Emerging Resistance of Gram Negative Pathogens in Community-Acquired Pneumonia

Francesco Amati; Marcos I. Restrepo

doi:10.1055/s-0040-1709137

Seminars in Respiratory and Critical Care Medicine, Inhaltsverzeichnis

Semin Respir Crit Care Med 2020; 41(04): 480-495
DOI: 10.1055/s-0040-1709137

Review Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Emerging Resistance of Gram Negative Pathogens in Community-Acquired Pneumonia

Francesco Amati

¹Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

²Department of Internal Medicine, Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

³Division of Pulmonary Diseases and Critical Care Medicine, University of Texas Health, San Antonio, San Antonio, Texas

,

Marcos I. Restrepo

³Division of Pulmonary Diseases and Critical Care Medicine, University of Texas Health, San Antonio, San Antonio, Texas

⁴Division of Pulmonary Diseases and Critical Care Medicine, South Texas Veterans Health Care System, San Antonio, Texas

› Institutsangaben

Abstract

In recent decades, there has been a growing interest about the role of gram negative bacteria in community-acquired pneumonia (CAP), especially Pseudomonas aeruginosa, Enterobacteriaceae, and Acinetobacter baumannii. The prevalence of these pathogens differs largely according to the local ecology and the geographical location. Identifying gram negative bacteria, and in particular resistant gram negative bacteria, is of paramount importance in patients with CAP because these pathogens are associated with higher clinical severity and unfavorable outcomes. The use of individualized risk factors to predict each pathogen is a helpful strategy that needs to be locally validated. However, it should be taken into account that most of the risk factors identified in the literature are heterogeneously defined or lack consistency. New diagnostic techniques, such as molecular testing, are promising methods for early detection of these gram negative pathogens. The increasing mechanisms of resistance to antibiotics of these pathogens have limited our therapeutic approach. This narrative review focuses on the epidemiology, risk factors, diagnosis, and therapeutic options for the most relevant gram negative bacteria that cause CAP.

