Modeling of the transmission dynamics of carbapenem resistant Klebsiella pneumoniae in hospitals and design of control strategies

Author(s):  
Suttikiat Changruenngam ◽  
Charin Modchang ◽  
Dominique J. Bicout

Abstract Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a major threat to global public health. Epidemiological and infection controls associated with CRKP are very challenging owing to several potential elements involved in a complicated cycle of transmission. Here, we proposed a comprehensive mathematical model to investigate the transmission dynamics of CRKP, determine factors affecting the prevalence, and evaluate the impact of interventions on the transmission. The model includes the essential compartments, which are uncolonized, asymptomatic colonized, symptomatic colonized, and relapsed patients. Moreover, the symptomatic colonized and relapsed patients are further classified into subpopulations according to their number of treatment failures or relapses. We found that the admission of colonized patients and the use of antibiotics have a significant influence on the endemic transmission. The proposed treatment efficacy, which is defined as a combination of the treatment duration and the probability of successful treatment, could also describe the effects of antibiotic treatment on the transmission. A high efficacy of the antibiotic treatment could significantly reduce the likelihood of readmission of a patient in the health care unit. In addition, our findings demonstrate that the CRKP transmission with different epidemiological characteristics needs to be controlled with distinct interventions.

2021 ◽  
Vol 12 ◽  
Author(s):  
Yingying Kong ◽  
Qingyang Sun ◽  
Hangfei Chen ◽  
Mohamed S. Draz ◽  
Xinyou Xie ◽  
...  

The presence and dissemination of carbapenem-resistant Klebsiella pneumoniae (CRKP) often cause life-threatening infections worldwide, but the therapeutic option is limited. In this study, whole-genome sequencing (WGS) was applied to assess the epidemiological characteristics and transmission dynamics of CRKP isolates recovered from two fetal outbreaks of nosocomial infections. Between April 2016 and March 2018, a total of 70 isolates of K. pneumoniae were collected from sterile samples in a tertiary hospital in Hangzhou, China. The minimal inhibitory concentrations (MICs) of 21 antimicrobial agents were determined using the broth microdilution methods. Pulsed-field gel electrophoresis (PFGE) was performed on 47 CRKP isolates, and 16 clonally related isolates were further characterized by Illumina sequencing. In addition, the complete genome sequences of three representative isolates (KP12, KP36, and KP37) were determined by Oxford Nanopore sequencing. The K. pneumoniae isolates were recovered from patients diagnosed with pulmonary infection, cancer, or encephalopathy. For all CRKP isolates, PFGE separated three clusters among all strains. The most predominant PFGE cluster contained 16 isolates collected from patients who shared close hospital units and represented a potential outbreak. All 16 isolates showed an extremely high resistance level (≥87.5%) to 18 antimicrobials tested but remain susceptible to colistin (CST). Multiple antimicrobial resistance and virulence determinants, such as the carbapenem resistance gene blaKPC-2, and genes encoding the virulence factor aerobactin and the regulator of the mucoid phenotype (rmpA and rmpA2), were observed in the 16 CRKP isolates. These isolates belonged to sequence type 11 (ST11) and capsular serotype KL64. A core genome single nucleotide polymorphism (cgSNP)-based phylogenetic analysis indicated that the 16 CRKP isolates could be partitioned into two separate clades (≤15 SNPs), suggesting the two independent transmission scenarios co-occurred. Moreover, a high prevalence of IncFIB/IncHI1B type virulence plasmid with the iroBCDN locus deleted, and an IncFII/IncR type blaKPC-2-bearing plasmid was co-harbored in ST11-KL64 CRKP isolates. In conclusion, our data indicated that the nosocomial dissemination of ST11-KL64 CRKP clone is a potential threat to anti-infective therapy. The development of novel strategies for surveillance, diagnosis, and treatment of this high-risk CRKP clone is urgently needed.


2021 ◽  
Vol 0 (0) ◽  
pp. 0
Author(s):  
Shunxiang Huang ◽  
Lin Wu ◽  
Jing Li ◽  
Ming-Zhen Xin ◽  
Yingying Wang ◽  
...  

