In Vitro Activity of Imipenem/Relebactam Against Enterobacteriaceae Isolates Obtained from Intra-abdominal, Respiratory Tract, and Urinary Tract Infections in China: Study for Monitoring Antimicrobial Resistance Trends (SMART), 2015–2018

2020 ◽  
Vol 71 (Supplement_4) ◽  
pp. S427-S435
Author(s):  
Qiwen Yang ◽  
Hui Zhang ◽  
Yunsong Yu ◽  
Haishen Kong ◽  
Qiong Duan ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Respiratory Tract ◽  
Urinary Tract Infections ◽  
Antimicrobial Drugs ◽  
In Vitro Susceptibility ◽  
United States Food ◽  
Enterobacteriaceae Infections ◽  
Tract Infections ◽  
Abdominal Infections

Abstract Background Considering the increasing incidence of carbapenem-resistant Enterobacteriaceae in China, this study aimed to establish the in vitro effectiveness of imipenem/relebactam (IMI/REL) on clinical Enterobacteriaceae isolates derived from intra-abdominal infections (IAIs), respiratory tract infections (RTIs), and urinary tract infections (UTIs) in China between 2015 and 2018. Methods In total, 8781 Enterobacteriaceae isolates from IAI, RTI, and UTI samples were collected from 22 hospitals across 7 geographic regions of China. Susceptibility to antimicrobial drugs was tested using the Clinical and Laboratory Standards Institute broth microdilution and breakpoints, and IMI/REL activity was assessed using United States Food and Drug Administration guidelines. Results In 2015–2018, the most frequently identified Enterobacteriaceae species was Escherichia coli (n = 4676 [53.3%]), followed by Klebsiella pneumoniae (n = 2949 [33.6%]) and Enterobacter cloacae (n = 542 [6.2%]). The Enterobacteriaceae isolates showed 95.2% overall susceptibility to IMI/REL, of which the susceptibility rates in isolates from IAI, RTI, and UTI were 95.8%, 91.4%, and 96.6%, respectively. Overall, the susceptibilities of both intensive care unit (ICU) and non-ICU Enterobacteriaceae isolates to colistin were 92.9%, followed by IMI/REL (90.7% [95.9%]) and amikacin (83.3% [92.3%]). In addition, IMI/REL restored 66.3% susceptibility in imipenem-nonsusceptible Enterobacteriaceae. Conclusions Given their high in vitro susceptibility, Enterobacteriaceae infections in China should be considered for IMI/REL treatment, especially with isolates that are not susceptible to carbapenems.

scholarly journals Ceftazidime/Avibactam: Who Says You Can’t Teach an Old Drug New Tricks?

2016 ◽  
Vol 19 (4) ◽  
pp. 448 ◽  
Author(s):  
Katie E. Barber ◽  
Jessica K. Ortwine ◽  
Ronda L Akins
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
The United States ◽  
Phase Iii ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Tract Infections ◽  
Abdominal Infections

Purpose: Gram-negative resistance continues to rise with treatment options becoming more limited. Ceftazidime/avibactam was recently approved in the United States and Europe, which combines an established third-generation cephalosporin with a new, unique, non-β-lactam β-lactamase inhibitor. This review conducts a thorough examination of structure, pharmacology, spectrum of activity, pharmacokinetics/pharmacodynamics, in vitro and clinical efficacy and safety/tolerability of ceftazidime/avibactam, as well as detailed future directions for the agent. Methods: Pubmed and clinicaltrials.gov searches, as well as abstracts from the 2015 Interscience Conference on Antimicrobial Agents and Chemotherapy/International Society of Chemotherapy (ICAAC/ICC) and ID Week meetings and the 2016 American Society of Microbiology Microbe meeting, were conducted from January 2004 – September 2016. Relevant search terms included ceftazidime, ceftazidime/avibactam, avibactam, NXL104 and AVE1330A. The US package insert for ceftazidime/avibactam (02/2015) and European public assessment report (06/2016) were also reviewed. Results: In vitro susceptibility for ceftazidime/avibactam displayed potent activity against many Enterobacteriaceae including extended-spectrum-β-lactamase (ESBL) and carbapenemase-producing strains, as well as Pseudomonas aeruginosa. Phase II clinical trials utilized for approval demonstrated comparable safety and efficacy to imipenem/cilistatin for treatment of complicated urinary tract infections (70.4% vs. 71.4%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (91.2% vs 93.4%). Phase III data displayed non-inferior efficacy of ceftazidime/avibactam compared to doripenem for complicated urinary tract infections (70.2% vs 66.2%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (82.5% vs 84.9%), as well as comparable safety. Ceftazidime/avibactam was well-tolerated but does require renal adjustments. Additionally, 3 case series and a single case report have demonstrated the potential for ceftazidime/avibactam against multidrug resistant organisms for compassionate use or failure after previous therapy. Conclusion: By adding avibactam to ceftazidime, clinicians’ antimicrobial armamentarium is expanded, potentially increasing the ability to combat multi-drug resistant gram-negative pathogens, particularly ESBL and carbapenemase-producing organisms, as well as Pseudomonas aeruginosa. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals In Vitro Efficacy of Flomoxef against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Associated with Urinary Tract Infections in Malaysia

