Expert Review of Anti-infective Therapy最新文献

Introduction: Ceftriaxone is the last available single dose therapy for gonorrhea that effectively treats infections at all sites. Over a quarter of isolates are now resistant to ceftriaxone in some countries. The introduction of carefully chosen combination therapy with ceftriaxone could retard the emergence of ceftriaxone resistance.

Areas covered: This review summarizes the findings of a PubMed search on the use of partner antimicrobial that could be used with ceftriaxone to prevent the emergence and spread of ceftriaxone resistance. We review 16 antimicrobials that could be partnered with ceftriaxone in terms of pharmacokinetic and pharmacodynamic compatibilities, activity against ceftriaxone resistant isolates and probability of antimicrobial resistance emerging.

Expert opinion: Of these 16 antimicrobials, we reject antimicrobials such as fosfomycin due to poor clinical efficacy and tigecycline due to its considerably longer half-life which would likely select for tetracycline resistance. The most promising agents for combination with ceftriaxone are zoliflodacin, delafloxacin, sitafloxacin, eravacycline and possibly gepotidacin and gentamicin. Clinical studies should be conducted to evaluate the efficacy of these combinations on the eradication of N. gonorrhoeae and their impact on AMR in N. gonorrhoeae and other bacterial species.

Background: Linezolid-associated thrombocytopenia (LAT) is a significant complication in intensive care unit (ICU) patients, increasing bleeding risk and leading to treatment discontinuation. This study aims to assess LAT incidence, identify risk and protective factors, and develop a predictive nomogram.

Research design and methods: This retrospective cohort study included 422 adult ICU patients treated with linezolid. Over 70 clinical, demographic, laboratory, and therapeutic variables were analyzed. Logistic regression identified key risk and protective factors for LAT, and a nomogram was developed for risk prediction.

Results: LAT occurred in 39.8% of patients. Risk factors included linezolid therapy > 10 days (OR 5.80, p < 0.01), solid organ tumor (OR 2.18, p = 0.03), hemodialysis (OR 5.12, p < 0.01), elevated lactate (OR 1.13, p = 0.03), and vasopressor use (OR 4.48, p < 0.01). Protective factors were surgery (OR 0.34, p < 0.01), IV N-acetylcysteine (OR 0.12, p < 0.01), oral N-acetylcysteine (OR 0.17, p < 0.01), higher baseline platelets (OR 0.79, p = 0.05), and acetaminophen (OR 0.42, p < 0.01). The nomogram showed strong discrimination (AUC 0.834, p < 0.001).

Conclusions: LAT is common in ICU patients and associated with adverse outcomes. Prolonged therapy, solid organ tumors, dialysis, high lactate, and vasopressor use increase risk; high platelet counts, N-acetylcysteine, and IV acetaminophen decrease risk. External validation and prospective trials are warranted.

Background: This study aims to evaluate the risk factors, clinical features, and clinical outcomes among pediatric hospitalized patients receiving treatment for Staphylococcus aureus bacteremia and compare the effects of antibiotics used in the treatment on clinical outcomes.

Research design and methods: This single-center retrospective study included patients aged between 1 month and 18 years who received treatment for Staphylococcus aureus bacteremia (SAB) betweenSeptember 2019 and September 2022.

Results: SAB was detected in 95 pediatric patients. In MRSA bacteremias, no difference in clinical outcomes was found between patients receiving vancomycin or teicoplanin. In MSSA bacteremias, the recurrence rate of SAB was 0% in the penicillin group and 23.5% in the cephalosporin group. The median duration of bacteremia-related hospital stay (10 vs. 14 days), and the median duration of bacteremia (2 vs. 3 days) were shorter in the ampicillin-sulbactam group than in the piperacillin-tazobactam group (p = 0.016, and p = 0.050, respectively).

Conclusions: Teicoplanin was found to have similar clinical outcomes to vancomycin in treating MRSA bacteremia. In addition, ampicillin sulbactam was found to have better clinical outcomes than other antibiotics in treating MSSA bacteremia. Teicoplanin and ampicillin sulbactam may be considered as a choice in the treatment of pediatric SAB.

Introduction: Doxycycline post-exposure prophylaxis ('doxyPEP') is an emerging strategy to prevent bacterial sexually transmitted infections (STIs). Users take 200 mg of doxycycline up to 72 hours after condomless sex, and data from randomized controlled trials and real-world implementation have shown doxyPEP to be effective in preventing syphilis, chlamydia, and to a lesser extent gonorrhea, in gay, bisexual, and other men-who-have-sex-with-men (GBMSM) and transgender women.

Areas covered: We discuss the potential benefits, risks, and important considerations for doxyPEP implementation, drawing on published literature and our own perspectives.

Expert opinion: Is doxyPEP the golden bullet? DoxyPEP provides significant benefits through STI prevention and holistic improvements in sexual health and wellbeing. Concerns over emergent antimicrobial resistance need to be weighed against STI-related morbidity and contextualized within society's overuse of antibiotics. Inequities in the doxyPEP evidence-base and implementation will undermine its ability to end the syphilis epidemic and reduce chlamydia associated morbidity in cisgender women. Moreover, contexts in which doxyPEP proves effective for gonorrhea prevention initially are unlikely to see a long-lasting impact. Rather than a golden bullet, doxyPEP is a bridge to the next set of STI prevention tools.

Background: Access to safe and effective antibiotics is crucial in low- and middle-income countries (LMICs) coupled with reducing their overuse to reduce antimicrobial resistance (AMR). We sought to systematically analyze the extent of branded generic antibiotics in Pakistan, particularly Watch antibiotics, given concerns with AMR in Pakistan.