Keywords

community-acquired pneumonia - Enterobacteriacea - Pseudomonas - Acinetobacter

Volltext

Referenzen

References
1 Metlay JP, Waterer GW, Long AC. , et al. Diagnosis and treatment of adults with community-acquired pneumonia. an official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med 2019; 200 (07) e45-e67
2 Eurich DT, Marrie TJ, Minhas-Sandhu JK, Majumdar SR. Ten-year mortality after community-acquired pneumonia. A prospective cohort. Am J Respir Crit Care Med 2015; 192 (05) 597-604
3 Aliberti S, Cilloniz C, Chalmers JD. , et al. Multidrug-resistant pathogens in hospitalised patients coming from the community with pneumonia: a European perspective. Thorax 2013; 68 (11) 997-999
4 Cillóniz C, Ewig S, Polverino E. , et al. Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax 2011; 66 (04) 340-346
5 Falcone M, Russo A, Giannella M. , et al. Individualizing risk of multidrug-resistant pathogens in community-onset pneumonia. PLoS One 2015; 10 (04) e0119528
6 El-Solh AA, Sikka P, Ramadan F, Davies J. Etiology of severe pneumonia in the very elderly. Am J Respir Crit Care Med 2001; 163 (3, Pt 1): 645-651
7 Arancibia F, Bauer TT, Ewig S. , et al. Community-acquired pneumonia due to gram-negative bacteria and Pseudomonas aeruginosa: incidence, risk, and prognosis. Arch Intern Med 2002; 162 (16) 1849-1858
8 Centers for Disease Control Prevention. Biggest Threats and Data: 2019 AR Threats Report. Available at: https://www.cdc.gov/drugresistance/biggest-threats.html . Accessed September 27 2019
9 Tzouvelekis LS, Markogiannakis A, Psichogiou M, Tassios PT, Daikos GL. Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. Clin Microbiol Rev 2012; 25 (04) 682-707
10 Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA. Carbapenems: past, present, and future. Antimicrob Agents Chemother 2011; 55 (11) 4943-4960
11 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 (01) 1-12
12 Livermore DM. Fourteen years in resistance. Int J Antimicrob Agents 2012; 39 (04) 283-294
13 Infectious Diseases Society of America. The 10 x '20 Initiative: pursuing a global commitment to develop 10 new antibacterial drugs by 2020. Clin Infect Dis 2010; 50 (08) 1081-1083
14 WHO publishes list of bacteria for which new antibiotics are urgently needed. Available at: https://www.who.int/news-room/detail/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed . Accessed September 27 2019
15 Kollef MH, Shorr A, Tabak YP, Gupta V, Liu LZ, Johannes RS. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest 2005; 128 (06) 3854-3862
16 Aliberti S, Di Pasquale M, Zanaboni AM. , et al. Stratifying risk factors for multidrug-resistant pathogens in hospitalized patients coming from the community with pneumonia. Clin Infect Dis 2012; 54 (04) 470-478
17 Shindo Y, Ito R, Kobayashi D. , et al. Risk factors for drug-resistant pathogens in community-acquired and healthcare-associated pneumonia. Am J Respir Crit Care Med 2013; 188 (08) 985-995
18 Micek ST, Kollef KE, Reichley RM, Roubinian N, Kollef MH. Health care-associated pneumonia and community-acquired pneumonia: a single-center experience. Antimicrob Agents Chemother 2007; 51 (10) 3568-3573
19 Prina E, Ranzani OT, Polverino E. , et al. Risk factors associated with potentially antibiotic-resistant pathogens in community-acquired pneumonia. Ann Am Thorac Soc 2015; 12 (02) 153-160
20 von Baum H, Welte T, Marre R, Suttorp N, Ewig S. ; CAPNETZ study group. Community-acquired pneumonia through Enterobacteriaceae and Pseudomonas aeruginosa: diagnosis, incidence and predictors. Eur Respir J 2010; 35 (03) 598-605
21 Restrepo MI, Babu BL, Reyes LF. , et al; GLIMP. Burden and risk factors for Pseudomonas aeruginosa community-acquired pneumonia: a multinational point prevalence study of hospitalised patients. Eur Respir J 2018; 52 (02) 1701190
22 Villafuerte D, Aliberti S, Soni NJ. , et al; GLIMP Investigators. Prevalence and risk factors for Enterobacteriaceae in patients hospitalized with community-acquired pneumonia. Respirology 2019; (e-pub ahead of print)
23 Kang C-I, Song J-H, Oh WS, Ko KS, Chung DR, Peck KR. ; Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study Group. Clinical outcomes and risk factors of community-acquired pneumonia caused by gram-negative bacilli. Eur J Clin Microbiol Infect Dis 2008; 27 (08) 657-661
24 Falguera M, Carratalà J, Ruiz-Gonzalez A. , et al. Risk factors and outcome of community-acquired pneumonia due to gram-negative bacilli. Respirology 2009; 14 (01) 105-111
