scholarly journals Meropenem-Vaborbactam Tested against Contemporary Gram-Negative Isolates Collected Worldwide during 2014, Including Carbapenem-Resistant, KPC-Producing, Multidrug-Resistant, and Extensively Drug-Resistant Enterobacteriaceae

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Mariana Castanheira ◽  
Michael D. Huband ◽  
Rodrigo E. Mendes ◽  
Robert K. Flamm
Keyword(s):  
The United States ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Asia Pacific ◽  
Drug Resistant ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant ◽  
Encoding Genes

ABSTRACT We evaluated the activity of meropenem-vaborbactam against contemporary nonfastidious Gram-negative clinical isolates, including Enterobacteriaceae isolates with resistance phenotypes and carbapenemase genotypes. Meropenem-vaborbactam (inhibitor at 8 μg/ml) and comparators were susceptibility tested by reference broth microdilution methods against 14,304 Gram-negative clinical isolates collected worldwide during 2014. Carbapenemase-encoding genes were screened by PCR and sequencing. Meropenem-vaborbactam (MIC50/90, ≤0.015/0.06 μg/ml) inhibited 99.1 and 99.3% of the 10,426 Enterobacteriaceae isolates tested at ≤1 and ≤2 μg/ml, respectively. Meropenem inhibited 97.3 and 97.7% of these isolates at the same concentrations. Against Enterobacteriaceae isolates displaying carbapenem-resistant Enterobacteriaceae (CRE) (n = 265), multidrug-resistant (MDR) (n = 1,210), and extensively drug-resistant (XDR) (n = 161) phenotypes, meropenem-vaborbactam displayed MIC50/90 values of 0.5/32, 0.03/1, and 0.5/32 μg/ml, respectively, whereas meropenem activities were 16/>32, 0.06/32, and 0.5/32 μg/ml, respectively. Among all geographic regions, the highest meropenem-vaborbactam activities were observed for CRE and MDR isolates from the United States (MIC50/90, 0.03/1 and 0.03/0.12 μg/ml, respectively). Meropenem-vaborbactam was very active against 135 KPC producers, and all isolates were inhibited by concentrations of ≤8 μg/ml (133 isolates by concentrations of ≤2 μg/ml). This combination had limited activity against isolates producing metallo-β-lactamases (including 25 NDM-1 and 16 VIM producers) and/or oxacillinases (27 OXA-48/OXA-163 producers) that were detected mainly in Asia-Pacific and some European countries. The activity of meropenem-vaborbactam was similar to that of meropenem alone against Pseudomonas aeruginosa, Acinetobacter spp., and Stenotrophomonas maltophilia. Meropenem-vaborbactam was active against contemporary Enterobacteriaceae isolates collected worldwide, and this combination demonstrated enhanced activity compared to those of meropenem and most comparator agents against CRE isolates and KPC producers, the latter of which are often MDR.

scholarly journals WCK 5222 (Cefepime-Zidebactam) Antimicrobial Activity against Clinical Isolates of Gram-Negative Bacteria Collected Worldwide in 2015

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Helio S. Sader ◽  
Mariana Castanheira ◽  
Michael Huband ◽  
Ronald N. Jones ◽  
Robert K. Flamm
Keyword(s):  
Antimicrobial Activity ◽  
Bacterial Infections ◽  
The United States ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Asia Pacific ◽  
Gram Negative ◽  
Content Type ◽  
Broth Microdilution Method

ABSTRACT WCK 5222 consists of cefepime combined with zidebactam, a bicyclo-acyl hydrazide β-lactam enhancer antibiotic with a dual action involving binding to Gram-negative bacterial PBP2 and β-lactamase inhibition. We evaluated the in vitro activity of cefepime-zidebactam against 7,876 contemporary (2015) clinical isolates of Enterobacteriaceae (n = 5,946), Pseudomonas aeruginosa (n = 1,291), and Acinetobacter spp. (n = 639) from the United States (n = 2,919), Europe (n = 3,004), the Asia-Pacific (n = 1,370), and Latin America (n = 583). The isolates were tested by a reference broth microdilution method for susceptibility against cefepime-zidebactam (1:1 and 2:1 ratios) and comparator agents. Cefepime-zidebactam was the most active compound tested against Enterobacteriaceae (MIC50/90, ≤0.03/0.12 μg/ml [1:1] and 0.06/0.25 μg/ml [2:1]; 99.9% of isolates were inhibited at ≤4 [1:1] and ≤8 μg/ml [2:1]). Cefepime-zidebactam was active against individual Enterobacteriaceae species (MIC50/90, ≤0.03 to 0.06/≤0.03 to 0.5 μg/ml [1:1]) and retained potent activity against carbapenem-resistant isolates (MIC50/90, 1/4 μg/ml; 99.3% of isolates were inhibited at ≤8 μg/ml [1:1]). Cefepime-zidebactam activity was consistent among geographic regions, and only one isolate showed MIC values of >8 μg/ml (1:1). Cefepime-zidebactam was also very active against P. aeruginosa with MIC50/90 values of 1/4 μg/ml, and 99.5% of isolates were inhibited at ≤8 μg/ml (1:1). The MIC values for cefepime-zidebactam at the 1:1 ratio were generally 2-fold lower than those for cefepime-zidebactam at the 2:1 ratio (MIC50/90, 2/8 μg/ml) and zidebactam alone (MIC50/90, 4/8 μg/ml). Against Acinetobacter spp., cefepime-zidebactam at 1:1 and 2:1 ratios (MIC50/90, 16/32 μg/ml for both) was 4-fold more active than cefepime or ceftazidime. Zidebactam exhibited potent in vitro antimicrobial activity against some organisms. These results support the clinical development of WCK 5222 for the treatment of Gram-negative bacterial infections, including those caused by multidrug-resistant isolates.

