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Evaluation of a Multiplex PCR Panel for the Microbiologic Diagnosis of Pneumonia in Hospitalized Patients: Experience from an Academic Medical Center

Zacharioudakis, Ioannis M; Zervou, Fainareti N; Yanina, Dubrovskaya; Inglima, Kenneth; See, Benjamin; Aguero-Rosenfeld, Maria
OBJECTIVES/OBJECTIVE:We evaluated the value of BioFire® FilmArray® pneumonia panel in establishing a microbiologic diagnosis of pneumonia. We evaluated opportunities for antimicrobial optimization from its use. METHODS:We included adult patients with pneumonia between May 2019-January 2020. The pneumonia panel was performed on high-quality sputum specimens and the results were prospectively compared with sputum cultures and other tests performed per standard of care. RESULTS: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 microbiologic diagnosis among the patients with culture submitted before antimicrobial administration (9/15 vs. 20/55; p = 0.09). The panel increased the microbiologic 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, not covered by empiric treatment and another 70 antimicrobials in 49 patients that could have been stopped. CONCLUSIONS:Incorporation of the pneumonia panel in the diagnostic work-up of pneumonia substantially increased the rate of microbiologic diagnosis and revealed abundant opportunities for antimicrobial optimization.
PMID: 33434669
ISSN: 1878-3511
CID: 4746732

Is Early Clearance of Blood Cultures the Be-All and End-All Outcome? [Letter]

Zacharioudakis, I M; Zervou, F N
ISSN: 1058-4838
CID: 4977972

Evaluation of a multiplex PCR panel for the microbiologic diagnosis of pneumonia in hospitalized patients: a retrospective analysis from an academic medical center [Meeting Abstract]

Zacharioudakis, I; Zervou, F; Inglima, K; See, B; Aguero-Rosenfeld, M E
Background: Pneumonia is a leading cause of hospitalization and mortality. Due to the low yield of available diagnostic tests, ATS/IDSA pneumonia guidelines recommend a microbiologic work-up only for hospitalized patients with severe pneumonia.
Method(s): From 5/2019 to 1/2020, we selected adult patients with clinical and radiographic findings highly suggestive of pneumonia. The BioFire FilmArray pneumonia panel was performed on sputum specimens that met quality microbiologic criteria and the results were compared to those of sputum cultures and other tests sent per standard of care. A limit of 105 copies/mL was used for positivity in semi-quantitative bacterial targets. The empiric antimicrobial regimen was reviewed to quantify the potential for antimicrobial optimization.
Result(s): Seventy patients were included in the analysis. Median age was 70 (IQR 53.5-81.75), and the majority (43 patients, 61.4%) were classified as Class IV and V using the pneumonia severity index, indicating severe cases of pneumonia. Sixty-nine patients completed at least a 5-day course for pneumonia and 14.3% died during their hospitalization. The fifteen patients (21.4%) that submitted a sputum culture before the initiation of antimicrobial therapy, had a trend towards a positive sputum culture (60% (9/15) vs 36.4% (20/55)) (p=0.09). The BioFire FilmArray pneumonia Panel increased the number of patients who received a microbiologic diagnosis from 29 (41%) to 59 (84.3%) (p< 0.001). The per isolate analysis revealed significantly more targets detected for Haemophilus influenzae (p=0.002) and Streptococcus pneumoniae (p=0.05). On review of empiric antimicrobial treatment, there was possibility for antimicrobial optimization in 80% of patients, including 9 cases of pathogens (4 MRSA, 3 Legionella pneumophila, 2 CTX-M gram-negative rods) where the pathogens were not covered and another 70 antimicrobials in 49 patients that could be stopped. Flow chart Bacterial Pathogens Detected in Standard of Care Alone Testing and with the Addition of Pneumonia Panel. Potential for Antimicrobial Optimization Using the Pneumonia Panel
Conclusion(s): Incorporation of the pneumonia panel in the diagnostic work-up of patients hospitalized with pneumonia substantially increased the rate of microbiologic diagnosis and had the potential to guide appropriate antimicrobial therapy. Future studies to quantify the effects on clinical outcomes and cost-effectiveness from tailored therapy are needed
ISSN: 2328-8957
CID: 4856832

