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Diagnostic stewardship in infectious diseases: steps towards intentional diagnostic testing

Zacharioudakis, Ioannis M; Zervou, Fainareti N
PMID: 35670110
ISSN: 1746-0921
CID: 5277712

Risk Factors for Hospital Readmission for Clostridioides difficile Infection: A Statewide Retrospective Cohort Study

Benitez, Gregorio; Shehadeh, Fadi; Kalligeros, Markos; Mylona, Evangelia K; Tran, Quynh-Lam; Zacharioudakis, Ioannis M; Mylonakis, Eleftherios
(1) Background: Clostridioides difficile infection (CDI) is associated with a high recurrence rate, and a significant proportion of patients with CDI are readmitted following discharge. We aimed to identify the risk factors for CDI-related readmission within 90 days following an index hospital stay for CDI. (2) Methods: We analyzed the electronic medical data of admitted patients in our health system over a two-year period. A multivariate logistic regression model, supplemented with bias-corrected and accelerated confidence intervals (BCa-CI), was implemented to assess the risk factors. (3) Results: A total of 1253 adult CDI index cases were included in the analysis. The readmission rate for CDI within 90 days of discharge was 11% (140/1253). The risk factors for CDI-related readmission were fluoroquinolone exposure within 90 days before the day of index CDI diagnosis (aOR: 1.58, 95% CI: 1.05-2.37), higher Elixhauser comorbidity score (aOR: 1.05, 95% CI: 1.02-1.07), and being discharged home (aOR: 1.64, 95% CI: 1.06-2.54). In contrast, a longer length of index stay (aOR: 0.97, 95% BCa-CI: 0.95-0.99) was associated with reduced odds of readmission for CDI. (4) Conclusion: More than 1 out of 10 patients were readmitted for CDI following an index hospital stay for CDI. Patients with recent previous fluoroquinolone exposure, greater overall comorbidity burden, and those discharged home are at higher risk of readmission for CDI.
PMID: 35631075
ISSN: 2076-0817
CID: 5284082

Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients: A Randomized Clinical Trial

Ortigoza, Mila B; Yoon, Hyunah; Goldfeld, Keith S; Troxel, Andrea B; Daily, Johanna P; Wu, Yinxiang; Li, Yi; Wu, Danni; Cobb, Gia F; Baptiste, Gillian; O'Keeffe, Mary; Corpuz, Marilou O; Ostrosky-Zeichner, Luis; Amin, Amee; Zacharioudakis, Ioannis M; Jayaweera, Dushyantha T; Wu, Yanyun; Philley, Julie V; Devine, Megan S; Desruisseaux, Mahalia S; Santin, Alessandro D; Anjan, Shweta; Mathew, Reeba; Patel, Bela; Nigo, Masayuki; Upadhyay, Rabi; Kupferman, Tania; Dentino, Andrew N; Nanchal, Rahul; Merlo, Christian A; Hager, David N; Chandran, Kartik; Lai, Jonathan R; Rivera, Johanna; Bikash, Chowdhury R; Lasso, Gorka; Hilbert, Timothy P; Paroder, Monika; Asencio, Andrea A; Liu, Mengling; Petkova, Eva; Bragat, Alexander; Shaker, Reza; McPherson, David D; Sacco, Ralph L; Keller, Marla J; Grudzen, Corita R; Hochman, Judith S; Pirofski, Liise-Anne; Parameswaran, Lalitha; Corcoran, Anthony T; Rohatgi, Abhinav; Wronska, Marta W; Wu, Xinyuan; Srinivasan, Ranjini; Deng, Fang-Ming; Filardo, Thomas D; Pendse, Jay; Blaser, Simone B; Whyte, Olga; Gallagher, Jacqueline M; Thomas, Ololade E; Ramos, Danibel; Sturm-Reganato, Caroline L; Fong, Charlotte C; Daus, Ivy M; Payoen, Arianne Gisselle; Chiofolo, Joseph T; Friedman, Mark T; Wu, Ding Wen; Jacobson, Jessica L; Schneider, Jeffrey G; Sarwar, Uzma N; Wang, Henry E; Huebinger, Ryan M; Dronavalli, Goutham; Bai, Yu; Grimes, Carolyn Z; Eldin, Karen W; Umana, Virginia E; Martin, Jessica G; Heath, Timothy R; Bello, Fatimah O; Ransford, Daru Lane; Laurent-Rolle, Maudry; Shenoi, Sheela V; Akide-Ndunge, Oscar Bate; Thapa, Bipin; Peterson, Jennifer L; Knauf, Kelly; Patel, Shivani U; Cheney, Laura L; Tormey, Christopher A; Hendrickson, Jeanne E
Importance/UNASSIGNED:There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective/UNASSIGNED:To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. Design, Setting, and Participants/UNASSIGNED:CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation. Interventions/UNASSIGNED:A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main Outcomes and Measures/UNASSIGNED:The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8. Results/UNASSIGNED:Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR<1] = 72%); the cOR for the secondary adjusted outcome was 0.92 (95% CrI, 0.74-1.16; P[cOR<1] = 76%). Exploratory subgroup analyses suggested heterogeneity of treatment effect: at day 28, cORs were 0.72 (95% CrI, 0.46-1.13; P[cOR<1] = 93%) for participants enrolled in April-June 2020 and 0.65 (95% CrI, 0.41 to 1.02; P[cOR<1] = 97%) for those not receiving remdesivir and not receiving corticosteroids at randomization. Median CCP SARS-CoV-2 neutralizing titer used in April to June 2020 was 1:175 (IQR, 76-379). Any adverse events (excluding transfusion reactions) were reported for 39 (8.2%) placebo recipients and 44 (9.4%) CCP recipients (P = .57). Transfusion reactions occurred in 2 (0.4) placebo recipients and 8 (1.7) CCP recipients (P = .06). Conclusions and Relevance/UNASSIGNED:In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use. Trial Registration/ Identifier: NCT04364737.
PMID: 34901997
ISSN: 2168-6114
CID: 5084962

