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Published in: Drugs 2/2013

01-02-2013 | Review Article

Ceftazidime-Avibactam: a Novel Cephalosporin/β-lactamase Inhibitor Combination

Authors: George G. Zhanel, Christopher D. Lawson, Heather Adam, Frank Schweizer, Sheryl Zelenitsky, Philippe R. S. Lagacé-Wiens, Andrew Denisuik, Ethan Rubinstein, Alfred S. Gin, Daryl J. Hoban, Joseph P. Lynch 3rd, James A. Karlowsky

Published in: Drugs | Issue 2/2013

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Abstract

Avibactam (formerly NXL104, AVE1330A) is a synthetic non-β-lactam, β-lactamase inhibitor that inhibits the activities of Ambler class A and C β-lactamases and some Ambler class D enzymes. This review summarizes the existing data published for ceftazidime-avibactam, including relevant chemistry, mechanisms of action and resistance, microbiology, pharmacokinetics, pharmacodynamics, and efficacy and safety data from animal and human trials. Although not a β-lactam, the chemical structure of avibactam closely resembles portions of the cephem bicyclic ring system, and avibactam has been shown to bond covalently to β-lactamases. Very little is known about the potential for avibactam to select for resistance. The addition of avibactam greatly (4-1024-fold minimum inhibitory concentration [MIC] reduction) improves the activity of ceftazidime versus most species of Enterobacteriaceae depending on the presence or absence of β-lactamase enzyme(s). Against Pseudomonas aeruginosa, the addition of avibactam also improves the activity of ceftazidime (~fourfold MIC reduction). Limited data suggest that the addition of avibactam does not improve the activity of ceftazidime versus Acinetobacter species or most anaerobic bacteria (exceptions: Bacteroides fragilis, Clostridium perfringens, Prevotella spp. and Porphyromonas spp.). The pharmacokinetics of avibactam follow a two-compartment model and do not appear to be altered by the co-administration of ceftazidime. The maximum plasma drug concentration (Cmax) and area under the plasma concentration-time curve (AUC) of avibactam increase linearly with doses ranging from 50 mg to 2,000 mg. The mean volume of distribution and half-life of 22 L (~0.3 L/kg) and ~2 hours, respectively, are similar to ceftazidime. Like ceftazidime, avibactam is primarily renally excreted, and clearance correlates with creatinine clearance. Pharmacodynamic data suggest that ceftazidime-avibactam is rapidly bactericidal versus β-lactamase-producing Gram-negative bacilli that are not inhibited by ceftazidime alone.
Clinical trials to date have reported that ceftazidime-avibactam is as effective as standard carbapenem therapy in complicated intra-abdominal infection and complicated urinary tract infection, including infection caused by cephalosporin-resistant Gram-negative isolates. The safety and tolerability of ceftazidime-avibactam has been reported in three phase I pharmacokinetic studies and two phase II clinical studies. Ceftazidime-avibactam appears to be well tolerated in healthy subjects and hospitalized patients, with few serious drug-related treatment-emergent adverse events reported to date.
In conclusion, avibactam serves to broaden the spectrum of ceftazidime versus ß-lactamase-producing Gram-negative bacilli. The exact roles for ceftazidime-avibactam will be defined by efficacy and safety data from further clinical trials. Potential future roles for ceftazidime-avibactam include the treatment of suspected or documented infections caused by resistant Gram-negative-bacilli producing extended-spectrum ß-lactamase (ESBL), Klebsiella pneumoniae carbapenemases (KPCs) and/or AmpC ß-lactamases. In addition, ceftazidime-avibactam may be used in combination (with metronidazole) for suspected polymicrobial infections. Finally, the increased activity of ceftazidime-avibactam versus P. aeruginosa may be of clinical benefit in patients with suspected or documented P. aeruginosa infections.
Literature
1.
go back to reference Andes D, Craig W. Cephalosporins. In: Mandell G, Bennett J, Dolin R, editors. Principles and practice of infectious diseases. 7th ed. Philadelphia: Churchill Livingstone Elsevier; 2010. p. 323–37. Andes D, Craig W. Cephalosporins. In: Mandell G, Bennett J, Dolin R, editors. Principles and practice of infectious diseases. 7th ed. Philadelphia: Churchill Livingstone Elsevier; 2010. p. 323–37.
2.
go back to reference Pitout JD. Infections with extended-spectrum beta-lactamase-producing enterobacteriaceae: changing epidemiology and drug treatment choices. Drugs. 2010;70(3):313–33.PubMedCrossRef Pitout JD. Infections with extended-spectrum beta-lactamase-producing enterobacteriaceae: changing epidemiology and drug treatment choices. Drugs. 2010;70(3):313–33.PubMedCrossRef
3.
go back to reference Bush K. Alarming beta-lactamase-mediated resistance in multidrug-resistant Enterobacteriaceae. Curr Opin Microbiol. 2010;13(5):558–64.PubMedCrossRef Bush K. Alarming beta-lactamase-mediated resistance in multidrug-resistant Enterobacteriaceae. Curr Opin Microbiol. 2010;13(5):558–64.PubMedCrossRef
4.
go back to reference Livermore DM, Woodford N. The beta-lactamase threat in Enterobacteriaceae, Pseudomonas and Acinetobacter. Trends Microbiol. 2006;14(9):413–20.PubMedCrossRef Livermore DM, Woodford N. The beta-lactamase threat in Enterobacteriaceae, Pseudomonas and Acinetobacter. Trends Microbiol. 2006;14(9):413–20.PubMedCrossRef
5.
go back to reference Livermore DM. Has the era of untreatable infections arrived? J Antimicrob Chemother. 2009;64(Suppl 1):i29–36.PubMedCrossRef Livermore DM. Has the era of untreatable infections arrived? J Antimicrob Chemother. 2009;64(Suppl 1):i29–36.PubMedCrossRef
6.
go back to reference Turner PJ. MYSTIC Europe 2007: activity of meropenem and other broad-spectrum agents against nosocomial isolates. Diagn Microbiol Infect Dis. 2009;63(2):217–22.PubMedCrossRef Turner PJ. MYSTIC Europe 2007: activity of meropenem and other broad-spectrum agents against nosocomial isolates. Diagn Microbiol Infect Dis. 2009;63(2):217–22.PubMedCrossRef
7.
go back to reference Hawser SP, Badal RE, Bouchillon SK, et al. Trending eight years of in vitro activity of ertapenem and comparators against Escherichia coli from intra-abdominal infections in North America–SMART 2002–2009. J Chemother. 2011;23(5):266–72.PubMed Hawser SP, Badal RE, Bouchillon SK, et al. Trending eight years of in vitro activity of ertapenem and comparators against Escherichia coli from intra-abdominal infections in North America–SMART 2002–2009. J Chemother. 2011;23(5):266–72.PubMed
8.
go back to reference Hoban DJ, Nicolle LE, Hawser S, et al. Antimicrobial susceptibility of global inpatient urinary tract isolates of Escherichia coli: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART) program: 2009–2010. Diagn Microbiol Infect Dis. 2011;70(4):507–11.PubMedCrossRef Hoban DJ, Nicolle LE, Hawser S, et al. Antimicrobial susceptibility of global inpatient urinary tract isolates of Escherichia coli: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART) program: 2009–2010. Diagn Microbiol Infect Dis. 2011;70(4):507–11.PubMedCrossRef
9.
go back to reference Bhattacharya S, Bonnet A, Dedhiya M, et al. inventors; Novexel SA and Forest laboratories holdings, assignees. Polymorphic and pseudopolymorphic forms of a pharmaceutical compound. International patent WO 042560 A2. 2011 April 14. Bhattacharya S, Bonnet A, Dedhiya M, et al. inventors; Novexel SA and Forest laboratories holdings, assignees. Polymorphic and pseudopolymorphic forms of a pharmaceutical compound. International patent WO 042560 A2. 2011 April 14.
