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Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study

Frontera, Jennifer A; Rahimian, Joseph O; Yaghi, Shadi; Liu, Mengling; Lewis, Ariane; de Havenon, Adam; Mainali, Shraddha; Huang, Joshua; Scher, Erica; Wisniewski, Thomas; Troxel, Andrea B; Meropol, Sharon; Balcer, Laura J; Galetta, Steven L
Background: Zinc impairs replication of RNA viruses such as SARS-CoV-1, and may be effective against SARS-CoV-2. However, to achieve adequate intracellular zinc levels, administration with an ionophore, which increases intracellular zinc levels, may be necessary. We evaluated the impact of zinc with an ionophore (Zn+ionophore) on COVID-19 in-hospital mortality rates. Methods: A multicenter cohort study was conducted of 3,473 adult hospitalized patients with reverse-transcriptase-polymerase-chain-reaction (RT-PCR) positive SARS-CoV-2 infection admitted to four New York City hospitals between March 10 through May 20, 2020. Exclusion criteria were: death or discharge within 24h, comfort-care status, clinical trial enrollment, treatment with an IL-6 inhibitor or remdesivir. Patients who received Zn+ionophore were compared to patients who did not using multivariable time-dependent cox proportional hazards models for time to in-hospital death adjusting for confounders including age, sex, race, BMI, diabetes, week of admission, hospital location, sequential organ failure assessment (SOFA) score, intubation, acute renal failure, neurological events, treatment with corticosteroids, azithromycin or lopinavir/ritonavir and the propensity score of receiving Zn+ionophore. A sensitivity analysis was performed using a propensity score-matched cohort of patients who did or did not receive Zn+ionophore matched by age, sex and ventilator status. Results: Among 3,473 patients (median age 64, 1947 [56%] male, 522 [15%] ventilated, 545[16%] died), 1,006 (29%) received Zn+ionophore. Zn+ionophore was associated with a 24% reduced risk of in-hospital mortality (12% of those who received Zn+ionophore died versus 17% who did not; adjusted Hazard Ratio [aHR] 0.76, 95% CI 0.60-0.96, P=0.023). More patients who received Zn+ionophore were discharged home (72% Zn+ionophore vs 67% no Zn+ionophore, P=0.003) Neither Zn nor the ionophore alone were associated with decreased mortality rates. Propensity score-matched sensitivity analysis (N=1356) validated these results (Zn+ionophore aHR for mortality 0.63, 95%CI 0.44-0.91, P=0.015). There were no significant interactions for Zn+ionophore with other COVID-19 specific medications. Conclusions: Zinc with an ionophore was associated with increased rates of discharge home and a 24% reduced risk of in-hospital mortality among COVID-19 patients, while neither zinc alone nor the ionophore alone reduced mortality. Further randomized trials are warranted.
PMID: 33140042
ISSN: n/a
CID: 4655962

Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients

Carlucci, Philip M; Ahuja, Tania; Petrilli, Christopher; Rajagopalan, Harish; Jones, Simon; Rahimian, Joseph
Introduction. COVID-19 has rapidly emerged as a pandemic infection that has caused significant mortality and economic losses. Potential therapies and prophylaxis against COVID-19 are urgently needed to combat this novel infection. As a result of in vitro evidence suggesting zinc sulphate may be efficacious against COVID-19, our hospitals began using zinc sulphate as add-on therapy to hydroxychloroquine and azithromycin.Aim. To compare outcomes among hospitalized COVID-19 patients ordered to receive hydroxychloroquine and azithromycin plus zinc sulphate versus hydroxychloroquine and azithromycin alone.Methodology. This was a retrospective observational study. Data was collected from medical records for all patients with admission dates ranging from 2 March 2020 through to 11 April 2020. Initial clinical characteristics on presentation, medications given during the hospitalization, and hospital outcomes were recorded. The study included patients admitted to any of four acute care NYU Langone Health Hospitals in New York City. Patients included were admitted to the hospital with at least one positive COVID-19 test and had completed their hospitalization. Patients were excluded from the study if they were never admitted to the hospital or if there was an order for other investigational therapies for COVID-19.Results. Patients taking zinc sulphate in addition to hydroxychloroquine and azithromycin (n=411) and patients taking hydroxychloroquine and azithromycin alone (n=521) did not differ in age, race, sex, tobacco use or relevant comorbidities. The addition of zinc sulphate did not impact the length of hospitalization, duration of ventilation or intensive care unit (ICU) duration. In univariate analyses, zinc sulphate increased the frequency of patients being discharged home, and decreased the need for ventilation, admission to the ICU and mortality or transfer to hospice for patients who were never admitted to the ICU. After adjusting for the time at which zinc sulphate was added to our protocol, an increased frequency of being discharged home (OR 1.53, 95 % CI 1.12-2.09) and reduction in mortality or transfer to hospice among patients who did not require ICU level of care remained significant (OR 0.449, 95 % CI 0.271-0.744).Conclusion. This study provides the first in vivo evidence that zinc sulphate may play a role in therapeutic management for COVID-19.
PMID: 32930657
ISSN: 1473-5644
CID: 4609522

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

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

Multidrug-Resistant Bacteroides fragilis Bacteremia in a US Resident: An Emerging Challenge

