Current - Issue
Year 2026 · Volume 6 · Issue 5
Review Article
Stability-Indicating Analytical Methods for Ceftazidime–Avibactam: A Comprehensive Review of Chromatographic, Spectrophotometric, and Emerging Approaches
Gokulamanikandan M1
Manoj V2
Ramakrishnan M3
Saravanan V S4
Prabhu S5
1 2 3 4 5 Department of Pharmaceutical Analysis, The Erode College of Pharmacy, Veppampalayam, Erode, Tamilnadu, India.
Published Online: September-October 2026
Pages: 294-300
Cite this article
↗ https://www.doi.org/10.59256/ijrtmr.20260605032
References
1. Shirley M. Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections. Drugs. 2018;78(6):675-692. PMID: 29671219.
2. Sharma R, Park TE, Moy S. Ceftazidime-Avibactam: A Novel Cephalosporin/β-Lactamase Inhibitor Combination for the Treatment of Resistant Gram-negative Organisms. Clin Ther. 2016;38(3):431-444. PMID: 26948862.
3. Zhen S, Wang H, Feng S. Update of clinical application in ceftazidime-avibactam for multidrug-resistant Gram-negative bacteria infections. Infection. 2022;50(6):1409-1423. PMID: 35781869.
4. Evaluation of the stability of ceftazidime/avibactam in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy utilizing a national stability protocol framework. JAC Antimicrob Resist. 2024;6(2):dlae056. PMID: 38585225.
5. Stability of reconstituted solutions of ceftazidime for injections: an HPLC and CE approach. PMID: 10701968.
6. Sillén H, Mitchell R, Sleigh R, Mainwaring G, Catton K, Houghton R, Glendining K. Determination of avibactam and ceftazidime in human plasma samples by LC-MS. Bioanalysis. 2015;7(12):1423-1434. PMID: 26168250.
7. Beaudoin ME, Gangl E. Bioanalytical method validation for the simultaneous determination of ceftazidime and avibactam in rat plasma.
Bioanalysis. 2016;8(2):111-122. PMID: 26652586.
8. Cheng Y, et al. Rapid, simple, and economical LC-MS/MS method for simultaneous determination of ceftazidime and avibactam in human plasma and its application in therapeutic drug monitoring. J Clin Pharm Ther. 2022;47(9):1426-1437. PMID: 35633089.
9. Das S, Li J, Riccobene T, Carrothers TJ, Newell P, Melnick D, Critchley IA, Stone GG, Nichols WW. Dose Selection and Validation for Ceftazidime-Avibactam in Adults with Complicated Intra-abdominal Infections, Complicated Urinary Tract Infections, and Nosocomial Pneumonia. Antimicrob Agents Chemother. 2019;63(4):e02187-18. PMID: 30670413.
10. Karlowsky JA, Biedenbach DJ, Kazmierczak KM, Stone GG, Sahm DF. Activity of Ceftazidime-Avibactam against Extended-Spectrum- and AmpC β-Lactamase-Producing Enterobacteriaceae Collected in the INFORM Global Surveillance Study from 2012 to 2014. Antimicrob Agents Chemother. 2016;60(5):2849-2857. PMID: 26926635.
11. Lahiri SD, et al. Avibactam and Class C β-Lactamases: Mechanism of Inhibition, Conservation of the Binding Pocket, and Implications for Resistance. Antimicrob Agents Chemother. 2014. PMID: 25022578.
12. Lahiri SD, Mangani S, Durand-Reville T, Benvenuti M, De Luca F, Sanyal G, Docquier JD. Structural insight into potent broad-spectrum inhibition with reversible recyclization mechanism: avibactam in complex with CTX-M-15 and Pseudomonas aeruginosa AmpC β-lactamases. Antimicrob Agents Chemother. 2013;57(6):2496-2505. PMID: 23439634.
13. Fröhlich C, Sørum V, Thomassen AM, Johnsen PJ, Leiros HS, Samuelsen Ø. OXA-48-Mediated Ceftazidime-Avibactam Resistance Is Associated with Evolutionary Trade-Offs. mSphere. 2019;4(2):e00024-19. PMID: 30918055.
14. Xiong L, Wang X, Wang Y, Yu W, Zhou Y, Chi X, Xiao T, Xiao Y. Molecular mechanisms underlying bacterial resistance to ceftazidime/avibactam. WIREs Mech Dis. 2022;14(6):e1571. PMID: 35891616.
15. Hernández-García M, Castillo-Polo JA, Cordero DG, Pérez-Viso B, García-Castillo M, Saez de la Fuente J, Morosini MI, Cantón R, Ruiz-Garbajosa P. Impact of Ceftazidime-Avibactam Treatment in the Emergence of Novel KPC Variants in the ST307-Klebsiella pneumoniae High-Risk Clone and Consequences for Their Routine Detection. J Clin Microbiol. 2022;60(3):e0224521. PMID: 35107303.
