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13 pages, 936 KB  
Article
The Change in Healthcare-Associated Infections in Intensive Care Units Associated with the Coronavirus Disease 2019 in Taiwan
by Chien-Ying Wang, Yu-Hsuan Chen, Chih-Chun Hsiao, Chun-Gu Cheng and Chun-An Cheng
Medicina 2025, 61(11), 1971; https://doi.org/10.3390/medicina61111971 - 3 Nov 2025
Viewed by 761
Abstract
Background and Objectives: Changes in the incidence of healthcare-associated infections (HAIs) during the coronavirus disease 2019 (COVID-19) pandemic and during periods with fewer or more COVID-19 cases have been inconclusively studied. Compared with 2015, in 2019, the abundances of the microorganisms Klebsiella [...] Read more.
Background and Objectives: Changes in the incidence of healthcare-associated infections (HAIs) during the coronavirus disease 2019 (COVID-19) pandemic and during periods with fewer or more COVID-19 cases have been inconclusively studied. Compared with 2015, in 2019, the abundances of the microorganisms Klebsiella pneumoniae and Enterococcus faecium increased in intensive care units (ICUs) in Taiwan. The trend in the incidence of HAIs in ICUs in Taiwan during the emergence of new infectious diseases is worth studying. Materials and Methods: We surveyed the incidence densities of different types of HAIs, device-associated HAIs, pathogens, and antimicrobial resistance in a dataset from the Taiwan Healthcare-associated Infection and Antimicrobial Resistance Surveillance System from 2015 to 2022. The change in incidence density trends was evaluated via Poisson regression, and the change in proportion trends was checked via the Mantel–Haenszel chi-square test. Results: The incidence of HAIs decreased from 5.7 to 5.17 episodes per 1000 person-days from the pre-COVID-19 period to the post-COVID-19 period. The incidences of healthcare-acquired pneumonia (HAP), device-associated HAIs decreased. However, the incidences of bloodstream infections (BSIs) increased. The percentages of patients with Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii infections significantly decreased. The percentage of patients with methicillin-resistant Staphylococcus aureus (MRSA) infection decreased, but that of patients with carbapenem-resistant K. pneumoniae (CRKP), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus faecium infections increased. The antimicrobial consumption related to CRKP increased and MRSA decreased. Conclusions: Overall, HAIs, HAP, and VAP decreased in incidence after the COVID-19 pandemic. These results revealed decreases in MRSA infection incidence under infection control protocols with more antimicrobial use. However, the proportion of CRKP among HAIs increased with broad-spectrum antimicrobial agent use. Based on the recent incidence of HAIs in ICUs, the quality of infection control in medical units can be enhanced to decrease HAI incidence. Full article
(This article belongs to the Special Issue Emerging Strategies in Infection Control and Antimicrobial Therapy)
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15 pages, 464 KB  
Article
RAPID-CARE: Rapid Antibiotic Optimization in the ICU After Implementation of a Pneumonia Multiplex PCR Test—A Real-World Evaluation
by Montserrat Rodríguez-Gómez, Fernando Martínez-Sagasti, María Calle-Romero, Andrea Prieto-Cabrera, Patricia De La Montaña-Díaz, Irene Díaz-De la Torre, Alberto Delgado-Iribarren García-Campero, Sara Domingo-Marín, Miguel Sánchez-García and Ignacio Martín-Loeches
Antibiotics 2025, 14(11), 1084; https://doi.org/10.3390/antibiotics14111084 - 27 Oct 2025
Viewed by 1421
Abstract
Background/Objectives: Lower respiratory tract infections (LRTIs) are frequent in the intensive care unit (ICU) and drive empiric broad-spectrum antibiotic use. Rapid multiplex PCR assays may improve pathogen detection and stewardship compared with conventional culture. We evaluated the real-world impact of the BioFire [...] Read more.
