Journal of Antimicrobial Chemotherapy最新文献

{"title":"In vitro and clinical data demonstrate negligible risk of drug-drug interactions with opelconazole, a novel inhaled antifungal agent.","authors":"Lindsey M R Cass, John Ayrton, Roger J Brüggemann, Jerome Moore, Ubaldo Martin, Laura Grey, Michele Hyman, Lance Berman","doi":"10.1093/jac/dkaf384","DOIUrl":"https://doi.org/10.1093/jac/dkaf384","url":null,"abstract":"<p><strong>Background: </strong>Invasive fungal diseases (IFDs) cause high morbidity and mortality among immune-compromised patients. Triazoles, which are recommended to treat IFDs, inhibit and/or are substrates for the phase 1 cytochrome P450 (CYP) pathway that metabolizes many drugs and frequently result in drug-drug interactions (DDIs). Nebulized opelconazole is an investigational inhaled antifungal in development for the treatment of pulmonary aspergillosis.</p><p><strong>Methods: </strong>In vitro studies first assessed effects of opelconazole on CYP isoforms and human transporter protein interactions. Subsequently, a Phase 1 study in healthy volunteers assessed whether repeat daily dosing of inhaled opelconazole inhibited or induced CYP1A2 and CYP3A4 using the substrates caffeine and midazolam, respectively.</p><p><strong>Results: </strong>In vitro analyses confirmed that opelconazole interactions with human CYPs were limited to competitive inhibition of CYP3A4 and weak induction potential for CYP3A4 and CYP1A2. These interactions occurred at concentrations higher than those expected at steady state following clinical dosing. Inhibition of a limited range of transporter proteins occurred at micromolar concentrations of opelconazole, but it was not found to be a substrate for carrier transporters. In the Phase 1 healthy volunteer study, inhaled opelconazole at steady state demonstrated no inhibition/induction of CYP3A4 or CYP1A2 and was generally well tolerated. The Phase 1 study results confirmed that the potential for interactions of opelconazole with CYP3A4 and CYP1A2 substrates during concomitant use was negligible.</p><p><strong>Conclusions: </strong>Systemic steady-state concentrations achieved after clinical dosing of inhaled opelconazole are unlikely to be associated with CYP-mediated DDIs or transporter-mediated DDIs.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time to anti-cancer treatment resumption after SARS-CoV-2 infection in patients with active haematological diseases undergoing combined antiviral treatments.","authors":"E Matteini, C Pinnetti, F Frondizi, E Rando, M Chiuchiarelli, E Metafuni, I Mastrorosa, E Alma, V Mazzotta, R Santangelo, S Marchetti, M Sanguinetti, S Sica, C Torti, A Antinori, A Cingolani","doi":"10.1093/jac/dkaf342","DOIUrl":"https://doi.org/10.1093/jac/dkaf342","url":null,"abstract":"<p><strong>Background and objectives: </strong>The management of SARS-CoV-2-infected patients with haematological malignancies and active disease is challenging, particularly in determining when to restart cancer therapy. This study evaluated the time to resumption of haematological therapy in adults with active haematological malignancies affected by SARS-CoV-2 infection and treated with either single-drug regimens (SR) or combined regimens (CR).</p><p><strong>Materials and methods: </strong>An observational cohort study was set up including patients with active haematological disease treated for SARS-CoV-2 infection between January 2022 and December 2023. Kaplan-Meier estimates and Cox regression models were fitted to analyse the time to restarting anti-cancer therapy and factors associated with resumption within 60 days.</p><p><strong>Results: </strong>Of the 79 patients included, 68 (86%) received SR, and 11 (14%) received CR. Patients on CR were more likely to require oxygen support (P = 0.006) and to have additional causes of immunosuppression (P = <0.001) compared with those on SR. The median time to restart therapy did not significantly differ between groups (38 days [IQR 21-70] for SR versus 30 days [IQR 18-77] for CR; P = 0.46). By Fine-Gray competing risk regression analysis, pneumonia (HR 0.36, 95% CI 0.18-0.71), but not CR (HR 0.62, 95% CI 0.23-1.69), independently reduced the likelihood of restarting therapy within 60 days of SARS-CoV-2 diagnosis.</p><p><strong>Conclusions: </strong>Combination regimens for SARS-CoV-2 did not affect the time to restart haematological therapy, whereas the occurrence of pneumonia was associated with delayed resumption of chemotherapy. The real benefit of COVID-19 combination therapy in the setting of haematologic malignancies, particularly for early treatment strategies, should be referred to the evidence from randomized controlled trials.