Prevalence, Pattern, Risks Factors and Consequences of Antibiotic Resistance in COPD: A Systematic Review

Figures & data

Table 1. Antimicrobial resistances rates in non-hospitalised patients.

		Resistance rate (number of samples resistant/number of samples tested, %)
Microorganism Author, year	State	Penicillin		Ampicillin^p/Amoxicillin ^x		Co-amoxiclav		Tetracycline ^t/Doxycycline ^d		Quinolones, Ciprofloxacin ^c/Levofloxacin ^l		Macrolides^x, Azithromycin^a/Erythromycin^e/Clarithromycin ^c		Cefuroxime		Piperacillin/Tazobactam		Colistin
H. influenzae
Median, range (%)				39.7	20.4–73.3	1.85	0–40	0.5	0.2–6.7	0	0–0	4	0–46.7	0.2	0–0.5
Maddi et al. [55]	Stable			11/15 ^p 8/15 ^x	(73.3) (53.3)	6/15	(40)	1/15 ^t	(6.7)	0/15^c,l	(0)	3/15^a 7/15^e 4/15^c	(20) (46.7) (26.7)
Pettigrew et al. [56]	Mixed									0/100^c,l	(0)	1/100^a	(1)
Pfaller et al. [57]	AE			−/− ^p	(26)	−/−	(0)	−/− ^t	(0.2)	−/−^c,l	(0)	−/−^a −/−^c	(1) (7)	−/−	(0.2)
Pfaller et al. [58]	AE			−/− ^p	(20.4)	−/−	(3.7)	−/− ^d	(0.5)	−/−^c,l	(0)	−/−^c	(0) (7.3)	−/−	(0.5)
Querol-Ribelles et al. [59]	AE					−/−	(0)			−/−^c,l	(0)	−/−^a −/−^c	(0) (0.6)	−/−	(0)
P. aeruginosa
Median, range (%)										51.3	50–52.6					19.2	19.2–19.2	2.6	2.6–2.6
Gallego et al. [60]	Mixed									41/78^c 39/78^l	(52.6) (50)					15/78	(19.2)	2/78	(2.6)
S. pneumoniae
Median, range (%)		11.3	3–15	1.2	1.2–1.2	1.2	1.1–3	22.1	20.2–24	1	0–4.2	33.1	24–35	16.9	13.6–20.2
Desai et al. [27]	Mixed	6/75	(8)									18/75^e	(24)
Pfaller et al. [57]	AE	-/-	(15)			−/−	(3)	-/- ^t	(24)	−/−^l	(1)	−/−^e	(35)
Pfaller et al. [58]	AE	13/89	(14.6)			1/89	(1.1)	18/89^t	(20.2)	0/89^l	(0)	29/89 ^e	(32.6)	18/89	(20.2)
Querol-Ribelles et al. [59]	AE	−/−	(3)	−/− ^x	(1.2)	−/−	(1.2)			−/−^l	(4.2)	−/−^a,c −/−^e	(33.1) (34.3)		(13.6)
M. catarrhalis
Median, range (%)		93	93–93	90.4	90.4–90.4	0	0–0	0.5	0.3–0.7	0	0–0	2	0–3.7	0	0–0
Pfaller et al. [57]	AE		(93)			0/323	(0)	1/323^t	(0.3)	0/323^c,l	(0)	−/−^e	(2)	0/323	(0)
Pfaller et al. [58]	AE			−/− ^p	(90.4)	−/−	(0)	-/- ^t	(0.7)	−/−^c,l	(0)	−/−^e	(3.7)	−/−	(0)
Querol-Ribelles et al. [59]	AE					−/−	(0)			^c,l	(0)	−/−^a,c	(0)	−/−	(0)

Since number of samples which were tested for individual antibiotic susceptibility was not always the same as the number of patients in a study data is shown as n/% for tests performed as opposed to the convention of n per study. Summary statistics for each bacterium are shown in bold type, with individual studies below. Studies which did not explicitly state the number of samples tested for antimicrobial susceptibility are listed above as percentages only and are denoted by “-/-”.

‘State’ refers to the status of the patients COPD during the study: stable, patients with stable (non-exacerbated COPD); AE, patients with acute exacerbations; mixed, a study cohort including patients with either exacerbated or stable COPD.

