Other specific DSP article suggested by Editorial Board
A pre-post quasi-experimental study of antimicrobial stewardship exploring the impact of a multidisciplinary approach aimed at attaining an aggressive joint pharmacokinetic/pharmacodynamic target with ceftazidime/avibactam on treatment outcome of KPC-producing Klebsiella pneumoniae infections and on ceftazidime/avibactam resistance development.
DOI: 10.1128/aac.00488-25
Authors: Gatti M et al
Abstract
To assess the impact of a multidisciplinary approach aimed at attaining aggressive joint pharmacokinetic/pharmacodynamic (PK/PD) target with ceftazidime/avibactam on treatment outcome of KPC-Klebsiella pneumoniae (Kp) infections and prevention of ceftazidime/avibactam resistance development, a pre-post quasi-experimental study on adult patients with documented KPC-Kp who were treated with ceftazidime/avibactam according to a multidisciplinary approach in the period 1 March 2021-31 October 2024 and patients receiving standard management with ceftazidime/avibactam in the period 1 January 2018-28 February 2021 was performed. Multivariate analysis was performed to identify variables associated with microbiological failure and 90-day resistance development to ceftazidime/avibactam in both pre- and post-intervention phases. A total of 116 and 102 patients in pre- and post-intervention phases were included. A significantly lower microbiological eradication rate (53.0% vs. 81.0%; P < 0.001), a lower clinical cure rate (48.3% vs. 70.6%; P < 0.001), and a higher rate of 90-day resistance development (15.5% vs. 5.9%; P = 0.02) were found in the pre-intervention phase. Continuous renal replacement therapy (odds ratio [OR] 5.20; 95% confidence interval [CI] 1.21-22.34) and a ceftazidime/avibactam MIC value ≥ 4 mg/L (OR 3.08; 95% CI 1.10-8.64) emerged as independent predictors of microbiological failure in the pre-intervention phase. Conversely, attaining aggressive joint PK/PD target (OR 0.03; 95% CI 0.005-0.20) and bloodstream infections (OR 0.09; 95% CI 0.02-0.53) resulted in protection against microbiological failure in the post-intervention phase. Attaining aggressive joint PK/PD targets resulted in protection against 90-day resistance development in the post-intervention phase (OR 0.07; 95% CI 0.01-0.69). Implementing a multidisciplinary approach for maximizing the attainment of aggressive joint PK/PD targets of ceftazidime/avibactam could represent an effective strategy for preventing resistance development to ceftazidime/avibactam in KPC-Kp infections.
Other specific DSP article suggested by Editorial Board
Clostridioides difficile evolution in a tertiary German hospital through a retrospective genomic characterization.
Authors:Lorenzo Diaz F et al
Abstract
Purpose: Clostridioides difficile is a major cause of healthcare-associated infections, contributing to significant morbidity and mortality. This study aimed to investigate the genomic characteristics, antimicrobial resistance (AMR) profiles, and temporal dynamics of C. difficile strains isolated from hospitalized patients in a German tertiary hospital over nearly two decades (1997-2015).
Methods: Whole-genome sequencing was performed on 46 toxigenic C. difficile isolates to determine sequence types (STs) and phylogenetic relationships and these were compared to national surveillance data on C. dificile. AMR profiling was conducted to identify key resistance determinants at genetic level while epsilometer minimum inhibitory concentration (MIC) analyses were used to correlate genetic resistance markers with phenotypic resistance. Longitudinal antibiotic usage data were analysed to assess potential associations with resistance profiles and strains evolution.
