We evaluated the value of BioFire® FilmArray® pneumonia panel in establishing a microbiological diagnosis of pneumonia. We evaluated opportunities for antimicrobial optimization from its use.We included adult patients with pneumonia between May 2019 and January 2020. The pneumonia panel was used on high-quality sputum specimens, and the results were prospectively compared with sputum cultures and other tests performed according to standard of care.Seventy patients were included, sixty-nine of whom completed a 5-day antimicrobial course for pneumonia, and 14.3% died during hospitalization. There was a trend of higher rate of microbiological diagnosis among the patients with culture submitted before antimicrobial administration (9/15 vs. 20/55; p = 0.09). The panel increased the microbiological diagnosis from 29/70 to 59/70 (p < 0.001) patients. The per isolate analysis revealed an increase in the isolation of Haemophilus influenzae (p = 0.002) and Streptococcus pneumoniae (p = 0.05). On review of empiric antimicrobials, there was potential for antimicrobial optimization in 56/70 patients, including 9 bacteria among 9 patients, which were not covered by empiric treatment and another 70 antimicrobials in 49 patients that could have been stopped.Incorporation of the pneumonia panel in the diagnostic work-up of pneumonia substantially increased the rate of microbiological diagnosis and revealed abundant opportunities for antimicrobial optimization.
Background. Intensive care unit (ICU) patients are at higher risk for Clostridium difficile infection (CDI).We performed a systematic review and meta-analysis of published studies from 1983 to 2015 using the PubMed, EMBASE, and Google Scholar databases to study the prevalence and outcomes of CDI in this patient population. Among the 9146 articles retrieved from the studies, 22 articles, which included a total of 80 835 ICU patients, were included in our final analysis. Results. The prevalence of CDI among ICU patients was 2% (95% confidence interval [CI], 1%-2%), and among diarrheic ICU patients the prevalence was 11% (95% CI, 6%-17%). Among CDI patients, 25% (95% CI, 5%-51%) were diagnosed with pseudomembranous colitis, and the estimated length of ICU stay before CDI acquisition was 10.74 days (95% CI, 5%-51%). The overall hospital mortality among ICU patients with CDI was 32% (95% CI, 26%-39%), compared with 24% (95% CI, 14%-36%) among those without CDI presenting a statistically significant difference in mortality risk (P = .030). It is worth noting that the length of ICU and hospital stay among CDI patients was significantly longer, compared with non-CDI patients (standardized mean of difference [SMD] = 0.49, 95% CI, .39%-.6%, P = .00 and SMD = 1.15, 95% CI, .44%-1.91%, P = .003, respectively). It is noteworthy that the morbidity score at ICU admission (Acute Physiology and Chronic Health Evaluation II [APACHE II]) was not statistically different between the 2 groups (P = .911), implying that the differences in outcomes can be attributed to CDI. Conclusions. The ICU setting is associated with higher prevalence of CDI. In this setting, CDI is associated with increased hospital mortality and prolonged ICU and overall hospital stay. These findings highlight the need for additional prevention and treatment studies in this setting.
Introduction: Evolving data suggests that booster vaccine doses enhance the immunogenicity of SARS-CoV-2 vaccination in solid organ transplant (SOT) recipients with higher IgG responses, neutralizing antibodies titers, and greater SARS-CoV-2–specific T-cell counts. However, antibody responses are attenuated by immunosuppression regimens and a significant proportion of patients continue to be at high risk for infection despite vaccination. Currently, there is no recommended framework for monitoring for potential vaccine-related immunological graft injury. Here, we describe kinetics of dd-cfDNA pre- and post-booster vaccination in kidney transplant recipients (KTRs), including dual organ recipients. Methods: Electronic medical records were reviewed to identify KTRs that received a SARS-CoV-2 booster vaccine dose in 2021 and were monitored with dd-cfDNA (AlloSure, CareDx) pre- and post-vaccination. dd-cfDNA was collected as part of standard of care assessment. Pre-booster dd-cfDNA levels were defined as the most recent result prior to booster dose administration. Post-vaccination results were collected up to 30 days post-booster administration. Results: 116 KTRs were identified for analysis. Patient demographics are summarized in Table 1. Median time from transplant to SARS-CoV-2 booster administration was 463 days (IQR 333 – 787.25 days, Table 1). Pre-booster dd-cfDNA levels were established a median of 9 days (IQR 2.25 – 16 days) prior to vaccination. The median level of dd-cfDNA pre-booster was 0.17% (IQR 0.12% – 0.25%). There was no significant difference in median levels of dd-cfDNA up to 30 days post-vaccine booster administration (Kruskal Wallis test with multiple comparisons, all p values >0.99, Figure 1). No adverse clinical events or acute rejection episodes were reported within 30 days of SARS-CoV-2 booster administration in this cohort. Conclusions: Median dd-cfDNA levels were not impacted by SARS-CoV-2 vaccine booster administration, suggesting that patterns of subclinical injury that may potentiate inflammation, allosensitization or allograft rejection are unlikely in this setting. The stability of dd-cfDNA demonstrated here further reinforces the safety profile of SARS-CoV-2 vaccine booster administration in KTRs.