AE, acute exacerbation.

Figure 1. PRISMA flow diagram.

Figure 2. Visual representation of distribution of: (A) origin of sample for antimicrobial susceptibility testing, (B) antibiotic susceptibility testing technique and (C) breakpoint antimicrobial susceptibility guidelines used, within included studies. CLSI, Clinical Laboratory Standards Institute; NCCLS, National Committee on Clinical Laboratory Standards; EUCAST, European Committee on Antimicrobial Susceptibility Testing.

Table 2. Risk of bias in included RCTs.

Study ID	Experimental	Comparator	Outcome	Weight	D1	D2	D3	D4	D5	Overall
Albert et al. [29]	Azithromycin	Placebo	Resistance rates	NA
Brill et al. [26]	Moxifloxacin/Doxycycline/Azithromycin	Placebo	Resistance rates	NA
DeAbate et al. [61]	5-day Grepafloxacin	10-day Grepafloxacin	Resistance rates	NA
Grossman et al. [62]	Ciprofloxacin	Cotrimoxazole	Resistance rates	NA
Khan et al. [63]	Levofloxacin	Azithromycin/Co-amoxicillin	Resistance rates	NA
Uzun et al. [31]	Azithromycin	Placebo	Resistance rates	NA

Tool used: Risk of Bias tool (RoB 2.0 tool).

, low risk; , some concerns; high risk.

D1, randomisation process; D2, deviations from the intended interventions; D3, missing outcome data; D4, measurement of the outcome; D5, selection of the reported result.

Table 3. Risk of bias in included non-randomised studies.

Study	C1	C2	C3	C4	C6	C7	C8
Agmy et al. [64]	+	!	+	–	+	+	–
Aogáin et al. [65]	+	+	+	+	+	+	+
Blasi et al. [66]	+	!	+	–	+	+	+
Butt et al. [67]	!	!	+	–	+	+	+
Casellas et al. [68]	+	!	+	+	+	+	+
Chen et al. [69]	!	!	+	–	+	+	+
Desai et al. [27]	+	+	+	+	+	+	+
Ding et al. [70]	!	!	+	–	+	+	–
Domenech et al. [71]	!	!	+	+	+	+	–
Domenech et al. [72]	+	+	+	+	+	+	+
Domenech et al. [73]	!	!	+	+	+	+	–
Domenech et al. [74]	+	+	+	+	+	+	+
Engler et al. [75]	+	+	+	–	!	!	+
Erkan et al. [76]	!	+	+	+	!	!	+
Estirado et al. [23]	+	+	+	+	+	+	+
Ewig et al. [77]	+	+	+	+	+	+	+
Firdaus et al. [78]	+	!	+	–	+	+	+
Gallego et al. [60]	+	+	+	+	+	+	+
Glogovska et al. [79]	!	!	+	+	!	!	+
Grochowalska et al. [80]	+	+	+	–	+	+	+
Guo et al. [22]	+	+	+	–	!	+	+
Hui et al. [81]	!	+	+	+	+	+	+
Inoue et al. [28]	!	!	+	–	+	+	+
Kennedy et al. [82]	!	!	+	+	+	+	+
Khilani et al. [83]	+	!	–	+	!	!	–
Kuwal et al. [84]	+	+	+	+	+	+	+
Larsen et al. [85]	+	+	–	+	!	!	+
Liu et al. [36]	+	!	+	+	+	+	+
Ma et al. [86]	+	!	+	+	+	+	+
Maddi et al. [55]	!	!	+	+	+	+	+
Montero et al. [33]	+	+	+	+	!	+	+
Nian et al. [87]	!	+	+	–	+	+	+
Nseir et al. [24]	+	+	+	+	!	!	+
Pan et al. [34]	+	+	+	+	!	!	+
Perez-Trallero et al. [88]	+	!	+	+	+	+	+
Pettigrew et al. [32]	+	+	+	+	+	+	+
Pfaller et al. [57]	+	+	+	+	+	+	–
Pfaller et al. [58]	+	+	+	+	+	+	–
Pomares et al. [30]	+	+	+	+	!	+	+
Querol-Ribelles et al. [59]	+	+	+	–	+	+	+
Rodrigo-Troyano et al. [25]	+	!	+	+	!	+	+
Rodrigo-Troyano et al. [89]	+	!	+	+	!	+	+
Sharma et al. [90]	+	!	+	+	!	!	+
Shoji et al. [91]	+	+	+	+	+	+	+
Shrestha et al. [92]	+	+	+	+	!	!	–
Srinivasan et al. [93]	!	!	+	–	+	+	+
Vandevelde et al. [94]	+	+	+	+	+	+	–
Varon et al. [95]	+	+	+	+	+	+	+
Vitacca et al. [35]	+	!	+	+	!	!	+
Xu et al. [96]	!	!	+	–	+	+	–
Ye et al. [97]	+	!	+	+	+	+	–
Zhao et al. [98]	+	+	+	+	+	+	+

