Carbapenem-resistant Klebsiella Pneumoniae Infection Research Articles

Carbapenem-Resistant Klebsiella pneumoniae Bacteremia: Counterbalance between the Endemic Load and the Infection Control Program in a Hospital

Carbapenem-resistant Klebsiella pneumoniae (CRKP) remains a significant public health threat, given the associated increased healthcare burden and mortality rate. The objective of the current study was to investigate the association between the incidence of CRKP bacteremia, antibiotic consumption, and infection control measures in a tertiary-care hospital spanning the years 2013–2018. The analyzed indices included the incidence of CRKP bacteremia, antibiotic consumption, the use of hand hygiene solutions, and isolation rates of multidrug-resistant (MDR) carriers. In the total hospital, the incidence of CRKP bacteremia exhibited an absolute decrease during the study period, although this decrease did not reach statistical significance. Antibiotics used to treat CRKP infections, including carbapenems, colistin, tigecycline, and fosfomycin, as well as all classes of antibiotics, correlated positively with an increased incidence of CRKP bacteremia. On the contrary, increased use of scrub disinfectant solutions correlated negatively with a decreased incidence of CRKP bacteremia (IRR: 0.74, 95%CI: 0.59–0.93, p-value: 0.008) in the Adults ICU. Additionally, increased isolation rates of MDR carrier patients correlated negatively with a decreased incidence of CRKP bacteremia (IRR: 0.35, 95%CI: 0.13–0.97, p-value: 0.044). In conclusion, the implementation of multimodal infection control measures in our hospital contributed to the containment of CRKP, particularly in specific hospital sectors. However, the study suggests the need for additional strategies to overcome the endemic plateau.

Enhancing resistance, but not virulence attributed to the high mortality caused by carbapenem-resistant Klebsiella pneumoniae

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a global threat due to its high mortality in clinical patients. However, the specific mechanisms underlying this increased mortality remain unclear. The objective of this study is to investigate how the development of a resistance phenotype contributes to the significantly higher mortality associated with this pathogen. To achieve this, a collection of isogeneic strains was generated. The clinical carbapenem-susceptible K. pneumoniae (CSKP) strain HKU3 served as the control isolate, while HKU3-KPC was created through conjugation with a blaKPC-2-bearing plasmid and served as clinical CRKP strain. Using a sepsis model, it was demonstrated that both HKU3 and HKU3-KPC exhibited similar levels of virulence. Flow cytometry, RNA-seq, and ELISA analysis were employed to assess immune cell response, M1 macrophage polarization, and cytokine storm induction, revealing that both strains elicited comparable types and levels of these immune responses. Subsequently, meropenem was utilized to treat K. pneumoniae infection, and it was found that meropenem effectively reduced bacterial load, inhibited M1 macrophage polarization, and suppressed serum cytokine production during HKU3 (CSKP) infection. However, these effects were not observed in the case of HKU3-KPC (CRKP) infection. These findings provide evidence that the high mortality associated with CRKP is attributed to its enhanced survival within the host during antibiotic treatment, resulting in a cytokine storm and subsequent host death. The development of an effective therapy for CRKP infections could significantly reduce the mortality caused by this pathogen.

Klebsiella pneumoniae infections after liver transplantation: Drug resistance and distribution of pathogens, risk factors, and influence on outcomes.

Liver transplantation (LT) is the only curative treatment for end-stage liver disease. However, LT recipients are susceptible to infection, which is the leading cause of early mortality after LT. Klebsiella pneumoniae infections (KPIs) in the bloodstream are common in LT recipients. We hypothesized that KPIs and carbapenem-resistant Klebsiella pneumoniae (CRKP) infections may affect the outcomes of LT recipients. To assess KPI incidence, timing, distribution, drug resistance, and risk factors following LT and its association with outcomes. This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University, a tertiary hospital, from January 2015 to January 2023. We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis. KPI incidence was 7.9% (n = 32), with lung/thoracic cavity the most frequent site of infection; the median time from LT to KPI onset was 7.5 d. Of 44 Klebsiella pneumoniae isolates, 43 (97.7%) and 34 (77.3%) were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline, respectively; > 70% were resistant to piperacillin/ tazobactam, ceftazidime, cefepime, aztreonam, meropenem, and levofloxacin. Female sex [odds ratio (OR) = 2.827, 95% confidence interval (CI): 1.256-6.364; P = 0.012], pre-LT diabetes (OR = 2.794, 95%CI: 1.070-7.294; P = 0.036), day 1 post-LT alanine aminotransferase (ALT) levels ≥ 1500 U/L (OR = 3.645, 95%CI: 1.671-7.950; P = 0.001), and post-LT urethral catheter duration over 4 d (OR = 2.266, 95%CI: 1.016-5.054; P = 0.046) were risk factors for KPI. CRKP infections, but not KPIs, were risk factors for 6-month all-cause mortality post-LT. KPIs occur frequently and rapidly after LT. Risk factors include female sex, pre-LT diabetes, increased post-LT ALT levels, and urethral catheter duration. CRKP infections, and not KPIs, affect mortality.

