scholarly journals Bioactivity assessment of the Saudi Arabian Marine Streptomyces sp. Al-Dhabi-90, metabolic profiling and its in vitro inhibitory property against multidrug resistant and extended-spectrum beta-lactamase clinical bacterial pathogens

2019 ◽  
Vol 12 (4) ◽  
pp. 549-556 ◽  
Author(s):  
Naif Abdullah Al-Dhabi ◽  
Abdul-Kareem Mohammed Ghilan ◽  
Galal Ali Esmail ◽  
Mariadhas Valan Arasu ◽  
Veeramuthu Duraipandiyan ◽  
...  
Keyword(s):  
Metabolic Profiling ◽  
Bacterial Pathogens ◽  
Multidrug Resistant ◽  
Beta Lactamase ◽  
Streptomyces Sp ◽  
Extended Spectrum Beta Lactamase ◽  
Inhibitory Property ◽  
Extended Spectrum ◽  
Marine Streptomyces

scholarly journals Detection of extended spectrum beta-lactamase genes in Pseudomonas aeruginosa isolated from patients in rural Eastern Cape Province, South Africa

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mojisola C. Hosu ◽  
Sandeep D. Vasaikar ◽  
Grace E. Okuthe ◽  
Teke Apalata
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Multidrug Resistant ◽  
High Rate ◽  
Infection Prevention And Control ◽  
Beta Lactamase ◽  
Eastern Cape ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
Resistance Patterns

AbstractThe proliferation of extended spectrum beta-lactamase (ESBL) producing Pseudomonas aeruginosa represent a major public health threat. In this study, we evaluated the antimicrobial resistance patterns of P. aeruginosa strains and characterized the ESBLs and Metallo- β-lactamases (MBL) produced. Strains of P. aeruginosa cultured from patients who attended Nelson Mandela Academic Hospital and other clinics in the four district municipalities of the Eastern Cape between August 2017 and May 2019 were identified; antimicrobial susceptibility testing was carried out against thirteen clinically relevant antibiotics using the BioMérieux VITEK 2 and confirmed by Beckman autoSCAN-4 System. Real-time PCR was done using Roche Light Cycler 2.0 to detect the presence of ESBLs; blaSHV, blaTEM and blaCTX-M genes; and MBLs; blaIMP, blaVIM. Strains of P. aeruginosa demonstrated resistance to wide-ranging clinically relevant antibiotics including piperacillin (64.2%), followed by aztreonam (57.8%), cefepime (51.5%), ceftazidime (51.0%), piperacillin/tazobactam (50.5%), and imipenem (46.6%). A total of 75 (36.8%) multidrug-resistant (MDR) strains were observed of the total pool of isolates. The blaTEM, blaSHV and blaCTX-M was detected in 79.3%, 69.5% and 31.7% isolates (n = 82), respectively. The blaIMP was detected in 1.25% while no blaVIM was detected in any of the strains tested. The study showed a high rate of MDR P. aeruginosa in our setting. The vast majority of these resistant strains carried blaTEM and blaSHV genes. Continuous monitoring of antimicrobial resistance and strict compliance towards infection prevention and control practices are the best defence against spread of MDR P. aeruginosa.

scholarly journals Multidrug-Resistant, Including Extended-Spectrum Beta Lactamase-Producing and Quinolone-Resistant, Escherichia coli Isolated from Poultry and Domestic Pigs in Dar es Salaam, Tanzania

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 406
Author(s):  
Zuhura I. Kimera ◽  
Fauster X. Mgaya ◽  
Gerald Misinzo ◽  
Stephen E. Mshana ◽  
Nyambura Moremi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Multidrug Resistant ◽  
Antibiotics Resistance ◽  
Beta Lactamase ◽  
Domestic Pigs ◽  
Extended Spectrum Beta Lactamase ◽  
Phenotypic Profile ◽  
E Coli ◽  
Extended Spectrum ◽  
Esbl Producers