C1, appropriate sample frame, +, Yes; C2, sampling method, !, Unclear; C3, sample size,-, No; C4, description of participants and setting; C6, validity of methods to identify cases; C7, standardisation of methods to identify cases; C8, appropriate statistical analysis.

Yes Unclear No Domain C5 and C9 not applicable. Tool used: Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies.

Maddi S, Kolsum U, Jackson S, et al. Ampicillin resistance in haemophilus influenzae from COPD patients in the UK. Int J COPD. 2017;12:1507–1518. DOI:https://doi.org/10.2147/COPD.S135338

 Google Scholar

Pettigrew MM, Gent JF, Revai K, Patel JA, Chonmaitree T. Microbial interactions during upper respiratory tract infections. Emerg Infect Dis. 2008;14(10):1584–1591. DOI:https://doi.org/10.3201/eid1410.080119

 PubMed Web of Science ®Google Scholar

Pfaller MA, Ehrhardt AF, Jones RN. Frequency of pathogen occurrence and antimicrobial susceptibility among community-acquired respiratory tract infections in the respiratory surveillance program study: Microbiology from the medical office practice environment. Am J Med. 2001;111:4S–38S.

 PubMed Web of Science ®Google Scholar

Pfaller MA, Jones RN. Gatifloxacin phase IV surveillance trial (TeqCES study) utilizing 5000 primary care physician practices: Report of pathogens isolated and susceptibility patterns in community-acquired respiratory tract infections. Diag Microbiol Infect Dis. 2002;44(1):77–84. DOI:https://doi.org/10.1016/s0732-8893(02)00446-7

 PubMed Web of Science ®Google Scholar

Querol-Ribelles J, Molina J, Naberan K, Esteban E, Herreras A, Garcia-de-Lomas J. Discrepancy between antibiotics administered in acute exacerbations of chronic bronchitis and susceptibility of isolated pathogens in respiratory samples: Multicentre study in the primary care setting. Int J Antimicrob Agents. 2006;28(5):472–476. DOI:https://doi.org/10.1016/j.ijantimicag.2006.05.034

 PubMed Web of Science ®Google Scholar

Gallego M, Pomares X, Espasa M, et al. Pseudomonas aeruginosa isolates in severe chronic obstructive pulmonary disease: Characterization and risk factors. BMC Pulm Med. 2014;14(1):103. DOI:https://doi.org/10.1186/1471-2466-14-103

 PubMedGoogle Scholar

Desai H, Richter S, Doern G, et al. Antibiotic resistance in sputum isolates of Streptococcus pneumoniae in chronic obstructive pulmonary disease is related to antibiotic exposure. COPD. 2010;7(5):337–344. DOI:https://doi.org/10.3109/15412555.2010.510162

 PubMedGoogle Scholar

Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD [published correction appears in N Engl J med. 2012;366(14):1356]. N Engl J Med. 2011;365(8):689–698. DOI:https://doi.org/10.1056/NEJMoa1104623

 PubMed Web of Science ®Google Scholar

Brill SE, Law M, El-Emir E, et al. Effects of different antibiotic classes on airway bacteria in stable COPD using culture and molecular techniques: a randomised controlled trial. Thorax. 2015;70(10):930–938. DOI:https://doi.org/10.1136/thoraxjnl-2015-207194

 PubMed Web of Science ®Google Scholar

DeAbate CA, Bettis R, Munk ZM, et al. Effectiveness of short-course therapy (5 days) with grepafloxacin in the treatment of acute bacterial exacerbations of chronic bronchitis. Clin Ther. 1999;21(1):172–188. DOI:https://doi.org/10.1016/S0149-2918(00)88277-6