<p style='text-indent:20px;'>Coronavirus disease 2019 (COVID-19) has rapidly spread around the world since the early 2020. Recently, a second wave of COVID-19 has resurged in many countries. The transmission dynamics and infectiousness of the COVID-19 pandemic remain unclear, and developing strategies to mitigate the severity of the pandemic is a top priority for global public health. According to the infection mechanism of COVID-19, a novel susceptible-asymptomatic-symptomatic-recovered (SASR) model with control variables in a patchy environment was proposed not only to consider the key characteristics of asymptomatic infection and the effects of seasonal variation but also to incorporate different control measures for multiple transmission routes. The basic reproduction number <inline-formula><tex-math id="M1">\begin{document}$ R_{0} $\end{document}</tex-math></inline-formula> was established to describe the spreading behavior in the natural state over a long time horizon, and the natural reproduction number <inline-formula><tex-math id="M2">\begin{document}$ R_{n} $\end{document}</tex-math></inline-formula>, which describes the development trend of the disease during a short time in the future, was defined according to the actual propagation characteristics. In addition, the effective reproduction number <inline-formula><tex-math id="M3">\begin{document}$ R_{e} $\end{document}</tex-math></inline-formula> considering the control strategies was proposed to evaluate the impact of non-pharmaceutical interventions. The results of numerical simulations for COVID-19 cases in Wuhan, China, based on the SASR model indicate that <inline-formula><tex-math id="M4">\begin{document}$ R_{0} $\end{document}</tex-math></inline-formula> was 3.58, <inline-formula><tex-math id="M5">\begin{document}$ R_{n} $\end{document}</tex-math></inline-formula> ranged from 2.37 to 4.91, and <inline-formula><tex-math id="M6">\begin{document}$ R_{e} $\end{document}</tex-math></inline-formula> decreased gradually from 4.83 on December 8, 2019 to 0.31 on March 8, 2020, reaching 1.40 on January 23, 2020, when the lockdown was lifted in Wuhan. We further concluded that the total number of infections, including asymptomatic infections, was approximately 301, 804 as of March 8, 2020, in Wuhan, China. In particular, this article proposes a dynamic method to distinguish the impact of natural factors and human interventions on the development of the pandemic, and provides a theoretical basis for fighting the global COVID-19 pandemic.</p>


Author(s):  
Wan Huang ◽  
Jisheng Zhang ◽  
Lingyi Zeng ◽  
Chengru Yang ◽  
Lining Yin ◽  
...  

BackgroundThis study aimed to determine the molecular characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates in a hospital in western Chongqing, southwestern China.MethodsA total of 127 unique CRKP isolates were collected from the Yongchuan Hospital of Chongqing Medical University, identified using a VITEK-2 compact system, and subjected to microbroth dilution to determine the minimal inhibitory concentration. Enterobacteriaceae intergenic repeat consensus polymerase chain reaction and multilocus sequence typing were used to analyze the homology among the isolates. Genetic information, including resistance and virulence genes, was assessed using polymerase chain reaction. The genomic features of the CRKP carrying gene blaKPC-2 were detected using whole-genome sequencing.ResultsST11 was the dominant sequence type in the homology comparison. The resistance rate to ceftazidime-avibactam in children was much higher than that in adults as was the detection rate of the resistance gene blaNDM (p &lt; 0.0001). Virulence genes such as mrkD (97.6%), uge (96.9%), kpn (96.9%), and fim-H (84.3%) had high detection rates. IncF (57.5%) was the major replicon plasmid detected, and sequencing showed that the CRKP063 genome contained two plasmids. The plasmid carrying blaKPC-2, which mediates carbapenem resistance, was located on the 359,625 base pair plasmid IncFII, together with virulence factors, plasmid replication protein (rep B), stabilizing protein (par A), and type IV secretion system (T4SS) proteins that mediate plasmid conjugation transfer.ConclusionOur study aids in understanding the prevalence of CRKP in this hospital and the significant differences between children and adults, thus providing new ideas for clinical empirical use of antibiotics.


2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Ana M. Rada ◽  
Elsa De La Cadena ◽  
Carlos Agudelo ◽  
Cesar Capataz ◽  
Nataly Orozco ◽  
...  

