Haley J. Morrill

Risk of hepatotoxicity associated with fluoroquinolones: A national case–control safety study

PURPOSE Results of a pharmacoepidemiologic evaluation of fluoroquinolone-associated hepatotoxicity using national hospital admissions data on Veterans Affairs (VA) patients are reported. METHODS In a retrospective case-control study, all adults with a primary diagnosis of hepatotoxicity on admission to a VA facility during a 6.5-year period (January 2002-June 2008) were identified. After the exclusion of patients whose records indicated known causes of hepatotoxicity or a history of liver disease, a subgroup of 7,862 patients with exposure to fluoroquinolone antibiotics in the six months prior to hospital admission were matched with nonexposed controls (n = 45,512). Conditional logistic regression was used to assess the overall and drug-specific risks of hepatotoxicity in the case group, controlling for comorbidities, concomitant use of known hepatotoxic medications, and other variables. RESULTS After adjusting for confounders, logistic regression analysis indicated a significantly higher overall risk of hepatotoxicity development among fluoroquinolone users relative to controls (odds ratio [OR], 1.20; 95% confidence interval [CI], 1.04-1.38). Drug-specific risk analyses focused on three fluoroquinolone agents (ciprofloxacin, levofloxacin, and moxifloxacin) indicated a significant association between ciprofloxacin use and an increased risk of hepatotoxicity (OR, 1.29; 95% CI, 1.05-1.58); when considered as independent variables, levofloxacin use and moxifloxacin use were not significantly associated with hepatotoxicity risk. CONCLUSION The findings of a national VA safety study suggested an increased hepatotoxicity risk asssociated with fluoroquinolone exposure in the study population.

Antimicrobial Stewardship in Long-Term Care Facilities: A Call to Action.

Antimicrobial resistance is a global public health crisis and a national security threat to the United States, as stated in an executive order signed by the president in September 2014. This crisis is a result of indiscriminant antimicrobial use, which promotes selection for resistant organisms, increases the risk of adverse drug events, and renders patients vulnerable to drug-resistant infections. Antimicrobial stewardship is a key measure to combat antimicrobial resistance and specifically seeks to do this by improving antimicrobial use. Antimicrobial stewardship compliments infection control practices and it is important to note that these 2 disciplines are distinct and cannot be discussed interchangeably. Antimicrobial stewardship promotes the appropriate diagnosis, drug, dose, and duration of treatment. The appropriate diagnosis falls into the hands of the prescriber and clinical staff. Optimal antimicrobial drug selection, dosing strategy, and duration of treatment, however, often require expertise in antimicrobial therapy, such as an infectious disease-trained physician or pharmacist. Therefore, successful antimicrobial stewardship programs must be comprehensive and interdisciplinary. Most antimicrobial stewardship programs focus on hospitals; yet, in long-term care, up to 75% of antimicrobial use is inappropriate or unnecessary. Thus, one of the most pressing areas in need for antimicrobial stewardship is in long-term care facilities. Unfortunately, there is little evidence that describes effective antimicrobial stewardship interventions in this setting. This review discusses the need for and barriers to antimicrobial stewardship in long-term care facilities. Additionally, this review describes prior interventions that have been implemented and tested to improve antimicrobial use in long-term care facilities.

Comparative Effectiveness of Linezolid and Vancomycin Among a National Veterans Affairs Cohort with Methicillin‐Resistant Staphylococcus aureus Pneumonia

As variability in vancomycin dosing, susceptibility, and tolerability has driven the need to compare newer agents with vancomycin in real‐world clinical settings, we sought to quantify the effectiveness of linezolid compared with vancomycin on clinical outcomes for the treatment of methicillin‐resistant Staphylococcus aureus (MRSA) pneumonia.

Impact of a Prospective Audit and Feedback Antimicrobial Stewardship Program at a Veterans Affairs Medical Center: A Six-Point Assessment.

Background Prospective audit and feedback is a core antimicrobial stewardship program (ASP) strategy; however its impact is difficult to measure. Methods Our quasi-experimental study measured the effect of an ASP on clinical outcomes, antimicrobial use, resistance, costs, patient safety (adverse drug events [ADE] and Clostridium difficile infection [CDI]), and process metrics pre- (9/10–10/11) and post-ASP (9/12–10/13) using propensity adjusted and matched Cox proportional-hazards regression models and interrupted time series (ITS) methods. Results Among our 2,696 patients, median length of stay was 1 day shorter post-ASP (5, interquartile range [IQR] 3–8 vs. 4, IQR 2–7 days, p<0.001). Mortality was similar in both periods. Mean broad-spectrum (-11.3%), fluoroquinolone (-27.0%), and anti-pseudomonal (-15.6%) use decreased significantly (p<0.05). ITS analyses demonstrated a significant increase in monthly carbapenem use post-ASP (trend: +1.5 days of therapy/1,000 patient days [1000PD] per month; 95% CI 0.1–3.0). Total antimicrobial costs decreased 14%. Resistance rates did not change in the one-year post-ASP period. Mean CDI rates/10,000PD were low pre- and post-ASP (14.2 ± 10.4 vs. 13.8 ± 10.0, p = 0.94). Fewer patients experienced ADEs post-ASP (6.0% vs. 4.4%, p = 0.06). Conclusions Prospective audit and feedback has the potential to improve antimicrobial use and outcomes, and contain bacterial resistance. Our program demonstrated a trend towards decreased length of stay, broad-spectrum antimicrobial use, antimicrobial costs, and adverse events.

