The Role of Delafloxacin in Patients with Community-Acquired Bacterial Pneumonia in the Outpatient Setting: A Budget Impact Model.

BACKGROUND AND OBJECTIVE: Community-acquired bacterial pneumonia (CABP) affects millions of people each year in the USA. The majority of patients with CABP are treated in the community setting with empirical antimicrobial therapy. Delafloxacin is an anionic fluoroquinolone approved for the treatment of adult patients with CABP. This de novo analysis sought to estimate the budget impact of delafloxacin in the treatment of adult patients with CABP in the outpatient setting from the payer's perspective. METHODS: A budget impact model (BIM) was developed from the perspective of a US third-party payer to estimate the cost of introducing delafloxacin for the outpatient treatment of CABP over a 1-year time horizon. Population, clinical, and cost inputs were based on the available literature, clinical trial data, and real-world evidence studies. Scenario analyses were conducted to evaluate the potential budget impact among COPD/asthma patients based on the findings from the phase III trial of delafloxacin for CABP, which indicated that patients with COPD or asthma may experience improved effectiveness with delafloxacin compared to moxifloxacin. RESULTS: In the base-case analysis, with a hypothetical plan of 1,000,000 members, the model estimated that adding delafloxacin to the formulary resulted in a total budget impact of $58,987. This increase was mainly attributed to treatment acquisition costs. In the scenario analysis that was restricted to COPD/asthma patients, adding delafloxacin to the formulary was estimated to result in a total budget impact of $5,042. CONCLUSION: The results of the budget impact analyses provide conservative estimates of the impact of adding delafloxacin to outpatient formularies in substitution of moxifloxacin.

The Real-World Economic and Clinical Management of Adult Patients with Skin and Soft Tissue Infections (SSTIs) with Oritavancin: Data from Two Multicenter Observational Cohort Studies.

BACKGROUND: Oritavancin is a FDA-approved single-dose IV therapy for the treatment of acute bacterial skin and skin structure infections caused (or suspected to be caused) by certain Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Published data describing the outcomes of patients with skin and soft tissue infections (SSTIs) who received oritavancin beyond its pivotal phase III clinical trials are scant. OBJECTIVE: The purpose of this report was to describe the results of two separate multicenter observational cohort studies that described the outcomes associated with two unique real-world usage patterns of oritavancin. METHODS: The first cohort (n = 115) examined patients 18 years or older who were treated with oritavancin at three outpatient sites for SSTIs caused by suspected or confirmed Gram-positive pathogens, including MRSA, to avoid hospital admission. Patients were included if they had not been discharged from the inpatient setting within the previous 24 h and received their single-dose oritavancin treatment at a hospital-based outpatient infusion center. The primary outcomes measured were 30-day healthcare costs and admissions (all cause and infection related). The second cohort (n = 151) was a multicenter, retrospective chart review of adult patients who were discharged early from seven hospitals in 2015 on oritavancin for SSTIs. The primary outcome was readmission of patients within 30 days (all cause and infection related). RESULTS: In cohort 1, 30-day mean healthcare costs were USD 3698. In the study of patients who started oritavancin in the outpatient setting, 7 patients (6.1%) were admitted to hospital within 30 days of the index treatment, and 3 of those (2.6% overall) were deemed to be due to an infection. In cohort 2, all-cause and infection-related 30-day readmission rates were 6.6% and 2.6%, respectively, among patients who received oritavancin at hospital discharge. CONCLUSIONS: Findings from these studies suggest that oritavancin may be a potentially useful agent to avoid hospitalization or shorten hospital length of stay among appropriate SSTI patients. Future comparator studies are required to properly ascertain the outcomes and potential benefits associated with oritavancin relative to other commonly used antibiotics in patients with SSTIs.

Combating resistance while maintaining innovation: the future of antimicrobial stewardship.

Antimicrobial resistance represents a significant global health threat. However, a commercial model that does not offer a return on investment resulting in a lack of investment in antibiotic R&D, means that the current pipeline of antibiotics lacks sufficient innovation to meet this challenge. Those responsible for defining, promoting and monitoring the rationale use of antibiotics (the antimicrobial stewardship programme) are key to addressing current shortcomings. In this personal perspective, we discuss the future role stewardship can play in stimulating innovation, a need to move away from a pharmacy budget dominated view of antibiotic use, and the impact of the ever-increasing sophistication and interdisciplinary nature of antimicrobial control programs. Changes are needed to optimize clinical outcomes for patients.

