ABSTRACTDespite no carbapenem use in food animals, carbapenem-resistant Klebsiella pneumoniae (CRKP) perseveres within food animals, rising significant concerns regarding public health risks originating from these non-clinical reservoirs. To investigate the potential link between CRKP in food animals and its infections in humans, we conducted a cross-sectional study encompassing human clinical, meat products, and farm animals, in Qingdao city, Shandong province, China. We observed a relatively higher presence of CRKP among hospital inpatients (7.3%) compared to that in the meat products (2.7%) and farm animals (pig, 4.6%; chicken, 0.63%). Multilocus sequence typing and core-genome phylogenetic analyses confirm there is no evidence of farm animals and meat products in the clinical acquisition of K. pneumoniae isolates and carbapenem-resistant genes. However, potential transmission of K. pneumoniae of ST659 and IncX3 plasmid harbouring blaNDM-5 gene from pigs to pork and farm workers was observed. Our findings suggest a limited role of farm animals and meat products in the human clinical acquisition of K. pneumoniae, and the transmission of K. pneumoniae is more common within settings, than between them.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (Cr-Kpn) is becoming a growing public health problem through the failure of adequate treatment. This study\'s objectives are to describe the sources of Cr-Kpn in our hospital over 22 months, associating factors with the outcome of Cr-Kpn-positive patients, especially those with NDM+OXA-48-like (New Delhi Metallo-β-Lactamase and oxacillinase-48), and the effectiveness of the treatments used.
METHODS: A retrospective observational cohort study including all hospitalized patients with Cr-Kpn isolates. We reported data as percentages and identified independent predictors for mortality over hospital time through multivariate analysis.
RESULTS: The main type of carbapenemases identified were NDM+OXA-48-like (49.4%). The statistical analysis identified that diabetes and co-infections with the Gram-negative, non-urinary sites of infection were factors of unfavorable evolution. The Cox regression model identified factors associated with a poor outcome: ICU admission (HR of 2.38), previous medical wards transition (HR of 4.69), and carbapenemase type NDM (HR of 5.98). We did not find the superiority of an antibiotic regimen, especially in the case of NDM+OXA-48-like.
CONCLUSIONS: The increase in the incidence of Cr-Kpn infections, especially with NDM+OXA-48-like pathogens, requires a paradigm shift in both the treatment of infected patients and the control of the spread of these pathogens, which calls for a change in public health policy regarding the use of antibiotics and the pursuit of a One Health approach.

UNASSIGNED: Ceftazidime-avibactam is a treatment option for carbapenem-resistant gram-negative bacilli (CR-GNB) infections. However, the risk factors associated with ceftazidime-avibactam (CAZ-AVI) treatment failure in kidney transplant (KT) recipients and the need for CAZ-AVI-based combination therapy remain unclear.
UNASSIGNED: From June 2019 to December 2023, a retrospective observational study of KT recipients with CR-GNB infection treated with CAZ-AVI was conducted, with the primary outcome being 30-day mortality and secondary outcomes being clinical cure, microbiological cure, and safety. Risk factors for 30-day mortality and clinical failure were also investigated.
UNASSIGNED: A total of 81 KT recipients treated with CAZ-AVI were included in this study. Forty recipients (49.4%) received CAZ-AVI monotherapy, with a 30-day mortality of 22.2%. The clinical cure and microbiological cure rates of CAZ/AVI therapy were 72.8% and 66.7%, respectively. CAZ-AVI alone or in combination with other medications had no effect on clinical cure or 30-day mortality. Multivariate logistic regression analysis revealed that a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio [OR]: 4.517; 95% confidence interval [CI]: 1.397-14.607; P = 0.012) was an independent risk factor for 30-day mortality. Clinical cure was positively associated with the administration of CAZ-AVI within 48 hours of infection onset (OR: 11.009; 95% CI: 1.344-90.197; P=0.025) and negatively associated with higher APACHE II scores (OR: 0.700; 95% CI: 0.555-0.882; P=0.002). Four (4.9%) recipients experienced recurrence within 90 days after the initial infection, 3 (3.7%) recipients experienced CAZ-AVI-related adverse events, and no CAZ-AVI resistance was identified.
UNASSIGNED: CAZ-AVI is an effective medication for treating CR-GNB infections following kidney transplantation, even as monotherapy. Optimization of CAZ/AVI therapy (used within 48 hours of infection onset) is positively associated with potential clinical benefit. Further larger-scale studies are needed to validate these findings.

