This study aims to delineate the epidemiological trends of carbapenem-resistant Klebsiella pneumoniae (CRKP) in pediatric patients before, during, and after coronavirus disease 2019 (COVID-19) pandemic and to assess the risk factors of CRKP hospital-acquired infections (CRKP-HAIs) across these three periods. We retrospectively collected the clinical data of pediatric patients diagnosed with K. pneumoniae infection at the Children’s Hospital of Nanjing Medical University from January 2018 to March 2024. Carbapenemase-related genes were detected by PCR, and statistical analysis was conducted using SPSS 25.0. The current study found that modifications in the COVID-19 pandemic prevention and control measures and antibiotic therapies impact the epidemiological trends and antimicrobial resistance of CRKP. Binary logistic regression analyses revealed various independent risk factors for CRKP-HAIs before, during, and after the COVID-19 pandemic. Healthcare institutions must intensify surveillance for HAIs, continuously monitor and avoid risk factors for CRKP-HAIs, and formulate targeted preventive and control measures to effectively reduce the incidence and spread of these infections. Further, consistent surveillance of CRKP strains coproducing carbapenemase genes is crucial for mitigating the potential health risks in pediatric patients.
Get full access to this article
View all access options for this article.
References
1.
ChiuSK, MaL, ChanMC, et al.Carbapenem nonsusceptible Klebsiella pneumoniae in Taiwan: Dissemination and increasing resistance of carbapenemase producers during 2012-2015. Sci Rep, 2018; 8(1):8468; doi: 10.1038/s41598-018-26691-z
2.
MartinRM, BachmanMA. Colonization, infection, and the accessory genome of klebsiella pneumoniae. Front Cell Infect Microbiol, 2018; 8:4; doi: 10.3389/fcimb.2018.00004
3.
PaczosaMK, MecsasJ. Klebsiella pneumoniae: Going on the offense with a strong defense. Microbiol Mol Biol Rev, 2016; 80(3):629–661; doi: 10.1128/MMBR.00078-15
4.
RangasamyT, GhimireL, JinL, et al.Host defense against Klebsiella pneumoniae pneumonia is augmented by lung-derived mesenchymal stem cells. J Immunol, 2021; 207(4):1112–1127; doi: 10.4049/jimmunol.2000688
Weiner-LastingerLM, AbnerS, EdwardsJR, et al.Antimicrobial-resistant pathogens associated with adult healthcare-associated infections: Summary of data reported to the National Healthcare Safety Network, 2015–2017. Infect Control Hosp Epidemiol, 2020; 41(1):1–18; doi: 10.1017/ice.2019.296
7.
WangZ, YangB, LiQ, et al.Clinical features of 69 cases with coronavirus disease 2019 in Wuhan, China. Clin Infect Dis, 2020; 71(15):769–777; doi: 10.1093/cid/ciaa272
8.
WuJ, LiuJ, ZhaoX, et al.Clinical characteristics of imported cases of coronavirus disease 2019 (COVID-19) in Jiangsu Province: A multicenter descriptive study. Clin Infect Dis, 2020; 71(15):706–712; doi: 10.1093/cid/ciaa199
9.
RawsonTM, MingD, AhmadR, et al.Antimicrobial use, drug-resistant infections and COVID-19. Nat Rev Microbiol, 2020; 18(8):409–410; doi: 10.1038/s41579-020-0395-y
10.
KnightGM, GloverRE, McQuaidCF, et al.Antimicrobial resistance and COVID-19: Intersections and implications. Elife, 2021; 10; doi: 10.7554/eLife.64139
11.
TomczykS, TaylorA, BrownA, et al.WHO AMR Surveillance and Quality Assessment Collaborating Centres Network. Impact of the COVID-19 pandemic on the surveillance, prevention and control of antimicrobial resistance: A global survey. J Antimicrob Chemother, 2021; 76(11):3045–3058; doi: 10.1093/jac/dkab300
12.