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 181
Author(s):  
Soo Tein Ngoi ◽  
Cindy Shuan Ju Teh ◽  
Chun Wie Chong ◽  
Kartini Abdul Jabar ◽  
Shiang Chiet Tan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Klebsiella Pneumoniae ◽  
Urinary Tract Infections ◽  
In Vitro Susceptibility ◽  
E Coli ◽  
Extended Spectrum ◽  
Tract Infections ◽  
Esbl Producers

The increasing prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has greatly affected the clinical efficacy of β-lactam antibiotics in the management of urinary tract infections (UTIs). The limited treatment options have resulted in the increased use of carbapenem. However, flomoxef could be a potential carbapenem-sparing strategy for UTIs caused by ESBL-producers. Here, we compared the in vitro susceptibility of UTI-associated ESBL-producers to flomoxef and established β-lactam antibiotics. Fifty Escherichia coli and Klebsiella pneumoniae strains isolated from urine samples were subjected to broth microdilution assay, and the presence of ESBL genes was detected by polymerase chain reactions. High rates of resistance to amoxicillin-clavulanate (76–80%), ticarcillin-clavulanate (58–76%), and piperacillin-tazobactam (48–50%) were observed, indicated by high minimum inhibitory concentration (MIC) values (32 µg/mL to 128 µg/mL) for both species. The ESBL genes blaCTX-M and blaTEM were detected in both E. coli (58% and 54%, respectively) and K. pneumoniae (88% and 74%, respectively), whereas blaSHV was found only in K. pneumoniae (94%). Carbapenems remained as the most effective antibiotics against ESBL-producing E. coli and K. pneumoniae associated with UTIs, followed by flomoxef and cephamycins. In conclusion, flomoxef may be a potential alternative to carbapenem for UTIs caused by ESBL-producers in Malaysia.

scholarly journals Clinico-Microbiological Investigation on Fosfomycin and Tigecycline Resistant Gram-Negative Bacilli Isolated from Urinary Tract Infections: A Potential Resurgence

2020 ◽  
Vol 13 (7) ◽  
Author(s):  
Maryam Dastborhan ◽  
Mojtaba Varshochi ◽  
Alka Hasani ◽  
Leila Dehghani ◽  
Elghar Soltani ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
The Difference ◽  
Conventional Antibiotics ◽  
Tract Infections

Background: Traditional antibiotics are no longer as effective as before for controlling pathogens associated with urinary tract infections (UTI), which shows the necessity of developing new and more effective antibiotics. Objectives: The current study aimed to evaluate in vitro susceptibility of fosfomycin and tigecycline towards common antibiotic-resistant Gram-negative bacilli isolated from the urinary tract. Besides, clinico-microbiological on fosfomycin and tigecycline resistant Gram-negative bacilli was investigated. Methods: In this descriptive cross-sectional study, 150 resistant Gram-negative bacilli were isolated from urine specimens send for culture, and antibiotic susceptibility assessment to the Division of Microbiology of Sina Hospital affiliated to Tabriz University of Medical Sciences which were collected from April-September 2017 are included. Antibiotic susceptibilities were evaluated according to the Clinical and Laboratory Standards published by the Institute and the criteria of the Food and Drug Administration. Results: Of 150 isolates, 138 (92%) were susceptible, and 2 (1.3%) were resistant to both fosfomycin and tigecycline, as confirmed by disk diffusion and Epsilonmeter tests. The difference was statistically significant (P = 0.001). Conclusions: Based on the results, resistance to the conventional antibiotics prescribed for the treatment of UTI was significantly high. Fosfomycin and tigecycline have an appropriate antimicrobial activity towards Gram-negative-resistant isolates involved in UTIs.

scholarly journals Antibacterial Activity of LCB10-0200 against Klebsiella pneumoniae

Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1185
Author(s):  
Sang-Hun Oh ◽  
Young-Rok Kim ◽  
Hee-Soo Park ◽  
Kyu-Man Oh ◽  
Young-Lag Cho ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Urinary Tract ◽  
Klebsiella Pneumoniae ◽  
Urinary Tract Infections ◽  
Antibacterial Agent ◽  
In Vitro Susceptibility ◽  
In Vivo Models ◽  
Tract Infections

Klebsiella pneumoniae is one of the important clinical organisms that causes various infectious diseases, including urinary tract infections, necrotizing pneumonia, and surgical wound infections. The increase in the incidence of multidrug-resistance K. pneumoniae is a major problem in public healthcare. Therefore, a novel antibacterial agent is needed to treat this pathogen. Here, we studied the in vitro and in vivo activities of a novel antibiotic LCB10-0200, a siderophore-conjugated cephalosporin, against clinical isolates of K. pneumoniae. In vitro susceptibility study found that LCB10-0200 showed potent antibacterial activity against K. pneumoniae, including the beta-lactamase producing strains. The in vivo efficacy of LCB10-0200 was examined in three different mouse infection models, including systemic, thigh, and urinary tract infections. LCB10-0200 showed more potent in vivo activity than ceftazidime in the three in vivo models against the drug-susceptible and drug-resistant K. pneumoniae strains. Taken together, these results show that LCB10-0200 is a potential antibacterial agent to treat infection caused by K. pneumoniae.

