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Molecular Epidemiology and Drug Resistant Mechanism of Carbapenem-Resistant Klebsiella pneumoniae in Elderly Patients With Lower Respiratory Tract Infection.

ABSTRACT: Infection by carbapenem-resistant Klebsiella pneumoniae (CRKp) hampers the treatment of elderly patients with lower respiratory tract infection (LRTI); however, relevant data with respect to the characteristics of CRKp in elderly patients with LRTIs are limited. In the present study, K. pneumoniae isolated from elderly patients with LRTIs was collected and identified by VITEK-MS. VITEK 2 compact was used for drug sensitivity test to screen CRKps, and broth dilution method was used for drug sensitivity of tigecycline and colistin. The resistance genes, virulence genes, and serotypes of CRKps were detected via polymerase chain reaction. The homology of CRKps was analyzed via PFGE and MLST. Moreover, plasmid conjugation experiment was carried out to determine the transferability of carbapenem resistance. PCR-based replicon typing (PBRT) and S1 nuclease-PFGE were conducted for plasmid profiling. From January 2019 to August 2019, 258 elderly patients with LRTIs caused by K. pneumoniae were observed; of these, 31 (12.02%) infections were caused by CRKp strains. Majority of the patients were admitted to the intensive care unit and neurosurgery wards. Intracranial hemorrhage and pneumonia were the most common underlying diseases. Furthermore, 29 patients infected by CRKp had been exposed to various antimicrobial drugs before the positive culture. All isolates exhibited high resistance to β-lactam antibiotics. The predominant carbapenem resistance gene was bla _KPC-2, and CRKps carrying bla _KPC-2 were all ST11 type. Two bla _NDM-5 carrying isolates were assigned to ST307 and ST1562, respectively. Conjugative assays revealed that plasmids harboring bla _NDM-5 gene were self-transmissible. Plasmid analysis suggested that two bla _NDM-5 were located on a ~45 kb IncX3 type plasmid. The high incidence of CRKp in elderly patients with LRTIs indicates the urgent need for further surveillance and strict infection control measures.

SUBMITTER: Shao C

PROVIDER: S-EPMC8172620 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Klebsiella pneumoniae is a human gut communal organism and notorious opportunistic pathogen. The relative high burden of asymptomatic colonization by K. pneumoniae is often compounded by multidrug resistance-a potential problem for individuals with significant comorbidities or other risk factors for infection. A carbapenem-resistant K. pneumoniae strain classified as multilocus sequence type 258 (ST258) is widespread in the United States and is usually multidrug resistant. Thus, treatment of ST258 infections is often difficult. Inasmuch as new preventive and/or therapeutic measures are needed for treatment of such infections, we developed an ST258 pneumonia model in cynomolgus macaques and tested the ability of an ST258 capsule polysaccharide type 2 (CPS2) vaccine to moderate disease severity. Compared with sham-vaccinated animals, those vaccinated with ST258 CPS2 had significantly less disease as assessed by radiography 24 h after intrabronchial installation of 108 CFU of ST258. All macaques vaccinated with CPS2 ultimately developed ST258-specific antibodies that significantly enhanced serum bactericidal activity and killing of ST258 by macaque neutrophils ex vivo Consistent with a protective immune response to CPS2, transcripts encoding inflammatory mediators were increased in infected lung tissues obtained from CPS-vaccinated animals compared with control, sham-vaccinated macaques. Taken together, our data provide support for the idea that vaccination with ST258 CPS can be used to prevent or moderate infections caused by ST258. As with studies performed decades earlier, we propose that this prime-boost vaccination approach can be extended to include multiple capsule types.IMPORTANCE Multidrug-resistant bacteria continue to be a major problem worldwide, especially among individuals with significant comorbidities and other risk factors for infection. K. pneumoniae is among the leading causes of health care-associated infections, and the organism is often resistant to multiple classes of antibiotics. A carbapenem-resistant K. pneumoniae strain known as multilocus sequence type 258 (ST258) is the predominant carbapenem-resistant Enterobacteriaceae in the health care setting in the United States. Infections caused by ST258 are often difficult to treat and new prophylactic measures and therapeutic approaches are needed. To that end, we developed a lower respiratory tract infection model in cynomolgus macaques in which to test the ability of ST258 CPS to protect against severe ST258 infection.