Timing of detection of immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their use to support the diagnosis are of increasing interest. We used the Gold Standard Diagnostics ELISA to evaluate the kinetics of SARS-CoV-2 IgG, IgA, and IgM antibodies in sera of 82 hospitalized patients with polymerase chain reaction (PCR)-confirmed coronavirus disease 2019 (COVID-19). Serum samples were collected 1-59 days post-onset of symptoms (PoS) and we examined the association of age, sex, disease severity, and symptoms' duration with antibody levels. We also tested sera of 100 ambulatory hospital employees with PCR-confirmed COVID-19 and samples collected during convalescence, 35-57 days PoS. All but four of the admitted patients (95.1%) developed antibodies to SARS-CoV-2. Antibodies were detected within 7 days PoS; IgA in 60.0%, IgM in 53.3%, and IgG in 46.7% of samples. IgG positivity increased to 100% on Day 21. We did not observe significant differences in the rate of antibody development in regard to age and sex. IgA levels were highest in patients with a severe and critical illness. In multiple regression analyses, only IgA levels were statistically significantly correlated with critical disease (p = .05) regardless of age, sex, and duration of symptoms. Among 100 ambulatory hospital employees who had antibody testing after 4 weeks PoS only 10% had positive IgA antibodies. The most frequently isolated isotype in sera of employees after 30 days PoS was IgG (88%). IgA was the predominant immunoglobulin in early disease and correlated independently with a critical illness. IgG antibodies remained detectable in almost 90% of samples collected up to two months after infection.
Abstract Background Studies to date indicate that most adults develop IgG antibody to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within 6 weeks of COVID-19 symptom onset. The seroconversion rate of solid organ transplant recipients (SOTR) following COVID-19 is unknown. Elucidation of humoral immune responses following COVID-19 in SOTR may inform risk of reinfection and the development of safe and effective vaccines for immunocompromised hosts. Methods We assessed the frequency of SARS-CoV-2 IgG detection among adult SOTR diagnosed with COVID-19 by nasopharyngeal PCR assays between 3/1/2020 and 6/5/2020. SARS-CoV-2 IgG was detected in serum using the Abbott IgG assay at the manufacturer’s recommended cut-off. Our primary objective was the frequency of SARS-CoV-2 IgG seropositivity after COVID-19. A secondary objective was to identify clinical factors associated with seroconversion. The mean age and nadir absolute lymphocyte count (ALC) were calculated between seropositive and negative SOTR and compared by Student’s t-test. Results Among 93 SOTR diagnosed with COVID-19, 19 died before SARS-CoV-2 IgG testing could be performed, and 18 had testing pending as of abstract submission. 56 SOTR (44 kidney, 5 heart, 4 liver, 1 lung, and 1 heart-kidney recipients) completed testing and were included in the analysis. Median age was 58 years (IQR 49.5–67), and all received maintenance immunosuppression at the time of COVID-19 diagnosis with median nadir ALC during illness of 400 (IQR 200–600). SARS-CoV-2 IgG testing was performed at a median of 60 days (IQR 50–70) from symptom onset, the shortest interval being 16 days. 47 out of 56 SOTR tested positive for SARS-CoV-2 IgG. The likelihood of seroconversion was not different between those who were tested at < or ≥ 60 days from symptom onset (p=0.26), nor did it vary significantly by age (p =0.59), gender (p=0.53) or nadir ALC (p =0.28). Conclusion 83% of evaluated SOTR with COVID-19 disease had detectable SARS-CoV-2 IgG in serum at a median of 60 days after symptom onset. Studies are ongoing to identify variables associated with poor antibody response among the nearly 20% of SOTR in this cohort who failed to seroconvert. The significance of seroconversion on risk of reinfection and vaccine immunogenicity remains to be determined. Disclosures All Authors: No reported disclosures
Invasive candidiasis is a common healthcare-associated infection with a high mortality rate that can exceed 60% in cases of septic shock. Blood culture performance is far from ideal, due to the long time to positivity and suppression by antifungal agents. The T2 Magnetic Resonance (T2MR) assay is an FDA-approved qualitative molecular diagnostic method that can detect and speciate the 5 most common Candida spp.; namely, Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, and Candida krusei, in approximately 5 h. In a multicenter clinical trial that included both a prospective and a contrived arm to represent the full range of clinically relevant concentrations of Candida spp., T2MR demonstrated a sensitivity and specificity of 91.1% and 98.1%, respectively. The utility of T2MR in candidemia depends on the prevalence of disease in each clinical setting. In intensive care units and other high-prevalence settings, the incorporation of T2MR in diagnostic algorithms is very appealing. T2MR is expected to allow timely initiation of antifungal therapy and help with anti-fungal stewardship. In low-prevalence settings, the positive predictive value of T2MR might not be enough to justify initiation of antifungal treatment in itself. The performance of T2MR has not been studied in cases of deep-seated candidiasis. Despite some promising evidence in published clinical trials, further studies are needed to determine the performance of T2MR in invasive candidiasis without candidemia. Overall, experience with T2MR in everyday clinical practice is evolving but, in the right setting, this technology is expected to provide “actionable information” for the management of patients evaluated for candidemia.
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