25 Chalmers JD, Taylor JK, Singanayagam A. , et al. Epidemiology, antibiotic therapy, and clinical outcomes in health care-associated pneumonia: a UK cohort study. Clin Infect Dis 2011; 53 (02) 107-113
26 Wu C-L, Ku S-C, Yang K-Y. , et al. Antimicrobial drug-resistant microbes associated with hospitalized community-acquired and healthcare-associated pneumonia: a multi-center study in Taiwan. J Formos Med Assoc 2013; 112 (01) 31-40
27 Charles PG, Whitby M, Fuller AJ. , et al; Australian CAP Study Collaboration. The etiology of community-acquired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy. Clin Infect Dis 2008; 46 (10) 1513-1521
28 Lupisan S, Suzuki A, Macalalad N. , et al. Etiology and epidemiology of community-acquired pneumonia in adults requiring hospital admission: a prospective study in rural Central Philippines. Int J Infect Dis 2019; 80: 46-53
29 Liu Y, Chen M, Zhao T. , et al. Causative agent distribution and antibiotic therapy assessment among adult patients with community acquired pneumonia in Chinese urban population. BMC Infect Dis 2009; 9: 31
30 Shorr AF, Zilberberg MD, Reichley R. , et al. Validation of a clinical score for assessing the risk of resistant pathogens in patients with pneumonia presenting to the emergency department. Clin Infect Dis 2012; 54 (02) 193-198
31 Maruyama T, Fujisawa T, Ishida T. , et al. A therapeutic strategy for all pneumonia patients: a 3-year prospective multicenter- cohort study using risk factors for multidrug resistant pathogens to select initial empiric therapy. Clin Infect Dis 2019; 68 (07) 1080-1088
32 Grenier C, Pépin J, Nault V. , et al. Impact of guideline-consistent therapy on outcome of patients with healthcare-associated and community-acquired pneumonia. J Antimicrob Chemother 2011; 66 (07) 1617-1624
33 Inghammar M, Borand L, Goyet S. , et al. Community-acquired pneumonia and gram-negative bacilli in Cambodia-incidence, risk factors and clinical characteristics. Trans R Soc Trop Med Hyg 2018; 112 (02) 57-63
34 Gross AE, Van Schooneveld TC, Olsen KM. , et al. Epidemiology and predictors of multidrug-resistant community-acquired and health care-associated pneumonia. Antimicrob Agents Chemother 2014; 58 (09) 5262-5268
35 Ishida T, Ito A, Washio Y. , et al. Risk factors for drug-resistant pathogens in immunocompetent patients with pneumonia: Evaluation of PES pathogens. J Infect Chemother 2017; 23 (01) 23-28
36 Bartlett JG. Diagnostic tests for agents of community-acquired pneumonia. Clin Infect Dis 2011; 52 (Suppl. 04) S296-S304
37 Restrepo MI, Mortensen EM, Velez JA, Frei C, Anzueto A. A comparative study of community-acquired pneumonia patients admitted to the ward and the ICU. Chest 2008; 133 (03) 610-617
38 Moran GJ, Krishnadasan A, Gorwitz RJ. , et al; EMERGEncy ID NET Study Group. Prevalence of methicillin-resistant staphylococcus aureus as an etiology of community-acquired pneumonia. Clin Infect Dis 2012; 54 (08) 1126-1133
39 Gadsby NJ, Russell CD, McHugh MP. , et al. Comprehensive molecular testing for respiratory pathogens in community-acquired pneumonia. Clin Infect Dis 2016; 62 (07) 817-823
40 Jain S, Self WH, Wunderink RG. , et al; CDC EPIC Study Team. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med 2015; 373 (05) 415-427
41 Johansson N, Kalin M, Tiveljung-Lindell A, Giske CG, Hedlund J. Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods. Clin Infect Dis 2010; 50 (02) 202-209
42 Bjarnason A, Westin J, Lindh M. , et al. Incidence, etiology, and outcomes of community-acquired pneumonia: a population-based study. Open Forum Infect Dis 2018; 5 (02) ofy010
43 Fekety Jr FR, Caldwell J, Gump D. , et al. Bacteria, viruses, and mycoplasmas in acute pneumonia in adults. Am Rev Respir Dis 1971; 104 (04) 499-507
44 Fang GD, Fine M, Orloff J. , et al. New and emerging etiologies for community-acquired pneumonia with implications for therapy. A prospective multicenter study of 359 cases. Medicine (Baltimore) 1990; 69 (05) 307-316
45 Musher DM, Roig IL, Cazares G, Stager CE, Logan N, Safar H. Can an etiologic agent be identified in adults who are hospitalized for community-acquired pneumonia: results of a one-year study. J Infect 2013; 67 (01) 11-18
46 Moberley S, Holden J, Tatham DP, Andrews RM. Vaccines for preventing pneumococcal infection in adults. Cochrane Database Syst Rev 2013; 1 (01) CD000422-CD000422
47 Griffin MR, Zhu Y, Moore MR, Whitney CG, Grijalva CGUS. U.S. hospitalizations for pneumonia after a decade of pneumococcal vaccination. N Engl J Med 2013; 369 (02) 155-163
48 Centers for Disease Control and Prevention (CDC). Current cigarette smoking among adults - United States, 2011. MMWR Morb Mortal Wkly Rep 2012; 61 (44) 889-894