Intestinal carbapenem-resistant Klebsiella pneumoniae undergoes complex transcriptional reprogramming following immune activation

ABSTRACT Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is a significant threat to public health worldwide. The primary reservoir for CR-Kp is the intestinal tract. There, 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, yet it may be relevant to devise strategies to tackle CR-Kp colonization and infection. Here, we adopted an in vivo model 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, treatment increased the concentration of oxidative species and amino acids in the mouse intestine. Genes encoding for proteins containing the domain of unknown function (DUF) 1471 were strongly upregulated, however their deletion did not impair CR-Kp fitness in vivo upon 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, although 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 toward bacterial fitness warrants further investigation. Additional analyses utilizing this model may identify key factors to tackle CR-Kp colonization of the intestine.

Dehydrozaluzanin C- derivative protects septic mice by alleviating over-activated inflammatory response and promoting the phagocytosis of macrophages

Host-directed therapy (HDT) is a new adjuvant strategy that interfere with host cell factors that are required by a pathogen for replication or persistence. In this study, we assessed the effect of dehydrozaluzanin C-derivative (DHZD), a modified compound from dehydrozaluzanin C (DHZC), as a potential HDT agent for severe infection. LPS-induced septic mouse model and Carbapenem resistant Klebsiella pneumoniae (CRKP) infection mouse model was used for testing in vivo. RAW264.7 cells, mouse primary macrophages, and DCs were used for in vitro experiments. Dexamethasone (DXM) was used as a positive control agent. DHZD ameliorated tissue damage (lung, kidney, and liver) and excessive inflammatory response induced by LPS or CRKP infection in mice. Also, DHZD improved the hypothermic symptoms of acute peritonitis induced by CRKP, inhibited heat-killed CRKP (HK-CRKP)-induced inflammatory response in macrophages, and upregulated the proportions of phagocytic cell types in lungs. In vitro data suggested that DHZD decreases LPS-stimulated expression of IL-6, TNF-α and MCP-1 via PI3K/Akt/p70S6K signaling pathway in macrophages. Interestingly, the combined treatment group of DXM and DHZD had a higher survival rate and lower level of IL-6 than those of the DXM-treated group; the combination of DHZD and DXM played a synergistic role in decreasing IL-6 secretion in sera. Moreover, the phagocytic receptor CD36 was increased by DHZD in macrophages, which was accompanied by increased bacterial phagocytosis in a clathrin- and actin-dependent manner. This data suggests that DHZD may be a potential drug candidate for treating bacterial infections.

Epidemiology and molecular characterization of carbapenem-resistant Klebsiella pneumoniae isolated from neonatal intensive care units in General Hospital of Ningxia Medical University, China, 2017-2021.