 PubMed Web of Science ®Google Scholar

Grossman RF, Beaupre A, LaForge J, Lampron N, Hanna K. A prospective randomised parallel single-blind comparison of oral ciprofloxacin with oral cotrimoxazole in the treatment of respiratory tract infections in patients with chronic obstructive lung disease. Drug Invest. 1994;8(2):110–117. DOI:https://doi.org/10.1007/BF03257434

 Google Scholar

Kahn JB, Khashab M, Ambruzs M. Study entry microbiology in patients with acute bacterial exacerbation of chronic bronchitis in a clinical trial stratifying by disease severity. Curr Med Res Opin. 2007;23(1):1–7. DOI:https://doi.org/10.1185/030079907X159515

 PubMed Web of Science ®Google Scholar

Uzun S, Djamin RS, Kluytmans JA, et al. Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2014;2(5):361–368. DOI:https://doi.org/10.1016/S2213-2600(14)70019-0

 PubMed Web of Science ®Google Scholar

Agmy G, Mohamed S, Gad Y, Farghally E, Mohammedin H, Rashed H. Bacterial profile, antibiotic sensitivity and resistance of lower respiratory tract infections in upper Egypt. Mediterranean J Hematol Infect Dis. 2013;5(1). DOI:https://doi.org/10.4084/mjhid.2013.056

 Google Scholar

Aogain MM, Zhao C, Purbojati RW, et al. The airway ‘resistome’ in chronic respiratory disease: A metagenomics approach. European Respiratory Journal. Conference: 29th International Congress of the European Respiratory Society, ERS, Spain. 2019;54.

 Google Scholar

Blasi F, Farrell DJ, Dubreuil L. Antibacterial activity of telithromycin and comparators against pathogens isolated from patients with community-acquired respiratory tract infections: The prospective resistant organism tracking and epidemiology for the ketolide telithromycin study year 5 (2003–2004). Diagn Microbiol Infect Dis. 2009;63(3):302–308. DOI:https://doi.org/10.1016/j.diagmicrobio.2008.11.012

 PubMed Web of Science ®Google Scholar

Butt HL, Cripps AW, Clancy RL. In vitro susceptibility patterns of nonserotypable haemophilus influenzae from patients with chronic bronchitis. Pathology. 1997;29(1):72–75. DOI:https://doi.org/10.1080/00313029700169584

 PubMed Web of Science ®Google Scholar

Casellas JM, Gilardoni M, Tome G, et al. Comparative in-vitro activity of levofloxacin against isolates of bacteria from adult patients with community-acquired lower respiratory tract infections. J Antimicrob Chemother. 1999;43:37–42. DOI:https://doi.org/10.1093/jac/43.suppl_3.37

 PubMedGoogle Scholar

Chen L, Xie Z, Yang Y. Composition of pathogenic bacteria of chronic obstructive pulmonary disease patients and drug resistance of gram-negative bacilli for various antibiotics. Biomed Res. 2018;29(4) DOI:https://doi.org/10.4066/biomedicalresearch.29-17-3313

 Google Scholar

Ding YL, Yao WZ, Zhou QT, Chen YH, Ning YZ. Effect of mechanical ventilation beginning time after admission and ventilation duration on pathogens and antibiotic susceptibility of lower respiratory tract infection in chronic obstructive pulmonary disease patients [Chinese]. Chin J Antibiot. 2011;36(2):154–159

 Google Scholar

Domenech A, Puig C, Martí S, et al. Infectious etiology of acute exacerbations in severe COPD patients. J Infect. 2013;67(6):516–523. DOI:https://doi.org/10.1016/j.jinf.2013.09.003

 PubMed Web of Science ®Google Scholar

Domenech A, Ardanuy C, Calatayud L, et al. Serotypes and genotypes of streptococcus pneumoniae causing pneumonia and acute exacerbations in patients with chronic obstructive pulmonary disease. J Antimicrob Chemother. 2011;66(3):487–493. DOI:https://doi.org/10.1093/jac/dkq480

 PubMed Web of Science ®Google Scholar

Domenech A, Ardanuy C, Pallares R, et al. Some pneumococcal serotypes are more frequently associated with relapses of acute exacerbations in COPD patients. PLoS One. 2013;8(3):e59027 DOI:https://doi.org/10.1371/journal.pone.0059027

