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 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 Multidrug-resistant and extended-spectrum beta-lactamase-producing uropathogens in children in Bhaktapur, Nepal

2020 ◽  
Vol 48 (1) ◽  
Author(s):  
Ganendra Bhakta Raya ◽  
Bhim Gopal Dhoubhadel ◽  
Dhruba Shrestha ◽  
Sunayana Raya ◽  
Ujjwal Laghu ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Beta Lactamase ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum

scholarly journals Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-ProducingEnterobacteriaceae

2018 ◽  
Vol 31 (2) ◽  
Author(s):  
Jesús Rodríguez-Baño ◽  
Belén Gutiérrez-Gutiérrez ◽  
Isabel Machuca ◽  
Alvaro Pascual
Keyword(s):  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Beta Lactamase ◽  
Content Type ◽  
Extended Spectrum Beta Lactamase ◽  
Development Of Resistance ◽  
Extended Spectrum ◽  
Invasive Infections ◽  
Risk Patients

SUMMARYTherapy of invasive infections due to multidrug-resistantEnterobacteriaceae(MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer β-lactam–β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole. These drugs might be considered in some specific situations. AmpC producers are resistant to cephamycins, but cefepime is an option. In the case of carbapenemase-producingEnterobacteriaceae(CPE), only some “second-line” drugs, such as polymyxins, tigecycline, aminoglycosides, and fosfomycin, may be active; double carbapenems can also be considered in specific situations. Combination therapy is associated with better outcomes for high-risk patients, such as those in septic shock or with pneumonia. Ceftazidime-avibactam was recently approved and is active against KPC and OXA-48 producers; the available experience is scarce but promising, although development of resistance is a concern. New drugs active against some CPE isolates are in different stages of development, including meropenem-vaborbactam, imipenem-relebactam, plazomicin, cefiderocol, eravacycline, and aztreonam-avibactam. Overall, therapy of MDR-E infection must be individualized according to the susceptibility profile, type, and severity of infection and the features of the patient.

scholarly journals Antibiotics Profile, Prevalence of Extended-Spectrum Beta-Lactamase (ESBL), and Multidrug-Resistant Enterobacteriaceae from Different Clinical Samples in Khartoum State, Sudan

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Ehssan H. Moglad
Keyword(s):  
Tracheal Aspirate ◽  
Multidrug Resistant ◽  
Vaginal Swab ◽  
Clinical Samples ◽  
Beta Lactamase ◽  
Biochemical Tests ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum ◽  
Different Sources

One of the global requirements for controlling the occurrence of resistance to antimicrobial drugs is to understanding the resistivity profile of various clinical isolates. Therefore, this study aimed to deliver the indication of different resistant profiles of clinically isolated Enterobacteriaceae from different sources of samples from Khartoum state, Sudan, and to determine the prevalence rate of extended-spectrum beta-lactamase (ESBL), multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) bacteria. A total of 144 Gram-negative bacteria were collected from different sources (vaginal swab, urine, catheter tip, sputum, blood, tracheal aspirate, pus, stool, pleural fluid, and throat swab). Samples were subcultured and identified according to their cultural characteristics and biochemical tests. Antimicrobial susceptibility test was performed for twenty-four antibiotics from eleven categories against all isolated Enterobacteriaceae according to the recommendation of Clinical and Laboratory Standards Institute (CLSI). The result showed that out of 144 isolates, Escherichia coli and Klebsiella pneumoniae were predominant isolates with the percentage of 47.9 and 25%, respectively. The prevalence of ESBL was higher in K. pneumonia (38.9%) than E. coli (34.8%). All isolated E. coli were sensitive to nitrofurantoin and tigecycline. There was a high prevalence of MDR Enterobacteriaceae, and only one isolate was XDR, while PDR was zero for all isolated bacteria. Active antimicrobial-resistant (AMR) observation through constant data sharing and management of all stakeholders is crucial to recognize and control the AMR global burden. Also, effective antibiotic stewardship procedures would be applied to limit the unreasonable expenditure of antibiotics in Sudan.

