scholarly journals In VitroActivity of Aztreonam-Avibactam against a Global Collection of Gram-Negative Pathogens from 2012 and 2013

2015 ◽  
Vol 59 (7) ◽  
pp. 4239-4248 ◽  
Author(s):  
Douglas J. Biedenbach ◽  
Krystyna Kazmierczak ◽  
Samuel K. Bouchillon ◽  
Daniel F. Sahm ◽  
Patricia A. Bradford
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clinical Isolates ◽  
Broth Microdilution ◽  
Gram Negative ◽  
Content Type ◽  
Class A ◽  
Medical Centers ◽  
Fixed Concentration ◽  
Class B

ABSTRACTThe combination of aztreonam plus avibactam is being developed for use in infections caused by metallo-β-lactamase-producingEnterobacteriaceaestrains that also produce serine β-lactamases. Thein vitroactivities of aztreonam-avibactam and comparator antimicrobials were determined against year 2012 and 2013 clinical isolates ofEnterobacteriaceae,Pseudomonas aeruginosa, andAcinetobacter baumanniiusing the broth microdilution methodology recommended by the Clinical and Laboratory Standards Institute (CLSI). A total of 28,501 unique clinical isolates were obtained from patients in 190 medical centers within 39 countries. MIC90values of aztreonam and aztreonam-avibactam against all collected isolates ofEnterobacteriaceae(n= 23,516) were 64 and 0.12 μg/ml, respectively, with 76.2% of the isolates inhibited by ≤4 μg/ml of aztreonam (the CLSI breakpoint) and 99.9% of the isolates inhibited by ≤4 μg/ml of aztreonam-avibactam using a fixed concentration of 4 μg/ml of avibactam. The MIC90was 32 μg/ml for both aztreonam and aztreonam-avibactam againstP. aeruginosa(n= 3,766). Aztreonam alone or in combination with avibactam had noin vitroactivity against isolates ofA. baumannii. PCR and sequencing were used to characterize 5,076 isolates for β-lactamase genes. Aztreonam was not active against mostEnterobacteriaceaeisolates producing class A or class C enzymes alone or in combination with class B metallo-β-lactamases. In contrast, >99% ofEnterobacteriaceaeisolates producing all observed Ambler classes of β-lactamase enzymes were inhibited by ≤4 μg/ml aztreonam in combination with avibactam, including isolates that produced IMP-, VIM-, and NDM-type metallo-β-lactamases in combination with multiple serine β-lactamases.

scholarly journals In Vitro Activity of Meropenem-Vaborbactam against Clinical Isolates of KPC-Positive Enterobacteriaceae

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Meredith A. Hackel ◽  
Olga Lomovskaya ◽  
Michael N. Dudley ◽  
James A. Karlowsky ◽  
Daniel F. Sahm
Keyword(s):  
Clinical Isolates ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Content Type ◽  
Class A ◽  
Microdilution Method ◽  
Fixed Concentration ◽  
Broth Microdilution Method ◽  
The U.S

ABSTRACT Vaborbactam (formerly RPX7009) is a novel inhibitor of serine β-lactamases, including Ambler class A carbapenemases, such as KPCs. The current study evaluated the in vitro activity of the combination agent meropenem-vaborbactam against a global collection of 991 isolates of KPC-positive Enterobacteriaceae collected in 2014 and 2015 using the Clinical and Laboratory Standards Institute (CLSI) standard broth microdilution method. The MIC90 of meropenem (when tested with a fixed concentration of 8 μg/ml of vaborbactam) for isolates of KPC-positive Enterobacteriaceae was 1 μg/ml, and MIC values ranged from ≤0.03 to >32 μg/ml; 99.0% (981/991) of isolates had meropenem-vaborbactam MICs of ≤4 μg/ml, the U.S. FDA-approved MIC breakpoint for susceptibility to meropenem-vaborbactam (Vabomere). Vaborbactam lowered the meropenem MIC50 from 32 to 0.06 μg/ml and the MIC90 from >32 to 1 μg/ml. There were no differences in the activity of meropenem-vaborbactam when the isolates were stratified by KPC variant type. We conclude that meropenem-vaborbactam demonstrates potent in vitro activity against a worldwide collection of clinical isolates of KPC-positive Enterobacteriaceae collected in 2014 and 2015.