 PubMed Web of Science ®Google Scholar

Domenech A, Ardanuy C, Tercero A, Garcia-Somoza D, Santos S, Linares J. Dynamics of the pneumococcal population causing acute exacerbations in COPD patients in a Barcelona hospital (2009–12): Comparison with 2001-04 and 2005-08 periods. J Antimicrob Chemother. 2014;69(4):932–939. DOI:https://doi.org/10.1093/jac/dkt476

 PubMed Web of Science ®Google Scholar

Engler K, Muhlemann K, Garzoni C, Pfahler H, Geiser T, Von Garnier C. Colonisation with pseudomonas aeruginosa and antibiotic resistance patterns in COPD patients. Swiss Med Wkly. 2011;142. DOI:https://doi.org/10.4414/smw.2012.13509

 Google Scholar

Erkan L, Uzun O, Findik S, Katar D, Sanic A, Atici AG. Role of bacteria in acute exacerbations of chronic obstructive pulmonary disease. Int J COPD. 2008;3(3):463–467

 Google Scholar

Estirado C, Ceccato A, Guerrero M, et al. Microorganisms resistant to conventional antimicrobials in acute exacerbations of chronic obstructive pulmonary disease. Respir Res. 2018;19(1):119. DOI:https://doi.org/10.1186/s12931-018-0820-1

 PubMedGoogle Scholar

Ewig S, Soler N, Gonzalez J, Celis R, El-Ebiary M, Torres A. Evaluation of antimicrobial treatment in mechanically ventilated patients with severe chronic obstructive pulmonary disease exacerbations. Crit Care Med. 2000;28(3):692–697

 PubMed Web of Science ®Google Scholar

Firdaus H, Khan NA, Fatima N, Shameem M, Bhargava R, Ahmad Z. Acute exacerbation of chronic obstructive pulmonary disease: Phenotypic screening and sensitivity of microbiological profile. J Clin Diagn Res. 2020; 14(6):LC15–LC20.

 Web of Science ®Google Scholar

Glogovska PT, Ivanova ZI, Popova TP, et al. Sputum isolates from ambulatory patients with chronic obstructive pulmonary disease—frequent pathogens and antibiotic resistance. J IMAB - Ann Proceed. 2015;21(2):770–774. DOI:https://doi.org/10.5272/jimab.2015212.770

 Google Scholar

Grochowalska A, Koziol-Montewka M, Sobieszczanska A. Analysis of acinetobacter baumannii resistance patterns in patients with chronic obstructive pulmonary disease (COPD) in terms of choice of effective empiric antibiotic therapy. Ann Agric Environ Med. 2017;24(2):307–311. DOI:https://doi.org/10.26444/aaem/74710

 PubMed Web of Science ®Google Scholar

Guo Z, Chang C, Chen Y, et al. [bacteriology in acute exacerbation in patients hospitalized frequently for acute exacerbation of chronic obstructive pulmonary disease. Zhonghua Yi Xue Za Zhi 2014;94(10):729–732 (in Chinese).

 Google Scholar

Hui DS, Ip M, Ling T, et al. A multicentre surveillance study on the characteristics, bacterial aetiologies and in vitro antibiotic susceptibilities in patients with acute exacerbations of chronic bronchitis. Respirology. 2011;16(3):532–539 DOI:https://doi.org/10.1111/j.1440-1843.2011.01943.x

 PubMed Web of Science ®Google Scholar

Inoue S, Watanuki Y, Miyazawa N, et al. High frequency of β-lactamase-negative, ampicillin-resistant strains of Haemophilus influenzae in patients with chronic bronchitis in Japan. J Infect Chemother. 2010;16(1):72–75. DOI:https://doi.org/10.1007/s10156-009-0020-5

 PubMed Web of Science ®Google Scholar

Kennedy M, Ramsheh MY, Williams CML, et al. Face mask sampling reveals antimicrobial resistance genes in exhaled aerosols from patients with chronic obstructive pulmonary disease and healthy volunteers. BMJ Open Resp Res. 2018;5(1):e000321. DOI:https://doi.org/10.1136/bmjresp-2018-000321

