Ceftazidime-Avibactam plus aztreonam synergistic combination tested against carbapenem-resistant Enterobacterales characterized phenotypically and genotypically: a glimmer of hope. 2023

Rawan Taha, and Ola Kader, and Sherine Shawky, and Shahinda Rezk
Microbiology Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.

BACKGROUND Carbapenemase-producing Enterobacterales (CPE) show rapid global dissemination and pose a significant therapeutic challenge. This study aimed to characterize carbapenemase-producing Klebsiella spp. and Escherichia coli (E. coli) phenotypically and genotypically and evaluate the effect of ceftazidime/ avibactam plus aztreonam combination. METHODS A total of 219 Klebsiella species and 390 E. coli strains were isolated from clinical samples, in which 80 Klebsiella spp. and 20 E coli isolates were resistant to tested carbapenems (imipenem, ertapenem, meropenem) by disk diffusion/broth dilution method and Vitek-2 compact system. MASTDISCS Combi Carba plus discs and real time PCR were used to determine type of carbapenemase phenotypically and genotypically, respectively. Interestingly, the synergistic effect between ceftazidime-avibactam (E-test) and aztreonam (disc) was tested against the CPE isolates. RESULTS Out of the carbapenem-resistant isolates, 76.25% Klebsiella spp. isolates were extensively drug-resistant (XDR) while 18.75% were pan drug-resistant (PDR), and 5% were multidrug-resistant (MDR). Regarding E. coli, 5% were PDR, 20% were MDR and 75% were XDR. More than one carbapenemase gene was detected in 99% of the isolates. In comparison between MAST-Carba plus discs and PCR results, sensitivity and specificity were (85.42-97.92%) in Klebsiella spp., and (69.64-100%) in E. coli, respectively. Moreover, a strong association was detected between both test results among Klebsiella spp. (p < 0.001) and E. coli (p = 0.012) isolates. Finally, ceftazidime-avibactam and aztreonam combination showed a synergistic effect in 98.8% of Klebsiella spp. and 95% of E coli. All 16 PDR isolates showed synergy. CONCLUSIONS This synergistic effect spots the light on new therapeutics for XDR and PDR CPE.

UI MeSH Term Description Entries
D007709 Klebsiella A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria whose organisms arrange singly, in pairs, or short chains. This genus is commonly found in the intestinal tract and is an opportunistic pathogen that can give rise to bacteremia, pneumonia, urinary tract and several other types of human infection.
D007711 Klebsiella pneumoniae Gram-negative, non-motile, capsulated, gas-producing rods found widely in nature and associated with urinary and respiratory infections in humans. Bacillus pneumoniae,Bacterium pneumoniae crouposae,Hyalococcus pneumoniae,Klebsiella pneumoniae aerogenes,Klebsiella rhinoscleromatis
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D002442 Ceftazidime Semisynthetic, broad-spectrum antibacterial derived from CEPHALORIDINE and used especially for Pseudomonas and other gram-negative infections in debilitated patients. Ceftazidime Anhydrous,Ceftazidime Pentahydrate,Fortaz,Fortum,GR-20263,LY-139381,Pyridinium, 1-((7-(((2-amino-4-thiazolyl)((1-carboxy-1-methylethoxy)imino)acetyl)amino)-2-carboxy-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-en-3-yl)methyl)-, inner salt, pentahydrate, (6R-(6alpha,7beta(Z)))-,Tazidime,GR 20263,GR20263,LY 139381,LY139381
D004338 Drug Combinations Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. Drug Combination,Combination, Drug,Combinations, Drug
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D001398 Aztreonam A monocyclic beta-lactam antibiotic originally isolated from Chromobacterium violaceum. It is resistant to beta-lactamases and is used in gram-negative infections, especially of the meninges, bladder, and kidneys. It may cause a superinfection with gram-positive organisms. Az-threonam,Azactam,Azthreonam,SQ-26,776,Urobactam,Az threonam,SQ 26,776,SQ26,776
D001618 beta-Lactamases Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. beta-Lactamase,beta Lactamase,beta Lactamases

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