Antimicrobial Agents and Chemotherapy最新文献

{"title":"Therapeutic effect of topical tamoxifen in murine cutaneous leishmaniasis caused by <i>Leishmania major</i>.","authors":"Parastoo Hassani-Abharian, Seyedamirmehdi Hejazi Dehaghani, Zabihollah Shahmoradi, Seyed Hossein Hejazi","doi":"10.1128/aac.00358-24","DOIUrl":"10.1128/aac.00358-24","url":null,"abstract":"<p><p>Iran is one of the endemic regions of cutaneous leishmaniasis (CL) caused by <i>Leishmania major</i>. There is no protective vaccine available against CL available, and the most effective strategy is a definitive treatment. Topical medications can be an excellent option for this purpose. Tamoxifen, a cancer control drug, has properties such as inducing cell apoptosis and anti-parasitic activity, which can be useful in controlling eukaryotic parasites such as <i>Leishmania</i>. The present study was conducted to investigate this theory in experimental CL caused by <i>L. major</i>. Forty female BALB/c mice aged 4 to 6 weeks were infected by injecting 1 × 10⁶ <i>L. major</i> metacyclics (MRHO/IR/75/ER) in the base of the tail. After the appearance of <i>Leishmania</i> nodules, mice were divided into five test and control groups. Two drug formulations were used: tamoxifen 1% in ethanol and tamoxifen citrate ointment 0.1%. The effectiveness of each formula was evaluated by determining the mean size of the ulcers and parasite burden after a 28-day treatment period. Both formulations showed reduced ulcer mean sizes. However, only the tamoxifen citrate ointment group demonstrated a statistically significant reduction (<i>P</i> = 0.049). The parasite burden decreased by 40.83% for the ointment group and 33.67% for the ethanol solution. Other control groups showed lesser reductions. This study partially demonstrated the effectiveness of topical tamoxifen on CL lesions in a murine model. It can provide a basis for further research on the therapeutic effects of different topical tamoxifen formulations.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0035824"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of collagen-related disorders and neurological events among patients with uncomplicated urinary tract infection following short treatment with fluoroquinolones: a cohort study.","authors":"Fanny S Mitrani-Gold, Shinyoung Ju, Myriam Drysdale, Anna Schultze, George Mu, John Logie","doi":"10.1128/aac.00690-24","DOIUrl":"10.1128/aac.00690-24","url":null,"abstract":"<p><p>Studies of fluoroquinolone (FQ) safety across indications show increased collagen/neurological adverse event (AE) risk, yet patients still receive FQs for uncomplicated urinary tract infections (uUTIs). This retrospective, cohort study investigated the risk of collagen/neurological AEs of special interest (AESIs) with short-term FQ use versus standard-of-care antibiotics (trimethoprim-sulfamethoxazole [SXT], nitrofurantoin [NTF]) among female outpatients with uUTIs. This study was conducted between December 2009 and 2019 using Optum's de-identified Clinformatics Data Mart Database. Adjusted absolute risks were calculated for composite/collagen/neurological AESIs (Kaplan-Meier cumulative hazards, after applying stabilized inverse probability of treatment weighting [sIPTW]). Adjusted hazard ratios were generated (sIPTW Cox proportional hazard modeling). Overall, 954,777 patients were included: FQ (<i>n</i> = 386,537 [40.5%]); SXT (<i>n</i> = 237,120 [24.8%]); NTF (<i>n</i> = 314,585 [32.9%]). Adjusted absolute risk range for collagen/neurological AESIs was <1%-4.5%. The hazard (95% CI) of tendon rupture was 25% higher with FQ versus SXT (1.25 [1.00-1.57]; <i>P</i> = 0.0497). Patients receiving FQ had lower hazard of neurological (0.95 [0.93-0.97]; <i>P</i> < 0.0001), central nervous system (0.85 [0.80-0.89]; <i>P</i> < 0.0001), and peripheral nervous system (0.96 [0.93-0.98]; <i>P</i> = 0.0016) AESIs versus NTF. Following a short treatment duration, FQs were associated with increased risk of tendon rupture versus SXT and reduced risk (adjusted hazard ratios) of neurological AESI versus NTF. Individual patient risk and consequences for known uncommon, yet serious, AEs need to inform appropriate antibiotic choice in treating uUTIs. Patient profile, efficacy, microbiome impact, safety, and surveillance should inform antibiotic selection for uUTI management, in accordance with guidelines.