The burden of community-acquired bacterial pneumonia in the era of antibiotic resistance.

INTRODUCTION: Community-acquired pneumonia (CAP) is a significant global health problem and leading cause of death and hospitalization in both the US and abroad. Increasing macrolide resistance among Streptococcus pneumoniae and other pathogens results in a greater disease burden, along with changing demographics and a higher preponderance of comorbid conditions. Areas covered: This review summarizes current data on the clinical and economic burden of CAP, with particular focus on community-acquired bacterial pneumonia (CABP). Incidence, morbidity and mortality, and healthcare costs for the US and other regions of the world are among the topics covered. Major factors that are believed to be contributing to the increased impact of CABP, including antimicrobial resistance, the aging population, and the incidence of comorbidities are discussed, as well as unmet needs in current CABP management. Expert commentary: The clinical and economic burden of CABP is staggering, far-reaching, and expected to increase in the future as new antibiotic resistance mechanisms emerge and the world's population ages. Important measures must be initiated to stabilize and potentially decrease this burden. Urgent needs in CABP management include the development of new antimicrobials, adjuvant therapies, and rapid diagnostics.

Burden of antimicrobial resistance in an era of decreasing susceptibility.

INTRODUCTION: Antimicrobial resistance has become a global problem. Many pathogens are becoming multidrug-resistant with the attendant increased risk of failure of standard therapies and the under-recognised outcomes such as increased morbidity, mortality, length of hospitalization and costs of treatment. Areas covered: We undertook a review of the literature using standard search engines including PubMed, Google Scholar, Scopus and internet sources. Key search terms included antimicrobial resistance, antibiotic resistance, bacterial resistance, clinical outcomes, economic consequences, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pneumoniae and Staphylococcus aureus. Expert commentary: Antimicrobial resistance among the five-species presented demonstrates a major, and increasing, deleterious impact seen in each of the key outcomes measured. These negative changes, at a personal, health system and Societal levels, further emphasise the growing problem of increasing antimicrobial resistance at a global level and the vital need for new antimicrobials.

Antibiotic treatment patterns, costs, and resource utilization among patients with community acquired pneumonia: a US cohort study.

OBJECTIVES: The current treatment options for patients with community-acquired pneumonia (CAP) often present a trade-off between the potential for treatment failure and safety concerns. We set out to investigate real-world outcomes associated with the use of currently available antimicrobial treatment options for CAP in both the outpatient and inpatient (non-intensive care unit [ICU]) settings. METHODS: This claims-based retrospective study included adult patients diagnosed with CAP and treated with antibiotic therapies, including any oral fluoroquinolone, macrolide, or beta-lactam monotherapy in the outpatient setting, and intravenous (IV) levofloxacin or IV azithromycin/ceftriaxone in the inpatient setting. Generalized linear model (GLM) regression was used to determine total charges for inpatient stay, the length of stay, and days of inpatient therapy. For outpatients, rates of adverse events (AEs), treatment failure, and hospitalization were compared by type of initial antibiotic therapy using logistic regression multivariate models that controlled for baseline characteristics. RESULTS: A total of 441,820 outpatients and 33,287 inpatients treated for CAP between 2007 and 2012 were included in this analysis. In the outpatient setting, fluoroquinolone therapy led to a higher rate of documented AEs (adjusted odds ratio [OR]: 1.23; 95% confidence interval [CI]: 1.20-1.25; p < 0.0001) but a lower rate of retreatment (adjusted OR: 0.9; 95% CI: 0.87-0.94; p < 0.0001) compared with macrolides. Both AEs and retreatment in these patients were associated with increased costs. For patients treated with the IV macrolide/beta-lactam combination compared with IV fluoroquinolone in the inpatient setting, a significantly longer length of stay in hospital (4.71 vs. 4.38 days; p < 0.0001) and greater overall costs ($3,535 more per stay; p < 0.0001) were observed. CONCLUSION: In both the inpatient and outpatient settings, the development of additional efficacious treatment options that have a reduced AE burden for patients with CAP may be warranted.

The Regulatory Pathway for Antifungal Drugs: A US Perspective.

