Journal of Antimicrobial Chemotherapy最新文献

{"title":"Surveying genetic markers of antibiotic resistance and genomic background in Chlamydia trachomatis: insights from a multiplex NGS-based approach in clinical strains from Portugal.","authors":"Zohra Lodhia, Jorge Costa Da Silva, Cristina Correia, Dora Cordeiro, Inês João, Teresa Carreira, Sandra Schäfer, Elzara Aliyeva, Clara Portugal, Isabel Monge, Elsa Gonçalves, Susana Matos, Ana Paula Dias, Rita Côrte-Real, Dina Carpinteiro, Sílvia Duarte, Luís Vieira, João Paulo Gomes, Vítor Borges, Maria José Borrego","doi":"10.1093/jac/dkaf036","DOIUrl":"10.1093/jac/dkaf036","url":null,"abstract":"<p><strong>Objectives: </strong>To survey genetic markers of potential antimicrobial resistance (AMR) to macrolides and fluoroquinolones among Chlamydia trachomatis-positive samples from the collection of the Portuguese National Reference Laboratory for Sexually Transmitted Infections (STIs), and explore a multiplex PCR approach coupled with NGS to provide complementary information regarding a strain's genomic backbone.</p><p><strong>Methods: </strong>A total of 502 C. trachomatis-positive samples, mostly anorectal exudates, were subjected to PCR and sequencing of five targets, including loci potentially driving AMR (23S rRNA, gyrA and parC) and loci potentially informative about a strain's genomic backbone with emphasis on differentiation of lymphogranuloma venereum (LGV)/non-LGV and L2/L2b (a 9 bp insertion in pmpH, a 74 bp insertion upstream from CT105 and the polymorphic CT442).</p><p><strong>Results: </strong>No samples evidenced 23S rRNA mutations recognizably linked to macrolide resistance. Three samples harboured the Ser83Ile mutation in GyrA putatively driving fluoroquinolone resistance: two recombinant L2-L2b/D-Da (0.4%) and one L2 (0.2%). The screened regions in pmpH, upstream CT105 and CT442 were fully concordant with LGV/non-LGV differentiation. As expected, the pmpH L2b-specific genetic trait locus was detected in all L2b and recombinant L2-L2b/D-Da ompA genotypes, but also in 96.0% of L2 specimens, which also likely possess an L2b genomic backbone. The insertion upstream from CT105 exhibited full LGV specificity, constituting a promising target for the development of rapid LGV diagnostic assays.</p><p><strong>Conclusions: </strong>This study contributes to enhancing the knowledge of C. trachomatis molecular epidemiology, suggesting that the known genetic determinants of AMR are not disseminated in clinical C. trachomatis strains, and presents an exploratory approach that can be suitable for LGV/non-LGV and L2/L2b genomic background differentiation.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1072-1079"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441018","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":"Vonoprazan improves the efficacy of bismuth quadruple therapy containing doxycycline and metronidazole as first-line Helicobacter pylori treatment in penicillin-allergic patients: a randomized controlled trial.","authors":"Tianlian Yan, Jinghua Wang, Renke Zhu, Dan Ma, Jianguo Gao, Jiewei Wang, Ye Chen, Kefang Sun, Qing Gu, Lan Li","doi":"10.1093/jac/dkae467","DOIUrl":"10.1093/jac/dkae467","url":null,"abstract":"<p><strong>Background: </strong>Helicobacter pylori eradication in penicillin-allergic patients presents challenges. Options of effective regimens are lacking in areas where tetracycline is unavailable.</p><p><strong>Objectives: </strong>To evaluate the efficacy of replacing the proton pump inhibitor (PPI) with a potassium-competitive acid blocker (P-CAB, vonoprazan) in standard bismuth quadruple therapy containing doxycycline and metronidazole as a first-line treatment for H. pylori.</p><p><strong>Methods: </strong>This prospective randomized clinical trial enrolled 332 naive patients with H. pylori infection and penicillin allergy. Participants were randomly assigned in a 1:1 ratio to either the 14 day P-CAB/BDM group (vonoprazan 20 mg twice daily, colloidal bismuth 200 mg twice daily, doxycycline 100 mg twice daily and metronidazole 400 mg three times daily) or the 14 day PPI/BDM group (rabeprazole 10 mg twice daily, and the same dose of the three other drugs as in the 14 day P-CAB/BDM group).</p><p><strong>Results: </strong>Eradication rates in the P-CAB/BDM and PPI/BDM groups were 90.4% and 71.1% (P value for superiority was 0.013), respectively, by ITT analysis. The efficacy of P-CAB/BDM remained non-inferior and even superior to PPI/BDM therapy in all ITT, modified ITT and PP analyses. The overall frequency of adverse events (39.8% and 40.4%; P = 0.911) and compliance (88.0% and 91.0%; P = 0.372) were similar between P-CAB and PPI regimens. Patients with higher body surface area were significantly associated with eradication failure in both groups (P < 0.05).