Research progress of heteroresistance to carbapenems in Pseudomonas aeruginosa
LIU Yu-yang1, CHEN Cha2,3, HUANG Bin1
1. Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; 2. Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; 3. Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China
Abstract：Heteroresistance refers to the co-existence of bacterial resistance and sensitivity to certain antimicrobial agents in the same clone. Carbapenems are the preferred drugs for the treatment of infection caused by Pseudomonas aeruginosa. With the increasing use of carbapenems, isolation rate of carbapenem-heteroresistant Pseudomonas aeruginosa (CHPA) gradually increased. However, there is no standard, efficient and low-cost detection method for CHPA that can be applied in clinical practice, leading to the failure of detection and treatment for CHPA infection. This paper reviewed the definition and detection methods of heteroresistance, as well as resistance mechanism, clinical and epidemiological characteristics of CHPA, provide references for clinical diagnosis and treatment of CHPA infection.
刘宇阳, 陈茶, 黄彬. 铜绿假单胞菌对碳青霉烯类抗生素异质性耐药的研究进展[J]. 中国感染控制杂志, 2021, 20(8): 763-768.
LIU Yu-yang, CHEN Cha, HUANG Bin. Research progress of heteroresistance to carbapenems in Pseudomonas aeruginosa. Chinese Journal of Infection Control, 2021, 20(8): 763-768.
Buehrle DJ, Shields RK, Clarke LG, et al. Carbapenem-resistant Pseudomonas aeruginosa bacteremia:risk factors for mortality and microbiologic treatment failure[J]. Antimicrob Agents Chemother, 2017, 61(1):e01243-16.
[2]
Kang CI, Kim SH, Kim HB, et al. Pseudomonas aeruginosa bacteremia:risk factors for mortality and influence of delayed receipt of effective antimicrobial therapy on clinical outcome[J]. Clin Infect Dis, 2003, 37(6):745-751.
[3]
Livermore DM. Multiple mechanisms of antimicrobial resis-tance in Pseudomonas aeruginosa:our worst nightmare?[J]. Clin Infect Dis, 2002, 34(5):634-640.
[4]
Alexander HE, Leidy G. Mode of action of streptomycin on type b Hemophilus influenzae:II. Nature of resistant variants[J]. J Exp Med, 1947, 85(6):607-621.
[5]
Bakthavatchalam YD, Veeraraghavan B, Devanga Ragupathi NK, et al. Draft genome sequence of reduced teicoplanin-susceptible and vancomycin-heteroresistant methicillin-resistant Staphylococcus aureus from sepsis cases[J]. J Glob Antimicrob Resist, 2017, 8:169-171.
[6]
Walsh CC, McIntosh MP, Peleg AY, et al. In vitro pharmacodynamics of fosfomycin against clinical isolates of Pseudomonas aeruginosa[J]. J Antimicrob Chemother, 2015, 70(11):3042-3050.
[7]
Engel H, Mika M, Denapaite D, et al. A low-affinity penicillin-binding protein 2x variant is required for heteroresistance in Streptococcus pneumoniae[J]. Antimicrob Agents Chemother, 2014, 58(7):3934-3941.
[8]
Bardet L, Baron S, Leangapichart T, et al. Deciphering hete-roresistance to colistin in a Klebsiella pneumoniae isolate from Marseille, France[J]. Antimicrob Agents Chemother, 2017, 61(6):e00356-17.
[9]
Halaby T, Kucukkose E, Janssen AB, et al. Genomic characterization of colistin heteroresistance in Klebsiella pneumoniae during a nosocomial outbreak[J]. Antimicrob Agents Chemother, 2016, 60(11):6837-6843.
[10]
Ikonomidis A, Neou E, Gogou V, et al. Heteroresistance to meropenem in carbapenem-susceptible Acinetobacter baumannii[J]. J Clin Microbiol, 2009, 47(12):4055-4059.
[11]
Metcalfe JZ, Streicher E, Theron G, et al. Mycobacterium tuberculosis subculture results in loss of potentially clinically relevant heteroresistance[J]. Antimicrob Agents Chemother, 2017, 61(11):e00888-17.
[12]
Dantas RCC, Silva RTE, Ferreira ML, et al. Molecular epidemiological survey of bacteremia by multidrug resistant Pseudo-monas aeruginosa:the relevance of intrinsic resistance mechanisms[J]. PLoS One, 2017, 12(5):e0176774.
[13]
He JC, Jia XJ, Yang SS, et al. Heteroresistance to carbapenems in invasive Pseudomonas aeruginosa infections[J]. Int J Antimicrob Agents, 2018, 51(3):413-421.
[14]
El-Halfawy OM, Valvano MA. Antimicrobial heteroresistance:an emerging field in need of clarity[J]. Clin Microbiol Rev, 2015, 28(1):191-207.
[15]
Markova N, Haydoushka I, Michailova L, et al. Cell wall deficiency and its effect on methicillin heteroresistance in Staphy-lococcus aureus[J]. Int J Antimicrob Agents, 2008, 31(3):255-260.
Fernández Cuenca F, Sánchez Mdel C, Caballero-Moyano FJ, et al. Prevalence and analysis of microbiological factors associated with phenotypic heterogeneous resistance to carbapenems in Acinetobacter baumannii[J]. Int J Antimicrob Agents, 2012, 39(6):472-477.
