M Hassanzai, S Bahmany, H A W van Onzenoort, J van Oldenrijk, B C P Koch, B C M de Winter
{"title":"Clinical validation of an innovative dried whole-blood spot method to quantify simultaneously vancomycin and creatinine in adult patients.","authors":"M Hassanzai, S Bahmany, H A W van Onzenoort, J van Oldenrijk, B C P Koch, B C M de Winter","doi":"10.1093/jac/dkaf041","DOIUrl":"10.1093/jac/dkaf041","url":null,"abstract":"<p><strong>Background: </strong>A drawback of vancomycin use is the need for therapeutic drug monitoring and renal function monitoring. Traditional blood sampling involves drawing blood through a venepuncture. An alternative method, dried blood spot (DBS) sampling allows for self-sampling at home.</p><p><strong>Objectives: </strong>To clinically validate a DBS method for simultaneous monitoring of vancomycin and creatinine.</p><p><strong>Methods: </strong>Hospitalized adults treated with intravenous vancomycin were included (trial registration NCT05257070). Blood sampling consisted of one venepuncture and one finger prick. Whole-blood DBS samples from patients were obtained by applying one drop of whole blood onto Whatman 903 filtrate paper. Bland-Altman analyses were used to assess the agreement and bias between the two measurements. Patients were asked to state their preferences for one of the two sampling methods.</p><p><strong>Results: </strong>The study involved a final analysis of 39 patient samples for the clinical validation of vancomycin and 46 patient samples for the clinical validation of creatinine. The difference between plasma and DBS concentrations was ≤20% for 77% of the vancomycin samples, the mean bias was -0.1379% (95% limit of agreement -5.899-5.623). The difference between plasma and DBS concentrations was ≤20% for 89% of the creatinine samples, the mean bias was 2.656% (95% limit of agreement -26.16-31.47). Most patients (18 out of 31) preferred a finger prick over a venepuncture and 12 patients indicated no preference.</p><p><strong>Conclusions: </strong>This is the first study that successfully clinically validated a DBS sampling method for simultaneous measurement of vancomycin and creatinine, allowing for direct use in (outpatient) practice.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1097-1107"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449168","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}
Heather Weerdenburg, Hannah Walker, Gabrielle M Haeusler, Theresa Cole, Nigel Curtis, Stephen Duffull, Amanda Gwee
{"title":"Relationship between posaconazole concentrations and clinical outcomes in paediatric cancer and haematopoietic stem cell transplant recipients.","authors":"Heather Weerdenburg, Hannah Walker, Gabrielle M Haeusler, Theresa Cole, Nigel Curtis, Stephen Duffull, Amanda Gwee","doi":"10.1093/jac/dkae473","DOIUrl":"10.1093/jac/dkae473","url":null,"abstract":"<p><strong>Background: </strong>Posaconazole is used to prevent and treat invasive fungal infections (IFIs) in immunocompromised children, including those undergoing cancer treatment or HSCT. Despite differences in pharmacokinetics and IFI epidemiology between children and adults, therapeutic targets established in adult studies are often applied to children.</p><p><strong>Objectives: </strong>This systematic review evaluated the correlation between serum posaconazole concentrations and clinical outcomes of IFI prophylaxis and treatment in children with malignancies or HSCT recipients.</p><p><strong>Methods: </strong>Four databases (Cochrane, Embase, MEDLINE and PubMed) were searched for studies involving children (≤18 years old) receiving cancer treatment or HSCT that reported posaconazole serum concentrations and treatment outcomes. Animal studies, those primarily in adult (>18 years old) populations, non-malignant conditions (excluding HSCT), case reports, letters, editorials, conference abstracts and narrative reviews were excluded. Bias was assessed using the Newcastle-Ottawa scale.