10.
go back to reference Coleman K. Diazabicyclooctanes (DBOs): a potent new class of non-beta-lactam beta-lactamase inhibitors. Curr Opin Microbiol. 2011;14(5):550–5.PubMedCrossRef Coleman K. Diazabicyclooctanes (DBOs): a potent new class of non-beta-lactam beta-lactamase inhibitors. Curr Opin Microbiol. 2011;14(5):550–5.PubMedCrossRef
11.
go back to reference Beale J. Antibacterial antibiotics. In: Beale J, Block J, editors. Wilson and Gisvold’s textbook of organic medicinal and pharmaceutical chemistry. 12th ed. Baltimore: Lippincott Williams & Wilkins; 2011. p. 258–329. Beale J. Antibacterial antibiotics. In: Beale J, Block J, editors. Wilson and Gisvold’s textbook of organic medicinal and pharmaceutical chemistry. 12th ed. Baltimore: Lippincott Williams & Wilkins; 2011. p. 258–329.
12.
go back to reference Caprile KA. The cephalosporin antimicrobial agents: a comprehensive review. J Vet Pharmacol Ther. 1988;11(1):1–32.PubMedCrossRef Caprile KA. The cephalosporin antimicrobial agents: a comprehensive review. J Vet Pharmacol Ther. 1988;11(1):1–32.PubMedCrossRef
13.
go back to reference Dunn GL. Ceftizoxime and other third-generation cephalosporins: structure-activity relationships. J Antimicrob Chemother. 1982;10(Suppl. C):1–10.PubMedCrossRef Dunn GL. Ceftizoxime and other third-generation cephalosporins: structure-activity relationships. J Antimicrob Chemother. 1982;10(Suppl. C):1–10.PubMedCrossRef
14.
go back to reference Neu HC. Beta-lactam antibiotics: structural relationships affecting in vitro activity and pharmacologic properties. Rev Infect Dis. 1986;8(Suppl. 3):S237–59.PubMedCrossRef Neu HC. Beta-lactam antibiotics: structural relationships affecting in vitro activity and pharmacologic properties. Rev Infect Dis. 1986;8(Suppl. 3):S237–59.PubMedCrossRef
15.
go back to reference Neu HC. Beta-lactamase stability of cefoxitin in comparison with other beta-lactam compounds. Diagn Microbiol Infect Dis. 1983;1(4):313–6.PubMedCrossRef Neu HC. Beta-lactamase stability of cefoxitin in comparison with other beta-lactam compounds. Diagn Microbiol Infect Dis. 1983;1(4):313–6.PubMedCrossRef
16.
go back to reference Miossec C, Merdjan H, Hodgson J. Safety and toxicokinetics of NXL104, a broad spectrum β-lactamase inhibitor, in the rat [abstract no. F-1461 plus poster]. In: 45th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2005 Dec 16–19; Washington (DC). Miossec C, Merdjan H, Hodgson J. Safety and toxicokinetics of NXL104, a broad spectrum β-lactamase inhibitor, in the rat [abstract no. F-1461 plus poster]. In: 45th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2005 Dec 16–19; Washington (DC).
17.
go back to reference Miossec C. NXL104 β-lactamase inhibitor [abstract no. plus oral presentation]. Challenge of antibacterial drug development; 2007 Mar 21–22; San Diego, CA. Miossec C. NXL104 β-lactamase inhibitor [abstract no. plus oral presentation]. Challenge of antibacterial drug development; 2007 Mar 21–22; San Diego, CA.
18.
go back to reference Popham DL, Young KD. Role of penicillin-binding proteins in bacterial cell morphogenesis. Curr Opin Microbiol. 2003;6(6):594–9.PubMedCrossRef Popham DL, Young KD. Role of penicillin-binding proteins in bacterial cell morphogenesis. Curr Opin Microbiol. 2003;6(6):594–9.PubMedCrossRef
19.
go back to reference Vollmer W, Blanot D, de Pedro MA. Peptidoglycan structure and architecture. FEMS Microbiol Rev. 2008;32(2):149–67.PubMedCrossRef Vollmer W, Blanot D, de Pedro MA. Peptidoglycan structure and architecture. FEMS Microbiol Rev. 2008;32(2):149–67.PubMedCrossRef
20.
go back to reference Sauvage E, Kerff F, Terrak M, et al. The penicillin-binding proteins: structure and role in peptidoglycan biosynthesis. FEMS Microbiol Rev. 2008;32(2):234–58.PubMedCrossRef Sauvage E, Kerff F, Terrak M, et al. The penicillin-binding proteins: structure and role in peptidoglycan biosynthesis. FEMS Microbiol Rev. 2008;32(2):234–58.PubMedCrossRef
21.
go back to reference Hayes MV, Orr DC. Mode of action of ceftazidime: affinity for the penicillin-binding proteins of Escherichia coli K12, Pseudomonas aeruginosa and Staphylococcus aureus. J Antimicrob Chemother. 1983;12(2):119–26.PubMedCrossRef Hayes MV, Orr DC. Mode of action of ceftazidime: affinity for the penicillin-binding proteins of Escherichia coli K12, Pseudomonas aeruginosa and Staphylococcus aureus. J Antimicrob Chemother. 1983;12(2):119–26.PubMedCrossRef
22.
23.
go back to reference Bush K, Fisher JF. Epidemiological expansion, structural studies, and clinical challenges of new beta-lactamases from gram-negative bacteria. Annu Rev Microbiol. 2011;65:455–78.PubMedCrossRef Bush K, Fisher JF. Epidemiological expansion, structural studies, and clinical challenges of new beta-lactamases from gram-negative bacteria. Annu Rev Microbiol. 2011;65:455–78.PubMedCrossRef
24.
go back to reference Ambler RP. The structure of beta-lactamases. Philos Trans R Soc Lond B Biol Sci. 1980;289(1036):321–31.PubMedCrossRef Ambler RP. The structure of beta-lactamases. Philos Trans R Soc Lond B Biol Sci. 1980;289(1036):321–31.PubMedCrossRef
25.
go back to reference Ambler RP, Coulson AF, Frere JM, et al. A standard numbering scheme for the class A beta-lactamases. Biochem J. 1991;276(Pt 1):269–70.PubMed Ambler RP, Coulson AF, Frere JM, et al. A standard numbering scheme for the class A beta-lactamases. Biochem J. 1991;276(Pt 1):269–70.PubMed
26.