Background/Objectives: Lower respiratory tract infections (LRTIs) are frequent in the intensive care unit (ICU) and drive empiric broad-spectrum antibiotic use. Rapid multiplex PCR assays may improve pathogen detection and stewardship compared with conventional culture. We evaluated the real-world impact of the BioFire® FilmArray® Pneumonia Panel Plus (FA-PNEU®) on antimicrobial management in suspected nosocomial LRTI. Methods: This was a single-centre, prospective observational cohort study conducted in a tertiary ICU (Madrid, Spain) between April 2021 and March 2025. Adult patients with suspected hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), or ventilator-associated tracheobronchitis (VAT) were included if paired respiratory samples underwent FA-PNEU® and conventional culture (CC). Diagnostic accuracy and prescribing changes were analysed. Results: A total of 344 samples from 236 patients were included. FA-PNEU® demonstrated high sensitivity (93.4%) and negative predictive value (97.9%) but moderate specificity (65.0%) and low positive predictive value (36.5%). False positives occurred in 85.8% of patients with prior antibiotic therapy targeting the detected organism. Antibiotic management was considered directly influenced by FA-PNEU® when any prescribing decision (initiation, escalation, de-escalation, or discontinuation) explicitly followed the panel’s results rather than other clinical or microbiological information. Using this definition, FA-PNEU® directly influenced antibiotic therapy in 57.6% of cases, while in 17.7%, prescribing was instead guided by a suspected alternative infection. In patients without prior antibiotics, treatment initiation or withholding was fully concordant with FA-PNEU® results, while in those already receiving therapy, 60.8% underwent modification, two-thirds in agreement with the panel. Conclusions: In critically ill patients with suspected nosocomial LRTI, FA-PNEU® provided rapid, high-sensitivity diagnostics that substantially influenced antimicrobial prescribing. Its greatest value lies in ruling out bacterial infection and guiding stewardship, though results must be interpreted within the full clinical and microbiological context. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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14 pages, 621 KB  
Article
Development and Validation of a Rapid LC-MS/MS Method for Quantifying Eravacycline in Epithelial Lining Fluid: Application to a Prospective Pulmonary Distribution Study in HAP/VAP Patients
by Jingjing He, Jingjing Lin, Xin Li, Nanyang Li, Jianguang Su, Jufang Wu, Jin Hu, Jing Zhang and Xiaofen Liu
Antibiotics 2025, 14(9), 957; https://doi.org/10.3390/antibiotics14090957 - 22 Sep 2025
Cited by 1 | Viewed by 1178
Abstract
Background: Eravacycline exhibits potent activity against multidrug-resistant pathogens and holds promise for the management of hospital-acquired and ventilator-associated pneumonia (HAP/VAP). However, sensitive and robust bioanalytical methods to quantify eravacycline in human pulmonary epithelial lining fluid (ELF) for pharmacokinetic (PK) and pulmonary penetration [...] Read more.
Background: Eravacycline exhibits potent activity against multidrug-resistant pathogens and holds promise for the management of hospital-acquired and ventilator-associated pneumonia (HAP/VAP). However, sensitive and robust bioanalytical methods to quantify eravacycline in human pulmonary epithelial lining fluid (ELF) for pharmacokinetic (PK) and pulmonary penetration studies in these infections remain limited. Methodology: A simple, rapid, and sensitive LC-MS/MS method was developed for the quantification of eravacycline in bronchoalveolar lavage fluid (BALF). Using urea as a volume normalizer, ELF concentrations were calculated from the eravacycline concentrations in BALF. This method was applied in a clinical study evaluating the pulmonary penetration after intravenous infusion in patients with HAP and VAP. Results: The developed LC-MS/MS method exhibited good linearity in the range of 1–200 ng/mL for quantifying eravacycline in BALF. In BALF, intra-day precision ranged from 1.4% to 6.0%, and inter-day precision from 1.6% to 9.9%, with accuracy between 98.0% and 102.4%. Matrix effects were within 97.4% to 107.6% for BALF samples from six different individuals, with extraction recoveries ranging from 103.5% to 107.2%. Stability studies demonstrated that eravacycline remained stable under various conditions, including storage at room temperature, freeze–thaw cycles, long-term (–70 °C) storage, and post-treatment handling. The method was successfully applied to clinical samples from four HAP or VAP patients, with measured eravacycline pulmonary penetration ratios of 4.29, 17.40, 5.22 and 4.70, indicating efficient pulmonary distribution. The measured eravacycline concentrations ranged from 0.0243 to 0.0436 μg/mL in BALF. The corresponding urea-corrected ELF concentrations ranged from 0.570 to 1.617 μg/mL. Conclusions: This study described a detailed and validated method for quantifying eravacycline concentrations in ELF from patients, providing a reliable analytical approach for investigating the pulmonary distribution of eravacycline. Full article
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26 pages, 748 KB  
Article
Beyond Culture: Real-Time PCR Performance in Detecting Causative Pathogens and Key Antibiotic Resistance Genes in Hospital-Acquired Pneumonia
by Lana Hani Abu Khadija, Shatha M. Alomari, Ahmad R. Alsayed, Heba A. Khader, Andi Dian Permana, Luai Z. Hasoun, Manar Saleh Zraikat, Walaa Ashran and Malek Zihlif
Antibiotics 2025, 14(9), 937; https://doi.org/10.3390/antibiotics14090937 - 17 Sep 2025
Cited by 1 | Viewed by 2417
Abstract
Introduction: The rise in hospital-acquired pneumonia (HAP) due to antibiotic-resistant bacteria is increasing morbidity, mortality, and inappropriate empirical antibiotic use. This prospective research aimed to evaluate the performance of a real-time polymerase chain reaction (PCR) assay for detecting causative microorganisms and antibiotic-resistance genes [...] Read more.
