Search

Huijuan Yao,1 Jingxian Liu,2 Xueyan Jiang,3 Feng Chen,2 Xiaotong Lu,1 Jian Zhang1 1Department of Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Clinical Laboratory, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Thoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Huijuan YaoXinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, People’s Republic of ChinaEmail yaohuijuan@xinhuamed.com.cnObjective: To evaluate the in-vitro antibacterial activity of drug combinations against carbapenem-resistant Klebsiella pneumoniae (CRKP) and to explore the guiding significance of the combined drug susceptibility results for determining the clinical efficacy in patients with CRKP infection.Methods: Antimicrobial susceptibility testing was performed using the Kirby–Bauer disk diffusion method. The clinical data of CRKP-infected patients and the drug susceptibility results of sample cultures were gathered and retrospectively analyzed.Results: All 16 CRKP patients had underlying diseases, of which the bloodstream infection was the most common one. Intensive care unit admission history, invasive operation history, and poor nutritional status were recorded to be the high-risk factors. The in-vitro drug susceptibility results indicated that CRKP exhibited 100%, 75.0%, and 66.7% susceptibilities to tigecycline, polymyxin, and ceftazidime/avibatan, respectively. In case of two-drug combinations, polymyxin+tigecycline, ceftazidime avibatan+tigecycline or (aztreonam, polymyxin B, fosfomycin), fosfomycin+polymycin, imipenem+tigecycline, and fosfomycin+tigecycline exhibited 100%, 87.5% (81.3%, 75.0%, 75.0%), 68.8%, 68.8%, and 62.5%, respectively, synergistic and/or cumulative antibacterial effects. Three-drug combinations such as imipene+tigecycline+polymyxin, imipenem+fosfomycin+tigecycline, imipenem+fosfomycin+polymyxin, and ceftazidime avibatan+polymyxin+fosfomycin demonstrated 75.0%, 68.8%, 62.5%, and 62.5% synergistic effects, respectively. The clinical efficacy results revealed that the combination of imipenem+tigecycline+fosfomycin showed the best results, followed by meropenem+fosfomycin, imipenem+tigecycline, ceftazidime avibatan, and ceftazidime+amikacin.Conclusion: The combined drug susceptibility results can facilitate guidance of the adjustment of antibacterial drug treatment regimens in patients with CRKP infection. For controlling the CRKP infection, it was found that treatment with carbapenems or ceftazidime avibatan demonstrated better antibacterial activity when combined with tigecycline and/or fosfomycin and/or polymyxin B.Keywords: carbapenem-resistant Klebsiella pneumoniae, infection, combined drug susceptibility, Kirby-Bauer disk diffusion method, clinical effect

Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) has recently aroused increasing attention, especially ST11, the predominant CRKP clone in China. Here, we report a case of hv-CRKP-associated infection and reveal the in-host evolution of its mechanism of resistance to tigecycline and polymyxin under clinical therapy. A total of 11 K. pneumoniae carbapenemase (KPC)-producing CRKP strains were consecutively isolated from a male patient who suffered from continuous and multisite infections. String and antimicrobial susceptibility tests identified seven hypermucoviscous strains and three tigecycline-resistant and four colistin-resistant strains. Galleria mellonella larvae infection model confirmed the hypervirulence. Pulsed-field gel electrophoresis (PFGE) separated three PFGE clusters among all strains, and further Southern blotting detected that blaKPC-2 was located on the same-sized plasmid. Whole-genome sequencing showed that all strains belonged to the hv-CRKP ST11-KL64 clone. Diverse hypervirulence factors and resistance genes were identified. Further sequencing with the Nanopore platform was performed on the CRKP-Urine1 strain, which contained one virulence plasmid (pVi-CRKP-Urine1) and two resistance plasmids (pKPC-CRKP-Urine1 and pqnrS1-CRKP-Urine1). The gene mutations responsible for tigecycline or colistin resistance were then amplified with PCR followed by sequencing, which indicated that mutations of ramR and lon were the potential loci for tigecycline resistance and that the pmrB, phoQ and mgrB genes for colistin resistance. A novel frameshift mutation of lon was identified in the high-level tigecycline-resistant strain (MIC, 128 mg/L). The results indicate that the hypervirulent ST11-KL64 clone is a potential threat to antiinfection treatment and is capable of rapid and diverse evolution of resistance during tigecycline and polymyxin treatment.

Objectives: This meta-analysis was performed to compare polymyxin monotherapy and polymyxin-based combination therapy for carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections. Methods: We conducted searches on MEDLINE, Embase and Cochrane Collaborative database for both observational studies and randomised controlled trials (RCTs) comparing polymyxin monotherapy with polymyxin-based combination therapy in patients with CR-KP infection. The primary outcome was mortality. We divided all included studies into several groups according to different combination-combination and different infection types. The odds ratio (OR) and 95% confidence intervals (CI) were calculated for outcome analysis. Results: Ten studies with 481 patients were included. Polymyxin monotherapy was associated with higher mortality than polymyxin-based combination therapy in treatment of CR-KP bloodstream infections (BSI) (OR 1.93, 95% CI 1.14–3.27, P = 0.01) and ventilator-associated pneumonia (VAP)/hospital-acquired pneumonia (HAP) (OR 3.82, 95% CI 1.15–12.71, P = 0.03). In subgroup analysis of different combinations, mortality was significantly higher with polymyxin monotherapy compared with combination therapy with tigecycline (OR 1.88, 95% CI 1.05–3.37, P = 0.03), or with cabapenem (OR 3.11, 95% CI 1.25–7.74, P = 0.01), but no differences were found in combinations with aminoglycosides (OR 1.29, 95% CI 0.72–2.29, P = 0.38). Three-drug combination therapy including polymyxin was also associated with significant survival benefit (OR 3.86, 95% CI 1.60–9.32, P = 0.003). Conclusions: Polymyxin-based combination therapy provides significant survival benefit in treatment of CR-KP, which appears to be more pronounced when a carbapenem or tigecycline is included in the regimen.

Sequence type 11 (ST11) carbapenem-resistant Klebsiella pneumoniae (CRKP) has become the dominant clone in China. In this review, we trace the prevalence of ST11 CRKP in the China Antimicrobial Surveillance Network (CHINET), the key antimicrobial resistance mechanisms and virulence evolution. The recent emergence of ST11 carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) strains in China due to the acquisition of a pLVPK-like virulence plasmid, which may cause severe infections in relatively healthy individuals that are difficult to treat with current antibiotics, has attracted worldwide attention. There is a very close linkage among IncF plasmids, NTEKPC and ST11 K. pneumoniae in China. Hybrid conjugative virulence plasmids are demonstrated to readily convert a ST11 CRKP strain to a CR-hvKP strain via conjugation. Understanding the molecular evolutionary mechanisms of resistance and virulence-bearing plasmids as well as the prevalence of ST11 CRKP in China allows improved tracking and control of such organisms.

ABSTRACT Carbapenem-resistant Klebsiella pneumoniae (CRKp) is an urgent public health threat. Worldwide dissemination of CRKp has been largely attributed to clonal group (CG) 258. However, recent evidence indicates the global emergence of a CRKp CG307 lineage. Houston, TX, is the first large city in the United States with detected cocirculation of both CRKp CG307 and CG258. We sought to characterize the genomic and clinical factors contributing to the parallel endemic spread of CG258 and CG307. CRKp isolates were collected as part of the prospective, Consortium on Resistance against Carbapenems in Klebsiella and other Enterobacterales 2 (CRACKLE-2) study. Hybrid short-read and long-read genome assemblies were generated from 119 CRKp isolates (95 originated from Houston hospitals). A comprehensive characterization of phylogenies, gene transfer, and plasmid content with pan-genome analysis was performed on all CRKp isolates. Plasmid mating experiments were performed with CG307 and CG258 isolates of interest. Dissection of the accessory genomes suggested independent evolution and limited horizontal gene transfer between CG307 and CG258 lineages. CG307 contained a diverse repertoire of mobile genetic elements, which were shared with other non-CG258 K. pneumoniae isolates. Three unique clades of Houston CG307 isolates clustered distinctly from other global CG307 isolates, indicating potential selective adaptation of particular CG307 lineages to their respective geographical niches. CG307 strains were often isolated from the urine of hospitalized patients, likely serving as important reservoirs for genes encoding carbapenemases and extended-spectrum β-lactamases. Our findings suggest parallel cocirculation of high-risk lineages with potentially divergent evolution. IMPORTANCE The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKp) infections in nosocomial settings remains a public health challenge. High-risk clones such as clonal group 258 (CG258) are particularly concerning due to their association with blaKPC carriage, which can severely complicate antimicrobial treatments. There is a recent emergence of clonal group 307 (CG307) worldwide with little understanding of how this successful clone has been able to adapt while cocirculating with CG258. We provide the first evidence of potentially divergent evolution between CG258 and CG307 with limited sharing of adaptive genes. Houston, TX, is home to the largest medical center in the world, with a large influx of domestic and international patients. Thus, our unique geographical setting, where two pandemic strains of CRKp are circulating, provides an indication of how differential accessory genome content can drive stable, endemic populations of CRKp. Pan-genomic analyses such as these can reveal unique signatures of successful CRKp dissemination, such as the CG307-associated plasmid (pCG307_HTX), and provide invaluable insights into the surveillance of local carbapenem-resistant Enterobacterales (CRE) epidemiology.

The carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) poses a severe therapeutic challenge to global public health, and research on CR-hvKP in older patients remain limited. In this study, we aimed to investigate the clinical and molecular characteristics and risk factors of CR-hvKP infections in older patients. We retrospectively investigated older patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in the intensive care unit (ICU) between January 2020 and December 2020. The clinical data, and microbiological data including antimicrobial susceptibility testing, phenotype experiment and detection of carbapenemases, string test, virulence genes, capsular serotype-specific (cps) genes, and multilocus sequence typing, of the CR-hvKP group defined by the presence of any one of the virulence genes, including rmpA, rmpA2, iucA, iroN, and peg-344 were compared with those of CR-non-hvKP strains. Of the 80 CRKP strains, 51 (63.8%) met the definition of CR-hvKP. The main mechanism of resistance to carbapenems was the presence of the blaKPC−2 gene. Sequence type (ST)11 (81.3%, 65/80) and ST15 (16.3%, 13/80) were the most common STs in CRKP strains. The minimum inhibitory concentration (MIC)50 values of the CR-hvKP group against the six tested antibiotics (ceftazidime, ceftazidime-avibactam, imipenem-avibactam, tigecycline, levofloxacin, and Cefoperazone-Sulbactam) exhibited elevated levels than the CR-non-hvKP group. Ceftazidime and imipenem by combining avibactam (4 μg/mL) significantly decreased the MIC90 values more than 16-fold than ceftazidime and imipenem alone against Klebsiella pneumoniae carbapenemase (KPC)-2-producing K. pneumoniae. Cardiovascular disease [odds ratio (OR) = 11.956] and ST11-K64 (OR = 8.385) appeared to be independent variables associated with CR-hvKP infection by multivariate analysis. In conclusion, higher MICs of the last line antibiotic agents (ceftazidime-avibactam, tigecycline) might be a critical consideration in the clinical management of older patients where the concentration of these toxic antibiotics matters because of underlying comorbidities. Caution regarding KPC-2-producing ST11-K64 CR-hvKP as being new significant “superbugs” is required as they are widespread, and infection control measures should be strengthened to curb further dissemination in nosocomial settings in China.

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) is a useful marker of inflammation. However, the prognostic function of the NLR in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) blood stream infection (BSI) remains largely unknown. The aim of this study was to explore the potential relationship between the NLR and mortality in these patients.MethodsWe performed a retrospective cohort study based on data retrieved from the computerized patient record system in a tertiary hospital from 1 January 2017 to 31 October, 2020. A total of 134 inpatients with CRKP BSI were enrolled in this study, including 54 fatal cases and 80 survival cases, 28 days after the onset of CRKP BSI. A logistic analysis was performed to assess the association between the NLR on the 4th day and 28-day mortality. Multivariate analyses were used to control for the confounders.ResultsThe overall 28-day mortality rate of patients with a CRKP BSI episode was 40.3% (54/134). We conducted a multivariate analysis of the data of 134 patients and found that the NLR on the 4th day [odds ratio (OR) 1.148, 95% confidence interval (CI) 1.076–1.225, p < 0.001] and antibiotic exposure before BSI onset (OR 3.847, 95% CI 1.322–11.196, p = 0.013) were independent risk factors for 28-day mortality of patients with CRKP BSI, while appropriate initial therapy (AIT, OR 0.073, 95% CI 0.017–0.307, p < 0.001) was an independent protective factor. Among patients treated with AITs, the Cox proportional hazards regression analysis revealed a significant difference in prognosis (p = 0.006) between the ceftazidime/avibactam contained (CAZ) group and non CAZ-AVI groups. After dividing the non CAZ-AVI group into the tigecycline (TGC), colistin (COL), and TGC + COL groups, there were no differences between the CAZ-AVI group and the TGC group (p = 0.093), but CAZ-AVI group showed lower 28-day mortality than COL (p = 0.002) and TGC + COL (p = 0.002) groups. Meanwhile, there was no difference in NLR on the 1st day (p = 0.958) of patients in different groups but significant difference in NLR on the 4th day (p = 0.047).ConclusionsThe NLR on the 4th day is a readily available and independent prognostic biomarker for patients with CRKP BSI. This marker may have the potential for use in evaluating the efficacy of different anti-infection therapy strategies at an early stage.

Multidrug-resistant gram-negative bacteria, such as carbapenem and colistin-resistant Klebsiella pneumoniae (ColR-CRKP), represent a major problem for health systems worldwide and have high lethality. This study investigated the genetic relationship, antimicrobial susceptibility profile, and resistance mechanisms to ColR-CRKP isolates from patients infected/colonized in a tertiary hospital in Salvador, Bahia/Brazil. From September 2016 to January 2018, 46 patients (56 ColR-CRKP positive cultures) were enrolled in the investigation but clinical and demographic data were obtained from 31 patients. Most of them were men (67.7%) and elderly (median age of 62 years old), and the median Charlson score was 3. The main comorbidities were systemic arterial hypertension (38.7%), diabetes (32.2%), and cerebrovascular disease (25.8%). The average hospitalization stay until ColR-CRKP identification in days were 35.12. A total of 90.6% used mechanical ventilation and 93.7% used a central venous catheter. Of the 31 patients who had the data evaluated, 12 had ColR-CRKP infection, and seven died (58.4%). Previous use of polymyxins was identified in 32.2% of the cases, and carbapenems were identified in 70.9%. The minimum inhibitory concentration (MIC) for colistin was > 16 μg/mL, with more than half of the isolates (55%) having a MIC of 256 μg/mL. The blaKPC gene was detected in 94.7% of the isolates, blaNDM in 16.0%, and blaGES in 1.7%. The blaOXA–48, blaVIM, and blaIMP genes were not detected. The mcr-1 test was negative in all 56 isolates. Alteration of the mgrB gene was detected in 87.5% (n = 49/56) of the isolates, and of these, 49.0% (24/49) had alteration in size probably due to IS903B, 22.4% (11/49) did not have the mgrB gene detected, 20.4% (10/49) presented the IS903B, 6.1% (3/49) had a premature stop codon (Q30*), and 2.1% (1/49) presented a thymine deletion at position 104 – 104delT (F35fs). The PFGE profile showed a monoclonal profile in 84.7% of the isolates in different hospital sectors, with ST11 (CC-258) being the most frequent sequence type. This study presents a prolonged outbreak of ColR-CRKP in which 83.9% of the isolates belonged to the same cluster, and 67.6% of the patients evaluated had not used polymyxin, suggesting the possibility of cross-transmission of ColR-CRKP isolates.

Purpose: Infection by carbapenem-resistant Klebsiella pneumoniae (CRKP) has high mortality. There is no clear optimal therapeutic choice for pneumonia caused by CRKP. The aim of this study was to compare the clinical outcomes and safety of the standard doses of polymyxin B-based regimens vs tigecycline-based regimens and to identify risk factors for mortality., Methods: This retrospective cohort study included patients with pneumonia caused by CRKP between January 1, 2020 and December 31, 2022. The primary outcomes were 7-day bacterial eradication rate and 14- and 28-day all-cause mortality. The secondary outcome was incidence of acute kidney injury., Results: Seventy-three patients were included in this study, 29 in the polymyxin B-based combination therapy group and 44 in tigecycline-based combination therapy group. There were no significant differences between the two groups in terms of the 7-day bacterial eradication rate (31.03% vs 20.45%, p  = 0.409), the 14-day all-cause mortality (37.93% vs 22.73%, p  = 0.160), and the incidence of acute kidney injury (14.29% vs 6.82%, p  = 0.526). The 28-day all-cause mortality in the polymyxin B-based therapy group was higher than in the tigecycline-based group (75.86% vs 45.45%, p  = 0.010). Binary logistic regression analysis revealed that male and previous use of carbapenems were independent factors associated with 28-day all-cause mortality for patients treated with polymyxin B ( p  < 0.05)., Conclusions: Polymyxin B-based combination therapy at the standard dose should be used with caution for patients with CRKP-induced pneumonia, especially for men who used carbapenems prior to CRKP detection.

ABSTRACT Despite 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 bla NDM-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.

To investigate the epidemiology of ST20 carbapenem-resistant Klebsiella pneumoniae (CRKP) in China, and further explore the genomic characteristics of bla IMP-4 and bla NDM-1 coharboring isolates and plasmid contributions to resistance and fitness. Seven ST20 CRKP isolates were collected nationwide, and antimicrobial susceptibility testing was performed. Antimicrobial resistance genes, virulence genes, and plasmid replicons were identified via whole-genome sequencing, and clonality assessed via core-genome multilocus sequence typing. Furthermore, we found four dual-metallo-β-lactamases (MBL)-harbouring isolates, the gene location was detected by Southern blotting, and plasmid location analysis showed that bla IMP-4 was located on a separate plasmid, a self-conjugative fusion plasmid, or the bacterial chromosome. These isolates were subjected to long-read sequencing, the presence of bla IMP-4 in different locations was identified by genomic comparison, and transposon units were detected via inverse PCR. We subsequently found that bla IMP-4 on the fusion plasmid and bacterial chromosome was formed via intact plasmid recombination by the IS 26 and ltrA , respectively, and the circular transposon unit was related to cointegration, however, bla IMP-4 in different locations did not affect the gene stability. The bla NDM-1 -harbouring plasmid contributed to the increased resistance to β-lactams and shortened survival lag time which was revealed in plasmid cured isolates. In summary, the K. pneumoniae ST20 clone is a high-risk resistant clone. With the use of ceftazidime/avibactam, MBL-positive isolates, especially dual-MBL-harbouring isolates, should be given additional attention.

