Host-directed therapies for antimicrobial resistant respiratory tract infections

Curr Opin Pulm Med. 2016 May;22(3):203-11. doi: 10.1097/MCP.0000000000000271.


Purpose of review: Antimicrobial-resistant respiratory tract infections (AMR-RTIs) are increasing, presenting important management challenges worldwide. Current management of AMR-RTI patients focuses on pathogen-directed antimicrobial treatment. Overt lung inflammation, parenchymal damage, and ineffective immune activation perpetrate increased patient morbidity and mortality. Immunomodulatory and tissue-regenerative host-directed therapies (HDT) may improve treatment outcomes. HDTs under investigation for improving AMR-RTI treatment outcomes are reviewed.

Recent findings: Various HDTs are being developed or evaluated for adjunctive AMR-RTI treatment. α-1 antitrypsin was shown to reduce Pseudomonas aeruginosa burden in the airways of cystic fibrosis patients. Cellular therapy by reinfusing autologous bone marrow-derived MSCs into MDR/XDR-TB patients shows promise, whereas adjunctive T cell-based therapies are considered. Cytotoxic therapy using etoposide, a topoisomerase II-inhibiting anticancer drug extends survival of patients with severe influenza H1N1 infection-induced hemophagocytic lymphohistiocytosis. Two other novel HDT candidates, DAS181 and resveratrol show antiinfluenza effects. Novel kinase inhibitors SB203580 (MAPK-2 antagonist) and LY294002 (phosphoinositide-3 kinases antagonist) exhibit promising anti-MERS-CoV activity. Palivizumab, an anti-RSV monoclonal antibody, effectively prevents RSV infection in high-risk paediatric populations. T-cell therapy is currently considered for adjunctive HDT of azole-resistant pulmonary aspergillosis.

Summary: Novel HDTs may revolutionize future treatment regimens for AMR-RTIs. Well designed multisite clinical trials are now necessary to accelerate progress.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Infective Agents / therapeutic use*
  • Cystic Fibrosis
  • Humans
  • Respiratory Tract Infections / therapy*
  • Treatment Outcome


  • Anti-Infective Agents