The Utility of Scoring Systems in Determining the Need for Echocardiography in Patients with Staphylococcus aureus Bacteremia

Zervou, Fainareti N; Zacharioudakis, Ioannis M
PMID: 33972992
ISSN: 1537-6591
CID: 4867272

Impact of Streptococcus pneumoniae Urinary Antigen Testing in Patients With Community-Acquired Pneumonia Admitted Within a Large Academic Health System

Greenfield, Adam; Marsh, Kassandra; Siegfried, Justin; Zacharioudakis, Ioannis; Ahmed, Nabeela; Decano, Arnold; Aguero-Rosenfeld, Maria E; Inglima, Kenneth; Papadopoulos, John; Dubrovskaya, Yanina
Background/UNASSIGNED:Limited data support use of pneumococcal urinary antigen testing (PUAT) for patients with community-acquired pneumonia (CAP) as an antimicrobial stewardship tool. At our institution, CAP guidelines and admission order set were standardized to include universal PUAT. Methods/UNASSIGNED:This was a retrospective study of adults hospitalized in 2019 who had PUAT performed. We compared incidence and timing of de-escalation in PUAT- positive vs -negative groups and described patients' outcomes. Results/UNASSIGNED:, in-hospital mortality, or 30-day infection-related readmission. Conclusions/UNASSIGNED:We observed earlier de-escalation in the PUAT-positive group. This seems to be due to discontinuation of atypical rather than anti-MRSA or antipseudomonal coverage. Further antimicrobial stewardship interventions are warranted.
PMID: 34993258
ISSN: 2328-8957
CID: 5107422

Coinfections and antimicrobial use in patients hospitalized with coronavirus disease 2019 (COVID-19) across a single healthcare system in New York City: A retrospective cohort study

Prasad, Prithiv J; Poles, Jordan; Zacharioudakis, Ioannis M; Dubrovskaya, Yanina; Delpachitra, Dinuli; Iturrate, Eduardo; Muñoz-Gómez, Sigridh
BACKGROUND AND OBJECTIVE/UNASSIGNED:With the coronavirus disease 2019 (COVID-19) pandemic, rates of in-hospital antimicrobial use increased due to perceived bacterial and fungal coinfections along with COVID-19. We describe the incidence of these coinfections and antimicrobial use in patients hospitalized with COVID-19 to help guide effective antimicrobial use in this population. SETTING/UNASSIGNED:This study was conducted in 3 tertiary-care referral university teaching hospitals in New York City. METHODS/UNASSIGNED:This multicenter retrospective observational cohort study involved all patients admitted with COVID-19 from January 1, 2020, to February 1, 2021. Variables of interest were extracted from a de-identified data set of all COVID-19 infections across the health system. Population statistics are presented as median with interquartile range (IQR) or proportions with 95% confidence intervals (CIs) as indicated. RESULTS/UNASSIGNED:Among 7,209 of patients admitted with COVID-19, 663 (9.2%) had a positive culture from the respiratory tract or blood sometime during their initial hospital admission. Positive respiratory cultures occurred found in 449 (6.2%) patients, and 20% were collected within 48 hours of admission. Blood culture positivity occurred in 334 patients (4.6%), with 33.5% identified within 48 hours of admission. A higher proportion of patients received antimicrobials in the first wave than in the later pandemic period (82.4% vs 52.0%). Antimicrobials were prescribed to 70.1% of inpatients, with a median of 6 antimicrobial days per patient. Infection-free survival decreased over the course of hospitalization. CONCLUSIONS/UNASSIGNED:We detected a very low incidence of coinfection with COVID-19 at admission. A longer duration of hospitalization was associated with an increased risk of coinfection. Antimicrobial use far exceeded the true incidence and detection of coinfections in these patients.
PMID: 36483377
ISSN: 2732-494x
CID: 5383182