</p><p><strong>Results: </strong>Nineteen studies were included: 12 reported outcomes of posaconazole prophylaxis; two of treatment; and five of both. For prophylaxis, breakthrough IFIs occurred in 1%-12% of children. All but one occurred with serum concentrations of ≤0.7 mg/L. For treatment, no clear association was observed between a trough concentration of >1.0 mg/L and treatment efficacy, with poor outcomes reported for serum concentrations ranging between 0.2 and 4.8 mg/L. Overall, quality of evidence was poor (medium to high risk of bias for 18 papers, low risk for 1 paper) and there was variation in IFI definitions across studies.</p><p><strong>Conclusions: </strong>This review supports current recommendations for posaconazole prophylaxis in paediatric oncology and HSCT recipients. The absence of a clear correlation found between serum trough concentrations and treatment efficacy highlights the need for further studies to determine optimal therapeutic targets for treatment.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"897-907"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556789","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}
Hongjie Xing, Likuan Zhang, Chenglong Li, Stefan Schwarz, Dexi Li, Xiang-Dang Du
{"title":"Identification of a mepR mutation associated with tigecycline resistance in a clinical Staphylococcus aureus isolate.","authors":"Hongjie Xing, Likuan Zhang, Chenglong Li, Stefan Schwarz, Dexi Li, Xiang-Dang Du","doi":"10.1093/jac/dkaf034","DOIUrl":"10.1093/jac/dkaf034","url":null,"abstract":"<p><strong>Objectives: </strong>To identify the role and function of mepR variants in conferring resistance to tigecycline in clinical Staphylococcus aureus.</p><p><strong>Methods: </strong>The identification of the mepR and mepA variants in S. aureus DMB26a was performed by whole-genome sequencing and Blast alignment. The effects of the mepRD and mepAD variants of DMB26a on tigecycline susceptibility were evaluated through deletion and complementation analyses, as well as the determination of gene expression levels by RT-qPCR. Minimal inhibitory concentrations (MICs) for DMB26a and its mutants were determined by antimicrobial susceptibility testing.</p><p><strong>Results: </strong>A mepR variant, designated mepRD, and a mepA variant, designated mepAD, were identified in the clinical tigecycline-resistant S. aureus isolate DMB26a, which showed 78.72% and 84.92% amino acid identity to the MepR and MepA proteins of S. aureus NCTC 8325-4, respectively. Our findings revealed that deletion of mepA in the tigecycline-susceptible S. aureus RN4220 did not lead to a decrease in the MIC of tigecycline, and that there was also no change in the tigecycline MIC after the complementation with mepAD. Furthermore, we constructed a mepR + mepA deletion strain of S. aureus RN4220 and complemented it with mepRD + mepAD. In that case, a 4-fold increase in the tigecycline MIC was observed in S. aureus RN4220ΔmepR + mepA-pLI50_mepRD + mepAD compared with S. aureus RN4220ΔmepR + mepA. In addition, the relative expression of mepAD was increased 6-fold under the regulation of mepRD.</p><p><strong>Conclusions: </strong>This study provides the identification of a mepR variant contributing indirectly to tigecycline resistance via mediating increased expression of mepA in a clinical S. aureus isolate.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1059-1066"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364531","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}
Maria Mazzitelli, Claudia Cozzolino, Cristina Gervasoni, Simone Pagano, Serena Reato, Diego Ripamonti, Laura Comi, Vincenzo Scaglione, Daniele Mengato, Giuseppe Formica, Filippo Lagi, Antonio Cascio, Marcello Trizzino, Valentina Iannone, Damiano Farinacci, Annamaria Cattelan
{"title":"Durability of doravirine/dolutegravir dual combination in a multicentre cohort of elderly people with HIV.","authors":"Maria Mazzitelli, Claudia Cozzolino, Cristina Gervasoni, Simone Pagano, Serena Reato, Diego Ripamonti, Laura Comi, Vincenzo Scaglione, Daniele Mengato, Giuseppe Formica, Filippo Lagi, Antonio Cascio, Marcello Trizzino, Valentina Iannone, Damiano Farinacci, Annamaria Cattelan","doi":"10.1093/jac/dkaf039","DOIUrl":"10.1093/jac/dkaf039","url":null,"abstract":"<p><strong>Background: </strong>Even though the doravirine/dolutegravir combination is not mentioned by guidelines, real-life data has begun to emerge on its use. We aimed to describe the durability of doravirine/dolutegravir in a multicentre Italian cohort of elderly people with HIV (EPWH).