The Impact of Next-Generation Sequencing Added to Multiplex PCR on Antibiotic Stewardship in Critically Ill Patients with Suspected Pneumonia
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ABSTRACT:
SUBMITTER: Kling K
PROVIDER: S-EPMC11241116 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
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| S-EPMC7661905 | biostudies-literature
Project description:BackgroundMultiplexed molecular rapid diagnostic tests (RDTs) may allow for rapid and accurate diagnosis of the microbial etiology of pneumonia. However, little data are available on multiplexed RDTs in pneumonia and their impact on clinical practice.MethodsThis retrospective study analyzed 659 hospitalized patients for microbiological diagnosis of suspected pneumonia.ResultsThe overall sensitivity of the Unyvero LRT Panel was 85.7% (95% CI 82.3-88.7) and the overall specificity was 98.4% (95% CI 98.2-98.7) with a negative predictive value of 97.9% (95% CI 97.6-98.1). The LRT Panel result predicted no change in antibiotics in 12.4% of cases but antibiotic de-escalation in 65.9% (405/615) of patients, of whom 278/405 (69%) had unnecessary MRSA coverage and 259/405 (64%) had unnecessary P. aeruginosa coverage.InterpretationIn hospitalized adults with suspected pneumonia, use of an RDT on respiratory samples can allow for early adjustment of initial antibiotics, most commonly de-escalation.
| S-EPMC7428672 | biostudies-literature
Project description:BackgroundAntibiotic stewardship in critically ill pneumonia patients is crucial yet challenging, partly due to the limited diagnostic yield of noninvasive infectious tests. In this study, we report an antibiotic prescription pattern informed by bronchoalveolar lavage (BAL) results, where clinicians de-escalate antibiotics based on the combination of quantitative cultures and multiplex PCR rapid diagnostic tests.MethodsWe analyzed data from SCRIPT, a single-center prospective cohort study of mechanically ventilated patients who underwent a BAL for suspected pneumonia. We used the novel Narrow Antibiotic Therapy (NAT) score to quantify day-by-day antibiotic prescription pattern for each suspected pneumonia episode etiology (bacterial, viral, mixed bacterial/viral, microbiology-negative, and non-pneumonia control). We also analyzed and compared clinical outcomes for each pneumonia etiology, including unfavorable outcomes (a composite of in-hospital mortality, discharge to hospice, or requiring lung transplantation during hospitalization), duration of ICU stay, and duration of intubation. Clinical outcomes were compared with the Mann-Whitney U test and Fisher's exact test.ResultsWe included 686 patients with 927 pneumonia episodes. NAT score analysis indicated that an antibiotic de-escalation pattern was evident in all pneumonia etiologies except resistant bacterial pneumonia. Microbiology-negative pneumonia was treated similarly to susceptible bacterial pneumonia in terms of antibiotic spectrum. Over a quarter of the time in viral pneumonia episodes, antibiotics were completely discontinued. Unfavorable outcomes were comparable across all pneumonia etiologies. Patients with viral and mixed bacterial/viral pneumonia had longer durations of ICU stay and intubation.ConclusionsBAL quantitative cultures and multiplex PCR rapid diagnostic tests resulted in prompt antibiotic de-escalation in critically ill pneumonia patients. There was no evidence of increased incidence of unfavorable outcomes.
| S-EPMC11419224 | biostudies-literature
Project description:Background and objectivesInappropriate vancomycin use is common in children's hospitals. We report a quality improvement (QI) intervention to reduce vancomycin use in our tertiary care PICU.MethodsWe retrospectively quantified the prevalence of infections caused by organisms requiring vancomycin therapy, including methicillin-resistant Staphylococcus aureus (MRSA), among patients with suspected bacterial infections. Guided by these data, we performed 3 QI interventions over a 3-year period, including (1) stakeholder education, (2) generation of a consensus-based guideline for empiric vancomycin use, and (3) implementation of this guideline through clinical decision support. Vancomycin use in days of therapy (DOT) per 1000 patient days was measured by using statistical process control charts. Balancing measures included frequency of bacteremia due to an organism requiring vancomycin not covered with empiric therapy, 30-day mortality, and cardiovascular, respiratory, and renal organ dysfunction.ResultsAmong 1276 episodes of suspected bacterial infection, a total of 19 cases of bacteremia (1.5%) due to organisms requiring vancomycin therapy were identified, including 6 MRSA bacteremias (0.5%). During the 3-year QI project, overall vancomycin DOT per 1000 patient days in the PICU decreased from a baseline mean of 182 DOT per 1000 patient days to 109 DOT per 1000 patient days (a 40% reduction). All balancing measures were unchanged, and all cases of MRSA bacteremia were treated empirically with vancomycin.ConclusionOur interventions reduced overall vancomycin use in the PICU without evidence of harm. Provider education and consensus building surrounding indications for empiric vancomycin use were key strategies.
