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Infectious Diseases and Therapy
Published in: Infectious Diseases and Therapy 1/2018

Open Access 01-03-2018 | Original Research

Antimicrobial Stewardship Opportunities in Critically Ill Patients with Gram-Negative Lower Respiratory Tract Infections: A Multicenter Cross-Sectional Analysis

Authors: Kimberly C. Claeys, Evan J. Zasowski, Trang D. Trinh, Abdalhamid M. Lagnf, Susan L. Davis, Michael J. Rybak

Published in: Infectious Diseases and Therapy | Issue 1/2018

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Abstract

Introduction

Lower respiratory tract infections (LRTIs) are a major cause of morbidity and death. Because of changes in how LRTIs are defined coupled with the increasing prevalence of drug resistance, there is a gap in knowledge regarding the current burden of antimicrobial use for Centers for Disease Control and Prevention (CDC)-defined LRTIs. We describe the infection characteristics, antibiotic consumption, and clinical and economic outcomes of patients with Gram-negative (GN) LRTIs treated in intensive care units (ICUs).

Methods

This was a retrospective, observational, cross-sectional study of adult patients treated in ICUs at two large academic medical centers in metropolitan Detroit, Michigan, from October 2013 to October 2015. To meet the inclusion criteria, patients must have had CDC-defined LRTI caused by a GN pathogen during ICU stay. Microbiological assessment of available Pseudomonas aeruginosa isolates included minimum inhibitory concentrations for key antimicrobial agents.

Results

Four hundred and seventy-two patients, primarily from the community (346, 73.3%), were treated in medical ICUs (272, 57.6%). Clinically defined pneumonia was common (264, 55.9%). Six hundred and nineteen GN organisms were identified from index respiratory cultures: P. aeruginosa was common (224, 36.2%), with 21.6% of these isolates being multidrug resistant. Cefepime (213, 45.1%) and piperacillin/tazobactam (174, 36.8%) were the most frequent empiric GN therapies. Empiric GN therapy was inappropriate in 44.6% of cases. Lack of in vitro susceptibility (80.1%) was the most common reason for inappropriateness. Patients with inappropriate empiric GN therapy had longer overall stay, which translated to a median total cost of care of $79,800 (interquartile range $48,775 to $129,600) versus $68,000 (interquartile range $38,400 to $116,175), p = 0.013. Clinical failure (31.5% vs 30.0%, p = 0.912) and in-hospital all-cause mortality (26.4% vs 25.9%, p = 0.814) were not different.