Merchan, Cristian; Parajuli, Sunita; Siegfried, Justin; Scipione, Marco R; Dubrovskaya, Yanina; Rahimian, Joseph
We describe a case of Bacteroides fragilis bacteremia associated with paraspinal and psoas abscesses in the United States. Resistance to b-lactam/b-lactamase inhibitors, carbapenems, and metronidazole was encountered despite having a recent travel history to India as the only possible risk factor for multidrug resistance. Microbiological cure was achieved with linezolid, moxifloxacin, and cefoxitin.
PMID: 27418986
ISSN: 2090-6625
CID: 2180272

Evaluation of Treatment Courses When Vancomycin Is Given Every 8 Hours in Adult Patients

Brumer, Erica; Dubrovskaya, Yanina; Scipione, Marco R; Aberle, Caitlin; Rahimian, Joseph; Papadopoulos, John
BACKGROUND: Several nomograms include recommendations to give intravenous (IV) vancomycin at 8-hour dosing intervals (Q8H). However, there is a lack of detailed data regarding this dosing recommendation. METHODS: A retrospective chart review of 100 patients who received 107 treatment courses of vancomycin Q8H for at least 5 days was performed. Distribution of vancomycin trough levels and rate of nephrotoxicity were evaluated. RESULTS: Median patient age was 38 years (interquartile range [IQR] 27-50 years), median weight was 67 kg (IQR 55-79 kg), and median creatinine clearance was 124 mL/min (IQR 101-147 mL/min). Median duration of Q8H dosing was 9 days (IQR 7-12 days). Within the initial 96 hours, only 7% (7 of 104) of maximum trough concentrations were >20 mg/L (median dose 15 mg/kg [IQR 15-18 mg/kg]). After 96 hours of Q8H dosing, 34% (30 of 89) of maximum troughs were >20 mg/L (median dose 17 mg/kg [IQR 15-20 mg/kg]), P = .0005. The rate of nephrotoxicity was 4%. CONCLUSION: We observed an increase in the percentage of trough levels >20 mg/L later during treatment courses of vancomycin IV Q8H with a relatively small corresponding increase in vancomycin dose. Close monitoring of trough levels (eg, every 3 days) with prolonged courses of vancomycin IV Q8H is warranted.
PMID: 25112304
ISSN: 1531-1937
CID: 1847672

In vitro evaluation of antibiotic synergy for polymyxin B-resistant carbapenemase-producing Klebsiella pneumoniae

Elemam, Azza; Rahimian, Joseph; Doymaz, Mehmet
Since carbapenemase-producing Klebsiella pneumoniae strains were first reported in North Carolina, these highly resistant organisms have been isolated with increasing frequency, especially in the New York City area. Polymyxin B is one of the few antimicrobials that retain reliable activity against these organisms. However, polymyxin B MICs are elevated against K. pneumoniae isolates with increasing frequency, leaving clinicians with few therapeutic options. We investigated several antimicrobial agents for potential synergy with polymyxin B against 12 clinical strains of carbapenemase-producing K. pneumoniae. A broth microdilution assay using a 96-well plate was developed in which graded dilutions of polymyxin B and the study drug were incubated with resistant isolates in a checkerboard pattern. Polymyxin B was studied in combination with cefazolin, ceftriaxone, cefepime, imipenem, gentamicin, tigecycline, doxycycline, and rifampin. All K. pneumoniae strains tested positive for K. pneumoniae carbapenemase (KPC) genes by real-time PCR and had elevated polymyxin B MIC values ranging from 16 to 128 mug/ml. Synergy was observed with the combination of polymyxin B and rifampin as well as with polymyxin B and doxycycline, resulting in at least a 4-fold decrease in the polymyxin B MIC. For both combinations, this effect occurred at physiologically achievable concentrations. Less pronounced synergy was noted with tigecycline and polymyxin B. No synergy was observed at physiologic concentrations with the other antimicrobials studied. These results suggest that rifampin, doxycycline, and tigecycline may be useful additions to polymyxin B in the treatment of infections caused by highly resistant carbapenemase-producing K. pneumoniae. Further studies are warranted to determine if these in vitro findings translate into clinical efficacy.
PMID: 20686085
ISSN: 0095-1137
CID: 158427

Infection with panresistant Klebsiella pneumoniae: a report of 2 cases and a brief review of the literature [Case Report]

Elemam, Azza; Rahimian, Joseph; Mandell, William
Infections caused by carbapenemase-producing Klebsiella pneumoniae have been reported with increasing frequency, thereby limiting the choice of effective antimicrobial agents available to clinicians. This has prompted the increased use of polymyxins and tigecycline, but resistance to these agents is already emerging. We report 2 cases of infection with panresistant K. pneumoniae.
PMID: 19527172
ISSN: 1058-4838
CID: 158423

Does nasal colonization or mupirocin treatment affect recurrence of methicillin-resistant Staphylococcus aureus skin and skin structure infections?

Rahimian, Joseph; Khan, Raymond; LaScalea, Keith A
Some patients with community-associated methicillin-resistant Staphylococcus aureus skin and skin structure infections have experienced frequent recurrences. We performed a retrospective study and determined that the presence of nasal colonization did not affect recurrence and nasal mupirocin treatment marginally decreased recurrence.
PMID: 17952848
ISSN: 0899-823x
CID: 158422

Diffuse cutaneous hyperpigmentation due to tigecycline or polymyxin B [Letter]

Knueppel, Ryan C; Rahimian, Joseph
PMID: 17554719
ISSN: 1058-4838
CID: 158421