Expert Review of Anti-infective Therapy

Introduction Intra-abdominal candidiasis (IAC) is a serious complication in critically ill patients, particularly after abdominal surgery or trauma. Differentiating Candida colonization from invasive infection is crucial, as misdiagnosis can lead to inappropriate antifungal use, increased resistance, and worse outcomes. However, IAC remains underrecognized due to the limitations of conventional culture-based diagnostics. Relevant literature was identified through a non-systematic search of the PubMed database. Areas Covered This review highlights the challenges in diagnosing and managing IAC, focusing on the limitations of traditional culture methods and the potential of non-culture-based diagnostics. Biomarkers such as 1-3-β-D-glucan (BDG) and Candida albicans germ tube antibody (CAGTA), along with molecular assays, improve diagnostic accuracy but have varying sensitivity and specificity, requiring a multimodal approach. Management involves early diagnosis, source control, and targeted antifungal therapy. Current guidelines, largely based on candidemia, recommend echinocandins as first-line therapy, with fluconazole for stable patients and amphotericin B for resistant strains. Expert Opinion Despite advances, IAC-specific research is lacking, necessitating improved diagnostic tools and tailored therapies. There is a need for more targeted studies to refine diagnostic algorithms and therapeutic strategies. Future efforts should focus on developing rapid, high-sensitivity and specific diagnostic tools, optimizing antifungal stewardship, and individualizing treatment approaches.

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.

Introduction: Candida (Candidozyma) auris is an emerging fungal pathogen that poses a significant threat to immunocompromised patients. Its high mortality rates, resistance to multiple antifungal classes, and ability to spread rapidly in healthcare settings underscore the need for timely and accurate diagnosis to guide effective clinical management. Areas covered: This special report provides an updated overview of C. auris infections in immunocompromised hosts. It discusses current phenotypic and molecular diagnostic tools, antifungal susceptibility testing methods, and infection control strategies. Emerging therapies, including investigational antifungals and combination regimens, are also examined in light of evolving resistance patterns and clinical challenges. Expert opinion: Despite notable advances in diagnostics and treatment, major obstacles remain in the clinical management of C. auris, particularly in vulnerable populations. Barriers to guideline implementation, lack of standardized screening protocols, and limited access to novel antifungal agents continue to hinder effective response. Future efforts should focus on expanding diagnostic capacity, developing innovative therapies, and implementing targeted surveillance strategies to reduce the global burden of C. auris.

Introduction: The increasing prevalence of antimicrobial resistance in Neisseria gonorrhoeae threatens the efficacy of ceftriaxone, the last widely effective treatment for gonorrhea. Resistance mechanisms challenge the adequacy of current dosing strategies and minimum inhibitory concentration (MIC) thresholds, with treatment failures documented at MICs as low as 0.125 mcg/mL. Limited clinical and pharmacodynamic data complicate efforts to define optimal dosing and resistance breakpoints. Areas covered: This review examines the evolution of ceftriaxone dosing recommendations in response to resistance trends, explores the genetic and pharmacokinetic factors driving reduced susceptibility, and critically evaluates the CDC's MIC 'alert value' of 0.125 mcg/mL. Surveillance data are analyzed alongside pharmacokinetic/pharmacodynamic (PK/PD) models, including Monte Carlo simulations and hollow fiber infection models (HFIM). Practical challenges, including injection site tolerability, lidocaine safety, and dosing limits for intramuscular administration, are reviewed. Expert opinion: Current PK/PD data and IV tolerability studies support ceftriaxone dose escalation up to 3.5 g IM as a feasible outpatient limit for strains with MICs up to 0.5 mcg/mL. However, the MIC at which even high-dose regimens fail remains unknown. Urgent priorities include validating higher doses through clinical pharmacokinetic and outcomes studies, refining MIC thresholds by anatomical site, and evaluating novel agents for reliable pharyngeal eradication.

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.

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: Although febrile neutropenia (FN) remains a major cause of morbidity and mortality in patients with hematologic malignancies and hematopoietic stem cell transplant (HSCT) recipients, the increasing prevalence of antimicrobial resistance necessitates a reassessment of antibiotic prophylaxis and treatment strategies. Areas covered: This review explores the prophylactic and therapeutic use of antibiotics in FN management, with a particular focus on patients with hematologic malignancies - particularly acute leukemia - and HSCT recipients. Expert opinion: Challenges in FN management, including antibiotic prophylaxis and treatment optimization, remain due to the complexity of the condition. Pathogens with emerging antibacterial resistance cause significant concern in the management of patients. Particularly due to selection potential of resistant Gram-negative bacteria (GNB), fluoroquinolones (FQs) have become less attractive agents for prophylaxis. Whereas, emerging data may help to revitalize long-abandoned aminoglycoside containing combination therapies particularly in high-risk patients with presumed sepsis. With only a few agents available for highly resistant bacteria alternative treatment strategies including pharmacokinetic/pharmacodynamic (PK/PD) concerning antibiotic applications may be warranted. Carefully designed, randomized, controlled trials providing large scale data which then can be analyzed with emerging artificial intelligence (AI) technologies are needed. The results from such trials may allow a better, data-driven approaches for management of FN.

Introduction: Bloodstream infections (BSIs) caused by Staphylococcus aureus are common worldwide, representing one of the most relevant issues in clinical infectious diseases practice. In particular, BSIs by methicillin-resistant S. aureus (MRSA-BSI) are still today a challenge since mortality burden remains elevated although decades of research. Areas covered: The following topics regarding MRSA-BSI were reviewed and discussed by resorting to best available evidence retrieved from PubMed/MEDLINE up to October 2024: i) epidemiology; ii) microbiology; iii) classification, with a focus on complicated and not complicated forms; iv) the structured approach to the patient; v) pharmacokinetics and pharmacodynamics of the main antimicrobial options; vi) controversies regarding the best therapeutic approach. Expert opinion: Despite ongoing efforts to better stratify and manage MRSA-BSI, there is no universally accepted classification system accurately distinguishing between uncomplicated/low risk and complicated/high risk forms. Biomarkers such as interleukin(IL)-10 hold promise in order to enable a more precise stratification, premise for an appropriate treatment plan. There is a theoretical rationale for implementing a combination therapy including a beta-lactam agent upfront, especially for patients considered at higher risk of unfavorable outcomes, but further data are necessary, and the same applies to newer adjuvants. Novel microbiological techniques may help in guiding antimicrobial duration.

Introduction: Non-adherence to any therapy may be related to skipping drug doses, discontinuation of therapy, or loss of follow-up. It leads to the ineffectiveness of treatment, which is associated with obvious individual health losses, significant social and financial costs, and, in the case of infectious diseases, epidemiological consequences resulting from the possibility of further spread of infection. Areas covered: This review article analyses the causes and effects of non-adherence to treatment in patients infected with the hepatitis C virus (HCV). It also presents strategies to reduce the risk of non-adherence, which can be implemented by simplifying the treatment process, improving the flow of information between the doctor and the patient, as well as improving patients' knowledge about hepatitis C infection, and facilitating the understanding of the risks associated with non-adherence. Expert opinion: Since the treatment of HCV infections is highly effective in almost all patients who complete medication, no new drugs are to be expected in the coming years. Therefore, the primary attention in the global elimination of HCV will be focused on screening programs, improving the availability of drugs, and reducing the risk of non-adherence.

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.