Leveraging Rapid Diagnostics and Electronic Health Records to Decrease Antimicrobial Utilization: a Step in the Right Direction

Zacharioudakis, Ioannis M; Zervou, Fainareti N; Decano, Arnold; Ahmed, Nabeela
PMID: 33319227
ISSN: 1537-6591
CID: 4717742

Characteristics, Comorbidities, and Outcomes in a Multicenter Registry of Patients with HIV and Coronavirus Disease-19

Dandachi, Dima; Geiger, Grant; Montgomery, Mary W; Karmen-Tuohy, Savannah; Golzy, Mojgan; Antar, Annukka A R; Llibre, Josep M; Camazine, Maraya; Díaz-De Santiago, Alberto; Carlucci, Philip M; Zacharioudakis, Ioannis M; Rahimian, Joseph; Wanjalla, Celestine N; Slim, Jihad; Arinze, Folasade; Kratz, Ann Marie Porreca; Jones, Joyce L; Patel, Shital M; Kitchell, Ellen; Francis, Adero; Ray, Manoj; Koren, David E; Baddley, John W; Hill, Brannon; Sax, Paul E; Chow, Jeremy
BACKGROUND:People with HIV (PWH) may have numerous risk factors for acquiring Coronavirus disease-19 (COVID-19) and developing severe outcomes, but current data are conflicting. METHODS:Healthcare providers enrolled consecutively by non-random sampling PWH with lab-confirmed COVID-19, diagnosed at their facilities between April 1st and July 1st, 2020. De-identified data were entered into an electronic Research Electronic Data Capture (REDCap). The primary endpoint was severe outcome, defined as a composite endpoint of intensive care unit (ICU) admission, mechanical ventilation, or death. The secondary outcome was the need for hospitalization. RESULTS:286 patients were included; the mean age was 51.4 years (SD, 14.4), 25.9% were female, and 75.4% were African-American or Hispanic. Most patients (94.3%) were on antiretroviral therapy (ART), 88.7% had HIV virologic suppression, and 80.8% had comorbidities. Within 30 days of positive SARS-CoV-2 testing, 164 (57.3%) patients were hospitalized, and 47 (16.5%) required ICU admission. Mortality rates were 9.4% (27/286) overall, 16.5% (27/164) among those hospitalized, and 51.5% (24/47) among those admitted to an ICU. The primary composite endpoint occurred in 17.5% (50/286) of all patients and 30.5% (50/164) of hospitalized patients. Older age, chronic lung disease, and hypertension were associated with severe outcomes. A lower CD4 count (<200 cells/mm³) was associated with the primary and secondary endpoints. There was no association between the antiretroviral regimen or lack of viral suppression and predefined outcomes. CONCLUSION/CONCLUSIONS:Severe clinical outcomes occurred commonly in PWH and COVID-19. The risk for poor outcomes was higher in those with comorbidities and lower CD4 cell counts, despite HIV viral suppression.
PMID: 32905581
ISSN: 1537-6591
CID: 4589222

SARS-CoV-2 antibodies: IgA correlates with severity of disease in early COVID-19 infection

Zervou, Fainareti N; Louie, Ping; Stachel, Anna; Zacharioudakis, Ioannis M; Ortiz-Mendez, Yadira; Thomas, Kristen; Aguero-Rosenfeld, Maria E
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.
PMID: 33932299
ISSN: 1096-9071
CID: 4865782

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

Zacharioudakis, Ioannis M; Prasad, Prithiv J; Zervou, Fainareti N; Basu, Atreyee; Inglima, Kenneth; Weisenberg, Scott A; Aguero-Rosenfeld, Maria E
PMID: 33119425
ISSN: 2325-6621
CID: 4646792