scholarly journals In VitroSusceptibility of Mycobacterium tuberculosis Isolates to an Oral Carbapenem Alone or in Combination with β-Lactamase Inhibitors

2014 ◽  
Vol 58 (11) ◽  
pp. 7010-7014 ◽  
Author(s):  
Yasuhiro Horita ◽  
Shinji Maeda ◽  
Yuko Kazumi ◽  
Norio Doi
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Human Blood ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

ABSTRACTWe evaluated the antituberculosis (anti-TB) activity of five β-lactams alone or in combination with β-lactamase inhibitors against 41 clinical isolates ofMycobacterium tuberculosis, including multidrug-resistant and extensively drug-resistant strains. Of those, tebipenem, an oral carbapenem, showed the most potent anti-TB activity against clinical isolates, with a MIC range of 0.125 to 8 μg/ml, which is achievable in the human blood. More importantly, in the presence of clavulanate, MIC values of tebipenem declined to 2 μg/ml or less.

scholarly journals Antibiotic Susceptibility of NDM-Producing Enterobacterales Collected in the United States in 2017 and 2018

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Joseph D. Lutgring ◽  
Rocío Balbuena ◽  
Natashia Reese ◽  
Sarah E. Gilbert ◽  
Uzma Ansari ◽  
...  
Keyword(s):  
United States ◽  
Antibiotic Susceptibility ◽  
Treatment Options ◽  
The United States ◽  
Multidrug Resistant ◽  
New Delhi ◽  
Drug Resistant ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant

ABSTRACT The treatment of infections caused by carbapenem-resistant Enterobacterales, especially New Delhi metallo-β-lactamase (NDM)-producing bacteria, is challenging. Although less common in the United States than some other carbapenemase producers, NDM-producing bacteria are a public health threat due to the limited treatment options available. Here, we report on the antibiotic susceptibility of 275 contemporary NDM-producing Enterobacterales collected from 30 U.S. states through the Centers for Disease Control and Prevention’s Antibiotic Resistance Laboratory Network. The aims of the study were to determine the susceptibility of these isolates to 32 currently available antibiotics using reference broth microdilution and to explore the in vitro activity of 3 combination agents that are not yet available. Categorical interpretations were determined using Clinical and Laboratory Standards Institute (CLSI) interpretive criteria. For agents without CLSI criteria, Food and Drug Administration (FDA) interpretive criteria were used. The percentage of susceptible isolates did not exceed 90% for any of the FDA-approved antibiotics tested. The antibiotics with breakpoints that had the highest in vitro activity were tigecycline (86.5% susceptible), eravacycline (66.2% susceptible), and omadacycline (59.6% susceptible); 18.2% of isolates were susceptible to aztreonam. All NDM-producing isolates tested were multidrug resistant, and 116 isolates were extensively drug resistant (42.2%); 207 (75.3%) isolates displayed difficult-to-treat resistance. The difficulty in treating infections caused by NDM-producing Enterobacterales highlights the need for containment and prevention efforts to keep these infections from becoming more common.

scholarly journals Battacin (Octapeptin B5), a New Cyclic Lipopeptide Antibiotic from Paenibacillus tianmuensis Active against Multidrug-Resistant Gram-Negative Bacteria

2011 ◽  
Vol 56 (3) ◽  
pp. 1458-1465 ◽  
Author(s):  
Chao-Dong Qian ◽  
Xue-Chang Wu ◽  
Yi Teng ◽  
Wen-Peng Zhao ◽  
Ou Li ◽  
...  
Keyword(s):  
Polymyxin B ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Content Type ◽  
Lipopeptide Antibiotic

