BACKGROUNDHydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use. METHODSWe examined the association between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding consecutive patients hospitalized with Covid-19, excluding those who were intubated, died, or discharged within 24 hours after presentation to the emergency department (study baseline). The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score. RESULTSOf 1446 consecutive patients, 70 patients were intubated, died, or discharged within 24 hours after presentation and were excluded from the analysis. Of the remaining 1376 patients, during a median follow-up of 22.5 days, 811 (58.9%) received hydroxychloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days); 45.8% of the patients were treated within 24 hours after presentation to the emergency department, and 85.9% within 48 hours. Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360). Overall, 346 patients (25.1%) had a primary end-point event (180 patients were intubated, of whom 66 subsequently died, and 166 died without intubation). In the main analysis, there was no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32). Results were similar in multiple sensitivity analyses.

No abstract

Background Patients hospitalized with COVID-19 are at increased risk of healthcare-associated infections especially with prolonged hospital stays. We sought to identify incidence, antimicrobial susceptibilities, and outcomes associated with bacterial/fungal secondary infections in a large cohort of patients with COVID-19. Methods We evaluated adult patients diagnosed with COVID-19 between March 2 to May 31, 2020 and hospitalized >24 hours. Data extracted from medical records included diagnoses, vital signs, laboratory results, microbiological data, and antibiotic use. Microbiologically-confirmed bacterial and fungal pathogens from clinical cultures were evaluated to characterize community- and healthcare-associated infections, including describing temporal changes in predominant organisms on presentation and throughout hospitalization. Univariable and multivariable logistic regression analyses were performed to investigate risk factors for healthcare-associated infections. Results A total of 3,028 patients were included and accounted for 899 positive clinical cultures. Overall, 516 (17%) with positive cultures met criteria for infection. Community-associated co-infections were identified in 183 (6%) patients, whereas healthcare-associated infections occurred in 350 (12%) patients. 57% of healthcare-associated infections were caused by Gram-negative bacteria and 19% by fungi. Antibiotic resistance increased with longer hospital stays, with incremental increases in the proportion of vancomycin-resistance among enterococci and ceftriaxone- and carbapenem-resistance among Enterobacterales. ICU stay, invasive mechanical ventilation, and steroids were associated with healthcare-associated infections. Conclusions Healthcare-associated infections occur in a small proportion of patients hospitalized with COVID-19 and are most often caused by Gram-negative and fungal pathogens. Antibiotic resistance is more prevalent with prolonged hospital stays. Antimicrobial stewardship is imperative in this population to minimize unnecessary broad-spectrum antibiotics.

Polymyxin B in combination with other antimicrobials can be considered a reasonable and safe treatment option for MDR Gram-negative respiratory tract infections in the setting of limited therapeutic options.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an increasingly common cause of health careassociated urinary tract infections. Antimicrobials with in vitro activity against CRKP are typically limited to polymyxins, tigecycline, and often, aminoglycosides. We conducted a retrospective cohort study of cases of CRKP bacteriuria at New York-Presbyterian Hospital from January 2005 through June 2010 to compare microbiologic clearance rates based on the use of polymyxin B, tigecycline, or an aminoglycoside. We constructed three active antimicrobial cohorts based on the active agent used and an untreated cohort of cases that did not receive antimicrobial therapy with Gram-negative activity. Microbiologic clearance was defined as having a follow-up urine culture that did not yield CRKP. Cases without an appropriate follow-up culture or that received multiple active agents or less than 3 days of the active agent were excluded. Eighty-seven cases were included in the active antimicrobial cohorts, and 69 were included in the untreated cohort. The microbiologic clearance rate was 88% in the aminoglycoside cohort (n ‫؍‬ 41), compared to 64% in the polymyxin B (P ‫؍‬ 0.02; n ‫؍‬ 25), 43% in the tigecycline (P < 0.001; n ‫؍‬ 21), and 36% in the untreated (P < 0.001; n ‫؍‬ 69) cohorts. Using multivariate analysis, the odds of clearance were lower for the polymyxin B (odds ratio [OR], 0.10; P ‫؍‬ 0.003), tigecycline (OR, 0.08; P ‫؍‬ 0.001), and untreated (OR, 0.14; P ‫؍‬ 0.003) cohorts than for the aminoglycoside cohort. Treatment with an aminoglycoside, when active in vitro, was associated with a significantly higher rate of microbiologic clearance of CRKP bacteriuria than treatment with either polymyxin B or tigecycline.

