0
Editorials |

Ventilator-Associated PneumoniaVentilator-Associated Pneumonia Diagnostics: The Role of Emerging Therapies and Diagnostics FREE TO VIEW

Marin H. Kollef, MD, FCCP
Author and Funding Information

From the Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine.

CORRESPONDENCE TO: Marin H. Kollef, MD, FCCP, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8052, St. Louis, MO 63110; e-mail: mkollef@dom.wustl.edu


FUNDING/SUPPORT: Dr Kollef is supported in part by the Barnes-Jewish Hospital Foundation.

FINANCIAL/NONFINANCIAL DISCLOSURES: The author has reported to CHEST the following conflicts of interest: Dr Kollef has served as a consultant for Cubist Pharmaceuticals Inc, Merck & Co Inc, Forest Laboratories Inc, Accelerate Diagnostics Inc, Cardeas Pharma Corp, Theravance Biopharma Inc, Sanofi Pasteur SA, Basilea Pharmaceutica Ltd, Medimmune LLC, AstraZeneca plc, bioMérieux Inc, and the Academy for Infection Management.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(6):1448-1450. doi:10.1378/chest.14-2745
Text Size: A A A
Published online

Ventilator-associated pneumonia (VAP) is one of the most common infections in patients who are mechanically ventilated and is frequently due to infection by antibiotic-resistant bacteria. Mortality, hospital lengths of stay, and health-care costs are typically greater among patients with respiratory failure complicated by VAP compared with patients who do not develop VAP.1 Moreover, we know that the administration of inappropriate initial antibiotic therapy for VAP, usually due to the presence of multidrug-resistant bacteria as the causative pathogens, is associated with greater hospital mortality and longer hospital lengths of stay.2

These outcome-influencing characteristics of VAP make it an important infection for intensivists to manage in an optimal manner. Such optimal management requires ICUs and hospitals to have consensus-derived strategies in place for the prevention, diagnosis, and treatment of VAP. Unfortunately, the overall perceived clinical importance of VAP has diminished somewhat in the United States over the past 10 years due to the imprecise undercoding of this nosocomial infection, using the US Centers for Disease Control and Prevention surveillance definitions applied retrospectively.3,4 This has resulted in the promotion of ventilator-associated events as a more appropriate surveillance tool for assessing the quality of ICU care in the United States and reducing VAP to a nonreportable condition.5 However, the emerging problem of antibiotic resistance has added a new premium to the importance of accurately diagnosing and treating VAP.

In this issue of CHEST (see page 1494), May et al6 describe a novel strategy for the rapid diagnosis of VAP, using exhaled breath condensate fluid (EBCF) obtained from heat-moisture exchangers to provide a substrate for testing with polymerase chain reaction (PCR) to identify bacterial DNA.6 These investigators showed in critically ill surgical patients that there was excellent concordance between pathogen identification using PCR of EBCF and pathogens isolated from BAL fluid. Additionally, they found that increasing DNA load among serial EBCF samples preceded the clinical suspicion of VAP.

The potential advantages of this type of diagnostic approach include noninvasive sampling of EBCF, ease of acquiring serial samples to potentially allow preemptive or targeted preventive treatments of early VAP or tracheobronchitis, and pathogen-specific characterization. The latter could help direct antibiotic therapy, limiting the unnecessary use of broad-spectrum antibiotics for pathogens that are not identified using this technique, thus promoting antibiotic stewardship principles. The main disadvantage of this type of PCR-directed diagnostic approach is that it does not provide true antimicrobial susceptibility testing of the causative pathogens. The latter would be important, for example, if a species of Klebsiella pneumoniae were identified in an ICU where sporadic cases of extended-spectrum β-lactamase-producing and carbapenemase-producing strains of K pneumoniae have been isolated.

Conventional microbiologic procedures typically require several days for isolation, identification, and antimicrobial susceptibility testing of isolated bacteria from clinical samples, including blood, respiratory tract, urine, and sterile-site specimens. Due to the time-consuming nature of these procedures, identification of resistant bacteria is often delayed, resulting in the administration of inappropriate initial antibiotic therapy. Delayed administration of appropriate antibiotic therapy is associated with the greatest adverse impact on the clinical outcomes of our sickest patients in the ICU setting.7 Therefore, rapid diagnostic methods must have the capability of influencing early antibiotic decision-making to allow for more appropriate therapy of antibiotic-resistant bacterial infection, as well as minimization of unnecessary use of broad-spectrum agents.

