Ceftazidime-avibactam activity against Escherichia coli and Klebsiella pneumoniae
,
Abstract
Background and Objectives: Carbapenem-resistant Enterobacteriaceae (CRE) infections are extremely difficult to treat and have a high fatality rate. The study's primary goal was to determine the rate of ceftazidime-avibactam susceptibility using disc diffusion and E-Test, as well as to evaluate the agreement between the two methods.
Materials and Methods: A total of 124 multidrug-resistant (including carbapenem) Escherichia coli and Klebisella pneumoniae isolates were included. Kirby Bauer's disc diffusion and E-test were used as the testing methods in this study.
Results: In this study 37.5% and 33.9% of the isolates were susceptible to ceftazidime-avibactam by E test and Disc diffusion respectively. There were five isolates which produced discordant results. Among the 56 isolates there was 91% agreement between the two methods.
Conclusion: Among the discordant isolates the alarming disparity in zone size was a significant concern. Since CRE infections are very common, an economical and practical method for testing ceftazidime-avibactam susceptibility is needed in all the clinical microbiology laboratories as it is a last resort drug.
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2. Gandra S, Mojica N, Klein EY, Ashok A, Nerurkar V, Kumari M, et al. Trends in antibiotic resistance among major bacterial pathogens isolated from blood cultures tested at a large private laboratory network in India, 2008-2014. Int J Infect Dis 2016; 50: 75-82.
3. Mesaros N, Nordmann P, Plésiat P, Roussel-Delvallez M, Van Eldere J, Glupczynski Y, et al. Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium. Clin Microbiol Infect 2007; 13: 560-578.
4. Castanheira M, Deshpande LM, Costello A, Davies TA, Jones RN. Epidemiology and carbapenem resistance mechanisms of carbapenem-non-susceptible Pseudomonas aeruginosa collected during 2009–11 in 14 European and Mediterranean countries. J Antimicrob Chemother 2014; 69: 1804-1814.
5. Del Barrio-Tofiño E, López-Causapé C, Cabot G, Rivera A, Benito N, Segura C, et al. Genomics and susceptibility profiles of extensively drug-resistant pseudomonas aeruginosa isolates from Spain. Antimicrob Agents Chemother 2017; 61(11): e01589-17.
6. Sader H, Castanheira M, Shortridge D, Mendes R, Flamm RK. Antimicrobial activity of ceftazidime-avibactam tested against multidrug-resistant Enterobacteriaceae and Pseudomonas aeruginosa isolates from U.S. Medical Centers, 2013 to 2016. Antimicrob Agents Chemother 2017; 61(11): e01045-17.
7. Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother 2010; 54: 969-976.
8. Logan LK, Weinstein RA. The epidemiology of Carbapenem-Resistant Enterobacteriaceae: the impact and evolution of a global menace. J Infect Dis 2017; 215(suppl_1): S28-S36.
9. Bush K. Carbapenemases: partners in crime. J Glob Antimicrob Resist 2013; 1: 7-16.
10. Potter RF, D’Souza AW, Dantas G. The rapid spread of Carbapenem-Resistant Enterobacteriaceae. Drug Resist Updat 2016; 29: 30-46.
11. Devanga Ragupathi NK, Veeraraghavan B, Muthuirulandi Sethuvel DP, Anandan S, Vasudevan K, Neeravi AR, et al. First Indian report on genome-wide comparison of multidrug-resistant Escherichia coli from blood stream infections. PLoS One 2020; 15(2): e0220428.
12. Shankar C, Jacob JJ, Sugumar SG, Natarajan L, Rodrigues C, Mathur P, et al. Distinctive mobile genetic elements observed in the clonal expansion of Carbapenem-Resistant Klebsiella pneumoniae in India. Microb Drug Resist 2021; 27: 1096-1104.
13. Shankar C, Venkatesan M, Rajan R, Mani D, Lal B, Prakash JAJ, et al. Molecular characterization of colistin-resistant Klebsiella pneumoniae & its clonal relationship among Indian isolates. Indian J Med Res 2019; 149: 199-207.
14. Tamma PD, Atiken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious diseases society of America guidance on the treatment of extended-spectrum beta-lactamase producing enterobacterales (ESBL-E), carbapenem-resistant enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Clin Infect Dis 2021; 72(7): e169-e183.
