Daniel Eiras

Combination Regimens for Treatment of Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections

ABSTRACT Previous studies reported decreased mortality in patients with carbapenemase-producing Klebsiella pneumoniae bloodstream infections (BSIs) treated with combination therapy but included carbapenem-susceptible and -intermediate isolates, as per revised CLSI breakpoints. Here, we assessed outcomes in patients with BSIs caused by phenotypically carbapenem-resistant K. pneumoniae (CRKP) according to the number of in vitro active agents received and whether an extended-spectrum beta-lactam (BL) antibiotic, including meropenem, or an extended-spectrum cephalosporin was administered. We retrospectively reviewed CRKP BSIs at two New York City hospitals from 2006 to 2013, where all isolates had meropenem or imipenem MICs of ≥4 μg/ml. Univariate and multivariable models were created to identify factors associated with mortality. Of 141 CRKP BSI episodes, 23% were treated with a single active agent (SAA), 26% were treated with an SAA plus BL, 28% were treated with multiple active agents (MAA), and 23% were treated with MAA plus BL. Ninety percent of isolates had meropenem MICs of ≥16 μg/ml. Thirty-day mortality was 33% overall and did not significantly differ across the four treatment groups in a multivariable model (P = 0.4); mortality was significantly associated with a Pitt bacteremia score of ≥4 (odds ratio [OR], 7.7; 95% confidence interval [CI], 3.2 to 18.1; P = 0.1), and immunosuppression was protective (OR, 0.4; 95% CI, 0.2 to 1.0; P = 0.04). Individual treatment characteristics were also not significantly associated with outcome, including use of SAAs versus MAA (26% versus 38%, P = 0.1) or BL versus no BL (26% versus 39%, P = 0.1). In summary, in patients with CRKP BSIs caused by isolates with high carbapenem MICs, the role of combination therapy remains unclear, highlighting the need for prospective studies to identify optimal treatment regimens.

Clinical Outcomes Associated with Polymyxin B Dose in Patients with Bloodstream Infections Due to Carbapenem-Resistant Gram-Negative Rods

ABSTRACT There is significant variation in the use of polymyxin B (PMB), and optimal dosing has not been defined. The purpose of this retrospective study was to evaluate the relationship between PMB dose and clinical outcomes. We included patients with bloodstream infections (BSIs) due to carbapenem-resistant Gram-negative rods who received ≥48 h of intravenous PMB. The objective was to evaluate the association between PMB dose and 30-day mortality, clinical cure at day 7, and development of acute kidney injury (AKI). A total of 151 BSIs were included. The overall 30-day mortality was 37.8% (54 of 151), and the median PMB dosage was 1.3 mg/kg (of total body weight)/day. Receipt of PMB dosages of <1.3 mg/kg/day was significantly associated with 30-day mortality (46.5% versus 26.3%; P = 0.02), and this association persisted in multivariable analysis (odds ratio [OR] = 1.58; 95% confidence interval [CI] = 1.05 to 1.81; P = 0.04). Eighty-two percent of patients who received PMB dosages of <1.3 mg/kg/day had baseline renal impairment. Clinical cure at day 7 was not significantly different between dosing groups. AKI was more common in patients receiving PMB dosages of ≥250 mg/day (66.7% versus 32.0%; P = 0.03), and this association persisted in multivariable analysis (OR = 4.32; 95% CI = 1.15 to 16.25; P = 0.03). PMB dosages of <1.3 mg/kg/day were administered primarily to patients with renal impairment, and this dosing was independently associated with 30-day mortality. However, dosages of ≥250 mg/day were independently associated with AKI. These data support the use of PMB without dose reduction in the setting of renal impairment.

Cutaneous Leishmaniasis: Current Treatment Practices in the USA for Returning Travelers

Opinion statementLeishmaniasis, a protozoal infection transmitted by sandfly bite, produces a clinical spectrum of disease ranging from asymptomatic infection to ulcerative skin and mucosal lesions to visceral involvement. Leishmaniasis is endemic in regions of Africa, the Middle East, south Asia, southern Europe, northern South America, and Central America. There has been an increase in imported leishmaniasis into developed, non-endemic countries due to increasing global travel. While pentavalent antimonials have been the mainstay of antileishmanial treatment for decades, newer therapeutic options have become available for all forms of infection, including liposomal amphotericin B, miltefosine, fluconazole, and ketoconazole. For the returning traveler with cutaneous leishmaniasis in the USA, treatment approaches are determined based on infecting species, initial presentation, extent and progression of disease, the advantages and drawbacks of available parenteral and oral drugs, and clinician-consultant experience.