Recently, several molecular diagnostic platforms for the rapid diagnosis of bacterial species and their accompanying resistance genes have been introduced and evaluated. These include the following: the LightCycler SeptiFast Test (Roche Molecular Systems Inc); peptide nucleic-acid fluorescence in situ hybridization (AdvanDx Inc); matrix-assisted, laser desorption-ionization, time-of-flight mass spectrometry (MALDI-TOF MS) (VITEK MS; bioMérieux, Inc); and the DNA-based microarray platforms Prove-it sepsis assay (Mobidiag Ltd) and the Verigene gram-positive blood culture assay (Nanosphere Inc).8 Additionally, automated microscopy methods such as the identification/antibiotic susceptibility testing system (Accelerate Diagnostics Inc) are in development using both genomic and phenotypic technologies to provide pathogen identification and antimicrobial susceptibilities in a rapid manner.9

Huang et al10 from the University of Michigan performed a quasi-experimental study to analyze the impact of MALDI-TOF MS in conjunction with an antimicrobial stewardship team intervention in patients with bloodstream infections. The antimicrobial stewardship team provided antibiotic recommendations after receiving real-time notification following blood-culture Gram stain, organism identification, and antimicrobial susceptibilities using conventional microbiology methods in the before period and MALDI-TOF MS in the after period. Use of MALDI-TOF MS significantly decreased time to organism identification and improved time to effective antibiotic therapy, as well as optimal, directed antibiotic therapy. Mortality rate, length of ICU stay, and recurrent bacteremia incidence were also lower during the intervention period. Similarly, the PCR-based GeneXpert MRSA/SA diagnostic platform (Cepheid) was studied at the Veterans Affairs Medical Center in Houston, Texas, demonstrating that for methicillin-susceptible Staphylococcus aureus bacteremia, the mean time to initiation of appropriate therapy was reduced from 49.8 h to 5.2 h, and the duration of unnecessary methicillin-resistant S aureus drug therapy was reduced by 61 h per patient.11

It is clear that we are entering a new era in the management and treatment of serious infections such as VAP. Within the next 3 to 5 years, new antibiotics directed against multidrug-resistant gram-negative bacteria will become available, including carbavance, ceftolozane-tazobactam, ceftazidime-avibactam, plazomicin, eravacycline, relebactam, brilacidin, BAL30072, aztreonam-avibactam, carbapenems with ME 1071, and S-649266, a novel siderophore cephalosporin. These agents will provide enhanced activity against β-lactamase producers, carbapenem-resistant bacteria, and, in some, cases even metallo-β-lactamase-producing bacteria. The challenge to ICU clinicians is how to most effectively use these agents, once they become available, to maximize patient benefits while minimizing the emergence of resistance. The use of rapid diagnostics seems to hold the key for achieving this important balance. There is an urgent need for clinical studies aimed at understanding how to best integrate the use of these new antibiotics with the emerging rapid diagnostic technologies in a way that is cost effective and sustainable for the long run.12

Acknowledgments

Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

Kollef MH, Hamilton CW, Ernst FR. Economic impact of ventilator-associated pneumonia in a large matched cohort. Infect Control Hosp Epidemiol. 2012;33(3):250-256. [CrossRef] [PubMed]
 
Kollef KE, Schramm GE, Wills AR, Reichley RM, Micek ST, Kollef MH. Predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia attributed to potentially antibiotic-resistant gram-negative bacteria. Chest. 2008;134(2):281-287. [CrossRef] [PubMed]
 
Skrupky LP, McConnell K, Dallas J, Kollef MH. A comparison of ventilator-associated pneumonia rates as identified according to the National Healthcare Safety Network and American College of Chest Physicians criteria. Crit Care Med. 2012;40(1):281-284. [CrossRef] [PubMed]
 
Kollef MH, Chastre J, Fagon JY, et al. Global prospective epidemiologic and surveillance study of ventilator-associated pneumonia due toPseudomonas aeruginosa. Crit Care Med. 2014;42(10):2178-2187. [CrossRef] [PubMed]
 
Magill SS, Klompas M, Balk R, et al. Developing a new, national approach to surveillance for ventilator-associated events. Crit Care Med. 2013;41(11):2467-2475. [CrossRef] [PubMed]
 
May AK, Brady JS, Romano-Keeler J, et al. A pilot study of noninvasive assessment of the lung microbiota as a potential tool for the early diagnosis of ventilator-associated pneumonia. Chest. 2015;147(6):1494-1502.
 