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0069024"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>bla</i>_GES-producing ST654 comprises a quarter of all carbapenem-resistant <i>Pseudomonas aeruginosa</i> in blood isolates from 15 hospitals.","authors":"Hadas Kon, Mor N Lurie-Weinberger, Moshe Bechor, Elizabeth Temkin, Ophir Kastel, David Schwartz, Alona Keren-Paz, Yehuda Carmeli","doi":"10.1128/aac.00965-24","DOIUrl":"10.1128/aac.00965-24","url":null,"abstract":"<p><p>Carbapenem-resistant <i>Pseudomonas aeruginosa</i> (CRPA) are of major clinical concern. We analyzed 85 <i>P</i>. <i>aeruginosa</i> blood isolates non-susceptible to carbapenems collected during 2021-2023 from 15 medical centers in Israel. We aimed to determine the prevalence of high-risk clones, examine clonality, test antibiotic susceptibility, and assess the presence of acquired resistance genes, including carbapenemases. Whole-genome sequencing was performed using Illumina sequencing technology. Susceptibly was determined using the broth microdilution method. In the entire sample, 43.5% were high-risk clones. A main clade (27.1% of isolates) found in multiple hospitals comprised 19 isolates belonging to the high-risk ST654 clone and four closely related isolates. The isolates in this main clade harbored a broad set of resistance genes, including GES-type genes, and 91% had a mutated outer membrane protein (OprD). Isolates in the main clade were uniformly tobramycin (TOB) resistant and 83% were ceftolozane/tazobactam resistant. In the entire sample, we found high resistance to most antipseudomonal agents, including new beta-lactam/beta-lactamase inhibitor combinations. No uniform susceptibility to an antipseudomonal agent was found. Carbapenemases were carried by 9.4% of isolates (5.9% <i>bla</i>_GES-5 and 3.5% <i>bla</i>_NDM-1) and <i>oprD</i> was mutated in 67% of isolates. Thus, the epidemiology of CRPA is explained by a combination of clonal expansion of a dominant high-risk clade and sporadic occurrence of mutated strains. Our findings highlight the importance of susceptibility testing using a wide panel of antibiotics when CRPA is detected. Prevention measures tracking and controlling emerging high-risk clades and clones are crucial to limit the spread of CRPA.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0096524"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multispecies emergence of dual <i>bla</i>_KPC/NDM carbapenemase-producing Enterobacterales recovered from invasive infections in Chile.","authors":"Ana M Quesille-Villalobos, Camila Solar, Jose R W Martínez, Lina Rivas, Valeria Quiroz, Ana M González, Roberto Riquelme-Neira, Juan A Ugalde, Anne Peters, Oscar Ortega-Recalde, Rafael Araos, Patricia García, Francois Lebreton, Jose M Munita, Lorena Diaz","doi":"10.1128/aac.01205-24","DOIUrl":"https://doi.org/10.1128/aac.01205-24","url":null,"abstract":"<p><p>Carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) represent a significant global threat. The emergence of dual CP-CRE is particularly alarming, as they can potentially compromise the efficacy of newer antibiotics, further decreasing therapeutic alternatives. Herein, we report the emergence of multiple species of CP-CRE recovered from invasive infections in Chile that simultaneously harbor <i>bla</i>_KPC and <i>bla</i>_NDM and provide an in-depth genomic characterization of these worrisome pathogens. We collected carbapenem-resistant Enterobacterales (CRE) isolates from invasive infections over a 4-year period, across 11 healthcare centers in Chile. Bacterial species and the presence of carbapenemase genes were confirmed using MALDI-TOF and PCR assays, respectively. Antimicrobial susceptibility testing was conducted through disk diffusion and broth microdilution methods. Dual CP-CRE isolates were subjected to short- and long-read whole genome sequencing to perform a detailed genomic characterization of the isolates and of the mobile genetic elements harboring the enzymes. From a total of 1,335 CRE isolates, we observed an increase in the prevalence of CP-CRE, from 11% in 2019 to 38% in 2022. A total of 11 dual CP-CRE isolates were recovered, all of them harboring <i>bla</i>_KPC and <i>bla</i>_NDM. Species corresponded to <i>Escherichia coli</i> (<i>n</i> = 6), <i>Klebsiella pneumoniae</i> (<i>n</i> = 2), <i>Klebsiella oxytoca</i> (<i>n</i> = 2), and <i>Citrobacter