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Objective To investigate the clinical features and risk factors of infections caused by cefepime- and ertapenem-heteroresistant Klebsiella pneumoniae (FEP-HR-KP and ETP-HR-KP, respectively). Methods We conducted a retrospective case-control study of 108 Klebsiella pneumoniae strains isolated from the body fluids of the inpatients in our hospital from January, 2014 to December, 2015. The heteroresistance of the isolated strains was detected using Kirby-Bauer disk diffusion test (K-B test) and E-test, and the results were further confirmed by population analysis profile (PAP) method. The risk factors for infections by FEP-HR-KP and ETP-HR-KP were analyzed using Chi-square test and logistic regression analysis. Results Of the total of 108 non-duplicate Klebsiella pneumoniae strains isolated, 41 (40.0%) were heteroresistant to cefepime, 63(58.3%) were heteroresistant to ertapenem, and 38 (35.2%) showed heteroresistance to both. The annual detection rate of FEP-HR-KP increased from 41.7% (20/48) in 2014 to 51.7% (31/60) in 2015, and that of ETP-HR-KP increased from 54.1% (26/48) in 2014 to 61.7% (37/60) in 2015. The strains were isolated mainly from blood specimens (25/66, 37.9%), and more than half (47/66, 71.2%) of the strains were isolated from the department of surgery. Multivariate logistic regression analysis revealed that soft tissue infection (OR=1.92, 95%CI: 0.91~3.91, P=0.049), mechanical ventilation (OR=2.45, 95%CI: 1.31~4.47, P=0.013), and use of cephalosporins (OR=2.10, 95%CI: 1.18~3.13, P=0.020) were independent risk factors for infections by FEP-HR-KP; use of cephalosporins (OR=2.08, 95%CI: 0.96~4.20, P=0.033), use of carbapenems (OR=2.52, 95%CI: 1.08~3.86, P=0.023) and drainage tube placement (OR=2.76, 95%CI: 1.49~4.90, P=0.018) were independent risk factors for ETP-HR-KP infections. Conclusion The Klebsiella pneumoniae strains isolated in our hospital show high rates of heteroresistance to cefepime and ertapenem. Avoiding unnecessary invasive operation and optimizing the use of antibiotics can help to reduce the generation of heteroresistant strains and improve the treatment efficacy for FEP-HR-KP and ETP-HR-KP infections.

Background: Intestinal microenvironmental perturbations may increase food allergy risk. We hypothesize that children with clinical food allergy, those with food sensitization, and healthy children can be differentiated by intestinal metabolites in the first years of life. Methods: In this ancillary analysis of the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we performed untargeted metabolomic profiling in 824 stool samples collected at ages 3–6 months, 1 year and 3 years. Subjects included 23 with clinical food allergy at age 3 and/or 6 years, 151 with food sensitization but no clinical food allergy, and 220 controls. We identified modules of correlated, functionally related metabolites and sought associations of metabolite modules and individual metabolites with food allergy/sensitization using regression models. Results: Several modules of functionally related intestinal metabolites were reduced among subjects with food allergy, including bile acids at ages 3–6 months and 1 year, amino acids at age 3–6 months, steroid hormones at 1 year, and sphingolipids at age 3 years. One module primarily containing diacylglycerols was increased in those with food allergy at age 3–6 months. Fecal caffeine metabolites at age 3–6 months, likely derived from breast milk, were increased in those with food allergy and/or sensitization (beta = 5.9, 95% CI 1.0–10.8, p =.02) and were inversely correlated with fecal bile acids and bilirubin metabolites, though maternal plasma caffeine levels were not associated with food allergy and/or sensitization. Conclusions: Several classes of bioactive fecal metabolites are associated with food allergy and/or sensitization including bile acids, steroid hormones, sphingolipids, and caffeine metabolites. [ABSTRACT FROM AUTHOR]