ABSTRACTHospital-acquired infections caused by drug-resistant bacteria are a significant challenge to patient safety. Numerous clinical isolates resistant to almost all commercially available antibiotics have emerged. Thus, novel antimicrobial agents, specifically those for multidrug-resistant Gram-negative bacteria, are urgently needed. In the current study, we report the isolation, structure elucidation, and preliminary biological characterization of a new cationic lipopeptide antibiotic, battacin or octapeptin B5, produced from aPaenibacillus tianmuensissoil isolate. Battacin kills bacteriain vitroand has potent activity against Gram-negative bacteria, including multidrug-resistant and extremely drug-resistant clinical isolates. Hospital strains ofEscherichia coliandPseudomonas aeruginosaare the pathogens most sensitive to battacin, with MICs of 2 to 4 μg/ml. The ability of battacin to disrupt the outer membrane of Gram-negative bacteria is comparable to that of polymyxin B, the last-line therapy for infections caused by antibiotic-resistant Gram-negative bacteria. However, the capacity of battacin to permeate bacterial plasma membranes is less extensive than that of polymyxin B. The bactericidal kinetics of battacin correlate with the depolarization of the cell membrane, suggesting that battacin kills bacteria by disrupting the cytoplasmic membrane. Other studies indicate that battacin is less acutely toxic than polymyxin B and has potentin vivobiological activity againstE. coli. Based on the findings of the current study, battacin may be considered a potential therapeutic agent for the treatment of infections caused by antibiotic-resistant Gram-negative bacteria.

scholarly journals Activity of Ceftolozane-Tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae Isolates Collected from Respiratory Tract Specimens of Hospitalized Patients in the United States during 2013 to 2015

2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Mariana Castanheira ◽  
Leonard R. Duncan ◽  
Rodrigo E. Mendes ◽  
Helio S. Sader ◽  
Dee Shortridge
Keyword(s):  
United States ◽  
Pseudomonas Aeruginosa ◽  
The United States ◽  
Drug Resistant ◽  
Broth Microdilution ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Encoding Genes ◽  
M 14

ABSTRACT The activities of ceftolozane-tazobactam and comparator agents against organisms deemed to be the cause of pneumonia among patients hospitalized in the United States during 2013 to 2015 were evaluated. Organisms included 1,576 Pseudomonas aeruginosa and 2,362 Enterobacteriaceae isolates susceptibility tested using reference broth microdilution methods. Ceftolozane-tazobactam, cefepime, ceftazidime, meropenem, and piperacillin-tazobactam inhibited 96.3%, 84.8%, 83.5%, 80.0%, and 78.6%, respectively, of the P. aeruginosa isolates. Ceftolozane-tazobactam inhibited 77.5 to 85.1% of isolates nonsusceptible to antipseudomonal β-lactams and 86.6% and 71.0% of the 372 (23.6% overall) multidrug- and 155 (9.8%) extensively drug-resistant isolates tested. The activity of this combination was greater than those of other β-lactams evaluated against P. aeruginosa groups across all U.S. census divisions. Ceftolozane-tazobactam was active against 90.6% of the Enterobacteriaceae , being less active than only meropenem (95.6% susceptible) among the β-lactams evaluated. Against 145 Escherichia coli and Klebsiella pneumoniae isolates carrying extended-spectrum-β-lactamase (ESBL)-encoding genes without carbapenemases, ceftolozane-tazobactam inhibited 82.8% of these isolates and was more active than cefepime and piperacillin-tazobactam (15.2% and 74.3% susceptible, respectively). ESBL genes included in this analysis were mainly bla CTX-M-15 -like (89 isolates) and bla CTX-M-14 -like (22) genes but also bla SHV (31) and bla TEM (3). Ceftolozane-tazobactam also displayed activity (84.6% susceptible) against 13 isolates harboring acquired AmpC genes. All β-lactams displayed limited activity against bla KPC -carrying isolates. Ceftolozane-tazobactam was the most active β-lactam tested against P. aeruginosa isolates from isolates that were the probable cause of pneumonia and displayed in vitro activity against Enterobacteriaceae , including isolates resistant to cephalosporins and carrying ESBL genes.

scholarly journals Retrospective Molecular Analysis of DIM-1 Metallo-β-Lactamase Discovered in Pseudomonas stutzeri from India in 2000

2013 ◽  
Vol 58 (1) ◽  
pp. 596-598 ◽  
Author(s):  
Lalitagauri M. Deshpande ◽  
Ronald N. Jones ◽  
Leah N. Woosley ◽  
Mariana Castanheira
Keyword(s):  
Molecular Analysis ◽  
Pseudomonas Stutzeri ◽  
Clinical Isolates ◽  
Gram Negative ◽  
Content Type ◽  
Environmental Source ◽  
Lactamase Gene ◽  
Encoding Genes