Background: Prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection with high mortality has attached physicians' attention. High visceral adipose tissue (VAT) and high subcutaneous adipose tissue (SAT) were confirmed by previous studies that were closely related to increased pneumonia severity, more complications, and higher mortality in COVID-19. Thus, we speculate that CT-quantified body composition may also be connected to all-cause mortality and bacterial clearance in patients with CRKP bloodstream infection (BSI).Methods: We investigated the associations of CT-quantified body composition with the mortality of CRKP bloodstream infectious patients. All CT images were obtained at the level of the L3/4 spinal level. The prognostic value of the body composition was analyzed using the Cox regression model, and precise clinical nomograms were established.Results: 72 eligible patients both suffered from CRKP bloodstream infection and performed abdominopelvic CT were included. Factors associated with 30-day all-in hospital mortality included total adipose tissue (TAT) [adjusted hazard ratio (HR) = 1.028, 95% confidence interval (CI), 1.003-1.053; P = 0.025], age [HR = 1.030, 95% CI, 1.000-1.061; P = 0.047] and SOFA scores [HR = 1.138, 95% CI 1.049-1.263; P = 0.002]. Compared with low-VAT, patients with high-VAT show a strikingly poor prognosis in both 30-day all-cause mortality (P = 0.0108, Fig. 2A) and 30-day CRKP BSI mortality (P = 0.0049, Fig. 2C). The results of TAT were similar to VAT.Conclusions: Our study suggested that CT-derived body composition could be a credible and effective alternative to assess the prognosis of patients with BSI owing to CRKP. CT-quantified TAT, age, and SOFA scores were independently associated with 30-day all-cause mortality in these severe infectious patients, while skeletal muscle did not have obvious statistical significance. [ABSTRACT FROM AUTHOR]

Objectives: This work was to investigate the activity and optimal treatments of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections caused by carbapenem resistant Klebsiella pneumoniae (BSIs-CRKP). Methods: A total of 318 nonduplicate BSIs-CRKP isolates were collected from Blood Bacterial Resistant Investigation Collaborative System (BRICS) program. The minimum inhibitory concentration (MIC) of CZA and AZA were determined by agar dilution method. Carbapenemase genes and multilocus sequence typing were amplified by PCR. Monte Carlo simulation (MCS) was conducted to calculate cumulative fraction of response (CFR) of different CZA or AZA administrations. Results: The MIC90 of CZA and AZA were 128/4 and 1/4 mg/L, respectively. There are 87.4 and 3.5% isolates carried bla KPC-2 and bla NDM-1. A total of 68 ST types were identified and 29 novel ST types. ST11 accounted for 66.6%. Further MCS showed CFR of CZA using two-step infusion therapy (rapid first-step 0.5 h infusion and slow second-step 3 h infusion, TSIT) (2.5 g 0.5 h, 3.75 g every 8 h with 3 h infusion and 3.75 g 0.5 h, 2.5 g every 8 h with 3 h infusion) was above 89%. The CFR of AZA with TSIT was above 96%. Conclusion: TSIT with sufficient pharmacokinetic conditions could be useful for enhancing the therapeutic efficacy of CZA and AZA against BSIs-CRKP. [ABSTRACT FROM AUTHOR]

Background: The worldwide outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) has become an urgent public health problem. High mortality and lack of effective treatments further pose new challenges to control this infection. However, studies about the evaluation of available antibiotics for CRKP infection are limited. The present study aimed to compare the efficacy of polymyxin B versus ceftazidime-avibactam (CAZ/AVI) in Chinese patients with CRKP infections and to identify risk factors affecting 7-day bacterial eradication and 28-day all-cause mortality. Methods: From January 8, 2018, to July 6, 2020, a total of 115 adult CRKP infected patients from two tertiary teaching hospitals in Shanghai, China were enrolled based on the inclusion and exclusion criteria. By reviewing electronic medical records of these patients, demographic and clinical data were extracted. The selected patients were divided into polymyxin B and CAZ/AVI groups according to primary antibiotic exposure to compare therapeutic effects. Binary logistic and cox's regression analysis were performed to identify risk factors for 7-day bacterial eradication and all-cause mortality. Results: One hundred and five patients were treated with polymyxin B (67.8%) or CAZ/AVI (32.2%). Patients in the CAZ/AVI group had significantly lower rates of 28-day mortality (8.1 vs 29.5%, p = 0.013), higher microbiological eradication and 28-day clinical success. Multivariate analysis showed that Charlson comorbidity index (≥3) and prior antibiotic use within 90 days were independent risk factors for poor microbiological eradication. Cox's regression analysis indicated that the length of hospitalization after CRKP infection and baseline creatinine clearance negatively affected 28-day mortality. Conclusion: CAZ/AVI was more effective than polymyxin B and appeared to be a promising drug for CRKP infection, especially for critically ill patients. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the present study was to assess the safety profile and outcomes of a ceftazidime–avibactam (CAZ-AVI)-based regimen and compare them with those of a tigecycline (TGC)-based regimen in intensive care unit (ICU) for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP), which is classified into hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). Methods: Clinical and microbiological cure rates, 28-day survival rates, and safety evaluation findings were compared between patients treated with CAZ-AVI-based regimen and those treated with TGC-based regimen in this retrospective study. Conventional multivariate logistic regression analysis and regression adjustment analysis with propensity score (PS) were performed to control for confounding variables. Results: A total of 105 cases of critically ill ICU patients with CRKP-induced HAP or VAP were included in the present study from July 2019 to September 2020; 62 patients (59%) received TGC-based regimen and 43 patients (41%) received CAZ-AVI-based regimen. The most common concomitant agent in the CAZ-AVI group and TGC group was carbapenem (44.2% versus 62.9%, P = 0.058), while only a small proportion of the study population received CAZ-AVI and TGC monotherapy (20.9% versus 6.5%, P = 0.027). The clinical and microbiological cure rates of the CAZ-AVI group were superior to those of the TGC group [51.2% versus 29.0% (P = 0.022) and 74.4% versus 33.9% (P < 0.001), respectively]. No significant differences in the 28-day survival rates were identified between the two groups (69.8% versus 66.1%, P = 0.695). Conventional multivariate logistic regression and PS analyses showed that patients who had used CAZ-AVI were more likely to have achieved a clinical cure [4.767 (95%CI 1.694-13.414), P=0.003;3.405 (95%CI 1.304-8.889), P=0.012] and microbiological success [6.664 (95%CI 2.626-16.915), P<0.001;7.778 (95%CI 2.717-22.265), P<0.001] than patients who used TGC. However, the difference in the 28-day survival rates between the two groups was not significant. According to the safety evaluation findings, the CAZ-AVI group exhibited a generally lower incidence of adverse reactions compared with that in the TGC group. Conclusions: CAZ-AVI may be a suitable alternative for TGC in the treatment of critically ill patients with CRKP-induced HAP or VAP. These observations require further confirmation in larger randomized prospective clinical trials. [ABSTRACT FROM AUTHOR]

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To explore the synergistic effect of ceftazidime/avicarbam combined with aztreonam against carbapenem-resistant isolates of Klebsiella pneumoniae (CRKP). Methods We collected 10 clinical isolates of CRKP from our hospital and determined the minimal inhibitory concentrations of the commonly used antibiotics in these isolates using agar plate double-dilution method. The carbapenemase genes and extended-spectrum β-lactamase genes of the bacteria were amplified by PCR, and the expression of carbapenemase genes was detected by RT-PCR. The bacterial genotypes were analyzed with multilocus sequence typing. The synergistic effect of ceftazidime/avicarbam combined with aztreonam against these CRKP isolates was determined using the checkerboard method. Results The 10 CRKP isolates were all sensitive to tigecycline but highly resistant to all the other antibiotics tested. The β-lactamase genes (NDM, CTX-M and SHV) were widely distributed in these isolates, and the strains with a high resistance to carbapenem also had high expression levels of carbapenemase genes (r=0.805, P=0.029). Four distinct ST genotypes were identified among the CRKP strains, and the genotype ST11 had the highest epidemic potential; NDM gene was present in the strains of 3 different ST genotypes. Ceftazidime/avicarbam combined with aztreonam showed a synergistic inhibitory effect in 7 CRKP strains and produced irrelevant effects in the other 3 strains. Conclusion The high resistance of CRKP strains can be attributed to the resistance genes they carry, and the combination of ceftazidime/avicarbam and aztreonam can produce a strong synergistic inhibitory effect in these strains.carbapenem-