Introduction: The rise in hospital-acquired pneumonia (HAP) due to antibiotic-resistant bacteria is increasing morbidity, mortality, and inappropriate empirical antibiotic use. This prospective research aimed to evaluate the performance of a real-time polymerase chain reaction (PCR) assay for detecting causative microorganisms and antibiotic-resistance genes from respiratory specimens compared to traditional methods. Additionally, we aimed to determine the molecular epidemiology of antibiotic resistance genes among HAP patients at The University of Jordan hospital. Methods: Lower respiratory tract samples were collected from HAP patients, including those with ventilator-associated pneumonia (VAP), between May 2024 and October 2024. Clinical data from the medical files were used to collect and analyze demographic and clinical information, including clinical outcomes. Real-time PCR was run to detect causative microbes and antibiotic resistance genes. Results: Among 83 HAP patients (median age 63, 61.45% male), 48.15% died. Culture identified Klebsiella (25.53%), Acinetobacter (22.34%), and Candida (24.47%) as the most common pathogens, while qPCR showed higher detection rates, including for A. baumannii (62.20%, p = 0.02) and K. pneumoniae (45.12%, p < 0.001). Carbapenem resistance was high; A. baumannii showed 100% resistance to most antibiotics except colistin (92.31%). The resistance genes ndm (60%) and oxa-48 (58.46%) were frequently detected and significantly associated with phenotypic resistance (p < 0.001). The qPCR identified resistance genes in all carbapenem-resistant cases. No gene significantly predicted mortality. Conclusions: Real-time PCR diagnostic technique combined with epidemiology of antibiotic resistance genes data may be a rapid and effective tool to improve HAP management. Large, multicenter studies are needed in the future to validate the performance of real-time PCR in HAP diagnosis, and appropriate management is also required. Full article
(This article belongs to the Special Issue Antibiotic Therapy in Respiratory Tract Infections (RTIs))
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23 pages, 752 KB  
Review
Antibiotic Therapy Duration for Multidrug-Resistant Gram-Negative Bacterial Infections: An Evidence-Based Review
by Andrea Marino, Egle Augello, Carlo Maria Bellanca, Federica Cosentino, Stefano Stracquadanio, Luigi La Via, Antonino Maniaci, Serena Spampinato, Paola Fadda, Giuseppina Cantarella, Renato Bernardini, Bruno Cacopardo and Giuseppe Nunnari
Int. J. Mol. Sci. 2025, 26(14), 6905; https://doi.org/10.3390/ijms26146905 - 18 Jul 2025
Cited by 9 | Viewed by 8881
Abstract
Determining the optimal duration of antibiotic therapy for infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) is a critical challenge in clinical medicine, balancing therapeutic efficacy against the risks of adverse effects and antimicrobial resistance. This narrative review synthesises current evidence and guidelines regarding [...] Read more.
Determining the optimal duration of antibiotic therapy for infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) is a critical challenge in clinical medicine, balancing therapeutic efficacy against the risks of adverse effects and antimicrobial resistance. This narrative review synthesises current evidence and guidelines regarding antibiotic duration for MDR-GNB infections, emphasising bloodstream infections (BSI), hospital-acquired and ventilator-associated pneumonia (HAP/VAP), complicated urinary tract infections (cUTIs), and intra-abdominal infections (IAIs). Despite robust evidence supporting shorter courses (3–7 days) in uncomplicated infections caused by more susceptible pathogens, data guiding optimal therapy duration for MDR-GNB remain limited, particularly concerning carbapenem-resistant Enterobacterales (CRE), difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), and carbapenem-resistant Acinetobacter baumannii (CRAB). Current guidelines from major societies, including IDSA and ESCMID, provide explicit antimicrobial selection advice but notably lack detailed recommendations on the duration of therapy. Existing studies demonstrate non-inferiority of shorter versus longer antibiotic courses in specific clinical contexts but frequently exclude critically ill patients or those infected with non-fermenting MDR pathogens. Individualised duration decisions must integrate clinical response, patient immunologic status, infection severity, source control adequacy, and pharmacologic considerations. Significant knowledge gaps persist, underscoring the urgent need for targeted research, particularly randomised controlled trials assessing optimal antibiotic duration for the most challenging MDR-GNB infections. Clinicians must navigate considerable uncertainty, relying on nuanced judgement and close monitoring to achieve successful outcomes while advancing antimicrobial stewardship goals. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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17 pages, 556 KB  
Article
Factors Associated with Mortality in Nosocomial Lower Respiratory Tract Infections: An ENIRRI Analysis
by Luis Felipe Reyes, Antoni Torres, Juan Olivella-Gomez, Elsa D. Ibáñez-Prada, Saad Nseir, Otavio T. Ranzani, Pedro Povoa, Emilio Diaz, Marcus J. Schultz, Alejandro H. Rodríguez, Cristian C. Serrano-Mayorga, Gennaro De Pascale, Paolo Navalesi, Szymon Skoczynski, Mariano Esperatti, Luis Miguel Coelho, Andrea Cortegiani, Stefano Aliberti, Anselmo Caricato, Helmut J. F. Salzer, Adrian Ceccato, Rok Civljak, Paolo Maurizio Soave, Charles-Edouard Luyt, Pervin Korkmaz Ekren, Fernando Rios, Joan Ramon Masclans, Judith Marin, Silvia Iglesias-Moles, Stefano Nava, Davide Chiumello, Lieuwe D. Bos, Antonio Artigas, Filipe Froes, David Grimaldi, Mauro Panigada, Fabio Silvio Taccone, Massimo Antonelli and Ignacio Martin-Loechesadd Show full author list remove Hide full author list
Antibiotics 2025, 14(2), 127; https://doi.org/10.3390/antibiotics14020127 - 26 Jan 2025
Cited by 3 | Viewed by 3064
Abstract
Background: Nosocomial lower respiratory tract infections (nLRTIs) are associated with unfavorable clinical outcomes and significant healthcare costs. nLRTIs include hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and other ICU-acquired pneumonia phenotypes. While risk factors for mortality in these infections are critical to guide [...] Read more.