ABSTRACT Carbapenem-resistant Enterobacterales (CRE) pose a significant threat to global public health. The most important mechanism for carbapenem resistance is the production of carbapenemases. Klebsiella pneumoniae carbapenemase (KPC) represents one of the main carbapenemases worldwide. Complex mechanisms of blaKPC dissemination have been reported in Colombia, a country with a high endemicity of carbapenem resistance. Here, we characterized the dynamics of dissemination of blaKPC gene among CRE infecting and colonizing patients in three hospitals localized in a highly endemic area of Colombia (2013 and 2015). We identified the genomic characteristics of KPC-producing Enterobacterales recovered from patients infected/colonized and reconstructed the dynamics of dissemination of blaKPC-2 using both short and long read sequencing. We found that spread of blaKPC-2 among Enterobacterales in the participating hospitals was due to intra- and interspecies horizontal gene transfer (HGT) mediated by promiscuous plasmids associated with transposable elements that was originated from a multispecies outbreak of KPC-producing Enterobacterales in a neonatal intensive care unit. The plasmids were detected in isolates recovered in other units within the same hospital and nearby hospitals. The gene “epidemic” was driven by IncN-pST15-type plasmids carrying a novel Tn4401b structure and non-Tn4401 elements (NTEKPC) in Klebsiella spp., Escherichia coli, Enterobacter spp., and Citrobacter spp. Of note, mcr-9 was found to coexist with blaKPC-2 in species of the Enterobacter cloacae complex. Our findings suggest that the main mechanism for dissemination of blaKPC-2 is HGT mediated by highly transferable plasmids among species of Enterobacterales in infected/colonized patients, presenting a major challenge for public health interventions in developing countries such as Colombia.


Author(s):  
Sharif Hala ◽  
Chakkiath Paul Antony ◽  
Mohammed Alshehri ◽  
Abdulhakeem O. Althaqafi ◽  
Asim Alsaedi ◽  
...  

Abstract Background Nosocomial infections caused by multi-drug resistant Enterobacteriaceae are a global public health threat that ought to be promptly identified, reported, and addressed accurately. Many carbapenem-resistant Enterobacteriaceae-associated genes have been identified in Saudi Arabia but not the endemic Klebsiella pneumoniae carbapenemases (KPCs), which are encoded by blaKPC-type genes. KPCs are known for their exceptional spreading potential. Methods We collected n = 286 multi-drug resistant (MDR) Klebsiella spp. isolates as part of screening for resistant patterns from a tertiary hospital in Saudi Arabia between 2014 and 2018. Antimicrobial susceptibility testing was carried out using both VITEK II and the broth microdilution of all collected isolates. Detection of resistance-conferring genes was carried out using Illumina whole-genome shotgun sequencing and PacBio SMRT sequencing protocols. Results A Carbapenem-resistant Enterobacteriaceae (CRE) Klebsiella quasipneumoniae subsp. similipneumoniae strain was identified as a novel ST-3510 carrying a blaKPC-2 carbapenemase encoding gene. The isolate, designated as NGKPC-421, was obtained from shotgun Whole Genome Sequencing (WGS) surveillance of 286 MDR Klebsiella spp. clinical isolates. The NGKPC-421 isolate was collected from a septic patient in late 2017 and was initially misidentified as K. pneumoniae. The sequencing and assembly of the NGKPC-421 genome resulted in the identification of a putative ~ 39.4 kb IncX6 plasmid harboring a blaKPC-2 gene, flanked by transposable elements (ISKpn6-blaKPC-2–ISKpn27). Conclusion This is the first identification of a KPC-2-producing CRE in the Gulf region. The impact on this finding is of major concern to the public health in Saudi Arabia, considering that it is the religious epicenter with a continuous mass influx of pilgrims from across the world. Our study strongly highlights the importance of implementing rapid sequencing-based technologies in clinical microbiology for precise taxonomic classification and monitoring of antimicrobial resistance patterns.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jun Li ◽  
Zi-Yan Huang ◽  
Ting Yu ◽  
Xiao-Yan Tao ◽  
Yong-Mei Hu ◽  
...  