| S-EPMC9647566 | biostudies-literature
Project description: Not available
| S-EPMC7599318 | biostudies-literature
Project description:Metagenomic next-generation sequencing (mNGS) and droplet digital PCR (ddPCR) have recently demonstrated a great potential for pathogen detection. However, few studies have been undertaken to compare these two nucleic acid detection methods for identifying pathogens in patients with bloodstream infections (BSIs). This prospective study was thus conducted to compare these two methods for diagnostic applications in a clinical setting for critically ill patients with suspected BSIs. Upon suspicion of BSIs, whole blood samples were simultaneously drawn for ddPCR covering 20 common isolated pathogens and four antimicrobial resistance (AMR) genes, mNGS, and blood culture. Then, a head-to-head comparison was performed between ddPCR and mNGS. A total of 60 episodes of suspected BSIs were investigated in 45 critically ill patients, and ddPCR was positive in 50 (83.3%), mNGS in 41 (68.3%, not including viruses), and blood culture in 10 (16.7%) episodes. Of the 10 positive blood cultures, nine were concordantly identified by both mNGS and ddPCR methods. The head-to-head comparison showed that ddPCR was more rapid (~4 h vs. ~2 days) and sensitive (88 vs. 53 detectable pathogens) than mNGS within the detection range of ddPCR, while mNGS detected a broader range of pathogens (126 vs. 88 detectable pathogens, including viruses) than ddPCR. In addition, a total of 17 AMR genes, including 14 blaKPC and 3 mecA genes, were exclusively identified by ddPCR. Based on their respective limitations and strengths, the ddPCR method is more useful for rapid detection of common isolated pathogens as well as AMR genes in critically ill patients with suspected BSI, whereas mNGS testing is more appropriate for the diagnosis of BSI where classic microbiological or molecular diagnostic approaches fail to identify causative pathogens.
| S-EPMC8165239 | biostudies-literature
Project description:BackgroundPneumonia is the most common hospital-acquired infection affecting patients in the intensive care unit (ICU). However, current national guidelines for the treatment of hospital-acquired pneumonia (HAP) are several years old and the diagnosis of pneumonia in mechanically ventilated patients (VAP) has been subject to considerable recent attention. The optimal duration of antibiotic therapy for HAP in the critically ill is uncertain.ObjectivesTo assess the effectiveness of short versus prolonged-course antibiotics for HAP in critically ill adults, including patients with VAP.Search methodsWe searched CENTRAL (2015, Issue 5), MEDLINE (1946 to June 2015), MEDLINE in-process and other non-indexed citations (5 June 2015), EMBASE (2010 to June 2015), LILACS (1982 to June 2015) and Web of Science (1955 to June 2015).Selection criteriaWe considered all randomised controlled trials (RCTs) comparing a fixed 'short' duration of antibiotic therapy with a 'prolonged' course for HAP (including patients with VAP) in critically ill adults.Data collection and analysisTwo review authors conducted data extraction and assessment of risk of bias. We contacted trial authors for additional information.Main resultsWe identified six relevant studies involving 1088 participants. This included two new studies published after the date of our previous review (2011). There was substantial variation in participants, in the diagnostic criteria used to define an episode of pneumonia, in the interventions and in the reported outcomes. We found no evidence relating to patients with a high probability of HAP who were not mechanically ventilated. For patients with VAP, overall a short seven- or eight-day course of antibiotics compared with a prolonged 10- to 15-day course increased 28-day antibiotic-free days (two studies; N = 431; mean difference (MD) 4.02 days; 95% confidence interval (CI) 2.26 to 5.78) and reduced recurrence of VAP due to multi-resistant organisms (one study; N = 110; odds ratio (OR) 0.44; 95% CI 0.21 to 0.95), without adversely affecting mortality and other recurrence outcomes. However, for cases of VAP specifically due to non-fermenting Gram-negative bacilli (NF-GNB), recurrence was greater after short-course therapy (two studies, N = 176; OR 2.18; 95% CI 1.14 to 4.16), though mortality outcomes were not significantly different. One study found that a three-day course of antibiotic therapy for patients with suspected HAP but a low Clinical Pulmonary Infection Score (CPIS) was associated with a significantly lower risk of superinfection or emergence of antimicrobial resistance, compared with standard (prolonged) course therapy.Authors' conclusionsOn the basis of a small number of studies and appreciating the lack of uniform definition of pneumonia, we conclude that for patients with VAP not due to NF-GNB a short, fixed course (seven or eight days) of antibiotic therapy appears not to increase the risk of adverse clinical outcomes, and may reduce the emergence of resistant organisms, compared with a prolonged course (10 to 15 days). However, for patients with VAP due to NF-GNB, there appears to be a higher risk of recurrence following short-course therapy. These findings do not differ from those of our previous review and are broadly consistent with current guidelines. There are few data from RCTs comparing durations of therapy in non-ventilated patients with HAP, but on the basis of a single study, short-course (three-day) therapy for HAP appears not to be associated with worse clinical outcome, and may reduce the risk of subsequent infection or the emergence of resistant organisms when there is low probability of pneumonia according to the CPIS.