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antifungal treatment strategies and their impact on resistance development in clinical settings.","authors":"Norman Van Rhijn, P Lewis White","doi":"10.1093/jac/dkaf382","DOIUrl":"https://doi.org/10.1093/jac/dkaf382","url":null,"abstract":"<p><p>Invasive fungal diseases, particularly among immunocompromised patients, represent a growing clinical challenge due to limited therapeutic options, diagnostic delays and escalating antifungal resistance. Fungal pathogens employ diverse resistance mechanisms, including genetic mutations of antifungal target enzymes, biofilm formation, efflux pump overexpression and reduced drug penetration, which compromise the efficacy of clinically available antifungal classes. This review explores antifungal treatment modalities and evaluates approaches to mitigate resistance development. Advanced diagnostics and therapeutic drug monitoring are pivotal for enabling timely, targeted therapies and personalizing treatment plans, thus minimizing reliance on broad-spectrum agents. New antifungal agents, such as rezafungin, olorofim and fosmanogepix, along with long-acting and advanced formulations plus combination regimens, show substantial promise for managing resistance and improving treatment outcomes. Additionally, the development of immunotherapies and antifungal vaccines offers new avenues for bolstering host defences against fungal pathogens. Addressing antifungal resistance demands a multifaceted 'One Health' approach that integrates robust diagnostics, antifungal stewardship (AFS), precision medicine and collaborative global efforts. By advancing drug formulations, enhancing diagnostic tools and implementing forward-thinking AFS practices, the healthcare community can better tackle the escalating burden of fungal infections and deliver improved patient outcomes.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aztreonam-amoxicillin/clavulanate combination therapy against blaNDM-producing Enterobacterales infections.","authors":"Efrat Orenbuch-Harroch, Gabriella Snoyman, Munther Aqeel Nashashibi, Violeta Temper, Yonatan Oster, Daniel Grupel, Dan Reshef, Jacob Moran-Gilad, Jacob Strahilevitz","doi":"10.1093/jac/dkaf379","DOIUrl":"https://doi.org/10.1093/jac/dkaf379","url":null,"abstract":"<p><strong>Background: </strong>Aztreonam plus ceftazidime/avibactam is recommended against NDM-producing Enterobacterales. Pairing with clavulanate can also restore aztreonam's activity.</p><p><strong>Objectives: </strong>To report on the clinical experience with antimicrobial susceptibility testing-guided aztreonam therapy combined with β-lactamase inhibitors, particularly amoxicillin-clavulanate, against NDM-producing Enterobacterales infections.</p><p><strong>Methods: </strong>All patients with infections caused by NDM-producing Enterobacterales that were resistant to aztreonam monotherapy but demonstrated in vitro synergy and thus eligible for aztreonam combination therapy, who received ≥5 days of aztreonam-based combination therapy, were included. Gradient strip-crossing methodology was validated against broth microdilution for susceptibility testing. Clinical response was assessed at 30 days post-treatment.</p><p><strong>Results: </strong>Clinical cure was achieved in 78% (7/9) of aztreonam/amoxicillin-clavulanate patients and 56% (9/16) of aztreonam/ceftazidime-avibactam patients. Treatment duration averaged 11.8 and 11.6 days, respectively. Among 21 sequenced isolates, blaNDM-1 was most prevalent. In vitro synergy was demonstrated in 52% with clavulanate and 90% of isolates with avibactam. Gradient strip-crossing showed 80% essential agreement and 100% categorical agreement for both combinations. Transient hepatic enzyme elevations occurred in three liver transplant recipients.</p><p><strong>Conclusions: </strong>Our findings suggest aztreonam/amoxicillin-clavulanate combination therapy guided by gradient strip-crossing as a potential broad-spectrum-sparing strategy for selected patients with NDM-producing Enterobacterales infections.