scholarly journals In VitroActivity of Ceftolozane-Tazobactam against Pseudomonas aeruginosa Isolates Obtained from Patients in Canadian Hospitals in the CANWARD Study, 2007 to 2012

2013 ◽  
Vol 57 (11) ◽  
pp. 5707-5709 ◽  
Author(s):  
A. Walkty ◽  
J. A. Karlowsky ◽  
H. Adam ◽  
M. Baxter ◽  
P. Lagacé-Wiens ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Broth Microdilution ◽  
Content Type ◽  
Fixed Concentration

ABSTRACTThein vitroactivity of ceftolozane in combination with tazobactam (fixed concentration of 4 μg/ml) was evaluated against 2,435Pseudomonas aeruginosaclinical isolates obtained from across Canada using Clinical and Laboratory Standards Institute broth microdilution methods. The MIC50and MIC90values for ceftolozane-tazobactam were 0.5 μg/ml and 1 μg/ml, respectively (a 32-fold-lower MIC90than that for ceftazidime). Eighty-nine percent (141/158) of multidrug-resistant isolates were inhibited by ≤8 μg/ml of ceftolozane-tazobactam.

scholarly journals Multiyear, Multinational Survey of the Incidence and Global Distribution of Metallo-β-Lactamase-Producing Enterobacteriaceae and Pseudomonas aeruginosa

2015 ◽  
Vol 60 (2) ◽  
pp. 1067-1078 ◽  
Author(s):  
Krystyna M. Kazmierczak ◽  
Sharon Rabine ◽  
Meredith Hackel ◽  
Robert E. McLaughlin ◽  
Douglas J. Biedenbach ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Surveillance Study ◽  
Citrobacter Freundii ◽  
Effective Agent ◽  
Gram Negative ◽  
Content Type ◽  
Species Numbers ◽  
Medical Centers ◽  
Genes Encoding

ABSTRACTMetallo-β-lactamases (MBLs) hydrolyze all classes of β-lactams except monobactams and are not inhibited by classic serine β-lactamase inhibitors. Gram-negative pathogens isolated from patient infections were collected from 202 medical centers in 40 countries as part of a global surveillance study from 2012 to 2014. Carbapenem-nonsusceptibleEnterobacteriaceaeandPseudomonas aeruginosawere characterized forblagenes encoding VIM, IMP, NDM, SPM, and GIM variants using PCR and sequencing. A total of 471 MBL-positive isolates included the following species (numbers of isolates are in parentheses):P. aeruginosa(308),Klebsiellaspp. (85),Enterobacterspp. (39),Proteeae(16),Citrobacter freundii(12),Escherichia coli(6), andSerratia marcescens(5) and were submitted by sites from 34 countries. Of these, 69.6% were collected in 9 countries (numbers of isolates are in parentheses): Russia (72), Greece (61), Philippines (54), Venezuela (29), and Kuwait, Nigeria, Romania, South Africa, and Thailand (20 to 25 isolates each). Thirty-two different MBL variants were detected (14 VIM, 14 IMP, and 4 NDM enzymes). Seven novel MBL variants were encountered in the study, each differing from a previously reported variant by one amino acid substitution: VIM-42 (VIM-1 [V223I]), VIM-43 (VIM-4 [A24V]), VIM-44 (VIM-2 [K257N]), VIM-45 (VIM-2 [T35I]), IMP-48 (IMP-14 [I69T]), IMP-49 (IMP-18 [V49F]), and NDM-16 (NDM-1 [R264H]). Thein vitroactivities of all tested antibiotics against MBL-positiveEnterobacteriaceaewere significantly reduced with the exception of that of aztreonam-avibactam (MIC90, 0.5 to 1 μg/ml), whereas colistin was the most effective agent against MBL-positiveP. aeruginosaisolates (>97% susceptible). Although the global percentage of isolates encoding MBLs remains relatively low, their detection in 12 species, 34 countries, and all regions participating in this surveillance study is concerning.