49 Rozenbaum MH, Pechlivanoglou P, van der Werf TS, Lo-Ten-Foe JR, Postma MJ, Hak E. The role of Streptococcus pneumoniae in community-acquired pneumonia among adults in Europe: a meta-analysis. Eur J Clin Microbiol Infect Dis 2013; 32 (03) 305-316
50 Paganin F, Lilienthal F, Bourdin A. , et al. Severe community-acquired pneumonia: assessment of microbial aetiology as mortality factor. Eur Respir J 2004; 24 (05) 779-785
51 Kawai S, Ochi M, Nakagawa T, Goto H. Antimicrobial therapy in community-acquired pneumonia among emergency patients in a university hospital in Japan. J Infect Chemother 2004; 10 (06) 352-358
52 Polverino E, Cilloniz C, Menendez R. , et al. Microbiology and outcomes of community acquired pneumonia in non cystic-fibrosis bronchiectasis patients. J Infect 2015; 71 (01) 28-36
53 Rello J, Rodriguez A, Torres A. , et al. Implications of COPD in patients admitted to the intensive care unit by community-acquired pneumonia. Eur Respir J 2006; 27 (06) 1210-1216
54 Ewig S, Birkner N, Strauss R. , et al. New perspectives on community-acquired pneumonia in 388 406 patients. Results from a nationwide mandatory performance measurement programme in healthcare quality. Thorax 2009; 64 (12) 1062-1069
55 Cillóniz C, Polverino E, Ewig S. , et al. Impact of age and comorbidity on cause and outcome in community-acquired pneumonia. Chest 2013; 144 (03) 999-1007
56 Friedman ND, Kaye KS, Stout JE. , et al. Health care--associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med 2002; 137 (10) 791-797
57 McDonald JR, Friedman ND, Stout JE, Sexton DJ, Kaye KS. Risk factors for ineffective therapy in patients with bloodstream infection. Arch Intern Med 2005; 165 (03) 308-313
58 Fleming-Dutra KE, Hersh AL, Shapiro DJ. , et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010–2011. JAMA 2016; 315 (17) 1864-1873
59 World Health Organization. WHO Global Strategy for Containment of Antimicrobial Resistance. Geneva, Switzerland: World Health Organization; 2001
60 Magiorakos A-P, 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 (03) 268-281
61 Ewig S, Torres A. Severe community-acquired pneumonia. Clin Chest Med 1999; 20 (03) 575-587
62 Dexter C, Murray GL, Paulsen IT, Peleg AY. Community-acquired Acinetobacter baumannii: clinical characteristics, epidemiology and pathogenesis. Expert Rev Anti Infect Ther 2015; 13 (05) 567-573
63 Chen C-T, Wang Y-C, Kuo S-C. , et al. Community-acquired bloodstream infections caused by Acinetobacter baumannii: a matched case-control study. J Microbiol Immunol Infect 2018; 51 (05) 629-635
64 Davis JS, McMillan M, Swaminathan A. , et al. A 16-year prospective study of community-onset bacteremic Acinetobacter pneumonia: low mortality with appropriate initial empirical antibiotic protocols. Chest 2014; 146 (04) 1038-1045
65 Ong CW, Lye DC, Khoo KL. , et al. Severe community-acquired Acinetobacter baumannii pneumonia: an emerging highly lethal infectious disease in the Asia-Pacific. Respirology 2009; 14 (08) 1200-1205
66 Wang JT, McDonald LC, Chang SC, Ho M. Community-acquired Acinetobacter baumannii bacteremia in adult patients in Taiwan. J Clin Microbiol 2002; 40 (04) 1526-1529
67 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 (04) 388-416
68 Chalmers JD, Rother C, Salih W, Ewig S. Healthcare-associated pneumonia does not accurately identify potentially resistant pathogens: a systematic review and meta-analysis. Clin Infect Dis 2014; 58 (03) 330-339
69 Tomczyk S, Jain S, Bramley AM. , et al. Antibiotic prescribing for adults hospitalized in the etiology of pneumonia in the community study. Open Forum Infect Dis 2017; 4 (02) ofx088
70 Attridge RT, Frei CR, Pugh MJ. , et al. Health care-associated pneumonia in the intensive care unit: guideline-concordant antibiotics and outcomes. J Crit Care 2016; 36: 265-271
71 Webb BJ, Sorensen J, Jephson A, Mecham I, Dean NC. Broad-spectrum antibiotic use and poor outcomes in community-onset pneumonia: a cohort study. Eur Respir J 2019; 54 (01) 190005
72 Shorr AF, Zilberberg MD, Micek ST, Kollef MH. Prediction of infection due to antibiotic-resistant bacteria by select risk factors for health care-associated pneumonia. Arch Intern Med 2008; 168 (20) 2205-2210
73 Park SC, Kim EY, Kang YA. , et al. Validation of a scoring tool to predict drug-resistant pathogens in hospitalised pneumonia patients. Int J Tuberc Lung Dis 2013; 17 (05) 704-709
74 Ma HM, Ip M, Woo J, Hui DS. Development and validation of a clinical risk score for predicting drug-resistant bacterial pneumonia in older Chinese patients. Respirology 2014; 19 (04) 549-555