Abstract Background The molecular characterization of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) isolates is not well studied. Our goal was to investigate the molecular epidemiology of CR-hvKP strains that were isolated from a Chinese hospital. Results All clinical carbapenem-resistant K. pneumoniae (CR-KP) isolates were collected and identified from patient samples between 2014 and 2017 from a Chinese hospital. The samples were subjected to screening for CR-hvKP by string test and the detection of the aerobactin gene. CR-hvKP isolates were further confirmed through neutrophil phagocytosis and a mice lethality assay. The CR-hvKP isolates were investigated for their capsular genotyping, virulence gene profiles, and the expression of carbapenemase genes by PCR and DNA sequencing. Multilocus sequence type (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to exclude the homology of these isolates. Twenty strains were identified as CR-hvKP. These strains were resistant to imipenem and several other antibiotics, however, most were susceptible to amikacin. Notably, two isolates were not susceptible to tigecycline. Capsular polysaccharide synthesis genotyping revealed that 17 of the 20 CR-hvKP strains belonged to the K2 serotype, while the others belonged to serotypes other than K1, K2, K5, K20, and K57. The strains were found to be positive for 10 types of virulence genes and a variety of these genes coexisted in the same strain. Two carbapenemase genes were identified: blaKPC-2 (13/20) and blaNDM-1 (1/20). PFGE typing revealed eight clusters comprising isolates that belonged to MLST types ST25, ST11 and ST375, respectively. PFGE cluster A was identified as the main cluster, which included 11 isolates that belong to ST25 and mainly from ICU department. Conclusions Our findings suggest that hospital-acquired infections may contribute in part to the CR-hvKP strains identified in this study. It also suggests that ST25 CR-hvKP strain has a clonal distribution in our hospital. Therefore, effective surveillance and strict infection control strategies should be implemented to prevent outbreak by CR-hvKP strains in hospitals setting.


2008 ◽  
Vol 29 (12) ◽  
pp. 1099-1106 ◽  
Author(s):  
Gopi Patel ◽  
Shirish Huprikar ◽  
Stephanie H. Factor ◽  
Stephen G. Jenkins ◽  
David P. Calfee

Background.Carbapenem-resistant Klebsiella pneumoniae is an emerging healthcare-associated pathogen.Objective.To describe the epidemiology of and clinical outcomes associated with carbapenem-resistant K. pneumoniae infection and to identify risk factors associated with mortality among patients with this type of infection.Setting.Mount Sinai Hospital, a 1,171-bed tertiary care teaching hospital in New York City.Design.Two matched case-control studies.Methods.In the first matched case-control study, case patients with carbapenem-resistant K. pneumoniae infection were compared with control patients with carbapenem-susceptible K. pneumoniae infection. In the second case-control study, patients who survived carbapenem-resistant K. pneumoniae infection were compared with those who did not survive, to identify risk factors associated with mortality among patients with carbapenem-resistant K. pneumoniae infection.Results.There were 99 case patients and 99 control patients identified. Carbapenem-resistant K. pneumoniae infection was independently associated with recent organ or stem-cell transplantation (P = .008), receipt of mechanical ventilation (P = .04), longer length of stay before infection (P = .01), and exposure to cephalosporins (P = .02) and carbapenems (P < .001). Case patients were more likely than control patients to die during hospitalization (48% vs 20%; P < .001) and to die from infection (38% vs 12%; P < .001). Removal of the focus of infection (ie, debridement) was independently associated with patient survival (P = .002). The timely administration of antibiotics with in vitro activity against carbapenem-resistant K. pneumoniae was not associated with patient survival.Conclusions.Carbapenem-resistant K. pneumoniae infection is associated with numerous healthcare-related risk factors and with high mortality. The mortality rate associated with carbapenem-resistant K. pneumoniae infection and the limited antimicrobial options for treatment of carbapenem-resistant K. pneumoniae infection highlight the need for improved detection of carbapenem-resistant K. pneumoniae infection, identification of effective preventive measures, and development of novel agents with reliable clinical efficacy against carbapenem-resistant K. pneumoniae.


Author(s):  
Enea Gino Di Domenico ◽  
Ilaria Cavallo ◽  
Francesca Sivori ◽  
Francesco Marchesi ◽  
Grazia Prignano ◽  
...  