This study aimed to retrospectively investigate the epidemiology and molecular characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from neonatal intensive care units (NICU) between 2017 and 2021. The antibacterial susceptibility of all strains was assessed using the VITEK 2 compact system. The presence of antibiotic resistance, virulence genes, sequence types (STs), capsular (K) types, and the wzi genes was determined through polymerase chain reaction (PCR). Molecular typing was performed by pulsed-field gel electrophoresis (PFGE) using the restriction enzyme XbaI. Additionally, the virulence potential of peg344-positive strains was evaluated using the string test and mouse intraperitoneal infection models. Whole-genome sequencing was conducted on the DNB system and PacBio platforms. A total of 46 CRKP isolates were collected during the study period. Out of these, 93.47% (43/46) were identified as CRKP strains belonging to the ST76-K10 type carrying blaNDM-5. It was observed that CRKP infection resulted in more severe clinical symptoms compared to CRKP colonization. Among the CRKP strains, a hypervirulent CRKP strain called KP-63, belonging to the ST23 type, was identified. This strain exhibited high mortality in the mouse infection model and was found to possess virulence genes. Genomic alignment analysis revealed a significant similarity between the virulence plasmid from KP-63 strain (pKP-63) and pK2044 from the hypervirulent K. pneumoniae strain NTUH-2044. There has been a potential dissemination of ST76-K10 type CRKP carrying blaNDM-5 in the NICU at Ningxia Hospital. Neonatal CRKP infection has been found to cause more severe clinical symptoms than colonization. Furthermore, we have discovered a CR-hvKP strain of ST23 with serotype K1, which exhibits a significant resemblance in its virulent plasmid to pK2044. Therefore, it is crucial to enforce effective measures to restrict the spread and hinder the evolution of CRKP within the hospital.

Risk Factors and Outcomes of Community-Acquired Carbapenem-Resistant Klebsiella pneumoniae Infection in Elderly Patients.

The increasing prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections is a global concern. Elderly patients have a diminished immune response and functional reserve, and are thus more vulnerable to bacterial infection. This study aimed to investigate the risk factors and outcomes in elderly patients with community-acquired CRKP infections. We performed a retrospective cohort study in a tertiary medical center between 1 January 2021, and 31 December 2021. All elderly patients who visited the emergency department during this period with culture-positive K. pneumoniae were enrolled, and their baseline demographics, laboratory profiles, management strategies, and outcomes were recorded and analyzed. We identified 528 elderly patients with K. pneumonia infection, and the proportion of patients with CRKP infection was 10.2% (54/528). Recent intensive care unit (ICU) admission and prior carbapenem use are independent risk factors for CRKP infection in elderly patients. Compared to patients with carbapenem-sensitive K. pneumoniae infection, those with CRKP infection had a significantly higher risk of adverse outcomes, including ICU care, respiratory failure, septic shock, and 90-day mortality. CRKP infection was also identified as an independent risk factor for 90-day mortality. Clinicians should be aware of the increasing prevalence of CRKP infections in elderly patients and judiciously choose appropriate antibiotics for these patients.

Efficacy of ceftazidime-avibactam in the treatment of carbapenem-resistant Klebsiella pneumoniae infections: Focus on solid organ transplantation recipients

IntroductionCeftazidime-avibactam (CAZ-AVI) is a new option to treat KPC- and OXA-48 carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. However, clinical evidence is limited regarding its use in treating CRKP infections, especially in solid organ transplantation (SOT) recipients. In this study, we assessed the efficacy of CAZ-AVI in treating CRKP infections in both the general population and the SOT recipients in comparison with other antibiotic regimens. MethodsThis is a single-centre retrospective cohort study of patients admitted between January 1, 2018 and June 30, 2021 with the diagnosis of CRKP infections receiving either CAZ-AVI or other regimens ≥ 72 hours and clinical outcomes were analysed. ResultsOf 200 patients with CRKP infections, 67 received CAZ-AVI, 133 received other regimens, and 50 were SOT recipients. In the SOT cohort, 30 patients received CAZ-AVI, and 20 received other regimens. The overall 30-day mortality was 38% in the SOT cohort. Compared with patients receiving other regimens, CAZ-AVI therapy resulted in lower 30-day mortality (23.3% vs. 60%, P = 0.014) and 90-day mortality (35.7% vs. 86.7%, P = 0.003), higher clinical cure (93.3% vs. 40%, P < 0.001) and microbiological clearance. Similar promising results of CAZ-AVI were also shown in the whole population cohort. Moreover, clinical outcomes of SOT recipients receiving CAZ-AVI were not inferior to those without SOT. ConclusionsCAZ-AVI therapy was associated with better clinical outcomes in CRKP infections in both the general population and SOT recipients. Considering the limitations of the present study, well-conducted RCTs are still warranted to confirm these findings.