go back to reference Jaurin B, Grundstrom T. ampC cephalosporinase of Escherichia coli K-12 has a different evolutionary origin from that of beta-lactamases of the penicillinase type. Proc Natl Acad Sci USA. 1981;78(8):4897–901.PubMedCrossRef Jaurin B, Grundstrom T. ampC cephalosporinase of Escherichia coli K-12 has a different evolutionary origin from that of beta-lactamases of the penicillinase type. Proc Natl Acad Sci USA. 1981;78(8):4897–901.PubMedCrossRef
27.
go back to reference Ouellette M, Bissonnette L, Roy PH. Precise insertion of antibiotic resistance determinants into Tn21-like transposons: nucleotide sequence of the OXA-1 beta-lactamase gene. Proc Natl Acad Sci USA. 1987;84(21):7378–82.PubMedCrossRef Ouellette M, Bissonnette L, Roy PH. Precise insertion of antibiotic resistance determinants into Tn21-like transposons: nucleotide sequence of the OXA-1 beta-lactamase gene. Proc Natl Acad Sci USA. 1987;84(21):7378–82.PubMedCrossRef
28.
go back to reference Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother. 2010;54(3):969–76.PubMedCrossRef Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother. 2010;54(3):969–76.PubMedCrossRef
29.
go back to reference Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother. 1995;39(6):1211–33.PubMedCrossRef Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother. 1995;39(6):1211–33.PubMedCrossRef
30.
go back to reference Majiduddin FK, Materon IC, Palzkill TG. Molecular analysis of beta-lactamase structure and function. Int J Med Microbiol. 2002;292(2):127–37.PubMedCrossRef Majiduddin FK, Materon IC, Palzkill TG. Molecular analysis of beta-lactamase structure and function. Int J Med Microbiol. 2002;292(2):127–37.PubMedCrossRef
31.
go back to reference Ghuysen JM. Serine beta-lactamases and penicillin-binding proteins. Annu Rev Microbiol. 1991;45:37–67.PubMedCrossRef Ghuysen JM. Serine beta-lactamases and penicillin-binding proteins. Annu Rev Microbiol. 1991;45:37–67.PubMedCrossRef
32.
go back to reference Tamilselvi A, Mugesh G. Zinc and antibiotic resistance: metallo-beta-lactamases and their synthetic analogues. J Biol Inorg Chem. 2008;13(7):1039–53.PubMedCrossRef Tamilselvi A, Mugesh G. Zinc and antibiotic resistance: metallo-beta-lactamases and their synthetic analogues. J Biol Inorg Chem. 2008;13(7):1039–53.PubMedCrossRef
33.
go back to reference Knox JR. Extended-spectrum and inhibitor-resistant TEM-type beta-lactamases: mutations, specificity, and three-dimensional structure. Antimicrob Agents Chemother. 1995;39(12):2593–601.PubMedCrossRef Knox JR. Extended-spectrum and inhibitor-resistant TEM-type beta-lactamases: mutations, specificity, and three-dimensional structure. Antimicrob Agents Chemother. 1995;39(12):2593–601.PubMedCrossRef
34.
go back to reference Docquier J, Stachyra T, Benvenuti M, et al. High resolution crystal structure of CTX-M-15 in complex with the new β-lactamase inhibitor NXL104 [abstract no. C1-1098 plus oral presentation]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA). Docquier J, Stachyra T, Benvenuti M, et al. High resolution crystal structure of CTX-M-15 in complex with the new β-lactamase inhibitor NXL104 [abstract no. C1-1098 plus oral presentation]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA).
35.
go back to reference Xu H, Hazra S, Blanchard JS. NXL104 irreversibly inhibits the beta-lactamase from Mycobacterium tuberculosis. Biochemistry. 2012;51(22):4551–7.PubMedCrossRef Xu H, Hazra S, Blanchard JS. NXL104 irreversibly inhibits the beta-lactamase from Mycobacterium tuberculosis. Biochemistry. 2012;51(22):4551–7.PubMedCrossRef
36.
go back to reference Docquier J, Benvenuti M, De Luca F, et al. Structure of the TRU-1 class C and OXA-10 class D β-lactamases in complex with NXL104: structural basis for broad-spectrum inhibition [abstract no. C1-1427 plus poster]. In: 50th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2010 Sep 12–15; Boston (MA). Docquier J, Benvenuti M, De Luca F, et al. Structure of the TRU-1 class C and OXA-10 class D β-lactamases in complex with NXL104: structural basis for broad-spectrum inhibition [abstract no. C1-1427 plus poster]. In: 50th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2010 Sep 12–15; Boston (MA).
37.
go back to reference Docquier J, Benvenuti M, De Luca F, et al. X-ray crystal structure of the Klebsiella pneumoniae OXA-48 class D carbapenemase inhibited by NXL104 [abstract no. C1-640 plus poster]. In: 50th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2010 Sep 12–15; Boston (MA). Docquier J, Benvenuti M, De Luca F, et al. X-ray crystal structure of the Klebsiella pneumoniae OXA-48 class D carbapenemase inhibited by NXL104 [abstract no. C1-640 plus poster]. In: 50th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2010 Sep 12–15; Boston (MA).
38.
go back to reference Docquier J, Benvenuti M, Bruneau J, et al. X-ray crystal structure of the Acinetobacter baumannii OXA-24/40 Class D carbapenemase inhibited by NXL104 [abstract no. P609]. Clin Microbiol Infect. 2011;17(Suppl. 4):S125. Plus poster presented at 21st European Congress of Clinical Microbiology and Infectious Diseases; 2011 May 7–10; Milan. Docquier J, Benvenuti M, Bruneau J, et al. X-ray crystal structure of the Acinetobacter baumannii OXA-24/40 Class D carbapenemase inhibited by NXL104 [abstract no. P609]. Clin Microbiol Infect. 2011;17(Suppl. 4):S125. Plus poster presented at 21st European Congress of Clinical Microbiology and Infectious Diseases; 2011 May 7–10; Milan.
39.
go back to reference Ehmann DE, Jahic H, Ross PL, et al. Avibactam is a covalent, reversible, non-beta-lactam beta-lactamase inhibitor. Proc Natl Acad Sci USA. 2012;109(29):11663–8.PubMedCrossRef Ehmann DE, Jahic H, Ross PL, et al. Avibactam is a covalent, reversible, non-beta-lactam beta-lactamase inhibitor. Proc Natl Acad Sci USA. 2012;109(29):11663–8.PubMedCrossRef
40.
go back to reference Stachyra T, Pechereau M, Bruneau J, et al. The nature of inhibition of TEM-1 β-Lactamase by the non-β-Lactam inhibitor NXL104 [abstract no. C1-1374 plus poster]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA). Stachyra T, Pechereau M, Bruneau J, et al. The nature of inhibition of TEM-1 β-Lactamase by the non-β-Lactam inhibitor NXL104 [abstract no. C1-1374 plus poster]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA).
