scholarly journals Study of <i>OmpK</i>35 and <i>OmpK</i>36 Expression in Carbapenem Resistant ESBL Producing Clinical Isolates of <i>Klebsiella pneumoniae</i>

2016 ◽  
Vol 06 (09) ◽  
pp. 662-670
Author(s):  
Amina Amal Mahmoud Nour El Din ◽  
Reem Abdel Hameed Harfoush ◽  
Hadir Ahmed Said Okasha ◽  
Dina Aly El Sayed Kholeif
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Isolates ◽  
Carbapenem Resistant

scholarly journals 610. Meropenem-vaborbactam (MV) In Vitro Activity Against Carbapenem-Resistant Klebsiella pneumoniae (CRKP) Isolates with Outer Membrane Porin Gene Mutations

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S285-S285 ◽  
Author(s):  
Mohamad Yasmin ◽  
Steven Marshall ◽  
Michael Jacobs ◽  
Daniel D Rhoads ◽  
Laura J Rojas ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Outer Membrane ◽  
Gene Mutations ◽  
Underlying Mechanism ◽  
Clinical Isolates ◽  
Historical Cohort ◽  
Carbapenem Resistant ◽  
Outer Membrane Porin ◽  
Tract Infections

Abstract Background Vaborbactam is a cyclic boronic acid β-lactamase inhibitor (BLI) developed to potently inhibit Ambler class A&C enzymes, including KPC carbapenemases. Metallo-β-lactamases (MBL) and some Class D oxacillinases (OXA) are not inactivated by vaborbactam. Meropenem-vaborbactam (MV) was recently approved for the treatment of carbapenem-resistant Enterobacteriaceae complicated urinary tract infections. Recent studies have identified outer membrane porin (Ompk35 and -36) mutations in Klebsiella pneumoniae (KP) as a mechanism of decreased susceptibility to MV. We evaluated the activity of MV against a historical cohort of KP clinical isolates with these porin gene mutations. Methods WGS of carbapenem-resistant KP clinical isolates was performed and those harboring mutations in Ompk35 or Ompk36 were selected for testing. Strain KP ATCC BAA-1705 was used as a positive control. Meropenem and MV minimum inhibitory concentrations (MIC) were determined by broth microdilution (BMD) in custom 96-well plates (ThermoFisher Scientific) with a constant 8 µg/mL vaborbactam concentration. The MIC of ceftazidime–avibactam (CZA) was determined by standard BMD reference methods and interpreted according to CLSI criteria. Results A total of 105 KP isolates with either partial or complete mutations in outer membrane porin genes were included in the analysis. All isolates were resistant to Meropenem. The median MV MIC was 0.03 µg/mL (range, 0.015 to >16 µg/mL). Eleven isolates (10.4%) were resistant to MV. Sixteen additional isolates (16.1%) demonstrated higher than expected MV MICs ranging from 1 to 4 µg/mL. Only 1/11 resistant isolates harbored a gene for MBL production. Gene mutations in blaKPC were not detected. See Table 1 for characteristics of resistant isolates. Conclusion Resistance and decreased susceptibility to MV is demonstrated in a historical cohort of KP clinical isolates dating back to 2013. WGS reliably identifies porin variants secondary to gene mutations in Ompk35 and Ompk36 as the underlying mechanism of decreased susceptibility. CZA appears to retain activity against these isolates. Caution should be exercised regarding the empiric use of MV against increasingly resistant KP as a result of non-β-lactamase-mediated mechanisms. Disclosures All authors: No reported disclosures.

scholarly journals Molecular and phenotypic characterization of clinical isolates belonging to a KPC-2-producing strain of ST15 Klebsiella pneumoniae from a Vietnamese pediatric hospital

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Björn Berglund ◽  
Ngoc Thi Bich Hoang ◽  
Maria Tärnberg ◽  
Ngai Kien Le ◽  
Maud Nilsson ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Resistance Genes ◽  
Resistance Rate ◽  
Clinical Isolates ◽  
Phenotypic Characterization ◽  
Polymorphism Analysis ◽  
Pediatric Hospital ◽  
Carbapenem Resistant ◽  
Global Epidemiology

