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In vitro activity of avibactam (NXL104) in combination with β-lactams against Gram-negative bacteria, including OXA-48 β-lactamase-producing Klebsiella pneumoniae.
Int J Antimicrob Agents. 2012 Jan; 39(1):86-9.IJ

Abstract

The objective of this study was to investigate the in vitro antibacterial activity of avibactam (formerly NXL104) in combination with imipenem, cefepime or ceftazidime against Gram-negative bacteria. Bacterial isolates included: Pseudomonas aeruginosa harbouring PER-1 β-lactamase (n=14); Acinetobacter baumannii harbouring PER-1, OXA-51 and OXA-58 (n=20); carbapenem-non-susceptible Klebsiella pneumoniae (n=25) and Escherichia coli (n=1) harbouring OXA-48; carbapenem-non-susceptible E. coli (n=1) harbouring both IMP-1 metallo-β-lactamase and extended-spectrum β-lactamase (ESBL); carbapenem-non-susceptible Serratia marcescens (n=1); and carbapenem-susceptible E. coli (n=20) and K. pneumoniae isolates (n=12) with CTX-M-15 ESBL. Minimum inhibitory concentrations (MICs) of imipenem, cefepime and ceftazidime were determined in combination with 4 mg/L avibactam by the Clinical and Laboratory Standards Institute (CLSI) method on Mueller-Hinton agar. Imipenem/avibactam and ceftazidime/avibactam displayed limited potency against A. baumannii isolates, whereas cefepime/avibactam and ceftazidime/avibactam were active against P. aeruginosa. Klebsiella pneumoniae isolates with OXA-48 β-lactamase were resistant to imipenem [MIC for 90% of the organisms (MIC(90)) ≥4 mg/L]. MIC(90) values for the combination of avibactam 4 mg/L with imipenem, cefepime and ceftazidime were in the susceptible range for all strains (MIC(90)≤0.5mg/L). All E. coli and K. pneumoniae isolates with CTX-M-15 β-lactamase were inhibited at ≤1 mg/L for combinations with avibactam and 100% were susceptible by CLSI breakpoint criteria to imipenem, cefepime and ceftazidime. In conclusion, combinations of imipenem, cefepime and ceftazidime with avibactam may present a promising therapeutic strategy to treat infections due to K. pneumoniae with OXA-48 enzyme as well as K. pneumoniae and E. coli with CTX-M-15 enzyme.

Authors+Show Affiliations

Department of Clinical Microbiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey. aktaszerrin@yahoo.comNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22041508

Citation

Aktaş, Z, et al. "In Vitro Activity of Avibactam (NXL104) in Combination With Β-lactams Against Gram-negative Bacteria, Including OXA-48 Β-lactamase-producing Klebsiella Pneumoniae." International Journal of Antimicrobial Agents, vol. 39, no. 1, 2012, pp. 86-9.
Aktaş Z, Kayacan C, Oncul O. In vitro activity of avibactam (NXL104) in combination with β-lactams against Gram-negative bacteria, including OXA-48 β-lactamase-producing Klebsiella pneumoniae. Int J Antimicrob Agents. 2012;39(1):86-9.
Aktaş, Z., Kayacan, C., & Oncul, O. (2012). In vitro activity of avibactam (NXL104) in combination with β-lactams against Gram-negative bacteria, including OXA-48 β-lactamase-producing Klebsiella pneumoniae. International Journal of Antimicrobial Agents, 39(1), 86-9. https://doi.org/10.1016/j.ijantimicag.2011.09.012
Aktaş Z, Kayacan C, Oncul O. In Vitro Activity of Avibactam (NXL104) in Combination With Β-lactams Against Gram-negative Bacteria, Including OXA-48 Β-lactamase-producing Klebsiella Pneumoniae. Int J Antimicrob Agents. 2012;39(1):86-9. PubMed PMID: 22041508.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro activity of avibactam (NXL104) in combination with β-lactams against Gram-negative bacteria, including OXA-48 β-lactamase-producing Klebsiella pneumoniae. AU - Aktaş,Z, AU - Kayacan,C, AU - Oncul,O, Y1 - 2011/10/29/ PY - 2011/01/23/received PY - 2011/08/29/revised PY - 2011/09/02/accepted PY - 2011/11/2/entrez PY - 2011/11/2/pubmed PY - 2012/3/30/medline SP - 86 EP - 9 JF - International journal of antimicrobial agents JO - Int. J. Antimicrob. Agents VL - 39 IS - 1 N2 - The objective of this study was to investigate the in vitro antibacterial activity of avibactam (formerly NXL104) in combination with imipenem, cefepime or ceftazidime against Gram-negative bacteria. Bacterial isolates included: Pseudomonas aeruginosa harbouring PER-1 β-lactamase (n=14); Acinetobacter baumannii harbouring PER-1, OXA-51 and OXA-58 (n=20); carbapenem-non-susceptible Klebsiella pneumoniae (n=25) and Escherichia coli (n=1) harbouring OXA-48; carbapenem-non-susceptible E. coli (n=1) harbouring both IMP-1 metallo-β-lactamase and extended-spectrum β-lactamase (ESBL); carbapenem-non-susceptible Serratia marcescens (n=1); and carbapenem-susceptible E. coli (n=20) and K. pneumoniae isolates (n=12) with CTX-M-15 ESBL. Minimum inhibitory concentrations (MICs) of imipenem, cefepime and ceftazidime were determined in combination with 4 mg/L avibactam by the Clinical and Laboratory Standards Institute (CLSI) method on Mueller-Hinton agar. Imipenem/avibactam and ceftazidime/avibactam displayed limited potency against A. baumannii isolates, whereas cefepime/avibactam and ceftazidime/avibactam were active against P. aeruginosa. Klebsiella pneumoniae isolates with OXA-48 β-lactamase were resistant to imipenem [MIC for 90% of the organisms (MIC(90)) ≥4 mg/L]. MIC(90) values for the combination of avibactam 4 mg/L with imipenem, cefepime and ceftazidime were in the susceptible range for all strains (MIC(90)≤0.5mg/L). All E. coli and K. pneumoniae isolates with CTX-M-15 β-lactamase were inhibited at ≤1 mg/L for combinations with avibactam and 100% were susceptible by CLSI breakpoint criteria to imipenem, cefepime and ceftazidime. In conclusion, combinations of imipenem, cefepime and ceftazidime with avibactam may present a promising therapeutic strategy to treat infections due to K. pneumoniae with OXA-48 enzyme as well as K. pneumoniae and E. coli with CTX-M-15 enzyme. SN - 1872-7913 UR - https://www.unboundmedicine.com/medline/citation/22041508/In_vitro_activity_of_avibactam__NXL104__in_combination_with_β_lactams_against_Gram_negative_bacteria_including_OXA_48_β_lactamase_producing_Klebsiella_pneumoniae_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-8579(11)00375-X DB - PRIME DP - Unbound Medicine ER -