochrane tool, and the certainty of evidence was rated using the GRADE approach. Pooled estimates were generated with a frequentist random-effects model, focusing on both absolute risk differences and relative measures.

Results:

Mortality: Across all antiviral agents, there was high-certainty evidence of little or no effect on mortality in both low-risk and high-risk patients compared with standard care or placebo.
Hospital Admission: In low-risk patients, none of the antivirals significantly altered admission rates (high certainty). In high-risk patients, oseltamivir had little or no effect on hospitalization (high certainty), whereas baloxavir may reduce admissions (low certainty).
Time to Alleviation of Symptoms: Baloxavir shortened symptom duration by approximately one day (moderate certainty) without increasing adverse events. Oseltamivir and zanamivir likely produced smaller decreases (<1 day; moderate certainty). Umifenovir may also shorten symptoms (low certainty).
Adverse Events: Baloxavir did not increase treatment-related adverse events (high certainty) but may lead to viral resistance in around 10% of cases (low certainty). Oseltamivir probably increases adverse events such as nausea and vomiting (moderate certainty).
Serious Outcomes (ICU Admission, Duration of Hospitalization): Data were limited, with uncertainty regarding meaningful reductions in these measures.

Conclusions: Baloxavir may reduce hospital admissions for high-risk patients and significantly shorten symptom duration without notable treatment-related adverse events. Oseltamivir shows little effect on mortality or hospitalization for nonsevere influenza, with only modest (likely not clinically important) reductions in symptom duration and a higher rate of adverse events. Other antivirals either demonstrate uncertain clinical benefits or likely provide no major advantages in this patient population.

Implications for Practice: These findings suggest that routine use of oseltamivir for outpatients with nonsevere influenza should be reconsidered, especially in low-risk groups. Baloxavir appears favorable for high-risk patients, though clinicians should monitor potential drug resistance. Given the minimal impact on major outcomes and the cost considerations, prescribers should weigh the benefits and harms of these antivirals, aligning treatment decisions with patient risk profiles and clinical judgment.

Study Strengths and Limitations: Strengths include a comprehensive search, large pooled population, and rigorous GRADE-based analysis of certainty. Limitations involve low event rates for hospital admissions and mortality, limiting power for certain outcomes, and sparse data on some antivirals (e.g., amantadine). Additionally, few trials reported ICU admissions or mechanical ventilation needs, restricting conclusions about severe complications.

Future Research: Further high-quality studies should evaluate patient-important outcomes such as mechanical ventilation and severe complications in diverse populations. Investigations into combination strategies, alternative dosing, and resistance patterns would help clarify the long-term viability of baloxavir and other antivirals, particularly in high-risk cohorts.

Reference:

Gao Y, Zhao Y, Liu M, et al. Antiviral Medications for Treatment of Nonsevere Influenza: A Systematic Review and Network Meta-Analysis. JAMA Internal Medicine. Published online January 13, 2025. DOI: http://doi.org/10.1001/jamainternmed.2024.7193
Baghdadi JD, Grady D, Morgan DJ. The Limited Role for Antiviral Therapy in Influenza. JAMA Internal Medicine. Published online January 13, 2025. DOI: http://doi.org/10.1001/jamainternmed.2024.7258

Joint ATS/CDC/ERS/IDSA Guideline Recommends Shorter, All-Oral Regimens for Drug-Susceptible and Drug-Resistant TB

5 Jan, 2025 | 11:30h | UTC

Introduction: This summary outlines new clinical practice guidelines from the American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America on updated treatment regimens for tuberculosis (TB) in low-incidence settings. These recommendations build on recent clinical trials, World Health Organization (WHO) guidance, and were developed using the GRADE and GRADE-ADOLOPMENT methodology. The guidelines aim to shorten treatment duration, reduce pill burden, and improve patient outcomes for both drug-susceptible (DS) and drug-resistant (DR) TB, and they apply to settings where mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies are routinely available. A separate news release from CIDRAP highlights the significance of these shorter, all-oral regimens for adults and children. Directly observed therapy (DOT) remains the standard of care.