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a prominent cause of nosocomial infections associated with high rates of morbidity and mortality, particularly in oncological patients. The hypermucoviscous (HMV) phenotype and biofilm production are key factors for CRKP colonization and persistence in the host. This study aims at exploring the impact of CRKP virulence factors on morbidity and mortality in oncological patients. A total of 86 CRKP were collected between January 2015 and December 2019. Carbapenem resistance-associated genes, antibiotic susceptibility, the HMV phenotype, and biofilm production were evaluated. The median age of the patients was 71 years (range 40–96 years). Clinically infected patients were 53 (61.6%), while CRKP colonized individuals were 33 (38.4%). The most common infectious manifestations were sepsis (43.4%) and pneumonia (18.9%), while rectal surveillance swabs were the most common site of CRKP isolation (81.8%) in colonized patients. The leading mechanism of carbapenem resistance was sustained by the KPC gene (96.5%), followed by OXA-48 (2.3%) and VIM (1.2%). Phenotypic CRKP characterization indicated that 55.8% of the isolates were strong biofilm-producers equally distributed between infected (54.2%) and colonized (45.8%) patients. The HMV phenotype was found in 22.1% of the isolates, which showed a significant (P&lt;0.0001) decrease in biofilm production as compared to non-HMV strains. The overall mortality rate calculated on the group of infected patients was 35.8%. In univariate analysis, pneumoniae significantly correlated with death (OR 5.09; CI 95% 1.08–24.02; P=0.04). The non-HMV phenotype (OR 4.67; CI 95% 1.13–19.24; P=0.03) and strong biofilm-producing strains (OR 5.04; CI95% 1.39–18.25; P=0.01) were also associated with increased CRKP infection-related mortality. Notably, the multivariate analysis showed that infection with strong biofilm-producing CRKP was an independent predictor of mortality (OR 6.30; CI 95% 1.392–18.248; P=0.004). CRKP infection presents a high risk of death among oncological patients, particularly when pneumoniae and sepsis are present. In infected patients, the presence of strong biofilm-producing CRKP significantly increases the risk of death. Thus, the assessment of biofilm production may provide a key element in supporting the clinical management of high-risk oncological patients with CRKP infection.


PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e41068 ◽  
Author(s):  
Vana Sypsa ◽  
Mina Psichogiou ◽  
Georgia-Aikaterina Bouzala ◽  
Linos Hadjihannas ◽  
Angelos Hatzakis ◽  
...  

2020 ◽  
Author(s):  
Xiaopin Hu ◽  
Guohang Yuan ◽  
Yaoyao Wu ◽  
Weijia Liu ◽  
Xiangyan Zhang ◽  
...  

Abstract Background: We determined epidemiological characteristics and resistance mechanisms of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains found in Southwest China and assessed disease burden to provide evidence-based strategies for control and treatment of CRKP infection. Methods: A total of 159 strains of CRKP were isolated from sputa, blood, urine, ascites and wound secretions from three tertiary hospitals in Southwest China between August 1st, 2018 and December 31st, 2019. The sensitivity of each strain to 12 antibiotic agents was determined by micro-broth dilution. Identification of carbapenemase genes and multi-locus sequence typing (MLST) were performed using polymerase chain reaction (PCR). The disease burdens of patients with CRKP were assessed based on invasive procedures, antibiotic use, laboratory tests and clinical outcomes. Results: Of 159 CRKP strains analyzed, 50.9% were isolated from sputum samples. The percentage of patients who underwent invasive procedures before positive cultures for CRKP were detected was 96.3%. The mortality of blood infection was highest (66.6%) among patients with CRKP infection. All strains were insensitive to carbapenems. The resistance rates to levofloxacin and amikacin were 85.5% and 81.8%, respectively. All CRKP strains produced carbapenemases, with a majority of isolates (81.1%) producing KPC-2. The MICs of strains harbouring both KPC-2 and NDM-1 were higher than those of strains with only KPC-2 or NDM-1. ST11 is the most popular clonotype found in Southwest China. Conclusions: CRKP strains in Southwest China are characterized by strong drug resistance and associated with poor clinical prognoses. It is therefore urgent to both strengthen control measures and improve prevention awareness.


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