Conclusion

Drug-resistant pathogens were frequently found and empiric GN therapy was inappropriate in nearly 50% of cases. Inappropriate therapy led to increased lengths of stay and was associated with higher costs of care.
Literature
1.
Hall MJ, DeFrances CJ, Williams SN, et al. National Hospital Discharge Survey: 2007 summary. Natl Health Stat Rep. 2010;29:24.
2.
Craven DE, Kunches LM, Kilinsky V, et al. Risk factors for pneumonia and fatality in patients receiving continuous mechanical ventilation. Am Rev Respir Dis. 1986;133(5):792–6.PubMed
3.
Craven DE, Driks MR. Nosocomial pneumonia in the intubated patient. Semin Respir Infect. 1987;2(1):20–33.PubMed
4.
Jimenez P, Torres A, Rodriguez-Roisin R, et al. Incidence and etiology of pneumonia acquired during mechanical ventilation. Crit Care Med. 1989;17(9):882–5.CrossRefPubMed
5.
Rello J, Quintana E, Ausina V, et al. Incidence, etiology, and outcome of nosocomial pneumonia in mechanically ventilated patients. Chest. 1991;100(2):439–44.CrossRefPubMed
6.
Craven DE, Steger KA. Nosocomial pneumonia in mechanically ventilated adult patients: epidemiology and prevention in 1996. Semin Respir Infect. 1996;11(1):32–53.PubMed
7.
George DL. Epidemiology of nosocomial ventilator-associated pneumonia. Infect Control Hosp Epidemiol. 1993;14(3):163–9.CrossRefPubMed
8.
Safdar N, Dezfulian C, Collard HR, et al. Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med. 2005;33(10):2184–93.CrossRefPubMed
9.
Hugonnet S, Eggimann P, Borst F, et al. Impact of ventilator-associated pneumonia on resource utilization and patient outcome infection control and hospital epidemiology. Infect Control Hosp Epidemiol. 2004;25(12):1090–6.CrossRefPubMed
10.
Klompas M. Complications of mechanical ventilation — the CDC’s new surveillance paradigm. N Engl J Med. 2013;368(16):1472–5.CrossRefPubMed
11.
Dudeck MA, Horan TC, Peterson KD, et al. National Healthcare Safety Network (NHSN) report, data summary for 2010, device-associated module. Am J Infect Control. 2011;39(10):798–816.CrossRefPubMed
12.
Hussein K, Sprecher H, Mashiach T, et al. Carbapenem resistance among Klebsiella pneumoniae isolates: risk factors, molecular characteristics, and susceptibility patterns. Infect Control Hosp Epidemiol. 2009;30(7):666–71.CrossRefPubMed
13.
Won SY, Munoz-Price LS, Lolans K, et al. Emergence and rapid regional spread of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. Clin Infect Dis. 2011;53(6):532–40.CrossRefPubMed
14.
Patel N, Harrington S, Dihmess A, et al. Clinical epidemiology of carbapenem-intermediate or -resistant Enterobacteriaceae. J Antimicrob Chemother. 2011;66(7):1600–8.CrossRefPubMed
15.
Sader HS, et al. Pseudomonas aeruginosa Antimicrobial Susceptibility Results from Four Years (2012 to 2015) of the International Network for Optimal Resistance Monitoring Program in the United States. Antimicrob Agents Chemother. 2016;60(8):4743–9.CrossRef
16.
Chia JH, Su LH, Lee MH, et al. Development of high-level carbapenem resistance in Klebsiella pneumoniae among patients with prolonged hospitalization and carbapenem exposure. Microbial Drug Resist. 2010;16(4):317–25.CrossRef
17.
18.
Fraser A, Paul M, Almanasreh N, et al. Benefit of appropriate empirical antibiotic treatment: thirty-day mortality and duration of hospital stay. Am J Med. 2006;119(11):970–6.CrossRefPubMed
19.
Kollef MH, Sherman G, Ward S, et al. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest. 1999;115(2):462–74.CrossRefPubMed
20.
Alvarez-Lerma F, ICU-Acquired Pneumonia Study Group. Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit. Intensive Care Med. 1996;22(5):387–94.CrossRefPubMed
21.
22.
Karvouniaris M, Makris D, Manoulakas E, et al. Ventilator-associated tracheobronchitis increases the length of intensive care unit stay. Infect Control Hosp Epidemiol. 2013;34(8):800–8.CrossRefPubMed
23.
Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18(3):268–81.CrossRefPubMed
24.
Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; twenty-third informational supplement. CLSI document M100–S23. Wayne, (PA): Clinical and Laboratory Standards Institute; 2013.
25.
26.
American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171(4):388–416.CrossRef
27.
Boucher HW, Talbot GH, Bradley JS, et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis. 2009;48(1):1–12.CrossRefPubMed
28.
29.
Wyrwich KW, Yu H, Sato R, et al. Community-acquired pneumonia: symptoms and burden of illness at diagnosis among US adults aged 50 years and older. Patient. 2013;6(2):125–34.CrossRefPubMed
30.