The main aim of this study was to compare and analyze the effectiveness of treatment regimens using ceftazidime/avibactam (CAZ/AVI) versus fosfomycin plus meropenem (FOS/MER) for managing bloodstream infections (BSI) or ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) in critically ill patients. Between 4 January 2019, and 16 July 2023, adult patients (≥18 years old) diagnosed with BSI or VAP due to culture confirmed CRKP in ICU of a tertiary care hospital were investigated retrospectively. A total of 71 patients were categorized into two groups: 30 patients in CAZ/AVI-based, and 41 patients in FOS/MER-based group. No substantial disparities were found in the total duration of ICU hospitalization, as well as the 14- and 30-day mortality rates, between patients treated with CAZ/AVI-based and FOS/MER-based therapeutic regimens. We consider that our study provides for the first time a comprehensive understanding of treatment outcomes and associated risk factors among patients with CRKP-related infections.

UNASSIGNED: Carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical isolations have rapidly increased in pediatric patients. To investigate a possible health care-associated infections of CRKP in a tertiary pediatric hospital, the circulating clones and carbapenem-resistant pattern between CRKP and carbapenem-resistant Acinetobacter baumannii (CRAB) isolates were compared to classify their epidemiological characteristics. The results will help to identify the epidemic pattern of the CRKP transmission in the hospital.
UNASSIGNED: Ninety-six CRKP and forty-eight CRAB isolates were collected in Kunming Children\'s Hospital from 2019 through 2022. These isolates were genotyped using repetitive extragenic palindromic-PCR (REP-PCR). Carbapenemase phenotypic and genetic characterization were investigated using a disk diffusion test and singleplex PCR, respectively. In addition, these characteristics of the two pathogens were compared.
UNASSIGNED: The rates of CRKP and CRAB ranged from 15.8% to 37.0% at the hospital. Forty-nine and sixteen REP genotypes were identified among the 96 and 48 CRKP and CRAB isolates tested, respectively. The CRKP isolates showed more genetic diversity than the CRAB isolates. Of the 96 CRKP isolates, 69 (72%) produced Class B carbapenemases. However, all 48 CRAB isolates produced Class D carbapenemase or extended-spectrum β-lactamases (ESBL) combined with the downregulation of membrane pore proteins. Furthermore, the carbapenemase genes bla KPC, bla IMP, and bla NDM were detected in CRKP isolates. However, CRAB isolates were all positive for the bla VIM, bla OXA-23, and bla OXA-51 genes.
UNASSIGNED: These CRKP isolates exhibited different biological and genetic characteristics with dynamic changes, suggesting widespread communities. Continuous epidemiological surveillance and multicenter research should be carried out to strengthen the prevention and control of infections.