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of sodium zirconium cyclosilicate usage for hyperkalaemia secondary to sulfamethoxazole/trimethoprim therapy.","authors":"Dixie Pyles, Nicole Kovacic Scherrer, Erika Zarfoss Ponce, Amanda Jo Shigle","doi":"10.1093/jac/dkaf380","DOIUrl":"https://doi.org/10.1093/jac/dkaf380","url":null,"abstract":"<p><strong>Background: </strong>Sulfamethoxazole/trimethoprim is utilized to treat various infections, but its use can be limited by hyperkalaemia. Sodium zirconium cyclosilicate is a potassium binder, which has been shown to lower potassium in chronic kidney disease.</p><p><strong>Objectives: </strong>To determine the safety and efficacy of sodium zirconium cyclosilicate for patients experiencing sulfamethoxazole/trimethoprim-induced hyperkalaemia.</p><p><strong>Methods: </strong>Patients receiving treatment with sulfamethoxazole/trimethoprim and sodium zirconium cyclosilicate therapy concomitantly for at least 48 h between 2021 and 2024 were identified. Efficacy was evaluated by potassium change from baseline, proportion of patients achieving normokalaemia by 24 and 48 h, and time to potassium normalization. Safety was assessed by evaluating hypokalaemia occurrence while on sodium zirconium cyclosilicate therapy.</p><p><strong>Results: </strong>There were 22 patients included. The median total daily dose of sulfamethoxazole/trimethoprim was 960 mg or 15 mg/kg/day. Fifteen patients (68%) were treated for confirmed Stenotrophomonas maltophilia or Pneumocystis pneumonia infections. Eight patients (36%) received a loading dose of sodium zirconium cyclosilicate 10 g three times daily for 48 h prior to receiving 10 g daily. The median difference in potassium at baseline and the end of sodium zirconium cyclosilicate therapy was 0.9 mmol/L. Fourteen patients of 22 (64%) and 19 of 21 patients (90%) achieved normokalaemia by 24 and 48 h, respectively. The median time to potassium normalization was 23.5 h. There were no instances of hypokalaemia while on sodium zirconium cyclosilicate therapy.</p><p><strong>Conclusions: </strong>Sodium zirconium cyclosilicate was efficacious at lowering elevated potassium in patients receiving sulfamethoxazole/trimethoprim therapy without inducing hypokalaemia. This suggests sodium zirconium cyclosilicate may be considered in patients with treatment-limiting hyperkalaemia due to sulfamethoxazole/trimethoprim, especially when sulfamethoxazole/trimethoprim is preferred therapy.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative in vitro activity of ceftazidime-avibactam plus aztreonam and the fixed combination aztreonam/avibactam against multidrug-resistant Pseudomonas aeruginosa.","authors":"Sophie E Müller, Sabryna Junker, Jacqueline Rehner, Maximilian Förster, Andreas Keller, Leidy-Alejandra G Molano, Sören L Becker","doi":"10.1093/jac/dkaf376","DOIUrl":"https://doi.org/10.1093/jac/dkaf376","url":null,"abstract":"<p><strong>Background and objectives: </strong>MDR Pseudomonas aeruginosa is difficult to treat, despite some new beta-lactam/beta-lactamase inhibitors. A combination of ceftazidime-avibactam and aztreonam (CAZ/AVI + AZT) is frequently used to treat Gram-negative bacteria expressing metallo-beta-lactamases. A fixed combination of aztreonam/avibactam was recently licenced for use in Europe, but it remains unknown whether there are differences between both options for use against P. aeruginosa. This study evaluates the comparative in vitro efficacy of the fixed combination aztreonam/avibactam compared to the three antibiotics CAZ/AVI + AZT against clinical MDR P. aeruginosa isolates.</p><p><strong>Methods: </strong>MICs for aztreonam/avibactam and CAZ/AVI + AZT were determined in 38 MDR P. aeruginosa isolates recovered from routine diagnostics using broth microdilution with checkerboard assays in triplicates as the reference method. Fractional inhibitory concentration (FIC) indices were calculated. Whole-genome sequencing was performed on all isolates.</p><p><strong>Results: </strong>At a fixed ceftazidime concentration of 8 mg/L (EUCAST breakpoint), 25 isolates exhibited lower MICs for CAZ/AVI + AZT compared to aztreonam/avibactam alone in microdilution assays. On FIC analysis, additive and synergistic effects were seen in 28 and 2 cases, respectively. Verona integron-encoded metallo-beta-lactamase (VIM) was the most prevalent carbapenemase (21/38 isolates), followed by Imipenemase (IMP, 4/38) and New Delhi metallo-beta-lactamase (NDM, 2/38). Lower MICs were observed for the combination CAZ/AVI + AZT in isolates carrying VIM-2 as compared to VIM-1.</p><p><strong>Conclusions: </strong>In vitro testing of CAZ/AVI + AZT revealed increased in vitro susceptibility among MDR P. aeruginosa isolates in comparison to the fixed combination of aztreonam/avibactam.