Vancomycin Dosing Considerations in a Real-World Cohort of Obese and Extremely Obese Patients

To compare the effects of empiric vancomycin dosing regimens on attainment of optimal target trough concentrations in obese (body mass index [BMI] 30–40 kg/m2) and extremely obese (BMI ≥ 40 kg/m2) patients.

Antimicrobial Resistance of Escherichia coli Urinary Isolates in the Veterans Affairs Health Care System

ABSTRACT We reviewed data for almost 300,000 clinical Escherichia coli urinary isolates (collected in 2009 through 2013) from 127 inpatient and outpatient facilities, to assess antibiotic resistance among Veterans Affairs health care system patients using Clinical and Laboratory Standards Institute and Centers for Disease Control and Prevention National Healthcare Safety Network definitions or guidance. Rates of resistance to amoxicillin or ampicillin/β-lactamase inhibitors were approximately 40% and rates of resistance to fluoroquinolones and trimethoprim-sulfamethoxazole approached 30%. Rates of resistance to nitrofurantoin, antipseudomonal penicillin/β-lactamase inhibitors, and carbapenems remained less than 10%. The percentage of isolates that were considered multidrug resistant varied (4% to 37%), depending on the definitions used.

Antimicrobial Stewardship in Rhode Island Long-Term Care Facilities: Current Standings and Future Opportunities.

Our survey of antimicrobial stewardship practices among Rhode Island long-term care facilities demonstrated opportunities to develop formal programs. Results suggest infection preventionists are largely responsible for ensuring appropriate antibiotic use in long-term care facilities and there is a need for increased interdisciplinary access to individuals with antimicrobial stewardship expertise. Infect Control Hosp Epidemiol 2016;37:979-982.

Risk stacking of pneumococcal vaccination indications increases mortality in unvaccinated adults with Streptococcus pneumoniae infections

BACKGROUND Several chronic disease states have been identified as pneumococcal vaccination indications due to their ability to increase pneumococcal disease development and subsequent mortality. However, the risk of mortality according to the number of these disease states present is unknown. We sought to determine the impact of concomitant, multiple risk factors (stacked risks) for pneumococcal disease on 30-day mortality in adults. METHODS This was a national case-control study of unvaccinated older Veterans (≥50years of age) admitted to Veterans Affairs medical centers from 2002 to 2011 with serious pneumococcal infections (pneumonia, bacteremia, meningitis) based on positive S. pneumoniae blood, cerebrospinal fluid, or respiratory cultures, respectively. Cases were those not alive 30days following culture, while controls were alive. Using logistic regression, we quantified risk of 30-day mortality among patients with stacked risk factors, including age ≥65years, alcohol abuse, chronic heart disease, chronic liver disease, chronic respiratory disease, diabetes mellitus, immunodeficiency, and smoking. RESULTS We identified 9730 serious pneumococcal infections, with an overall 30-day mortality rate of 18.6% (1764 cases, 7966 controls). Infection types included pneumonia (62%), bacteremia (26%), and bacteremic pneumonia (11%). Along with eight individual risk factors, we assessed 247 combinations of risk factors. Most cases (85%) and controls (74%) had at least two risk factors. Mortality increased as risks were stacked, up to six risk factors (one: OR 1.5, CI 1.08-2.07; two: OR 2.01, CI 1.47-2.75; three: OR 2.71, CI 1.99-3.69; four: OR 3.27, CI 2.39-4.47; five: OR 3.63, CI 2.60-5.07; six: OR 4.23, CI 2.69-6.65), with each additional risk factor increasing mortality an average of 55% (±13%). CONCLUSIONS Among adults ≥50years with serious pneumococcal disease, mortality risk increased approximately 55% as vaccination indications present increased. Mortality with six stacked indications was double that of two indications.

Are non-allergic drug reactions commonly documented as medication “allergies”? A national cohort of Veterans' admissions from 2000 to 2014

Adverse drug reactions (ADRs) including medication allergies are not well‐described among large national cohorts. This study described the most common documented medication allergies and their reactions among a national cohort of Veterans Affairs (VA) inpatients.

Overconsumption of Antibiotics

This Article is brought to you for free and open access by the Pharmacy Practice at DigitalCommons@URI. It has been accepted for inclusion in Pharmacy Practice Faculty Publications by an authorized administrator of DigitalCommons@URI. For more information, please contact digitalcommons@etal.uri.edu. Citation/Publisher Attribution Morrill, H. J., & LaPlante, K. L. (2015). Overconsumption of antibiotics. Lancet Infectious Diseases, 15(4), 377-378. doi: 10.1016/S1473-3099(15)70083-6 Available at: http://dx.doi.org/10.1016/S1473-3099(15)70083-6 Follow this and additional works at: https://digitalcommons.uri.edu/php_facpubs