Knowledge, Perception, Attitudes and Behavior on Influenza Immunization and the Determinants of Vaccination.

BACKGROUND: We sought to determine the knowledge of, perception, attitudes, and behaviors toward influenza virus and immunization, and the determinants of vaccination among students, patients, and Healthcare Workers (HCWs) at the American University of Beirut and its affiliated Medical Center. METHODS: We conducted a cross-sectional study between October 2016 and January 2017 utilizing a self-administered questionnaire that was provided to 247 randomly selected adult participants. Data collected included socio-demographic characteristics, prior vaccination against influenza, knowledge, perception, attitudes, and behaviors toward influenza and influenza immunization. A multivariable regression model was used to evaluate for independent associations between the different variables and regular or yearly vaccination as a primary outcome. RESULTS: The overall survey response rate was 77%. A substantial proportion of respondents (47.4%) had never received the influenza vaccine. Only 10.2% of students, 19.1% of patients, and 35.6% of HCWs reported regular or yearly influenza vaccine uptake. HCWs had the lowest knowledge score about influenza and its vaccine despite high self-reported levels of knowledge. Barriers to vaccinations included lack of information (31%), fear of adverse effects (29%), and a perception of not being at risk (23%). Several factors were independently associated with regular or yearly vaccination uptake including having children (adjusted OR = 3.8; 95% CI 1.2-12.5), a "very good" self-reported level of knowledge (OR = 16.3; 95% CI 1.4-194.2) and being afraid of the consequences of influenza (OR = 0.2; 95% CI 0.1-0.6). CONCLUSION: Adherence rates with regular or yearly vaccination against influenza remain low across all study groups. We were able to identify predictors as well as barriers to vaccination. Future awareness and vaccination campaigns should specifically aim at correcting misconceptions about vaccination, particularly among HCWs, along with addressing the barriers to vaccination. Predictors of vaccination should be integrated in the design of future campaigns.

Changes in antibiotic use following implementation of a telehealth stewardship pilot program.

Starting in 2016, we initiated a pilot tele-antibiotic stewardship program at 2 rural Veterans Affairs medical centers (VAMCs). Antibiotic days of therapy decreased significantly (P < .05) in the acute and long-term care units at both intervention sites, suggesting that tele-stewardship can effectively support antibiotic stewardship practices in rural VAMCs.

Polymyxins: To Combine or Not to Combine?

Polymyxins have been a mainstay for the treatment of extensively drug resistant (XDR) Gram-negative bacteria for the past two decades. Many questions regarding the clinical use of polymyxins have been answered, but whether the administration of polymyxins in combination with other antibiotics leads to better outcomes remains unknown. This review discusses the limitations of observational studies that suggest a benefit of combinations of colistin and carbapenems to treat infections caused by carbapenem-resistant Enterobacteriaceae (CRE), especially Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae, and summarizes the results of randomized controlled trials in which treatment with colistin in combination with meropenem or rifampin does not lead to better clinical outcomes than colisitn monotherapy in infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB). Although the introduction of new antibiotics makes it possible to treat certain strains of CRE and carbapenem-resistant P. aeruginosa (CRPA) with polymyxin-sparing regimens, the use of polymyxins is, for now, still necessary in CRAB and in CRE and CRPA harboring metallo-beta-lactamases. Therefore, strategies must be developed to optimize polymyxin-based treatments, informed by in vitro hollow fiber models, careful clinical observations, and high-quality evidence from appropriately designed trials.

Therapies for multidrug resistant and extensively drug-resistant non-fermenting gram-negative bacteria causing nosocomial infections: a perilous journey toward 'molecularly targeted' therapy.

INTRODUCTION: Non-fermenting Gram-negative bacilli are at the center of the antimicrobial resistance epidemic. Acinetobacter baumannii and Pseudomonas aeruginosa are both designated with a threat level to human health of 'serious' by the Centers for Disease Control and Prevention. Two other major non-fermenting Gram-negative bacilli, Stenotrophomonas maltophilia and Burkholderia cepacia complex, while not as prevalent, have devastating effects on vulnerable populations, such as those with cystic fibrosis, as well as immunosuppressed or hospitalized patients. Areas covered: In this review, we summarize the clinical impact, presentations, and mechanisms of resistance of these four major groups of non-fermenting Gram-negative bacilli. We also describe available and promising novel therapeutic options and strategies, particularly combination antibiotic strategies, with a focus on multidrug resistant variants. Expert commentary: We finally advocate for a therapeutic approach that incorporates in vitro antibiotic susceptibility testing with molecular and genotypic characterization of mechanisms of resistance, as well as pharmacokinetics and pharmacodynamics (PK/PD) parameters. The goal is to begin to formulate a precision medicine approach to antimicrobial therapy: a clinical-decision making model that integrates bacterial phenotype, genotype and patient's PK/PD to arrive at rationally-optimized combination antibiotic chemotherapy regimens tailored to individual clinical scenarios.

