scholarly journals In Vitro Activity of Plazomicin among Carbapenem-resistant Enterobacteriaceae

2021 ◽  
Vol 9 (A) ◽  
pp. 1203-1207
Author(s):  
Sara Essam ◽  
Nada Nawar ◽  
Mohamed ElBashaar ◽  
May Soliman ◽  
May Abdelfattah
Keyword(s):  
Therapeutic Option ◽  
Vitro Activity ◽  
Clinical Samples ◽  
In Vitro Activity ◽  
University Hospitals ◽  
Therapeutic Drugs ◽  
Carbapenem Resistant ◽  
Global Threat ◽  
Carbapenem Resistant Enterobacteriaceae

Background:  Carbapenem-resistant Enterobacteriaceae (CRE) have been disseminated worldwide and became a global threat. Due to limited therapeutic drugs plazomicin - a new semisynthetic aminoglycoside - have been suggested as an alternative option owing to its stability against aminoglycosides modifying enzymes (AMEs). This study aims to assess the in vitro activity of plazomicin against CRE isolates and to detect different types of carbapenemases among these isolates. Material and Methods: In this study, 102 CRE isolates were collected from different clinical samples at Cairo University hospitals and the presence of carbapenemases was detected by modified carbapenem inhibition method (mCIM) and multiplex PCR tests. Plazomicin susceptibility testing was done using E test. Results: The most frequently detected carbapenemase genes were blaNDM in 75 (73.5%) isolates, followed by blaOXA-48 in 57 (55.9%) and blaKPC in 16 (15.5%) isolates. Plazomicin was active against 32 (31.4%) isolates. Among the isolates carrying blaNDM gene only and those carrying blaOXA-48 gene only, 21% and 41% were sensitive to plazomicin, respectively. Plazomicin showed the highest sensitivity against CRE isolates compared to the other tested antibiotics. Conclusion: Plazomicin might be a good option for treatment of infections caused by CRE. In health care settings where blaNDM gene is prevalent, plazomicin may not be a good therapeutic option for CRE infections.

scholarly journals In Vitro Activity of Eravacycline in Combination with Colistin Against Carbapenem-Resistant A. baumannii Isolates

2019 ◽  
Author(s):  
H. Selcuk Ozger ◽  
Tugba Cuhadar ◽  
Serap Suzuk Yildiz ◽  
Zehra Demirbas Gulmez ◽  
Murat Dizbay ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Vitro Activity ◽  
Synergistic Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Similar Activity ◽  
Microdilution Method ◽  
Carbapenem Resistant ◽  
Broth Microdilution Method

AbstractThe synergistic activity of eravacycline in combination with colistin on carbapenem-resistant A.baumannii (CRAB) isolates was evaluated in this study. Minimum inhibitory concentrations (MICs) of eravacycline and colistin were determined by the broth microdilution method. MICs values ranged between 1 to 4 mg and 0,5 to 128 mg/L for eravacycline and colistin, respectively. In-vitro synergy between eravacycline and colistin was evaluated by using the chequerboard methodology. Synergistic activity was found in 10 % of the strains, and additive effect in 20 %. No antagonism was detected. Similar activity was also observed in colistin resistant CRAB isolates. The result of this study indicates that eravacycline and colistin combination may be a potential therapeutic option for the treatment of CRAB related infections.

scholarly journals 1378. Evaluation of the In vitro Activity of Meropenem-Vaborbactam Against Carbapenem-Resistant Enterobacteriaceae, Including Isolates Resistant to Ceftazidime–Avibactam

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S422-S422
Author(s):  
William R Wilson ◽  
Ellen Kline ◽  
Chelsea Jones ◽  
Kristin Morder ◽  
Cornelius J Clancy ◽  
...  
Keyword(s):  
Premature Stop Codon ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Wild Type ◽  
In Vitro Susceptibility ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Carbapenem Resistant Enterobacteriaceae ◽  
Research Grant