Purpose: Carbapenemase-producing Enterobacteriaceae (CPE) infection constitutes a public health threat. Timely and efficient diagnosis is of paramount importance for prompt and effective therapy. In order to quickly and comprehensively detect the five major families of carbapenemases (blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48-like), colorimetric loop-mediated isothermal amplification (LAMP) was employed. Materials and Methods: Five sets of LAMP primers were designed, each of which can, respectively, amplify all the carbapenemase subtypes described in this work. Twenty whole genome sequencing-verified-"standard strains", including 1 blaNDM-1, 1 blaNDM-5, 1 blaNDM-6, 1 blaNDM-7, 2 blaIMP-4, 1 blaIMP-8, 2 blaKPC-2, 1 blaKPC-3, 1 blaKPC-4, 1 blaKPC-5, 1 blaKPC-6, 1 blaKPC-7, 1 blaOXA-48 and 1 blaOXA-181 carrier, and 1 blaVIM and blaOXA-244, 1 blaKPC-2 and blaIMP-4, 1 blaKPC-2 and blaVIM-1 and 1 blaKPC-2 and blaNDM-1-co-carriers, were used to establish a 25-microliter visual LAMP reaction system (kept at 65°C for 30 minutes in water bath). Color change from bright pink to yellow indicated positive amplification. In addition, 126 pre-verified clinical carbapenem-resistant Enterobacteriaceae (CRE) isolates, including 65 CPE (23 blaNDM, 2 blaOXA-48-like, 1 blaKPC and blaVIM, 2 blaIMP, and 37 blaKPC carriers) and 61 non-CPE, were also detected. Results: With the lowest detection limit of 10 colony forming units (CFU) per reaction for LAMP and 103 CFU per reaction for PCR, the LAMP system demonstrated dramatically higher sensitivity while retaining the same specificity. Furthermore, we demonstrated concordant results between the two methods for the 126 clinical isolates. Conclusion: Therefore, LAMP could be used for rapid identification of the five major carbapenemase gene families in routine clinical laboratories. [ABSTRACT FROM AUTHOR]

The newly emerging NDM-5 confers increased antibiotic resistance and attracts extensive global attention, but the prevalence, dissemination mechanism, and clinical significance of NDM-5 among clinical Escherichia coli (E. coli) infections have not been thoroughly characterized to date. In the present study, 109 unique carbapenem-resistant E. coli (CR-EC) isolates were collected in Southwest China, from 2013 to 2017, among which 41 (37.61%) CR-EC isolates were identified as NDM-5-producers, with most isolates carrying the IncF-type plasmids. Molecular epidemiological studies revealed ST167 being the most common sequence type (ST). Moreover, we described the first report of a clinical CR-EC isolate co-harboring bla KPC–2 and bla NDM–5, which showed a higher level of resistance to carbapenems. In addition, bla NDM–5 plasmid transformation and conjugation indicated that bla NDM–5 itself did confer resistance to carbapenems. Complete sequencing of the bla NDM–5-harboring IncF plasmid revealed highly conserved regions (ble MBL- trpF - tat) and some transposons around bla NDM–5. Our findings revealed a new potential threat of NDM-5-postive CR-EC in mainland China and emphasized an urgent need to control their further spread. [ABSTRACT FROM AUTHOR]

Purpose: Pseudomonas aeruginosa is recognized as a major cause of severe and potentially life-threatening infection. However, P. aeruginosa isolates with the phenotype of being carbapenem resistant and cephalosporin susceptible (Carb-R/Ceph-S) have not been thoroughly characterized to date. The aim of this study was to assess the mechanisms, risk factors, and clinical impact of Carb-R/Ceph-S P. aeruginosa bacteremia on mortality.Patients and methods: We conducted a retrospective case–case–control study of the risk factors and clinical outcomes of hospitalized patients with Carb-R/Ceph-S P. aeruginosa bacteremia from 2011 to 2017 in Chongqing, China. Case patients infected with Carb-R/Ceph-S P. aeruginosa, carbapenem-susceptible and cephalosporin-susceptible (Carb-S/Ceph-S) P. aeruginosa, and controls with no P. aeruginosa bacteremia were compared at a ratio of 1:1:2. Real-time reverse transcription polymerase chain reaction was performed to assess resistance mechanisms. A multivariate logistic regression model was performed to investigate several potential predictors for mortality.Results: We collected 63 Carb-R/Ceph-S P. aeruginosa isolates during the study period. None of these isolates possessed carbapenemase or extended-spectrum β-lactamase-encoding genes. The overall 30-day mortality rate was 27.0%. Real-time reverse transcription polymerase chain reaction analysis showed that an overexpression of efflux systems and decreased expression of OprD were associated with Carb-R/Ceph-S P. aeruginosa. Multivariate analysis indicated that 30-day readmission, central venous catheters, and exposure to carbapenems were unique independent predictors for acquiring Carb-R/Ceph-S P. aeruginosa bacteremia. Additionally, hematologic malignancy was a peculiar predictor for Carb-S/Ceph-S P. aeruginosa bacteremia. Notably, total parenteral nutrition was the only common factor of both Carb-R/Ceph-S and Carb-S/Ceph-S groups compared to controls. In a multivariate analysis for the outcome, intensive care unit admission and septic shock were identified as the independent predictors for mortality.Conclusion: Our findings can potentially improve the ability of physicians to identify the high-risk patients, and carbapenems were noted to potentially increase the risk of Carb-R/Ceph-S P. aeruginosa. Additionally, cephalosporin should be considered a valuable therapeutic option for such cases of bacteremia. [ABSTRACT FROM AUTHOR]