Background: Nosocomial lower respiratory tract infections (nLRTIs) are associated with unfavorable clinical outcomes and significant healthcare costs. nLRTIs include hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and other ICU-acquired pneumonia phenotypes. While risk factors for mortality in these infections are critical to guide preventive strategies, it remains unclear whether they vary based on their requirement of invasive mechanical ventilation (IMV) at any point during the hospitalization. Objectives: This study aims to identify risk factors associated with short- and long-term mortality in patients with nLRTIs, considering differences between those requiring IMV and those who do not. Methods: This multinational prospective cohort study included ICU-admitted patients diagnosed with nLRTI from 28 hospitals across 13 countries in Europe and South America between May 2016 and August 2019. Patients were selected based on predefined inclusion and exclusion criteria, and clinical data were collected from medical records. A random forest classifier determined the most optimal clustering strategy when comparing pneumonia site acquisition [ward or intensive care unit (ICU)] versus intensive mechanical ventilation (IMV) necessity at any point during hospitalization to enhance the accuracy and generalizability of the regression models. Results: A total of 1060 patients were included. The random forest classifier identified that the most efficient clustering strategy was based on ventilation necessity. In total, 76.4% of patients [810/1060] received IMV at some point during the hospitalization. Diabetes mellitus was identified to be associated with 28-day mortality in the non-IMV group (OR [IQR]: 2.96 [1.28–6.80], p = 0.01). The 90-day mortality-associated factor was MDRP infection (1.98 [1.13–3.44], p = 0.01). For ventilated patients, chronic liver disease was associated with 28-day mortality (2.38 [1.06–5.31] p = 0.03), with no variable showing statistical and clinical significance at 90 days. Conclusions: The risk factors associated with 28-day mortality differ from those linked to 90-day mortality. Additionally, these factors vary between patients receiving invasive mechanical ventilation and those in the non-invasive ventilation group. This underscores the necessity of tailoring therapeutic objectives and preventive strategies with a personalized approach. Full article
(This article belongs to the Special Issue Nosocomial Infections and Complications in ICU Settings)
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19 pages, 1288 KB  
Review
Transforming Microbiological Diagnostics in Nosocomial Lower Respiratory Tract Infections: Innovations Shaping the Future
by Ingrid G. Bustos, Lina F. Martinez-Lemus, Luis Felipe Reyes and Ignacio Martin-Loeches
Diagnostics 2025, 15(3), 265; https://doi.org/10.3390/diagnostics15030265 - 23 Jan 2025
Cited by 5 | Viewed by 3802
Abstract
Introduction: Nosocomial lower respiratory tract infections (nLRTIs), including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), remain significant challenges due to high mortality, morbidity, and healthcare costs. Implementing accurate and timely diagnostic strategies is pivotal for guiding optimized antimicrobial therapy and addressing the growing [...] Read more.
Introduction: Nosocomial lower respiratory tract infections (nLRTIs), including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), remain significant challenges due to high mortality, morbidity, and healthcare costs. Implementing accurate and timely diagnostic strategies is pivotal for guiding optimized antimicrobial therapy and addressing the growing threat of antimicrobial resistance. Areas Covered: This review examines emerging microbiological diagnostic methods for nLRTIs. Although widely utilized, traditional culture-based techniques are hindered by prolonged processing times, limiting their clinical utility in timely decision-making. Advanced molecular tools, such as real-time PCR and multiplex PCR, allow rapid pathogen identification but are constrained by predefined panels. Metagenomic next-generation sequencing (mNGS) provides comprehensive pathogen detection and resistance profiling yet faces cost, complexity, and interpretation challenges. Non-invasive methods, including exhaled breath analysis using electronic nose (e-nose) technology, gene expression profiling, and biomarker detection, hold promise for rapid and bedside diagnostics but require further validation to establish clinical applicability. Expert Opinion: Integrating molecular, metagenomic, biomarker-associated, and traditional diagnostics is essential for overcoming limitations. Continued technological refinements and cost reductions will enable broader clinical implementation. These innovations promise to enhance diagnostic accuracy, facilitate targeted therapy, and improve patient outcomes while contributing to global efforts to mitigate antimicrobial resistance. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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24 pages, 1004 KB  
Review
Ventilator-Associated Pneumonia After Cardiac Arrest and Prevention Strategies: A Narrative Review
by Harinivaas Shanmugavel Geetha, Yi Xiang Teo, Sharmitha Ravichandran and Amos Lal
Medicina 2025, 61(1), 78; https://doi.org/10.3390/medicina61010078 - 5 Jan 2025
Cited by 2 | Viewed by 8174
Abstract
Background and Objectives: Ventilator-associated pneumonia (VAP) poses a significant threat to the clinical outcomes and hospital stays of mechanically ventilated patients, particularly those recovering from cardiac arrest. Given the already elevated mortality rates in cardiac arrest cases, the addition of VAP further [...] Read more.