41.
go back to reference Stachyra T, Pechereau MC, Bruneau JM, et al. Mechanistic studies of the inactivation of TEM-1 and P99 by NXL104, a novel non-beta-lactam beta-lactamase inhibitor. Antimicrob Agents Chemother. 2010;54(12):5132–8.PubMedCrossRef Stachyra T, Pechereau MC, Bruneau JM, et al. Mechanistic studies of the inactivation of TEM-1 and P99 by NXL104, a novel non-beta-lactam beta-lactamase inhibitor. Antimicrob Agents Chemother. 2010;54(12):5132–8.PubMedCrossRef
42.
go back to reference Bonnefoy A, Dupuis-Hamelin C, Steier V, et al. In vitro activity of AVE1330A, an innovative broad-spectrum non-beta-lactam beta-lactamase inhibitor. J Antimicrob Chemother. 2004;54(2):410–7.PubMedCrossRef Bonnefoy A, Dupuis-Hamelin C, Steier V, et al. In vitro activity of AVE1330A, an innovative broad-spectrum non-beta-lactam beta-lactamase inhibitor. J Antimicrob Chemother. 2004;54(2):410–7.PubMedCrossRef
43.
go back to reference Miossec C, Claudon M, Platel D, et al. The β-lactamase inhibitor NXL104 does not induce ampC β-lactamase expression in Enterobacter cloacae: evaluation of ampC expression by quantitative polymerase chain reaction (Q-PCR) [abstract no. F-128 plus poster]. In: 46th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA). Miossec C, Claudon M, Platel D, et al. The β-lactamase inhibitor NXL104 does not induce ampC β-lactamase expression in Enterobacter cloacae: evaluation of ampC expression by quantitative polymerase chain reaction (Q-PCR) [abstract no. F-128 plus poster]. In: 46th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA).
44.
go back to reference Livermore DM, Mushtaq S, Barker K, et al. Characterization of beta-lactamase and porin mutants of Enterobacteriaceae selected with ceftaroline + avibactam (NXL104). J Antimicrob Chemother. 2012;67(6):1354–8.PubMedCrossRef Livermore DM, Mushtaq S, Barker K, et al. Characterization of beta-lactamase and porin mutants of Enterobacteriaceae selected with ceftaroline + avibactam (NXL104). J Antimicrob Chemother. 2012;67(6):1354–8.PubMedCrossRef
45.
go back to reference Li M, Conklin B, Bonomo R, et al. Effect of N152G substitution of CMY-2 β-lactamase activity and inhibition [abstract no. A-1012 plus poster]. In: 111th General Meeting of the American Society of Microbiology; 2011 May 21–24; New Orleans (LA). Li M, Conklin B, Bonomo R, et al. Effect of N152G substitution of CMY-2 β-lactamase activity and inhibition [abstract no. A-1012 plus poster]. In: 111th General Meeting of the American Society of Microbiology; 2011 May 21–24; New Orleans (LA).
46.
go back to reference Skalweit M, Li M, Conklin B, et al. Effect of N152G, S and T substitution on CMY-2 β-lactamase activity and inhibition [abstract no. C1-601 plus poster]. In: 51st Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2011 Sep 17–20; Chicago (IL). Skalweit M, Li M, Conklin B, et al. Effect of N152G, S and T substitution on CMY-2 β-lactamase activity and inhibition [abstract no. C1-601 plus poster]. In: 51st Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2011 Sep 17–20; Chicago (IL).
47.
go back to reference Aktas Z, Kayacan C, Oncul O. In vitro activity of NXL104 in combination with β-lactams against Gram-negative bacteria, including OXA-48 beta-lactamase producing Klebsiella pneumoniae [abstract no. E-808 plus poster]. In: 50th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2010 Sep 12–15; Boston (MA). Aktas Z, Kayacan C, Oncul O. In vitro activity of NXL104 in combination with β-lactams against Gram-negative bacteria, including OXA-48 beta-lactamase producing Klebsiella pneumoniae [abstract no. E-808 plus poster]. In: 50th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2010 Sep 12–15; Boston (MA).
48.
go back to reference Aktas Z, Kayacan C, Oncul O. In vitro activity of avibactam (NXL104) in combination with beta-lactams against Gram-negative bacteria, including OXA-48 beta-lactamase-producing Klebsiella pneumoniae. Int J Antimicrob Agents. 2012;39(1):86–9.PubMedCrossRef Aktas Z, Kayacan C, Oncul O. In vitro activity of avibactam (NXL104) in combination with beta-lactams against Gram-negative bacteria, including OXA-48 beta-lactamase-producing Klebsiella pneumoniae. Int J Antimicrob Agents. 2012;39(1):86–9.PubMedCrossRef
49.
go back to reference Biedenbach D, Konrardy M, Sader H, et al. In vitro activity of ceftazidime/NXL104 against pathogens collected during a phase II complicated urinary tract infection (cUTI) clinical trial [abstract no. E-137 plus poster]. In: 51st Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2011 Sep 17–20; Chicago (IL). Biedenbach D, Konrardy M, Sader H, et al. In vitro activity of ceftazidime/NXL104 against pathogens collected during a phase II complicated urinary tract infection (cUTI) clinical trial [abstract no. E-137 plus poster]. In: 51st Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2011 Sep 17–20; Chicago (IL).
50.
go back to reference Castanheira M, Rhomberg P, Jones R, et al. Potent activity of ceftazidime/NXL104 tested against Enterobacteriaceae isolates carrying multiple β-lactamase enzymes [abstract no. P 1265]. Clin Microbiol Infect. 2010;16(Suppl. 2):S355. Plus poster presented at 20th European Congress of Clinical Microbiology and Infectious Diseases; 2010 Apr 10–13; Vienna. Castanheira M, Rhomberg P, Jones R, et al. Potent activity of ceftazidime/NXL104 tested against Enterobacteriaceae isolates carrying multiple β-lactamase enzymes [abstract no. P 1265]. Clin Microbiol Infect. 2010;16(Suppl. 2):S355. Plus poster presented at 20th European Congress of Clinical Microbiology and Infectious Diseases; 2010 Apr 10–13; Vienna.
51.
go back to reference Crandon J, Banevicius M, Nicolau D. Comparative potency of ceftazidime (CAZ) and ceftazidime-NXL104 (CAZ104) against a resistant population of clinical Pseudomonas aeruginosa (PSA) isolates [abstract no. 585 plus poster]. In: 49th Annual Meeting of the Infectious Diseases Society of America; 2011 Sep 12–15; Boston (MA). Crandon J, Banevicius M, Nicolau D. Comparative potency of ceftazidime (CAZ) and ceftazidime-NXL104 (CAZ104) against a resistant population of clinical Pseudomonas aeruginosa (PSA) isolates [abstract no. 585 plus poster]. In: 49th Annual Meeting of the Infectious Diseases Society of America; 2011 Sep 12–15; Boston (MA).