75 Webb BJ, Dascomb K, Stenehjem E. , et al. Derivation and multicenter validation of the drug resistance in pneumonia clinical prediction score. Antimicrob Agents Chemother 2016; 60 (05) 2652-2663
76 Schreiber MP, Chan CM, Shorr AF. Resistant pathogens in nonnosocomial pneumonia and respiratory failure: is it time to refine the definition of health-care-associated pneumonia?. Chest 2010; 137 (06) 1283-1288
77 Aliberti S, Reyes LF, Faverio P. , et al; GLIMP investigators. Global initiative for meticillin-resistant Staphylococcus aureus pneumonia (GLIMP): an international, observational cohort study. Lancet Infect Dis 2016; 16 (12) 1364-1376
78 Shindo Y, Hasegawa Y. Regional differences in antibiotic-resistant pathogens in patients with pneumonia: Implications for clinicians. Respirology 2017; 22 (08) 1536-1546
79 Cillóniz C, Gabarrús A, Ferrer M. , et al. Community-acquired pneumonia due to multidrug- and non-multidrug-resistant Pseudomonas aeruginosa . Chest 2016; 150 (02) 415-425
80 Hatchette TF, Gupta R, Marrie TJ. Pseudomonas aeruginosa community-acquired pneumonia in previously healthy adults: case report and review of the literature. Clin Infect Dis 2000; 31 (06) 1349-1356
81 Patel P, Whittier S, Frank E. Person-to-person transmission of Pseudomonas pneumonia in the community: documentation by pulsed-field electrophoresis. South Med J 2002; 95 (06) 653-656
82 Mandell LA, Wunderink RG, Anzueto A. , et al; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 (Suppl. 02) S27-S72
83 Cole PJ. Inflammation: a two-edged sword--the model of bronchiectasis. Eur J Respir Dis Suppl 1986; 147: 6-15
84 Finch S, McDonnell MJ, Abo-Leyah H, Aliberti S, Chalmers JD. A comprehensive analysis of the impact of Pseudomonas aeruginosa colonization on prognosis in adult bronchiectasis. Ann Am Thorac Soc 2015; 12 (11) 1602-1611
85 Crousilles A, Maunders E, Bartlett S. , et al. Which microbial factors really are important in Pseudomonas aeruginosa infections?. Future Microbiol 2015; 10 (11) 1825-1836
86 Aydemir Y, Aydemir Ö, Kalem F. Relationship between the GOLD combined COPD assessment staging system and bacterial isolation. Int J Chron Obstruct Pulmon Dis 2014; 9: 1045-1051
87 Ko FW, Ip M, Chan PK, Ng SS, Chau SS, Hui DS. A one-year prospective study of infectious etiology in patients hospitalized with acute exacerbations of COPD and concomitant pneumonia. Respir Med 2008; 102 (08) 1109-1116
88 López-Palomo C, Martín-Zamorano M, Benítez E. , et al. Pneumonia in HIV-infected patients in the HAART era: incidence, risk, and impact of the pneumococcal vaccination. J Med Virol 2004; 72 (04) 517-524
89 Madeddu G, Porqueddu EM, Cambosu F. , et al. Bacterial community acquired pneumonia in HIV-infected inpatients in the highly active antiretroviral therapy era. Infection 2008; 36 (03) 231-236
90 Sibila O, Laserna E, Maselli DJ. , et al. Risk factors and antibiotic therapy in P. aeruginosa community-acquired pneumonia. Respirology 2015; 20 (04) 660-666
91 Kotsanas D, Wijesooriya WR, Korman TM. , et al. “Down the drain”: carbapenem-resistant bacteria in intensive care unit patients and handwashing sinks. Med J Aust 2013; 198 (05) 267-269
92 Lerner A, Adler A, Abu-Hanna J, Meitus I, Navon-Venezia S, Carmeli Y. Environmental contamination by carbapenem-resistant Enterobacteriaceae. J Clin Microbiol 2013; 51 (01) 177-181
93 Razazi K, Derde LPG, Verachten M, Legrand P, Lesprit P, Brun-Buisson C. Clinical impact and risk factors for colonization with extended-spectrum β-lactamase-producing bacteria in the intensive care unit. Intensive Care Med 2012; 38 (11) 1769-1778
94 Carbonne H, Le Dorze M, Bourrel AS. , et al. Relation between presence of extended-spectrum β-lactamase-producing Enterobacteriaceae in systematic rectal swabs and respiratory tract specimens in ICU patients. Ann Intensive Care 2017; 7 (01) 13
95 Detsis M, Karanika S, Mylonakis E. ICU acquisition rate, risk factors, and clinical significance of digestive tract colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae: a systematic review and meta-analysis. Crit Care Med 2017; 45 (04) 705-714
96 Ghafourian S, Sadeghifard N, Soheili S, Sekawi Z. Extended spectrum beta-lactamases: definition, classification and epidemiology. Curr Issues Mol Biol 2015; 17: 11-21
97 van Vught LA, Endeman H, Meijvis SC. , et al. The effect of age on the systemic inflammatory response in patients with community-acquired pneumonia. Clin Microbiol Infect 2014; 20 (11) 1183-1188
