Background Despite advances in microbiologic techniques, for patients with complex infections it often remains a challenge to identify the causative infectious pathogen. Traditional cultures (Cx) may fail to grow microorganisms due to inadequate sampling, prior antibiotic use, or the inherent insensitivity of culture methods for fastidious pathogens. Molecular tests allow for the detection of microbial nucleic acids directly from clinical specimens and do not require the presence of viable organisms for identification. Universal polymerase chain reaction testing (UPCR) is offered though the University of Washington Department of Laboratory Medicine and Pathology as a metagenomic approach using broad-range PCR primers followed by sequencing to hypothetically identify any pathogen present. The testing is composed of 3 separate tests for bacterial (BUPCR), fungal (FUPCR), and acid-fast (AFUPCR) organisms. The utility of UPCR has not been formally evaluated. Our objective is to describe the diagnostic utility of UPCR by comparing Cx and UPCR results, and their impact on management. Figure 1:Introduction - Types of Universal PCR Testing Methods We retrospectively collected data on UPCR and culture results and changes in antimicrobial therapy based on UPCR results for all patients with at least 1 UPCR test done during the 2-year study period. Results 367 UPCR tests were performed over 24 months on 155 patients. From 367 tests, 119 were FUPCR, 111 AFUPCR, and 137 BUPCR. 32/155 (20.6%) patients had positive UPCR. 25/32 were BUPCR and 7/32 were FUPCR. No AFUPCR was positive. In 8/155 (5.2%) patients management was changed based on UPCR results: Positive UPCR results directed treatment in 5 patients: 4 patients had positive UPCR and negative culture, and 1 had both UPCR and Cx positive but for different organisms. In all 5 therapy was changed in favor of UPCR result. All 5 tests were BUPCR.Negative UPCR led to antimicrobial discontinuation in 3 patients. 11/155 (7.1%) patients had negative UPCR and positive Cx, 10 of which were BUPCR and 1 AFUPCR. These results did not change management. Figure 2:Results – Type of Tissue and Test ResultsFigure 3:Results – Universal PCR Test Type and ResultsFigure 4:Results - Summary Conclusion Based on the real-world experience, UPCR results have limited impact on antimicrobial management in our institution. Further studies may try to identify clinical scenarios where UPCR may be of better clinical utility. Disclosures All Authors: No reported disclosures.
Our previous work has demonstrated that acute morphine administration causes powerful suppression of augmented breaths (ABs) at the low‐to‐mid dosage range for analgesia in adult rats. The present study was performed to determine the extent to which this suppression of ABs persists in the course of prolonged morphine administration. We studied breathing non‐invasively in adult rats in 2 separate experiments: Exp 1: animals were monitored immediately before, and repeatedly following s.c. bolus injections of morphine, 4 mg/kg loading dose and maintenance doses of 2 mg/kg given each hour for 8 consecutive hours (n=8). Exp 2: Animals were monitored immediately before and again repeatedly across 10 consecutive days of morphine treatment self‐administered via oral dosing in drinking water (n=7). Appropriate sham/control experiments were performed using saline injections and normal drinking water. In Exp 1, morphine injection caused a potent suppression of ABs, observed immediately upon first injection (6.0 ± 2.9 vs 0.5 ± 0.5 ABs/15 min, pre vs. post), and persisting throughout the 8 hours of study (P<0.001). This occurred despite there being no depression of minute ventilation. The prevalence of ABs in the sham injection condition remained unchanged across the 8 hours of study. In Exp 2, morphine concentration in drinking water was titrated up to 0.4 mg/mL across days 1 to 5, and remained constant at 0.4 mg/mL through day 10. This concentration was chosen so as to avoid taste aversion and drinking abstinence commonly seen when attempting to use higher concentrations of morphine. Animals self‐administered an average of 33.1 ± 6.9 mg/day (1.4 mg/kg/hr) on day 7 and 36.6 ± 3.4 mg/kg/day (1.5 mg/kg/hr) on day 10. This relatively low dosage was sub‐analgesic in efficacy as confirmed by lack of prolongation of tail flick latency. Despite the low dosage, continuously administered morphine caused significantly fewer ABs to be expressed on day 10 of morphine treatment (3.3 ± 1.5 ABs/15 min) compared to either pre‐treatment (7.0 ± 1.8) or day 10 of the control (6.3 ± 1.8) condition. No depression of minute ventilation was observed across the 10 days of treatment. These results confirm that the opioid‐induced suppression of ABs occurs rapidly and persists across extended treatment of at least 10 days. Moreover, this side effect occurs even in the sub‐analgesic dose range in the absence of any depression of minute ventilation.Support or Funding InformationThis work was supported by research funds provided by the Central Michigan University College of Medicine, and an Early Career Grant awarded by the Office of Research and Sponsored Programs at Central Michigan University.
Background Respiratory infections are a common cause of hospital admissions resulting in significant morbidity and mortality. Isolating specific pathogens from the respiratory tract is a diagnostic challenge. Traditional testing modalities are prone to contamination, time consuming, and have low sensitivity. Next generation genetic sequencing technology has made possible the development of a number of hypothesis free, fast, and highly accurate genome-based identification tests. In this study, we aim at assessing the initial use and performance of one of these tests, the Explify Respiratory panel, at a large quaternary hospital in west Michigan. Methods We performed retrospective analysis on 16 patients with suspected lower respiratory infections. Subjects were chosen for inclusion in the analysis based on the suspicion of pulmonary infection without an identified pathogen. The patient population included 5 immunocompromised patients, 3 with hematologic malignancy, 4 with solid tumor malignancy, and 2 transplant recipients. Results The test resulted in: lack of identified organism (5 patients), identification of non-pathogenic organisms (6 patients), and identification of organisms that were either identified by other traditional testing or did not impact provider’s therapeutic plan (5 patients). The results of Explify testing in all 16 patients did not have a clinical impact on patient care or treatment plan. Conclusion Explify testing seemed to be an appealing cost-effective tool that could replace other available testing modalities such as culture, other sequencing tests, and serological testing with faster turn-around time and less cost. However, it failed to demonstrate any benefit to clinicians in identifying respiratory pathogens while resulting in added cost burden to the patient. Moreover, it resulted in clinical delays of further investigation while awaiting the results. It remains unclear if the lack of clinical impact results from the extensive interventions and treatments that patients receive prior to Explify testing or from the poor sensitivity and performance of the test.This study emphasizes the importance of continuous evaluation of new diagnostic testing before widespread implementation to improve patient care and minimize cost burden. Disclosures All Authors: No reported disclosures
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