A 17-Year Nationwide Study of Burkholderia cepacia Complex Bloodstream Infections Among Patients in the United States Veterans Health Administration.

Background: Burkholderia cepacia complex (Bcc) are a group of multidrug-resistant gram-negative bacteria rarely reported in patients without cystic fibrosis (CF) or immunocompromising conditions. We investigated Bcc bloodstream infections (BSIs) in a cohort of non-CF patients from the US Veterans Health Administration (VHA). Methods: Using VHA databases, we identified patients with Bcc BSI at facilities nationwide from 1999 through 2015. We ascertained clinical characteristics, treatments, and outcomes and identified factors associated with 30-day mortality in logistic regression analysis. Results: We identified 248 patients with Bcc BSI, who were of advanced age (mean, 68 years), chronically ill, and had severe disease. The most common sources were central venous catheters (41%) and pneumonia (20%). Most cases were hospital-acquired (155 [62%]) or healthcare-associated (70 [28%]). Mortality at 14, 30, and 90 days was 16%, 25%, and 36%, respectively. Trimethoprim-sulfamethoxazole (TMP-SMX) and fluoroquinolones were active against 94% and 88% of isolates, respectively. Susceptibility to ceftazidime and meropenem occurred in approximately 70% of the isolates. The most prescribed antibiotics were fluoroquinolones (35%), followed by carbapenems (20%), TMP-SMX (18.5%), and ceftazidime (11%). In regression analysis, age (OR, 1.06 [95% confidence interval {CI}, 1.02-1.10], per added year) and the Pitt bacteremia score (OR, 1.65 [95% CI, 1.44-1.94], per unit increase) were associated with higher 30-day mortality. Conclusions: In this large cohort of BSIs caused by Bcc, cases were mostly hospital-acquired and we observed high mortality, significant resistance to ceftazidime, and limited use of TMP-SMX. These observations add to our understanding of Bcc infection in non-CF patients and highlight the need for interventions to improve their outcome.

Influence of Aging and Environment on Presentation of Infection in Older Adults.

In older adults, pathophysiologic, clinical, and environmental factors all affect the presentation of infections. We explore how age-related changes influence the manifestation and evaluation of infections in this population. Specific topics include immunosenescence, age-related organ-specific physiologic changes, and frailty. We also describe clinical factors influencing infection risk and presentation in older adults, including temperature regulation, cognitive decline, and malnutrition. Finally, we discuss the influence of the setting in which older adults reside on the clinical evaluation of infection. Understanding the influence of all these changes may facilitate the prevention, early recognition, and treatment of infections in older adults.

Carbapenem-Resistant Enterobacter cloacae in Patients from the US Veterans Health Administration, 2006-2015.

We analyzed carbapenem-resistant Enterobacteriaceae (CRE) trends among patients from the US Veterans Health Administration (VHA). After the emergence of CRE in the eastern United States, resistance rates remained stable in Klebsiella pneumoniae but increased in Enterobacter cloacae complex, suggesting a "second epidemic". VHA offers a vantage point for monitoring nationwide CRE trends.

Treatment options for infections caused by carbapenem-resistant Enterobacteriaceae: can we apply "precision medicine" to antimicrobial chemotherapy?

INTRODUCTION: For the past three decades, carbapenems played a central role in our antibiotic armamentarium, trusted to effectively treat infections caused by drug-resistant bacteria. The utility of this class of antibiotics has been compromised by the emergence of resistance especially among Enterobacteriaceae. AREAS COVERED: We review the current mainstays of pharmacotherapy against infections caused by carbapenem-resistant Enterobacteriaceae (CRE) including tigecycline, aminoglycosides, and rediscovered 'old' antibiotics such as fosfomycin and polymyxins, and discuss their efficacy and potential toxicity. We also summarize the contemporary clinical experience treating CRE infections with antibiotic combination therapy. Finally, we discuss ceftazidime/avibactam and imipenem/relebactam, containing a new generation of beta-lactamase inhibitors, which may offer alternatives to treat CRE infections. We critically evaluate the published literature, identify relevant clinical trials and review documents submitted to the United States Food and Drug Administration. EXPERT OPINION: Defining the molecular mechanisms of resistance and applying insights about pharmacodynamic and pharmacokinetic properties of antibiotics, in order to maximize the impact of old and new therapeutic approaches should be the new paradigm in treating infections caused by CRE. A concerted effort is needed to carry out high-quality clinical trials that: i) establish the superiority of combination therapy vs. monotherapy; ii) confirm the role of novel beta-lactam/beta-lactamase inhibitor combinations as therapy against KPC- and OXA-48 producing Enterobacteriaceae; and, iii) evaluate new antibiotics active against CRE as they are introduced into the clinic.