scholarly journals In Vitro Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Asia-Pacific Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015

2018 ◽  
Vol 62 (7) ◽  
Author(s):  
James A. Karlowsky ◽  
Krystyna M. Kazmierczak ◽  
Samuel K. Bouchillon ◽  
Boudewijn L. M. de Jonge ◽  
Gregory G. Stone ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Hong Kong ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Asia Pacific ◽  
Surveillance Program ◽  
Asia Pacific Region ◽  
Content Type ◽  
Medical Centers

ABSTRACT The in vitro activities of ceftazidime-avibactam and comparators against 9,149 isolates of Enterobacteriaceae and 2,038 isolates of Pseudomonas aeruginosa collected by 42 medical centers in nine countries in the Asia-Pacific region from 2012 to 2015 were determined as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance program. Antimicrobial susceptibility testing was conducted by Clinical and Laboratory Standards Institute (CLSI) broth microdilution, and isolate subset analysis was performed on the basis of the resistant phenotypes and β-lactamase content. Ceftazidime-avibactam demonstrated potent in vitro activity (MIC, ≤8 μg/ml) against all Enterobacteriaceae tested (99.0% susceptible) and was the most active against isolates that were metallo-β-lactamase (MBL) negative (99.8% susceptible). Against P. aeruginosa , 92.6% of all isolates and 96.1% of MBL-negative isolates were susceptible to ceftazidime-avibactam (MIC, ≤8 μg/ml). The rates of susceptibility to ceftazidime-avibactam ranged from 97.0% (Philippines) to 100% (Hong Kong, South Korea) for Enterobacteriaceae and from 83.1% (Thailand) to 100% (Hong Kong) among P. aeruginosa isolates, with lower susceptibilities being observed in countries where MBLs were more frequently encountered (Philippines, Thailand). Ceftazidime-avibactam inhibited 97.2 to 100% of Enterobacteriaceae isolates, per country, that carried serine β-lactamases, including extended-spectrum β-lactamases, AmpC cephalosporinases, and carbapenemases (KPC, GES, OXA-48-like). It also inhibited 91.3% of P. aeruginosa isolates that were carbapenem nonsusceptible in which no acquired β-lactamase was detected. Among MBL-negative Enterobacteriaceae isolates that were ceftazidime nonsusceptible, meropenem nonsusceptible, colistin resistant, and multidrug resistant, ceftazidime-avibactam inhibited 96.1, 87.7, 100, and 98.8% of isolates, respectively, and among MBL-negative P. aeruginosa isolates that were ceftazidime nonsusceptible, meropenem nonsusceptible, colistin resistant, and multidrug resistant, ceftazidime-avibactam inhibited 79.6, 83.6, 83.3, and 68.2% of isolates, respectively. Overall, clinical isolates of Enterobacteriaceae and P. aeruginosa collected in nine Asia-Pacific countries from 2012 to 2015 were highly susceptible to ceftazidime-avibactam.

scholarly journals 616. Evaluation of In Vitro Susceptibility to Ceftazidime/Avibactam of Clinical Isolates of Carbapenem Nonsusceptible Gram-Negative Bacilli from Colombia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S287-S287
Author(s):  
Tobias M Appel ◽  
Maria F Mojica ◽  
Elsa De La Cadena ◽  
Christian Pallares ◽  
Maria Virginia Villegas
Keyword(s):  
Therapeutic Option ◽  
Generation Cephalosporin ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Fixed Concentration ◽  
Class B

