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Management of community-acquired bacterial pneumonia in adults: Limitations of current antibiotics and future therapies.

ABSTRACT: Community-acquired bacterial pneumonia (CABP) is one of the leading causes of morbidity and mortality in India and worldwide. Evidence indicates that Gram-positive, Gram-negative, and atypical bacteria are encountered with near-equal frequency. Despite guideline recommendations and antibiotic options for the management of CABP, burden of morbidity and mortality is high, which is attributable to a variety of factors. Failure of empirical therapy, probably because of insufficient microbial coverage, increasing bacterial resistance, and adverse effects of existing treatments, underlies the unsuccessful treatment of CABP, especially in India. Multiple novel therapies that have entered clinical development phases have potential to address some of these issues. This article discusses the current treatment guidelines in CABP, management limitations, and emerging potential treatment options in the management of CABP.

SUBMITTER: Nayar S

PROVIDER: S-EPMC6852216 | biostudies-literature | 2019 Nov-Dec

REPOSITORIES: biostudies-literature

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Management of community-acquired bacterial pneumonia in adults: Limitations of current antibiotics and future therapies.

Nayar Sandeep S Hasan Ashfaq A Waghray Pradyut P Ramananthan Srinivasan S Ahdal Jaishid J Jain Rishi R

Lung India : official organ of Indian Chest Society 20191101 6

Community-acquired bacterial pneumonia (CABP) is one of the leading causes of morbidity and mortality in India and worldwide. Evidence indicates that Gram-positive, Gram-negative, and atypical bacteria are encountered with near-equal frequency. Despite guideline recommendations and antibiotic options for the management of CABP, burden of morbidity and mortality is high, which is attributable to a variety of factors. Failure of empirical therapy, probably because of insufficient microbial coverag ...[more]

PMID: 31670301

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Project description:UnlabelledHospital-acquired pneumonia (HAP) and health-care-associated pneumonia (HCAP) are leading causes of death, morbidity, and resource utilization in hospitalized patients, and are associated with a broad range of Gram-positive and Gram-negative pathogens. Here, we discuss the different definitions of HAP and HCAP, review current guidelines regarding the treatment of these conditions, highlight the shortcomings of current therapeutic options, and discuss new antibiotic treatments. To optimize therapeutic outcomes in patients with HAP/HCAP, initial antimicrobial treatment must be appropriate and should be given as soon as possible; inappropriate or delayed therapy greatly increases morbidity and mortality. Selection of the most appropriate antimicrobial agent depends on the causative pathogen(s); initial broad-spectrum therapy is commonly recommended and should cover all pathogens that may be present. Treatment selection should also take into consideration the following factors: knowledge of underlying local risk factors for antimicrobial resistance, disease staging, and risk factors related to specific pathogens such as Pseudomonas aeruginosa, Acinetobacter spp., and methicillin-resistant Staphylococcus aureus (MRSA). Guidelines consistently emphasize the importance of treating HAP and HCAP with early and appropriate broad-spectrum antibiotics, and recent developments in this field have resulted in the availability of several additional treatment options. Telavancin shows potent activity against Gram-positive bacteria including MRSA and can be administered once daily; it was approved in the USA and European Union for the treatment of HAP after demonstrating non-inferiority to vancomycin. Ceftobiprole medocaril exhibits rapid antimicrobial activity against a broad range of both Gram-positive and Gram-negative pathogens, including MRSA. It was approved for the treatment of HAP (excluding ventilator-associated pneumonia) and community-acquired pneumonia in Europe in 2013. These new treatments may offer effective alternative therapeutic options for the management of HAP.FundingBasilea Pharmaceutica Ltd., Basel, Switzerland.

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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Management of community-acquired bacterial pneumonia in adults: Limitations of current antibiotics and future therapies.

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Management of community-acquired bacterial pneumonia in adults: Limitations of current antibiotics and future therapies.

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