Resistance Trends and Treatment Options in Gram-Negative Ventilator-Associated Pneumonia

  • Nathaniel J. Rhodes
  • Caroline E. Cruce
  • J. Nicholas O’Donnell
  • Richard G. Wunderink
  • Alan R. Hauser
Antimicrobial Development and Drug Resistance (A Pakyz, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Antimicrobial Development and Drug Resistance


Purpose of Review

Hospital-acquired and ventilator-associated pneumonia (VAP) are frequent causes of infection among critically ill patients. VAP is the most common hospital-acquired bacterial infection among mechanically ventilated patients. Unfortunately, many of the nosocomial Gram-negative bacteria that cause VAP are increasingly difficult to treat. Additionally, the evolution and dissemination of multi- and pan-drug resistant strains leave clinicians with few treatment options. VAP patients represent a dynamic population at risk for antibiotic failure and under-dosing due to altered antibiotic pharmacokinetic parameters. Since few antibiotic agents have been approved within the last 15 years, and no new agents specifically targeting VAP have been approved to date, it is anticipated that this problem will worsen. Given the public health crisis posed by resistant Gram-negative bacteria, it is essential to establish a firm understanding of the current epidemiology of VAP, the changing trends in Gram-negative resistance in VAP, and the current issues in drug development for Gram-negative bacteria that cause VAP.

Recent Findings

Rapid identification technologies and phenotypic methods, new therapeutic strategies, and novel treatment paradigms have evolved in an attempt to improve treatment outcomes for VAP; however, clinical data supporting alternative treatment strategies and adjunctive therapies remain sparse. Importantly, new classes of antimicrobials, novel virulence factor inhibitors, and beta-lactam/beta-lactamase inhibitor combinations are currently in development. Conscientious stewardship of new and emerging therapeutic agents will be needed to ensure they remain effective well into the future.


Ventilator-associated pneumonia Gram-negative bacteria epidemiology Rapid diagnostic technologies Antibacterial agents Novel therapeutics Drug development 


Compliance with Ethical Standards

Conflict of Interest

NJR: discloses reciept of travel expenses and honoria from American Society of Healthsystem Pharmacists

CC: no relevant disclosures

JNO: no relevant disclosures

RGW: discloses reciept of payment for continuing medical education from Medscape and consulting fees from Meiji-Seiko, Merck, Nabriva, Polyphor, Roche/Genetech, Shionogi, The Medicines Company, Accelerate Diagnostics, Curetis, and bioMerieux

ARH: discloses board membership with Microbiotix, NIH grant funding, travel funds and expenses from Cystic Fibrosis Foundation and American Society of Microbiology, and consulting fees from MedImmune

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmacy PracticeMidwestern University, Chicago College of PharmacyDowners GroveUSA
  2. 2.Department of PharmacyNorthwestern Memorial HospitalChicagoUSA
  3. 3.Department of Pharmacy PracticeAlbany College of Pharmacy and Health SciencesAlbanyUSA
  4. 4.Department of Internal Medicine, Division of Pulmonary Critical CareNorthwestern University Feinberg School of MedicineChicagoUSA
  5. 5.Department of Internal Medicine, Division of Infectious DiseasesNorthwestern University Feinberg School of MedicineChicagoUSA
  6. 6.Department of Microbiology-ImmunologyNorthwestern University Feinberg School of MedicineChicagoUSA

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