Abstract Background Carbapenem-resistant Klebsiella pneumoniae are becoming increasingly common in hospital settings worldwide and are a source of increased morbidity, mortality and health care costs. The global epidemiology of carbapenem-resistant K. pneumoniae is characterized by different strains distributed geographically, with the strain ST258 being predominant in Europe and USA, and ST11 being most common in East Asia. ST15 is a less frequently occurring strain but has nevertheless been reported worldwide as a source of hospital outbreaks of carbapenem-resistant K. pneumoniae. Methods In this study, whole-genome sequencing and antimicrobial susceptibility testing was used to characterize 57 clinical isolates of carbapenem-resistant K. pneumoniae belonging to a strain of ST15, which were collected at a Vietnamese pediatric hospital from February throughout September 2015. Results Aside from the carbapenem resistance gene blaKPC-2, which was carried by all isolates, prevalence of resistance genes to other antibiotics including aminoglycosides, macrolides, quinolones, fosfomycin and trimethoprim, was also high. All isolates were multidrug-resistant. Susceptibility was highest to ceftazidime/avibactam (96%), gentamicin (91%) and tigecycline (82%). Notably, the colistin resistance rate was very high (42%). Single-nucleotide polymorphism analysis indicated that most isolates belonged to a single clone. Conclusions The diverse variety of antibiotic resistance genes and the high antibiotic resistance rates to last-resort antibiotics such as carbapenems and colistin, is indicative of a highly adaptable strain. This emphasizes the importance of implementation of infection controls measures, continued monitoring of antibiotic resistance and prudent use of antibiotics to prevent further selection of resistant strains and the emergence of pan-resistant clones.

scholarly journals 1189. A Comprehensive Characterization of the Emerging Carbapenem-Resistant Klebsiella pneumoniae Clinical Isolates From a Public Hospital in Lima, Peru

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S359-S360 ◽  
Author(s):  
Fiorella Krapp ◽  
Catherine Amaro ◽  
Karen Ocampo ◽  
Lizeth Astocondor ◽  
Noemi Hinostroza ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Dna Extraction ◽  
Antibiotic Susceptibility ◽  
Tertiary Care ◽  
Clinical Isolates ◽  
Molecular Characteristics ◽  
Care Hospital ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
String Test

Abstract Background In contrast with other countries in Latin America, Peru had been notoriously spared by the global dissemination of carbapenem-resistant Klebsiella pneumoniae (CR-Kp), until recently. Even though, isolated cases of KPC-producing K. pneumoniae had been reported since 2013, it was not until 2016 that the first outbreak of NDM- producing K. pneumoniae was described in Peru. By 2017, rapid emergence of CR-Kp took place in Hospital Cayetano Heredia (HCH), a tertiary care hospital in Lima. Here, we provide a description of clinical, microbiological and molecular characteristics of CR-Kp isolates recovered at HCH. Methods Retrospective review of all CR-Kp clinical isolates recovered at HCH until December 2017. Antibiotic susceptibility data were obtained during routine care (Vitek or disc diffusion) and was assessed using CLSI breakpoints. DNA extraction was performed by heat shock, and PCR was performed to assess carriage of blaNDM gene. String test was performed to detect hypermucoviscosity. Results The first case of CR-Kp in HCH dated from July 2015. Since then, a total of 69 CR-Kp clinical isolates, from 60 patients have been recovered until December 2017. A significant increase in the number of cases was observed during 2017 (Figure 1). The average age of patients was 55. Urinary, and respiratory sources of infection or colonization were the most common ones (35% and 30%, respectively), followed by blood stream (17%) and intraabdominal (10%) infections. Isolate recovery and DNA extraction was achieved in 40 cases. Of these, 15 (38%) had a positive PCR for blaNDM carbapenemase gene (Figure 2). Antibiotic susceptibility testing revealed that amikacin was the most effective antimicrobial with the rest of antimicrobials having extremely high rates of resistance (Figure 3). String test was positive in two of these isolates, suggesting that hypervirulent CR-KP might be emerging in this region. Conclusion An epidemic of CR-Kp has established in our hospital, representing the first one reported in Peru. The different mechanisms of carbapenem resistance found suggest a polyclonal expansion. Amikacin remains the only active antimicrobial within the routinely tested antibiotics, highlighting the need to add other antimicrobials to the routine panel. Disclosures All authors: No reported disclosures.