98 Bonnel AR, Bunchorntavakul C, Reddy KR. Immune dysfunction and infections in patients with cirrhosis. Clin Gastroenterol Hepatol 2011; 9 (09) 727-738
99 Huang X, Li G, Yi L, Li M, Wang J. [The epidemiology of multidrug-resistant bacteria colonization and analysis of its risk factors in intensive care unit] (in Chinese). Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2015; 27 (08) 667-671
100 Kaplan V, Angus DC, Griffin MF, Clermont G, Scott Watson R, Linde-Zwirble WT. Hospitalized community-acquired pneumonia in the elderly: age- and sex-related patterns of care and outcome in the United States. Am J Respir Crit Care Med 2002; 165 (06) 766-772
101 Sahuquillo-Arce JM, Menéndez R, Méndez R. , et al. Age-related risk factors for bacterial aetiology in community-acquired pneumonia. Respirology 2016; 21 (08) 1472-1479
102 Leung WS, Chu CM, Tsang KY, Lo FH, Lo KF, Ho PL. Fulminant community-acquired Acinetobacter baumannii pneumonia as a distinct clinical syndrome. Chest 2006; 129 (01) 102-109
103 Kamoshida G, Kikuchi-Ueda T, Nishida S, Tansho-Nagakawa S, Ubagai T, Ono Y. Pathogenic bacterium Acinetobacter baumannii inhibits the formation of neutrophil extracellular traps by suppressing neutrophil adhesion. Front Immunol 2018; 9: 178
104 Kim YA, Kim JJ, Won DJ, Lee K. Seasonal and temperature-associated increase in community-onset Acinetobacter baumannii complex colonization or infection. Ann Lab Med 2018; 38 (03) 266-270
105 Ghare S, Patil M, Hote P. , et al. Ethanol inhibits lipid raft-mediated TCR signaling and IL-2 expression: potential mechanism of alcohol-induced immune suppression. Alcohol Clin Exp Res 2011; 35 (08) 1435-1444
106 Janssen WJ. Alveolar macrophage dysfunction and chronic alcohol use. Time to think about zinc. Am J Respir Crit Care Med 2013; 188 (06) 635-636
107 Eugenin EA. Community-acquired pneumonia infections by Acinetobacter baumannii: how does alcohol impact the antimicrobial functions of macrophages?. Virulence 2013; 4 (06) 435-436
108 Anstey NM, Currie BJ, Hassell M, Palmer D, Dwyer B, Seifert H. Community-acquired bacteremic Acinetobacter pneumonia in tropical Australia is caused by diverse strains of Acinetobacter baumannii, with carriage in the throat in at-risk groups. J Clin Microbiol 2002; 40 (02) 685-686
109 Peleg AY, Weerarathna T, McCarthy JS, Davis TME. Common infections in diabetes: pathogenesis, management and relationship to glycaemic control. Diabetes Metab Res Rev 2007; 23 (01) 3-13
110 Sopori M. Effects of cigarette smoke on the immune system. Nat Rev Immunol 2002; 2 (05) 372-377
111 Carugati M, Aliberti S, Reyes LF. , et al. Microbiological testing of adults hospitalised with community-acquired pneumonia: an international study. ERJ Open Res 2018; 4 (04) 00096-02018
112 Falguera M, Trujillano J, Caro S. , et al; NAC-CALIDAD (Proyecto Integrado de Investigación de la Sociedad Española de Patología del Aparato Respiratorio sobre Infecciones Respiratorias de Vías Bajas) Study Group. A prediction rule for estimating the risk of bacteremia in patients with community-acquired pneumonia. Clin Infect Dis 2009; 49 (03) 409-416
113 Metersky ML, Ma A, Bratzler DW, Houck PM. Predicting bacteremia in patients with community-acquired pneumonia. Am J Respir Crit Care Med 2004; 169 (03) 342-347
114 van der Eerden MM, Vlaspolder F, de Graaff CS, Groot T, Jansen HM, Boersma WG. Value of intensive diagnostic microbiological investigation in low- and high-risk patients with community-acquired pneumonia. Eur J Clin Microbiol Infect Dis 2005; 24 (04) 241-249
115 Chalasani NP, Valdecanas MA, Gopal AK, McGowan Jr JE, Jurado RL. Clinical utility of blood cultures in adult patients with community-acquired pneumonia without defined underlying risks. Chest 1995; 108 (04) 932-936
116 Marrie TJ. Blood cultures in ambulatory patients who are discharged from emergency with community-acquired pneumonia. Can J Infect Dis 2004; 15 (01) 21-24
117 Cillóniz C, Ewig S, Polverino E. , et al. Community-acquired pneumonia in outpatients: aetiology and outcomes. Eur Respir J 2012; 40 (04) 931-938
118 Kennedy M, Bates DW, Wright SB, Ruiz R, Wolfe RE, Shapiro NI. Do emergency department blood cultures change practice in patients with pneumonia?. Ann Emerg Med 2005; 46 (05) 393-400
119 Benenson RS, Kepner AM, Pyle II DN, Cavanaugh S. Selective use of blood cultures in emergency department pneumonia patients. J Emerg Med 2007; 33 (01) 1-8
120 Cillóniz C, Gabarrús A, Almirall J. , et al. Bacteraemia in outpatients with community-acquired pneumonia. Eur Respir J 2016; 47 (02) 654-657