scholarly journals 1358. In vitro Activity of Ceftazidime–Avibactam and Comparator Agents Against Pseudomonas aeruginosa Causing Intra-Abdominal, Lower Respiratory, and Urinary Tract Infections Collected in Latin America as Part of the INFORM Global Surveillance Program, 2012–2016

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S416-S416
Author(s):  
Mark Wise ◽  
Krystyna Kazmierczak ◽  
Gregory G Stone ◽  
Dan Sahm
Keyword(s):  
Latin America ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Infection Types ◽  
Tract Infections ◽  
Abdominal Infections

Abstract Background The non-β-lactam β-lactamase inhibitor avibactam (AVI) is active against class A, C, and some class D β-lactamases, in combination with ceftazidime (CAZ) has been approved by the FDA and EMA for treatment of intra-abdominal infections (IAI), lower respiratory tract infections (LRTI), and urinary tract infections (UTI). This study reports on the in vitro activity of (CAZ-AVI) and comparators vs. P. aeruginosa collected from IAIs, LRTIs, and UTIs in Latin America as part of the INFORM surveillance study from 2012 to 2016. Methods For INFORM surveillance over 2012–2016 in Latin America, 1,595 nonduplicate P. aeruginosa isolates linked to IAIs, LRTIs, and UTIs were collected from 26 clinical sites in six countries. Susceptibility testing was done using broth microdilution according to CLSI guidelines and using CLSI 2018 breakpoints. CAZ was tested with AVI at a fixed concentration of 4 mg/mL. Meropenem (MEM) nonsusceptible organisms were screened for β-lactamase genes by PCR. Results Among the full collection of P. aeruginosa, CAZ-AVI showed consistently higher % susceptibilities than all comparators except for colistin (CST) for all infection sources. The addition of AVI to CAZ resulted in an increase in susceptibility ranging from 14.2% (IAI) to 19.5% (UTI). Against the non-metallo-β-lactamase (MBL) harboring subset, CAZ-AVI showed extremely potent activity (MIC90, 8 mg/mL) for all infection sources. In this subset, the activity of CAZ-AVI approached that of colistin for IAIs (susceptibility of 93.3% vs. 96.4%, respectively). Conclusion CAZ-AVI demonstrated very good in vitro activity against P. aeruginosa isolates, especially those without MBLs. More isolates were susceptible to CAZ-AVI than to MEM for all infection types. Disclosures M. Wise, Pfizer Inc.: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary. K. Kazmierczak, Pfizer Inc.: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary. G. G. Stone, Pfizer Inc.: Employee, Salary. AstraZeneca: Former Employee and Shareholder, Salary. D. Sahm, Pfizer Inc.: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary.

Mecillinam: Old Molecule, New Option

2018 ◽  
Vol 13 (03) ◽  
pp. 229-233
Author(s):  
Mevliye Yetik ◽  
Fulya Bayındır Bilman
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Susceptibility Testing ◽  
Diffusion Method ◽  
First Line ◽  
Disk Diffusion Method ◽  
In Vitro Susceptibility ◽  
E Coli ◽  
Tract Infections

Background Mecillinam is a β-lactam antibiotic that is increasingly being used for the treatment of uncomplicated urinary tract infections. Nevertheless, the international guidelines still recommend nitrofurantoin, fosfomycin trometamol, and pivmecillinam as first-line agents in the treatment of such infections. Aim The objective of this study was to determine the in vitro efficacy of mecillinam against Escherichia coli and Klebsiella pneumoniae strains isolated from children with urinary tract infections. Materials Methods We investigated E. coli and K. pneumoniae isolates, obtained within the period from January 2016 to October 2017, from urine samples of patients aged 0 to 16 years. Antibiotics susceptibility testing was conducted through the disk diffusion method based on the guidelines provided by EUCAST (European Committee on Antimicrobial Susceptibility Testing). Extended-spectrum β-lactamase (ESBL)-positivity was detected by the double-disk synergy test. Isolates with mecillinam inhibition-zone diameter breakpoints lower than < 15 mm were considered to be resistant according to EUCAST criteria. Results A total of 450 isolates were assessed in the study, 135 of which were ESBL-producing E.coli, 230 were non-ESBL-producing E. coli, 35 were ESBL-producing K. pneumoniae, and 50 were non-ESBL-producing K. pneumoniae isolates. Mecillinam susceptibility was observed in most of the non-ESBL-producing and ESBL-producing E. coli isolates (230/230, 100% and 115/135, 85.1%, respectively). The rates of susceptibility of the non-ESBL-producing and ESBL-producing K. pneumoniae isolates were 37/50 (74%) and 24/35 (68.6%), respectively. Conclusion The in vitro susceptibility results obtained support the usage of mecillinam as a first-line agent. The high susceptibility of non-ESBL-producing E. coli and K. pneumoniae isolates established in vitro brings the hope that this antibiotic could soon be used in clinical practice in Turkey.

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