</p><p><strong>Methods: </strong>We included all EPWH who ever started the doravirine/dolutegravir combination in six Italian centres and were followed up until treatment discontinuation (TD) for any reason (virological failure, death, treatment interruption for other reasons) on 31 March 2024. Descriptive statistics were used to describe the study population; Kaplan-Meier curves and Cox regression analyses were used to estimate incidence and associated predictors of time to TD.</p><p><strong>Results: </strong>We included 157 people; 61.1% were male, the median age was 59 years (IQR: 55-64), 75.2% had multimorbidity, 38.9% were on polypharmacy, and 91.1% had HIV-RNA of <50 copies/mL. No genotype resistance test was available for 19.4% of people who started doravirine/dolutegravir. The main reasons for starting doravirine/dolutegravir were high cardiovascular risk (51.6%), simplification (52.9%) and drug-drug interactions (25.5%). During a median follow-up of 27.85 (IQR: 22.92-31.79) months, 8 (5.1%) participants experienced TD (2 toxicities, 2 virological failures, 2 switches to long-acting drugs, 1 death and 1 transferred). The incidence of TD was 2.27 per 100 person-years of follow-up. Multivariable Cox regression analyses did not show any factors as predictors of TD.</p><p><strong>Conclusions: </strong>In this multicentre cohort of EPWH with clinical complexity, the doravirine/dolutegravir combination showed good durability over time. TD probability was very low, and no significant factors seem to predict it, likely due to the limited number and heterogeneity of cases of TD.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1089-1096"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390872","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":"Defective HIV-1 DNA pol sequences are not associated with HIV-1 DNA levels and drive most APOBEC-context drug resistance mutations.","authors":"Enagnon Kazali Alidjinou, Pauline Coulon, Macha Tetart, Aurélie Guigon, Ava Diarra, Emmanuelle Aissi, Hélène Bazus, Vincent Derdour, Agnès Meybeck, Nathalie Viget, Didier Hober, Laurence Bocket, Olivier Robineau","doi":"10.1093/jac/dkaf016","DOIUrl":"10.1093/jac/dkaf016","url":null,"abstract":"<p><strong>Introduction: </strong>The specificity of HIV-1 DNA genotypic resistance tests (GRTs) is hampered by the detection of the APOBEC-context drug resistance mutations (AC DRMs), usually harboured by replication-incompetent proviruses. We sought factors associated with defective sequences in the HIV-1 pol region. In addition, AC DRMs and their link with defective sequences were investigated.</p><p><strong>Methods: </strong>We included ART-treated patients with viral suppression or plasma viral load (VL) lower than 200 copies/mL, who underwent HIV-1 DNA genotyping, with successful sequencing of protease (PR), reverse transcriptase (RT) and integrase (IN) regions. Sequencing was performed using either the Sanger method or the Sentosa® NGS approach with a 20% cut-off. All hypermutated sequences and/or those containing at least one stop codon were considered defective.</p><p><strong>Results: </strong>A total of 613 HIV-1 DNA GRTs were analysed. Defective sequences were identified for 186 samples (30.3%) including 65 PR sequences, 92 RT sequences and 65 IN sequences. No association, including HIV-1 DNA levels, was found with the detection of defective pol sequences. A total of 226 AC DRMs were recorded in all sequences. Most of these mutations (78%) were harboured by defective sequences. AC DRMs did not emerge in the plasma viral population, and likely do not impact the virological response to ART.</p><p><strong>Conclusions: </strong>Defectives pol sequences were not associated with HIV-1 DNA levels and harboured most of the AC DRMs. Such mutations likely have no clinical impact, and should not be reported in routine practice. Consensus guidelines for reporting HIV-1 DNA GRTs are needed, especially for the assessment and management of AC DRMs.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"941-946"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028836","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}