Association of SARS-CoV-2 genomic load in nasopharyngeal samples with adverse COVID-19 patient outcomes: A retrospective analysis from an academic hospital center in New York City [Meeting Abstract]

Zacharioudakis, I; Prasad, P; Zervou, F; Basu, A; Inglima, K; Weisenberg, S; Aguero-Rosenfeld, M E
Background: SARS-CoV-2, the cause of COVID-19 pneumonia, is associated with heterogenous presentations ranging from asymptomatic infection to severe respiratory failure. We explored the association of SARS-CoV-2 genomic load as a risk factor for adverse patient outcomes.
Method(s): We included adult patients admitted to the hospital with clinical and radiographic findings of pneumonia and a confirmatory polymerase chain reaction (PCR) test of SARS-CoV-2 within 24 hours of admission. We segregated patients into 3 genomic load status groups: low (Cycle threshold (Ct) >=35) intermediate (25< Ct< 35) and high (Ct <=25) using real-time PCR. The primary outcome was a composite outcome of death, intubation and/or use of extracorporeal membrane oxygenation. Secondary outcomes included severity of pneumonia on admission, as measured by the Pneumonia Severity Index (PSI). Sensitivity analyses were performed to include Acute Respiratory Distress Syndrome (ARDS) in the composite outcome and varying Ct classification breakpoints.
Result(s): Of 457 patients positive for SARS-CoV-2 assay from March 31st to April 10th 2020, 316 met inclusion criteria and were included in the final analysis. Included patients were followed for a median of 25 days (IQR 21-28). High genomic load at presentation was associated with higher Charlson Comorbidity Index scores (p=0.005), transplant recipient status (p< 0.001) and duration of illness less than 7 days (p=0.005). Importantly, patients with high genomic load were more likely to reach the primary endpoint (p=0.001), and had higher PSI scores on admission (p=0.03). In multivariate analysis, high genomic load remained an independent predictor of primary outcome. Results remained significant in sensitivity analyses.
Conclusion(s): High genomic load of SARS-CoV-2 in nasopharyngeal samples at the time of admission is independently associated with mortality and intubation. This finding should prompt further research on the role of viral load as a clinical predictor and possible modifiable risk factor for adverse outcomes as treatment strategies evolve in this global pandemic. (Table Presented)
ISSN: 2328-8957
CID: 4856822

Association of SARS-CoV-2 genomic load trends with clinical status in COVID-19:A retrospective analysis from an academic hospital center in New York City [Meeting Abstract]

Zacharioudakis, I; Zervou, F; Prasad, P; Shao, Y; Basu, A; Inglima, K; Weisenberg, S; Aguero-Rosenfeld, M E
Background: The Infectious Diseases Society of America has identified the potential use of SARS-CoV-2 genomic load for prognostication purposes as a key research question.
Method(s): We designed a retrospective cohort study that included adult patients with COVID-19 pneumonia who had at least 2 positive nasopharyngeal tests at least 24 hours apart to study the correlation between the change in the genomic load of SARS-CoV-2 in nasopharyngeal samples, as reflected by the Cycle threshold (Ct) value of the real-time Polymerase Chain Reaction (PCR) assay, with change in clinical status. The Sequential Organ Failure Assessment (SOFA) score was used as a surrogate for patients' clinical status. A linear mixed-effects regression analysis was performed.
Result(s): Among 457 patients who presented to the emergency department between 3/31/2020- 4/10/2020, we identified 42 patients who met the inclusion criteria. The median initial SOFA score was 2 (IQR 2-3). 20 out of 42 patients had a lower SOFA score on their subsequent tests. We identified a statistically significant inverse correlation between the change in SOFA score and change in the Ct value with a decrease in SOFA score by 0.05 (SE 0.02; p < 0.05) for an increase in Ct values by 1. This correlation was independent of the duration of symptoms.
Conclusion(s): Our findings suggest that an increasing Ct value in sequential tests may be of prognostic value for patients diagnosed with COVID-19 pneumonia. Before repeat testing can be recommended routinely in clinical practice as a predictor of disease outcomes, prospective studies with a standardized interval between repeat tests should confirm our findings. (Table Presented)
ISSN: 2328-8957
CID: 4856812