</p><p><strong>Conclusions: </strong>The 14 day P-CAB/BDM therapy provided a satisfactory eradication rate of >90% (ITT analysis) and had a good safety profile as first-line H. pylori therapy, providing an alternative option for penicillin-allergic patients.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"927-934"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573032","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":"rpoB mutations and their association with rifampicin resistance in clinical Staphylococcus epidermidis.","authors":"Sofie Marie Edslev, Mia Aarris, Karen Leth Nielsen, Frederik B Hertz, Thor Bech Johannesen, Camille Kolenda, Frederic Laurent, Emeli Månsson, Bo Söderquist, Marc Stegger","doi":"10.1093/jac/dkaf035","DOIUrl":"10.1093/jac/dkaf035","url":null,"abstract":"<p><strong>Background: </strong>Staphylococcus epidermidis is a ubiquitous member of the healthy skin and mucous microbiota but is also an opportunistic pathogen responsible for various infections, often treated with antibiotics like rifampicin. Resistance to rifampicin in S. epidermidis arises primarily through nonsynonymous mutations in the rpoB gene.</p><p><strong>Objectives: </strong>To investigate the prevalence of rpoB mutations and their association with phenotypic rifampicin resistance in clinical S. epidermidis isolates from Denmark, France, and Sweden.</p><p><strong>Methods: </strong>All clinical isolates (N = 942) were whole-genome sequenced to identify mutations in rpoB and subsequently linked to phenotypic rifampicin resistance based on antimicrobial susceptibility testing.</p><p><strong>Results: </strong>A total of 64 (6.8%) isolates were resistant to rifampicin. They carried all mutational changes in the rifampicin resistance-determining region (RRDR). Among 12 identified nonsynonymous mutations, 11 were exclusively observed in resistant strains, including novel mutations not previously described in S. epidermidis.</p><p><strong>Conclusions: </strong>This study highlights the diverse genetic variants of rpoB associated with rifampicin resistance in clinical S. epidermidis isolates, including novel mutations. The strong correlation between mutational changes in RRDR and phenotypic resistance reinforces the role of rpoB mutations as a primary mechanism of resistance in clinical isolates.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1067-1071"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364610","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":"One day in Denmark: whole-genome sequence-based analysis of Escherichia coli isolates from clinical settings.","authors":"Ana Rita Rebelo, Valeria Bortolaia, Pimlapas Leekitcharoenphon, Dennis Schrøder Hansen, Hans Linde Nielsen, Svend Ellermann-Eriksen, Michael Kemp, Bent Løwe Røder, Niels Frimodt-Møller, Turid Snekloth Søndergaard, John Eugenio Coia, Claus Østergaard, Henrik Westh, Frank M Aarestrup","doi":"10.1093/jac/dkaf028","DOIUrl":"10.1093/jac/dkaf028","url":null,"abstract":"<p><strong>Background: </strong>WGS can potentially be routinely used in clinical microbiology settings, especially with the increase in sequencing accuracy and decrease in cost. Escherichia coli is the most common bacterial species analysed in those settings, thus fast and accurate diagnostics can lead to reductions in morbidity, mortality and healthcare costs.</p><p><strong>Objectives: </strong>To evaluate WGS for diagnostics and surveillance in a collection of clinical E. coli; to examine the pool of antimicrobial resistance (AMR) determinants circulating in Denmark and the most frequent STs; and to evaluate core-genome MLST (cgMLST) and SNP-based clustering approaches for detecting genetically related isolates.</p><p><strong>Methods: </strong>We analysed the genomes of 699 E. coli isolates collected throughout all Danish Clinical Microbiology Laboratories. We used rMLST and KmerFinder for species identification, ResFinder for prediction of AMR, and PlasmidFinder for plasmid identification. We used Center for Genomic Epidemiology MLST, cgMLSTFinder and CSI Phylogeny to perform typing and clustering analysis.</p><p><strong>Results: </strong>Genetic AMR determinants were detected in 56.2% of isolates. We identified 182 MLSTs, most frequently ST-69, ST-73, ST-95 and ST-131. Using a maximum 15-allele difference as the threshold for genetic relatedness, we identified 23 clusters. SNP-based phylogenetic analysis within clusters revealed from 0 to 13 SNPs, except two cases with 111 and 461 SNPs.