Background and Objectives: Ventilator-associated pneumonia (VAP) poses a significant threat to the clinical outcomes and hospital stays of mechanically ventilated patients, particularly those recovering from cardiac arrest. Given the already elevated mortality rates in cardiac arrest cases, the addition of VAP further diminishes the chances of survival. Consequently, a paramount focus on VAP prevention becomes imperative. This review endeavors to comprehensively delve into the nuances of VAP, specifically in patients requiring mechanical ventilation in post-cardiac arrest care. The overarching objectives encompass (I) exploring the etiology, risk factors, and pathophysiology of VAP, (II) delving into available diagnostic modalities, and (III) providing insights into the management options and recent treatment guidelines. Methods: A literature search was conducted using PubMed, MEDLINE, and Google Scholar databases for articles about VAP and Cardiac arrest. We used the MeSH terms “VAP”, “Cardiac arrest”, “postcardiac arrest syndrome”, and “postcardiac arrest syndrome”. The clinical presentation, diagnostic, and management strategies of VAP were summarized, and all authors reviewed the selection and decided which studies to include. Key Content and Findings: The incidence and mortality rates of VAP exhibit significant variability, yet a recurring pattern emerges, marked by prolonged hospitalization and exacerbated clinical outcomes. This pattern is attributed to the elevated incidence of drug-resistant infections and the delayed initiation of antimicrobial treatment. This review focuses on VAP, aiming to offer valuable insights into the efficient identification and management of this fatal complication in post-cardiac arrest patients. Conclusion: The prognosis for survival after cardiac arrest is already challenging, and the outlook becomes even more daunting when complicated by VAP. The timely diagnosis of VAP and initiation of antibiotics pose considerable challenges, primarily due to the invasive nature of obtaining high-quality samples and the time required for speciation and identification of antimicrobial sensitivity. The controversy surrounding prophylactic antibiotics persists, but promising new strategies have been proposed; however, they are still awaiting well-designed clinical trials. Full article
(This article belongs to the Section Pulmonology)
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26 pages, 1655 KB  
Review
Duration of Antimicrobial Treatment in Adult Patients with Pneumonia: A Narrative Review
by Dimitra Dimopoulou, Charalampos D. Moschopoulos, Konstantina Dimopoulou, Anastasia Dimopoulou, Maria M. Berikopoulou, Ilias Andrianakis, Sotirios Tsiodras, Anastasia Kotanidou and Paraskevi C. Fragkou
Antibiotics 2024, 13(11), 1078; https://doi.org/10.3390/antibiotics13111078 - 12 Nov 2024
Cited by 2 | Viewed by 10506
Abstract
Pneumonia remains a major global health concern, causing significant morbidity and mortality among adults. This narrative review assesses the optimal duration of antimicrobial treatment in adults with community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). Current evidence about the impact of [...] Read more.
Pneumonia remains a major global health concern, causing significant morbidity and mortality among adults. This narrative review assesses the optimal duration of antimicrobial treatment in adults with community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). Current evidence about the impact of treatment duration on clinical outcomes demonstrates that shorter antibiotic courses are non-inferior, regarding safety and efficacy, compared to longer courses, particularly in patients with mild to moderate CAP, which is in line with the recommendations of international guidelines. Data are limited regarding the optimal antimicrobial duration in HAP patients, and it should be individually tailored to each patient, taking into account the causative pathogen and the clinical response. Shorter courses are found to be as effective as longer courses in the management of VAP, except for pneumonia caused by non-fermenting Gram-negative bacteria; however, duration should be balanced between the possibility of higher recurrence rates and the documented benefits with shorter courses. Additionally, the validation of reliable biomarkers or clinical predictors that identify patients who would benefit from shorter therapy is crucial. Insights from this review may lead to future research on personalized antimicrobial therapies in pneumonia, in order to improve patient outcomes. Full article
(This article belongs to the Special Issue Antimicrobial Treatment of Lower Respiratory Tract Infections)
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10 pages, 251 KB  
Article
Monitoring Immune Dysfunction in Critically Ill Patients with Carbapenem-Resistant Acinetobacter baumannii Sepsis Treated with Regimens Including Cefiderocol: A Pilot Study to Identify Accessible Biomarkers to Stratify Patients’ Prognosis
by Antonella Frattari, Ennio Polilli, Laura Timelli, Francesca Spagnuolo, Paolo Fazii and Giustino Parruti
Antibiotics 2024, 13(11), 1001; https://doi.org/10.3390/antibiotics13111001 - 23 Oct 2024
Cited by 1 | Viewed by 2255
Abstract
Background: Multidrug-resistant Acinetobacter baumannii (CRAB) infections are a serious problem in critical care. This study aims to develop an early prognostic score for immune paralysis, using practical and cost-effective parameters, to predict ICU mortality in patients with CRAB infections being treated with Cefiderocol. [...] Read more.