Cryptococcal meningitis (CM), a common and serious opportunistic infection mostly caused by Cryptococcus neoformans , is primarily treated with fluconazole. Nevertheless, Cryptococcus neoformans strains that undergo repeated exposure to azoles can gradually acquire heteroresistance to fluconazole. The management of this specific CM infection poses a substantial challenge. Determining a globally accepted definition for fluconazole heteroresistance and developing effective and prompt methods for identifying heteroresistance is of utmost importance. We collected data on the clinical and epidemiological characteristics of patients diagnosed with CM. All the available Cryptococcus neoformans strains isolated from these patients were collected and subjected to antifungal susceptibility testing and evaluation of fluconazole heteroresistance. AIDS was present in 40.5% of the patients, whereas 24.1% did not have any underlying diseases. Patients with chronic diseases or impaired immune systems are susceptible to infection by Cryptococcus neoformans , a fungus that frequently (39.6%, 19/48) shows heteroresistance to fluconazole, as confirmed by population analysis profile (PAP).IMPORTANCEFluconazole heteroresistance poses a significant threat to the efficacy of fluconazole in treating cryptococcal meningitis (CM). Unfortunately, the standard broth microdilution method often misses the subtle percentages of subpopulations exhibiting heteroresistance. While the population analysis profile (PAP) method is esteemed as the gold standard, its time-consuming and labor-intensive nature makes it impractical for routine clinical use. In contrast, the Kirby-Bauer (KB) disk diffusion method offers a simple and effective screening solution. Our study highlights the value of KB over PAP and minimum inhibitory concentration (MIC) by demonstrating that when adjusting the inoculum concentration to 1.0 McFarland and subjecting samples to a 72-hour incubation period at 35°C, the KB method closely mirrors the outcomes of the PAP approach in detecting fluconazole heteroresistance. This optimization of the KB method not only enhances assay efficiency but also provides a blueprint for developing a timely and effective strategy for identifying heteroresistance., Competing Interests: The authors declare no conflict of interest.