15. Tsuji BT, Pogue JM, Zavascki AP, Paul M, Daikos GL, Forrest A, et al. International consensus guidelines for the optimal use of the polymyxins: endorsed by theAmerican college of clinical pharmacy (ACCP), European society of clinical microbiologyand infectious diseases (ESCMID), Infectious diseases society of America (IDSA), International society for anti-infective pharmacology (ISAP), Society ofcritical care medicine (SCCM), and Society of infectious diseases pharmacists (SIDP). Pharmacotherapy 2019; 39: 10-39.
16. Wang J, Pan Y, Shen J, Xu Y. The efficacy and safety of tigecycline for the treatment of bloodstream infections: a systematic review and meta-analysis. Ann Clin Microbiol Antimicrob 2017; 16: 24.
17. Abboud MI, Damblon C, Brem J, Smargiasso N, Mercuri P, Gilbert B, et al. Interaction of avibactam with class B metallo-β-lactamases. Antimicrob Agents Chemother 2016; 60: 5655-5662.18. Ehmann DE, Jahić H, Ross PL, Gu RF, Hu J,
Kern G, et al. Avibactam is a covalent, reversible, non- β-lactam β-lactamase inhibitor. Proc Natl Acad Sci U S A 2012; 109: 11663-11668.
19. Zhanel GG, Lawson CD, Adam H, Schweizer F, Zelenitsky S, Lagacé-Wiens PR, et al. Ceftazidime-avibactam: a novel cephalosporin/ β-lactamase inhibitor combination. Drugs 2013; 73: 159-177.
20. Bush K. Game changers: new β-lactamase inhibitor combinations targeting antibiotic resistance in Gram-negative bacteria. ACS Infect Dis 2018; 4: 84-87.
21. Nichols WW, Bradford PA, Stone GG. The primary pharmacology of ceftazidime/avibactam: microbiology from clinical studies, and development of resistance during treatment. J Antimicrob Chemother 2023; 78: 871-892.
22. Nichols WW, Bradford PA, Lahiri SD, Stone GG. The primary pharmacology of ceftazidime/avibactam: in vitro translational biology. J Antimicrob Chemother 2022; 77: 2321-2340.
23. Sherry NL, Baines SL, Howden BP. Ceftazidime/avibactam susceptibility by three different susceptibility testing methods in carbapenemase-producing Gram-negative bacteria from Australia. Int J Antimicrob Agents 2018; 52: 82-85.
24. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18: 268-281.
25. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 31st ed. CLSI supplement M100. Clinical and Laboratory Standards Institute; 2021.
26. Soman R, Veeraraghavan B, Hegde A, Jiandani P, Mehta Y, Nagavekar V, et al. Indian consensus on the management of CRE infection in critically ill patients (ICONIC) - India. Expert Rev Anti Infect Ther 2019; 17: 647-660.
27. Tzouvelekis LS, Markogiannakis A, Psichogiou M, Tassios PT, Daikos GL. Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae:an evolving crisis of global dimensions. Clin Microbiol Rev 2012; 25: 682-707.
28. Spiliopoulou I, Kazmierczak K, Stone GG. In vitro activity of ceftazidime/avibactam against isolates of carbapenem-non-susceptible Enterobacteriaceae collected during the INFORM global surveillance programme (2015-17). J Antimicrob Chemother 2020; 75: 384-391.
29. Han R, Yang X, Yang Y, Guo Y, Yin D, Ding L, et al. Assessment of Ceftazidime-Avibactam 30/20-μg Disk, Etest versus Broth Microdilution Results When Tested against Enterobacterales Clinical Isolates. Microbiol Spectr 2022; 10(1): e0109221.
30. Wang Q, Zhang F, Wang Z, Chen H, Wang X, Zhang Y, et al. Evaluation of the Etest and disk diffusion method for detection of the activity of ceftazidime-avibactam against Enterobacterales and Pseudomonas aeruginosa in China. BMC Microbiol 2020; 20: 187.
31. Kim T, Lee SC, Bae M, Sung H, Kim MN, Jung J, et al. In vitro activities and inoculum effects of ceftazidime-avibactam and aztreonam-avibactam against carbapenem-resistant Enterobacterales isolates from South Korea. Antibiotics (Basel) 2020; 9: 912.
32. Hobson CA, Cointe A, Jacquier H, Choudhury A, Magnan M, Courroux C, et al. Cross-resistance to cefiderocol and ceftazidime-avibactam in KPC β-lactamase mutants and the inoculumeffect. Clin Microbiol Infect 2021; 27: 1172.e7-1172.e10.
33. Keepers TR, Gomez M, Biek D, Critchley I, Krause KM. Effect of in vitro testing parameters on ceftazidime-avibactam minimum inhibitory concentrations. Int Sch Res Notices 2015; 2015: 489547.