16. Blessy M, Patel RD, Prajapati PN, Agrawal YK. Development of forced degradation and stability indicating studies of drugs – A review. J Pharm Anal. 2014;4(3):159-165. PMID: 29403878.
17. Gaibani P, Lewis RE, Volpe SL, Giannella M, Campoli C, Landini MP, Viale P, Re MC, Ambretti S. In vitro interaction of ceftazidime-avibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates. Int J Infect Dis. 2017;65:1-3. PMID: 28951106.
18. Temkin E, Torre-Cisneros J, Beovic B, et al. Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms. Antimicrob Agents Chemother. 2017;61(2):e01964-16. PMID: 27895014.
19. Zhu L, Hu Q, Liu L, Ye S. Ceftazidime-Avibactam as a Salvage Treatment for Severely Infected Immunosuppressed Children. Drug Des Devel Ther. 2024;18:3399-3413. PMID: 39100219.
20. Fares MY, Hegazy MA, El-Sayed GM, Abdelrahman MM, Abdelwahab NS. Quality by design approach for green HPLC method development for simultaneous analysis of two thalassemia drugs in biological fluid with pharmacokinetic study. RSC Adv. 2022;12(22):13896-13916. PMID: 35548387.
21. Alqahtani A, Alqahtani T, Al Fatease A, Tolba EH. A quality by design HPLC method for cephalosporin analysis in pharmaceuticals and water samples with environmental impact assessment. Sci Rep. 2025;15. PMID: 39747994.
22. Development of a green HPLC method for the analysis of artesunate and amodiaquine impurities using Quality by Design. PMID: 32846400.
23. Development and validation of an UPLC-MS/MS assay for the simultaneous quantification of seven commonly used antibiotics (including ceftazidime) in human plasma and its application in therapeutic drug monitoring. J Antimicrob Chemother. 2024;79(4):883. PMID: 38416407.
24. Wang X, Du L, Zhang B, Li Y, Tao Z, Zhang L, Qu J, McFadden J, Qu H, Yang J, Liu J. Hydrogel-based fluorescence assay kit for simultaneous determination of ceftazidime and avibactam. Mikrochim Acta. 2024;191(11):675. PMID: 39414650.
25. Al-Kadhi NS, Mohamed MA, Ahmed HA, Nassar HF. Facile synthesis and eco-friendly analytical methods for concurrent estimation of selected pharmaceutical drugs in their solutions: application to quality by design, lean six sigma, and stability studies. BMC Chem. 2023;17(1):136. PMID: 37817268.
2. Sharma R, Park TE, Moy S. Ceftazidime-Avibactam: A Novel Cephalosporin/β-Lactamase Inhibitor Combination for the Treatment of Resistant Gram-negative Organisms. Clin Ther. 2016;38(3):431-444. PMID: 26948862.
3. Zhen S, Wang H, Feng S. Update of clinical application in ceftazidime-avibactam for multidrug-resistant Gram-negative bacteria infections. Infection. 2022;50(6):1409-1423. PMID: 35781869.
4. Evaluation of the stability of ceftazidime/avibactam in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy utilizing a national stability protocol framework. JAC Antimicrob Resist. 2024;6(2):dlae056. PMID: 38585225.
5. Stability of reconstituted solutions of ceftazidime for injections: an HPLC and CE approach. PMID: 10701968.
6. Sillén H, Mitchell R, Sleigh R, Mainwaring G, Catton K, Houghton R, Glendining K. Determination of avibactam and ceftazidime in human plasma samples by LC-MS. Bioanalysis. 2015;7(12):1423-1434. PMID: 26168250.
7. Beaudoin ME, Gangl E. Bioanalytical method validation for the simultaneous determination of ceftazidime and avibactam in rat plasma.
Bioanalysis. 2016;8(2):111-122. PMID: 26652586.
8. Cheng Y, et al. Rapid, simple, and economical LC-MS/MS method for simultaneous determination of ceftazidime and avibactam in human plasma and its application in therapeutic drug monitoring. J Clin Pharm Ther. 2022;47(9):1426-1437. PMID: 35633089.
9. Das S, Li J, Riccobene T, Carrothers TJ, Newell P, Melnick D, Critchley IA, Stone GG, Nichols WW. Dose Selection and Validation for Ceftazidime-Avibactam in Adults with Complicated Intra-abdominal Infections, Complicated Urinary Tract Infections, and Nosocomial Pneumonia. Antimicrob Agents Chemother. 2019;63(4):e02187-18. PMID: 30670413.