UNASSIGNED: Carbapenem-Resistant Klebsiella pneumoniae (CRKP) is a significant public health threat, because it is associated with substantial morbidity and mortality. However, the risk factors associated with treatment failure of ceftazidime-avibactam (CAZ-AVI) and the need for CAZ-AVI-based combination remain unclear.
UNASSIGNED: We conducted a retrospective study of critically ill patients (age: > 18 years) diagnosed with CRKP infections and treated with CAZ-AVI for at least 24 h between June 2020 and December 2022 at Henan Provincial People\'s Hospital.
UNASSIGNED: This study included a total of 103 patients who received CAZ-AVI. Of these, 91 (88.3%) patients received the standard dosage of 2.5 g every q8h, while only 20 (19.4%) received monotherapy. The Kaplan-Meier curves showed that the all-cause 30-day mortality was significantly higher among patients who experienced septic shock than those who did not. There was no significant difference in mortality between monotherapy and combination therapy. Dose reduction of CAZ-AVI was associated with a significantly increased mortality rate. Independent risk factors for the 30-day mortality included higher APACHE II score (HR: 1.084, 95% CI: 1.024-1.147, p = 0.005) and lower lymphocyte count (HR: 0.247, 95% CI: 0.093-0.655, p = 0.005). Conversely, a combination therapy regimen containing carbapenems was associated with lower mortality (HR: 0.273, 95% CI: 0.086-0.869, p = 0.028).
UNASSIGNED: Our study suggests that CAZ-AVI provides clinical benefits in terms of survival and clinical response in critically ill patients with CRKP infection. A higher APACHE II score and lower lymphocyte count were associated with 30-day mortality, while the combination therapy regimen containing carbapenems was the only protective factor. CAZ-AVI dose reduction was associated with an increased mortality rate. Futher large-scale studies are needed to validate these findings.

OBJECTIVE: To determine the effect of Wen Run Fei Ning formula (WRFNF) intervention in class I integron-mediated carbapenem-resistant Klebsiella pneumoniae.
METHODS: A drug-susceptibility test and PCR amplification were used to screen for carbapenem-resistant K. pneumoniae containing class I integrons. Following nasal drip and tail vein injection to infect healthy male rats with carbapenem-resistant K. pneumoniae, three models were created: control (group A); model (group B, tail vein injection); and model-WRFNF treatment group (group C, by tail vein injection). Rats in Group C were gavaged with pre-warmed WRFNF extract. On the third, fifth, and seventh days after the experiment, the rats in groups A and B were gavaged with an equal quantity of saline and killed in batches.
RESULTS: Group C showed considerably higher serum IL-6 and TNF- levels on days 3, 5, and 7 compared to group A, as well as a significant increase in peripheral blood leukocyte count and a histopathologic inflammatory cell infiltration of the lungs. As the WRFNF delivery duration was prolonged, group C\'s histopathologic inflammatory cell infiltration gradually improved in contrast to group B, with the biggest improvement occurring on day 7. Compared to group B, group C\'s serum IL-6 and TNF- levels were lower. When the trial\'s duration was increased to 7 days, the levels of IL-6 and TNF- in group C decreased on day 7 compared to on day 5.
CONCLUSIONS: WRFNF decreased inflammatory cell infiltration as well as IL-6 and TNF expression in the lung of the rats infected with carbapenem-resistant K. pneumoniae.

BACKGROUND: This study aimed to evaluate the different efficacies between monotherapy and combination therapy with ceftazidime/avibactam (CAZ/AVI) in treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infection.
METHODS: We retrospectively analyzed observational multicenter data from 38 hospitals in China. Multivariate regression analysis was used to explore the association between combination therapy with CAZ/AVI and in-hospital mortality. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to validate our findings.
RESULTS: A total of 132 eligible patients were divided into CAZ/AVI combination therapy (n = 43) and monotherapy (n = 89) cohorts. Multivariate logistic regression showed that there was no statistically significant relationship between combination therapy and a lower risk of in-hospital mortality [odds ratio (OR) 0.907, 95% confidence interval (CI) 0.329-2.498, p = 0.850]. In the subgroup of critical patients who were in the intensive care unit (ICU) (OR 0.943, 95% CI 0.221-4.033, p = 0.937) or with sequential organ failure assessment (SOFA) ≥ 3 (OR 0.733, 95% CI 0.191-2.808, p = 0.650), CAZ/AVI combination therapy was not a lower risk factor for in-hospital mortality. Moreover, in the subgroup of patients using CAZ/AVI plus tigecycline (accounting for 46.5% in the combination therapy) compared with CAZ/AVI monotherapy, there was no statistical difference between the two groups in in-hospital mortality, nor in the subgroup of patients with CRKP-associated pneumonia.
CONCLUSIONS: Combination therapy (or CAZ/AVI combined with tigecycline) and monotherapy with CAZ/AVI had similar prognoses in patients with only CRKP infection (or CRKP-associated pneumonia), as well as in critically ill patients. Larger randomized controlled trials are warranted to confirm these findings.