High-risk clones of carbapenem resistant Klebsiella pneumoniae recovered from pediatric patients in Southern Brazil.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) exhibit high mortality rates in pediatric patients and usually belong to international high-risk clones. This study aimed to investigate the molecular epidemiology and carbapenem resistance mechanisms of K.pneumoniae isolates recovered from pediatric patients, and correlate them with phenotypical data. Twenty-five CRKP isolates were identified, and antimicrobial susceptibility was assessed using broth microdilution. Carbapenemase production and β-lactamase genes were detected by phenotypic and genotypic tests. Multilocus sequence typing was performed to differentiate the strains and whole-genome sequencing was assessed to characterize a new sequence type. Admission to the intensive care unit and the use of catheters were significantly positive correlates of CRKP infection, and the mortality rate was 36%. Almost all isolates showed multidrug-resistant phenotype, and most frequent resistant gene was blaKPC. We observed the dissemination of ST307 and clones belonging to CG258, which are considered high risk. In pediatric patients, these clones present with high genomic plasticity, favoring adaptation of the KPC and NDM enzymes to healthcare environments.

Understanding blaNDM-1 gene regulation in CRKP infections: toward novel antimicrobial strategies for hospital-acquired pneumonia

BackgroundThe escalating challenge of Carbapenem-resistant Klebsiella pneumoniae (CRKP) in hospital-acquired pneumonia (HAP) is closely linked to the blaNDM-1 gene. This study explores the regulatory mechanisms of blaNDM-1 expression and aims to enhance antibacterial tactics to counteract the spread and infection of resistant bacteria.MethodsKP and CRKP strains were isolated from HAP patients' blood samples. Transcriptomic sequencing (RNA-seq) identified significant upregulation of blaNDM-1 gene expression in CRKP strains. Bioinformatics analysis revealed blaNDM-1 gene involvement in beta-lactam resistance pathways. CRISPR-Cas9 was used to delete the blaNDM-1 gene, restoring sensitivity. In vitro and in vivo experiments demonstrated enhanced efficacy with Imipenem and Thanatin or Subatan combination therapy.ResultsKP and CRKP strains were isolated with significant upregulation of blaNDM-1 in CRKP strains identified by RNA-seq. The Beta-lactam resistance pathway was implicated in bioinformatics analysis. Knockout of blaNDM-1 reinstated sensitivity in CRKP strains. Further, co-treatment with Imipenem, Thanatin, or Subactam markedly improved antimicrobial effectiveness.ConclusionSilencing blaNDM-1 in CRKP strains from HAP patients weakens their Carbapenem resistance and optimizes antibacterial strategies. These results provide new theoretical insights and practical methods for treating resistant bacterial infections.

Carbapenemase-Producing Klebsiella pneumoniae Infections in Diabetic and Nondiabetic Hospitalized Patients.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has recently attracted widespread attention due to its limited treatment options and significant morbidity and mortality rates. This study aimed to examine the relationship between risk factors and antimicrobial resistance in individuals with and without diabetes for the development of carbapenemase-producing K. pneumoniae infections. Between May 2019 and January 2021, a prospective study involving patients with and without diabetes who were infected with K. pneumonia, was carried out in a tertiary care hospital. Six hundred K. pneumoniae isolates were collected from various clinical samples, such as pus/wound samples, urine, respiratory samples, blood, and body fluids. An antimicrobial susceptibility test in K. pneumoniae was performed and compared between diabetics and nondiabetics. Univariate and multivariate logistic regression were used to identify independent risk factors for K. pneumoniae infections in the diabetic group and nondiabetic group separately. Multiplex PCR was used to detect genes that produce carbapenemase. A total of 600 patients were infected with K. pneumoniae, with 300 (50%) being diabetic and 300 (50%) being nondiabetic. We found that diabetics had higher antimicrobial resistance to numerous routinely used drugs for infection than the nondiabetic group. In the multivariate analysis of the variables, it was found that immunosuppressive therapy, prior antibiotic use, mechanical ventilation, and urinary catheter use were all significant risk factors influencing the development of K. pneumoniae infections in diabetic patients. Diabetics had a higher prevalence of carbapenemase-producing K. pneumoniae than nondiabetics. Outcome measures in K. pneumoniae patients revealed that the diabetic group had considerably higher infection-related mortality. We found that CRKP infection was associated with higher resistance to antibiotics in the diabetic group. Furthermore, the diabetic group had a higher prevalence of carbapenemase-producing K. pneumoniae than the nondiabetic group. Crucially, in order to lower mortality without worsening antibiotic resistance and metabolic damage, more focus has to be placed on sensible and efficient antibiotic and supportive care therapies.