34. Sader HS, Rhomberg PR, Chandrasekaran S, Trejo M, Fedler KA, Boyken LD, et al. Correlation between broth microdilution and disk diffusionresults when testing ceftazidime-avibactam against a challenge collectionof Enterobacterales isolates: results from a multilaboratory study. J Clin Microbiol 2020; 58(4): e01757-19.
2. Gandra S, Mojica N, Klein EY, Ashok A, Nerurkar V, Kumari M, et al. Trends in antibiotic resistance among major bacterial pathogens isolated from blood cultures tested at a large private laboratory network in India, 2008-2014. Int J Infect Dis 2016; 50: 75-82.
3. Mesaros N, Nordmann P, Plésiat P, Roussel-Delvallez M, Van Eldere J, Glupczynski Y, et al. Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium. Clin Microbiol Infect 2007; 13: 560-578.
4. Castanheira M, Deshpande LM, Costello A, Davies TA, Jones RN. Epidemiology and carbapenem resistance mechanisms of carbapenem-non-susceptible Pseudomonas aeruginosa collected during 2009–11 in 14 European and Mediterranean countries. J Antimicrob Chemother 2014; 69: 1804-1814.
5. Del Barrio-Tofiño E, López-Causapé C, Cabot G, Rivera A, Benito N, Segura C, et al. Genomics and susceptibility profiles of extensively drug-resistant pseudomonas aeruginosa isolates from Spain. Antimicrob Agents Chemother 2017; 61(11): e01589-17.
6. Sader H, Castanheira M, Shortridge D, Mendes R, Flamm RK. Antimicrobial activity of ceftazidime-avibactam tested against multidrug-resistant Enterobacteriaceae and Pseudomonas aeruginosa isolates from U.S. Medical Centers, 2013 to 2016. Antimicrob Agents Chemother 2017; 61(11): e01045-17.
7. Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother 2010; 54: 969-976.
8. Logan LK, Weinstein RA. The epidemiology of Carbapenem-Resistant Enterobacteriaceae: the impact and evolution of a global menace. J Infect Dis 2017; 215(suppl_1): S28-S36.
9. Bush K. Carbapenemases: partners in crime. J Glob Antimicrob Resist 2013; 1: 7-16.
10. Potter RF, D’Souza AW, Dantas G. The rapid spread of Carbapenem-Resistant Enterobacteriaceae. Drug Resist Updat 2016; 29: 30-46.
11. Devanga Ragupathi NK, Veeraraghavan B, Muthuirulandi Sethuvel DP, Anandan S, Vasudevan K, Neeravi AR, et al. First Indian report on genome-wide comparison of multidrug-resistant Escherichia coli from blood stream infections. PLoS One 2020; 15(2): e0220428.
12. Shankar C, Jacob JJ, Sugumar SG, Natarajan L, Rodrigues C, Mathur P, et al. Distinctive mobile genetic elements observed in the clonal expansion of Carbapenem-Resistant Klebsiella pneumoniae in India. Microb Drug Resist 2021; 27: 1096-1104.
13. Shankar C, Venkatesan M, Rajan R, Mani D, Lal B, Prakash JAJ, et al. Molecular characterization of colistin-resistant Klebsiella pneumoniae & its clonal relationship among Indian isolates. Indian J Med Res 2019; 149: 199-207.
14. Tamma PD, Atiken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious diseases society of America guidance on the treatment of extended-spectrum beta-lactamase producing enterobacterales (ESBL-E), carbapenem-resistant enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Clin Infect Dis 2021; 72(7): e169-e183.
15. Tsuji BT, Pogue JM, Zavascki AP, Paul M, Daikos GL, Forrest A, et al. International consensus guidelines for the optimal use of the polymyxins: endorsed by theAmerican college of clinical pharmacy (ACCP), European society of clinical microbiologyand infectious diseases (ESCMID), Infectious diseases society of America (IDSA), International society for anti-infective pharmacology (ISAP), Society ofcritical care medicine (SCCM), and Society of infectious diseases pharmacists (SIDP). Pharmacotherapy 2019; 39: 10-39.
16. Wang J, Pan Y, Shen J, Xu Y. The efficacy and safety of tigecycline for the treatment of bloodstream infections: a systematic review and meta-analysis. Ann Clin Microbiol Antimicrob 2017; 16: 24.