freundii</i> (<i>n</i> = 1). Dual CP-CRE isolates exhibited resistance to all tested β-lactams except for cefiderocol. The <i>bla</i>_KPC and <i>bla</i>_NDM encoding genes were located on independent plasmids. Platforms harboring <i>bla</i>_KPC were diverse and included IncN, IncF, and IncFIB plasmids. In contrast, <i>bla</i>_NDM-7 was only found on fairly conserved IncX3 plasmids. We report that a rapid increase of CP-CRE in Chile, alongside with the emergence of multiple bacterial species of CP-CRE co-harboring <i>bla</i>_KPC-2/3 and <i>bla</i>_NDM-7, underscores a critical public health challenge. Our data suggest that the dissemination of <i>bla</i>_NDM-7 was predominantly facilitated by IncX3 plasmids, whereas the spread of <i>bla</i>_KPC involved multiple plasmid backbones. Active surveillance and genomic monitoring are critical to inform public policy and curtail the spread of these highly resistant pathogens.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0120524"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783561","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":"Continuous infusion of piperacillin/tazobactam optimizes intraoperative antibiotic exposure in patients undergoing elective pelvic exenteration surgery.","authors":"Dwane Jackson, Marta Ulldemolins, Xin Liu, Craig Harris, Angela Tognolini, Steven C Wallis, Chandra Sumi, Suzanne L Parker, Victoria Eley, Jason A Roberts","doi":"10.1128/aac.01116-24","DOIUrl":"10.1128/aac.01116-24","url":null,"abstract":"<p><p>Patients undergoing elective pelvic exenteration surgery who receive piperacillin/tazobactam as surgical prophylaxis are at risk of suboptimal intraoperative antibiotic exposure. With this work, we aimed to study the plasma pharmacokinetics of piperacillin and tazobactam in this population to provide dosing recommendations that optimize antibiotic exposure. We developed a prospective, observational, pharmacokinetic study of piperacillin/tazobactam in patients undergoing pelvic exenteration. Population pharmacokinetic analysis and Monte Carlo simulations were performed with Monolix and Simulx software. Probabilities of target attainment of different dosing regimens against the minimum inhibitory concentration (MIC) breakpoints (8 and 16 mg/L) were calculated. Twelve patients were included in the study, with a median age of 50.0 years [interquartile interval (45.3-57.5)] and a median weight of 79.0 kg (61.3-88.3). Median surgical time was 10.5 h (9.8-11.7). A two-compartment linear model best fitted piperacillin and tazobactam data (190 plasma samples). Monte Carlo simulations showed that a lower dose of 2 g/0.25 g loading dose followed by 4 g/0.5 g q8h by continuous infusion provided ≥90% probability of target attainment for MIC = 16 mg/L for most of the patients. For non-continuous infusion regimens, only the 2-hourly bolus re-dosing achieved intraoperative concentrations of piperacillin ≥16 mg/L. Patients with weights ≥ 100 kg and glomerular filtration rates ≥ 120 mL/min required 4 g/0.5 g q6h by continuous infusion after a loading dose. In conclusion, continuous infusion of lower doses of piperacillin/tazobactam is as adequate as the 2-hourly re-dosing recommended by the current guidelines for surgical prophylaxis in pelvic exenteration. Patients with higher weights and glomerular filtration rates are at greater risk of inadequate exposure.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0111624"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidrug tolerance conferred by loss-of-function mutations in anti-sigma factor RshA of <i>Mycobacterium abscessus</i>.","authors":"Wassihun Wedajo Aragaw, Tewodros T Gebresilase, Dereje A Negatu, Véronique Dartois, Thomas Dick","doi":"10.1128/aac.01051-24","DOIUrl":"10.1128/aac.01051-24","url":null,"abstract":"<p><p>Low-level drug resistance in noncanonical pathways can constitute steppingstones toward acquisition of high-level on-target resistance mutations in the clinic. To capture these intermediate steps in <i>Mycobacterium abscessus</i> (Mab), we performed classic mutant selection experiments with moxifloxacin at twofold its minimum inhibitory concentration (MIC) on solid medium. We found that low-level resistance emerged reproducibly as loss-of-function mutations in RshA (MAB_3542c), an anti-sigma factor that negatively regulates activity of SigH, which orchestrates