Impact of Socioeconomic Status and Race on Sepsis Epidemiology and Outcomes.

BACKGROUND: Socioeconomic status (SES) is a complex variable that is derived primarily from an individual's education, income, and occupation and has been found to be inversely related to outcomes of health conditions. Sepsis is the sixth most common admitting diagnosis and one of the most costly conditions for in-hospital spending in the United States. The objective of this review is to report on the relationship between SES and sepsis incidence and associated outcomes. CONTENT: Sepsis epidemiology varies when explored by race, education, geographic location, income, and insurance status. Sepsis incidence was significantly increased in individuals of Black race compared with non-Hispanic white race; in persons who have less formal education, who lack insurance, and who have low income; and in certain US regions. People with low SES are likely to have onset of sepsis significantly earlier in life and to have poorly controlled comorbidities compared with those with higher SES. Sepsis mortality and hospital readmission is increased in individuals who lack insurance, who reside in low-income or medically underserved areas, who live far from healthcare, and who lack higher level education; however, a person's race was not consistently found to increase mortality. SUMMARY: Interventions to minimize healthcare disparity for individuals with low SES should target sepsis prevention with increasing measures for preventive care for chronic conditions. Significant barriers described for access to care by people with low SES include cost, transportation, poor health literacy, and lack of a social network. Future studies should include polysocial risk scores that are consistently defined to allow for meaningful comparison across studies.

Therapeutic Monitoring of Vancomycin for Serious Methicillin-resistant Staphylococcus aureus Infections: A Revised Consensus Guideline and Review by the American Society of Health-system Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists.

Recent clinical data on vancomycin pharmacokinetics and pharmacodynamics suggest a reevaluation of current dosing and monitoring recommendations. The previous 2009 vancomycin consensus guidelines recommend trough monitoring as a surrogate marker for the target area under the curve over 24 hours to minimum inhibitory concentration (AUC/MIC). However, recent data suggest that trough monitoring is associated with higher nephrotoxicity. This document is an executive summary of the new vancomycin consensus guidelines for vancomycin dosing and monitoring. It was developed by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists vancomycin consensus guidelines committee. These consensus guidelines recommend an AUC/MIC ratio of 400-600 mg*hour/L (assuming a broth microdilution MIC of 1 mg/L) to achieve clinical efficacy and ensure safety for patients being treated for serious methicillin-resistant Staphylococcus aureus infections.

Executive Summary: Therapeutic Monitoring of Vancomycin for Serious Methicillin-Resistant Staphylococcus aureus Infections: A Revised Consensus Guideline and Review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists.

BACKGROUND: Recent vancomycin PK/PD and toxicodynamic studies enable a reassessment of the current dosing and monitoring guideline in an attempt to further optimize the efficacy and safety of vancomycin therapy. The area-under-the-curve to minimum inhibitory concentration (AUC/MIC) has been identified as the most appropriate pharmacokinetic/pharmacodynamic (PK/PD) target for vancomycin. The 2009 vancomycin consenus guidelines recommended specific trough concentrations as a surrogate marker for AUC/MIC. However, more recent toxicodynamic studies have reported an increase in nephrotoxicity associated with trough monitoring. METHODS AND RESULTS: This is the executive summary of the new vancomycin consensus guidelines for dosing and monitoring vancomycin therapy and was developed by the American Society of Health-Systems Pharmacists, Infectious Diseases Society of America, Pediatric Infectious Diseases Society and the Society of Infectious Diseases Pharmacists vancomycin consensus guidelines committee. CONCLUSIONS: The recommendations provided in this document are intended to assist the clinician in optimizing vancomycin for the treatment of invasive MRSA infections in adult and pediatric patients. An AUC/MIC by broth microdilution (BMD) ratio of 400 to 600 (assuming MICBMD of 1 mg/L) should be advocated as the target to achieve clinical efficacy while improving patient safety for patients with serious MRSA infections. In such cases, AUC-guided dosing and monitoring is the most accurate and optimal way to manage vancomycin therapy.

Fitness Cost of Fluoroquinolone Resistance in Clinical Isolates of Pseudomonas aeruginosa Differs by Type III Secretion Genotype.