Meron W Shiferaw, Monica A Donnelley, George R Thompson
{"title":"Prevalence of antifungal allergies in the general population.","authors":"Meron W Shiferaw, Monica A Donnelley, George R Thompson","doi":"10.1093/jac/dkaf037","DOIUrl":"10.1093/jac/dkaf037","url":null,"abstract":"<p><strong>Objectives: </strong>Invasive fungal infections are increasing in frequency and are associated with high patient morbidity and mortality. The use of antifungal therapy is thus also increasing, and patients reporting hypersensitivity or allergic reactions to the limited antifungal agents currently available complicates management. There are no prior studies defining the incidence of antifungal allergies reported by patients.</p><p><strong>Methods: </strong>A multicentre retrospective cohort review of all patient encounters at five large academic centres during 2023 was conducted. The primary outcome of this study was to find the prevalence of reported antifungal allergy across the University of California Health System, and secondarily determine the incidence of antifungal allergies among patients with documented administration of antifungal agent.</p><p><strong>Results: </strong>A total of 1 704 176 patients were included and 2602 patients exhibited a documented antifungal allergy. Prevalences of antifungal allergies were: fluconazole 1591 (0.093%), general antifungal allergy 395 (0.023%), triazole 361 (0.021%), itraconazole 145 (0.008%), amphotericin 110 (0.006%) and flucytosine <10 (0.001%). In the secondary outcome (incidence), 9829 patients received an antifungal agent and 298 reported an antifungal allergy (2.98%).</p><p><strong>Conclusions: </strong>Increasing age and use of antifungal therapy are associated with antifungal allergy prevalence. Antifungal allergy rates (prevalence and incidence) are also comparable to the rates reported for antibacterial agents and are highest with fluconazole.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1080-1083"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441016","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}
Shreya S Khera, Sharmistha Mishra, Oscar Javier Pico Espinosa, Kevin Gough, Charlie Tan, Sharon Walmsley, Alice Zhabokritsky, Malika Sharma, Adrienne K Chan, Jerome A Leis, Myo Minn Oo, Darrell H S Tan
{"title":"Early clinical experience using tecovirimat during the 2022 mpox epidemic in Toronto underscores ongoing clinical equipoise and the need for randomized trials.","authors":"Shreya S Khera, Sharmistha Mishra, Oscar Javier Pico Espinosa, Kevin Gough, Charlie Tan, Sharon Walmsley, Alice Zhabokritsky, Malika Sharma, Adrienne K Chan, Jerome A Leis, Myo Minn Oo, Darrell H S Tan","doi":"10.1093/jac/dkaf010","DOIUrl":"10.1093/jac/dkaf010","url":null,"abstract":"<p><strong>Background: </strong>Tecovirimat is an antiviral drug that was used compassionately for treating mpox in high-income settings during the 2022 global outbreak. Randomized controlled trials of its efficacy have not yet been completed.</p><p><strong>Objectives: </strong>To describe medication adherence, tolerability and clinical outcomes of adults receiving open-label tecovirimat for mpox infection.</p><p><strong>Methods: </strong>We conducted a prospective observational study and a retrospective case series of adults with mpox cared for at three academic hospitals in Toronto, Canada, between May and August 2022. We present a descriptive analysis of those prescribed oral tecovirimat 600 mg twice daily for 14 days for the management of severe manifestations.</p><p><strong>Results: </strong>Of 69 consenting participants, all were cisgender men, of whom 60 (87%) identified as gay, and 6 (9%) as bisexual. Nearly half (46%) were living with HIV, with a median (IQR) CD4 count of 468 (328-678) cells/mm3, among whom plasma HIV RNA was <20 copies/mL in 29 (91%) participants. One-third (33%) of participants received tecovirimat during the course of their illness. All participants experienced a decline in number of symptoms over time, but three treated participants initially experienced worsening symptoms despite therapy. Self-reported adherence to tecovirimat was excellent and tolerability was good.