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrice-weekly post-haemodialysis ceftazidime can achieve adequate pre-dialysis concentrations and clinical cure in patients with melioidosis.","authors":"Simon Smith, Christopher W Reilly, James Stewart, Thomas Ragh, Vanessa J Muller, Ibrahim Ismail, Josh Hanson","doi":"10.1093/jac/dkaf383","DOIUrl":"https://doi.org/10.1093/jac/dkaf383","url":null,"abstract":"<p><strong>Background: </strong>Melioidosis is an opportunistic infection caused by Burkholderia pseudomallei. Prolonged IV antibiotic therapy is required to cure the disease. Current guidelines recommend daily ceftazidime for people receiving chronic intermittent haemodialysis (CIHD).</p><p><strong>Methods: </strong>We reviewed all cases of culture-confirmed B. pseudomallei infection from 2016 to 2025. In patients receiving CIHD, we recorded their weekly CIHD schedule, their ceftazidime dosing regimen, the ceftazidime MIC for their initial B. pseudomallei isolate and all pre-dialysis ceftazidime concentrations.</p><p><strong>Results: </strong>There were 449 cases of melioidosis; 26 (5.8%) occurred in people already receiving-or who were commenced on-CIHD during their hospital admission. Of these, 24 (92%) survived to the completion of their intensive IV phase of antibiotic therapy. There were nine who had ceftazidime pre-dialysis concentrations measured. Of these, eight were commenced on ceftazidime 2 g daily, but five had their dosing regimen changed; this was a daily dose reduction in three and a change to thrice-weekly dosing regimen of 2 g/2 g/3 g post-haemodialysis in two. One patient was administered thrice-weekly dosing post-haemodialysis for the duration of their intensive phase. No cases had evidence of neurotoxicity, all received oral eradication therapy, and all had clinical cure.</p><p><strong>Conclusions: </strong>In patients receiving thrice-weekly CIHD, post-haemodialysis ceftazidime administered 2 g/2 g/3 g achieved adequate serum pre-dialysis concentrations, can achieve good clinical outcomes and may be a potential treatment approach for people with melioidosis. The availability of therapeutic drug monitoring and clinical breakpoints suggest a more individualized approach is possible in people with melioidosis receiving CIHD.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The long walk to a short half-life: the discovery of augmented renal clearance and its impact on antibiotic dosing.","authors":"Jeffrey Lipman, Russell E Lewis","doi":"10.1093/jac/dkaf378","DOIUrl":"https://doi.org/10.1093/jac/dkaf378","url":null,"abstract":"<p><strong>Background and objectives: </strong>Renal function monitoring traditionally focuses on detecting impairment to prevent antibiotic toxicity. However, augmented renal clearance (ARC) represents the opposite challenge-enhanced elimination causing subtherapeutic drug concentrations. The aim of this review is to describe ARC's discovery and its impact on antibiotic therapy over two decades.</p><p><strong>Methods: </strong>Narrative commentary examining ARC's discovery, clinical significance, diagnostic challenges and management strategies for antibiotic dosing in critically ill patients, with future research priorities.</p><p><strong>Results: </strong>ARC was first noted in the late 1990s at Baragwanath Hospital, South Africa, where unexpectedly high creatinine clearance rates (>200 mL/min) were measured in ICU patients. Subsequent pharmacokinetic studies confirmed elevated antibiotic clearance with reduced systemic exposures. ARC, defined as creatinine clearance of >130 mL/min/1.73 m2, occurs in 65%-80% of critically ill patients with normal serum creatinine, particularly younger patients with sepsis, trauma or burns. The phenomenon results from increased cardiac output and renal blood flow during systemic inflammatory responses, can persist for weeks after ICU admission, and affects all renally eliminated drugs. ARC is often undiagnosed unless some form of creatine clearance is directly measured. Importantly, ARC is a major risk factor for antibiotic failure and resistance selection.</p><p><strong>Conclusions: </strong>ARC represents a significant but underrecognized challenge affecting antibiotic dosing in critically ill patients. Therapeutic drug monitoring remains the most reliable method to ensure adequate antibiotic exposure. Future research priorities include validated predictive models, simpler diagnostic methods and evidence-based dosing guidelines for high-risk populations.