ABSTRACTAmong 220 clinical isolates of Gram-negative bacilli collected in India during 2000, 22 strains showing elevated imipenem MICs were evaluated for carbapenemase production. One DIM-1-producingPseudomonas stutzeriisolate was detected, and no other carbapenemase-encoding genes were identified. This detection of a DIM-1-producingP. stutzeriisolate from India predating the finding of this gene in the index Dutch strain and the very recent detection of DIM-1 in Africa suggest an unidentified environmental source of this metallo-β-lactamase gene.

scholarly journals Complete Genome Sequences of Four Extensively Drug-Resistant Acinetobacter baumannii Isolates from Thailand

2020 ◽  
Vol 9 (40) ◽  
Author(s):  
Peechanika Chopjitt ◽  
Thidathip Wongsurawat ◽  
Piroon Jenjaroenpun ◽  
Parichart Boueroy ◽  
Rujirat Hatrongjit ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Complete Genome ◽  
Sequence Type ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Genome Sequences ◽  
Content Type ◽  
Type Isolate ◽  
Resistant Genes ◽  
Extensively Drug Resistant

ABSTRACT Here, we report the complete genome sequences of four clinical isolates of extensively drug-resistant Acinetobacter baumannii (XDRAB), isolated in Thailand. These results revealed multiple antimicrobial-resistant genes, each involving two sequence type 16 (ST16) isolates, ST2, and a novel sequence type isolate, ST1479.

scholarly journals Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Zhaojing Zong ◽  
Wei Jing ◽  
Jin Shi ◽  
Shu'an Wen ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Significant Difference ◽  
Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

scholarly journals Antimicrobial Activity of Ceftazidime-Avibactam Tested against Multidrug-Resistant Enterobacteriaceae and Pseudomonas aeruginosa Isolates from U.S. Medical Centers, 2013 to 2016

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Helio S. Sader ◽  
Mariana Castanheira ◽  
Dee Shortridge ◽  
Rodrigo E. Mendes ◽  
Robert K. Flamm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Large Collection ◽  
Content Type ◽  
Negative Results ◽  
Medical Centers ◽  
Extensively Drug Resistant ◽  
Genes Encoding

ABSTRACT The in vitro activity of ceftazidime-avibactam and many comparator agents was determined against various resistant subsets of organisms selected among 36,380 Enterobacteriaceae and 7,868 Pseudomonas aeruginosa isolates. The isolates were consecutively collected from 94 U.S. hospitals, and all isolates were tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories). Enterobacteriaceae isolates resistant to carbapenems (CRE) and/or ceftazidime-avibactam (MIC ≥ 16 μg/ml) were evaluated for the presence of genes encoding extended-spectrum β-lactamases and carbapenemases. Ceftazidime-avibactam inhibited >99.9% of all Enterobacteriaceae at the susceptible breakpoint of ≤8 μg/ml and was active against multidrug-resistant (MDR; n = 2,953; MIC50/90, 0.25/1 μg/ml; 99.2% susceptible), extensively drug-resistant (XDR; n = 448; MIC50/90, 0.5/2 μg/ml; 97.8% susceptible), and CRE (n = 513; MIC50/90, 0.5/2 μg/ml; 97.5% susceptible) isolates. Only 82.2% of MDR Enterobacteriaceae (n = 2,953) and 64.2% of ceftriaxone-nonsusceptible Klebsiella pneumoniae (n = 1,063) isolates were meropenem susceptible. Among Enterobacter cloacae (22.2% ceftazidime nonsusceptible), 99.8% of the isolates, including 99.3% of the ceftazidime-nonsusceptible isolates, were ceftazidime-avibactam susceptible. Only 23 of 36,380 Enterobacteriaceae (0.06%) isolates were ceftazidime-avibactam nonsusceptible, including 9 metallo-β-lactamase producers and 2 KPC-producing strains with porin alteration; the remaining 12 strains showed negative results for all β-lactamases tested. Ceftazidime-avibactam showed potent activity against P. aeruginosa (MIC50/90, 2/4 μg/ml; 97.1% susceptible), including MDR (MIC50/90, 4/16 μg/ml; 86.5% susceptible) isolates, and inhibited 71.8% of isolates nonsusceptible to meropenem, piperacillin-tazobactam, and ceftazidime (n = 628). In summary, ceftazidime-avibactam demonstrated potent activity against a large collection (n = 44,248) of contemporary Gram-negative bacilli isolated from U.S. patients, including organisms resistant to most currently available agents, such as CRE and meropenem-nonsusceptible P. aeruginosa.

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