Key Recommendations:

Four-Month Regimen for DS-TB in Adults:

For people aged 12 years or older with isoniazid- and rifampin-susceptible pulmonary TB, a new four-month regimen of isoniazid, rifapentine, moxifloxacin, and pyrazinamide (2HPZM/2HPM) is conditionally recommended. This shortened course is based on a large, randomized trial (Study 31/A5349) demonstrating noninferior efficacy compared to the standard six-month regimen (84.6% vs 85.4% cure, respectively), no increase in adverse events, and potential benefits in completion rates. Exclusions include TB meningitis and other complicated forms of extrapulmonary TB, and clinicians should obtain rapid fluoroquinolone susceptibility tests before initiating this regimen.

Four-Month Regimen for DS-TB in Children:

For children and adolescents aged 3 months to 16 years with nonsevere, drug-susceptible pulmonary TB, a four-month regimen of isoniazid, rifampin, pyrazinamide, and ethambutol for the initial phase, followed by isoniazid and rifampin, is strongly recommended. Evidence from the SHINE trial showed high success (97.1% vs 96.9%) and similar safety with the shorter course compared to the 6-month regimen. Nonsevere TB generally excludes extensive cavitary disease, advanced extrapulmonary TB, or complicated forms. Close clinical and radiographic follow-up is important to confirm effective cure.

Six-Month BPaL Regimen for Rifampin-Resistant, Fluoroquinolone-Resistant or Intolerant TB:

For rifampin-resistant (RR) pulmonary TB with resistance or patient intolerance to fluoroquinolones in adolescents aged 14 and older and adults, a six-month all-oral bedaquiline, pretomanid, and linezolid (BPaL) regimen is strongly recommended, replacing much longer regimens that often included injectables. Clinical trials (Nix-TB, ZeNix) demonstrated higher cure rates and lower toxicity with this regimen compared to longer regimens, though vigilance is needed for linezolid-related adverse events (e.g., neuropathy, myelosuppression). Baseline and monthly lab and ECG checks are advised.

Six-Month BPaLM Regimen for Rifampin-Resistant, Fluoroquinolone-Susceptible TB:

For RR pulmonary TB that remains fluoroquinolone-susceptible in adolescents aged 14 and older and adults, a six-month bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) regimen is strongly recommended over traditional 15-month or longer regimens in patients with MDR/RR-TB. Data from the TB-PRACTECAL trial showed high success rates and fewer serious adverse events. BPaLM is the first-line recommendation for this group. Close monitoring of cardiac status (QTc prolongation) and blood counts is advised.

Both BPaL and BPaLM regimens require detailed drug susceptibility testing and cautious management of potential drug–drug interactions, particularly for patients with comorbidities or HIV infection. Of note, the certainty of evidence for the outcomes in the DR-TB trials was rated as very low, due to multiple factors including bias, small event numbers, lack of blinding, and inconsistent outcomes.

Conclusion: These new recommendations markedly shorten TB treatment courses for adults and children in low-incidence settings with access to appropriate diagnostic tools, while avoiding injectables and reducing serious toxicities. By replacing older, more complex regimens with all-oral, shorter-duration therapy, and using DOT as the standard of care, the guidelines aim to improve adherence, lessen the burden on healthcare systems, and enhance patient quality of life. Ongoing research will further refine dosing, safety for special populations (e.g., pregnant individuals), and the role of advanced drug susceptibility testing.

Reference:

Jussi J. Saukkonen, Raquel Duarte, Sonal S. Munsiff, et al. “Updates on the Treatment of Drug-Susceptible and Drug-Resistant Tuberculosis: An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.” American Journal of Respiratory and Critical Care Medicine, (2025). https://doi.org/10.1164/rccm.202410-2096ST

News release commentary: “New guidelines expand recommendations for shorter, all-oral TB treatments” (CIDRAP). https://www.cidrap.umn.edu/tuberculosis/new-guidelines-expand-recommendations-shorter-all-oral-tb-treatments

Guideline: Management of Urinary Tract Infections in Pediatrics and Adults

5 Nov, 2024 | 18:59h | UTC

Introduction: Urinary tract infections (UTIs) are among the most common infections worldwide, significantly impacting patient quality of life and imposing substantial clinical and economic burdens. Despite advancements in diagnosis and treatment, UTIs continue to cause high morbidity and mortality, ranging from simple cystitis to life-threatening sepsis. Addressing the discrepancy between evidence quality and recommendation strength in existing guidelines, the WikiGuidelines Group has developed a consensus statement. This guideline aims to provide evidence-based recommendations for the prevention, diagnosis, and management of UTIs across diverse clinical settings.