Results: Five predominant STs were identified: ST1 (30%), ST54 (24%), ST3 (22%), ST11 (11%), and ST37 (4%). Phylogenetic analysis showed that ST1 (ribotype 027) emerged as the dominant and persistent lineage, replacing ST11 and ST54 over time. AMR profiling detected several resistance genetic markers such as CDD-1/CDD-2 (carbapenem resistance), ErmB (macrolide-lincosamide-streptogramin B resistance/MLS resistance), and mutations in gyrA (fluoroquinolone resistance) and rpoB (rifampicin resistance). MIC analyses confirmed high resistance rates to moxifloxacin (87%) and rifampicin (59%), while susceptibility to fidaxomicin, metronidazole, and vancomycin remained. The tetM gene, associated with doxycycline resistance, declined as ST11 and ST54 frequencies decreased. Longitudinal analysis revealed a reduction in moxifloxacin resistance following its decreased use, whereas increased doxycycline use paradoxically correlated with reduced resistance.
Conclusion: This study highlights the dynamic strain evolution of C. difficile, reflecting national trends in strain evolution. The findings emphasize the strong correlation between epsilometer MIC values and molecular resistance markers. This observation reinforces the integration of genetic surveillance with antibiotic stewardship in the clinical routine to effectively mitigate CDI recurrence. Further research is needed to better understand the complex interactions between antibiotic exposure and strain evolution in hospital environments
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Other specific DSP article suggested by Editorial Board
A Game Changer for Acute Gastroenteritis in the Pediatric Emergency Department: Multiplex Stool PCR Test.
DOI: 10.1002/jcla.70067
Authors: Barut D et al
Abstract
Objective: This study evaluated the diagnostic performance of the FilmArray GI Panel multiplex polymerase chain reaction (PCR) compared to conventional stool culture (CSC) and microscopic stool analysis in children with bacterial acute infectious gastroenteritis (AIG) in the emergency department (ED). It also assessed the impact of PCR use on clinical decision-making, antibiotic stewardship, and ED workflow.
Methods: A retrospective analysis was conducted in a tertiary pediatric ED. Children diagnosed with AIG who underwent CSC, microscopy, and multiplex PCR were included. Data on demographics, clinical findings, diagnostic results, antibiotic prescriptions, and patient outcomes were collected. Diagnostic performance metrics-sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)-were compared.
Results: Among 257 pediatric patients, enteropathogens were detected in 31.9% via CSC and 39.3% via multiplex PCR. PCR showed superior sensitivity (96.2%) and NPV (97.4%) compared to CSC. The median turnaround time for PCR (7.9 h) was significantly shorter than for CSC (47.5 h, p < 0.001). Antibiotic use was significantly lower in PCR-negative cases (p < 0.001), and ED length of stay was also reduced.
Conclusion: The FilmArray GI Panel offers improved sensitivity and faster results than conventional methods, enhancing diagnostic accuracy and reducing unnecessary antibiotic use. Its integration in ED protocols can support antimicrobial stewardship and streamline care.
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Bacterial multiplex polymerase chain reaction tests for the diagnosis and management of pneumonia: ready for prime time?
Authors: Ling L et al
Abstract
Background: The diagnosis and management of pneumonia is often challenging due to its overlapping clinical presentations with other respiratory illnesses, low pathogen identification rates, and slow turnaround time of conventional bacterial cultures. These factors contribute to both inadequate empiric therapy and overuse of broad-spectrum antibiotics, which can negatively impact outcomes. Recently, multiplex polymerase chain reaction (mPCR) assays capable of rapidly detecting multiple bacterial respiratory pathogens and resistance genes have emerged. However, their clinical utility in pneumonia management remains uncertain.
Objective: To assess the utility of bacterial mPCR assays in pneumonia diagnosis, their impact on antimicrobial usage, and their effect on patient outcomes.
Methods: A comprehensive literature review was conducted using MEDLINE to identify observational studies and randomised controlled trials (RCTs) evaluating the accuracy and clinical impact of bacterial mPCR tests for pneumonia.
Results: Bacterial mPCR assays demonstrate high sensitivity for pathogen detection, rapid turnaround compared to conventional cultures, and the ability to identify many common resistance genes. They may also improve pathogen detection in patients who received empirical antibiotics prior to specimen collection. However, mPCRs do not detect all potential pathogens, cannot reliably differentiate colonisation from infection, and may show discordance between genetic and phenotypic resistance. mPCR panels also generally require lower respiratory tract specimens, limiting their utility since many pneumonia patients cannot produce adequate sputum. Observational studies and RCTs suggest that mPCR may help optimise antibiotic selection, but RCTs have not clearly demonstrated reductions in overall antibiotic use or improved clinical outcomes including mortality. Implementation of mPCR without structured antimicrobial stewardship may limit clinical impact.