121 Bartlett JG, Mundy LM. Community-acquired pneumonia. N Engl J Med 1995; 333 (24) 1618-1624
122 Wong LK, Barry AL, Horgan SM. Comparison of six different criteria for judging the acceptability of sputum specimens. J Clin Microbiol 1982; 16 (04) 627-631
123 Miller JM, Binnicker MJ, Campbell S. , et al. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2018 update by the Infectious Diseases Society of America and the American Society for Microbiology. Clin Infect Dis 2018; 67 (06) e1-e94
124 Buchan BW. , et al. Clinical Evaluation and Potential Impact of a Semi-Quantitative Multiplex Molecular Assay for the Identification of Pathogenic Bacteria and Viruses in Lower Respiratory specimens. American Thoracic Society Conference, May 20th 2018, San Diego CA
125 Woodhead M, Blasi F, Ewig S. , et al; Joint Taskforce of the European Respiratory Society and European Society for Clinical Microbiology and Infectious Diseases. Guidelines for the management of adult lower respiratory tract infections--full version. Clin Microbiol Infect 2011; 17 (Suppl. 06) E1-E59
126 Lim WS, Baudouin SV, George RC. , et al; Pneumonia Guidelines Committee of the BTS Standards of Care Committee. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax 2009; 64 (Suppl. 03) iii1-iii55
127 Ruppé É, Woerther PL, Barbier F. Mechanisms of antimicrobial resistance in Gram-negative bacilli. Ann Intensive Care 2015; 5 (01) 61
128 Torres A, Cillóniz C, Ferrer M. , et al. Bacteraemia and antibiotic-resistant pathogens in community acquired pneumonia: risk and prognosis. Eur Respir J 2015; 45 (05) 1353-1363
129 Tamma PD, Girdwood SC, Gopaul R. , et al. The use of cefepime for treating AmpC β-lactamase-producing Enterobacteriaceae . Clin Infect Dis 2013; 57 (06) 781-788
130 Harris PNA, Tambyah PA, Lye DC. , et al; MERINO Trial Investigators and the Australasian Society for Infectious Disease Clinical Research Network (ASID-CRN). Effect of piperacillin-tazobactam vs meropenem on 30-day mortality for patients with E. coli or Klebsiella pneumoniae bloodstream infection and ceftriaxone resistance: a randomized clinical trial. JAMA 2018; 320 (10) 984-994
131 Jacoby GA. AmpC beta-lactamases. Clin Microbiol Rev 2009; 22 (01) 161-182
132 Cheng L, Nelson BC, Mehta M. , et al. Piperacillin/tazobactam versus other antibacterial agents for treatment of bloodstream infections due to AmpC -lactamase-producing Enterobacteriaceae . Antimicrob Agents Chemother 2017; 61 (06) e00276-e17
133 Alekshun MN, Levy SB. Molecular mechanisms of antibacterial multidrug resistance. Cell 2007; 128 (06) 1037-1050
134 van Duin D, Kaye KS, Neuner EA, Bonomo RA. Carbapenem-resistant Enterobacteriaceae: a review of treatment and outcomes. Diagn Microbiol Infect Dis 2013; 75 (02) 115-120
135 Gutiérrez-Gutiérrez B, Salamanca E, de Cueto M. , et al; REIPI/ESGBIS/INCREMENT Investigators. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study. Lancet Infect Dis 2017; 17 (07) 726-734
136 Paul M, Daikos GL, Durante-Mangoni E. , et al. Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant gram-negative bacteria: an open-label, randomised controlled trial. Lancet Infect Dis 2018; 18 (04) 391-400
137 Livermore DM. ; British Society for Antimicrobial Chemotherapy Working Party on The Urgent Need: Regenerating Antibacterial Drug Discovery and Development. Discovery research: the scientific challenge of finding new antibiotics. J Antimicrob Chemother 2011; 66 (09) 1941-1944
138 O'Neill J. (chair). Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. 2014 . Available at: https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf . Accessed February 24, 2020
139 Kostyanev T, Bonten MJM, O'Brien S. , et al. The Innovative Medicines Initiative's New Drugs for Bad Bugs programme: European public-private partnerships for the development of new strategies to tackle antibiotic resistance. J Antimicrob Chemother 2016; 71 (02) 290-295
140 Awad SS, Rodriguez AH, Chuang YC. , et al. A phase 3 randomized double-blind comparison of ceftobiprole medocaril versus ceftazidime plus linezolid for the treatment of hospital-acquired pneumonia. Clin Infect Dis 2014; 59 (01) 51-61
141 Nicholson SC, Welte T, File Jr TM. , et al. A randomised, double-blind trial comparing ceftobiprole medocaril with ceftriaxone with or without linezolid for the treatment of patients with community-acquired pneumonia requiring hospitalisation. Int J Antimicrob Agents 2012; 39 (03) 240-246
142 ClinicalTrials.gov. Clinical Study of S-649266 for the Treatment of Nosocomial Pneumonia Caused by Gram-negative Pathogens (APEKS-NP). Available at: https://clinicaltrials.gov/ct2/show/NCT03032380 . Accessed February 24, 2020; ClinicalTrials.gov Identifier: NCT03032380