52.
go back to reference Endimiani A, Choudhary Y, Bonomo RA. In vitro activity of NXL104 in combination with beta-lactams against Klebsiella pneumoniae isolates producing KPC carbapenemases. Antimicrob Agents Chemother. 2009;53(8):3599–601.PubMedCrossRef Endimiani A, Choudhary Y, Bonomo RA. In vitro activity of NXL104 in combination with beta-lactams against Klebsiella pneumoniae isolates producing KPC carbapenemases. Antimicrob Agents Chemother. 2009;53(8):3599–601.PubMedCrossRef
53.
go back to reference Gin A, Dilay L, Karlowsky JA, et al. Piperacillin-tazobactam: a beta-lactam/beta-lactamase inhibitor combination. Expert Rev Anti Infect Ther. 2007;5(3):365–83.PubMedCrossRef Gin A, Dilay L, Karlowsky JA, et al. Piperacillin-tazobactam: a beta-lactam/beta-lactamase inhibitor combination. Expert Rev Anti Infect Ther. 2007;5(3):365–83.PubMedCrossRef
54.
go back to reference Lagacé-Wiens P, Simner P, Tailor F, et al. Activity of ceftazidime (CAZ)/NXL104 (CAZ104) versus CAZ alone and other comparators against 4548 Gram-negative bacilli—results from CANWARD 2009-10 [abstract no. E-1816 plus poster]. In: 51st Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2011 Sep 17–20; Chicago (IL). Lagacé-Wiens P, Simner P, Tailor F, et al. Activity of ceftazidime (CAZ)/NXL104 (CAZ104) versus CAZ alone and other comparators against 4548 Gram-negative bacilli—results from CANWARD 2009-10 [abstract no. E-1816 plus poster]. In: 51st Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2011 Sep 17–20; Chicago (IL).
55.
go back to reference Lagace-Wiens PR, Tailor F, Simner P, et al. Activity of NXL104 in combination with beta-lactams against genetically characterized Escherichia coli and Klebsiella pneumoniae isolates producing class A extended-spectrum beta-lactamases and class C beta-lactamases. Antimicrob Agents Chemother. 2011;55(5):2434–7.PubMedCrossRef Lagace-Wiens PR, Tailor F, Simner P, et al. Activity of NXL104 in combination with beta-lactams against genetically characterized Escherichia coli and Klebsiella pneumoniae isolates producing class A extended-spectrum beta-lactamases and class C beta-lactamases. Antimicrob Agents Chemother. 2011;55(5):2434–7.PubMedCrossRef
56.
go back to reference Levasseur P, Girard AM, Claudon M, et al. In vitro antibacterial activity of the ceftazidime-avibactam (NXL104) combination against Pseudomonas aeruginosa clinical isolates. Antimicrob Agents Chemother. 2012;56(3):1606–8.PubMedCrossRef Levasseur P, Girard AM, Claudon M, et al. In vitro antibacterial activity of the ceftazidime-avibactam (NXL104) combination against Pseudomonas aeruginosa clinical isolates. Antimicrob Agents Chemother. 2012;56(3):1606–8.PubMedCrossRef
57.
go back to reference Levasseur P, Miossec C, Girard A, et al. In vitro antibacterial activity of ceftazidime (CAZ) in combination with the β-lactamase inhibitor, NXL104 [abstract no. E-186 plus poster]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA). Levasseur P, Miossec C, Girard A, et al. In vitro antibacterial activity of ceftazidime (CAZ) in combination with the β-lactamase inhibitor, NXL104 [abstract no. E-186 plus poster]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA).
58.
go back to reference Livermore DM, Mushtaq S, Warner M, et al. Activities of NXL104 combinations with ceftazidime and aztreonam against carbapenemase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2011;55(1):390–4.PubMedCrossRef Livermore DM, Mushtaq S, Warner M, et al. Activities of NXL104 combinations with ceftazidime and aztreonam against carbapenemase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2011;55(1):390–4.PubMedCrossRef
59.
go back to reference Mushtaq S, Warner M, Livermore DM. In vitro activity of ceftazidime + NXL104 against Pseudomonas aeruginosa and other non-fermenters. J Antimicrob Chemother. 2010;65(11):2376–81.PubMedCrossRef Mushtaq S, Warner M, Livermore DM. In vitro activity of ceftazidime + NXL104 against Pseudomonas aeruginosa and other non-fermenters. J Antimicrob Chemother. 2010;65(11):2376–81.PubMedCrossRef
60.
go back to reference Sader H, Castanheira M, Farrell J, et al. Antimicrobial activity of ceftazidime/NXL104 tested against Gram-negative organisms, including multidrug-resistant subjects, causing infections in USA and European medical centers [abstract no. E-811 plus poster]. In: 50th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2010 Sep 12–15; Boston (MA). Sader H, Castanheira M, Farrell J, et al. Antimicrobial activity of ceftazidime/NXL104 tested against Gram-negative organisms, including multidrug-resistant subjects, causing infections in USA and European medical centers [abstract no. E-811 plus poster]. In: 50th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2010 Sep 12–15; Boston (MA).
61.
go back to reference Sader H, Farrell D, Bell J, et al. Antimicrobial activity of ceftazidime/NXL104 (CAZ104) tested against Gram-negative organisms causing infections in medical centers from Europe (EU), Latin America (LA) and the Asia-Pacific Region (APAC) [abstract no. C2-1251 plus poster]. In: 51st Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2011 Sep 17–20; Chicago (IL). Sader H, Farrell D, Bell J, et al. Antimicrobial activity of ceftazidime/NXL104 (CAZ104) tested against Gram-negative organisms causing infections in medical centers from Europe (EU), Latin America (LA) and the Asia-Pacific Region (APAC) [abstract no. C2-1251 plus poster]. In: 51st Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2011 Sep 17–20; Chicago (IL).
62.
go back to reference Sahm D, Pillar C, Brown N, et al. Activity of ceftazidime/NXL104 and select comparators against geographically diverse clinical isolates of Pseudomonas aeruginosa [abstract no. E-194 plus poster]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA). Sahm D, Pillar C, Brown N, et al. Activity of ceftazidime/NXL104 and select comparators against geographically diverse clinical isolates of Pseudomonas aeruginosa [abstract no. E-194 plus poster]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA).
63.
go back to reference Tailor F, Lagacé-Wiens P, Simner P, et al. Activity of avibactam (NXL-104) in combination with β-lactams against molecularly characterized AmpC- and ESBL-producing Escherichia coli and Klebsiella pneumoniae for CANWARD 2007–2010 [abstract no. F1-165 plus poster]. In: 51st Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2011 Sep 17–20; Chicago (IL). Tailor F, Lagacé-Wiens P, Simner P, et al. Activity of avibactam (NXL-104) in combination with β-lactams against molecularly characterized AmpC- and ESBL-producing Escherichia coli and Klebsiella pneumoniae for CANWARD 2007–2010 [abstract no. F1-165 plus poster]. In: 51st Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2011 Sep 17–20; Chicago (IL).
