Issues in antibiotic therapy for hospital-acquired and ventilator-associated pneumonia: emerging concepts to improve outcomes

ABSTRACT

Introduction:Ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) result in significant morbidity and mortality. The emergence of multi-drug resistant organisms has complicated the matter, as many of these pathogens now represent key causes of VAP and HAP. While anumber of new medications have been approved, acomprehensive appreciation of pharmacokinetic and pharmacodynamic principles, which, are often neglected, is key to effective treatment.

Areas covered: The authors discuss the central pharmacokinetic and pharmacodynamic principles underlying antibiotic utilization, especially as they pertain to the treatment of VAP and HAP. They further address the concept of and implications of augmented renal clearance for the patient with nosocomial pneumonia. Finally, the authors review the evolving data on colistin and inhaled antibiotics in the management of pneumonia.

Expert opinion: An enhanced understanding of the pharmacokinetic and pharmacodynamic principles along with insight into the concept of augmented renal clearance can help guide drug development and improve the way we currently dose and deliver most antibiotics. There is now mounting data on the limited efficacy and substantial nephrotoxicity of colistin, which makes it difficult to justify its continued use. While the concept of inhaled antibiotics is enticing, we lack conclusive data proving the efficacy of this paradigm.

KEYWORDS:

• Antibiotics
• pharmacokinetics
• pneumonia
• resistance
• ventilator

Article highlights

• Ventilator-associated pneumonia (VAP) is associated with significant morbidity and mortality with crude mortality rates exceeding 40%.

• Multidrug resistant (MDR) organisms now represent a leading cause of hospital acquired pneumonia (HAP) and VAP.

• There is a significant impact of MDR VAP with rising ICU and hospital length of stay, increased mechanical ventilatory time, and increased healthcare costs.

• Antibiotic dosing should be adjusted relying upon the principles of pharmacokinetics and pharmacodynamics with consideration of continuous infusions to achieve target drug concentrations in the lungs.

• Augmented renal clearance should be accounted for when dosing antibiotics.

• The use of colistin for MDR VAP has limited efficacy and significant nephrotoxicity associated with it and its use should be reconsidered as newer agents become available.

• Inhaled antibiotics are not yet a reliable alternative for treating MDR VAP.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.