[18]
da Silva AEB, Martins AF, Nodari CS, et al. Carbapenem-heteroresistance among isolates of the Enterobacter cloacae complex:is it a real concern?[J]. Eur J Clin Microbiol Infect Dis, 2018, 37(1):185-186.
[19]
Zheng C, Li S, Luo ZY, et al. Mixed infections and rifampin heteroresistance among Mycobacterium tuberculosis clinical isolates[J]. J Clin Microbiol, 2015, 53(7):2138-2147.
[20]
Wong SS, Ho PL, Woo PC, et al. Bacteremia caused by staphylococci with inducible vancomycin heteroresistance[J]. Clin Infect Dis, 1999, 29(4):760-767.
[21]
Nicoloff H, Hjort K, Levin BR, et al. The high prevalence of antibiotic heteroresistance in pathogenic bacteria is mainly caused by gene amplification[J]. Nat Microbiol, 2019, 4(3):504-514.
[22]
Mei SC, Gao YL, Zhu CT, et al. Research of the heteroresistance of Pseudomonas aeruginosa to imipenem[J]. Int J Clin Exp Med, 2015, 8(4):6129-6132.
[23]
Qin X, Zhou C, Zerr DM, et al. Heterogeneous antimicrobial susceptibility characteristics in Pseudomonas aeruginosa isolates from cystic fibrosis patients[J]. mSphere, 2018, 3(2):e00615-17.
Wootton M, Howe RA, Hillman R, et al. A modified population analysis profile (PAP) method to detect hetero-resistance to vancomycin in Staphylococcus aureus in a UK hospital[J]. J Antimicrob Chemother, 2001, 47(4):399-403.
[26]
Sherman EX, Wozniak JE, Weiss DS. Methods to evaluate colistin heteroresistance in Acinetobacter baumannii[J]. Metho-ds Mol Biol, 2019, 1946:39-50.
[27]
Sautrey G, Duval RE, Chevalley A, et al. Capillary electrophoresis for fast detection of heterogeneous population in colistin-resistant Gram-negative bacteria[J]. Electrophoresis, 2015, 36(20):2630-2633.
[28]
Bradley P, Gordon NC, Walker TM, et al. Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis[J]. Nat Commun, 2015, 6:10063.
[29]
Andersson DI, Nicoloff H, Hjort K. Mechanisms and clinical relevance of bacterial heteroresistance[J]. Nat Rev Microbiol, 2019, 17(8):479-496.
Iyer RN, Hittinahalli V. Modified PAP method to detect hete-roresistance to vancomycin among methicillin resistant Staphy-lococcus aureus isolates at a tertiary care hospital[J]. Indian J Med Microbiol, 2008, 26(2):176-179.
[32]
van Hal SJ, Wehrhahn MC, Barbagiannakos T, et al. Performance of various testing methodologies for detection of heteroresistant vancomycin-intermediate Staphylococcus aureus in bloodstream isolates[J]. J Clin Microbiol, 2011, 49(4):1489-1494.
[33]
Li J, Rayner CR, Nation RL, et al. Heteroresistance to colistin in multidrug-resistant Acinetobacter baumannii[J]. Antimicrob Agents Chemother, 2006, 50(9):2946-2950.
[34]
Band VI, Hufnagel DA, Jaggavarapu S, et al. Antibiotic combinations that exploit heteroresistance to multiple drugs effectively control infection[J]. Nat Microbiol, 2019, 4(10):1627-1635.
[35]
Zwe YH, Chin SF, Kohli GS, et al. Whole genome sequencing (WGS) fails to detect antimicrobial resistance (AMR) from heteroresistant subpopulation of Salmonella enterica[J]. Food Microbiol, 2020, 91:103530.
[36]
Ikonomidis A, Tsakris A, Kantzanou M, et al. Efflux system overexpression and decreased OprD contribute to the carbape-nem heterogeneity in Pseudomonas aeruginosa[J]. FEMS Microbiol Lett, 2008, 279(1):36-39.
[37]
Cabot G, Ocampo-Sosa AA, Tubau F, et al. Overexpression of AmpC and efflux pumps in Pseudomonas aeruginosa isolates from bloodstream infections:prevalence and impact on resistance in a Spanish multicenter study[J]. Antimicrob Agents Chemother, 2011, 55(5):1906-1911.
[38]
Terzi HA, Kulah C, Ciftci IH. The effects of active efflux pumps on antibiotic resistance in Pseudomonas aeruginosa[J]. World J Microbiol Biotechnol, 2014, 30(10):2681-2687.
[39]
Arabestani MR, Rajabpour M, Yousefi Mashouf R, et al. Expression of efflux pump MexAB-OprM and OprD of Pseudomonas aeruginosa strains isolated from clinical samples using qRT-PCR[J]. Arch Iran Med, 2015, 18(2):102-108.
[40]
Anderson SE, Sherman EX, Weiss DS, et al. Aminoglycoside heteroresistance in Acinetobacter baumannii AB5075[J]. mSphere, 2018, 3(4):e00271-18.
Band VI, Crispell EK, Napier BA, et al. Antibiotic failure mediated by a resistant subpopulation in Enterobacter cloacae[J]. Nat Microbiol, 2016, 1(6):16053.
[43]
Morand B, Mühlemann K. Heteroresistance to penicillin in Streptococcus pneumoniae[J]. Proc Natl Acad Sci U S A, 2007, 104(35):14098-14103.
