Treatment of Gram-negative pneumonia in the critical care setting: is the beta-lactam antibiotic backbone broken beyond repair?

Abstract

Beta-lactam antibiotics form the backbone of treatment for Gram-negative pneumonia in mechanically ventilated patients in the intensive care unit. However, this beta-lactam antibiotic backbone is increasingly under pressure from emerging resistance across all geographical regions, and health-care professionals in many countries are rapidly running out of effective treatment options. Even in regions that currently have only low levels of resistance, the effects of globalization are likely to increase local pressures on the beta-lactam antibiotic backbone in the near future. Therefore, clinicians are increasingly faced with a difficult balancing act: the need to prescribe adequate and appropriate antibiotic therapy while reducing the emergence of resistance and the overuse of antibiotics. In this review, we explore the burden of Gram-negative pneumonia in the critical care setting and the pressure that antibiotic resistance places on current empiric therapy regimens (and the beta-lactam antibiotic backbone) in this patient population. New treatment approaches, such as systemic and inhaled antibiotic alternatives, are on the horizon and are likely to help tackle the rising levels of beta-lactam antibiotic resistance. In the meantime, it is imperative that the beta-lactam antibiotic backbone of currently available antibiotics be supported through stringent antibiotic stewardship programs.

Fig. 1

Etiology of pneumonia in the hospital and critical care setting. EMR Europe and Mediterranean Region. Data from Sader et al. [23] (2014)

Fig. 2

Evolving resistance patterns for Gram-negative pathogens associated with pneumonia in the critical care patient. Approximate years in which resistant organisms were identified are shown. AmpC AmpC-producing Enterobacteriaceae, ESBL extended-spectrum β-lactamase-producing Enterobacteriaceae, NDM-1 New Delhi metallo-β-lactamase-1-producing Enterobacteriaceae. Adapted from [33] and [94]