Nephrotoxicity Associated with Intravenous Polymyxin B Once versus Twice Daily Dosing Regimen

Nephrotoxicity is a known adverse effect of polymyxin B (PMB). Animal data suggest that once-daily dosing may reduce the rate and delay the onset of acute kidney injury (AKI). ABSTRACT Nephrotoxicity is a known adverse effect of polymyxin B (PMB). Animal data suggest that once-daily dosing may reduce the rate and delay the onset of acute kidney injury (AKI). In a multicenter retrospective study, we evaluated adult patients with a creatinine clearance (CrCl) of ≥30 ml/min who received ≥48 h of PMB therapy. The primary endpoint was the difference in rate of AKI comparing once- and twice-daily PMB dosing. The secondary endpoints included the time to AKI and the recovery of renal function. Of 273 eligible patients, 100 from each group were matched on the basis of propensity scores. In the matched groups, nephrotoxicity, defined according to risk, injury, failure, loss, and end-stage renal disease (RIFLE) criteria, was more frequent with once- than with twice-daily dosing (47% versus 17%, respectively; P = 0.0005). After adjusting for residual differences by multivariate conditional logistic regression, once-daily dosing was more likely to result in nephrotoxicity (adjusted odds ratio, 2.5; 95% confidence interval [CI], 1.413 to 4.541; P = 0.002). Among 64 patients who developed AKI, the median onsets were similar between the groups (7 days with once versus 6 days with twice-daily dosing, P = 0.095). Of 37 patients who had their serum creatinine evaluated subsequently, 29/37 (78%) had recovery of renal function. No patient required renal replacement therapy. Our findings suggest that AKI is significantly more common with PMB once daily than with twice-daily dosing with no difference in time to AKI. A prospective randomized study is warranted to validate these results.

Painting the Gown Red: Using a Colored Paint Quality Improvement Process to Evaluate Healthcare Worker Personal Protective Equipment for Highly Pathogenic Infections

Abstract Background Personal protective equipment (PPE) and strict infection control techniques are the primary methods by which healthcare workers (HCW) can avoid exposure during the treatment of patients with highly pathogenic infections such as Ebola Virus Disease (EVD) or the Middle East Respiratory Syndrome coronavirus (MERS-CoV). There is currently no consensus for the types of PPE that are recommended to be worn by HCWs, nor is there a universal process for the donning and doffing of PPE. Methods HCWs from Bellevue Hospital participate in quarterly PPE trainings as part of the Special Pathogens Program (SPP), which consist of didactic sessions as well as an evaluation of donning and doffing techniques. A total of 50 HCWs completed the training curriculum in 2017. During the doffing process, PPE trainers applied corn start powder paint (Chameleon Colors; American Fork, UT) to the participants’ gloved hands between multiple steps of PPE removal. At the end of the process, the areas where paint was found on was documented including the outer surgical gown, the powered air purifying respirator (PAPR) helmet and shroud, the inner impermeable suit, the knee-high boots and boot covers, and the extended-cuff gloves. Results The areas of PPE that were most marked with paint were the lower shoulders and upper arms of the surgical gowns, the top sides of the PAPR shroud, the front upper chest area, and the center back of the inner impermeable suits. In a majority of cases no powder paint was noted on the knee-high boots. In a minority of cases, paint was observed on the inside upper chest area of the surgical gown. These paint markings were used to discuss potential breaches in PPE doffing technique in real-time, as well as identify areas to target in future PPE trainings. Conclusion The powdered paint quality improvement process for donning and doffing PPE is a method to evaluate the complex PPE dressing procedure. It is particularly useful given the fact that it is incumbent on each hospital or healthcare system to develop its own processes and procedures for PPE, as well as maintain readiness through periodic trainings. Powdered paint can identify vulnerabilities in their process as well as areas that require further education. Disclosures All authors: No reported disclosures.

Knowledge, Attitudes, and Practices Regarding Antimicrobial Stewardship Among Antimicrobial Prescribers at Five Acute Care Hospitals

 The survey results will be used to develop and implement clinical AS interventions at NYP. Future research efforts will focus on the identification of changes in antimicrobial prescribing practices and clinical outcomes associated with enhanced AS educational initiatives and increased postprescription review and feedback resources. CONCLUSION Contact Information: Elizabeth Salsgiver, MPH Weill Cornell Medical College Phone: 802-598-6065 Email: ELS7021@med.cornell.edu