scholarly journals Mechanisms of fosfomycin resistance in clinical isolates of carbapenem-resistant Klebsiella pneumoniae

2020 ◽  
Vol 22 ◽  
pp. 238-243
Author(s):  
Peng Liu ◽  
Shuo Chen ◽  
Zhuo-ying Wu ◽  
Meng Qi ◽  
Xiang-yang Li ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Isolates ◽  
Carbapenem Resistant ◽  
Fosfomycin Resistance

scholarly journals Emergence of clinical isolates of highly carbapenem-resistant Klebsiella pneumoniae co-harboring blaNDM-5 and blaOXA-181 or -232 in Nepal

2020 ◽  
Vol 92 ◽  
pp. 247-252
Author(s):  
Jatan B. Sherchan ◽  
Tatsuya Tada ◽  
Shovita Shrestha ◽  
Hiroki Uchida ◽  
Tomomi Hishinuma ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Isolates ◽  
Carbapenem Resistant

scholarly journals Colistin resistance superimposed to endemic carbapenem-resistant Klebsiella pneumoniae: a rapidly evolving problem in Italy, November 2013 to April 2014

2014 ◽  
Vol 19 (42) ◽  
Author(s):  
M. Monaco ◽  
T Giani ◽  
M Raffone ◽  
F Arena ◽  
A Garcia-Fernandez ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Isolates ◽  
Colistin Resistance ◽  
Klebsiella Pneumoniae Carbapenemase ◽  
European Survey ◽  
Carbapenem Resistant

Consecutive non-replicate clinical isolates (n=191) of carbapenem non-susceptible Enterobacteriaceae were collected from 21 hospital laboratories across Italy from November 2013 to April 2014 as part of the European Survey on Carbapenemase-producing Enterobacteriaceae (EuSCAPE) project. Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP) represented 178 (93%) isolates with 76 (43%) respectively resistant to colistin, a key drug for treating carbapenamase-producing Enterobacteriaceae. KPC-KP colistin-resistant isolates were detected in all participating laboratories. This underscores a concerning evolution of colistin resistance in a setting of high KPC-KP endemicity.

scholarly journals Polyphasic characterization of carbapenem-resistant Klebsiella pneumoniae clinical isolates suggests vertical transmission of the blaKPC-3 gene

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247058
Author(s):  
Catarina Ferreira ◽  
Santosh K. Bikkarolla ◽  
Karolin Frykholm ◽  
Saga Pohjanen ◽  
Margarida Brito ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Vertical Transmission ◽  
Carbapenem Resistance ◽  
Clinical Isolates ◽  
Host Bacterium ◽  
Whole Genome ◽  
Healthcare Facilities ◽  
Genetic Elements ◽  
Dna Mapping ◽  
Carbapenem Resistant

Carbapenem-resistant Klebsiella pneumoniae are a major global threat in healthcare facilities. The propagation of carbapenem resistance determinants can occur through vertical transmission, with genetic elements being transmitted by the host bacterium, or by horizontal transmission, with the same genetic elements being transferred among distinct bacterial hosts. This work aimed to track carbapenem resistance transmission by K. pneumoniae in a healthcare facility. The study involved a polyphasic approach based on conjugation assays, resistance phenotype and genotype analyses, whole genome sequencing, and plasmid characterization by pulsed field gel electrophoresis and optical DNA mapping. Out of 40 K. pneumoniae clinical isolates recovered over two years, five were carbapenem- and multidrug-resistant and belonged to multilocus sequence type ST147. These isolates harboured the carbapenemase encoding blaKPC-3 gene, integrated in conjugative plasmids of 140 kbp or 55 kbp, belonging to replicon types incFIA/incFIIK or incN/incFIIK, respectively. The two distinct plasmids encoding the blaKPC-3 gene were associated with distinct genetic lineages, as confirmed by optical DNA mapping and whole genome sequence analyses. These results suggested vertical (bacterial strain-based) transmission of the carbapenem-resistance genetic elements. Determination of the mode of transmission of antibiotic resistance in healthcare facilities, only possible based on polyphasic approaches as described here, is essential to control resistance propagation.