a response to oxidative stress in mycobacteria. Since oxidative stress is generated in response to many antibiotics, we went on to show that deletion of <i>rshA</i> confers low to moderate resistance-by measure of MIC-to a dozen agents recommended or evaluated for the treatment of Mab pulmonary infections. Interestingly, this moderate resistance was associated with a wide range of drug tolerance, up to 1,000-fold increased survival of a Δ<i>rshA</i> Mab mutant upon exposure to several β-lactams and DNA gyrase inhibitors. Consistent with the putative involvement of the SigH regulon, we showed that addition of the transcription inhibitor rifabutin (RBT) abrogated the high-tolerance phenotype of Δ<i>rshA</i> to representatives of the β-lactam and DNA gyrase inhibitor classes. In a survey of 10,000 whole Mab genome sequences, we identified several loss-of-function mutations in <i>rshA</i> as well as non-synonymous polymorphisms in two cysteine residues critical for interactions with SigH. Thus, the multidrug multiform resistance phenotype we have uncovered may not only constitute a step toward canonical resistance acquisition during treatment but also contribute directly to treatment failure.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0105124"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted delivery of flagellin by nebulization offers optimized respiratory immunity and defense against pneumococcal pneumonia.","authors":"Mara Baldry, Charlotte Costa, Yasmine Zeroual, Delphine Cayet, Jeoffrey Pardessus, Daphnée Soulard, Frédéric Wallet, Delphine Beury, David Hot, Ronan MacLoughlin, Nathalie Heuzé-Vourc'h, Jean-Claude Sirard, Christophe Carnoy","doi":"10.1128/aac.00866-24","DOIUrl":"10.1128/aac.00866-24","url":null,"abstract":"<p><p>Novel therapeutic strategies are urgently needed to combat pneumonia caused by <i>Streptococcus pneumoniae</i> strains resistant to standard-of-care antibiotics. Previous studies have shown that targeted stimulation of lung innate immune defenses through intranasal administration of the Toll-like receptor 5 agonist flagellin improves the treatment of pneumonia when combined with antibiotics. To promote translation to the clinic application, this study assessed the direct delivery of flagellin to the airways through nebulization using a vibrating mesh nebulizer in mice. Intranasal delivery achieved approximately 40% lung deposition of the administered flagellin dose, whereas nebulization yielded less than 1%. Despite these differences, nebulized flagellin induced transient activation of lung innate immunity characterized by cytokine/chemokine production and neutrophil infiltration into airways analogous to intranasal administration. Furthermore, inhalation by nebulization resulted in an accelerated resolution of systemic pro-inflammatory responses. Lastly, adjunct therapy combining nebulized flagellin and amoxicillin proved effective against antibiotic-resistant pneumococcal pneumonia in mice. We posit that flagellin aerosol therapy represents a safe and promising approach to address bacterial pneumonia within the context of antimicrobial resistance.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0086624"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Gatti and Pea, \"Are the pharmacokinetic data of meropenem studied in CSF of a mixed population composed of patients with cerebral infections and patients with extracerebral infections really helpful for clinicians treating CNS infections?\"","authors":"Sebastian G Wicha, Christina Kinast, Max Münchow, Sandra Wittova, Sebastian Greppmair, Alexandra K Kunzelmann, Michael Zoller, Michael Paal, Michael Vogeser, Katharina Habler, Thomas Weig, Nicole Terpolilli, Suzette Heck, Konstantinos Dimitriadis, Christina Scharf, Uwe Liebchen","doi":"10.1128/aac.01468-24","DOIUrl":"10.1128/aac.01468-24","url":null,"abstract":"","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0146824"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic drug monitoring of posaconazole delayed-release tablets and injections in pediatric patients.","authors":"Juan Wu, Changcheng Chen, Chengjuan Luo, Botao Ning, Yue Liu, Zhuo Li, Shunguo Zhang, Zhiling Li","doi":"10.1128/aac.01112-24","DOIUrl":"10.1128/aac.01112-24","url":null,"abstract":"<p><p>This study aimed to investigate the dose and trough concentration (<i>C</i>_min) of posaconazole