Ferrer R, Martin-Loeches I, Phillips G, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med. 2014;42(8):1749-1755. [CrossRef] [PubMed]
 
Tojo M, Fujita T, Ainoda Y, et al. Evaluation of an automated rapid diagnostic assay for detection of Gram-negative bacteria and their drug-resistance genes in positive blood cultures. PLoS One. 2014;9(4):e94064. [CrossRef] [PubMed]
 
Burnham CA, Frobel RA, Herrera ML, Wickes BL. Rapid ertapenem susceptibility testing andKlebsiella pneumoniaecarbapenemase phenotype detection inKlebsiella pneumoniaeisolates by use of automated microscopy of immobilized live bacterial cells. J Clin Microbiol. 2014;52(3):982-986. [CrossRef] [PubMed]
 
Huang AM, Newton D, Kunapuli A, et al. Impact of rapid organism identification via matrix-assisted laser desorption/ionization time-of-flight combined with antimicrobial stewardship team intervention in adult patients with bacteremia and candidemia. Clin Infect Dis. 2013;57(9):1237-1245. [CrossRef] [PubMed]
 
Parta M, Goebel M, Thomas J, Matloobi M, Stager C, Musher DM. Impact of an assay that enables rapid determination ofStaphylococcusspecies and their drug susceptibility on the treatment of patients with positive blood culture results. Infect Control Hosp Epidemiol. 2010;31(10):1043-1048. [CrossRef] [PubMed]
 
Kollef MH, Micek ST. Rational use of antibiotics in the ICU: balancing stewardship and clinical outcomes. JAMA. 2014;312(14):1403-1404. [CrossRef] [PubMed]
 

Figures

Tables

References

Kollef MH, Hamilton CW, Ernst FR. Economic impact of ventilator-associated pneumonia in a large matched cohort. Infect Control Hosp Epidemiol. 2012;33(3):250-256. [CrossRef] [PubMed]
 
Kollef KE, Schramm GE, Wills AR, Reichley RM, Micek ST, Kollef MH. Predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia attributed to potentially antibiotic-resistant gram-negative bacteria. Chest. 2008;134(2):281-287. [CrossRef] [PubMed]
 
Skrupky LP, McConnell K, Dallas J, Kollef MH. A comparison of ventilator-associated pneumonia rates as identified according to the National Healthcare Safety Network and American College of Chest Physicians criteria. Crit Care Med. 2012;40(1):281-284. [CrossRef] [PubMed]
 
Kollef MH, Chastre J, Fagon JY, et al. Global prospective epidemiologic and surveillance study of ventilator-associated pneumonia due toPseudomonas aeruginosa. Crit Care Med. 2014;42(10):2178-2187. [CrossRef] [PubMed]
 
Magill SS, Klompas M, Balk R, et al. Developing a new, national approach to surveillance for ventilator-associated events. Crit Care Med. 2013;41(11):2467-2475. [CrossRef] [PubMed]
 
May AK, Brady JS, Romano-Keeler J, et al. A pilot study of noninvasive assessment of the lung microbiota as a potential tool for the early diagnosis of ventilator-associated pneumonia. Chest. 2015;147(6):1494-1502.
 
Ferrer R, Martin-Loeches I, Phillips G, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med. 2014;42(8):1749-1755. [CrossRef] [PubMed]
 
Tojo M, Fujita T, Ainoda Y, et al. Evaluation of an automated rapid diagnostic assay for detection of Gram-negative bacteria and their drug-resistance genes in positive blood cultures. PLoS One. 2014;9(4):e94064. [CrossRef] [PubMed]
 
Burnham CA, Frobel RA, Herrera ML, Wickes BL. Rapid ertapenem susceptibility testing andKlebsiella pneumoniaecarbapenemase phenotype detection inKlebsiella pneumoniaeisolates by use of automated microscopy of immobilized live bacterial cells. J Clin Microbiol. 2014;52(3):982-986. [CrossRef] [PubMed]
 
Huang AM, Newton D, Kunapuli A, et al. Impact of rapid organism identification via matrix-assisted laser desorption/ionization time-of-flight combined with antimicrobial stewardship team intervention in adult patients with bacteremia and candidemia. Clin Infect Dis. 2013;57(9):1237-1245. [CrossRef] [PubMed]
 
Parta M, Goebel M, Thomas J, Matloobi M, Stager C, Musher DM. Impact of an assay that enables rapid determination ofStaphylococcusspecies and their drug susceptibility on the treatment of patients with positive blood culture results. Infect Control Hosp Epidemiol. 2010;31(10):1043-1048. [CrossRef] [PubMed]
 
Kollef MH, Micek ST. Rational use of antibiotics in the ICU: balancing stewardship and clinical outcomes. JAMA. 2014;312(14):1403-1404. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543