</p><p><strong>Conclusions: </strong>Our experience prescribing tecovirimat for mpox suggests it is safe and well tolerated, but the evolution of symptoms in some tecovirimat-treated patients underscores the ongoing uncertainty regarding its efficacy. In the context of considerable community demand for the drug, efforts should be made to connect mpox patients to rigorous randomized controlled trials, given this ongoing clinical equipoise.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"935-940"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441014","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":"High-level cefiderocol and ceftazidime/avibactam resistance in KPC-producing Klebsiella pneumoniae associated with mutations in KPC and the sensor histidine kinase EnvZ.","authors":"Jacqueline Findlay, Gabriele Bianco, Matteo Boattini, Patrice Nordmann","doi":"10.1093/jac/dkaf048","DOIUrl":"10.1093/jac/dkaf048","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1155-1157"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449244","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}
Adam Valcek, Diana Isabela Costescu Strachinaru, Patrick Soentjens, Anke Stoefs, Charles Van der Henst
{"title":"Identification of the czc metal efflux operon on a new plasmid type in a Pseudomonas aeruginosa clinical isolate belonging to ST357 O11.","authors":"Adam Valcek, Diana Isabela Costescu Strachinaru, Patrick Soentjens, Anke Stoefs, Charles Van der Henst","doi":"10.1093/jac/dkaf058","DOIUrl":"10.1093/jac/dkaf058","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1158-1160"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556843","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}
Alasdair P MacGowan, Pippa Griffin, Marie L G Attwood, Aimee M Daum, Matthew B Avison, Alan R Noel
{"title":"The pharmacodynamics of fosfomycin in combination with meropenem against Klebsiella pneumoniae studied in an in vitro model of infection.","authors":"Alasdair P MacGowan, Pippa Griffin, Marie L G Attwood, Aimee M Daum, Matthew B Avison, Alan R Noel","doi":"10.1093/jac/dkaf020","DOIUrl":"10.1093/jac/dkaf020","url":null,"abstract":"<p><strong>Background: </strong>Intravenous fosfomycin is used in combination with other antimicrobials for the management of severe and/or multidrug resistant Gram-negative infection. We used an in vitro pharmacokinetic model to study the combination of fosfomycin plus meropenem.</p><p><strong>Methods: </strong>Six Klebsiella pneumoniae fosfomycin MICs 8-1024 mg/L, meropenem MICs 0.06->1024 mg/L were employed. A dilutional pharmacokinetic model was used to generate fosfomycin exposure ranges up to a fAUC/MIC 500. Exposure-ranging experiments were repeated in the presence of meropenem at exposures associated with 2 g 8-hourly human dosing for strains with meropenem MICs ≥32 mg/L and at half the bacteriostatic fT > MIC for strains with MICs <32 mg/L. The log change in bacterial burden from the initial inoculum after 24 h drug exposure was taken as the primary endpoint and fAUC/MIC ratios for antibacterial effects were calculated. The risk of emergence of resistance was assessed by measurement of the population profiles.</p><p><strong>Results: </strong>Fosfomycin fAUC/MIC for bacteriostatic effect at 24 h were >500 for 5/6 K. pneumoniae strains. Meropenem fT > MIC for static effect were 16.6%-77.9% for the strains with meropenem MIC ≤ 64 mg/L. Strains with MICs of >1024 mg/L were not tested. Fosfomycin fAUC/MICs in the presence of meropenem were all reduced and for 5/6 strains the fAUC/MIC for static effect was <10 and <30 for a 2 log drop. Addition of meropenem suppressed changes in fosfomycin population profiles. There were no changes in meropenem population profiles exposed to the combination.</p><p><strong>Conclusion: </strong>Addition of meropenem to fosfomycin had a dramatic impact on the fosfomycin fAUC/MIC exposures required for bacteriostatic and bactericidal effects and suppressed emergence of fosfomycin resistance.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"967-975"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065746","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}