Project description:Background: The increasing prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses an immediate threat to treatment worldwide. This retrospective study assessed the molecular epidemiology and determined the risk factors for and outcomes of CRKP infections in a general teaching hospital in Shanghai, China. Methods: From January 2013 to July 2015, 100 consecutive unique CRKP isolates isolated from hospitalized patients were collected. Isolates were screened for antibiotic resistance genes by polymerase chain reaction and molecular typing was performed by pulsed-field gel electrophoresis (PFGE). Patients infected with CRKP comprised the case group and were compared to the control group of patients infected with carbapenem-susceptible Klebsiella pneumoniae. Therapeutic effects were compared in the CRKP infection group. Results: Among the 100 CRKP isolates, the percentages of multidrug-resistant, extensively drug-resistant (XDR), and pandrug-resistant were 50.0, 50.0, and 0%, respectively. All the CRKP isolates produced KPC-2 and could be divided into 18 PFGE clusters (A-O) and 70 subtypes. No dominant intra-hospital PFGE type was detected using a cutoff of 80% similarity. The ratio of CRKP infection to colonization was 51 to 49. Risk factors correlated with CRKP infection included pulmonary disease (p = 0.038), ICU stay (p = 0.002), invasive ventilation (p = 0.009), blood transfusion (p = 0.028), parenteral nutrition (p = 0.004), sputum suction (p = 0.006), medical history of previous hospitalization (p = 0.022), exposure to antibiotics 90 days before infection (p = 0.030), and antibiotic exposure during hospital stay including carbapenems (p = 0.013), enzyme inhibitors (p = 0.021), nitroimidazoles (p = 0.029), and glycopeptides (p = 0.000). Multivariable analysis showed that sputum suction (odds ratio 3.090, 95% confidence intervals 1.004-9.518, p = 0.049) was an independent risk factor for CRKP infections. Patients infected with CRKP with longer carbapenems treatment course (p = 0.002) showed better outcome. Conclusion: This study showed the severity of CRKP infection in eastern China. Sputum suction was an independent risk factor for CRKP infection. Prolonged duration of treatment with carbapenems benefited the patients infected with CRKP.

Project description:Carbapenem-resistantKlebsiella pneumoniae(CR-Kp) is significant threat to public health worldwide. The primary reservoir for CR-Kp is the intestinal tract, where the bacterium is usually present at low density, but can bloom following antibiotic treatment, mostly in hospital settings. The impact of disturbances in the intestinal environment on the fitness, survival, expansion, and drug susceptibility of this pathogen is not well-understood. Nevertheless, gaining such knowledge could lead to innovative intervention strategies for addressing colonization and infection. Here, we adopted anin vivomodel to examine the transcriptional adaptation of a CR-Kp clinical isolate to immune activation in the intestine. We report that as early as 6 hours following host treatment with anti-CD3 antibody, CR-Kp underwent rapid transcriptional changes including downregulation of genes involved in sugar utilization and amino acid biosynthesis, and upregulation of genes involved in amino acid uptake and catabolism, antibiotic resistance, and stress response. In agreement with these findings, the concentration of oxidative species and amino acids was increased in the mouse intestine following treatment. Genes encoding for proteins containing the domain of unknown function (DUF) 1471 were particularly upregulated, however their deletion did not impair CR-Kp fitness in vivoupon immune activation. Transcription factor enrichment analysis identified the global regulator cAMP-Receptor Protein CRP as a potential orchestrator of the observed transcriptional signature. In keeping with the recognized role of CRP in regulating utilization of alternative carbon sources, CRP deletion in CR-Kp resulted in strongly impaired gut colonization, but this effect was not amplified by immune activation. Thus, following intestinal colonization, which occurs in a CRP-dependent manner, CR-Kp can rapidly respond to immune cues by implementing a well-defined and complex transcriptional program whose direct relevance towards bacterial fitness remains cryptic. Further analyses utilizing this model may identify key factors to tackle the intestinal stage of CR-Kp colonization.

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Molecular Epidemiology and Drug Resistant Mechanism of Carbapenem-Resistant Klebsiella pneumoniae in Elderly Patients With Lower Respiratory Tract Infection.

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