We determined the phenotypic profile of multidrug-resistant (MDR) Escherichia coli isolated from 698 samples (390 and 308 from poultry and domestic pigs, respectively). In total, 562 Enterobacteria were isolated. About 80.5% of the isolates were E. coli. Occurrence of E. coli was significantly higher among domestic pigs (73.1%) than in poultry (60.5%) (p = 0.000). In both poultry and domestic pigs, E. coli isolates were highly resistant to tetracycline (63.5%), nalidixic acid (53.7%), ampicillin (52.3%), and trimethoprim/sulfamethoxazole (50.9%). About 51.6%, 65.3%, and 53.7% of E. coli were MDR, extended-spectrum beta lactamase-producing enterobacteriaceae (ESBL-PE), and quinolone-resistant, respectively. A total of 68% of the extended-spectrum beta lactamase (ESBL) producers were also resistant to quinolones. For all tested antibiotics, resistance was significantly higher in ESBL-producing and quinolone-resistant isolates than the non-ESBL producers and non-quinolone-resistant E. coli. Eight isolates were resistant to eight classes of antimicrobials. We compared phenotypic with genotypic results of 20 MDR E. coli isolates, ESBL producers, and quinolone-resistant strains and found 80% harbored blaCTX-M, 15% aac(6)-lb-cr, 10% qnrB, and 5% qepA. None harbored TEM, SHV, qnrA, qnrS, qnrC, or qnrD. The observed pattern and level of resistance render this portfolio of antibiotics ineffective for their intended use.

scholarly journals Ceftolozane-tazobactam versus meropenem for definitive treatment of bloodstream infection due to extended-spectrum beta-lactamase (ESBL) and AmpC-producing Enterobacterales (“MERINO-3”): study protocol for a multicentre, open-label randomised non-inferiority trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Adam G. Stewart ◽  
Patrick N. A. Harris ◽  
Mark D. Chatfield ◽  
Roberta Littleford ◽  
David L. Paterson
Keyword(s):  
Bloodstream Infection ◽  
Generation Cephalosporin ◽  
Multidrug Resistant ◽  
Definitive Treatment ◽  
Resistant Organism ◽  
Third Generation ◽  
Beta Lactamase ◽  
Open Label ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum

Abstract Background Extended-spectrum beta-lactamase (ESBL) and AmpC-producing Enterobacterales are common causes of bloodstream infection. ESBL-producing bacteria are typically resistant to third-generation cephalosporins and result in a sizeable economic and public health burden. AmpC-producing Enterobacterales may develop third-generation cephalosporin resistance through enzyme hyper-expression. In no observational study has the outcome of treatment of these infections been surpassed by carbapenems. Widespread use of carbapenems may drive the development of carbapenem-resistant Gram-negative bacilli. Methods This study will use a multicentre, parallel group open-label non-inferiority trial design comparing ceftolozane-tazobactam and meropenem in adult patients with bloodstream infection caused by ESBL or AmpC-producing Enterobacterales. Trial recruitment will occur in up to 40 sites in six countries (Australia, Singapore, Italy, Spain, Saudi Arabia and Lebanon). The sample size is determined by a predefined quantity of ceftolozane-tazobactam to be supplied by Merck, Sharpe and Dohme (MSD). We anticipate that a trial with 600 patients contributing to the primary outcome analysis would have 80% power to declare non-inferiority with a 5% non-inferiority margin, assuming a 30-day mortality of 5% in both randomised groups. Once randomised, definitive treatment will be for a minimum of 5 days and a maximum of 14 days with the total duration determined by treating clinicians. Data describing demographic information, risk factors, concomitant antibiotics, illness scores, microbiology, multidrug-resistant organism screening, discharge and mortality will be collected. Discussion Participants will have bloodstream infection due to third-generation cephalosporin non-susceptible E. coli and Klebsiella spp. or Enterobacter spp., Citrobacter freundii, Morganella morganii, Providencia spp. or Serratia marcescens. They will be randomised 1:1 to ceftolozane-tazobactam 3 g versus meropenem 1 g, both every 8 h. Secondary outcomes will be a comparison of 14-day all-cause mortality, clinical and microbiological success at day 5, functional bacteraemia score, microbiological relapse, new bloodstream infection, length of hospital stay, serious adverse events, C. difficile infection, multidrug-resistant organism colonisation. The estimated trial completion date is December 2024. Trial registration The MERINO-3 trial is registered under the US National Institute of Health ClinicalTrials.gov register, reference number: NCT04238390. Registered on 23 January 2020.

scholarly journals 1564. Activity of bacteriophage against multidrug resistant Klebsiella pneumoniae