Background: Multidrug-resistant Acinetobacter baumannii (CRAB) infections are a serious problem in critical care. This study aims to develop an early prognostic score for immune paralysis, using practical and cost-effective parameters, to predict ICU mortality in patients with CRAB infections being treated with Cefiderocol. Methods: We carried out an observational pilot study on consecutive patients hospitalized in the ICU with ensuing septic Acinetobacter baumannii infections treated with Cefiderocol monotherapy or Cefiderocol including combinations. We investigated the predictive power of lymphocyte counts, lymphocyte subpopulations, serum cholinesterase levels, and reactivation of herpes viruses. Results: Overall, 36 of 39 patients entered in our analysis: 20 survivors and 16 deceased. A total of 12 patients developed bacteremia, 19 patients had HAP/VAP, and 5 patients had a soft tissue infection. Univariate analyses of factors associated with unfavorable outcome revealed a significant association for age (OR: 1.5, CI: 1.11–2.02), SAPS II (OR: 1.05, CI: 1.01–1.1), SOFA score (OR: 1.37, CI: 1.06–1.76), lymphocytopenia (OR: 32.5, CI: 3.45–306.4), viral reactivation (OR: 9.75, CI: 1.72–55.4), and cholinesterase drop <1600 U/L (OR: 39.7, CI: 5.8–271.6). At variance, monotherapy or associations with Cefiderocol were not associated. In the final multivariable model, the only independent predictors of death were age (OR: 1.42, CI: 0.98–2.05), lymphocytopenia (OR: 18.2, CI: 0.87–371), and cholinesterase drop to below 1600 U/L (OR: 9.7, CI: 0.77–123.7). Conclusions: Age, lymphocytopenia, and serum cholinesterase drops, which were nearly significantly associated with an unfavorable outcome, may help pinpoint patients with acute immune paralysis during sepsis. Knowledge of such an immune state may in turn directly influence patients’ care. Full article
30 pages, 1048 KB  
Review
Novel Antibiotics for Gram-Negative Nosocomial Pneumonia
by Maria Panagiota Almyroudi, Aina Chang, Ioannis Andrianopoulos, Georgios Papathanakos, Reena Mehta, Elizabeth Paramythiotou and Despoina Koulenti
Antibiotics 2024, 13(7), 629; https://doi.org/10.3390/antibiotics13070629 - 5 Jul 2024
Cited by 8 | Viewed by 5088
Abstract
Nosocomial pneumonia, including hospital-acquired pneumonia and ventilator-associated pneumonia, is the leading cause of death related to hospital-acquired infections among critically ill patients. A growing proportion of these cases are attributed to multi-drug-resistant (MDR-) Gram-negative bacteria (GNB). MDR-GNB pneumonia often leads to delayed appropriate [...] Read more.
Nosocomial pneumonia, including hospital-acquired pneumonia and ventilator-associated pneumonia, is the leading cause of death related to hospital-acquired infections among critically ill patients. A growing proportion of these cases are attributed to multi-drug-resistant (MDR-) Gram-negative bacteria (GNB). MDR-GNB pneumonia often leads to delayed appropriate treatment, prolonged hospital stays, and increased morbidity and mortality. This issue is compounded by the increased toxicity profiles of the conventional antibiotics required to treat MDR-GNB infections. In recent years, several novel antibiotics have been licensed for the treatment of GNB nosocomial pneumonia. These novel antibiotics are promising therapeutic options for treatment of nosocomial pneumonia by MDR pathogens with certain mechanisms of resistance. Still, antibiotic resistance remains an evolving global crisis, and resistance to novel antibiotics has started emerging, making their judicious use crucial to prolong their shelf-life. This article presents an up-to-date review of these novel antibiotics and their current role in the antimicrobial armamentarium. We critically present data for the pharmacokinetics/pharmacodynamics, the in vitro spectrum of antimicrobial activity and resistance, and in vivo data for their clinical and microbiological efficacy in trials. Where possible, available data are summarized specifically in patients with nosocomial pneumonia, as this cohort may exhibit ‘critical illness’ physiology that affects drug efficacy. Full article
(This article belongs to the Special Issue Antimicrobial Treatment of Lower Respiratory Tract Infections)
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13 pages, 911 KB  
Article
Efficacy and Safety of Ceftazidime–Avibactam Alone versus Ceftazidime–Avibactam Plus Fosfomycin for the Treatment of Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia: A Multicentric Retrospective Study from the SUSANA Cohort
by Marco Fois, Andrea De Vito, Francesca Cherchi, Elena Ricci, Michela Pontolillo, Katia Falasca, Nicolò Corti, Agnese Comelli, Alessandra Bandera, Chiara Molteni, Stefania Piconi, Francesca Colucci, Paolo Maggi, Vincenzo Boscia, Aakash Fugooah, Sara Benedetti, Giuseppe Vittorio De Socio, Paolo Bonfanti and Giordano Madeddu
Antibiotics 2024, 13(7), 616; https://doi.org/10.3390/antibiotics13070616 - 2 Jul 2024
Cited by 4 | Viewed by 3086
Abstract
Hospital-acquired pneumonia (HAP) and ventilation-associated pneumonia (VAP) are challenging clinical conditions due to the challenging tissue penetrability of the lung. This study aims to evaluate the potential role of fosfomycin (FOS) associated with ceftazidime/avibactam (CZA) in improving the outcome in this setting. We [...] Read more.