scholarly journals Carbapenem-Resistant Klebsiella pneumonia Isolated from Patients Admitted in Tertiary Care Hospital in Saudi Arabia

2020 ◽  
pp. 76-85
Author(s):  
Enas Sh. Khater ◽  
AbdAlazim A. AlFaki ◽  
Shehata Said Abd Elmoaty
Keyword(s):  
Risk Factors ◽  
Klebsiella Pneumoniae ◽  
Positive Predictive Value ◽  
General Hospital ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Screening Test ◽  
Clinical Isolates ◽  
Invasive Procedures ◽  
Carbapenem Resistant

Background: Carbapenem-resistant klebsiella pneumoniae is an emerging threat worldwide causing high rates of morbidity and mortality Aim: To evaluate the prevalence of carbapenem-resistant K. pneumonia (CRKP), associated risk factors, type of infections caused by CRKP and their antimicrobial susceptibility. To evaluate Carbapenemase Detection Set (D70C) as screening test for CRKP Place and Duration of the Study: A cross sectional study and prospective cohort study was performed from June 2019 to February 2020 in intensive care unit and medical units of Al Quwayiyah General hospital. Methodology: 541 samples were collected from different patient sources. Klebsiella pneumoniae strain was only selected identified to the species level and AST was done using the Vitek-2. Minimum inhibitory concentration (MIC) of meropenem and imipenem was carried out. A Carbapenemase Detection Set (D70C) was used as screening test for CRKP while Modified Hodge test and multiplex PCR as confirmatory tests. Results: A total of 132 isolates were diagnosed as Enterobacteriaceae out of 541 patient samples.78 clinical isolates were klebsiella pneumoniae which were collected. Out of the 78 clinical isolates CRKP were 36 (46.2%) and CSKP were 42 (53.8%).) CRKP cases aged from (18-84 years) with the median patient age 59 year. Seventeen of 36 patients (47.2%) were males. the majority of the nosocomial CRKP infections were pneumonia 12 (33.3%) followed by urinary tract infection 9 (25%). The most common associated disease was diabetes (30%) followed by renal disease (27.8%). For invasive procedures, Urinary catheter was 27(75%) and 29(69%) followed by Mechanical ventilation 25(69.4%) and 22(52.4%) in CRKP and CSKP patients respectively. Reports of PCR for the 41 isolates which sent to regional laboratory for confirmation revealed that 36 isolates had carbapenemase genes; twenty eight (77.8%) K. pneumonia isolates positive for bla OXA-48 and 5 (13.9%) isolates were positive for blaNDM. in 2 (5.6%) bla KPC were detected, one isolate contained blaIMP. 5 isolates contain both blaOXA-48 and blaNDM. The sensitivity of MHT was analysed to be 91.7%. (95%Cl ratio 77.53% - 98.25%) and the specificity was 100% (95%Cl ratio 54.07% to 100%). The positive predictive value was 100% and the Negative predictive value was 66.7% ( 95%Cl ratio 40.36% to 85.53%). The sensitivity of Carbapenemase Detection Set (D70C) was 94.4% (81.34% to 99.32%) and the specificity was 80% (95%Cl ratio 28.36% to 99.49%). The positive predictive value was 97.1% (95%Cl ratio 85.46% to 99.49%).and the Negative predictive value was 66.7% (95%Cl ratio 32.67% to 89.18%). Conclusion: CRKP prevalence was 46.2% among K. pneumoniae isolates in Al Quwayiya General Hospital. Using invasive procedures such as urinary catheters or mechanical ventilator and misuse of antibiotics were risk factors associated with CRKP indicating that infection control guidelines and effective preventive measures should be strictly applied. It is very important to monitor and report changes in antimicrobial-resistant isolates but Carbapenemase Detection Set (D70C) has low specificity makes it less reliable and need PCR confirmation.

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