Conclusions: Bacterial mPCR assays offer rapid and sensitive pathogen detection, but their integration into pneumonia management requires careful consideration of clinical context and expert antimicrobial stewardship guidance. Future research should focus on optimising their diagnostic and therapeutic applications, evaluating cost-effectiveness, and assessing patient-centered outcomes.
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The Value of the Galactomannan Test in Diagnosing COVID-19-Associated Pulmonary Aspergillosis: A Review.
Authors: Salehi M et al
Abstract
COVID-19-associated pulmonary aspergillosis (CAPA) is a complication of COVID-19. Galactomannan (GM) is a non-invasive test used to diagnose invasive aspergillosis. The existing studies on the diagnostic value of GM were collected to determine a GM level for predicting CAPA. All articles on the value of GM in CAPA diagnosis published until November 2023 were reviewed. The main databases were searched using the following keywords: “aspergillus”, “aspergillosis”, “SARS-CoV-2”, “COVID”, “2019 ncovnCOV”, “novel coronavirus”, “COVID-19”, “galactomannan”, and “CAPA”. Studies with reported levels of serum or BAL GM were included. Patients were classified into two groups: non-confirmed and proven aspergillosis. Finally, the receiver operating characteristic (ROC) curve analysis was used to determine a GM level to predict the likelihood of CAPA. A total of 26 articles were selected, of which 239 patients were included. A count of 123 patients (50%) were in the non-confirmed group and 124 (50%) patients were proven. The median serum GM was 0.51 in the non-confirmed group and 0.47 in the proven group (p= 0.73). The level of GM in BAL fluid was 0.10 in the non-confirmed and 2.80 in the proven group, which was statistically different (p<0.001). With 81.3 % sensitivity and 79.5% specificity, the BAL GM cut-off was 1.01 ODI. The results showed that BAL GM ≥1.01 can be used to predict CAPA. Serum GM did not show any predictive value in diagnosing CAPA. However, BAL GM level can be a reliable diagnostic test in patients with CAPA.
Other specific DSP article suggested by Editorial Board
Effect of an educational antimicrobial stewardship program on antibiotic prescriptions’ appropriateness in three medical units of a large university hospital: an interrupted time series analysis.
Authors: Giovannenze F et al
Abstract
Background: Antimicrobial Stewardship (AMS) Programs aim to enhance antibiotic prescription quality, reduce antibiotic use, and combat multidrug-resistant pathogens. However, the optimal AMS intervention for different clinical settings remains unclear, with previous studies predominantly focusing on antibiotic consumption rather than prescription appropriateness.
Aim: This study evaluates the impact of an education-based AMS intervention on antibiotic prescription appropriateness in three medical units of a 1500-bed university hospital.
Methods: A retrospective interventional, interrupted time series study was conducted to test the effect of an educational program in three medical units of our 1500-bed university hospital in Rome, from June 2018 to October 2019. The intervention comprised six educational meetings held over three months (December 2018 to February 2019). The primary outcome was the appropriateness of antibiotic prescriptions, with in-hospital survival as a secondary outcome.
Findings: Out of 609 antibiotic prescriptions evaluated, the program led to a significant and sustained reduction in inappropriate prescriptions in one unit (change in level (CL) -18.15%, p <0.01; change in trend (CT) -3.21%, p=0.01), while it failed to demonstrate a significant reduction in the other two units and globally in the three units.
Conclusions: The same educational AMS program led to variable results in terms of antibiotic appropriateness in three medical units with similar structural and organizational features. Larger and more tailored high-quality AMS interventional studies are needed to better understand the impact of educational programs on appropriateness of antibiotic prescriptions.