Research design and methods: Data on registered antibiotics was collected from the Drug Regulatory Authority of Pakistan (DRAP) and the Pharmaguides. Two hundred and fifty-seven antibiotics were analyzed using the AWaRe classification.

Results: Of these, 99 were registered in Pakistan including 91 single entities and 8 combinations, with 6,025 brands and 14,076 presentations. Distribution across AWaRe categories included Access - 37, Watch - 56, and Reserve - 6. Cephalosporins (2186 brands, 6447 presentations) and Quinolones (1333 brands, 2586 presentations) are the most prevalent, with ciprofloxacin (393 brands, 1158 presentations) leading in brand and presentation counts. Six antibiotics from the WHO Essential Medicines List lacked registered brands in Pakistan, while many available antibiotics were not included in the WHO framework.

Conclusion: Extensive availability of branded generic antibiotics, particularly Watch antibiotics, in Pakistan poses a serious risk, exacerbated by the current misuse of antibiotics. Improving regulatory frameworks and strengthening stewardship are critical to reducing AMR in Pakistan along with addressing uncontrolled registration by DRAP.

Background: To evaluate the efficacy of a new D-mannose dietary supplement containing D-mannose, Propolis-Quercetin, Bacillus Coagulans, Hyaluronic Acid and Chondroitin Sulfate with fosfomycin in reducing rUTI episodes and improving quality of life.

Research design and methods: Single-blind, randomized controlled trial conducted at tertiary-care hospital in Italy. Women aged 21-65 with a history of rUTIs were randomized into three groups: fosfomycin, the dietary supplement, and a combination of both treatments. Primary outcome was frequency of rUTI episodes per month.

Results: Combination therapy demonstrated greatest reduction in rUTI episodes per month at 12 months compared to fosfomycin or supplement monotherapy (0.23 ± 0.37 vs 0.58 ± 0.67 and 1.12 ± 0.96 for fosfomycin and supplement monotherapy respectively; p < 0.05) and to supplement monotherapy at 6 months (0.69 ± 1.03 vs 1.43 ± 1.33; p < 0.05), with significant improvement of ICIQ-FLUTS domains compared to other groups at 12 months (p < 0.05). Combination therapy had lower number of women matching rUTI criteria (55.32% vs 76.47% and 84%; p < 0.05) and symptoms remission at 12 months (89.36% vs 56.86% and 20%; p < 0.001).

Conclusions: Combining fosfomycin and an integrated D-mannose supplement for managing rUTIs offers a potential reduction in antibiotic reliance. Further large-scale studies are recommended to confirm these findings.

Trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT06659016).

Introduction: Traditional microbiological diagnostics face challenges in pathogen identification speed and antimicrobial resistance (AMR) evaluation. Artificial intelligence (AI) offers transformative solutions, necessitating a comprehensive review of its applications, advancements, and integration challenges in clinical microbiology.

Areas covered: This review examines AI-driven methodologies, including machine learning (ML), deep learning (DL), and convolutional neural networks (CNNs), for enhancing pathogen detection, AMR prediction, and diagnostic imaging. Applications in virology (e.g. COVID-19 RT-PCR optimization), parasitology (e.g. malaria detection), and bacteriology (e.g. automated colony counting) are analyzed. A literature search was conducted using PubMed, Scopus, and Web of Science (2018-2024), prioritizing peer-reviewed studies on AI's diagnostic accuracy, workflow efficiency, and clinical validation.

Expert opinion: AI significantly improves diagnostic precision and operational efficiency but requires robust validation to address data heterogeneity, model interpretability, and ethical concerns. Future success hinges on interdisciplinary collaboration to develop standardized, equitable AI tools tailored for global healthcare settings. Advancing explainable AI and federated learning frameworks will be critical for bridging current implementation gaps and maximizing AI's potential in combating infectious diseases.

Introduction: Urinary tract infections (UTIs) caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria are challenging to treat. This systematic review evaluates bacteriophage therapy.

Research design and methods: A comprehensive search was conducted in PubMed, Embase, Web of Science, and Cochrane databases. Studies reporting bacteriophage therapy in UTIs, with outcomes related to safety and efficacy, were included. Studies unrelated to UTIs or lacking clear outcomes were excluded. Bias was assessed using RoB2 and JBI appraisal tools for series and case reports. Data were synthesized narratively due to study heterogeneity.

Results: From 576 articles screened, 12 studies met the inclusion criteria, comprising 89 participants, many with MDR and XDR infections. Phage therapy was generally well-tolerated. Efficacy varied, with some studies showing complete infection resolution, particularly in high-risk patients, while others reported partial or no improvement. Phage therapy often served as the sole viable treatment for XDR infections, yielding positive results despite small sample sizes and data heterogeneity.

Conclusions: Phage therapy shows promise as an alternative or adjunct to antibiotics for UTIs, especially those with limited treatment options, but uncertainties remain regarding dosing and administration. Further randomized trials are needed to confirm its efficacy and safety.

Protocol registration: www.crd.york.ac.uk/prospero identifier isCRD42023431617.

Introduction: The success in the coronavirus infectious disease 2019 (COVID-19) pandemic containment largely originated from vaccine- and infection-elicited immunity, with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection only marginally mitigated by the availability of antiviral drugs. The current lack of effective antiviral prophylactic and therapeutic agents in immunocompromised patients highlights the need for a radical change in the design of both drug manufacturing and clinical trials.

Areas covered: In this review, the authors summarize their suggestions for manufacturers, by reviewing classes of small molecule antivirals and passive immunotherapies and highlighting their limitations and unexploited potential.

Expert opinion: Molecular and serological testing of patients can improve appropriateness. Efficacy of antivirals can be improved by combining different therapeutic classes while preserving economical sustainability. Respiratory delivery should be better investigated in clinical trials.