MengQ, LiW, JiangH, et al.Comparison of the distribution and changes in the antibiotic resistance of clinical bacterial isolates from the lower respiratory tract of children in Shenzhen before the epidemic, during the epidemic, and during the period of normalized prevention and control of COVID-19. Infect Dis Ther, 2023; 12(2):563–575; doi: 10.1093/jac/dkab300
LuMC, ChenYT, TangHL, et al.Transmission and evolution of OXA-48-producing Klebsiella pneumoniae ST11 in a single hospital in Taiwan. J Antimicrob Chemother, 2020; 75(2):318–326; doi: 10.1093/jac/dkz431
15.
Van DuinD, AriasCA, KomarowL, et al.Multi-Drug Resistant Organism Network Investigators. Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): A prospective cohort study. Lancet Infect Dis, 2020; 20(6):731–741; doi: 10.1016/S1473-3099(19)30755-8
16.
MandellLA, WunderinkRG, AnzuetoA, et al.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 2):S27–S72; doi: 10.1086/511159
17.
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; doi: 10.1164/rccm.200405-644ST
18.
HoranTC, AndrusM, DudeckMA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control, 2008; 36(5):309–332; doi: 10.1016/j.ajic.2008.03.002
Office of the National Health and Family Planning Commission, Office of the State Administration of Traditional Chinese Medicine, Bureau of Pharmaceutical Equipment of the General Logistics Department of Health.. Notice on the issuance of The Guiding Principles of Clinical Application of Antibacterials (Edition 2015). State Health Office Medical Development No. 43. 2015-07-24.
21.
ZhangP, ShiQ, HuH, et al.Emergence of ceftazidime/avibactam resistance in carbapenem-resistant Klebsiella pneumoniae in China. Clin Microbiol Infect, 2020; 26(1):124.e1–e4; doi: 10.1016/j.cmi.2021.05.026
22.
RogersBA, SidjabatHE, SilveyA, et al.Treatment options for New Delhi metallo-beta-lactamase-harboring enterobacteriaceae. Microb Drug Resist, 2013; 19(2):100–103; doi: 10.1089/mdr.2012.0063
23.
GuoX, WangQ, XuH, et al.Emergence of IMP-8-producing Comamonas thiooxydans causing urinary tract infection in China. Front Microbiol, 2021; 12:585716; doi: 10.3389/fmicb.2021.585716
24.
WangX, WangY, ZhouY, et al.Emergence of a novel mobile colistin resistance gene, mcr-8, in NDM-producing Klebsiella pneumoniae. Emerg Microbes Infect, 2018; 7(1):122; doi: 10.1038/s41426-018-0124-z
25.
China Antimicrobial Resistance Surveillance System (CARSS) data. Available from: https://www.carss.cn/Report [Last accessed: April17, 2024].
26.
GandraS, Alvarez-UriaG, StwalleyD, et al.Microbiology clinical culture diagnostic yields and antimicrobial resistance proportions before and during the COVID-19 pandemic in an Indian community hospital and two US community hospitals. Antibiotics (Basel), 2023; 12(3); doi: 10.3390/antibiotics12030537
27.
KleinEY, Van BoeckelTP, MartinezEM, et al.Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. Proc Natl Acad Sci U S A, 2018; 115(15):E3463–Ee70; doi: 10.1073/pnas.1717295115
28.
SulisG, BatomenB, KotwaniA, et al.Sales of antibiotics and hydroxychloroquine in India during the COVID-19 epidemic: An interrupted time series analysis. PLoS Med, 2021; 18(7):e1003682; doi: 10.1371/journal.pmed.1003682
29.
HuY, LiuC, ShenZ, et al.Prevalence, risk factors and molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae in patients from Zhejiang, China, 2008-2018. Emerg Microbes Infect, 2020; 9(1):1771–1779; doi: 10.1080/22221751.2020.1799721
30.