Piaopiao Zhang,1 Jie Wang,2 Hangbin Hu,1 Sheng Zhang,3 Juying Wei,4 Qing Yang,1 Tingting Qu1 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Respiratory Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3Infection Control Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 4Hematological Diseases Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Tingting QuState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79# Qingchun East Road, Hangzhou 310001, People’s Republic of ChinaTel/Fax +86 57187236673Email qutingting@zju.edu.cnPurpose: The aim was to examine the clinical characteristics and risk factors for bloodstream infection (BSI) due to carbapenem-resistant Klebsiella pneumoniae (CRKP) in patients with hematologic malignancies.Materials and Methods: A single-centre, retrospective case–control study representing 734 patients with hematologic malignancies between January 1, 2017, and December 31, 2018, was conducted. Demographic and clinical data were collected from the hospital electronic medical records system.Results: Among the 734 patients with hematologic malignancies, 3% (22/734) of the patients developed CRKP BSI during their hospitalization. Overall 28-day all-cause mortality reached 77.3% (17/22). Patients with Pitt bacteremia score (PBS) > 4, pneumonia and septic shock were more frequent in the non-survivors versus the survivors. Compared with the non-survivors in antimicrobial treatment, combination therapy of tigecycline and polymyxin B was more common in the survivors. The independent risk factors associated with CRKP BSI were CRKP rectal colonization (OR, 11.067; CI=4.43– 27.644; P< 0.001; 3 points), severe neutropenia (OR, 4.095; CI=0.876– 19.141; P=0.073; 1 point) and invasive mechanical ventilation (IMV) within the previous 30 days to onset of BSI (OR, 18.444; CI=1.787– 190.343; P=0.014; 4 points). The total risk score of ≥ 5 indicated that the probability of CRKP BSI occurrence was above 48%.Conclusion: CRKP BSI in patients with hematologic malignancies is associated with high mortality. The risk factor-based prediction model might help clinicians to start prompt effective anti-infective therapy in patients with suspicion of CRKP BSI and improve outcomes.Keywords: carbapenem-resistant Klebsiella pneumoniae, bloodstream infection, hematologic malignancy, risk factors, prediction

Abstract Background Carbapenem-resistant Klebsiella pneumoniae (CR-KP) is an urgent public health issue in Italy. This pattern of resistance is due mainly to dissemination of carbapenemase genes. Molecular characterization of carbapenem-resistant Klebsiella pneumoniae (CR-KP) strains was performed over a three-year period. In-depth analysis was performed on a subset of emerging CR-KP ST101 and ST307 clones. Methods A prospective study was performed on 691 patients with CR-KP bloodstream infections hospitalized in 19 hospitals located in three large provinces in Southern Italy. Carbapenemase genes were identified via genotyping methods. Multi-locus sequence typing (MLST) and Whole Genome Sequencing (WGS) were carried out on ST101 and ST307 isolates. Results Among the CR-KP isolates, bla KPC was found in 95.6%, bla VIM was found in 3.5%, bla NDM was found in 0.1% and bla OXA-48 was found in 0.1%. The bla KPC-3 variant was identified in all 104 characterized KPC-KP isolates. MLST of 231 representative isolates revealed ST512 in 45.5%, ST101 in 20.3% and ST307 in 18.2% of the isolates. cgMLST of ST307 and ST101 isolates revealed presence of more than one beta-lactam resistance gene. Amino acid substitution in the chromosomal colistin-resistance gene pmrB was found in two ST101 isolates. Conclusions ST512 is widespread in Southern Italy, but ST101 and ST307 are emerging since they were found in a significant proportion of cases. Aggressive infection control measures and a continuous monitoring of these high-risk clones are necessary to avoid rapid spread of CR-KP, especially in hospital settings.

Abstract Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) is considered as a serious global threat. CRKPs occurred only sporadically in the Second Hospital of Shanxi Medical University. Our study aimed to investigate and control the first outbreak of CRKP in our hospital occurred between October 2017 and August 2019. Methods The antimicrobial stewardship (AMS) workers have been implemented control measures properly. Clinical and epidemiological data were retrospectively collected from medical records. Carbapenemase genes were detected by modified carbapenem inactivation method (mCIM) test and the EDTA-modified carbapenem inactivation method (eCIM) test. Resistance genes were identified by polymerase chain reaction (PCR) and sequencing. Genetic relatedness was studied by multilocus sequence typing (MLST). Results During the outbreak, 31 patients were infected with CRKP isolates. 20 (64.5%) patients were infected with KPC-2 and/or NDM-1 producing K. pneumoniae. Mostly MLST-sequence types belonged to ST11 (21/31). The outbreak was two major K. pneumoniae clusters present in epidemiologically linked patients. Conclusions Setting up AMS workers is potentially a highly efficient strategy for the successful control of the outbreak. A multimodal and multidisciplinary infection control strategy proved to be crucial. The emergence of CRKP in our hospital emphasizes the importance of continuous monitoring of these isolates, which helps to limit the spread of CRKPs and improve the level of management.

Xia Chen, Qingnuan Liu, Wen-en Liu, Qun Yan Department of Clinical Laboratory, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Qun Yan Tel +86-731-84327440Fax +86-731-84327332Email yanqun@csu.edu.cnPurpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has become a critical clinical concern for its high mortality. Rectal carriage of CRKP has been reported playing an important role in CRKP infection; however, the extent to which carrier develops clinical CRKP infection is unclear. This study aimed to identify risk factors for developing subsequential CRKP clinical infection in rectal carriers with CRKP.Patients and Methods: Patients were screened for rectal carriage of CRKP in a tertiary university hospital; then, rectal CRKP carriers were divided into case group (those who developed subsequential clinical infection) and control group. Demographics, comorbid conditions, invasive procedures, antimicrobial exposure and other clinical parameters of those two groups were compared and analyzed using univariate and multivariate logistic regression analyses. Antimicrobial susceptibility profile and carbapenemase phenotype/genotype of those CRKP isolates were determined. MLST was applied to elucidate the molecular epidemiology of rectal CRKP isolates and clinical infection ones.Results: Eight hundred and thirty-five patients were screened for rectal CRKP carriage. A total of 62 CRKP rectal carriers were identified; among them, 37.1% (23/62) developed CRKP clinical infection. CRKP isolates were resistant to most of the tested antimicrobial agents. ST11 was the dominant MLST type in rectal CRKP isolates (71.0%), and all the 23 clinical infection isolates were ST11. Multivariate analysis revealed that admission to the intensive care unit (ICU) (OR, 6.753; P=0.006), being in coma condition (OR, 11.085; P=0.015) and receiving central venous catheter (OR, 8.628; P=0.003) were independent risk factors for progressing to subsequential CRKP infection among those rectal carriers.Conclusion: This study identified independent risk factors for developing subsequential CRKP clinical infection among CRKP rectal carriers, with being in coma condition as a new finding. It would help clinician target those high-risk rectal CRKP-colonized patients for prevention of subsequential clinical infection.Keywords: carbapenem-resistant Klebsiella pneumoniae, infection, risk factors, rectal carriage

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 < 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.

BackgroundThe sequence type 11 (ST11) carbapenem-resistant Klebsiella pneumoniae (CRKP) carrying blaKPC−2 has been widespread all over the world, and it has been reported frequently in China. The blaKPC−2 located on the mobile genetic element brings tremendous pressure to control the spread and outbreak of resistant bacteria. Whole-genome sequencing (WGS) technology can comprehensively and in-depth display the molecular characteristics of drug-resistant bacteria, providing a basis for evaluating the genetic diversity within the CRKP genome.MethodsThe ST11 CRKP in this study was collected in the intensive care unit of a major teaching hospital. PCR and Sanger sequencing confirmed the existence of blaKPC−2. The AST-GN card and the microbroth dilution test were used for antimicrobial susceptibility testing. The transferability of plasmid was verified by a conjugation test. The whole genome is sequenced using the Illumina HiSeq short-read and Oxford Nanopore long-read sequencing technology.ResultsThe studied strain was named CRKP63, which is a multi-drug resistance bacteria, which carries blaKPC−2 and blaSHV−182. Its genome consists of a circular chromosome of 5,374,207 bp and an IncFII plasmid named pKPC-063001 of 359,625 bp. In the drug-resistant plasmid pKPC-063001, the key carbapenem resistance gene blaKPC−2 was located in the genetic context with insertion sequence ISKpn27 upstream and ISKpn6 downstream and bracketed by IS26. The three copies of the IS26–ISKpn27–blaKPC−2–ISKpn6–IS26 unit were present in tandem. blaKPC−2 can be transferred horizontally between other species by conjugation, the complete type IV secretion system (T4SS) structure helps to improve the adaptability of bacteria to the external environment, strengthen the existence of drug-resistant bacteria, and accelerate the spread of drug resistance.ConclusionHigh-throughput sequencing has discovered the different surrounding environments of blaKPC−2, which provides a new idea for further revealing the transmission and inheritance of blaKPC−2 at the molecular level. In order to control the further spread and prevalence of drug-resistant bacteria, we should pay close attention to the changes in the genetic environment of blaKPC−2 and further study the transcription and expression of T4SS.

