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Editorials: Point and Counterpoint |

Rebuttal From Dr Wunderink FREE TO VIEW

Richard G. Wunderink, MD, FCCP
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: The author has reported to CHEST the following: R. G. W. has received consultation fees from Bayer.

Pulmonary and Critical Care Division, Northwestern University Feinberg School of Medicine, Chicago, IL

CORRESPONDENCE TO: Richard G. Wunderink, MD, FCCP, 676 N St. Clair St, Arkes 14-015, Chicago, IL 60611


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2017;151(4):743-744. doi:10.1016/j.chest.2016.11.004
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Dr Kollef and I completely agree on the pragmatic Scottish verdict of “not proven” regarding the issue of aerosolized antibiotics. No clinical trials have met the rigorous US Food and Drug Administration criteria for an indication in hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP), and all published studies represent off-label use. However, although the theoretical benefits of antibiotic aerosolization have not yet been proved in clinical trials, the verdict on the current state of antibiotic treatment for HAP/VAP is clearly “guilty as charged.”

High clinical failure rates were documented in clinical trials even prior to the emergence of significant antibiotic resistance. Current antibiotics under development offer little potential for superior treatment but are mainly designed to fight a rearguard action against the emergence of antibiotic resistance. The current crisis in antibiotics is not due to a new phenomenon but rather reflects the inability and reluctance of the pharmaceutical industry to continue to invest in new antibiotics to treat resistant infections.

Unfortunately, patients and their loved ones have the mistaken idea that pneumonia is a preventable and treatable complication of mechanical ventilation or hospitalization. Multiple studies have demonstrated that this is only partially true, particularly in the treatment of VAP. Only the recent appearance of articles about extremely drug-resistant and pan-drug-resistant bacteria in the lay press and the presidential executive orders regarding the crisis in antibiotic resistance have raised awareness that pneumonia has not necessarily been a treatable infection. However, the idea that pneumonia should be treatable drives a reluctance to shift to more comfort care measures in patients undergoing prolonged mechanical ventilation.

To expect new antibiotics, optimized pharmacokinetics/pharmacodynamic protocols, and antibiotic stewardship to lead to improved outcomes for patients with HAP/VAP meets Einstein's definition of insanity, paraphrased as “doing the same thing over and over again and expecting different results.” Although each of these measures may have an important role in slowing the development of resistance, they are unlikely to decrease morbidity or mortality.

Aerosolized antibiotics are not the only possibility to take HAP/VAP treatment to a different level. Adjunctive passive immunization with monoclonal or polyclonal antibodies, extremely narrow-spectrum antibiotics that are effective against a single pathogen while leaving the remainder of the normal respiratory microbiome intact, and availability of rapid accurate diagnostic platforms with improved determination of antibiotic susceptibility offer other exciting potentials. What is clear is that we need to keep searching for better therapies for patients with HAP/VAP until the verdict for one of these “not (yet) proven” therapies is reversed.

References

Kollef M.H. . Counterpoint: Should inhaled antibiotic therapy be used routinely for the treatment of bacterial lower respiratory tract infections in the ICU setting? No. Chest. 2017;151:740-743 [PubMed]journal
 
Fink M.P. .Snydman D.R. .Niederman M.S. .et al Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. The Severe Pneumonia Study Group. Antimicrob Agents Chemother. 1994;38:547-557 [PubMed]journal. [CrossRef] [PubMed]
 
Tommasi R. .Brown D.G. .Walkup G.K. .et al ESKAPEing the labyrinth of antibacterial discovery. Nat Rev Drug Discov. 2015;14:529-542 [PubMed]journal. [CrossRef] [PubMed]
 
Report to the President on Combating Antibiotic Resistance. President's Council of Advisors on Science and Technology: Executive Office of the President, September 2014.https://www.whitehouse.gov/sites/default/files/microsites/ostp/PCAST/pcast_carb_report_sept2014.pdf. Accessed December 2, 2016.
 
Martin-Loeches I. .Wunderink R.G. .Nanchal R. .et al Determinants of time to death in hospital in critically ill patients around the world. Intensive Care Med. 2016;42:1454-1460 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Tables

References

Kollef M.H. . Counterpoint: Should inhaled antibiotic therapy be used routinely for the treatment of bacterial lower respiratory tract infections in the ICU setting? No. Chest. 2017;151:740-743 [PubMed]journal
 
Fink M.P. .Snydman D.R. .Niederman M.S. .et al Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. The Severe Pneumonia Study Group. Antimicrob Agents Chemother. 1994;38:547-557 [PubMed]journal. [CrossRef] [PubMed]
 
Tommasi R. .Brown D.G. .Walkup G.K. .et al ESKAPEing the labyrinth of antibacterial discovery. Nat Rev Drug Discov. 2015;14:529-542 [PubMed]journal. [CrossRef] [PubMed]
 
Report to the President on Combating Antibiotic Resistance. President's Council of Advisors on Science and Technology: Executive Office of the President, September 2014.https://www.whitehouse.gov/sites/default/files/microsites/ostp/PCAST/pcast_carb_report_sept2014.pdf. Accessed December 2, 2016.
 
Martin-Loeches I. .Wunderink R.G. .Nanchal R. .et al Determinants of time to death in hospital in critically ill patients around the world. Intensive Care Med. 2016;42:1454-1460 [PubMed]journal. [CrossRef] [PubMed]
 
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