Outcomes among HIV-positive patients hospitalized with COVID-19

Karmen-Tuohy, Savannah; Carlucci, Philip M; Zervou, Fainareti N; Zacharioudakis, Ioannis M; Rebick, Gabriel; Klein, Elizabeth; Reich, Jenna; Jones, Simon; Rahimian, Joseph
BACKGROUND:SARS-CoV-2 infection continues to cause significant morbidity and mortality worldwide. Preliminary data on SARS-CoV-2 infection suggests that some immunocompromised hosts experience worse outcomes. We performed a retrospective matched cohort study to characterize outcomes in HIV-positive patients with SARS-CoV-2 infection. METHODS:Leveraging data collected from electronic medical records for all patients hospitalized at NYU Langone Health with COVID-19 between March 2, 2020 and April 23, 2020, we matched 21 HIV-positive patients to 42 non-HIV patients using a greedy nearest neighbor algorithm. Admission characteristics, laboratory results, and hospital outcomes were recorded and compared between the two groups. RESULTS:While there was a trend toward increased rates of ICU admission, mechanical ventilation, and mortality in HIV-positive patients, these differences were not statistically significant. Rates for these outcomes in our cohort are similar to those previously published for all patients hospitalized with COVID-19. HIV-positive patients had significantly higher admission and peak CRP values. Other inflammatory markers did not differ significantly between groups, though HIV-positive patients tended to have higher peak values during their clinical course. Three HIV-positive patients had superimposed bacterial pneumonia with positive sputum cultures, and all three patients expired during hospitalization. There was no difference in frequency of thrombotic events or myocardial infarction between these groups. CONCLUSION/CONCLUSIONS:This study provides evidence that HIV coinfection does not significantly impact presentation, hospital course, or outcomes of patients infected with SARS-CoV-2, when compared to matched non-HIV patients. A larger study is required to determine if the trends we observed apply to all HIV-positive patients.
PMID: 32568770
ISSN: 1944-7884
CID: 4506692

Association of SARS-CoV-2 Genomic Load with COVID-19 Patient Outcomes

Zacharioudakis, Ioannis M; Prasad, Prithiv J; Zervou, Fainareti N; Atreyee Basu; Inglima, Kenneth; Weisenberg, Scott A; Aguero-Rosenfeld, Maria E
ISSN: n/a
CID: 4641142

Varying Vaccination Rates Among Patients Seeking Care for Acute Respiratory Illness: A Systematic Review and Meta-analysis

Shehadeh, Fadi; Zacharioudakis, Ioannis M; Kalligeros, Markos; Mylona, Evangelia K; Karki, Tanka; van Aalst, Robertus; Chit, Ayman; Mylonakis, Eleftherios
Background/UNASSIGNED:Complications following influenza infection are a major cause of morbidity and mortality, and the Centers for Disease Control Advisory Committee on Immunization Practices recommends universal annual vaccination. However, vaccination rates have remained significantly lower than the Department of Health and Human Services goal. The aim of this work was to assess the vaccination rate among patients who present to health care providers with influenza-like illness and identify groups with lower vaccination rates. Methods/UNASSIGNED:We performed a systematic search of the PubMed and EMBASE databases with a time frame of January 1, 2010, to March 1, 2019 and focused on the vaccination rate among patients seeking care for acute respiratory illness in the United States. A random effects meta-analysis was performed to estimate the pooled seasonal influenza vaccination rate, and we used a time trend analysis to identify differences in annual vaccination over time. Results/UNASSIGNED: = .027). Conclusions/UNASSIGNED:In conclusion, because of the significantly lower influenza vaccination rates in black and Hispanic communities, societal initiatives and community outreach programs should focus on these populations and on children and adolescents aged 9-17 years.
PMID: 32685605
ISSN: 2328-8957
CID: 4531882

Oral vancomycin prophylaxis against recurrent Clostridioides difficile infection: Efficacy and side effects in two hospitals