Klebsiella pneumoniae is a Gram-negative opportunistic pathogen responsible for a variety of community and hospital infections. Infections caused by carbapenem-resistant K. pneumoniae (CRKP) constitute a major threat for public health and are strongly associated with high rates of mortality, especially in immunocompromised and critically ill patients. Adhesive fimbriae, capsule, lipopolysaccharide (LPS), and siderophores or iron carriers constitute the main virulence factors which contribute to the pathogenicity of K. pneumoniae. Colistin and tigecycline constitute some of the last resorts for the treatment of CRKP infections. Carbapenemase production, especially K. pneumoniae carbapenemase (KPC) and metallo-β-lactamase (MBL), constitutes the basic molecular mechanism of CRKP emergence. Knowledge of the mechanism of CRKP appearance is crucial, as it can determine the selection of the most suitable antimicrobial agent among those most recently launched. Plazomicin, eravacycline, cefiderocol, temocillin, ceftolozane–tazobactam, imipenem–cilastatin/relebactam, meropenem–vaborbactam, ceftazidime–avibactam and aztreonam–avibactam constitute potent alternatives for treating CRKP infections. The aim of the current review is to highlight the virulence factors and molecular pathogenesis of CRKP and provide recent updates on the molecular epidemiology and antimicrobial treatment options.

Background: The worldwide outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) has become an urgent public health problem. High mortality and lack of effective treatments further pose new challenges to control this infection. However, studies about the evaluation of available antibiotics for CRKP infection are limited. The present study aimed to compare the efficacy of polymyxin B versus ceftazidime-avibactam (CAZ/AVI) in Chinese patients with CRKP infections and to identify risk factors affecting 7-day bacterial eradication and 28-day all-cause mortality.Methods: From January 8, 2018, to July 6, 2020, a total of 115 adult CRKP infected patients from two tertiary teaching hospitals in Shanghai, China were enrolled based on the inclusion and exclusion criteria. By reviewing electronic medical records of these patients, demographic and clinical data were extracted. The selected patients were divided into polymyxin B and CAZ/AVI groups according to primary antibiotic exposure to compare therapeutic effects. Binary logistic and cox’s regression analysis were performed to identify risk factors for 7-day bacterial eradication and all-cause mortality.Results: One hundred and five patients were treated with polymyxin B (67.8%) or CAZ/AVI (32.2%). Patients in the CAZ/AVI group had significantly lower rates of 28-day mortality (8.1 vs 29.5%, p = 0.013), higher microbiological eradication and 28-day clinical success. Multivariate analysis showed that Charlson comorbidity index (≥3) and prior antibiotic use within 90 days were independent risk factors for poor microbiological eradication. Cox’s regression analysis indicated that the length of hospitalization after CRKP infection and baseline creatinine clearance negatively affected 28-day mortality.Conclusion: CAZ/AVI was more effective than polymyxin B and appeared to be a promising drug for CRKP infection, especially for critically ill patients.

Objectives: This work was to investigate the activity and optimal treatments of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections caused by carbapenem resistant Klebsiella pneumoniae (BSIs-CRKP).Methods: A total of 318 nonduplicate BSIs-CRKP isolates were collected from Blood Bacterial Resistant Investigation Collaborative System (BRICS) program. The minimum inhibitory concentration (MIC) of CZA and AZA were determined by agar dilution method. Carbapenemase genes and multilocus sequence typing were amplified by PCR. Monte Carlo simulation (MCS) was conducted to calculate cumulative fraction of response (CFR) of different CZA or AZA administrations.Results: The MIC90 of CZA and AZA were 128/4 and 1/4 mg/L, respectively. There are 87.4 and 3.5% isolates carried blaKPC-2 and blaNDM-1. A total of 68 ST types were identified and 29 novel ST types. ST11 accounted for 66.6%. Further MCS showed CFR of CZA using two-step infusion therapy (rapid first-step 0.5 h infusion and slow second-step 3 h infusion, TSIT) (2.5 g 0.5 h, 3.75 g every 8 h with 3 h infusion and 3.75 g 0.5 h, 2.5 g every 8 h with 3 h infusion) was above 89%. The CFR of AZA with TSIT was above 96%.Conclusion: TSIT with sufficient pharmacokinetic conditions could be useful for enhancing the therapeutic efficacy of CZA and AZA against BSIs-CRKP.

Background: The dwindling antibiotic reserve owing to augmented drug-resistant bacteria is a major handicap for treating physicians. Klebsiella pneumoniae , a gram-negative encapsulated member of the Enterobacteriaceae family, is one such pathogenic bacteria. Carbapenemase-producing Klebsiella pneumoniae is globally recognized as one of the most critical bacterial threats to public health due to its extremely limited treatment options. Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections pose therapeutic challenges due to simultaneous resistance to various other groups of antibiotics. In this study, we have evaluated the synergistic effect of fosfomycinagainst CRKP isolates when used in combination with colistin by applying the Checkerboard method., Methods: A laboratory-based prospective study was conducted in the Department of Microbiology, JSS Hospital, Mysuru, for a period of one year after obtaining ethical clearance. Klebsiella pneumoniae isolates obtained from clinical samples were screened for carbapenem resistance by the VITEK-2 compact system (bioMérieux, Marcy-l'Étoile, France). The minimum inhibitory concentration (MIC) of colistin and fosfomycin was individually ascertained by broth microdilution (BMD). Finally, the synergistic activity of the fosfomycin-colistin combination was determined by the BMD-based Checkerboard method., Results: Among the 50 CRKP isolates, 36 (72%) isolates showed synergism, eight (16%) isolates showed indifference and six (12%) isolates showed partial synergism, while none of them showed additivity and antagonism by the Checkerboard method. These results are found to be statistically significant (chi-square value of 116.204 and p-value of < 0.00001)., Conclusion: This study showed a promising in-vitro synergy between the drugs fosfomycin and colistin by Checkerboard BMD testing protocol. Colistin being a reserve antibiotic, monotherapy comes with the limitations of higher chances of resistance as well as toxicity, which can be overcome by combination therapy, thereby decreasing CRKP-associated mortality rates and delivering holistic patient benefit., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. JSS Medical College and Hospital Institutional Ethical Committee issued approval (JSS/MC/PG/31/2022-23). The collected data were anonymized before conducting the analysis. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, P et al.)

This research focused on evaluating the clinical results of patients suffering from pneumonia caused by carbapenem-resistant Klebsiella pneumoniae (CRKP), who received treatment with either ceftazidime-avibactam (CZA) alone or in combination with other antibiotics. From January 2020 to December 2023, we retrospectively analyzed CRKP-related pneumonia patients treated in two Chinese tertiary hospitals. Mortality was measured at 14 and 30 days as the primary outcome. Secondary outcomes included the 14-day microbiological cure rate and the 14-day clinical cure rate. Factors contributing to clinical failure were evaluated via both univariate analysis and multivariate logistic regression. To account for confounding factors, propensity score matching (PSM) was utilized. Among the 195 patients with CRKP infections, 103 (52.8 %) received CZA combination therapy, and 92 (47.2 %) patients received CZA monotherapy. The combination therapy group exhibited superior clinical and microbiological cure rates compared to the monotherapy group, with a 14-day clinical cure rate of 60.1 % vs. 45.7 % ( P  = 0.042) and a 14-day microbiological cure rate of 72.8 % vs. 58.6 % ( P  = 0.038), respectively. Combination therapy reduced mortality rates at 14 days (7.8 % vs. 17.4 %, P  = 0.041), but not at 30 days (14.6 % vs. 25.0 %, P  = 0.066). Even after using PSM, the group treated with the CZA combination continued to had a lower mortality rate at 14 days (5.9 % vs. 17.6 %, P  = 0.039). The 14-day clinical cure rate for the combination therapy group was 63.2 %, and the 14-day microbial cure rate was 77.9 %. Both of these statistics were notably greater than those observed in the monotherapy group. Furthermore, the multivariate logistic regression model indicated a significant link between combination therapy and a decrease in clinical failure. Carbapenems were noted to be the most effective class of concomitant agents. Our findings indicate that patients with pneumonia due to CRKP benefit from combination treatment of CZA rather than monotherapy; administering carbapenem in combination with CZA in the early stages could provide considerable survival benefits., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Li-fen Hu reports financial support was provided by The First Affiliated Hospital of Anhui Medical University Clinical Research Project. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

This study aimed to assess the in vitro efficacy of ceftazidime-avibactam (CZA) in combination with various antimicrobial agents against carbapenem-resistant Klebsiella pneumoniae (CRKP). We selected 59 clinical CRKP isolates containing distinct drug resistance mechanisms. The minimum inhibitory concentrations (MICs) of meropenem (MEM), colistin (COL), eravacycline (ERA), amikacin (AK), fosfomycin (FOS), and aztreonam (ATM), both individually and in combination with CZA, were tested using the checkerboard method. The interactions of antimicrobial agent combinations were assessed by fractional inhibitory concentration index (FICI) and susceptible breakpoint index (SBPI). The time-kill curve assay was employed to dynamically evaluate the effects of these drugs alone and in combination format. In the checkerboard assay, the combination of CZA+MEM showed the highest level of synergistic effect against both KPC-producing and carbapenemase-non-producing isolates, with synergy rates of 91.3% and 100%, respectively. Following closely was the combination of FOS+CZA . For metallo-beta-lactamases (MBLs) producing strains, ATM+CZA displayed complete synergy, while the combination of MEM+CZA showed a synergy rate of only 57.14% for NDM-producing strains and 91.67% for IMP-producing strains. In the time-kill assay, MEM+CZA also demonstrated significant synergistic effects against the two KPC-2-producing isolates (Y070 and L70), the two carbapenemase-non-producing isolates (Y083 and L093), and the NDM-1-producing strain L13, with reductions in log 10 CFU/mL exceeding 10 compared to the control. Against the IMP-producing strain Y047, ATM+CZA exhibited the highest synergistic effect, resulting in a log 10 CFU/mL reduction of 10.43 compared to the control. The combination of CZA and MEM exhibited good synergistic effects against KPC-producing and non-enzyme-producing strains, followed by the FOS+CZA combination. Among MBL-producing strains, ATM+CZA demonstrated the most pronounced synergistic effect. However, the combinations of CZA with ERA, AK, and COL show irrelevant effects against the tested clinical isolates., Importance: Our study confirmed the efficacy of the combination CZA+MEM against KPC-producing and non-carbapenemase-producing strains. For metalloenzyme-producing strains, CZA+ATM demonstrated the most significant synergy. Additionally, CZA exhibited a notable synergy effect when combined with FOS. These combination therapies present promising new options for the treatment of CRKP infection., Competing Interests: The authors declare no conflict of interest.