Safety and efficacy of a phage cocktail on murine wound infections caused by carbapenem-resistant Klebsiella pneumoniae

ObjectivesCarbapenem-resistant Klebsiella pneumoniae (CRKP) is a leading pathogen causing difficult-to-treat, healthcare-associated wound infections. Phages are an alternative approach against CRKP. This study established murine wound infection models with a CRKP clinical strain of sequence type 11 and capsular type KL64, which is the dominant type in China, carrying genes encoding KPC-2 and NDM-1 carbapenemases. MethodsA cocktail was made comprising three lytic phages of different viral families against the strain. The phage cocktail restricted bacterial growth for 10 hours in vitro. The efficacy and safety of the phage cocktail in treating a murine wound CRKP infection were then evaluated. Mice were randomly assigned into four groups (16 for each) comprising a phage treatment group, infected with bacteria and 30 minutes later with phages, and three control groups administered with PBS (negative control), bacteria (infection control), or phages (phage control) on the wound. Wound tissues were processed for counting bacterial loads on days 1, 3, and 7 post-infection and examined for histopathological change on days 3 and 7. Two remaining mice in each group were monitored for wound healing until day 14. ResultsCompared with the infection control group, the wound bacterial load in the phage treatment group decreased by 4.95 × 102 CFU/g (> 100-fold; P < 0.05) at day 7 post-treatment, and wounds healed on day 10, as opposed to day 14 in the infection control group. No adverse events associated with phages were observed. ConclusionThe phage cocktail significantly reduced the wound bacterial load and promoted wound healing with good safety.

Risk Factors and Predictive Nomogram for Carbapenem-Resistant Klebsiella pneumoniae in Children in a Grade 3 First-Class General Hospital in Central China.

This study determined risk factors for Carbapenem-resistant Klebsiella pneumoniae (CRKP)in children admitted to a grade 3 first-class general hospital and developed an individualized line graph predictive model. The clinical data of 185 children infected with Klebsiella pneumoniae from January 2015 to December 2019 were analyzed retrospectively. Patients were grouped according to carbapenem resistance: CRKP group (50 cases) and CSKP (carbapenem-sensitive Klebsiella pneumoniae) group (135 cases). Risk factors for CRKP in children were screened by logistic regression analysis. The predictive model was established using R software and validated using the Bootstrap method. Age (odds ratio [OR]=0.104, 95% confidence interval [CI]: 0.026-0.408), intensive care unit admission (OR =2.829, 95% CI: 1.138-7.030), mechanical ventilation (OR =7.510, 95% CI: 3.140-17.961), surgery history (OR =5.005, 95% CI: 1.507-16.618) and glucocorticoid (OR =0.235, 95% CI: 0.099-0.557) were independent risk factors for CRKP in children (P < 0.05), The total risk score of each factor was 362.5, and the risk rate was 0.1-0.9. In receiver-operating characteristic curve analysis, the area under the curve of CRKP predicted by the total risk score was 0.872 (95% CI=0.844-0.901; P < 0.001). The correction curve indicated that the consistency between the observed value and the predicted value was good. This study successfully established a model based on the risk factors, with high accuracy and good predictive value for CRKP in children. Hospitals should take necessary preventive measures against the risk factors for drug-resistant bacteria, such as optimizing the configuration of ICU space, timely isolation of infected children, and adequate disinfection of ICU equipment. Which may reduce CRKP infection rate.

Risk factors in ICU patients with initial acquisition of carbapenemase-resistant Klebsiella Pneumoniae.