| S-EPMC7025798 | biostudies-literature
Project description:ObjectivesTo investigate the potential impact of the syndromic multiplex FilmArray® Pneumonia plus Panel (FAPP) on the antimicrobial treatment guidance of patients with ventilated hospital-acquired pneumonia (VHAP).MethodsRespiratory fluids from 100 adult patients with VHAP, receiving invasive mechanical ventilation in three intensive care units from one French university hospital, were tested prospectively using FAPP. Conventional cultures were performed in parallel as routine practice. Clinicians were left blinded to the FAPP results. Antimicrobial therapies based on FAPP results were simulated by independent blinded experts according to a predefined algorithm and compared to 1) those prescribed in practice according to local guidelines (real-life), and 2) those that complied with the international ERS/ESICM/ESCMID/ALAT recommendations. The primary endpoint was the number of days of broad-spectrum antimicrobial therapy. Secondary endpoints were the rates of microbiological treatment failure and cost-effectiveness ratio.ResultsThe predicted median duration of broad-spectrum antibiotics was 0 [0-1.25] day in the FAPP-based simulation, versus 2 [0-6] days in real-life (p<0.0001) and 2 [2-3.25] days in the recommendations-based simulation (p<0.0001). Treatment failure was predicted in 3% of cases with FAPP results versus observed in 11% in real-life (p=0.08) and 6% with recommendations-based simulation (p=0.37). The incremental cost-effectiveness ratio was 1 121 € [-7021; 6794] to avoid one day of non-optimized antimicrobial therapy.ConclusionsOur results suggest that using FAPP in patients with VHAP has the potential to reduce the use of broad-spectrum antimicrobial therapy without increasing the risk of microbial treatment failure.
| S-EPMC9043525 | biostudies-literature
Project description:Significant alterations in the pharmacokinetics (PK) of antimicrobials have been reported in critically ill patients. We describe PK parameters of imipenem in intensive care unit (ICU) patients with suspected ventilator-associated pneumonia and evaluate several dosage regimens.This French multicentre, prospective, open-label study was conducted in ICU patients with a presumptive diagnosis of ventilator-associated pneumonia caused by Gram-negative bacilli, who empirically received imipenem intravenously every 8?h. Plasma imipenem concentrations were measured during the fourth imipenem infusion using six samples (trough, 0.5, 1, 2, 5 and 8?h). Data were analysed with a population approach using the stochastic approximation expectation maximization algorithm in Monolix?4.2. A Monte Carlo simulation was performed to evaluate the following six dosage regimens: 500, 750 or 1000?mg with administration every 6 or 8?h. The pharmacodynamic target was defined as the probability of achieving a fractional time above the minimal inhibitory concentration (MIC) of >40%.Fifty-one patients were included in the PK analysis. Imipenem concentration data were best described by a two-compartment model with three covariates (creatinine clearance, total bodyweight and serum albumin). Estimated clearance (between-subject variability) was 13.2?l?h(-1) (38%) and estimated central volume 20.4?l (31%). At an MIC of 4??g?ml(-1) , the probability of achieving 40% fractional time > MIC was 91.8% for 0.5?h infusions of 750?mg every 6?h, 86.0% for 1000?mg every 8?h and 96.9% for 1000?mg every 6?h.This population PK model accurately estimated imipenem concentrations in ICU patients. The simulation showed that for these patients, the best dosage regimen of imipenem is 750?mg every 6?h and not 1000?mg every 8?h.
| S-EPMC4243876 | biostudies-literature
Project description:BackgroundClinical guidelines suggest testing for respiratory viruses during the influenza season, but are unclear which categories of patients on the intensive care unit (ICU) should be tested.ObjectiveWe described the clinical practice of diagnostic testing for respiratory virus infections in patients presenting to ICU with suspected community-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP).Study designProspective observational study in consecutive CAP and HAP patients with an ICU stay of more than 24h in two tertiary care hospitals in The Netherlands, from 2011 to December 2013. The proportion of patients receiving diagnostic testing with PCR for the presence of respiratory viruses in respiratory tract specimens was determined.ResultsIn total, 1452 patients were included, of which 712 patients presented with CAP and 740 with HAP. In CAP, 282 of 712 (40%) were tested for respiratory viruses (190 of 417 (46%) during the influenza season). In HAP, 95 of 740 (13%) were tested (50 of 372 (13%) during the influenza season). Regardless of the season, virus diagnostic tests were ordered significantly more often in patients with comorbidities, and in those presenting with elevated CRP and leucopenia. In patients who were tested during the influenza season, the prevalence of influenza was 14% in patients with CAP and 10% in those with HAP. Influenza was absent during the summer in both groups.ConclusionsLess than half of patients admitted to the ICU with suspected pneumonia were tested for the presence of viral pathogens, either in or outside the influenza season.
| S-EPMC7106504 | biostudies-literature