Objectives: This study aimed to isolate a phage capable of lysing carbapenem-resistant Klebsiella pneumoniae (CRKP) and to analyse its biological characteristics and whole-genome sequence., Methods: The phage was isolated and purified from the sewage. Transmission electron microscopy (TEM) was employed to observe the bacteriophage's morphology. Phenotypic characterization of the bacteriophages was determined. The genomic information was analysed. Evolutionary relationships were established through comparative genomics, proteomics, and phylogenetic analysis., Results: The isolation of a virulent phage, named Klebsiella phage vB&#95;KpnM&#95;KpVB3, was notable for forming 6-7 mm transparent circular zones, each surrounded by a distinct halo. The phage had a head diameter of ca. 30 nm and a tail length of ca. 20 nm, being identified as a member of the Myoviridae family and the Caudovirales order. The optimal multiplicity of infection (MOI) was 0.00001, with an incubation period of 20 minutes and a lysis period of 60 minutes, and the number of released phages after lysis was 133±35 PFU/cell. The phage was relatively stable at temperatures ranging from 10°C to 40°C and at pH values ranging from 3 to 11. Its lytic efficiency against CRKP was 30.30%. It has been shown to be able to destroy the biofilm of host bacteria. The bacteriophage genome consists of double-stranded DNA (dsDNA) with a total length of 48,394 base pairs, a GC content of 48.99%, and 78 open reading frames (ORFs)., Conclusion: The study resulted in the isolation vB&#95;KpnM&#95;KpVB3, a phage demonstrating potential therapeutic efficacy against infections caused by CRKP., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Infections remain a major cause of morbidity and mortality in kidney transplant (KT) recipients. This study was performed to identify the overall prevalence of early infections, prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection after KT, one-year postoperative mortality in patients with early infections and risk factors for CRKP infections. Methods: We conducted a retrospective study of all patients who received KT in our hospital between January 2017 and December 2019. We evaluated the demographic, clinical, infection characteristics and the one-year postoperative outcomes. Results: Among the 419 patients who received KT between January 2017 and December 2019, 150 patients had at least one infection within 90 days after KT. The total prevalence of early infections was 36.1% (150/415), the prevalence of early CRKP infections was 10.4% (43/415), and the one-year postoperative mortality was 15.3% (23/150) in patients with early infections. The risk factors independently related to one-year postoperative mortality were mechanical ventilation (MV) > 48 h (Odds ratio (OR)= 13.879, 95%Confidence interval (CI): 2.265~85.035; P=0.004) and CRKP infection (OR=6.751, 95% CI: 1.051~43.369; P =0.044). MV> 48 h was independently related to CRKP infection (OR=3.719, 95% CI: 1.024~13.504; P=0.046). Kaplan-Meier survival curves showed that the one-year survival rate of patients infected with CRKP in the early postoperative stage was significantly lower than that of uninfected patients. Conclusions: In general, the prevalence of early infections after KT is high, and CRKP infection is closely correlated with poor prognosis. The effective prevention and treatment of CRKP infection is an important way to improve the one-year survival rate after KT. [ABSTRACT FROM AUTHOR]

Background: Hypermucoviscous carbapenem-resistant Klebsiella pneumoniae (hmCRKp) is emerging globally and approaching the worst-case scenario in health care system. Aims: The main objective in this study was to determine the hypermucoviscous characteristics among the carbapenem-resistant K. pneumoniae (CRKp) isolated from a teaching hospital in Malaysia. The association of hypermucoviscous phenotype with the virulence traits and clinical presentations were also investigated. Methods: A retrospective study was conducted in University Malaya Medical Centre (UMMC). The presence of hypermucoviscous K. pneumoniae was identified among a collection of CRKp clinical isolates (first isolate per patient) from 2014 to 2015 using string test. Correlation between clinical and microbial characteristics of the hmCRKp was investigated. Results: A total of nine (7.5%) hmCRKp were detected among 120 CRKp isolates. Majority of the isolates were hospital acquired or health care-associated infections. None of the patients had typical pyogenic liver abscess. All of the hmCRKp isolates harbored carbapenemase genes and were multidrug resistant. K1/K serotype, peg-344, allS, and magA were not identified among hmCRKp isolates, whereas aerobactin siderophore receptor gene (iutA), iroB, rmpA, and rmpA2 were detected. Only three hmCRKp isolates were resistant to serum bactericidal. Conclusions: All the isolates presented inconclusive evidence for the interpretation of hypervirulence. Therefore, more study should be performed in the future to have a better understanding of the virulence mechanisms in correlation with the clinical and microbial determinants. [ABSTRACT FROM AUTHOR]

Background & objectives: The prevalence of severe infections due to carbapenem-resistant Klebsiella pneumoniae (CRKP) strains has increased worldwide. With rising resistance to polymyxins, the treatment has become challenging. Given the paucity of novel agents and limited data on combination therapy for CRKP, the present study was performed to test antibiotic combinations, for synergy against clinical isolates of CRKP. Methods: A total of 50 clinical isolates of CRKP were included. Modified carbapenem inactivation method was performed for the detection of carbapenemases. In vitro synergy testing was done for the following combinations: meropenem+colistin, imipenem+tigecycline and polymyxin B+levofloxacin. It was performed with epsilometric test and microdilution checkerboard method. The time kill assay (TKA) was used to confirm the results. The fractional inhibitory concentration was also calculated. Results: All CRKP isolates (100%) were ESBL producers and were completely resistant to amoxicillin-clavulanic acid, cefepime, cefotaxime, ceftazidime and piperacillin-tazobactam. Resistance to ciprofloxacin, amikacin and tetracycline was 96, 88 and 54 per cent, respectively. Overall, 78 (39/50) and 88 per cent (44/50) of the 50 CRKP isolates exhibited synergy by TKA for meropenem-colistin and imipenem-tigecycline, respectively. No synergy was detected for levofloxacin-polymyxin B combination. The best combination among the three was that of imipenem and tigecycline followed by meropenem-colistin. Interpretation & conclusions: Of the three combinations tested, imipenem and tigecycline followed by meropenem-colistin were found to be best. No synergy was detected for levofloxacin-polymyxin B combination. [ABSTRACT FROM AUTHOR]

Background: No clinical study has investigated the use of ceftazidime-avibactam combination schemes with an in vitro non-susceptible antimicrobial that could be superior to ceftazidime-avibactam monotherapy against carbapenem-resistant Klebsiella pneumoniae. Methods: We performed a retrospective cohort study at two tertiary hospitals in China for patients with carbapenem-resistant Klebsiella pneumoniae infection treated with ceftazidime-avibactam for at least 72 h. A Cox proportional hazards regression model was used to evaluate covariates that potentially affected 30-day mortality. Results: Sixty-two patients were eligible for our study; 41 (66.1%) received ceftazidime-avibactam combination therapy and 21 (33.9%) received ceftazidime-avibactam monotherapy. The overall 30-day mortality was 33.9% (21 patients): 24.4% (10/41) and 47.6% (11/21), P = 0.028, in combination and monotherapy groups, respectively. Combination therapy was significantly associated with lower 30-day mortality (Hazard ratio, 0.167; 95% Confidence Interval, 0.060–0.465, P = 0.001). At the same time, a higher APACHE II score, use of vasoactive drugs and comorbidity of organ transplantation were considered factors that increased mortality. The propensity score showed no significant alterations with other variables after adding it to the final model. In the subgroup analysis, the protective effect was revealed when combined with carbapenems, tigecycline or fosfomycin were applied, and in the following subgroups of patients: with sepsis, with creatinine clearance > 50 mL/min, stayed in the intensive care unit ≤ 30 days or underwent mechanical ventilation. Conclusions: Ceftazidime-avibactam combined with another in vitro non-susceptible antimicrobial, especially carbapenems, fosfomycin and tigecycline, could significantly decrease the 30-day mortality rate for critically ill patients with carbapenem-resistant Klebsiella pneumoniae infection. Further investigation should be carried out to confirm this conclusion and identify autofit antimicrobials in ceftazidime-avibactam combination schemes. [ABSTRACT FROM AUTHOR]

