Deckers C, Montesinos I, Plum PE
… +2 more, Bassetti M, Honoré PM
Expert Rev Anti Infect Ther
· 2025 Aug · PMID 40492348
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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 crucia...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.
Rajagopalan K, Bullano M, Gelone D
… +3 more, Bo T, Taduka V, Syed SS
Expert Rev Anti Infect Ther
· 2025 Aug · PMID 40478680
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BACKGROUND: Antiviral (AV) treatment options (e.g. Valganciclovir, VGCV) for cytomegalovirus (CMV) infections present a challenging benefit-risk profile (e.g. bone-marrow suppression) and potentially increased resistance...BACKGROUND: Antiviral (AV) treatment options (e.g. Valganciclovir, VGCV) for cytomegalovirus (CMV) infections present a challenging benefit-risk profile (e.g. bone-marrow suppression) and potentially increased resistance and refractoriness. Maribavir (MBV), a new AV treatment approved for refractory/resistant post-transplant CMV infections, demonstrated superior viral clearance in SOLSTICE trial. RESEARCH DESIGN AND METHODS: A retrospective lab-linked claims analysis of solid organ transplant (SOT) patients on VGCV (≥900 mg BID) treatment who newly switched to MBV (i.e. index date) between 1 December 2021 and31 December 2023. MBV treatment effectiveness (CMV viremia clearance/no treatment switch) and tolerability (e.g. leukopenia) during 3-months pre- and post-index was examined. RESULTS: Of the 1,247 post-SOT VGCV-treated patients, 81 switched to MBV; the mean age was 55 years, and 73% had kidney transplant. Among 33 with follow-up labs, 88% ( = 29) achieved viral clearance. Of the remaining 48 without follow-up labs, 60.4% ( = 29) did not switch to other AV treatments. The combined treatment effectiveness was 71.6%. Tolerability issues decreased after MBV initiation: with leukopenia, neutropenia, nausea, and diarrhea decreasing by 14.29%, 3.57%, 14.29%, and 17.86%, respectively. CONCLUSION: MBV-treated patients had 10-15% lower tolerability issues; over 7 in 10 demonstrated treatment effectiveness in this real-world analysis. MBV's favorable benefit-risk profile makes it a potentially valuable addition to the CMV treatment armamentarium. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT02931539.
Quindós G, Marcos-Arias C, Miranda-Cadena K
… +4 more, Sevillano E, Jauregizar N, Schneider J, Eraso E
Expert Rev Anti Infect Ther
· 2025 Aug · PMID 40464716
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INTRODUCTION: High worldwide prevalence and significant morbidity of vulvovaginal candidiasis (VVC) requires better therapeutic approaches to improve quality of life of affected women. Although treatment of acute episode...INTRODUCTION: High worldwide prevalence and significant morbidity of vulvovaginal candidiasis (VVC) requires better therapeutic approaches to improve quality of life of affected women. Although treatment of acute episodes is often straightforward, complicated and recurrent vulvovaginal candidiasis (RVVC) presents medical challenges. AREA COVERED: This review focuses on therapy of VVC particularly by topical antifungals , especially imidazoles, compared to oral treatment with fluconazole, itraconazole, ibrexafungerp, or oteseconazole. Candidiasis by non-, VVC in pregnant women and RVVC are complex challenges . Current treatment, alternatives, and roles played by topical azoles in VVC are highlighted. EXPERT OPINION: VVC requires personalized treatment considering whether the woman is pregnant or not, concomitant treatments, clinical presentations (acute or recurrent) and the species involved. Although therapeutic tools are increasing, the usefulness of topical drugs, such as clotrimazole and miconazole, is very relevant. In addition, we it is also necessary to expand the therapeutic tools with new antifungals and formulations, and repurposing current drugs against fluconazole-resistant species of .
Expert Rev Anti Infect Ther
· 2025 Aug · PMID 40436735
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INTRODUCTION: Infection continues to be one of the most common complications after solid organ transplantation (SOT). Past years have witnessed major advances in the diagnosis, prevention and treatment of post-transplant...INTRODUCTION: Infection continues to be one of the most common complications after solid organ transplantation (SOT). Past years have witnessed major advances in the diagnosis, prevention and treatment of post-transplant infection. Nevertheless, controversial issues and unmet needs remain. AREAS COVERED: We review recent contributions to the use of organs from hepatitis C or human immunodeficiency virus-positive donors or those with positive cultures for multidrug resistant organisms (MDROs), diagnostic next-generation sequencing, selective digestive decolonization (SDD), immune monitoring strategies for individualized risk assessment, vaccines and prophylactic monoclonal antibodies, and the prospects of adoptive T-cell immunotherapy and chimeric antigen receptor cell products. Based on these lessons, plausible future developments in the prevention and management of post-transplant infection are proposed. EXPERT COMMENTARY: We expect that current barriers for the acceptance of increased infection risk donors will be overcome, and that the arrival of new antibiotics will allow the use of organs from donors colonized or infected by MDROs. 'Pathogen-agnostic' high-throughput diagnostic approaches will progressively replace conventional microbiology methods. Prophylaxis will be individualized by means of peri-transplant SDD, a repertoire of immune biomarkers (including the changes in human virome), and passive pre-exposure immunization. Finally, advanced cellular therapies will become the standard care of SOT recipients.
Larcher R, Dinh A, Monnin B
… +5 more, Laffont-Lozes P, Loubet P, Lavigne JP, Bruyere F, Sotto A
Expert Rev Anti Infect Ther
· 2026 Jun · PMID 40435529
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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 D...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.
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 analyz...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.
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, a...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.
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 introd...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.
Posteraro B, Cosio T, Torelli R
… +5 more, De Carolis E, Magrì C, Posteraro P, De Angelis G, Sanguinetti M
Expert Rev Anti Infect Ther
· 2025 Aug · PMID 40356193
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INTRODUCTION: () 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 healt...INTRODUCTION: () 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 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 , 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 .
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 LA...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, < 0.01), solid organ tumor (OR 2.18, = 0.03), hemodialysis (OR 5.12, < 0.01), elevated lactate (OR 1.13, = 0.03), and vasopressor use (OR 4.48, < 0.01). Protective factors were surgery (OR 0.34, < 0.01), IV N-acetylcysteine (OR 0.12, < 0.01), oral N-acetylcysteine (OR 0.17, < 0.01), higher baseline platelets (OR 0.79, = 0.05), and acetaminophen (OR 0.42, < 0.01). The nomogram showed strong discrimination (AUC 0.834, < 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.
Expert Rev Anti Infect Ther
· 2025 Jun · PMID 40300086
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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 a...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 bacteremia and compare the effects of antibiotics used in...BACKGROUND: This study aims to evaluate the risk factors, clinical features, and clinical outcomes among pediatric hospitalized patients receiving treatment for 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 ( = 0.016, and = 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.