Biomaterial Database

Time-Kill Evaluation of Antibiotic Combinations Containing Ceftazidime-Avibactam against Extensively Drug-Resistant Pseudomonas aeruginosa and Their Potential Role against Ceftazidime-Avibactam-Resistant Isolates. 2021

María M Montero, and Sandra Domene Ochoa, and Carla López-Causapé, and Sonia Luque, and Luisa Sorlí, and Núria Campillo, and Inmaculada López Montesinos, and Eduardo Padilla, and Núria Prim, and Ariadna Angulo-Brunet, and Santiago Grau, and Antonio Oliver, and Juan P Horcajada

Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona (UAB), CEXS-Universitat Pompeu Fabra Barcelona, Barcelona, Spain.

Ceftazidime-avibactam (CZA) has emerged as a promising solution to the lack of new antibiotics against Pseudomonas aeruginosa infections. Data from in vitro assays of CZA combinations, however, are scarce. The objective of our study was to perform a time-kill analysis of the effectiveness of CZA alone and in combination with other antibiotics against a collection of extensively drug-resistant (XDR) P. aeruginosa isolates. Twenty-one previously characterized representative XDR P. aeruginosa isolates were selected. Antibiotic susceptibility was tested by broth microdilution, and results were interpreted using CLSI criteria. The time-kill experiments were performed in duplicate for each isolate. Antibiotics were tested at clinically achievable free-drug concentrations. Different treatment options, including CZA alone and combined with amikacin, aztreonam, meropenem, and colistin, were evaluated to identify the most effective combinations. Seven isolates were resistant to CZA (MIC ≥ 16/4 mg/liter), including four metallo-β-lactamase (MBL)-carrying isolates and two class A carbapenemases. Five of them were resistant or intermediate to aztreonam (MIC ≥ 16 mg/liter). Three isolates were resistant to amikacin (MIC ≥ 64 mg/liter) and one to colistin (MIC ≥ 4 mg/liter). CZA monotherapy had a bactericidal effect in 100% (14/14) of the CZA-susceptible isolates. Combination therapies achieved a greater overall reduction in bacterial load than monotherapy for the CZA-resistant isolates. CZA plus colistin was additive or synergistic in 100% (7/7) of the CZA-resistant isolates, while CZA plus amikacin and CZA plus aztreonam were additive or synergistic in 85%. CZA combined with colistin, amikacin, or aztreonam was more effective than monotherapy against XDR P. aeruginosa isolates. A CZA combination could be useful for treating XDR P. aeruginosa infections, including those caused by CZA-resistant isolates. IMPORTANCE The emergence of resistance to antibiotics is a serious public health problem worldwide and can be a cause of mortality. For this reason, antibiotic treatment is compromised, and we have few therapeutic options to treat infections. The main goal of our study is to search for new treatment options for infections caused by difficult-to-treat resistant germs. Pseudomonas aeruginosa is a Gram-negative bacterium distributed throughout the world with the ability to become resistant to most available antibiotics. Ceftazidime-avibactam (CZA) emerged as a promising solution to the lack of new antibiotics against infections caused by P. aeruginosa strains. This study intended to analyze the effect of CZA alone or in combination with other available antibiotics against P. aeruginosa strains. The combination of CZA with other antibiotics could be more effective than monotherapy against extensively drug-resistant P. aeruginosa strains.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
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
D011550	Pseudomonas aeruginosa	A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection.	Bacillus aeruginosus,Bacillus pyocyaneus,Bacterium aeruginosum,Bacterium pyocyaneum,Micrococcus pyocyaneus,Pseudomonas polycolor,Pseudomonas pyocyanea
D011552	Pseudomonas Infections	Infections with bacteria of the genus PSEUDOMONAS.	Infections, Pseudomonas,Pseudomonas aeruginosa Infection,Infection, Pseudomonas,Pseudomonas Infection,Pseudomonas aeruginosa Infections
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
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
D053961	Azabicyclo Compounds	Bicyclic bridged compounds that contain a nitrogen which has three bonds. The nomenclature indicates the number of atoms in each path around the rings, such as [2.2.2] for three equal length paths. Some members are TROPANES and BETA LACTAMS.	Azabicyclo(1.1.0)Butanes,Azabicyclo(2.2.2)Octanes,Azabicyclo(3.3.1)Nonanes,Azabicyclo(4.3.0)Nonanes,Azabicyclo(5.2.2)Undecanes
D024901	Drug Resistance, Multiple, Bacterial	The ability of bacteria to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).	Drug Resistance, Extensive, Bacterial,Drug Resistance, Extensively, Bacterial,Extensive Antibacterial Drug Resistance,Extensively Antibacterial Drug Resistance,Multidrug Resistance, Bacterial,Multiple Antibacterial Drug Resistance,Bacterial Multidrug Resistance,Bacterial Multidrug Resistances,Resistance, Bacterial Multidrug