Treatment of Hospital or Ventilator-Associated Pneumonia Due to Carbapenem-Resistant Enterobacteriaceae: Leveraging Molecular Resistance Testing and Combination Therapy to Improve Outcomes

TO THE EDITOR—The recently published updated Infectious Diseases Society of America guideline on the management of adults with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) recommend that patients with HAP/VAP due to “carbapenem-resistant pathogens” susceptible only to polymyxins should receive, in addition to colistin by inhalation, systemic monotherapy with either polymyxin B or colistin [1]. This recommendation ignores the molecular heterogeneity of resistance mechanisms in these organisms and conflicts with accumulating data supporting the use of combination therapy for bacteremic infections due to some carbapenem-resistant Enterobacteriaceae (CRE), particularly those due to Klebsiella pneumoniae [2–4]. These retrospective studies provide evidence that, despite the presence of phenotypic carbapenem resistance, the addition of a carbapenem to a polymyxin to which the organism is susceptible is associated with improved outcomes in the treatment of infection due to carbapenemase-positive organisms. This has best been demonstrated with bacteremic infections due to carbapenemase-producing K. pneumoniae (KPC) that, have relatively low minimum inhibitory concentrations (MICs) (ie, ≤8 μg/mL) [5,6]. Although the relevant studies deal with bacteremic infections, there is no reason to presume that the same principles do not apply to the treatment of HAP/VAP. The predictability of response is, however, complicated by the fact that CRE oftenexpressmore thanonemechanismof resistance. For example, KPC-producing K. pneumoniae may possess altered porin expression and function, the presence of which is an independent risk factor for poor outcomes in KPC-infected patients treated with colistin and doripenem in combination [6]. Furthermore, the specific