Key Recommendations:

Cranberry Products:
- Recommendation: Cranberry juice or supplements are recommended for preventing symptomatic, culture-verified UTIs in women with recurrent UTIs, children, and individuals susceptible after interventions.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
Methenamine Hippurate:
- Recommendation: Methenamine hippurate is recommended as an alternative to prophylactic antibiotics for preventing recurrent UTIs in patients with intact bladder anatomy.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
Topical Estrogen:
- Recommendation: Vaginal estrogen therapy is recommended for postmenopausal women to reduce recurrent UTIs by restoring the vaginal microbiome.
- Quality of Evidence: High
- Recommendation Strength: Strong
Empirical Treatment Regimens:
- Recommendation: For uncomplicated cystitis, nitrofurantoin is recommended as a first-line agent. For pyelonephritis, trimethoprim/sulfamethoxazole or a first-generation cephalosporin are reasonable first-line agents, depending on local resistance rates.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
Treatment Duration for Acute Cystitis in Adults:
- Recommendation:
  - Nitrofurantoin: 5 days
  - Trimethoprim/sulfamethoxazole: 3 days
  - Oral fosfomycin: Single dose
- Quality of Evidence: High
- Recommendation Strength: Strong
Treatment Duration for Acute Pyelonephritis in Adults:
- Recommendation:
  - Fluoroquinolones: 5–7 days
  - Dose-optimized β-lactams: 7 days
- Quality of Evidence: High
- Recommendation Strength: Strong
Antimicrobial Stewardship:
- Recommendation: De-escalation of antibiotics and the use of mostly or all oral treatment regimens are recommended to optimize antimicrobial use and reduce adverse effects.
- Quality of Evidence: High
- Recommendation Strength: Strong

Conclusion: The consensus highlights a significant lack of high-quality prospective data in many areas related to UTIs, limiting the ability to provide clear recommendations. Implementing these evidence-based guidelines can enhance patient care by promoting effective prevention strategies, accurate diagnosis based on clinical symptoms, appropriate treatment durations, and robust antimicrobial stewardship. This approach is expected to improve clinical outcomes, reduce antimicrobial resistance, and preserve the effectiveness of current treatments.

Reference: Nelson Z, Aslan AT, Beahm NP, et al. Guidelines for the Prevention, Diagnosis, and Management of Urinary Tract Infections in Pediatrics and Adults: A WikiGuidelines Group Consensus Statement. JAMA Network Open. 2024;7(11). DOI: http://doi.org/10.1001/jamanetworkopen.2024.44495

Cohort Study: Lower Risk of Cardiovascular Complications in Post–COVID-19 Vaccine Myocarditis Compared to Conventional Etiologies

7 Sep, 2024 | 20:36h | UTC

Study Design and Population: This French nationwide cohort study included 4,635 individuals aged 12-49 hospitalized for myocarditis between December 2020 and June 2022. The cohort was divided into three groups: 558 patients with post–COVID-19 mRNA vaccine myocarditis, 298 with post–COVID-19 infection myocarditis, and 3,779 with conventional myocarditis.

Main Findings: At 18 months of follow-up, the frequency of cardiovascular events was significantly lower in the postvaccine myocarditis group (5.7%) compared to conventional myocarditis (13.2%) with a weighted hazard ratio (wHR) of 0.55 (95% CI, 0.36-0.86). Hospital readmission for myopericarditis occurred in 3.2% of postvaccine cases, 4.0% of post–COVID-19 cases, and 5.8% of conventional cases. The all-cause mortality rate was 0.2% for postvaccine myocarditis, 1.3% for post–COVID-19 myocarditis, and 1.3% for conventional myocarditis.