Although there was a flurry of new antifungal drugs approved in the early part of the last decade, the growing need for newer agents to treat systemic fungal infections has escalated due to increasing resistance to the 2 main classes of drugs developed to date and shifts in the etiology of these diseases. In addition to this microbial shift, there are more at-risk patients who are being managed in increasingly heroic ways and are thus highly susceptible to these more common resistant fungi and yeasts. However, as we acknowledge the need for new drugs to treat these desperately ill patients, there is a basic problem facing the pharmaceutical industry as it tries to balance the conundrum of antifungal development. Globally there is a relatively low, but growing, number of systemic fungal infections, which creates significant hurdles in conducting clinical trials in a timely and economical manner. In the United States, there have been some significant moves to easing these hurdles and, potentially, to bringing new drugs to the clinic more quickly and efficiently. We will discuss the current unmet clinical need and the current US regulatory positions to encourage further investment in this critical field.

Role of gemifloxacin in community-acquired pneumonia.

Community-acquired pneumonia (CAP) is the leading cause of death due to bacterial infection. It accounts for 10 million physician office visits in the USA annually. However, 80% of these are managed in the community, usually with oral antibiotic therapy. Typically, such courses have lasted 10 days or longer. Streptococcus pneumoniae accounts for 25% of all CAP infections; resistance among S. pneumoniae to all classes of antibiotics, including fluoroquinolones, poses new and shifting challenges to the primary care physician. Gemifloxacin is a potent agent, active against pneumococci and atypical pathogens. Administered once daily for 5 days, gemifloxacin is highly efficacious and well tolerated. Gemifloxacin administered for 5-7 days is a cost effective and safe alternative to both parenteral and oral antimicrobials, which may not cover the emerging resistant respiratory pathogens.

Antibiotic development: a victim of market forces?

The emergence of antibiotic-resistant bacteria is a major health concern as the number of clinically useful treatment options diminishes. However, this area of research has not proven to be highly attractive to the pharmaceutical industry; indeed, several major companies have announced the termination of efforts in the arena of antibiotics. The rationale behind these strategic shifts may not be immediately evident to the general public or even to physicians. This feature review addresses some of the factors that have played a role in the current paucity of new antibiotics under development, and discusses the dangerous repercussions if major changes are not implemented soon.

National and regional assessment of antimicrobial resistance among community-acquired respiratory tract pathogens identified in a 2005-2006 U.S. Faropenem surveillance study.

Surveillance studies conducted in the United States over the last decade have revealed increasing resistance among community-acquired respiratory pathogens, especially Streptococcus pneumoniae, that may limit future options for empirical therapy. The objective of this study was to assess the scope and magnitude of the problem at the national and regional levels during the 2005-2006 respiratory season (the season when community-acquired respiratory pathogens are prevalent) in the United States. Also, since faropenem is an oral penem being developed for the treatment of community-acquired respiratory tract infections, another study objective was to provide baseline data to benchmark changes in the susceptibility of U.S. respiratory pathogens to the drug in the future. The in vitro activities of faropenem and other agents were determined against 1,543 S. pneumoniae isolates, 978 Haemophilus influenzae isolates, and 489 Moraxella catarrhalis isolates collected from 104 U.S. laboratories across six geographic regions during the 2005-2006 respiratory season. Among S. pneumoniae isolates, the rates of resistance to penicillin, amoxicillin-clavulanate, and cefdinir were 16, 6.4, and 19.2%, respectively. The least effective agents were trimethoprim-sulfamethoxazole (SXT) and azithromycin, with resistance rates of 23.5 and 34%, respectively. Penicillin resistance rates for S. pneumoniae varied by region (from 8.7 to 22.5%), as did multidrug resistance rates for S. pneumoniae (from 8.8 to 24.9%). Resistance to beta-lactams, azithromycin, and SXT was higher among S. pneumoniae isolates from children than those from adults. beta-Lactamase production rates among H. influenzae and M. catarrhalis isolates were 27.4 and 91.6%, respectively. Faropenem MICs at which 90% of isolates are inhibited were 0.5 mug/ml for S. pneumoniae, 1 mug/ml for H. influenzae, and 0.5 mug/ml for M. catarrhalis, suggesting that faropenem shows promise as a treatment option for respiratory infections caused by contemporary resistant phenotypes.