64.
go back to reference Walkty A, DeCorby M, Lagace-Wiens PR, et al. In vitro activity of ceftazidime combined with NXL104 versus Pseudomonas aeruginosa isolates obtained from patients in Canadian hospitals (CANWARD 2009 study). Antimicrob Agents Chemother. 2011;55(6):2992–4.PubMedCrossRef Walkty A, DeCorby M, Lagace-Wiens PR, et al. In vitro activity of ceftazidime combined with NXL104 versus Pseudomonas aeruginosa isolates obtained from patients in Canadian hospitals (CANWARD 2009 study). Antimicrob Agents Chemother. 2011;55(6):2992–4.PubMedCrossRef
65.
go back to reference Zhanel GG, Adam HJ, Low DE, et al. Antimicrobial susceptibility of 15,644 pathogens from Canadian hospitals: results of the CANWARD 2007–2009 study. Diagn Microbiol Infect Dis. 2011;69(3):291–306.PubMedCrossRef Zhanel GG, Adam HJ, Low DE, et al. Antimicrobial susceptibility of 15,644 pathogens from Canadian hospitals: results of the CANWARD 2007–2009 study. Diagn Microbiol Infect Dis. 2011;69(3):291–306.PubMedCrossRef
66.
go back to reference Zhanel GG, Sniezek G, Schweizer F, et al. Ceftaroline: a novel broad-spectrum cephalosporin with activity against meticillin-resistant Staphylococcus aureus. Drugs. 2009;69(7):809–31.PubMedCrossRef Zhanel GG, Sniezek G, Schweizer F, et al. Ceftaroline: a novel broad-spectrum cephalosporin with activity against meticillin-resistant Staphylococcus aureus. Drugs. 2009;69(7):809–31.PubMedCrossRef
67.
go back to reference Borgonovi M, Merdjan H, Girard A, et al. Importance of NXL104 pharmacokinetics (PK) in the pharmacodynamics (PD) of ceftazidime + NXL104 combinations in an in vitro hollow fiber infection model [abstract no. A-023 plus poster]. In: 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2008 Oct 25–28; Washington (DC). Borgonovi M, Merdjan H, Girard A, et al. Importance of NXL104 pharmacokinetics (PK) in the pharmacodynamics (PD) of ceftazidime + NXL104 combinations in an in vitro hollow fiber infection model [abstract no. A-023 plus poster]. In: 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2008 Oct 25–28; Washington (DC).
68.
go back to reference Borgonovi M, Miossec C, Lowther J. The efficacy of ceftazidime combined with NXL104, a novel β-lactamase inhibitor, in a mouse model of kidney infections induced by β-lactamase producing Enterobacteriaceae [abstract no. P794]. Clin Microbiol Infect. 2007;13(Suppl. 2):S199–200. Plus poster presented at 17th European Congress of Clinical Microbiology and Infectious Diseases; 2007 Mar 31–Apr 3; Munich. Borgonovi M, Miossec C, Lowther J. The efficacy of ceftazidime combined with NXL104, a novel β-lactamase inhibitor, in a mouse model of kidney infections induced by β-lactamase producing Enterobacteriaceae [abstract no. P794]. Clin Microbiol Infect. 2007;13(Suppl. 2):S199–200. Plus poster presented at 17th European Congress of Clinical Microbiology and Infectious Diseases; 2007 Mar 31–Apr 3; Munich.
69.
go back to reference Cottagnoud P, Merdjan H, Acosta F, et al. Pharmacokinetics of the new β-lactamase inhibitor NXL104 in an experimental rabbit meningitis model; restoration of the bacteriological efficacy of ceftazidime (CAZ) against a class C producing K. pneumoniae [abstract no. F1-321 plus poster]. In: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL). Cottagnoud P, Merdjan H, Acosta F, et al. Pharmacokinetics of the new β-lactamase inhibitor NXL104 in an experimental rabbit meningitis model; restoration of the bacteriological efficacy of ceftazidime (CAZ) against a class C producing K. pneumoniae [abstract no. F1-321 plus poster]. In: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL).
70.
go back to reference Levasseur P, Girard A, Delachaume C, et al. NXL104, a novel β-lactamase inhibitor, restores the bactericidal activity of ceftazidime against ESBL and AmpC producing strains of Enterobacteriaceae [abstract no. F-127 plus poster]. In: 46th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA). Levasseur P, Girard A, Delachaume C, et al. NXL104, a novel β-lactamase inhibitor, restores the bactericidal activity of ceftazidime against ESBL and AmpC producing strains of Enterobacteriaceae [abstract no. F-127 plus poster]. In: 46th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA).
71.
go back to reference Levasseur P, Girard A, Lavallade L, et al. Efficacy of ceftazidime (CAZ)/NXL104 combination in murine septicaemia caused by CTX-M-producing Enterobacteriaceae species [abstract no. A1-005 plus poster]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA). Levasseur P, Girard A, Lavallade L, et al. Efficacy of ceftazidime (CAZ)/NXL104 combination in murine septicaemia caused by CTX-M-producing Enterobacteriaceae species [abstract no. A1-005 plus poster]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA).
72.
go back to reference Levasseur P, Miossec C, Girard A, et al. Use of NXL104, a β-lactamase inhibitor, to detect Klebsiella pneumoniae carbapenemase (KPC) in Enterobacteriaceae [abstract no. D-291b plus poster]. In: 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2008 Oct 25–28; Washington (DC). Levasseur P, Miossec C, Girard A, et al. Use of NXL104, a β-lactamase inhibitor, to detect Klebsiella pneumoniae carbapenemase (KPC) in Enterobacteriaceae [abstract no. D-291b plus poster]. In: 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2008 Oct 25–28; Washington (DC).
73.
go back to reference Livermore DM, Mushtaq S, Warner M, et al. NXL104 combinations versus Enterobacteriaceae with CTX-M extended-spectrum beta-lactamases and carbapenemases. J Antimicrob Chemother. 2008;62(5):1053–6.PubMedCrossRef Livermore DM, Mushtaq S, Warner M, et al. NXL104 combinations versus Enterobacteriaceae with CTX-M extended-spectrum beta-lactamases and carbapenemases. J Antimicrob Chemother. 2008;62(5):1053–6.PubMedCrossRef
74.
go back to reference Mendes R, Woosley L, Deshpande L, et al. Characterization of resistance mechanisms and epidemiology of Enterobacteriaceae collected during a phase II clinical trial for ceftazidime-avibactam [abstract no. P1676]. Clin Microbiol Infect. 2012;18(Suppl 3):464. Plus poster presented at 22nd European Congress of Clinical Microbiology and Infectious Diseases; 2012 Mar 31–Apr 3; London. Mendes R, Woosley L, Deshpande L, et al. Characterization of resistance mechanisms and epidemiology of Enterobacteriaceae collected during a phase II clinical trial for ceftazidime-avibactam [abstract no. P1676]. Clin Microbiol Infect. 2012;18(Suppl 3):464. Plus poster presented at 22nd European Congress of Clinical Microbiology and Infectious Diseases; 2012 Mar 31–Apr 3; London.
75.
go back to reference Merdjan H, Girard A, Miossec C, et al. Pharmacokinetics (PK) and efficacy of ceftazidime (CAZ)/NXL104 combination in a murine pneumonia model caused by an AmpC-producing Klebsiella pneumoniae [abstract no. A1-006 plus poster]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA). Merdjan H, Girard A, Miossec C, et al. Pharmacokinetics (PK) and efficacy of ceftazidime (CAZ)/NXL104 combination in a murine pneumonia model caused by an AmpC-producing Klebsiella pneumoniae [abstract no. A1-006 plus poster]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA).