Implications for Practice: Postvaccine myocarditis patients, primarily young males, experience fewer complications compared to conventional myocarditis, but long-term follow-up is still needed. These findings should guide future mRNA vaccine recommendations and clinical management for myocarditis patients.

Reference: Semenzato L. et al. (2024). Long-term Prognosis of Myocarditis Attributed to COVID-19 mRNA Vaccination, SARS-CoV-2, or Conventional Etiologies. JAMA, Online. DOI: http://doi.org/10.1001/jama.2024.16380

Link: https://jamanetwork.com/journals/jama/fullarticle/2822933

Phase 3 RCT: Butantan-DV Dengue Vaccine is Safe and Shows 67.3% Efficacy Over 3.7 Years in Participants Aged 2–59 Years – Lancet Infect Dis

10 Aug, 2024 | 20:23h | UTC

Study Design and Population: This double-blind, randomized, placebo-controlled, phase 3 trial conducted in Brazil evaluated the efficacy and safety of the Butantan-dengue vaccine (Butantan-DV) in 16,235 healthy participants aged 2–59 years. Participants, who had not previously received a dengue vaccine, were randomly assigned to receive either a single dose of Butantan-DV or a placebo and were followed up for an average of 3.7 years.

Main Findings: The study found that Butantan-DV demonstrated 67.3% efficacy against virologically confirmed dengue (VCD) caused by any dengue virus serotype, with no cases of VCD caused by DENV-3 or DENV-4. The proportions of serious adverse events were similar between the vaccine and placebo groups, indicating that the vaccine was generally well tolerated.

Implications for Practice: The results support the potential of the Butantan-DV vaccine as an effective intervention for preventing symptomatic dengue, particularly from DENV-1 and DENV-2, across a broad age range regardless of dengue serostatus. Continued development and monitoring are warranted to confirm long-term efficacy and safety.

Reference: Nogueira, M. L., et al. (2024). Efficacy and safety of Butantan-DV in participants aged 2–59 years through an extended follow-up: results from a double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil. The Lancet Infectious Diseases. DOI: https://doi.org/10.1016/S1473-3099(24)00376-1.

Phase 2 RCT: Preventive subcutaneous L9LS monoclonal antibody reduces malaria incidence by 66-70% in Malian children – N Engl J Med

7 May, 2024 | 15:31h | UTC

This phase 2 randomized clinical trial investigated the safety and efficacy of the monoclonal antibody L9LS in preventing Plasmodium falciparum infection and clinical malaria in children aged 6 to 10 years in Mali. The trial was structured in two parts: initial dose assessment in adults followed by a randomized, placebo-controlled test in children over a 6-month malaria season. A total of 225 children participated, divided equally among three groups to receive either 150 mg of L9LS, 300 mg of L9LS, or a placebo. Results demonstrated a significant reduction in the rate of P. falciparum infection—66% efficacy with the 150-mg dose and 70% efficacy with the 300-mg dose. Similarly, efficacy against clinical malaria was 67% with the 150-mg dose and 77% with the 300-mg dose. Both doses were well-tolerated with no safety concerns reported, underscoring the potential of L9LS as a preventative treatment against malaria in endemic regions.

Reference (link to abstract – $ for full-text):

Kayentao, K. et al. (2024). Subcutaneous Administration of a Monoclonal Antibody to Prevent Malaria. N Engl J Med, 390(17), 1549-1559. DOI: 10.1056/NEJMoa2312775

RCT: No significant benefit of adjuvant prednisone for patients with cystic fibrosis with exacerbations unresponsive to antibiotics – Eur Respir J