Abstract Background Ceftazidime/avibactam (CZA) is a combination of a third-generation cephalosporin and a diazabicyclooctane β-lactamase inhibitor, which is active against a broad range of class A, C and D β-lactamases. In Colombia, high rates of multidrug-resistant Enterobacteriaceae (Ent)and P. aeruginosa (Pae) have been reported. Of special concern are KPC enzymes endemic in Ent and found in Pae, which are associated with higher mortality and healthcare costs, as well as limited therapeutic options. Herein, we evaluate the susceptibility of clinical isolates of carbapenem nonsusceptible Ent (CNS-E) and Pae (CNS-P) to CZA with the aim of understanding its role as a therapeutic option for these bacteria. Methods Three hundred ninety-nine nonduplicate clinical isolates of carbapenem nonsusceptible Gram-negative bacilli were collected in 13 medical centers from 12 Colombian cities, from January 2016 to October 2017 (137 K. pneumoniae [Kpn], 76 E. coli, 34 Enterobacter spp., 21 S. marcescens [Sma] and 131 Pae). CNS-E was defined as minimum inhibitory concentrations (MIC) ≥1 mg/L for ertapenem and CNS-P was defined as MIC ≥4 mg/L for meropenem. MIC were determined by broth microdilution and interpreted according to current CLSI guidelines. CZA MIC were determined using double dilutions of ceftazidime and a fixed concentration of avibactam of 4 mg/L. Comparator agents were ceftazidime, cefepime, piperacillin/tazobactam, imipenem, meropenem, tigecycline (TGC), and fosfomycin (FOS). Results Antimicrobial activity of CZA and comparators is shown in Table 1. CZA susceptibility ranged from 69% in Kpn to 81% in Sma, whereas 49% of CNS-P were susceptible to CZA. In both, CNS-E and CNS-P, CZA was superior to all other tested β-lactam compounds. Notably, in CNS-E CZA susceptibility was comparable to FOS and TGC (except for TGC in Sma). Conclusion CZA is the most active β-lactam against CNS-E and CNS-P. CZA nonsusceptibility suggests the presence of other resistance mechanisms, such as class B β-lactamases that are not inhibited by avibactam, and which are more frequently reported in CNS-P. Our results highlight the key role of new agents such as CZA in KPC endemic countries and the need for surveillance studies to determine the nature of resistance mechanisms. Disclosures All authors: No reported disclosures.

scholarly journals In VitroActivity of Ceftazidime-Avibactam against Contemporary Pseudomonas aeruginosa Isolates from U.S. Medical Centers by Census Region, 2014

2016 ◽  
Vol 60 (4) ◽  
pp. 2537-2541 ◽  
Author(s):  
Michael D. Huband ◽  
Mariana Castanheira ◽  
Robert K. Flamm ◽  
David J. Farrell ◽  
Ronald N. Jones ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibacterial Activities ◽  
Broth Microdilution ◽  
Content Type ◽  
Medical Centers

ABSTRACTThein vitroantibacterial activities of ceftazidime-avibactam and comparator agents were evaluated using reference broth microdilution methods against 1,743Pseudomonas aeruginosaisolates collected in 2014 from 69 U.S. medical centers, representing each of the nine census regions. Ceftazidime-avibactam demonstrated potent activity againstP. aeruginosa, including many isolates not susceptible to ceftazidime, meropenem, and piperacillin-tazobactam. In each of the nine census regions, ceftazidime-avibactam demonstrated the highest percentage of susceptible isolates.

scholarly journals In Vitro Activity of Cefepime-Zidebactam, Ceftazidime-Avibactam, and Other Comparators against Clinical Isolates of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii: Results from China Antimicrobial Surveillance Network (CHINET) in 2018

2020 ◽  
Vol 65 (1) ◽  
pp. e01726-20
Author(s):  
Yang Yang ◽  
Yan Guo ◽  
Dandan Yin ◽  
Yonggui Zheng ◽  
Shi Wu ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Clinical Isolates ◽  
Surveillance Network ◽  
Gram Negative ◽  
Content Type ◽  
Highly Active ◽  
Carbapenem Resistant ◽  
Almost All