 PubMed Web of Science ®Google Scholar

Khilnani GC, Dubey D, Hadda V, et al. Predictors and microbiology of ventilator-associated pneumonia among patients with exacerbation of chronic obstructive pulmonary disease. Lung India. 2019;36(6):506–511. DOI:https://doi.org/10.4103/lungindia.lungindia_13_19

 PubMed Web of Science ®Google Scholar

Kuwal A, Joshi V, Dutt N, Singh S, Agarwal KC, Purohit G. A prospective study of bacteriological etiology in hospitalized acute exacerbation of COPD patients: Relationship with lung function and respiratory failure. Turk Toraks Dergisi/Turkish Thoracic J. 2018;19(1):19–27. DOI:https://doi.org/10.5152/TurkThoracJ.2017.17035

 PubMed Web of Science ®Google Scholar

Larsen MV, Janner JH, Nielsen SD, Friis-Møller A, Ringbaek T, Lange P. Bacteriology in acute exacerbation of chronic obstructive pulmonary disease in patients admitted to hospital. Scand J Infect Dis. 2009;41(1):26–32. DOI:https://doi.org/10.1080/00365540802484828

 PubMed Web of Science ®Google Scholar

Liu H, Zheng D, Lin Y, et al. Association of sputum microbiome with clinical outcome of initial antibiotic treatment in hospitalized patients with acute exacerbations of COPD. Pharmacol Res. 2020;160:105095 DOI:https://doi.org/10.1016/j.phrs.2020.105095

 PubMed Web of Science ®Google Scholar

Ma X, Cui J, Wang J, et al. Multicentre investigation of pathogenic bacteria and antibiotic resistance genes in Chinese patients with acute exacerbation of chronic obstructive pulmonary disease. J Int Med Res. 2015;43(5):699–710. DOI:https://doi.org/10.1177/0300060515587577

 PubMed Web of Science ®Google Scholar

Montero M, Domínguez M, Orozco-Levi M, et al. Mortality of COPD patients infected with multi-resistant pseudomonas aeruginosa: a case and control study. Infection 2009;37(1):16–19. DOI:https://doi.org/10.1007/s15010-008-8125-9

 PubMed Web of Science ®Google Scholar

Nian L, Liangyi X, Gang J, Wei L, Yongliang J. Analysis on constituents and drug resistance of pathogenic bacteria causing chronic obstructive pulmonary disease. Biomed Res (India). 2017;28(20):8939–8942.

 Google Scholar

Nseir S, Di Pompeo C, Cavestri B, et al. Multiple-drug-resistant bacteria in patients with severe acute exacerbation of chronic obstructive pulmonary disease: Prevalence, risk factors, and outcome. Crit Care Med. 2006;34(12):2959–2966. DOI:https://doi.org/10.1097/01.CCM.0000245666.28867.C6

 PubMed Web of Science ®Google Scholar

Pan W, Yu J, Zhang L, et al. Predictors of in-hospital mortality in patients with acute exacerbation of COPD requiring ventilation: a retrospective study. Int J Clin Exp Med. 2016;9(11):22093–22101.

 Web of Science ®Google Scholar

Perez-Trallero E, Marimon JM, Larruskain J, Alonso M, Ercibengoa M. Antimicrobial susceptibilities and serotypes of streptococcus pneumoniae isolates from elderly patients with pneumonia and acute exacerbation of chronic obstructive pulmonary disease. Antimicrob Agent Chemother. 2011;55(6):2729–2734. DOI:https://doi.org/10.1128/AAC.01546-10

 PubMed Web of Science ®Google Scholar

Pettigrew MM, Tsuji BT, Gent JF, et al. Effect of fluoroquinolones and macrolides on eradication and resistance of Haemophilus influenzae in chronic obstructive pulmonary disease. Antimicrob Agents Chemother. 2016;60(7):4151–4158. DOI:https://doi.org/10.1128/AAC.00301-16

 PubMed Web of Science ®Google Scholar

Pomares X, Montón C, Bullich M, et al. Clinical and safety outcomes of long-term azithromycin therapy in severe COPD beyond the first year of treatment. Chest 2018;153(5):1125–1133. DOI:https://doi.org/10.1016/j.chest.2018.01.044