6 May, 2024 | 06:32h | UTC

This randomized, double-blind, placebo-controlled trial investigated the effectiveness of adjuvant oral prednisone in enhancing lung function recovery in patients with cystic fibrosis (CF) experiencing pulmonary exacerbations (PExs) unresponsive to initial intravenous (IV) antibiotic treatment. The study involved 173 participants, with 76 not achieving more than 90% of their baseline forced expiratory volume in one second (ppFEV1) by Day 7 of antibiotic treatment and subsequently randomized to receive either oral prednisone (1 mg·kg−1 twice daily, up to 60 mg/day) or placebo for an additional 7 days. Results showed that 50% of the prednisone group and 39% of the placebo group recovered over 90% of their baseline ppFEV1 by Day 14. However, the difference was not statistically significant (11% difference; 95% CI -11, 34%; p=0.34). Additionally, prednisone did not significantly prolong the time to the next exacerbation compared to placebo. This study concludes that adjuvant oral prednisone does not significantly improve lung function recovery or delay subsequent exacerbations in CF patients not responding to initial antibiotic therapy.

Reference (link to abstract – $ for full-text):

Valerie Waters et al. (2024). A randomized trial of oral prednisone for cystic fibrosis pulmonary exacerbation treatment. European Respiratory Journal, DOI: 10.1183/13993003.02278-2023

RCT: Azithromycin fails to prevent moderate or severe chronic lung disease in preterm infants – Lancet Respir Med

6 May, 2024 | 06:28h | UTC

This randomized, placebo-controlled trial evaluated the effectiveness of azithromycin in preventing chronic lung disease (CLD) in preterm infants born at less than 30 weeks’ gestation across 28 UK neonatal intensive care units. A total of 799 infants were randomized to receive either intravenous azithromycin or a placebo. The primary outcome measured was survival without moderate or severe CLD at 36 weeks postmenstrual age. Results showed no significant difference between the azithromycin group (42% survival without CLD) and the placebo group (45% survival without CLD), with an adjusted odds ratio of 0.84 (95% CI 0.55–1.29, p=0.43). Pulmonary Ureaplasma spp colonization did not affect the treatment outcome. Given the lack of efficacy and the presence of several serious adverse events in the azithromycin group, the study concluded that azithromycin should not be recommended for preventing CLD in this population.

Reference (link to free full-text):

John Lowe et al. (2024). Azithromycin therapy for prevention of chronic lung disease of prematurity (AZTEC): a multicentre, double-blind, randomised, placebo-controlled trial. The Lancet Respiratory Medicine. DOI: https://doi.org/10.1016/S2213-2600(24)00079-1

Invited Commentary: Need for a Structural Approach to Promote Child Survival – JAMA Network Open

News Release: Eight out of ten child deaths in low-income countries could be prevented – Barcelona Institute for Global Health

RCT | Limited antibiotic efficacy in children with sinusitis lacking nasopharyngeal pathogens

27 Jul, 2023 | 13:08h | UTC

Identifying Children Likely to Benefit From Antibiotics for Acute Sinusitis: A Randomized Clinical Trial – JAMA (free for a limited period)

Editorial: Acute Bacterial Sinusitis: Limitations of Test-Based Treatment – JAMA (free for a limited period)

News Release: Bacterial testing in kids with sinusitis could slash antibiotic use – University of Pittsburgh

Commentary: Trial suggests bacterial test could reduce antibiotics in kids with sinusitis – CIDRAP

Commentary on Twitter

In children with acute sinusitis, antibiotic treatment had minimal benefit for those without nasopharyngeal bacterial pathogens. The antibiotic effect did not depend on the color of nasal discharge. https://t.co/hgRx1Qou53 pic.twitter.com/zYs8Mfbjjp

— JAMA (@JAMA_current) July 26, 2023

Global, regional, and national burden of meningitis and its etiologies, 1990–2019

25 Jul, 2023 | 13:55h | UTC

Global, regional, and national burden of meningitis and its aetiologies, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019 – The Lancet Neurology

Commentary on Twitter

Although largely preventable, meningitis still causes hundreds of thousands of deaths globally each year.