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S782-S782
Author(s):  
Sailaja Puttagunta ◽  
Maya Kahan-Haanum ◽  
Sharon Kredo-Russo ◽  
Eyal Weinstock ◽  
Efrat Khabra ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Unmet Need ◽  
Multidrug Resistant ◽  
Beta Lactamase ◽  
Bacterial Strains ◽  
Antibiotic Resistant ◽  
Extended Spectrum Beta Lactamase ◽  
Novel Approach ◽  
Infection Types

Abstract Background The prevalence of extended-spectrum beta-lactamase (ESBL) producing and carbapenem resistant (CR) Klebsiella pneumoniae (KP) has significantly risen in all geographic regions. Infections due to these bacteria are associated with high mortality across different infection types. Even with newer options, there remains an unmet need for safe and effective therapeutic options to treat infections caused by ESBL and CR KP. Phage therapy offers a novel approach with an unprecedented and orthogonal mechanism of action for treatment of diseases caused by pathogenic bacterial strains that are insufficiently addressed by available antibiotics. Phage-based therapies confer a high strain-level specificity and have a strong intrinsic safety profile. Here we describe the identification of novel phages that can effectively target antibiotic resistant KP strains. Host range of the 21 phages on 33 strain KP panel via solid culture infectivity assays. Red marks resistance to infection while sensitivity to phage is marked in green Methods KP clinical strains were isolated from human stool specimens preserved in glycerol. Selective culturing was carried, followed by testing of individual colonies for motility, indole and urease production, sequenced and analyzed by Kleborate tool to determine antibiotic resistant genes. Natural phages were isolated from plaques that developed on susceptible bacterial targets, sequenced and characterized. Results Antibiotic-resistant KP strains encoding beta lactamase genes or a carbapenemase (n=33) were isolated from healthy individuals (n=3), and patients with inflammatory bowel disease (n=26) or primary sclerosing cholangitis (n=3). Isolates sequencing revealed bla CTX-M15 and/or bla SHV encoding strains and carbapenamase KPC-2. A panel of 21 phages targeting the beta-lactamase- and carbapenemase-producing KP strains were identified. Phage sequencing revealed that all phages belong to the Caudovirales order and include 6 Siphoviridae, 14 Myoviridae, and 1 Podoviridae. In vitro lytic activity of the phages was tested on the isolated bacteria and revealed a coverage of 70% of the 33 isolated antibiotic resistant strains, >50% of which were targeted by multiple phages. Conclusion Collectively, these results demonstrate the feasibility of identifying phage with potent activity against antibiotic resistant KP strains, and may provide a novel therapeutic approach for treatment of ESBL and CR KP infections. Disclosures All Authors: No reported disclosures

scholarly journals Clinical extended-spectrum beta-lactamase antibiotic resistance plasmids have diverse transfer rates and can spread in the absence of antibiotic selection

2019 ◽  
Author(s):  
Fabienne Benz ◽  
Jana S. Huisman ◽  
Erik Bakkeren ◽  
Joana A. Herter ◽  
Tanja Stadler ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Conjugative Transfer ◽  
Beta Lactamase ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
Resistance Plasmids ◽  
Serovar Typhimurium ◽  
Spreading Potential

AbstractHorizontal gene transfer, mediated by conjugative plasmids, is a major driver of the global spread of antibiotic resistance. However, the relative contributions of factors that underlie the spread of clinically relevant plasmids are unclear. Here, we quantified conjugative transfer dynamics of Extended Spectrum Beta-Lactamase (ESBL) producing plasmids in the absence of antibiotics. We showed that clinical Escherichia coli strains natively associated with ESBL-plasmids conjugate efficiently with three distinct E. coli strains and one Salmonella enterica serovar Typhimurium strain, reaching final transconjugant frequencies of up to 1% within 24 hours in vitro. The variation of final transconjugant frequencies varied among plasmids, donors and recipients and was better explained by variation in conjugative transfer efficiency than by variable clonal expansion. We identified plasmid-specific genetic factors, specifically the presence/absence of transfer genes, that influenced final transconjugant frequencies. Finally, we investigated plasmid spread within the mouse intestine, demonstrating qualitative agreement between plasmid spread in vitro and in vivo. This suggests a potential for the prediction of plasmid spread in the gut of animals and humans, based on in vitro testing. Altogether, this may allow the identification of resistance plasmids with high spreading potential and help to devise appropriate measures to restrict their spread.

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