delayed-release tablets and injections, and their correlation with efficacy and safety in pediatric patients. Patients younger than 18 years old received posaconazole delayed-release tablets or injections for prophylaxis or treatment of invasive fungal disease (IFD). Blood samples were collected to determine the plasma <i>C</i>_mins, and dose regimen adjustments were made if necessary. Clinical data were collected. A total of 210 <i>C</i>_mins of 113 pediatric patients were detected. The median <i>C</i>_mins were 1.0 and 1.3 mg/L for tablets and injections, respectively (<i>P</i> < 0.05). The median doses required to achieve the target <i>C</i>_min were about 6.0 mg/kg of body weight/day, and no statistical difference was observed between different age groups, formulations, or indications (<i>P</i> > 0.05). Concomitant treatment of tacrolimus and diarrhea were found to affect <i>C</i>_mins of tablets, while age, gender, and BMI were found to be correlated with <i>C</i>_mins of injections. IFD breakthrough occurred in 9.2% of patients with a median <i>C</i>_mins of 0.74 mg/L for prophylaxis, and infection progression occurred in 43.2% of patients with a median <i>C</i>_mins of 0.97 mg/L for treatment, respectively. Transaminitis was the most common adverse event. Posaconazole delayed-release tablets and injections are safe for prophylaxis and treatment of IFD in pediatric patients. An empirical initial dose of 6.0 mg/kg of body weight/day is appropriate for prophylaxis, while a higher dose should be required for the treatment of IFD. It is necessary to adjust the dose regimen according to the results of therapeutic drug monitoring.This study is registered with chictr.gov.cn under identifier ChiCTR2300070008.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0111224"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibacterial and antifungal drug concentrations in intra-abdominal abscesses: a prospective clinical study.","authors":"Alicia Cancela Costa, Fabian Grass, Ignacio Andres Cano, Florian Desgranges, Constant Delabays, Antonios Kritikos, Emmanouil Glampedakis, Thierry Buclin, Rafael Duran, Benoit Guery, Jean-Luc Pagani, Emilie Uldry, Laurent Arthur Decosterd, Frederic Lamoth","doi":"10.1128/aac.01178-24","DOIUrl":"https://doi.org/10.1128/aac.01178-24","url":null,"abstract":"<p><p>Secondary peritonitis with intra-abdominal abscesses (IAA) is difficult to treat because of the supposed low rate of penetration of antimicrobial drugs at the site of infection. However, clinical data about the actual bioavailability of antimicrobial drugs in IAA are scarce. This prospective observational study aimed at assessing the drug penetration in IAA of the antibiotics (piperacillin-tazobactam, carbapenems) and antifungals (fluconazole, echinocandins) that are usually recommended for the treatment of intra-abdominal infections. Patients with IAA who underwent a radiological or surgical drainage procedure were included. Antimicrobial drug concentrations were measured in IAA (C_IAA) and in a simultaneous plasma sample (C_plasma) to assess the C_IAA/C_plasma ratio. The pharmacodynamic target was defined as a C_IAA equal or superior to the clinical breakpoints of susceptibility of the most relevant intra-abdominal pathogens. Clinical outcomes were assessed at hospital discharge. A total of 54 antimicrobial drug measurements were performed in 39 IAA samples originating from 36 patients. Despite important inter-individual variability, piperacillin-tazobactam exhibited the highest C_IAA/C_plasma ratios (median 2). The rates of target achievement were 75%-80% for piperacillin-tazobactam and meropenem but 0% for imipenem and ertapenem. These results tended to correlate with clinical outcomes (96% success rate versus 73%, respectively, <i>P</i> = 0.07). Among antifungals, fluconazole exhibited higher C_IAA/C_plasma ratios and rates of target achievement compared to echinocandins. However, no differences in clinical outcomes were observed. These results provide unique information about antimicrobial drug penetration in IAA in real clinical conditions and suggest that piperacillin-tazobactam and meropenem may have better efficacy compared to imipenem or ertapenem.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0117824"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783534","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}