Hospital-acquired pneumonia (HAP) and ventilation-associated pneumonia (VAP) are challenging clinical conditions due to the challenging tissue penetrability of the lung. This study aims to evaluate the potential role of fosfomycin (FOS) associated with ceftazidime/avibactam (CZA) in improving the outcome in this setting. We performed a retrospective study including people with HAP or VAP treated with CZA or CZA+FOS for at least 72 h. Clinical data were collected from the SUSANA study, a multicentric cohort to monitor the efficacy and safety of the newer antimicrobial agents. A total of 75 nosocomial pneumonia episodes were included in the analysis. Of these, 34 received CZA alone and 41 in combination with FOS (CZA+FOS). People treated with CZA alone were older, more frequently male, received a prolonged infusion more frequently, and were less frequently affected by carbapenem-resistant infections (p = 0.01, p = 0.06, p < 0.001, p = 0.03, respectively). No difference was found in terms of survival at 28 days from treatment start between CZA and CZA+FOS at the multivariate analysis (HR = 0.32; 95% CI = 0.07–1.39; p = 0.128), while prolonged infusion showed a lower mortality rate at 28 days (HR = 0.34; 95% CI = 0.14–0.96; p = 0.04). Regarding safety, three adverse events (one acute kidney failure, one multiorgan failure, and one urticaria) were reported. Our study found no significant association between combination therapy and mortality. Further investigations, with larger and more homogeneous samples, are needed to evaluate the role of combination therapy in this setting. Full article
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10 pages, 1346 KB  
Article
The Impact of Next-Generation Sequencing Added to Multiplex PCR on Antibiotic Stewardship in Critically Ill Patients with Suspected Pneumonia
by Kendall Kling, Chao Qi, Richard G. Wunderink and Chiagozie Pickens
Diagnostics 2024, 14(13), 1388; https://doi.org/10.3390/diagnostics14131388 - 29 Jun 2024
Cited by 4 | Viewed by 2489
Abstract
Introduction: In patients with suspected pneumonia who are tested with respiratory culture and multiplex PCR, the potential added benefit of next-generation sequencing technologies is unknown. Methods: This was a single-center, retrospective study in which residual bronchoalveolar lavage (BAL) specimens were retrieved from hospitalized [...] Read more.
Introduction: In patients with suspected pneumonia who are tested with respiratory culture and multiplex PCR, the potential added benefit of next-generation sequencing technologies is unknown. Methods: This was a single-center, retrospective study in which residual bronchoalveolar lavage (BAL) specimens were retrieved from hospitalized patients. We compared its research-use-only Respiratory Pathogen Illumina Panel (RPIP) results to culture and BioFire® FilmArray Pneumonia Panel (BioFire® PN) results from critically ill patients. Results: In total, 47 BAL specimens from 47 unique patients were included. All BAL samples were tested with culture and multiplex PCR. In total, 38 of the 47 BALs were consistent with a clinical picture of pneumonia per chart review. Additional testing of the 38 samples with the RPIP identified a new bacterium in 20 patients, a new virus in 4 patients, a new bacterium plus virus in 4 patients, and no additional organisms in 10 patients. In 17 (44.5%) of these patients, the RPIP results could have indicated an antibiotic addition. Compared with cultures, the RPIP had an overall sensitivity of 64% and specificity of 98%, with a 0% sensitivity for fungus and 14% sensitivity for mycobacteria. Compared with BioFire® PN, the RPIP was 70% sensitive and 99% specific, with a 74% sensitivity for bacteria and 33% sensitivity for viruses. The RPIP was 29% more sensitive for HAP/VAP bacterial targets compared with CAP. Conclusions: Emerging NGS technologies such as the RPIP may have a role in identifying the etiology of pneumonia, even when patients have BAL culture and multiplex PCR results available. Similar to prior studies evaluating RPIP, our study showed this platform lacked sensitivity when compared with cultures, particularly for fungi and mycobacteria. However, the high specificity of the test can be leveraged when clinicians are seeking to rule out certain infections. Full article
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14 pages, 449 KB  
Article
Pneumonia Characteristics in an Intensive Care Unit Setting during and after the COVID-19 Pandemic—A Single-Center Prospective Study
by Jakub Sleziak, Katarzyna Pilarczyk, Michal Matysiak and Wieslawa Duszynska
J. Clin. Med. 2024, 13(10), 2824; https://doi.org/10.3390/jcm13102824 - 10 May 2024
Cited by 4 | Viewed by 3541
Abstract
Background: During and after the COVID-19 pandemic, there was a suspicion of varying rates of respiratory tract infections (RTIs), particularly pneumonia (PN). Methods: This research evaluated epidemiological indicators of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) in the COVID-19 pandemic and post-pandemic [...] Read more.