Kollef MH, Hamilton CW, Ernst FR. Economic impact of ventilator-associated pneumonia in a large matched cohort. Infect Control Hosp Epidemiol. 2012;33(3):250–6.CrossRefPubMed
31.
Restrepo MI, Anzueto A, Arroliga AC, et al. Economic burden of ventilator-associated pneumonia based on total resource utilization. Infect Control Hosp Epidemiol. 2010;31(5):509–15.CrossRefPubMed
32.
Sader HS, Farrell DJ, Flamm RK, et al. Antimicrobial susceptibility of Gram-negative organisms isolated from patients hospitalised with pneumonia in US and European hospitals: results from the SENTRY Antimicrobial Surveillance Program, 2009–2012. Int J Antimicrob Agents. 2014;43(4):328–34.CrossRefPubMed
33.
Tato M, García-Castillo M, Bofarull AM, et al. In vitro activity of ceftolozane/tazobactam against clinical isolates of Pseudomonas aeruginosa and Enterobacteriaceae recovered in Spanish medical centres: results of the CENIT study. Int J Antimicrob Agents. 2015;46(5):502–10.CrossRefPubMed
34.
Farrell DJ, Sader HS, Flamm RK, et al. Ceftolozane/tazobactam activity tested against Gram-negative bacterial isolates from hospitalised patients with pneumonia in US and European medical centres (2012). Int J Antimicrob Agents. 2014;43(6):533–9.CrossRefPubMed
35.
Martin-Loeches I, Torres A, Rinaudo M, et al. Resistance patterns and outcomes in intensive care unit (ICU)-acquired pneumonia. Validation of European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC) classification of multidrug resistant organisms. J Infect. 2015;70(3):213–22.CrossRefPubMed
36.
Adrie C, Garrouste-Orgeas M, Ibn Essaied W, et al. Attributable mortality of ICU-acquired bloodstream infections: impact of the source, causative micro-organism, resistance profile and antimicrobial therapy. J Infect. 2017;74(2):131–41.CrossRefPubMed
37.
Nseir S, Martin-Loeches I, Makris D, et al. Impact of appropriate antimicrobial treatment on transition from ventilator-associated tracheobronchitis to ventilator-associated pneumonia. Crit Care. 2014;18(3):R129.CrossRefPubMedPubMedCentral
38.
Chin T, Kushner B, Dersch-Mills D, et al. Antibiotic utilization patterns in patients with ventilator-associated pneumonia: a Canadian context. Can J Infect Dis Med Microbiol 2006;2006:3702625.
39.
Cheng WL, Hsueh PR, Lee CC, et al. Bacteremic pneumonia caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: appropriateness of empirical treatment matters. J Microbiol Immunol Infect. 2016;49(2):208–15.CrossRefPubMed
40.
Park SY, Park HJ, Moon SM, et al. Impact of adequate empirical combination therapy on mortality from bacteremic Pseudomonas aeruginosa pneumonia. BMC Infect Dis. 2012;12:308.CrossRefPubMedPubMedCentral
41.
Joung MK, Kwon KT, Kang CI, et al. Impact of inappropriate antimicrobial therapy on outcome in patients with hospital-acquired pneumonia caused by Acinetobacter baumannii. J Infect. 2010;61(3):212–8.CrossRefPubMed
42.
Stevens V, Dumyati G, Fine LS, et al. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis. 2011;53(1):42–8.CrossRefPubMed
43.
44.
Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003;290(19):2588–98.CrossRefPubMed
45.
Pugh R, Grant C, Cooke RP, et al. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev. 2015;24(8):CD007577.
46.
Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61–111.CrossRefPubMedPubMedCentral
47.
Klompas M, Berra L. Should ventilator-associated events become a quality indicator for ICUs? Respir Care. 2016;61(6):723–36.CrossRefPubMed
48.
Chang HC, Chen CM, Kung SC, et al. Differences between novel and conventional surveillance paradigms of ventilator-associated pneumonia. Am J Infect Control. 2015;43(2):133–6.CrossRefPubMed
49.
Chalmers JD, Rother C, Salih W, et al. Healthcare-associated pneumonia does not accurately identify potentially resistant pathogens: a systematic review and meta-analysis. Clin Infect Dis. 2014;58(3):330–9.CrossRefPubMed
50.
Kalil AC, Metersky ML, Klompas M, et al. Executive summary: management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):575–82.CrossRefPubMedPubMedCentral
Metadata
Title
Antimicrobial Stewardship Opportunities in Critically Ill Patients with Gram-Negative Lower Respiratory Tract Infections: A Multicenter Cross-Sectional Analysis
Authors
Kimberly C. Claeys
Evan J. Zasowski
Trang D. Trinh
Abdalhamid M. Lagnf
Susan L. Davis
Michael J. Rybak
Publication date
01-03-2018
Publisher
Springer Healthcare
Published in
Infectious Diseases and Therapy / Issue 1/2018
Print ISSN: 2193-8229
Electronic ISSN: 2193-6382
DOI
https://doi.org/10.1007/s40121-017-0179-5

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