Fluoroquinolone (FQ) resistance is highly prevalent among clinical strains of Pseudomonas aeruginosa, limiting treatment options. We have reported previously that highly virulent strains containing the exoU gene of the type III secretion system are more likely to be FQ-resistant than strains containing the exoS gene, as well as more likely to acquire resistance-conferring mutations in gyrA/B and parC/E. We hypothesize that FQ-resistance imposes a lower fitness cost on exoU compared to exoS strains, thus allowing for better adaptation to the FQ-rich clinical environment. We created isogenic mutants containing a common FQ-resistance conferring point mutation in parC from three exoU to three exoS clinical isolates and tested fitness in vitro using head-to-head competition assays. The mutation differentially affected fitness in the exoU and exoS strains tested. While the addition of the parC mutation dramatically increased fitness in one of the exoU strains leaving the other two unaffected, all three exoS strains displayed a general decrease in fitness. In addition, we found that exoU strains may be able to compensate for the fitness costs associated with the mutation through better regulation of supercoiling compared to the exoS strains. These results may provide a biological explanation for the observed predominance of the virulent exoU genotype in FQ-resistant clinical subpopulations and represent the first investigation into potential differences in fitness costs of FQ-resistance that are linked to the virulence genotype of P. aeruginosa. Understanding the fitness costs of antibiotic resistance and possibilities of compensation for these costs is essential for the rational development of strategies to combat the problem of antibiotic resistance.

Early response assessment to guide management of methicillin-resistant Staphylococcus aureus bloodstream infections with vancomycin therapy.

BACKGROUND: A subset of vancomycin-treated patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) developed persistent positive blood cultures. Treatment eventually failed. METHODS: A retrospective study was conducted to determine whether early response on day 3 after initiation of vancomycin therapy for MRSA BSI was associated with reduced rates of persistent bacteremia, end-of-treatment failure, and infection-related mortality. Patients' medical charts were reviewed. Susceptibility testing and molecular characterization of bacterial isolates were performed. RESULTS: In this elderly cohort (n = 111; median age 70 years, interquartile range: 57-80 years), early response was observed in 62% of patients and was significantly (P < 0.0001) associated with lower rates of end-of-treatment failure (19% vs 57%) and infection-related death (1% vs 29%), but not with persistent bacteremia (17% vs 29%, P = 0.23). Nearly half (46%; 46 of 100 patients) remained on vancomycin therapy for the entire treatment course; those who continued despite lack of early response had a trend toward a higher risk of death than those who were switched to alternative therapy (38% vs 10%, P = NS). Most (68%) isolates had vancomycin MIC of >1 µg/mL, whereas 10% showed heterogeneous glycopeptide-intermediate Staph aureus (hGISA) phenotype. Nearly half (47%) were typed with staphylococcal cassette chromosome mec IV or V. In a multivariate logistic regression model, lack of response at day 3 was the strongest predictor for end-of-treatment failure, after adjustment for confounders such as age, Acute Physiology And Chronic Health Evaluation II score, intensive care unit admission, vancomycin MIC >1 µg/mL, unbound trough concentration <4 to 5× MIC, and continued vancomycin therapy without change. CONCLUSIONS: Early response assessment after initiation of vancomycin therapy appeared to be useful for considering further diagnostic workup or a switch to alternative therapy to affect a positive outcome in patients with MRSA BSI.

An antimicrobial stewardship program with a focus on reducing fluoroquinolone overuse.

The fluoroquinolones have become the leading class of antimicrobial agents prescribed to adults in the United States. Resistance of key pathogens to fluoroquinolones has developed rapidly in parallel with increased prescribing of these drugs. We describe our pharmacist-led antimicrobial stewardship program that focused on reducing inappropriate prescribing of fluoroquinolones, with the goals of limiting the development of resistance and improving patient outcomes. Core strategies were regular monitoring and reporting of resistance trends observed on institutional antibiograms, performing drug audits and related studies with intervention and feedback to prescribers, implementing an automatic parenteral-to-oral conversion program, establishing and implementing a beta-lactam-based institutional guideline for empiric therapy, and educating prescribers. This successful program reduced empiric prescribing of fluoroquinolones by 30%, improved susceptibility for all antipseudomonal agents against Pseudomonas aeruginosa overall by 10%, and decreased mortality associated with P. aeruginosa infections by 2-fold. Our stewardship program clearly demonstrated that pharmacists can take on leadership roles to positively change antimicrobial prescribing at the institutional level and improve patient outcomes.

Systemic antifungal therapy: new options, new challenges.

The frequency of invasive fungal infections has increased dramatically in recent decades because of an expanding population at risk. Until now, treatment options for invasive mycoses have been primarily amphotericin B and the azoles, fluconazole and itraconazole. Traditional agents are limited by an inadequate spectrum of activity, drug resistance, toxicities, and drug-drug interactions. The recent approval of caspofungin and voriconazole clearly has expanded the number of existing antifungal drugs available. However, the enthusiasm that accompanies their availability is counterbalanced by limited clinical experience, high drug acquisition costs, and distinctive toxicities. The pharmacologic characteristics, extent of clinical experience (efficacy and toxicity), and drug acquisition costs among available systemic antifungal agents are compared, with emphasis on the new agents. Also, recommendations on the role of each agent are provided according to the most common indications for systemic antifungal therapy: invasive candidiasis, invasive aspergillosis, and febrile neutropenia.