Background: During and after the COVID-19 pandemic, there was a suspicion of varying rates of respiratory tract infections (RTIs), particularly pneumonia (PN). Methods: This research evaluated epidemiological indicators of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) in the COVID-19 pandemic and post-pandemic period, including pathogens, ventilator-associated pneumonia (VAP), selected risk factors, and PN mortality. Results: At 1740 patients, throughout the 22,774 patient-days (Pt-D) and 18,039 ventilation days (Vt-D), there were 681 PN cases (39.14%): CAP 336 (19.31%) and HAP 345 (19.83%). CAP caused by SARS-CoV-2 was diagnosed in 257/336 (76.49%) patients. The clinical manifestations of PNs were CAP with 336/681 (49.34%), VAP with 232/681 (34.07%), and non-ventilator HAP (NV-HAP) with 113/681 cases (16.59%). The incidence rate of CAP/1000 Pt-D has been over 3 times higher in the pandemic period of 2020–2021 (20.25) than in the post-pandemic period of 2022 (5.86), p = 0.000. Similarly, higher incidence rates of VAP/1000 Pt-D were found in the pandemic period (p = 0.050). For NV-HAP, this difference was not statistically significant (p = 0.585). VAP occurred more frequently in the group of patients with PN in the course of COVID-19 compared to patients without COVID-19 (52/234 [22.2%] vs. 180/1506 [11.95%]); (p = 0.000). The most common CAP pathogen (during the pandemic) was SARS CoV-2 234/291 (80.4%), followed by MSSA/MRSA 8/291 (2.75%), whereas the most common VAP/NV-HAP pathogen was Acinetobacter baumannii XDR/MDR. The highest PN mortality was found in the patients with CAP caused by SARS-CoV-2 159/257 (61.87%). Conclusions: Pneumonias were diagnosed in nearly 40% of Intensive Care Unit (ICU) patients. Surveillance of pneumonias during the specific observation period was beneficial in the epidemiological and microbiological analysis of the ICU patients. Full article
(This article belongs to the Special Issue Critical Care during COVID-19 Pandemic)
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14 pages, 547 KB  
Article
Clinical Efficacy of Sitafloxacin–Colistin–Meropenem and Colistin–Meropenem in Patients with Carbapenem-Resistant and Multidrug-Resistant Acinetobacter baumannii Hospital-Acquired Pneumonia (HAP)/Ventilator-Associated Pneumonia (VAP) in One Super-Tertiary Hospital in Bangkok, Thailand: A Randomized Controlled Trial
by Manasawee Wantanatavatod and Panuwat Wongkulab
Antibiotics 2024, 13(2), 137; https://doi.org/10.3390/antibiotics13020137 - 30 Jan 2024
Cited by 2 | Viewed by 4021
Abstract
Background: Carbapenem-resistant A. baumannii (CRAB) hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) is now a therapeutic problem worldwide. Method: An open-label, randomized, superiority, single-blind trial was conducted in Rajavithi Hospital, a super-tertiary care facility in Bangkok, Thailand. CRAB HAP/VAP patients were randomly assigned to receive [...] Read more.
Background: Carbapenem-resistant A. baumannii (CRAB) hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) is now a therapeutic problem worldwide. Method: An open-label, randomized, superiority, single-blind trial was conducted in Rajavithi Hospital, a super-tertiary care facility in Bangkok, Thailand. CRAB HAP/VAP patients were randomly assigned to receive either sitafloxacin–colistin–meropenem or colistin–meropenem. Outcomes in the two groups were then assessed with respect to mortality, clinical response, and adverse effects. Result: Between April 2021 and April 2022, 77 patients were treated with combinations of either sitafloxacin plus colistin plus meropenem (n = 40) or colistin plus meropenem (n = 37). There were no significant differences between the two groups with respect to all-cause mortality rates at 7 days and 14 days (respectively, 7.5% vs. 2.7%; p = 0.616, and 10% vs. 10%; p = 1). Patients who received sitafloxacin–colistin–meropenem showed improved clinical response compared with patients who received colistin–meropenem in terms of both intention-to-treat (87.5% vs. 62.2%; p = 0.016) and per-protocol analysis (87.2% vs. 67.7%; p = 0.049). There were no significant differences between the two groups with respect to adverse effects. Conclusions: Adding sitafloxacin as a third agent to meropenem plus colistin could improve clinical outcomes in CRAB HAP/VAP with little or no impact on adverse effects. In short, sitafloxacin–meropenem–colistin could be another therapeutic option for combatting CRAB HAP/VAP. Full article
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