10. Karlowsky JA, Biedenbach DJ, Kazmierczak KM, Stone GG, Sahm DF. Activity of Ceftazidime-Avibactam against Extended-Spectrum- and AmpC β-Lactamase-Producing Enterobacteriaceae Collected in the INFORM Global Surveillance Study from 2012 to 2014. Antimicrob Agents Chemother. 2016;60(5):2849-2857. PMID: 26926635.
11. Lahiri SD, et al. Avibactam and Class C β-Lactamases: Mechanism of Inhibition, Conservation of the Binding Pocket, and Implications for Resistance. Antimicrob Agents Chemother. 2014. PMID: 25022578.
12. Lahiri SD, Mangani S, Durand-Reville T, Benvenuti M, De Luca F, Sanyal G, Docquier JD. Structural insight into potent broad-spectrum inhibition with reversible recyclization mechanism: avibactam in complex with CTX-M-15 and Pseudomonas aeruginosa AmpC β-lactamases. Antimicrob Agents Chemother. 2013;57(6):2496-2505. PMID: 23439634.
13. Fröhlich C, Sørum V, Thomassen AM, Johnsen PJ, Leiros HS, Samuelsen Ø. OXA-48-Mediated Ceftazidime-Avibactam Resistance Is Associated with Evolutionary Trade-Offs. mSphere. 2019;4(2):e00024-19. PMID: 30918055.
14. Xiong L, Wang X, Wang Y, Yu W, Zhou Y, Chi X, Xiao T, Xiao Y. Molecular mechanisms underlying bacterial resistance to ceftazidime/avibactam. WIREs Mech Dis. 2022;14(6):e1571. PMID: 35891616.
15. Hernández-García M, Castillo-Polo JA, Cordero DG, Pérez-Viso B, García-Castillo M, Saez de la Fuente J, Morosini MI, Cantón R, Ruiz-Garbajosa P. Impact of Ceftazidime-Avibactam Treatment in the Emergence of Novel KPC Variants in the ST307-Klebsiella pneumoniae High-Risk Clone and Consequences for Their Routine Detection. J Clin Microbiol. 2022;60(3):e0224521. PMID: 35107303.
16. Blessy M, Patel RD, Prajapati PN, Agrawal YK. Development of forced degradation and stability indicating studies of drugs – A review. J Pharm Anal. 2014;4(3):159-165. PMID: 29403878.
17. Gaibani P, Lewis RE, Volpe SL, Giannella M, Campoli C, Landini MP, Viale P, Re MC, Ambretti S. In vitro interaction of ceftazidime-avibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates. Int J Infect Dis. 2017;65:1-3. PMID: 28951106.
18. Temkin E, Torre-Cisneros J, Beovic B, et al. Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms. Antimicrob Agents Chemother. 2017;61(2):e01964-16. PMID: 27895014.
19. Zhu L, Hu Q, Liu L, Ye S. Ceftazidime-Avibactam as a Salvage Treatment for Severely Infected Immunosuppressed Children. Drug Des Devel Ther. 2024;18:3399-3413. PMID: 39100219.
20. Fares MY, Hegazy MA, El-Sayed GM, Abdelrahman MM, Abdelwahab NS. Quality by design approach for green HPLC method development for simultaneous analysis of two thalassemia drugs in biological fluid with pharmacokinetic study. RSC Adv. 2022;12(22):13896-13916. PMID: 35548387.
21. Alqahtani A, Alqahtani T, Al Fatease A, Tolba EH. A quality by design HPLC method for cephalosporin analysis in pharmaceuticals and water samples with environmental impact assessment. Sci Rep. 2025;15. PMID: 39747994.
22. Development of a green HPLC method for the analysis of artesunate and amodiaquine impurities using Quality by Design. PMID: 32846400.
23. Development and validation of an UPLC-MS/MS assay for the simultaneous quantification of seven commonly used antibiotics (including ceftazidime) in human plasma and its application in therapeutic drug monitoring. J Antimicrob Chemother. 2024;79(4):883. PMID: 38416407.
24. Wang X, Du L, Zhang B, Li Y, Tao Z, Zhang L, Qu J, McFadden J, Qu H, Yang J, Liu J. Hydrogel-based fluorescence assay kit for simultaneous determination of ceftazidime and avibactam. Mikrochim Acta. 2024;191(11):675. PMID: 39414650.
25. Al-Kadhi NS, Mohamed MA, Ahmed HA, Nassar HF. Facile synthesis and eco-friendly analytical methods for concurrent estimation of selected pharmaceutical drugs in their solutions: application to quality by design, lean six sigma, and stability studies. BMC Chem. 2023;17(1):136. PMID: 37817268.
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