143 Torres A, Zhong N, Pachl J. , et al. Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial. Lancet Infect Dis 2018; 18 (03) 285-295
144 ClinicalTrials.gov. Safety and Efficacy Study of Ceftolozane/Tazobactam to Treat Ventilated Nosocomial Pneumonia (MK-7625A-008) (ASPECT-NP). Available at: https://clinicaltrials.gov/ct2/show/NCT02070757 . Accessed February 24, 2020; ClinicalTrials.gov Identifier: NCT02070757
145 ClinicalTrials.gov. Imipenem/Relebactam/Cilastatin Versus Piperacillin/Tazobactam for Treatment of Participants With Bacterial Pneumonia (MK-7655A-014) (RESTORE-IMI 2). Available at: https://clinicaltrials.gov/ct2/show/NCT02493764 . Accessed February 24, 2020; ClinicalTrials.gov Identifier: NCT02493764
146 McKinnell J, Connolly L, Pushkin R. , et al. Improved Outcomes With Plazomicin Compared With Colistin in Patients With Bloodstream Infections Caused by Carbapenem-resistant Enterobacteriaceae (CRE): Results From the CARE Study. Poster presented at IDWeek 2017, San Diego, CA. Poster; 2017
147 ClinicalTrials.gov. Pivotal Study in VAP Suspected or Confirmed to be Due to Pseudomonas Aeruginosa (PRISM-MDR). Available at: https://clinicaltrials.gov/ct2/show/NCT03409679 . Accessed February 24, 2020; ClinicalTrials.gov Identifier: NCT03409679
148 Wunderink RG, Giamarellos-Bourboulis EJ, Rahav G. , et al. Effect and safety of meropenem-vaborbactam versus best available therapy in patients with carbapenem-resistant Enterobacteriaceae infections: the TANGO II Randomized Clinical Trial. Infect Dis Ther 2018; 7 (04) 439-455
149 Bassetti M, Righi E, Russo A, Carnelutti A. New antibiotics for pneumonia. Clin Chest Med 2018; 39 (04) 853-869
150 Watkins RR, Van Duin D. Current trends in the treatment of pneumonia due to multidrug-resistant Gram-negative bacteria. F1000 Res 2019; 8 (F1000): 121
151 Sabouri Ghannad M, Mohammadi A. Bacteriophage: time to re-evaluate the potential of phage therapy as a promising agent to control multidrug-resistant bacteria. Iran J Basic Med Sci 2012; 15 (02) 693-701
152 Abedon ST. Phage therapy of pulmonary infections. Bacteriophage 2015; 5 (01) e1020260
153 Golkar Z, Bagasra O, Pace DG. Bacteriophage therapy: a potential solution for the antibiotic resistance crisis. J Infect Dev Ctries 2014; 8 (02) 129-136
154 Viertel TM, Ritter K, Horz HP. Viruses versus bacteria-novel approaches to phage therapy as a tool against multidrug-resistant pathogens. J Antimicrob Chemother 2014; 69 (09) 2326-2336
155 Schooley RT, Biswas B, Gill JJ. , et al. Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob Agents Chemother 2017; 61 (10) e0095417
156 Tkhilaishvili T, Wang L, Perka C, Trampuz A, Gonzalez Moreno M. Using bacteriophages as a Trojan horse to the killing of dual-species biofilm formed by Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus. Front Microbiol 2020;11:695. doi: 10.3389/fmicb.2020.00695
157 Eijsink VGL, Axelsson L, Diep DB, Håvarstein LS, Holo H, Nes IF. Production of class II bacteriocins by lactic acid bacteria; an example of biological warfare and communication. Antonie van Leeuwenhoek 2002; 81 (1-4): 639-654
158 Brown CL, Smith K, McCaughey L, Walker D. Colicin-like bacteriocins as novel therapeutic agents for the treatment of chronic biofilm-mediated infection. Biochem Soc Trans 2012; 40 (06) 1549-1552
159 McCaughey LC, Ritchie ND, Douce GR, Evans TJ, Walker D. Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection. Sci Rep 2016; 6: 30201
160 François B, Jafri HS, Bonten M. Alternatives to antibiotics. Intensive Care Med 2016; 42 (12) 2034-2036
161 Tkaczyk C, Hua L, Varkey R. , et al. Identification of anti-alpha toxin monoclonal antibodies that reduce the severity of Staphylococcus aureus dermonecrosis and exhibit a correlation between affinity and potency. Clin Vaccine Immunol 2012; 19 (03) 377-385
162 DiGiandomenico A, Keller AE, Gao C. , et al. A multifunctional bispecific antibody protects against Pseudomonas aeruginosa . Sci Transl Med 2014; 6 (262) 262ra155
163 DiGiandomenico A, Warrener P, Hamilton M. , et al. Identification of broadly protective human antibodies to Pseudomonas aeruginosa exopolysaccharide Psl by phenotypic screening. J Exp Med 2012; 209 (07) 1273-1287
164 ClinicalTrials.gov. Effort to Prevent Nosocomial Pneumonia Caused by Pseudomonas Aeruginosa in Mechanically Ventilated Subjects (EVADE). Available at: https://clinicaltrials.gov/ct2/show/NCT02696902 . Accessed February 24, 2020; trial number NCT02696902