TiriB, SensiE, MarsilianiV, et al.Antimicrobial stewardship program, COVID-19, and infection control: Spread of carbapenem-resistant Klebsiella pneumoniae colonization in ICU COVID-19 patients. What did not work? J Clin Med, 2020; 9(9); doi: 10.3390/jcm9092744
31.
KongZ, LiuX, LiC, et al.Clinical molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae among pediatric patients in Jiangsu Province, China. Infect Drug Resist, 2020; 13:4627–4635; doi: 10.2147/IDR.S293206
32.
PuD, ZhaoJ, ChangK, et al.“Superbugs” with hypervirulence and carbapenem resistance in Klebsiella pneumoniae: The rise of such emerging nosocomial pathogens in China. Sci Bull (Beijing), 2023; 68(21):2658–2670; doi: 10.1016/j.scib.2023.09.040
33.
TeoJQ, TangCY, TanSH, et al.Genomic surveillance of carbapenem-resistant Klebsiella pneumoniae from a major public health hospital in Singapore. Microbiol Spectr, 2022; 10(5):e0095722; doi: 10.1128/spectrum.00957-22
34.
NahaS, SandsK, MukherjeeS, et al.OXA-181-Like Carbapenemases in Klebsiella pneumoniae ST14, ST15, ST23, ST48, and ST231 from septicemic neonates: Coexistence with NDM-5, resistome, transmissibility, and genome diversity. mSphere, 2021; 6(1); doi: 10.1128/mSphere.01156-20
35.
SunL, ChenY, QuT, et al.Characterisation of a novel hybrid IncFII(pHN7A8):IncR:IncN plasmid co-harboring bla(NDM-5) and bla(KPC-2) from a clinical ST11 carbapenem-resistant Klebsiella pneumoniae strain. Infect Drug Resist, 2023; 16:7621–7628; doi: 10.2147/IDR.S435195
36.
XiaoW, WangX, QuY, et al.Identification of two novel carbapenemase-encoding hybrid plasmids harboring bla(NDM-5) and bla(KPC-2) in a clinical ST11-KL47 Klebsiella pneumoniae. Infect Drug Resist, 2023; 16:4073–4081; doi: 10.2147/IDR.S408824
37.
GaoH, LiuY, WangR, et al.The transferability and evolution of NDM-1 and KPC-2 co-producing Klebsiella pneumoniae from clinical settings. EBioMedicine, 2020; 51:102599; doi: 10.1016/j.ebiom.2019.102599
38.
WunderinkRG, Giamarellos-BourboulisEJ, RahavG, 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(4):439–455; doi: 10.1007/s40121-018-0214-1
39.
IslerB, AslanAT, AkovaM, et al.Treatment strategies for OXA-48-like and NDM producing Klebsiella pneumoniae infections. Expert Rev Anti Infect Ther, 2022; 20(11):1389–1400; doi: 10.1080/14787210.2022.2128764
40.
WuW, FengY, TangG, et al.NDM Metallo-β-Lactamases and their bacterial producers in health care settings. Clin Microbiol Rev, 2019; 32(2); doi: 10.1128/CMR.00115-18
MikhailS, SinghNB, KebriaeiR, et al.Evaluation of the synergy of ceftazidime-avibactam in combination with meropenem, amikacin, aztreonam, colistin, or fosfomycin against well-characterized multidrug-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa. Antimicrob Agents Chemother, 2019; 63(8); doi: 10.1128/AAC.00779-19
43.
FalconeM, DaikosGL, TiseoG, et al.Efficacy of ceftazidime-avibactam plus aztreonam in patients with bloodstream infections caused by metallo-β-lactamase-producing Enterobacterales. Clin Infect Dis, 2021; 72(11):1871–1878; doi: 10.1093/cid/ciaa586
44.
MontagnaniC, TersigniC, D’ArienzoS, et al.Resistance patterns from urine cultures in children aged 0 to 6 years: Implications for empirical antibiotic choice. Infect Drug Resist, 2021; 14:2341–2348; doi: 10.2147/IDR.S293279
45.