ABSTRACTThis study evaluated the in vitro activity of cefepime-zidebactam in comparison with that of ceftazidime-avibactam and other comparators against clinically significant Gram-negative bacillus isolates. A total of 3,400 nonduplicate Gram-negative clinical isolates were collected from 45 medical centers across China in the CHINET Program in 2018, including Enterobacterales (n = 2,228), Pseudomonas aeruginosa (n = 657), and Acinetobacter baumannii (n = 515). The activities of cefepime-zidebactam and 20 comparators were determined by broth microdilution as recommended by the Clinical and Laboratory Standards Institute. Cefepime-zidebactam demonstrated potent activity against almost all Enterobacterales (MIC50/90, 0.125/1 mg/liter) and good activity against P. aeruginosa (MIC50/90, 2/8 mg/liter). Among the 373 carbapenem-resistant Enterobacteriaceae isolates, 57.3% (213/373) and 15.3% (57/373) were positive for blaKPC-2 and blaNDM, respectively. Cefepime-zidebactam showed a MIC of ≤2 mg/liter for 92.0% (196/213) of blaKPC-2 producers and 79.7% (47/59) of blaNDM producers. Ceftazidime-avibactam showed good in vitro activity against Enterobacterales (MIC50/90, 0.25/2 mg/liter; 94.0% susceptible) and P. aeruginosa (MIC50/90, 4/16 mg/liter; 86.9% susceptible). Ceftazidime-avibactam was active against 9.1% of carbapenem-resistant Escherichia coli isolates (63.6% were blaNDM producers) and 84.6% of Klebsiella pneumoniae isolates (74.3% were blaKPC producers). Most (90.1%) blaKPC-2 producers were susceptible to ceftazidime-avibactam. Cefepime-zidebactam demonstrated limited activity (MIC50/90, 16/32 mg/liter) against the 515 A. baumannii isolates (79.2% were carbapenem resistant), and ceftazidime-avibactam was less active (MIC50/90, 64/>64 mg/liter). Cefepime-zidebactam was highly active against clinical isolates of Enterobacterales and P. aeruginosa, including blaKPC-2-positive Enterobacterales and blaNDM-positive Enterobacterales and carbapenem-resistant P. aeruginosa. And ceftazidime-avibactam was highly active against blaKPC-2-positive Enterobacterales and carbapenem-resistant P. aeruginosa.

scholarly journals Antimicrobial Activity of Ceftazidime-Avibactam against Gram-Negative Organisms Collected from U.S. Medical Centers in 2012

2013 ◽  
Vol 58 (3) ◽  
pp. 1684-1692 ◽  
Author(s):  
Helio S. Sader ◽  
Mariana Castanheira ◽  
Robert K. Flamm ◽  
David J. Farrell ◽  
Ronald N. Jones
Keyword(s):  
The Novel ◽  
Gram Negative ◽  
Content Type ◽  
Class A ◽  
Medical Centers ◽  
Fixed Concentration ◽  
Clinically Significant ◽  
Gram Negative Organisms ◽  
Inhibitor Combination ◽  
Lactamase Inhibitor

ABSTRACTThe activities of the novel β-lactam–β-lactamase inhibitor combination ceftazidime-avibactam and comparator agents were evaluated against a contemporary collection of clinically significant Gram-negative bacilli. Avibactam is a novel non-β-lactam β-lactamase inhibitor that inhibits Ambler class A, C, and some D enzymes. A total of 10,928 Gram-negative bacilli—8,640Enterobacteriaceae, 1,967Pseudomonas aeruginosa, and 321Acinetobactersp. isolates—were collected from 73 U.S. hospitals and tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories, North Liberty, IA, USA). Ceftazidime was combined with avibactam at a fixed concentration of 4 μg/ml. Overall, 99.8% ofEnterobacteriaceaestrains were inhibited at a ceftazidime-avibactam MIC of ≤4 μg/ml. Ceftazidime-avibactam was active against extended-spectrum β-lactamase (ESBL)-phenotypeEscherichia coliandKlebsiella pneumoniae, meropenem-nonsusceptible (MIC ≥ 2 μg/ml)K. pneumoniae, and ceftazidime-nonsusceptibleEnterobacter cloacae. Among ESBL-phenotypeK. pneumoniaestrains, 61.1% were meropenem susceptible and 99.3% were inhibited at a ceftazidime-avibactam MIC of ≤4 μg/ml. AmongP. aeruginosastrains, 96.9% were inhibited at a ceftazidime-avibactam MIC of ≤8 μg/ml, and susceptibility rates for meropenem, ceftazidime, and piperacillin-tazobactam were 82.0, 83.2, and 78.3%, respectively. Ceftazidime-avibactam was the most active compound tested against meropenem-nonsusceptibleP. aeruginosa(MIC50/MIC90, 4/16 μg/ml; 87.3% inhibited at ≤8 μg/ml).Acinetobacterspp. (ceftazidime-avibactam MIC50/MIC90, 16/>32 μg/ml) showed high rates of resistance to most tested agents. In summary, ceftazidime-avibactam demonstrated potent activity against a large collection of contemporary Gram-negative bacilli isolated from patients in U.S. hospitals in 2012, including organisms that are resistant to most currently available agents, such asK. pneumoniaecarbapenemase (KPC)-producingEnterobacteriaceaeand meropenem-nonsusceptibleP. aeruginosa.

