Investigational drugs in phase I and phase II clincial trials for the treatment of hospital-acquired pneumonia

ABSTRACT

Introduction: Hospital acquired pneumonia (HAP) is one of the main infections acquired by patients during a stay in hospital. The main issue when dealing with patients with HAP and ventilator associated pneumonia (VAP) is the increasing role of multi-drug resistant organisms (MDROs).

Areas covered: In this review the authors summarize the actual situation of MDROs as a cause of HAP and VAP. They also review the current treatment options stated in the most important international guidelines. Finally, they focus on the investigational drugs that have reached the phase III stage of development and the novel compounds that are being studied in phase I and II clinical trials.

Expert opinion: Thanks to their excellent activity against MDROs, drugs in development for the treatment of HAP and VAP can significantly improve the therapeutic options available. In selected patients, the possibility to administer directed therapy with monoclonal antibodies to specific pathogens is an exciting strategy in the fight against widespread resistance.

KEYWORDS:

• Ceftazidime/avibactam
• ceftolozane/tazobactam
• imipenem/relevactam
• hospital acquired pneumonia
• multidrug resistant microorganisms
• plazomicin
• tedizolid

Article highlights

• The main issue when dealing with patients with HAP and VAP is the increasing role of multi-drug resistant organisms. Patients with infections caused by MRSA, P. aeruginosa, Acinetobacter spp., or other MDR Enterobacteriaceae are at a higher risk of receiving inappropriate initial antimicrobial therapy.

• Currently, up to six drugs for the treatment of hospital-acquired infections, including HAP and VAP, have reached phase III in clinical development.

• The most promising antibiotics that are currently in advanced stages of development with potential utility for patients with HAP/VAP include tedizolid, ceftolozane/tazobactam, ceftazidime/avibactam, imipenem/relevactam, plazomicin, and inhaled amikacin.

• Due to the wide microbiological spectrum of these new compounds, de-escalation strategies will have to be addressed in the guidelines in order to avoid the emergence of bacteria with novel mechanisms of resistance.

• In selected patients the possibility to administer directed therapy with monoclonal antibodies directed to specific pathogens is an exciting strategy to fight against the widespread of resistance.

This box summarizes key points contained in the article.

Acknowledgments

The authors want to thank Dr Adria Curran (infectious Diseases Department, hospital Vall d’Hebron, Barcelona) for his help in reviewing the manuscript.

Declaration of interest

The authors are supported by Research Network RD12/0017/0003, the Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2008–2011, Instituto de Salud Carlos III, Fondos FEDER. They are also supported by the Plan Nacional de I+D+I and the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía y Competitividad, the Spanish Network for Research in Infectious Diseases (REIPI RD12/0015) – co-financed by the European Regional Development Fund ‘A way to achieve Europe’ (ERDF). R Ferrer has also participated on an advisory board for ceftolozane/tazobactam for Merck, Sharp and Dohme. The authors have no other 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 apart from those disclosed.