</p><p><strong>Conclusions: </strong>WGS data are useful to characterize clinical E. coli isolates, including predicting AMR profiles and subtyping in concordance with surveillance data. We have shown that it is possible to adequately cluster isolates through a cgMLST approach, but it remains necessary to define proper interpretative criteria.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1011-1021"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065612","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":"Type IV PilD mutant stimulates the formation of persister cells in Pseudomonas aeruginosa.","authors":"Huifang Qiu, Weijun Dai","doi":"10.1093/jac/dkaf030","DOIUrl":"10.1093/jac/dkaf030","url":null,"abstract":"<p><strong>Background: </strong>Pseudomonas aeruginosa clinical isolates that lack motility do not express type IV pilin, yet the biological roles of this absence in the infection process remain poorly understood.</p><p><strong>Objectives: </strong>We asked whether the absence of motility in these bacteria is associated with increased antibiotic persistence.</p><p><strong>Methods: </strong>In this study, we analysed type IV PilD protein sequences in the database and conducted antibiotic-tolerant persister cell assays.</p><p><strong>Results: </strong>We found that PilD variants were common in P. aeruginosa clinical isolates. Our results revealed that inactivation of PilD resulted in a significantly higher level of surviving persister cells following ciprofloxacin treatment. This PilD-mediated persistence did not involve previously described mechanisms, such as phenazine pyocyanin, biofilm or stringent response.</p><p><strong>Conclusions: </strong>Our findings connect the non-motility of clinical P. aeruginosa isolates with the survival of persister cells, highlighting the clinical significance for the development of strategies to eradicate P. aeruginosa infections.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1031-1036"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189186","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":"Assessing the appropriateness of antifungal prescribing: key results from the implementation of a novel audit tool in Australian hospitals.","authors":"A Khanina, N Singh, R James, D C M Kong, M A Slavin, K A Thursky","doi":"10.1093/jac/dkaf044","DOIUrl":"10.1093/jac/dkaf044","url":null,"abstract":"<p><strong>Objectives: </strong>To utilize the Antifungal National Antimicrobial Prescribing Survey (Antifungal NAPS), a novel tool utilizing international consensus metrics for antifungal stewardship, to assess the quality of systemic antifungal prescribing in Australian hospitals, in order to identify quality improvement targets.</p><p><strong>Methods: </strong>Participating hospitals were directed to audit all systemic antifungals or focus on a specific antifungal drug or class. Data entry into the Antifungal NAPS online portal occurred between October 2022 and June 2023. The data collection tool comprised patient details, reasons precluding use of antifungals, prescription details (guideline compliance, appropriateness, and reasons for inappropriate prescribing) and patient outcomes. Descriptive statistics were used to analyse the data.</p><p><strong>Results: </strong>Eleven hospitals contributed data for 516 prescriptions for 438 patients. Of these, 77.1% of prescriptions were appropriate, with the highest appropriateness for prophylactic (189/222; 85.1%), followed by directed (105/130; 80.8%) and empirical therapy (104/164; 63.4%). Fluconazole was the most commonly prescribed agent, which had the lowest rate of appropriateness (132/209; 63.2%). The most common reasons for inappropriate prescribing were no antifungal required (35/105; 33.3%), incorrect dose or frequency (30/105; 28.6%) and incorrect duration (19/105; 18.1%). Compliance with guidelines was 73.6%.</p><p><strong>Conclusions: </strong>This study outlines the successful implementation of the Antifungal NAPS, a standardized electronic audit tool for the assessment of antifungal prescribing quality. Key areas for quality improvement identified were the overuse of empirical fluconazole for urinary tract and intra-abdominal infections, the importance of invasive fungal infection risk assessment to guide prophylaxis prescribing and greater infectious diseases and antifungal stewardship oversight of antifungal prescribing to guide optimal prescribing.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1127-1136"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408060","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":"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}

{"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":"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}

{"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}