scholarly journals In Vitro Activity of Ceftazidime Combined with NXL104 versus Pseudomonas aeruginosa Isolates Obtained from Patients in Canadian Hospitals (CANWARD 2009 Study)

2011 ◽  
Vol 55 (6) ◽  
pp. 2992-2994 ◽  
Author(s):  
A. Walkty ◽  
M. DeCorby ◽  
P. R. S. Lagacé-Wiens ◽  
J. A. Karlowsky ◽  
D. J. Hoban ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Content Type ◽  
Presence And Absence

ABSTRACTThein vitroactivity of ceftazidime in combination with NXL104 versus 470Pseudomonas aeruginosaclinical isolates was evaluated using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methods. Ceftazidime had MIC90s of 8 μg/ml and 32 μg/ml in the presence and absence of NXL104, respectively. Of 25 multidrug-resistantP. aeruginosaisolates, the percentages with a ceftazidime MIC of ≤8 μg/ml with and without NXL104 were 60% and 4%, respectively. These data suggest that the ceftazidime-NXL104 combination may prove useful for treating manyP. aeruginosainfections.

scholarly journals Assessment of theIn VitroActivity of Ceftazidime-Avibactam against Multidrug-Resistant Klebsiella spp. Collected in the INFORM Global Surveillance Study, 2012 to 2014

2016 ◽  
Vol 60 (8) ◽  
pp. 4677-4683 ◽  
Author(s):  
Meredith Hackel ◽  
Krystyna M. Kazmierczak ◽  
Daryl J. Hoban ◽  
Douglas J. Biedenbach ◽  
Samuel K. Bouchillon ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Surveillance Study ◽  
Gram Negative ◽  
Content Type ◽  
Class A ◽  
Highly Active ◽  
Class D ◽  
Class B ◽  
Klebsiella Spp

ABSTRACTIncreasing resistance in Gram-negative bacilli, includingKlebsiellaspp., has reduced the utility of broad-spectrum cephalosporins. Avibactam, a novel non-β-lactam β-lactamase inhibitor, protects β-lactams from hydrolysis by Gram-negative bacteria that produce extended-spectrum β-lactamases (ESBLs) and serine carbapenemases, including Ambler class A and/or class C and some class D enzymes. In this analysis, we report thein vitroactivity of ceftazidime-avibactam and comparators against multidrug-resistant (MDR)Klebsiellaspp. from the 2012-2014 INFORM surveillance study. Isolates collected from 176 sites were sent to a central laboratory for confirmatory identification and tested for susceptibility to ceftazidime-avibactam and comparator agents, including ceftazidime alone. A total of 2,821 of 10,998 (25.7%)Klebsiellaspecies isolates were classified as MDR, based on resistance to three or more classes of antimicrobials. Among the MDR isolates, 99.4% had an ESBL screen-positive phenotype, and 27.4% were not susceptible to meropenem as an example of a carbapenem. Ceftazidime-avibactam was highly active against MDR isolates, including ESBL-positive and serine carbapenemase-producing isolates, with MIC50/90values of 0.5/2 μg/ml and 96.6% of all MDR isolates and ESBL-positive MDR isolates inhibited at the FDA breakpoint (MIC value of ≤8 μg/ml). Ceftazidime-avibactam did not inhibit isolates producing class B enzymes (metallo-β-lactamases) either alone or in combination with other enzymes. Thesein vitroresults support the continued investigation of ceftazidime-avibactam for the treatment of MDRKlebsiellaspecies infections.

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