LiS, ChenZ, HuangL, et al.Safety of quinolones in children: A systematic review and meta-analysis. Paediatr Drugs, 2022; 24(5):447–464; doi: 10.1007/s40272-022-00513-2
46.
HuangG, ZengQL, KeGB, et al.Influence of COVID-19 targeted prevention and control measures on the distribution and drug resistance transition of Klebsiella pneumoniae. Med J West China, 2023; 35(01):97–101; doi: 10.3969/j.issn.1672-3511.2023.01.017
47.
LouT, DuX, ZhangP, et al.Risk factors for infection and mortality caused by carbapenem-resistant Klebsiella pneumoniae: A large multicentre case-control and cohort study. J Infect, 2022; 84(5):637–647; doi: 10.1016/j.jinf.2022.03.010
48.
ZhuWM, YuanZ, ZhouHY. Risk factors for carbapenem-resistant Klebsiella pneumoniae infection relative to two types of control patients: A systematic review and meta-analysis. Antimicrob Resist Infect Control, 2020; 9(1):23; doi: 10.1186/s13756-020-0686-0
49.
LiJ, LiY, SongN, et al.Risk factors for carbapenem-resistant Klebsiella pneumoniae infection: A meta-analysis. J Glob Antimicrob Resist, 2020; 21:306–313; doi: 10.1016/j.jgar.2019.09.006
50.
TianL, TanR, ChenY, et al.Epidemiology of Klebsiella pneumoniae bloodstream infections in a teaching hospital: Factors related to the carbapenem resistance and patient mortality. Antimicrob Resist Infect Control, 2016; 5:48; doi: 10.1186/s13756-016-0145-0
51.
WyresKL, HoltKE. Klebsiella pneumoniae as a key trafficker of drug resistance genes from environmental to clinically important bacteria. Curr Opin Microbiol, 2018; 45:131–139; doi: 10.1016/j.mib.2018.04.004
52.
ZhuJ, ChenY, YangX. Antibiotic resistance, molecular characteristics and risk factors of carbapenem-resistant Klebsiella pneumoniae in clinical isolates. Infect Drug Resist, 2022; 15:6671–6680; doi: 10.2147/IDR.S383010
53.
HallerS, KramerR, BeckerK, et al.Extensively drug-resistant Klebsiella pneumoniae ST307 outbreak, north-eastern Germany, June to October 2019. Euro Surveill, 2019; 24(50); doi: 10.2807/1560-7917.ES.2019.24.50.1900734
54.
MagiorakosAP, BurnsK, Rodríguez BañoJ, et al.Infection prevention and control measures and tools for the prevention of entry of carbapenem-resistant Enterobacteriaceae into healthcare settings: Guidance from the European Centre for Disease Prevention and Control. Antimicrob Resist Infect Control, 2017; 6:113; doi: 10.1186/s13756-017-0259-z
55.
QinX, WuS, HaoM, et al.The colonization of carbapenem-resistant Klebsiella pneumoniae: Epidemiology, resistance mechanisms, and risk factors in patients admitted to intensive care units in China. J Infect Dis, 2020; 221(Suppl 2):S206–S214; doi: 10.1093/infdis/jiz622
56.
ÇölkesenF, TarakçıA, EroğluE, et al.Carbapenem-resistant Klebsiella pneumoniae infection and its risk factors in older adult patients. Clin Interv Aging, 2023; 18:1037–1045; doi: 10.2147/CIA.S406214
57.
PandaS, DashA, ChhotrayP, et al.Risk factors and clinical outcomes of carbapenem-resistant Klebsiella pneumonia infection in intensive care unit: A retrospective observational study in a tertiary care hospital in Eastern India. Int J Crit Illn Inj Sci, 2022; 12(4):217–221; doi: 10.4103/ijciis.ijciis_34_22
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