Zacharioudakis, Ioannis M; Zervou, Fainareti N; Dubrovskaya, Yanina; Phillips, Michael S
OBJECTIVE:The data regarding the effectiveness of chemical prophylaxis against recurrent C. difficile infection (CDI) remain conflicting. DESIGN/METHODS:Retrospective cohort study on the effectiveness of oral vancomycin for prevention of recurrent CDI. SETTING/METHODS:Two academic centers in New York. METHODS:Two participating hospitals implemented an automated alert recommending oral vancomycin 125 mg twice daily in patients with CDI history scheduled to receive systemic antimicrobials. Measured outcomes included breakthrough and recurrent CDI rates, defined as CDI during and 1 month after initiation of prophylaxis, respectively. A self-controlled, before-and-after study design was employed to examine the effect of vancomycin prophylaxis on the prevalence of vancomycin-resistant Enterococcus spp (VRE) colonization and infection. RESULTS:We included 264 patients in the analysis. Breakthrough CDI was identified in 17 patients (6.4%; 95% confidence interval [CI], 3.8%-10.1%) and recurrent in 22 patients (8.3%; 95% CI, 5.3%-12.3%). Among the 102 patients with a history of CDI within the 3 months preceding prophylaxis, 4 patients (3.9%; 95% CIs, 1.1%-9.7%) had breakthrough CDI and 9 had recurrent disease (8.8%; 95% CIs, 4.1%-16.1%). In the 3-month period following vancomycin prophylaxis, we detected a statistically significant increase in both the absolute number of VRE (χ2, 0.003) and the ratio of VRE to VSE isolates (χ2, 0.003) compared to the combined period of 1.5 months preceding and the 3-4.5 months following prophylaxis. This effect persisted 6 months following prophylaxis. CONCLUSIONS:Prophylactic vancomycin is an effective strategy to prevent CDI recurrence, but it increases the risk of VRE colonization. Thus, a careful selection of patients with high benefit-to-risk ratio is needed for the implementation of this preventive policy.
PMID: 32539877
ISSN: 1559-6834
CID: 4484552

In-depth analysis of T2Bacteria positive results in patients with concurrent negative blood culture: a case series

Kalligeros, Markos; Zacharioudakis, Ioannis M; Tansarli, Giannoula S; Tori, Katerina; Shehadeh, Fadi; Mylonakis, Eleftherios
BACKGROUND:T2Bacteria assay uses T2 magnetic resonance (T2MR) technology for the rapid diagnosis of bacterial bloodstream infections (BSIs). This FDA cleared technology can detect 5 of the most prevalent pathogens causing bacteremia (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecium). Because the significance of discordant results between the T2Bacteria assay and blood culture (BC) remains a challenge, in this case series we reviewed the medical records of patients who had a positive T2Bacteria test and a concurrent negative BC. METHODS:Among 233 participants, we identified 20 patients with 21 (9%) discordant T2Bacteria-positive/BC-negative (T2+/BC-) results. We classified these results based on clinical cultures and clinical evidence. RESULTS:When we analyzed these 21 discordant results in-depth, 11 (52.5%) fulfilled criteria for probable BSI, 4 (19%) for possible BSI, and 6 (28.5%) were presumptive false positives. Among the probable/possible BSIs, discordant results were often associated with patients diagnosed with closed space and localized infections [pyelonephritis (n = 7), abscess (n = 4), pneumonia (n = 1), infected hematoma (n = 1), and osteomyelitis (n = 1)]. Also, within the preceding 2 days of the T2+/BC- blood sample, 80% (16/20) of the patients had received at least one dose of an antimicrobial agent which was active against the T2Bacteria-detected pathogen. CONCLUSIONS:In the majority of discrepant results, the T2Bacteria assay detected a plausible pathogen that was supported by clinical and/or microbiologic data. Discrepancies appear to be associated with closed space and localized infections and the recent use of effective antibacterial agents. The clinical significance and potential implications of such discordant results should be further investigated.
PMID: 32380973
ISSN: 1471-2334
CID: 4506682