Purpose: Carbapenemase-producing Enterobacteriaceae (CPE) infection constitutes a public health threat. Timely and efficient diagnosis is of paramount importance for prompt and effective therapy. In order to quickly and comprehensively detect the five major families of carbapenemases ( bla KPC , bla NDM , bla VIM , bla IMP , and bla OXA-48-like ), colorimetric loop-mediated isothermal amplification (LAMP) was employed., Materials and Methods: Five sets of LAMP primers were designed, each of which can, respectively, amplify all the carbapenemase subtypes described in this work. Twenty whole genome sequencing-verified-"standard strains", including 1 bla NDM-1 , 1 bla NDM-5 , 1 bla NDM-6 , 1 bla NDM-7 , 2 bla IMP-4 , 1 bla IMP-8 , 2 bla KPC-2 , 1 bla KPC-3 , 1 bla KPC-4 , 1 bla KPC-5 , 1 bla KPC-6 , 1 bla KPC-7 , 1 bla OXA-48 and 1 bla OXA-181 carrier, and 1 bla VIM and bla OXA-244 , 1 bla KPC-2 and bla IMP-4 , 1 bla KPC-2 and bla VIM-1 and 1 bla KPC-2 and bla NDM-1 -co-carriers, were used to establish a 25-microliter visual LAMP reaction system (kept at 65°C for 30 minutes in water bath). Color change from bright pink to yellow indicated positive amplification. In addition, 126 pre-verified clinical carbapenem-resistant Enterobacteriaceae (CRE) isolates, including 65 CPE (23 bla NDM , 2 bla OXA-48-like , 1 bla KPC and bla VIM , 2 bla IMP , and 37 bla KPC carriers) and 61 non-CPE, were also detected., Results: With the lowest detection limit of 10 colony forming units (CFU) per reaction for LAMP and 10 3 CFU per reaction for PCR, the LAMP system demonstrated dramatically higher sensitivity while retaining the same specificity. Furthermore, we demonstrated concordant results between the two methods for the 126 clinical isolates., Conclusion: Therefore, LAMP could be used for rapid identification of the five major carbapenemase gene families in routine clinical laboratories., Competing Interests: All authors reported no conflicts of interest in this work., (© 2021 Feng et al.)

The newly emerging NDM-5 confers increased antibiotic resistance and attracts extensive global attention, but the prevalence, dissemination mechanism, and clinical significance of NDM-5 among clinical Escherichia coli ( E. coli ) infections have not been thoroughly characterized to date. In the present study, 109 unique carbapenem-resistant E. coli (CR-EC) isolates were collected in Southwest China, from 2013 to 2017, among which 41 (37.61%) CR-EC isolates were identified as NDM-5-producers, with most isolates carrying the IncF-type plasmids. Molecular epidemiological studies revealed ST167 being the most common sequence type (ST). Moreover, we described the first report of a clinical CR-EC isolate co-harboring bla KPC- 2 and bla NDM- 5 , which showed a higher level of resistance to carbapenems. In addition, bla NDM- 5 plasmid transformation and conjugation indicated that bla NDM- 5 itself did confer resistance to carbapenems. Complete sequencing of the bla NDM- 5 -harboring IncF plasmid revealed highly conserved regions ( ble MBL - trpF - tat ) and some transposons around bla NDM- 5 . Our findings revealed a new potential threat of NDM-5-postive CR-EC in mainland China and emphasized an urgent need to control their further spread., (Copyright © 2020 Zou, Jia, Liu, Li, Wu and Huang.)

Purpose: Carbapenem-resistant Enterobacteriaceae (CRE) have been increasingly reported worldwide and pose a serious public threat, but the clinical significance of extended-spectrum β-lactamase (ESBL) production in CRE is not well established., Patients and Methods: A retrospective case-case-control study was conducted to identify the clinical characteristics of patients with ESBL-CRE. The susceptibility of isolates obtained from these patients was assessed. The detection of ESBL and carbapenemase-related genes was performed by PCR methods. Predictors of 30-day mortality in patients with ESBL-CRE infection were also identified in our study., Results: A total of 149 patients with CRE infection caused by Enterobacter cloacae (n=74), Escherichia coli (n=38), and Klebsiella pneumoniae (n=37) were identified in Chongqing, Southwestern China, between January 2011 and December 2014. Of the 35 isolates detected with carbapenemase-related genes, 16 isolates had New Delhi metallo-β-lactamase (NDM), nine isolates had K. pneumoniae carbapenemase (KPC), seven isolates had imipenemase (IMP), and four isolates had oxacillinase (OXA)-1. One strain of enterobacter cloacae carried both NDM-1 and IMP-8 genes. ESBL isolates included the genes CTX-M (72/149), SHV (64/149), and TEM (54/149). All ESBL-CRE isolates exhibited ertapenem resistance, and the rate of cephalosporin resistance was relatively high in general. Independent risk factors for infection with ESBL-CRE included previous exposure to β-lactam antibiotics, transfer from another hospital, and some underlying diseases. In addition, solid tumors, hypoalbuminemia, and central venous catheters were independent predictors of mortality in patients with ESBL-CRE infection., Conclusion: Physicians should understand the peculiar predictors for the identification of these organisms among high-risk patients., Competing Interests: Disclosure The authors report no conflicts of interest in this work.