scholarly journals Extended-Spectrum Beta-Lactamase (ESBL)-Producing Escherichia coli Isolated from Flies in the Urban Center of Berlin, Germany

2019 ◽  
Vol 16 (9) ◽  
pp. 1530 ◽  
Author(s):  
Wibke Wetzker ◽  
Yvonne Pfeifer ◽  
Solvy Wolke ◽  
Andrea Haselbeck ◽  
Rasmus Leistner ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Continuous Monitoring ◽  
Companion Animals ◽  
Multidrug Resistant ◽  
Beta Lactamase ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum ◽  
Ciprofloxacin Resistance ◽  
Multiple Pathogens

Background: The monitoring of antimicrobial resistance (AMR) in microorganisms that circulate in the environment is an important topic of scientific research and contributes to the development of action plans to combat the spread of multidrug-resistant (MDR) bacteria. As a synanthropic vector for multiple pathogens and a reservoir for AMR, flies can be used for surveillance. Methods: We collected 163 flies in the inner city of Berlin and examined them for extended-spectrum β-lactamase (ESBL)-producing Escherichia coli genotypically and phenotypically. Results: The prevalence of ESBL-producing E. coli in flies was 12.9%. Almost half (47.6%) of the ESBL-positive samples showed a co-resistance to ciprofloxacin. Resistance to carbapenems or colistin was not detected. The predominant ESBL-type was CTX-M-1, which is associated with wildlife, livestock, and companion animals as a potential major source of transmission of MDR E. coli to flies. Conclusions: This field study confirms the permanent presence of ESBL-producing E. coli in an urban fly population. For continuous monitoring of environmental contamination with multidrug-resistant (MDR) bacteria, flies can be used as indicators without much effort.

scholarly journals Detection of extended-spectrum beta-lactamase-producing E. coli and Klebsiella spp. in effluents of different hospitals sewage in Biratnagar, Nepal

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Sanjay Mahato ◽  
Ajay Mahato ◽  
Elina Pokharel ◽  
Ankita Tamrakar
Keyword(s):  
Multidrug Resistant ◽  
Resistance Pattern ◽  
Beta Lactamase ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum ◽  
Amoxicillin Clavulanate ◽  
Baseline Information ◽  
Klebsiella Spp

Abstract Objective This study was aimed to determine prevalence and resistance pattern like multidrug resistant (MDR) or ESBL nature of E. coli and Klebsiella spp. from various sewage drain samples with an idea to deliver baseline information that could be utilized for defining guidelines for the treatment of hospital sewages. Results Of 10 sewage samples analyzed, 7 (70%) contained E. coli while 6 (60%) contained Klebsiella. Except one sample, all positive samples contained both E. coli and Klebsiella spp. E. coli isolates were resistant to ampicillin, amoxicillin, cefoxitin, cefuroxime, and cefpodoxime; while 85.7% were resistant to amoxicillin/clavulanate, ceftazidime, cefotaxime and ceftriaxone. 71.4%, 57.1%, 42.9%, and 28.6% were resistant to aztreonam, trimethoprim/sulfamethoxazole, nitrofurantoin, and gentamicin. Most were sensitive to chloramphenicol, ofloxacin, ciprofloxacin, and azithromycin. 85.7% and 57.1% of E. coli were MDR and ESBL isolates, respectively. Klebsiella were resistant to ampicillin, amoxicillin, and amoxicillin/clavulanate. 83.4% of Klebsiella were resistant to cefoxitin. 66.7% of strains were resistant to cefuroxime, ceftazidime, cefotaxime, ceftriaxone, and cefpodoxime. Klebsiella showed 50% resistant to aztreonam and trimethoprim/sulfamethoxazole, while 33.3% were resistant to chloramphenicol, nitrofurantoin, ofloxacin, and ciprofloxacin. Klebsiella were sensitive to azithromycin and gentamicin. 66.7% and 33.3% of Klebsiella were MDR and ESBL isolates, respectively.

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