76.
go back to reference Miossec C, Poirel L, Livermore D, et al. In vitro activity of the new β-lactamase inhibitor NXL104: restoration of ceftazidime (CAZ) efficacy against carbapenem-resistant Enterobacteriaceae strains [abstract no. F1-318 plus poster]. In: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL). Miossec C, Poirel L, Livermore D, et al. In vitro activity of the new β-lactamase inhibitor NXL104: restoration of ceftazidime (CAZ) efficacy against carbapenem-resistant Enterobacteriaceae strains [abstract no. F1-318 plus poster]. In: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL).
77.
go back to reference Mushtaq S, Warner M, Miossec C, et al. NXL104/cephalosporin combinations vs. Enterobacteriaceae with CTX-M ESBLs [abstract no. F1-319 plus poster]. In: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL). Mushtaq S, Warner M, Miossec C, et al. NXL104/cephalosporin combinations vs. Enterobacteriaceae with CTX-M ESBLs [abstract no. F1-319 plus poster]. In: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL).
78.
go back to reference Pechereau M, Claudon M, Black M, et al. Activité in vitro de NXL104 sur CTX-M-15 et KPC-2: un nouvel inhibiteur de β-lactamases à spectre étendu (BLSE) et de carbapénèmases de classe A [abstract no. 468 plus poster]. 28ème Réunion Interdisciplinaire de Chimiothérapie Anti-infectieuse; 2008 Dec 3–4; Paris. Pechereau M, Claudon M, Black M, et al. Activité in vitro de NXL104 sur CTX-M-15 et KPC-2: un nouvel inhibiteur de β-lactamases à spectre étendu (BLSE) et de carbapénèmases de classe A [abstract no. 468 plus poster]. 28ème Réunion Interdisciplinaire de Chimiothérapie Anti-infectieuse; 2008 Dec 3–4; Paris.
79.
go back to reference Pechereau M, Claudon M, Black M, et al. Activité in vitro de NXL104 sur SHV-4: un nouvel inhibiteur des β-lactamases à spectre étendu [abstract no. 382 plus poster]. 26ème Réunion Interdisciplinaire de Chimiothérapie Anti-infectieuse; 2006 Dec 7–8; Paris. Pechereau M, Claudon M, Black M, et al. Activité in vitro de NXL104 sur SHV-4: un nouvel inhibiteur des β-lactamases à spectre étendu [abstract no. 382 plus poster]. 26ème Réunion Interdisciplinaire de Chimiothérapie Anti-infectieuse; 2006 Dec 7–8; Paris.
80.
go back to reference Shackcloth J, Williams L, Northwood J, et al. In vitro activity of AVE1330A, a novel β-lactamase inhibitor, in combination with aztreonam or ceftazidime against ceftazidime-resistant isolates of species of the Enterobacteriaceae [abstract no. P1571]. Clin Microbiol Infect. 2005;11(Suppl. 2):S511. Plus poster presented at 15th European Congress of Clinical Microbiology and Infectious Diseases; 2005 Apr 2–5; Copenhagen. Shackcloth J, Williams L, Northwood J, et al. In vitro activity of AVE1330A, a novel β-lactamase inhibitor, in combination with aztreonam or ceftazidime against ceftazidime-resistant isolates of species of the Enterobacteriaceae [abstract no. P1571]. Clin Microbiol Infect. 2005;11(Suppl. 2):S511. Plus poster presented at 15th European Congress of Clinical Microbiology and Infectious Diseases; 2005 Apr 2–5; Copenhagen.
81.
go back to reference Stachyra T, Levasseur P, Pechereau MC, et al. In vitro activity of the {beta}-lactamase inhibitor NXL104 against KPC-2 carbapenemase and Enterobacteriaceae expressing KPC carbapenemases. J Antimicrob Chemother. 2009;64(2):326–9.PubMedCrossRef Stachyra T, Levasseur P, Pechereau MC, et al. In vitro activity of the {beta}-lactamase inhibitor NXL104 against KPC-2 carbapenemase and Enterobacteriaceae expressing KPC carbapenemases. J Antimicrob Chemother. 2009;64(2):326–9.PubMedCrossRef
82.
go back to reference Stachyra T, Pechereau M, Petrella S, et al. Activity of the new β-lactamase inhibitor NXL104 against KPC β-lactamases [abstract no. F1-320 plus poster]. In: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL). Stachyra T, Pechereau M, Petrella S, et al. Activity of the new β-lactamase inhibitor NXL104 against KPC β-lactamases [abstract no. F1-320 plus poster]. In: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL).
83.
go back to reference Weiss W, Pulse M, Endimiani A, et al. Efficacy of NXL104 in combination with ceftazidime in murine infection models [abstract no. B-1339 plus poster]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA). Weiss W, Pulse M, Endimiani A, et al. Efficacy of NXL104 in combination with ceftazidime in murine infection models [abstract no. B-1339 plus poster]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA).
84.
go back to reference Citron D, Goldstein E. In vitro activity of NXL104/ceftazidime against β-lactamase producing anaerobic bacteria [abstract no. E-192 plus poster]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA). Citron D, Goldstein E. In vitro activity of NXL104/ceftazidime against β-lactamase producing anaerobic bacteria [abstract no. E-192 plus poster]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA).
85.
go back to reference Citron DM, Tyrrell KL, Merriam V, et al. In vitro activity of ceftazidime-NXL104 against 396 strains of beta-lactamase-producing anaerobes. Antimicrob Agents Chemother. 2011;55(7):3616–20.PubMedCrossRef Citron DM, Tyrrell KL, Merriam V, et al. In vitro activity of ceftazidime-NXL104 against 396 strains of beta-lactamase-producing anaerobes. Antimicrob Agents Chemother. 2011;55(7):3616–20.PubMedCrossRef
86.
go back to reference Dubreuil LJ, Mahieux S, Neut C, et al. Anti-anaerobic activity of a new beta-lactamase inhibitor NXL104 in combination with beta-lactams and metronidazole. Int J Antimicrob Agents. 2012;39(6):500–4.PubMedCrossRef Dubreuil LJ, Mahieux S, Neut C, et al. Anti-anaerobic activity of a new beta-lactamase inhibitor NXL104 in combination with beta-lactams and metronidazole. Int J Antimicrob Agents. 2012;39(6):500–4.PubMedCrossRef
87.
go back to reference Zhanel G, Brunham R. Third-generation cephalosporins. Can J Hosp Pharm. 1988;41(4):183–94. Zhanel G, Brunham R. Third-generation cephalosporins. Can J Hosp Pharm. 1988;41(4):183–94.
88.
go back to reference Merdjan H, Tarral A, Girard A, et al. Safety, single dose pharmacokinetics, and pharmacodynamics of β-lactamase inhibitor NXL104 in healthy young male adults [abstract no. A-809 plus poster]. In: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL). Merdjan H, Tarral A, Girard A, et al. Safety, single dose pharmacokinetics, and pharmacodynamics of β-lactamase inhibitor NXL104 in healthy young male adults [abstract no. A-809 plus poster]. In: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL).