Abstract Background Meropenem-vaborbactam (M-V) is a novel antibiotic for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections. Our objective was to determine the in vitro activity of meropenem-vaborbactam against genetically-diverse CRE isolates, including those that have developed resistance to Ceftazidime–Avibactam (C-A). Methods Minimum inhibitory concentrations (MICs) were determined for meropenem (MER), M-V, and C-A by reference broth microdilution (BMD) methods in triplicate. Vaborbactam and avibactam were tested at fixed concentrations of 8 and 4 µg/mL, respectively. Quality control strains were used and within expected ranges. Polymerase chain reaction (PCR) with DNA sequencing was used to detect resistance determinants, including Klebsiella pneumoniae carbapenemase (KPC) subtypes and porin mutations. Results A total of 117 CRE isolates were tested, including K. pneumoniae (Kp; n = 83), E. cloacae (n = 17), E. coli (n = 10), and E. aerogenes (n = 7). Seventy-nine percent harbored blaKPC. KPC subtypes included KPC-2 (n = 32), KPC-3 (n = 41), KPC-3 variants (n = 16), and KPC [not typed] (n = 4, all E. coli). Among 74 K. pneumoniae, 95% had a premature stop codon in ompk35 and ompK36 genotypes included wild type (n = 48), IS5 insertion (n = 13), 135–136 DG duplication (n = 9), and other mutations (n = 4). The median (range) MICs for MER, C-A, and M-V were 8 (0.06 to ≥128), 1 (0.25 to ≥512), and 0.03 (0.015––16), respectively. Corresponding rates of susceptibility were 23, 84, and 98%, respectively. Fifty-three percent and 95% of C-A-resistant isolates were susceptible to MER and M-V, respectively. Among Kp, C-A MICs did not vary by KPC subtype or porin genotype. On the other hand, median M-V MICs were higher among KPC-2 than KPC-3 Kp (0.12 vs. 0.03; P = 0.002), and among Kp with ompK36 porin mutations compared with wild type (0.25 vs. 0.03; P < 0.001). Among Kp with KPC-3 variants (n = 16), the median M-V MIC was 0.03 (0.015––2); 100% were M-V susceptible. Median M-V MICs did not vary by CRE species. Only two isolates were M-V resistant, both were E. cloacae that did not harbor blaKPC. Conclusion M-V demonstrates high rates of in vitro susceptibility against diverse CRE isolates, including those that are resistant to C-A. As this agent is introduced into the clinic, it will be important to identify K. pneumoniae isolates harboring KPC-2 with ompK36 porin mutations that demonstrate higher MICs. Disclosures M. H. Nguyen, Merck: Grant Investigator, Research grant. Astellas: Grant Investigator, Research grant.

scholarly journals Plazomicin: a new aminoglycoside in the fight against antimicrobial resistance

2020 ◽  
Vol 7 ◽  
pp. 204993612095260
Author(s):  
Justin A. Clark ◽  
David S. Burgess
Keyword(s):  
Clinical Data ◽  
Vitro Activity ◽  
Original Research ◽  
Drug Resistant ◽  
In Vitro Activity ◽  
Carbapenem Resistant ◽  
Tract Infections ◽  
Carbapenem Resistant Enterobacteriaceae

Objective: To review the mechanism of action, mechanisms of resistance, in vitro activity, pharmacokinetics, pharmacodynamics, and clinical data for a novel aminoglycoside. Data sources: A PubMed search was performed from January 2006 to August 2019 using the following search terms: plazomicin and ACHN-490. Another search was conducted on clinicaltrials.gov for published clinical data. References from selected studies were also used to find additional literature. Study selection and data extraction: All English-language studies presenting original research ( in vitro, in vivo, pharmacokinetic, and clinical) were evaluated. Data synthesis: Plazomicin has in vitro activity against several multi-drug-resistant organisms, including carbapenem-resistant Enterobacteriaceae. It was Food and Drug Administration (FDA) approved to treat complicated urinary tract infections (cUTIs), including acute pyelonephritis, following phase II and III trials compared with levofloxacin and meropenem, respectively. Despite the FDA Black Box Warning for aminoglycoside class effects (nephrotoxicity, ototoxicity, neuromuscular blockade, and pregnancy risk), it exhibited a favorable safety profile with the most common adverse effects being decreased renal function (3.7%), diarrhea (2.3%), hypertension (2.3%), headache (1.3%), nausea (1.3%), vomiting (1.3%), and hypotension (1.0%) in the largest in-human trial. Relevance to patient care and clinical practice: Plazomicin will likely be used in the treatment of multi-drug-resistant cUTIs or in combination to treat serious carbapenem-resistant Enterobacteriaceae infections. Conclusions: Plazomicin appears poised to help fill the need for new agents to treat infections caused by multi-drug-resistant Enterobacteriaceae.

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