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Community-Acquired Bacterial Pneumonia-Changing Epidemiology, Resistance Patterns, and Newer Antibiotics: Spotlight on Delafloxacin.

ABSTRACT: Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality both in the USA and globally. As the burden of CAP continues to increase due to several factors, the advances in its diagnosis, prevention, and treatment have taken on even greater interest and importance. The majority of CAP patients are treated empirically, and selection of appropriate antibiotic treatment is increasingly difficult because the epidemiology of CAP is changing, in part due to antimicrobial resistance, and the causative CAP pathogens differ between countries and regions. There is also an increasing prevalence of chronic co-morbid diseases among CAP patients. Treatment of CAP has become challenging because of these factors along with the varying safety profiles and efficacy of well-established antibiotics, as well as limited new therapeutic options. Recently, however, new antibiotics have been approved, which will expand the treatment options for CAP, particularly in those patients with underlying complications. Recently approved delafloxacin, an anionic fluoroquinolone, has a unique structure and distinct chemical characteristics; it demonstrated non-inferiority to moxifloxacin in a phase III clinical trial, but was shown to be superior to moxifloxacin at early clinical response in CAP patients who also have chronic obstructive pulmonary disease (COPD) or asthma as a co-morbidity, and in CAP patients who may have severe illness. Delafloxacin could offer an additional therapy against resistant isolates and among these difficult-to-treat patients. This review summarizes the development, latest research, and safety profile of the new antibiotic delafloxacin, and its potential future role in the treatment of CAP.

SUBMITTER: Sharma R

PROVIDER: S-EPMC7511281 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Community-Acquired Bacterial Pneumonia-Changing Epidemiology, Resistance Patterns, and Newer Antibiotics: Spotlight on Delafloxacin.

Sharma Roopali R Sandrock Christian E CE Meehan Joni J Theriault Nicolette N

Clinical drug investigation 20201001 10

Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality both in the USA and globally. As the burden of CAP continues to increase due to several factors, the advances in its diagnosis, prevention, and treatment have taken on even greater interest and importance. The majority of CAP patients are treated empirically, and selection of appropriate antibiotic treatment is increasingly difficult because the epidemiology of CAP is changing, in part due to antimicrobial resistance, ...[more]

PMID: 32889706

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Project description:Delafloxacin is a novel fluoroquinolone with activity against Gram-positive, Gram-negative, and atypical pathogens, including fluoroquinolone-nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA). The microbiological results of a phase 3 clinical trial in adults with community-acquired pneumonia (CAP) comparing delafloxacin (300?mg intravenously [i.v.] with the option to switch to 450?mg orally every 12 h) to moxifloxacin (400?mg i.v. with the option to switch to 400?mg orally once a day [QD]) were determined. Patients from 4 continents, predominately Europe but also South America and Asia, were enrolled. The microbiological intent-to-treat (MITT) population included 520 patients, and 60.5% of these patients had a bacterial pathogen identified. Multiple diagnostic methods were employed, including culture, serology, PCR, and urinary antigen tests. Based on baseline MIC90 values, delafloxacin exhibited at least 16-fold greater activity than moxifloxacin for Gram-positive and fastidious Gram-negative pathogens. Delafloxacin retained activity against resistant phenotypes found in Streptococcus pneumoniae (penicillin-, macrolide-, and multiple-drug resistant), Haemophilus species (?-lactamase producing and macrolide nonsusceptible), and S. aureus (MRSA and fluoroquinolone-nonsusceptible methicillin-susceptible S. aureus [MSSA]). The microbiological success rates were 92.7% for S. pneumoniae (87.5% for penicillin-resistant S. pneumoniae [PRSP]), 92.6% for S. aureus (100% for MRSA), 100% for Escherichia coli, 82.4% for Klebsiella pneumoniae, 100% for Klebsiella oxytoca, 100% for Moraxella catarrhalis, 91.7% for Haemophilus influenzae, 88.6% for Haemophilus parainfluenzae, 96.7% for Mycoplasma pneumoniae, 93.1% for Legionella pneumophila, and 100% for Chlamydia pneumoniae There was little correlation between MICs and outcomes, with a high proportion of favorable outcomes observed across all delafloxacin baseline MIC values. Delafloxacin may be considered a treatment option as monotherapy for CAP in adults, where broad-spectrum coverage including MRSA activity is desirable.

Project description:To develop and validate a model to predict resistance to community-acquired pneumonia antibiotics (CAP-resistance) among patients with healthcare-associated pneumonia (HCAP), and to compare the model's predictive performance to a model including only guideline-defined criteria for HCAP.Retrospective cohort study.Six Veterans Affairs Medical Centers in the northwestern United States.Culture-positive inpatients with HCAP.Patients were identified based upon guideline-defined criteria for HCAP. Relevant cultures obtained within 48 hours of admission were assessed to determine bacteriology and antibiotic susceptibility. Medical records for the year preceding admission were assessed to develop predictive models of CAP-resistance with logistic regression. The predictive performance of cohort-developed and guideline-defined models was compared.CAP-resistant organisms were identified in 118 of 375 culture-positive patients. Of guideline-defined criteria, CAP-resistance was associated (odds ratio (OR) [95% confidence interval (CI)]) with: admission from nursing home (2.6 [1.6-4.4]); recent antibiotic exposure (1.7 [1.0-2.8]); and prior hospitalization (1.6 [1.0-2.6]). In the cohort-developed model, CAP-resistance was associated with: admission from nursing home or recent nursing home discharge (2.3 [1.4-3.8]); positive methicillin-resistant Staphylococcus aureus (MRSA) history within 90 days of admission (6.4 [2.6-17.8]) or 91-365 days (2.3 [0.9-5.9]); cephalosporin exposure (1.8 [1.1-2.9]); recent infusion therapy (1.9 [1.0-3.5]); diabetes (1.7 [1.0-2.8]); and intensive care unit (ICU) admission (1.6 [1.0-2.6]). Area under the receiver operating characteristic curve (aROC [95% CI]) for the cohort-developed model (0.71 [0.65-0.77]) was significantly higher than for the guideline-defined model (0.63 [0.57-0.69]) (P = 0.01).Select guideline-defined criteria predicted CAP-resistance. A cohort-developed model based primarily on prior MRSA history, nursing home residence, and specific antibiotic exposures provided improved prediction of CAP-resistant organisms in HCAP.

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Community-Acquired Bacterial Pneumonia-Changing Epidemiology, Resistance Patterns, and Newer Antibiotics: Spotlight on Delafloxacin.

Publications

Community-Acquired Bacterial Pneumonia-Changing Epidemiology, Resistance Patterns, and Newer Antibiotics: Spotlight on Delafloxacin.

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