 PubMed Web of Science ®Google Scholar

Rodrigo-Troyano A, Suarez-Cuartin G, Peiró M, et al. Pseudomonas aeruginosa resistance patterns and clinical outcomes in hospitalized exacerbations of COPD. Respirology. 2016;21(7):1235–1242. DOI:https://doi.org/10.1111/resp.12825

 PubMed Web of Science ®Google Scholar

Rodrigo-Troyano A, Melo V, Marcos PJ, et al. Pseudomonas aeruginosa in chronic obstructive pulmonary disease patients with frequent hospitalized exacerbations: a prospective ­multicentre study. Respiration. 2018;96(5):417–424. DOI:https://doi.org/10.1159/000490190

 PubMed Web of Science ®Google Scholar

Sharma P, Narula S, Sharma K, Lohchab K, Kumar N. Sputum bacteriology and antibiotic sensitivity pattern in COPD exacerbation in india. Egypt J Chest Dis Tubercul. 66(4):593–597. DOI:https://doi.org/10.1016/j.ejcdt.2017.08.003

 Google Scholar

Shoji H, Vazquez-Sanchez D, Gonzalez-Diaz A, et al. Overview of pneumococcal serotypes and genotypes causing diseases in patients with chronic obstructive pulmonary disease in a Spanish hospital between 2013 and 2016. Infect Drug Resist. 2018;11:1387–1400. DOI:https://doi.org/10.2147/IDR.S165093

 PubMed Web of Science ®Google Scholar

Shrestha R, Shrestha B, Shakya Shrestha S, Pant A, Prajapati B, Karmacharya BM. Study of pre-disposing factors of acute exacerbation of chronic obstructive pulmonary disease and antibiotic prescribing pattern with reference to antibiotic sensitivity test. Kathmandu Univ Med J. 13(51):259–264. DOI:https://doi.org/10.3126/kumj.v13i3.16817

 Google Scholar

Srinivasan SV, Ahmed JS. Gram negative organisms as a cause of acute exacerbation of ‘COPD’ and assess the multi drug resistant in the gram-negative isolates. Int J Res Ayurveda Pharm. 2017;8(2):91–94. DOI:https://doi.org/10.7897/2277-4343.08272

 Google Scholar

Vandevelde NM, Tulkens PM, et al. Characterisation of a collection of streptococcus pneumoniae isolates from patients suffering from acute exacerbations of chronic bronchitis: In vitro susceptibility to antibiotics and biofilm formation in relation to antibiotic efflux and serotypes/serogroups. Int J Antimicrob Agent. 2014;44(3):209–217. DOI:https://doi.org/10.1016/j.ijantimicag.2014.05.016

 PubMed Web of Science ®Google Scholar

Varon F, Torres-Caro C, Herrera-Diaz C, et al. Microbiological characterization of severe exacerbations in chronic obstructive pulmonary disease (COPD) in patients admitted to the ICU with or without associated pneumonia: A retrospective cross-sectional study. Infectio. 2019;23(4):307–312. DOI:https://doi.org/10.22354/in.v23i4.803

 Google Scholar

Vitacca M, Marino S, Comini L, et al. Bacterial colonization in COPD patients admitted to a rehabilitation respiratory unit and impact on length of stay: a real-life study. COPD. 2018;15(6):581–587. DOI:https://doi.org/10.1080/15412555.2019.1572731

 PubMedGoogle Scholar

Xu P, Song W, Liu Y, Pi J, Li Y, Yang H. Analysis of bacterial pathogens isolated from lower respiratory tract in patients with acute exacerbation of chronic obstructive pulmonary diseases [Chinese]. Chinese J Infect Chemother. 10(2):108–111.

 Google Scholar

Ye F, He LX, Cai BQ, et al. Spectrum and antimicrobial resistance of common pathogenic bacteria isolated from patients with acute exacerbation of chronic obstructive pulmonary disease in mainland of china. Chin Med J. 2013;126(12):2207–2214.

 PubMed Web of Science ®Google Scholar

Zhao JN, Zhang XX, He XC, et al. Multidrug-resistant tuberculosis in patients with chronic obstructive pulmonary disease in china. PLoS One. 2015;10(8):e0135205. DOI:https://doi.org/10.1371/journal.pone.0135205

 PubMed Web of Science ®Google Scholar