UNASSIGNED: Carbapenem-resistant Klebsiella pneumoniae (CRKP) have been extensively disseminated worldwide, resulting in increased mortality. We performed a retrospective analysis of the epidemiology and risk factors for the outcome of CRKP infection in a general teaching hospital in China.
UNASSIGNED: A molecular and clinical study was conducted for 98 CRKP in a tertiary hospital from January 2013 to December 2016. Carbapenemase gene detection, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) were performed. Logistic regression was also used to identify the risk factors associated with 30-day mortality.
UNASSIGNED: The production of KPC carbapenemase was the main resistant mechanism, and KPC carbapenemase increased annually with a significant difference. However, the molecular outcome revealed the dominance and diversity in CRKP with 24 sequence types (STs) and 59 PFGE types (PTs). The ST11 CRKP strains, which showed a significant increasing trend year by year, were documented as predominant in our study. Additionally, the predominant ST11 CRKP corresponding to PT10 and PT15 continued to exhibit their characteristic patterns. Importantly, the newly identified PT09 and PT16 strains, corresponding to the ST11 lineage, were only discovered in 2016. Meanwhile, factors affecting 30-day mortality and ST11 proportionality with CRKP infection were assessed, and ST11, appropriate empirical treatment, and hospital stays were found to be independently associated with 30-day mortality.
UNASSIGNED: The ST11 CRKP strains played a dominant role in the process; however, the homology of these strains was polymorphic, and the advantage clusters were subject to changes through evolution. Furthermore, in addition to appropriate empirical treatment and hospital stays, ST11 CRKP was independently associated with 30-day mortality. To the best of our knowledge, this association was reported for the first time.

The emergence of carbapenem-resistant Klebsiella pneumoniae poses a significant threat to public health. In this study, we aimed to investigate the distribution and genetic diversity of plasmids carrying beta-lactamase resistance determinants in a collection of carbapenem-resistant K. pneumoniae blood isolates. Blood isolates of carbapenem-resistant K. pneumoniae bacteremia were collected and identified. Whole-genome sequencing, assembly and analysis were performed for the prediction of antimicrobial resistance determinants. Plasmidome analysis was also performed. Our plasmidome analysis revealed two major plasmid groups, IncFII/IncR and IncC, as key players in the dissemination of carbapenem resistance among carbapenem-resistant K. pneumoniae. Notably, plasmids within the same group exhibited conservation of encapsulated genes, suggesting that these plasmid groups may serve as conservative carriers of carbapenem-resistant determinants. Additionally, we investigated the evolution and expansion of IS26 integrons in carbapenem-resistant K. pneumoniae isolates using long-read sequencing. Our findings revealed the evolution and expansion of IS26 structure, which may have contributed to the development of carbapenem resistance in these strains. Our findings indicate that IncC group plasmids are associated with the endemic occurrence of carbapenem-resistant K. pneumoniae, highlighting the need for targeted interventions to control its spread. Although our study focuses on the endemic presence of carbapenem-resistant K. pneumoniae, it is important to note that carbapenem-resistant K. pneumoniae is indeed a global problem, with cases reported in multiple regions worldwide. Further research is necessary to better understand the factors driving the worldwide dissemination of carbapenem-resistant K. pneumoniae and to develop effective strategies for its prevention and control.