Characteristics, Comorbidities, and Outcomes in a Multicenter Registry of Patients With Human Immunodeficiency Virus and Coronavirus Disease 2019.

BACKGROUND: People living with human immunodeficiency virus (HIV) may have numerous risk factors for acquiring coronavirus disease 2019 (COVID-19) and developing severe outcomes, but current data are conflicting. METHODS: Health-care providers enrolled consecutively, by nonrandom sampling, people living with HIV (PWH) with lab-confirmed COVID-19, diagnosed at their facilities between 1 April and 1 July 2020. Deidentified data were entered into an electronic Research Electronic Data Capture (REDCap) system. The primary endpoint was a 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: There were 286 patients included; the mean age was 51.4 years (standard deviation, 14.4), 25.9% were female, and 75.4% were African American or Hispanic. Most patients (94.3%) were on antiretroviral therapy, 88.7% had HIV virologic suppression, and 80.8% had comorbidities. Within 30 days of testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 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 were no associations between the ART regimen or lack of viral suppression and the predefined outcomes. CONCLUSIONS: Severe clinical outcomes occurred commonly in PWH with COVID-19. The risks for poor outcomes were higher in those with comorbidities and lower CD4 cell counts, despite HIV viral suppression. CLINICAL TRIALS REGISTRATION: NCT04333953.

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

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 µg/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.

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

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.

Outcomes Among HIV-Positive Patients Hospitalized With COVID-19.

BACKGROUND: SARS-CoV-2 infection continues to cause significant morbidity and mortality worldwide. Preliminary data on SARS-CoV-2 infection suggest 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 with 42 non-HIV patients using a greedy nearest-neighbor algorithm. Admission characteristics, laboratory test results, and hospital outcomes were recorded and compared between the 2 groups. RESULTS: Although there was a trend toward increased rates of intensive care unit 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 C-reactive protein values. Other inflammatory markers did not differ significantly between groups, although 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 3 patients died during hospitalization. There was no difference in frequency of thrombotic events or myocardial infarction between these groups. 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 with matched non-HIV patients. A larger study is required to determine whether the trends we observed apply to all HIV-positive patients.

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

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.

Infection with panresistant Klebsiella pneumoniae: a report of 2 cases and a brief review of the literature.

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.

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

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.

Identification of novel hsp65 RFLPs for Mycobacterium leprae.

Leprosy or Hansen's disease is a chronic infectious disease caused by an acid-fast bacillus, Mycobacterium leprae (M. leprae). The bacilli proliferate in macrophages infiltrating the skin and gain entry to the dermal nerves via the laminar surface of Schwann cells where they replicate. After entry, the Schwann cells proliferate and then die. Conclusive identification of M. leprae DNA in a sample can be obtained by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the heat shock 65 gene (hsp65). Molecular epidemiology will make it possible to study the global distributions of M. leprae, explore the relationship between genotypes-incidence rates, mode of transmission, and the type of disease (tuberculoid vs. lepromatous). We amplified DNA using PCR for the hsp65 gene from 24 skin lesions from patients diagnosed with various types of leprosy. Fifteen out of 24 were positive for the hsp65 gene. Digestion with HaeIII-PAGE for the RFLP confirmation of the presence of M. leprae DNA showed the typical pattern in 5 out of 24 and 2 novel patterns in 10 out of 24 patients. We confirmed the presence of M. leprae DNA by sequencing the genes for gyraseA or B and folP, which contained only M. leprae specific single nucleotide polymorphisms (SNPs). Thus, we describe novel hsp65 RFLPs for M. leprae found in a high frequency making them ideal for future epidemiology and transmission studies.

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

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.

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

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.

Pyogenic liver abscess: recent trends in etiology and mortality.

BACKGROUND: Pyogenic liver abscess, a potentially life-threatening disease, has undergone significant changes in epidemiology, management, and mortality over the past several decades. METHODS: We reviewed the data for patients admitted to Bellevue Hospital and New York University Downtown Hospital (New York, New York) over a 10-year period. RESULTS: Of 79 cases reviewed, 43% occurred in patients with underlying biliary disease. The most common symptoms were fever, chills, and right upper quadrant pain or tenderness. The most common laboratory abnormalities were an elevated white blood cell count (in 68% of cases), temperature >or=38.1 degrees C (90%), a low albumin level (70.2%), and an elevated alkaline phosphatase level (67%). Seventy percent of the abscesses were in the right lobe, and 77% were solitary. Klebsiella pneumoniae was identified in 41% of cases in which a pathogen was recovered. Eighteen (50%) of 36 Asian patients had K. pneumoniae isolated, in contrast to 6 (27.3%) of 22 non-Asian patients (not statistically significant). Fifty-six percent of cases involved treatment with percutaneous drainage. Although prior reports noted mortality of 11%-31%, we observed only 2 deaths (mortality, 2.5%). CONCLUSIONS: The data suggest that K. pneumoniae has become the predominant etiology of pyogenic liver abscess and that mortality from this disease has decreased substantially.

Bartonella quintana endocarditis with positive serology for Coxiella burnetii.

Both Bartonella quintana and Coxiella burnetii are known to cause of blood culture negative endocarditis. In such case, the diagnosis is usually established by serology. A case of Bartonella quintana endocarditis is described where the serology was falsely positive for Coxiella burnetii. This case demonstrates the difficulty in distinguishing these two etiologic agents by routine serologic testing.