BackgroundInfections remain a major cause of morbidity and mortality in kidney transplant (KT) recipients. This study was performed to identify the overall prevalence of early infections, prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection after KT, one-year postoperative mortality in patients with early infections and risk factors for CRKP infections.MethodsWe conducted a retrospective study of all patients who received KT in our hospital between January 2017 and December 2019. We evaluated the demographic, clinical, infection characteristics and the one-year postoperative outcomes.ResultsAmong the 419 patients who received KT between January 2017 and December 2019, 150 patients had at least one infection within 90 days after KT. The total prevalence of early infections was 36.1% (150/415), the prevalence of early CRKP infections was 10.4% (43/415), and the one-year postoperative mortality was 15.3% (23/150) in patients with early infections. The risk factors independently related to one-year postoperative mortality were mechanical ventilation (MV) > 48 h (Odds ratio (OR)= 13.879, 95%Confidence interval (CI): 2.265~85.035; P=0.004) and CRKP infection (OR=6.751, 95% CI: 1.051~43.369; P =0.044). MV> 48 h was independently related to CRKP infection (OR=3.719, 95% CI: 1.024~13.504; P=0.046). Kaplan-Meier survival curves showed that the one-year survival rate of patients infected with CRKP in the early postoperative stage was significantly lower than that of uninfected patients.ConclusionsIn general, the prevalence of early infections after KT is high, and CRKP infection is closely correlated with poor prognosis. The effective prevention and treatment of CRKP infection is an important way to improve the one-year survival rate after KT.

ABSTRACT We assessed the prevalence of polymyxin B (PMB)- and tigecycline (TGC)-heteroresistant Klebsiella pneumoniae isolates and investigated the combined effect of PMB and TGC against dual-heteroresistant K. pneumoniae. Ninety-five nonduplicated carbapenem-resistant K. pneumoniae (CRKP) clinical isolates were collected from a tertiary-care teaching hospital in China. PCR was used to detect the resistant genes among the CRKP isolates. Population analysis profiling (PAP) was carried out to evaluate the existence of heteroresistance. A time-kill assay of PMB combined with TGC was conducted against heteroresistant K. pneumoniae strains. Real-time PCR was performed to determine the pmrA, phoP, and acrB expression levels. Among them, 74 isolates (77.9%) were susceptible to TGC, and 90 isolates (94.7%) were susceptible to PMB. In addition, of the TGC-susceptible isolates, 49 strains (66.2%) exhibited heteroresistant phenotypes. All of the PMB-susceptible isolates showed heteroresistant phenotypes. Forty-six isolates (48.4%) were heteroresistant to both TGC and PMB. All of the isolates carried the blaKPC gene, and one strain carried both blaKPC and blaNDM genes. The time-kill assay revealed in four isolates that early bactericidal activity could be triggered by the combination of PMB and TGC, and there was no regrowth, even at a relatively lower concentration (0.125 mg/liter PMB with 1 mg/liter TGC). Upregulated expression of pmrA, phoP, and acrB indicated that heteroresistance could be related to two-component systems and the AcrAB-TolC efflux pump. The combination of PMB and TGC may be a treatment strategy for those infected with CRKP heteroresistant to PMB and/or TGC. IMPORTANCE Tigecycline and colistin are two of the last treatment options remaining for carbapenem-resistant Enterobacteriaceae. Unfortunately, tigecycline resistance and colistin heteroresistance are also increasing rapidly. In the current study, we identified a high prevalence of heteroresistance to both PMB and TGC among clinical isolates of carbapenem-resistant K. pneumoniae (CRKP). The resistant subpopulations could survive pressure from TGC or PMB but were killed by the combination at a relatively low dose. It is proposed that the combination of PMB and TGC may be a treatment strategy for patients who are infected with CRKP heteroresistant to PMB or TGC.

Carbapenem-resistant (CR) Klebsiella pneumoniae represents an urgent worldwide threat. We focused on CR K. pneumoniae in selected facilities of the University Hospital Bratislava (UHB) to investigate sequence types (STs), clonal relatedness, and antimicrobial resistance. Suspected carbapenem-nonsusceptible K. pneumoniae strains were obtained from hospitalized patients. Further examination included carbapenemase confirmation, cgMLST, and quantitative susceptibility testing. Of the total 41 CR K. pneumoniae strains, 26 (63.4%) were determined as ST11 in hospital No. 1; of these ST11, 22 (84.6%) were found in the first internal clinic. Six (14.6%) ST258 and three (7.3%) ST584 occurred in hospital No. 2; the most, i.e., four (66.7%), ST258 were detected in the geriatric clinic. In hospital No. 3, we found two (4.8%) ST584 and one (2.4%) ST258. Of the ST11 set, 24 (92.3%) produced NDM-1. Furthermore, seven (87.5) ST258 and five (100%) ST584 strains generated KPC-2. Antimicrobial resistance was as follows: ertapenem 97.6%, meropenem 63.4%, tigecycline 7.3%, eravacycline 7.3%, and colistin 2.5%. We revealed a presumably epidemiological association of ST11 with transmission, particularly in the first internal clinic of hospital No. 1, while ST258 and ST584 were related to interhospital dissemination between medical facilities No. 2 and No. 3. It is essential to prevent the circulation of these pathogens within and between healthcare facilities.

Objective: To verify the effects of comprehensive infection prevention and control (IPC) interventions for the prevention of the cross-transmission of carbapenem-resistant Klebsiella pneumoniae (CRKP) within intensive care units (ICUs) in an epidemic region.Methods: A historical control, quasi-experimental design was performed. The study was conducted between January 2017 and December 2019, following the implementation of a multimodal IPC bundle. The baseline period was established from January 2013 to June 2013, when only basic IPC measures were applied.Results: A total of 748 patients were enrolled during the entire study. The incidence of ICU-acquired CRKP colonization/infection was 1.16 per 1,000 patient-days during the intervention period, compared with 10.19 per 1,000 patient-days during the baseline period (p = 0.002). The slope of the monthly incidence of CRKP at admission showed an increasing trend (p = 0.03). The incidence of ICU-acquired catheter-related bloodstream infections caused by CRKP decreased from 2.54 to 0.96 per 1,000 central-line-days (p = 0.08). Compliance with contact precautions and terminal room disinfection improved during the intervention period. All environmental surface culture samples acquired after terminal room disinfection were negative for CRKP.Conclusion: Our findings suggest that in epidemic settings, multimodal IPC intervention strategies and consistent monitoring of compliance, may limit the spread of CRKP in ICUs.

The emergence and prevalence of carbapenem-resistant Enterobacteriaceae (CRE) have drawn worldwide attention. Ceftazidime/avibactam (CAZ/AVI) gives us a valuable alternative strategy to treat CRE infections. Unfortunately, CAZ/AVI resistance could occur during CAZ/AVI treatment. The CAZ/AVI-resistant Carbapenem-resistant Klebsiella pneumoniae (CR-KP) (KP137060) and earlier CAZ/AVI-susceptible isolate (KP135194) from the same hospitalized patient were collected at Fujian Medical University Union Hospital between October and November 2019. In this study, CAZ/AVI MICs of CAZ/AVI-susceptible and -resistant isolates (KP135194 and KP137060) were 4 mg/L and 128 mg/L, respectively; and the two isolates had the same antibiotic resistance pattern to other carbapenems. Two strains were then submitted for whole-genome sequencing and bioinformatic analysis. ompK36 was not detected in two isolates. No mutation was observed in blaKPC-2, ompK35 and ompK37 in this study and there was no significant difference of the expression in blaKPC-2, ompK35 and ompK37 between the two isolates (p>0.05). Two isolates were sequence type 11 and harbored blaKPC-2, blaSHV-182 and blaTEM-1B. Compared with KP135194, KP137060 harbored an additional blaNDM-5 positive plasmid. blaNDM-5 gene could be successfully transferred into E. coli J53 at a conjugation frequency of 1.14×10-4. Plasmid stability testing showed that blaKPC-2- and blaNDM-5-harboring plasmids were still stably maintained in the hosts. Growth assay and growth competition experiments showed there was no significant difference in fitness cost between two CR-KP isolates. Our study described the acquisition of a blaNDM-5-harboring plasmid leading to resistance to ceftazidime/avibactam in KPC-2-producing Klebsiella pneumoniae during treatment. This phenomenon deserves further exploration.