OBJECTIVE: To identify the risk factors associated with antimicrobial use on the initial acquisition of carbapenem-resistant Klebsiella pneumoniae (CRKP) in elderly intensive care unit (ICU) patients.METHODS: Respiratory secretion, blood, urine, anal swab and peritoneal drainage samples from all elderly patients with non-colonised CRKP who had been hospitalised from January 2021 to December 2022 were collected, and screened for CRKP colonisation using surveillance culture at the time of the first ICU admission and weekly thereafter in Zhejiang Provincial Hospital of Chinese Medicine, Zhejiang, China. Cumulative antibiotic variables included duration of antibiotic use, total amount of antimicrobials received in grams, total antibiotic consumption (defined daily dose) and the types of antimicrobial exposure. A time-dependent model based on Cox regression analysis was used to investigate the effect of each variable on the initial acquisition of CRKP infection or colonisation.RESULTS: Of 214 patients, 44 were infected or had CRKP colonies and death rate was 34.1%. males were the risk factor for acquiring CRKP in culture (HR 2.12, 95% CI 1.06-4.21; P = 0.033). It is notable that the hazard of acquiring CRKP increased by 9% with every single-point increase in the APACHE II score (HR 1.09, 95% CI 1.01-1.18; P = 0.025). The hazard of acquiring CRKP doubled when carbapenems were administered (HR 1.81, 95% CI 1.42-2.30; P < 0.001), In contrast, exposure to quinolone antimicrobials had a smaller effect on acquiring CRKP (HR 1.07; 95% CI 1.01-1.14; P = 0.024).CONCLUSION: This study found that male sex, APACHE II score and exposure to quinolones and carbapenems were independent risk factors for acquiring CRKP.

A critical role of outer membrane vesicles in antibiotic resistance in carbapenem-resistant Klebsiella pneumoniae

BackgroundThis study aimed to illustrate the status of carbapenem-resistant Enterobacterales (CRE) infections in a Chinese tertiary hospital and to investigate the role of outer membrane vesicles (OMVs) in antibiotic resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP).MethodsThe data of CRE infections was collected from laboratory records, and the CRE isolates from two distinct periods (2015/07 to 2017/07 and 2020/04 to 2021/04) were enrolled to detect the carbapenemase genes by polymerase chain reaction (PCR). Multilocus sequence typing (MLST) was used to analyze the molecular characterization of CRKP. The conjugation assay was performed to verify the transmission of the antibiotic resistance plasmid. The OMVs of CRKP were isolated with a method combining an electrophoretic technique with a 300 kDa cut-off dialysis bag. The protein components in CRKP OMVs were analyzed by liquid chromatography tandem-mass spectrometry (LC–MS/MS), and the meropenem-hydrolyzing bioactivity of KPC in CRKP OMVs was determined with different treatments in vitro.ResultsA total of 178 CRE isolates, including 100 isolates from 2015/07 to 2017/07 and 78 isolates from 2020/04 to 2021/04, were collected for the detection of carbapenemase genes. We found that the carbapenemase gene blaKPC was the most prevalent, followed by blaNDM. By MLST, we found that sequence type (ST) 11 CRKP (96.1%) was the leading type during 2015/07 to 2017/07 and that the ST15 CRKP increased to 46.2% in the late period of 2020/04 to 2021/04. The diameters of Klebsiella pneumoniae OMVs ranged from 100 to 200 nm, and by proteomics analysis the most proteins from OMVs belonged to the “enzyme” group. The KPC enzyme was found in the OMVs from CRKP, and the OMVs could protect inside KPC from proteinase K digestion. Moreover, the KPC enzymes within OMVs, which could be released after Triton X-100 treatment, could hydrolyze meropenem.ConclusionsCRE has increasingly caused infections in hospitals, and blaKPC-positive CRKP infections have constituted a major proportion of infections in the past decade. The OMVs play a critical role in antibiotic resistance in CRKP.

Analysis of Risk Factors for Carbapenem Resistant Klebsiella pneumoniae Infection and Construction of Nomogram Model: A Large Case-Control and Cohort Study from Shanxi, China.