Polymyxin B (PB) has reemerged as a common treatment against multidrug-resistant Gram-negative pathogens. However, nephrotoxicity remains a significant dose-limiting side effect, and contemporary pharmacokinetic (PK) data are limited. This study sought to evaluate PB exposure differences in various loading and nonloading strategies according to total body weight (TBW) and adjusted body weight (ABW). Patients treated with PB had plasma samples obtained for clinical care and analyzed using liquid chromatography-tandem mass spectrometry. Compartmental PK models with linear and allometric scaling of TBW were explored. Semiparametric Monte Carlo simulation evaluated the total (i.e., protein bound plus unbound) area under the plasma concentration-time curve (AUC) during the first 24 h of therapy and at 96 h posttherapy for each regimen at the 10th, 50th, and 90th percentiles of TBW and ABW in the derivation cohort. Literature-based values of the 24-h total AUC/MIC ratio (AUC/MIC) of ≥50 defined efficacy, and literature-based values of the 72- to 96-h AUC of ≥100 μg · h/ml defined toxicity. Fifty-two patients contributed 156 PB plasma samples. A two-compartment model with allometric scaling of TBW produced a comparable fit (Akaike information criterion [AIC] = 376.7) to that achieved with linear scaling (AIC = 378). The regimen of a loading dose of 2.5 mg/kg of body weight plus a fixed dose of 100 mg every 12 h had the highest probability of achieving a 24-h AUC/MIC of ≥50 with the lowest probability of toxicity in all groups at 24 h, aside from those with the lowest 10th percentile of body weight. This is the first study to suggest that a weight-based loading and fixed maintenance (i.e., weight-independent) dosing strategy for polymyxin B may maximize efficacy while balancing toxicity concerns for most patients.

While antifungal use at our hospital increased, candidemia rates remained stable. C. parapsilosis was the most common species but other non-C. albicans species increased during the study period. Local epidemiology should be monitored in pediatric populations for potential impact on management strategies.

Background Little is known about the epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteriuria following kidney transplantation. We determined the incidence of post-transplant CRKP bacteriuria in adults who underwent kidney transplant from 2007 to 2010 at two New York City centers. Methods We conducted a case-control study to identify factors associated with CRKP bacteriuria compared to of carbapenem-susceptible K. pneumoniae (CSKP) bacteriuria, assessed whether CRKP bacteriuria was associated with mortality or graft failure, and compared outcomes of treated episodes of CRKP and CSKP bacteriuria. Results Of 1852 transplants, 20 (1.1%) patients developed CRKP bacteriuria. Factors associated with CRKP bacteriuria included receipt of multiple organs (odds ratio [OR] 4.7, 95% confidence interval [CI] = 1.1–20.4), deceased donor allograft (OR 5.9, 95% CI 1.3–26.8), transplant admission length of stay (OR 1.1 per day, 95% CI 1.0–1.1), pre-transplant CRKP infection or colonization (OR 18.3, 95% CI 2.0–170.5), diabetes mellitus (OR 2.8, 95% CI 1.0–7.8), and receipt of antimicrobials other than trimethoprim-sulfamethoxazole (OR 4.3, 95% CI 1.6–11.2). Conclusion Compared to CSKP bacteriuria, CRKP bacteriuria was associated with increased mortality (30% vs. 10%, P = 0.03) but not graft failure. Treated episodes of CRKP bacteriuria were less likely to achieve microbiologic clearance (83% vs. 97%; P = 0.05) and more likely to recur within 3 months (50% vs. 22%, P = 0.02) than CSKP episodes. CRKP bacteriuria after kidney transplant is associated with mortality and antimicrobial failure after treatment.