New @IHME_UW #GBDStudy in @TheLancetNeuro assesses incident cases and deaths due to acute infectious meningitis by aetiology and age from 1990–2019. https://t.co/S3KtMA7DMs pic.twitter.com/AYuSJHsNwK

— The Lancet (@TheLancet) July 20, 2023

M-A | Exposure to smoke, overcrowding, poor living conditions, and contact with TB cases identified as risk conditions for pediatric TB

24 Jul, 2023 | 12:43h | UTC

Risk factors for the development of tuberculosis among the pediatric population: a systematic review and meta-analysis – European Journal of Pediatrics

Phase 2 Trial | Maternal GBS6 vaccine shows promise in infant group B strep prevention

21 Jul, 2023 | 13:34h | UTC

Potential for Maternally Administered Vaccine for Infant Group B Streptococcus – New England Journal of Medicine

Commentary: Maternal strep B vaccine slashes risk of infection among infants – CIDRAP

Cohort Study| Childhood development delayed by 4.39 months due to COVID-19 pandemic

13 Jul, 2023 | 13:11h | UTC

Association Between the COVID-19 Pandemic and Early Childhood Development – JAMA Pediatrics

Commentary: Studies describe pandemic’s lasting influence on children – CIDRAP

Global Burden of Disease Study | Understanding global trends of infectious diseases in younger population, 1990-2019

10 Jul, 2023 | 13:54h | UTC

The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990–2019: a systematic analysis of the Global Burden of Disease Study 2019 – The Lancet

News Release: Global efforts to reduce infectious diseases must extend beyond early childhood – Murdoch Children’s Research Institute

Commentary: Global infectious disease burden shifting from younger to older youth – CIDRAP

RCT | Lower rates of treatment failure with standard-course vs. short-course therapy in pediatric UTIs

5 Jul, 2023 | 01:09h | UTC

Short-Course Therapy for Urinary Tract Infections in Children: The SCOUT Randomized Clinical Trial – JAMA Pediatrics (link to abstract – $ for full-text)

See also: Visual Abstract

Commentary: Treatment Failure Down With Standard-Course Therapy in Pediatric UTI – HealthDay

Cluster RCT | Point-of-care CRP testing cuts antibiotic prescriptions in respiratory illnesses in primary care

1 Jun, 2023 | 11:58h | UTC

Implementation of point-of-care testing of C-reactive protein concentrations to improve antibiotic targeting in respiratory illness in Vietnamese primary care: a pragmatic cluster-randomised controlled trial – The Lancet Infectious Diseases

Commentary: Use of CRP testing reduced antibiotics for respiratory infections, trial finds – CIDRAP

Review | Invasive mold infections in children: navigating troubled waters with a broken compass

31 May, 2023 | 14:05h | UTC

Invasive Mold Infections in Children: Navigating Troubled Waters with a Broken Compass – Infectious Diseases and Therapy

M-A | Shorter vs. longer-term antibiotic treatments for community-acquired pneumonia in children

31 May, 2023 | 13:42h | UTC

Shorter Versus Longer-term Antibiotic Treatments for Community-Acquired Pneumonia in Children: A Meta-analysis – Pediatrics (link to abstract – $ for full-text)

Commentary: Meta-analysis supports shorter antibiotic courses for kids’ pneumonia – CIDRAP

Appropriate Use of Short-Course Antibiotics in Common Infections: Best Practice Advice From the American College of Physicians – Annals of Internal Medicine

Efficacy of short-course antibiotic treatments for community-acquired pneumonia in adults: A systematic review and meta-analysis – Antimicrobial Agents and Chemotherapy

Short-Course vs Long-Course Antibiotic Therapy for Children With Nonsevere Community-Acquired Pneumonia: A Systematic Review and Meta-analysis – JAMA Pediatrics

Short- vs Standard-Course Outpatient Antibiotic Therapy for Community-Acquired Pneumonia in Children: The SCOUT-CAP Randomized Clinical Trial – JAMA Pediatrics

Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia: The SAFER Randomized Clinical Trial – JAMA Pediatrics

Effect of Amoxicillin Dose and Treatment Duration on the Need for Antibiotic Re-treatment in Children With Community-Acquired Pneumonia: The CAP-IT Randomized Clinical Trial – JAMA

Pediatrics – Infectious Diseases