Healthcare-associated infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are now a global public health problem, increasing the burden of disease and public healthcare expenditures in various countries. The aim of this study was to analyse the risk factors for CRKP infections and to develop nomogram models to help clinicians predict CRKP infections at an early stage to facilitate diagnosis and treatment. The clinical data of patients with Klebsiella pneumoniae (KP) infections in our hospital from January 2018 to January 2023 were collected. 174 patients with CRKP infections and 219 patients with CSKP infections were selected for case-control study. 27 predictors related to CRKP infections were determined. The least absolute shrinkage and selection operator (Lasso) regression was used to screen the characteristic variables, Multivariate logistic regression analysis was performed on the selected variables and a nomogram model was established. The discrimination and calibration of the nomogram model were evaluated by receiver operator curves (ROC) and calibration curves. Six predictive factors of ICU stay, fever time, central venous catheterization time, catheter indwelling time, carbapenem use and tetracycline use screened by lasso regression were included in the logistic regression model, and the nomogram was drawn to visualize the results. The area under ROC curve of training set and validation set was 0.894 (95% CI: 0.857, 0.931) and 0.872 (95% CI: 0.805, 0.939); The results of decision curve analysis also show that the model has good prediction accuracy. This study established a nomogram to predict CRKP infection based on lasso-logistic regression model, which has certain guiding significance for early diagnosis of CRKP infections.

Shift in the dominant sequence type of carbapenem-resistant Klebsiella pneumonia infection from ST278-NDM-1 to ST11-KPC-2 in neonatal patients in a children's hospital in Shanghai, China, 2017-2021.

To investigate the clinical characteristics and molecular epidemiology of CRKP infection in neonatal patients in a children's hospital in China from 2017 to 2021. Species identification and antibiotic susceptibilities were tested with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and VITEK 2 systems. The clinical data were collected from medical records. Carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates were investigated by antimicrobial susceptibility testing, carbapenemase genes and multilocus sequence typing. Six kinds of resistant genes and 23 STs were detected. BlaNDM-1 (n=83, 55.3%) was the predominant carbapenemase gene, followed by blaKPC-2 (n=45, 30.0%), blaNDM-5 (n=7, 4.7%), blaIMP-38 (n=6, 4.0%). BlaNDM-1 was predominant in 2017 and 2018, whereas blaKPC-2 increased in 2019 and became the predominant gene from 2020 to 2021. ST11 accounted for most infections (n=35, 23.3%), followed by ST278 (n=23, 15.3%), ST17 (n=17, 11. 3%) and ST2735 (n=16, 10.7%). ST278 and ST17 were predominant in 2017 and 2018, whereas ST11 increased in 2019 and became the predominant sequence type from 2020 to 2021. Compared with blaNDM-1, the CRKP strains producing blaKPC-2 were characterized by high resistance to gentamicin, amikacin and levofloxacin and the change trend of drug resistance rate before and after COVID-19 was consistent with that of blaNDM-1 and blaKPC-2. The main sequence type of CRKP infection changed dynamically from ST278-NDM-1 to ST11-KPC-2 during the years 2017-2021 in the newborns. Antibiotic exposure and the prevalence of COVID-19 since 2020 may have led to changes in hospital population and lead to the changes.

OXA-48 Dominance Meets Ceftazidime-Avibactam: A Battle Against Life-Threatening Carbapenem-Resistant Klebsiella pneumoniae Infections in the Intensive Care Unit.

Objective In this study, we aimed to describe the outcomes in ICU patients with bloodstream infection (BSI) or ventilatory-associated pneumonia (VAP) due to carbapenem-resistant Klebsiella pneumoniae (CRKP) who received ceftazidime-avibactam treatment at a tertiary care university hospital. Methods Patients aged 18 years or older who were admitted to the Anesthesiology and Reanimation ICU at Bursa Uludag University Faculty of Medicine Hospital between June 13, 2021, and July 16, 2023, and diagnosed with BSI or VAP due to CRKPwere included in this study. Results A total of 42 patients treated with ceftazidime-avibactam were included. Total crude mortality rates were 33.3% on day 14 and 54.8% on day 30. Mortality rates on the 14th and 30th days were 37.5% and 62.5% in patients with BSI and 27.8% and 44.4% in patients with VAP, respectively. There was no statistically significant difference between monotherapy and combination therapy in terms of mortality rates on days 14 and 30, respectively (3/11 vs. 11/31, p=0.620; 5/11 vs. 18/31, p=0.470). Immunosuppression (10/11 vs. 13/31, p=0.005), the Sequential Organ Failure Assessment (SOFA) score ≥8(at the initiation of treatment; 19/25 vs. 4/17, p<0.001), INCREMENT-CPE score ≥10 (12/16 vs. 3/10, p=0.024) and longer duration (in days) from culture collection to treatment initiation (5.0 ± 0.61 vs. 3.11 ± 0.48, p=0.024) were found to have a statistically significant effect on 30-day mortality. In multivariate analysis, a SOFA score≥8at the initiation of treatment (p=0.037, OR: 17.442, 95% CI: 1.187-256.280) was found to be a significant risk factor affecting mortality (30-day). Conclusion The mortality rates of patients with CRKP infection who were followed up in the ICU were found to be high, and it was observed that whether ceftazidime-avibactam treatment was given as a combination or monotherapy did not affect mortality.Further multicentre studies with a larger number of patientsare needed to gain a comprehensive understanding of the topic, given that this treatment is typically reserved for documented infections.