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequential antibiotic exposure restores antibiotic susceptibility.","authors":"Farhan R Chowdhury, Brandon L Findlay","doi":"10.1093/jac/dkaf350","DOIUrl":"https://doi.org/10.1093/jac/dkaf350","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of antibiotic resistance continues to rise, rendering many valuable antimicrobial drugs ineffective. Pairwise cyclic antibiotic therapy, where treatment is rapidly switched between two antibiotics, has been demonstrated in vitro to limit the evolution of antibiotic resistance. However, what happens when resistance inevitably evolves to one of the drugs?</p><p><strong>Methods: </strong>In this study, we perform over 450 evolution experiments to test the resilience of four proposed cyclic therapies. We use soft agar gradient evolution and 'flat plates' to identify resistance trade-offs that are resilient to compensatory mitigation. Resensitizations were detected by antimicrobial susceptibility assays, and their mechanistic underpinnings were elucidated via genomic and phenotypic analyses.</p><p><strong>Results: </strong>Resistance evolves readily and collateral sensitivity (CS) (where resistance to drug A leads to hypersensitivity to drug B) does not hinder the evolution of multidrug resistance and does not predict or promote resensitization. However, if resistance to drug B increases susceptibility to A, a phenomenon we term backward CS, resistance to A can be reduced or even reversed. For example, we show that Escherichia coli cells frequently become hypersensitive to β-lactams upon aminoglycoside resistance acquisition, due to conflicting modifications to the proton motive force and efflux pumps. We also find for the first time that polymyxin B resistance can be entirely reversed by exposure to tigecycline, through the acquisition of compensatory mutations that reduce the fitness penalty of tigecycline resistance.</p><p><strong>Conclusions: </strong>The longevity of drug cycling protocols can be significantly improved by leveraging backwards CS to resensitize cells as antibiotic resistance evolves.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of topical hydrophilic gel of paromomycin combined with systemic or locally administered leishmanicidal drugs for treatment of experimental leishmaniasis caused by Leishmania (Viannia) braziliensis.","authors":"Líndicy Leidicy Alves, Dian Carlo Pinheiro Rosa, Mariana Lourenço Freire, Gláucia Fernandes Cota, Ana Rabello, Eliane de Morais-Teixeira","doi":"10.1093/jac/dkaf362","DOIUrl":"https://doi.org/10.1093/jac/dkaf362","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed at evaluating the combination of a topical hydrophilic gel of paromomycin (PA) with intralesion meglumine antimoniate (Glu IL) or systemic administration of liposomal amphotericin B (AmphLipo) for the treatment of cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis.</p><p><strong>Materials and methods: </strong>Initially, to guide the subsequent evaluation of binary combinations, in vivo studies were conducted to evaluate the different therapeutic regimens in monotherapy: PA, twice a day for 30 consecutive days, AmphLipo, single dose or five doses (both with a total dose of 10 mg/kg) and Glu IL, single lesion infiltration (weekly or biweekly). Clinical efficacy was evaluated by measuring the size of the lesion and parasitological efficacy by limited dilution assay of the parasite culture.</p><p><strong>Results: </strong>PA showed a tendency to reduce the size of the lesion, but without a significant difference in relation to the control. AmphLipo reduced the parasite load in the spleen (P < 0.05), but there was no difference in the size of the lesion between the treated groups and the control group. Glu IL showed complete epithelialization in 80% (weekly) and 100% (fortnightly) of the animals (P < 0.05) but did not reduce the parasite load. Instead, all binary combinations (PA + GluIL, PA + AmphLipo and GluIL + AmphLipo) reduced the size of the lesions by 100% (P < 0.05). No animal showed weight loss or toxic effects, such as ruffled fur, aggressiveness, diarrhoea or other adverse reactions.</p><p><strong>Conclusions: </strong>The combinations tested were more effective in healing the lesions than the monotherapies, representing a promising alternative for the treatment of cutaneous leishmaniasis and encouraging new clinical trials.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}