BackgroundDue to the critical condition and poor immunity of patients, the intensive care unit (ICU) has always been the main hospital source of multidrug-resistant bacteria. In recent years, with the large-scale use of antibiotics, the detection rate and mortality of carbapenem-resistant Klebsiella pneumoniae (CRKP) have gradually increased. This study explores the molecular characteristics and prevalence of CRKP isolated from the ICU ward of a tertiary hospital in China.MethodsA total of 51 non-duplicated CRKP samples isolated from the ICU were collected from July 2018–July 2020. The enzyme production of the strains was preliminarily screened by carbapenemase phenotypic test, and drug-resistant and virulence genes were detected by PCR. The transferability of plasmid was verified by conjugation test. The minimal inhibitory concentration (MIC) was determined by microbroth dilution method and genetic diversity was detected by multilocus sequence typing and pulsed-field gel electrophoresis.ResultsblaKPC-2 was the only carbapenemase detected. The major virulence genes were uge (100%), mrkD (94.1%), kpn (94.1%), and fim-H (72.5%), while wcag, ironB, alls and magA genes were not detected. One sequence type ST1373 strain, hypervirulent K. pneumoniae (hvKP), was detected. CRKP strains were highly resistant to quinolones, cephalosporins, aminoglycosides, and polymyxin, but susceptive to tigecycline and ceftazidime–avibactam. The success rate of conjugation was 12.2%, indicating the horizontal transfer of blaKPC-2. Homology analysis showed that there was a clonal transmission of ST11 CRKP in the ICU of our hospital.ConclusionThe present study showed the outbreak and dissemination in ICU were caused by ST11 CRKP, which were KPC-2 producers, and simultaneously, also carried some virulence genes. ST11 CRKP persisted in the ward for a long time and spread among different areas. Due to the widespread dispersal of the transferable blaKPC-2 plasmid, the hospital should promptly adopt effective surveillance and strict infection control strategies to prevent the further spread of CRKP. Ceftazidime–avibactam showed high effectiveness against CRKP and could be used for the treatment of ICU infections.

Copyright of China Tropical Medicine is the property of China Tropical Medicine Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The emergence and prevalence of carbapenem-resistant Enterobacteriaceae (CRE) have drawn worldwide attention. Ceftazidime/avibactam (CAZ/AVI) gives us a valuable alternative strategy to treat CRE infections. Unfortunately, CAZ/AVI resistance could occur during CAZ/AVI treatment. The CAZ/AVI-resistant Carbapenem-resistant Klebsiella pneumoniae (CR-KP) (KP137060) and earlier CAZ/AVI-susceptible isolate (KP135194) from the same hospitalized patient were collected at Fujian Medical University Union Hospital between October and November 2019. In this study, CAZ/AVI MICs of CAZ/AVI-susceptible and -resistant isolates (KP135194 and KP137060) were 4 mg/L and 128 mg/L, respectively; and the two isolates had the same antibiotic resistance pattern to other carbapenems. Two strains were then submitted for whole-genome sequencing and bioinformatic analysis. ompK36 was not detected in two isolates. No mutation was observed in bla KPC-2, ompK35 and ompK37 in this study and there was no significant difference of the expression in bla KPC-2, ompK35 and ompK37 between the two isolates (p >0.05). Two isolates were sequence type 11 and harbored bla KPC-2, bla SHV-182 and bla TEM-1B. Compared with KP135194, KP137060 harbored an additional bla NDM-5 positive plasmid. bla NDM-5 gene could be successfully transferred into E. coli J53 at a conjugation frequency of 1.14×10-4. Plasmid stability testing showed that bla KPC-2- and bla NDM-5-harboring plasmids were still stably maintained in the hosts. Growth assay and growth competition experiments showed there was no significant difference in fitness cost between two CR-KP isolates. Our study described the acquisition of a bla NDM-5-harboring plasmid leading to resistance to ceftazidime/avibactam in KPC-2-producing Klebsiella pneumoniae during treatment. This phenomenon deserves further exploration. [ABSTRACT FROM AUTHOR]

Aim: The aim of our study was to determine the factors associated with mortality in neonates with carbapenem-resistant Klebsiella pneumoniae (CRKP).Material and Methods: This retrospective, single-center study was conducted in the Neonatal Intensive Care Unit of Harran University Faculty of Medicine between January 2017 and July 2018 who had CRKP growth in their blood, urine or cerebrospinal fluid cultures. The discharged group was designated as the control group (Group 1), whereas the group that faced mortality was classified as the case group (Group 2). The demographic data, clinical findings and laboratory and microbiological results of the two groups were compared to identify risk factors.Results: A total of 58 patients (36 in Group 1 and 22 in Group 2) exhibited CRKP growth during the study period. Low birth weight (p = 0.039), previous antifungal (p = 0.002) or amikacin use (p = 0.040), congenital anomalies (p = 0.002), total parenteral nutrition (TPN) administration (p = 0.002), surgery (p = 0.035), thrombocytopenia (p = 0.007), low platelet mass index (p = 0.011), elevated C-reactive protein (p = 0.004), high carbapenem minimum inhibitory concentration (MIC) (p = 0.029) and high amikacin MIC (p = 0.019) were associated with mortality. In a multivariate regression analysis, previous antifungal use (p = 0.028), congenital anomalies (p = 0.032) and TPN use (p = 0.013) were independent factors in predicting mortality.Conclusion: Previous antifungal use, congenital anomalies and TPN use were found to be independent risk factors for mortality in neonates with CRKP infection. [ABSTRACT FROM AUTHOR]

Tigecycline is an alternative antibiotic for managing carbapenem-resistant Gram-negative bacterial infections. However, disk diffusion and automated testing often show false-intermediate or false-resistant results in tigecycline susceptibility, misleading clinical antimicrobial therapy. Broth microdilution (BMD) is the reference method for testing tigecycline susceptibility, but it is labor intensive and time consuming to perform in clinical laboratories. Therefore, a simple and accurate method is urgently needed. We evaluated the performance of VITEK 2, E-test, Kirby–Bauer disk diffusion (KB), and modified KB disk diffusion (mKB) versus BMD in testing tigecycline susceptibility of 372 strains of carbapenem-resistant Klebsiella pneumoniae (CRKP) and 346 strains of carbapenem-resistant Acinetobacter baumannii (CRAB). BMD confirmed that 96.8% of CRKP and 91% of CRAB strains were susceptible to tigecycline. E-test, VITEK 2, KB, and mKB yielded categorical agreement of 96.7/59.3%, 69.9/54.3%, 78.5/87.3%, and 96.5%/91% for CRKP/CRAB, respectively. No very major error was found for either CRKP or CRAB by any method. No major error was found for CRKP or CRAB by the mKB method. The mKB method enhanced by R-buffer is simple, accurate, and inexpensive for clinical laboratories to test the susceptibility of CRKP and CRAB isolates to tigecycline. [ABSTRACT FROM AUTHOR]

Background: Due to the critical condition and poor immunity of patients, the intensive care unit (ICU) has always been the main hospital source of multidrug-resistant bacteria. In recent years, with the large-scale use of antibiotics, the detection rate and mortality of carbapenem-resistant Klebsiella pneumoniae (CRKP) have gradually increased. This study explores the molecular characteristics and prevalence of CRKP isolated from the ICU ward of a tertiary hospital in China. Methods: A total of 51 non-duplicated CRKP samples isolated from the ICU were collected from July 2018–July 2020. The enzyme production of the strains was preliminarily screened by carbapenemase phenotypic test, and drug-resistant and virulence genes were detected by PCR. The transferability of plasmid was verified by conjugation test. The minimal inhibitory concentration (MIC) was determined by microbroth dilution method and genetic diversity was detected by multilocus sequence typing and pulsed-field gel electrophoresis. Results: blaKPC-2 was the only carbapenemase detected. The major virulence genes were uge (100%), mrkD (94.1%), kpn (94.1%), and fim-H (72.5%), while wcag , ironB , alls and magA genes were not detected. One sequence type ST1373 strain, hypervirulent K. pneumoniae (hvKP), was detected. CRKP strains were highly resistant to quinolones, cephalosporins, aminoglycosides, and polymyxin, but susceptive to tigecycline and ceftazidime–avibactam. The success rate of conjugation was 12.2%, indicating the horizontal transfer of blaKPC-2. Homology analysis showed that there was a clonal transmission of ST11 CRKP in the ICU of our hospital. Conclusion: The present study showed the outbreak and dissemination in ICU were caused by ST11 CRKP, which were KPC-2 producers, and simultaneously, also carried some virulence genes. ST11 CRKP persisted in the ward for a long time and spread among different areas. Due to the widespread dispersal of the transferable blaKPC-2 plasmid, the hospital should promptly adopt effective surveillance and strict infection control strategies to prevent the further spread of CRKP. Ceftazidime–avibactam showed high effectiveness against CRKP and could be used for the treatment of ICU infections. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Klebsiella pneumonia (CRKP) is a global threat that varies by region. The global distribution, evolution, and clinical implications of the ST11 CRKP clone remain obscure. We conducted a multicenter molecular epidemiological survey using isolates obtained from 28 provinces and municipalities across China between 2011 and 2021. We integrated sequences from public databases and performed genetic epidemiology analysis of ST11 CRKP. Among ST11 CRKP, KL64 serotypes exhibited considerable expansion, increasing from 1.54% to 46.08% between 2011 and 2021. Combining our data with public databases, the phylogenetic and phylogeography analyses indicated that ST11 CRKP appeared in the Americas in 1996 and spread worldwide, with key clones progressing from China's southeastern coast to the inland by 2010. Global phylogenetic analysis showed that ST11 KL64 CRKP has evolved to a virulent, resistant clade with notable regional spread. Single-nucleotide polymorphism (SNP) analysis identified BMPPS (bmr3, mltC, pyrB, ppsC, and sdaC) as a key marker for this clade. The BMPPS SNP clade is associated with high mortality and has strong anti-phagocytic and competitive traits in vitro. The high-risk ST11 KL64 CRKP subclone showed strong expansion potential and survival advantages, probably owing to genetic factors. [ABSTRACT FROM AUTHOR]