Genomic Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Isolated from Neonatal Patients in Southwest China During 2017-2021.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is spreading worldwide, becoming a serious threat to public health. The present study aimed to analyze the molecular epidemiology and drug resistance mechanism of CRKP isolated from neonatal patients in Sichuan, Southwest China. CRKP isolates were collected from neonatal patients of West China Second University Hospital from June 2017 to June 2021. Antimicrobial susceptibility testing was performed using broth microdilution. Whole-genome sequencing of all isolates were performed to determine the antimicrobial resistance genes, sequence typing, phylogenetic relationships. In total, 41 nonduplicate CRKP isolates were collected. All isolates were highly resistant to the cephalosporins and carbapenems, however, they were all susceptible to amikacin, tigecycline, ciprofloxacin, and colistin. Various resistance genes were detected, blaNDM-5 (n = 35, 85.4%) was the predominant carbapenemase genes. The most common replicon type was IncX3, which was harbored by 36 (87.8%) isolates, followed by IncFIB (n = 34, 82.9%), and IncFII (n = 32, 78.0%). The 41 CRKP isolates belonged to 8 sequence types (STs) and ST789 (n = 29, all had blaNDM-5) was the dominant sequence type. The study revealed that blaNDM was the most dominant carbapenemase resistance gene. ST789 CRKP strains carrying blaNDM-5 were a tremendous menace to neonates in this hospital. Therefore, effectively implement prevention and control measures need to be taken for the prevention and treatment of CRKP infection in the neonatal ward.

Conjugative plasmids facilitate the transmission of tmexCD2-toprJ2 among carbapenem-resistant Klebsiella pneumoniae

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great threat to global public health. The emergence of tmexCD-toprJ greatly weakened the efficacy of tigecycline in the treatment of CRKP infections. In this study, we did a comprehensive investigation of the prevalence and genomic features of tmexCD-toprJ in clinical CRKP from 2018 to 2020 in Henan province, China. The results demonstrated tmexCD-toprJ was at a low prevalence in CRKP from patients (7/2031, 0.34 %). Among the seven tmexCD-toprJ positive CRKP, KP18-29 that carried tmexCD1-toprJ1, blaNDM-1 and mcr-8.2 was resistant to tigecycline, carbapenem and colistin simultaneously. While, tmexCD2-toprJ2 together with one or two carbapenemase genes were detected in the remaining strains. Four strains (KP18-231, KP18-2110-2, KP19-3023 and KP19-3088) isolated at different times but shared the same sequence type (ST) 2667 exhibited high genomic similarity, indicating the clonal dissemination of CRKP ST2667 co-producing KPC-2 and TMexCD-TOprJ. Notably, conjugative transmission of the IncFrepB(R1701) plasmid co-harboring tmexCD2-toprJ2 and blaKPC-2 among clinical CRKP isolates belonging to different STs (ST2667, ST978 and ST147) revealed further propagation of tmexCD-toprJ among K. pneumoniae. Such IncFrepB(R1701) plasmids pose a substantial threat to public health due to their mobile resistance to both tigecycline and carbapenem. Online data mining showed isolates carried both carbapenemase genes and tmexCD-toprJ were dominantly isolated from humans, and isolates of animal origins usually carried mcr genes and tmexCD-toprJ, suggesting that these critical resistance genes co-existed in diverse niches. Global surveillance of K. pneumoniae co-harboring tmexCD-toprJ and mcr/carbapenemase genes in various settings with a One Health strategy was warranted.