89.
go back to reference Felices M, Gualano V, Tarral A, et al. Combined population pharmacokinetic analysis of four phase 1 studies with NXL104 [abstract no. P 1599]. Clin Microbiol Infect. 2010;16(Suppl. 2):S466. Plus poster presented at 20th European Congress of Clinical Microbiology and Infectious Diseases; 2010 Apr 10–13; Vienna. Felices M, Gualano V, Tarral A, et al. Combined population pharmacokinetic analysis of four phase 1 studies with NXL104 [abstract no. P 1599]. Clin Microbiol Infect. 2010;16(Suppl. 2):S466. Plus poster presented at 20th European Congress of Clinical Microbiology and Infectious Diseases; 2010 Apr 10–13; Vienna.
90.
go back to reference Li J, Knebel W, Riggs M, et al. Population pharmacokinetic modeling of ceftazidime (CAZ) and avibactam (AVI) in healthy volunteers and patients with complicated intra-abdominal Infection (cIAI) [abstract no. A-634 plus poster]. In: 52nd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2012 Sep 9–12; San Francisco (CA). Li J, Knebel W, Riggs M, et al. Population pharmacokinetic modeling of ceftazidime (CAZ) and avibactam (AVI) in healthy volunteers and patients with complicated intra-abdominal Infection (cIAI) [abstract no. A-634 plus poster]. In: 52nd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2012 Sep 9–12; San Francisco (CA).
91.
go back to reference Merdjan H, Tarral A, Haazen W, et al. Pharmacokinetics and tolerability of NXL104 in normal subjects and patients with varying degrees of renal insufficiency. [abstract no. P 1598]. Clin Microbiol Infect. 2010;16(Suppl. 2):S465. Plus poster presented at 20th European Congress of Clinical Microbiology and Infectious Diseases; 2010 Apr 10–13; Vienna. Merdjan H, Tarral A, Haazen W, et al. Pharmacokinetics and tolerability of NXL104 in normal subjects and patients with varying degrees of renal insufficiency. [abstract no. P 1598]. Clin Microbiol Infect. 2010;16(Suppl. 2):S465. Plus poster presented at 20th European Congress of Clinical Microbiology and Infectious Diseases; 2010 Apr 10–13; Vienna.
92.
go back to reference Bowker K, Noel A, MacGowan A. Pharmacodynamics of NXL104 plus either ceftaroline or ceftazidine against an AmpC producing Enterobacter spp [abstract no. A2-556 plus poster]. In: 51st Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2011 Sep 17–20; Chicago (IL). Bowker K, Noel A, MacGowan A. Pharmacodynamics of NXL104 plus either ceftaroline or ceftazidine against an AmpC producing Enterobacter spp [abstract no. A2-556 plus poster]. In: 51st Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2011 Sep 17–20; Chicago (IL).
93.
go back to reference Endimiani A, Hujer KM, Hujer AM, et al. Evaluation of ceftazidime and NXL104 in two murine models of infection due to KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2010;55(1):82–5.PubMedCrossRef Endimiani A, Hujer KM, Hujer AM, et al. Evaluation of ceftazidime and NXL104 in two murine models of infection due to KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2010;55(1):82–5.PubMedCrossRef
94.
go back to reference Crandon JL, Schuck VJ, Banevicius MA, et al. Comparative in vitro and in vivo efficacy of human simulated exposures of ceftazidime and ceftazidime-avibactam against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2012;56(12):6137–46.PubMedCrossRef Crandon JL, Schuck VJ, Banevicius MA, et al. Comparative in vitro and in vivo efficacy of human simulated exposures of ceftazidime and ceftazidime-avibactam against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2012;56(12):6137–46.PubMedCrossRef
95.
go back to reference Lucasti C, Popescu I, Ramesh M, et al. Efficacy and safety of ceftazidime/NXL104 plus metronidazole vs. meropenem in the treatment of complicated intra-abdominal infections in hospitalised adults [abstract no. P1532]. Clin Microbiol Infect. 2011;17(Suppl. 4):S437. Plus poster presented at 21st European Congress of Clinical Microbiology and Infectious Diseases; 2011 May 7–10; Milan. Lucasti C, Popescu I, Ramesh M, et al. Efficacy and safety of ceftazidime/NXL104 plus metronidazole vs. meropenem in the treatment of complicated intra-abdominal infections in hospitalised adults [abstract no. P1532]. Clin Microbiol Infect. 2011;17(Suppl. 4):S437. Plus poster presented at 21st European Congress of Clinical Microbiology and Infectious Diseases; 2011 May 7–10; Milan.
96.
go back to reference Vazquez J, González Patzán L, Stricklin D, et al. Efficacy and safety of ceftazidime avibactam versus imipenem cilastatin for complicated urinary tract infections including acute pyelonephritis, in hospitalized adults: results of a prospective investigator-blinded randomized study. Curr Med Res Opin. 2012;28(12):1921–31.PubMedCrossRef Vazquez J, González Patzán L, Stricklin D, et al. Efficacy and safety of ceftazidime avibactam versus imipenem cilastatin for complicated urinary tract infections including acute pyelonephritis, in hospitalized adults: results of a prospective investigator-blinded randomized study. Curr Med Res Opin. 2012;28(12):1921–31.PubMedCrossRef
97.
go back to reference Tarral A, Lipka J, Gyaw S, et al. Effect of age and gender on the pharmacokinetics (PK) and safety of NXL104 in healthy subjects (protocol NXL104/1004) [abstract no. A1-007 plus poster]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA). Tarral A, Lipka J, Gyaw S, et al. Effect of age and gender on the pharmacokinetics (PK) and safety of NXL104 in healthy subjects (protocol NXL104/1004) [abstract no. A1-007 plus poster]. In: 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2009 Sep 12–15; San Francisco (CA).
98.
go back to reference Li J, Edeki T, Das S, et al. Effect of a supratherapeutic dose of ceftazidime-avibactam on the QTc interval in a thorough QT study [abstract no. P1417]. Clin Microbiol Infect. 2012;18(Suppl. 3):372. Plus poster presented at 22nd European Congress of Clinical Microbiology and Infectious Diseases; 2012 Mar 31–Apr 3; London. Li J, Edeki T, Das S, et al. Effect of a supratherapeutic dose of ceftazidime-avibactam on the QTc interval in a thorough QT study [abstract no. P1417]. Clin Microbiol Infect. 2012;18(Suppl. 3):372. Plus poster presented at 22nd European Congress of Clinical Microbiology and Infectious Diseases; 2012 Mar 31–Apr 3; London.
Metadata
Title
Ceftazidime-Avibactam: a Novel Cephalosporin/β-lactamase Inhibitor Combination
Authors
George G. Zhanel
Christopher D. Lawson
Heather Adam
Frank Schweizer
Sheryl Zelenitsky
Philippe R. S. Lagacé-Wiens
Andrew Denisuik
Ethan Rubinstein
Alfred S. Gin
Daryl J. Hoban
Joseph P. Lynch 3rd
James A. Karlowsky
Publication date
01-02-2013
Publisher
Springer International Publishing AG
Published in
Drugs / Issue 2/2013
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.1007/s40265-013-0013-7

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