17. Abboud MI, Damblon C, Brem J, Smargiasso N, Mercuri P, Gilbert B, et al. Interaction of avibactam with class B metallo-β-lactamases. Antimicrob Agents Chemother 2016; 60: 5655-5662.18. Ehmann DE, Jahić H, Ross PL, Gu RF, Hu J,
Kern G, et al. Avibactam is a covalent, reversible, non- β-lactam β-lactamase inhibitor. Proc Natl Acad Sci U S A 2012; 109: 11663-11668.
19. Zhanel GG, Lawson CD, Adam H, Schweizer F, Zelenitsky S, Lagacé-Wiens PR, et al. Ceftazidime-avibactam: a novel cephalosporin/ β-lactamase inhibitor combination. Drugs 2013; 73: 159-177.
20. Bush K. Game changers: new β-lactamase inhibitor combinations targeting antibiotic resistance in Gram-negative bacteria. ACS Infect Dis 2018; 4: 84-87.
21. Nichols WW, Bradford PA, Stone GG. The primary pharmacology of ceftazidime/avibactam: microbiology from clinical studies, and development of resistance during treatment. J Antimicrob Chemother 2023; 78: 871-892.
22. Nichols WW, Bradford PA, Lahiri SD, Stone GG. The primary pharmacology of ceftazidime/avibactam: in vitro translational biology. J Antimicrob Chemother 2022; 77: 2321-2340.
23. Sherry NL, Baines SL, Howden BP. Ceftazidime/avibactam susceptibility by three different susceptibility testing methods in carbapenemase-producing Gram-negative bacteria from Australia. Int J Antimicrob Agents 2018; 52: 82-85.
24. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18: 268-281.
25. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 31st ed. CLSI supplement M100. Clinical and Laboratory Standards Institute; 2021.
26. Soman R, Veeraraghavan B, Hegde A, Jiandani P, Mehta Y, Nagavekar V, et al. Indian consensus on the management of CRE infection in critically ill patients (ICONIC) - India. Expert Rev Anti Infect Ther 2019; 17: 647-660.
27. Tzouvelekis LS, Markogiannakis A, Psichogiou M, Tassios PT, Daikos GL. Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae:an evolving crisis of global dimensions. Clin Microbiol Rev 2012; 25: 682-707.
28. Spiliopoulou I, Kazmierczak K, Stone GG. In vitro activity of ceftazidime/avibactam against isolates of carbapenem-non-susceptible Enterobacteriaceae collected during the INFORM global surveillance programme (2015-17). J Antimicrob Chemother 2020; 75: 384-391.
29. Han R, Yang X, Yang Y, Guo Y, Yin D, Ding L, et al. Assessment of Ceftazidime-Avibactam 30/20-μg Disk, Etest versus Broth Microdilution Results When Tested against Enterobacterales Clinical Isolates. Microbiol Spectr 2022; 10(1): e0109221.
30. Wang Q, Zhang F, Wang Z, Chen H, Wang X, Zhang Y, et al. Evaluation of the Etest and disk diffusion method for detection of the activity of ceftazidime-avibactam against Enterobacterales and Pseudomonas aeruginosa in China. BMC Microbiol 2020; 20: 187.
31. Kim T, Lee SC, Bae M, Sung H, Kim MN, Jung J, et al. In vitro activities and inoculum effects of ceftazidime-avibactam and aztreonam-avibactam against carbapenem-resistant Enterobacterales isolates from South Korea. Antibiotics (Basel) 2020; 9: 912.
32. Hobson CA, Cointe A, Jacquier H, Choudhury A, Magnan M, Courroux C, et al. Cross-resistance to cefiderocol and ceftazidime-avibactam in KPC β-lactamase mutants and the inoculumeffect. Clin Microbiol Infect 2021; 27: 1172.e7-1172.e10.
33. Keepers TR, Gomez M, Biek D, Critchley I, Krause KM. Effect of in vitro testing parameters on ceftazidime-avibactam minimum inhibitory concentrations. Int Sch Res Notices 2015; 2015: 489547.
34. Sader HS, Rhomberg PR, Chandrasekaran S, Trejo M, Fedler KA, Boyken LD, et al. Correlation between broth microdilution and disk diffusionresults when testing ceftazidime-avibactam against a challenge collectionof Enterobacterales isolates: results from a multilaboratory study. J Clin Microbiol 2020; 58(4): e01757-19.
| Files | ||
| Issue | Vol 17 No 1 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v17i1.17797 | |
| Keywords | ||
| Infection; Resistance; Susceptibility; Enterobacteriaceae; Carbapenem | ||
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How to Cite
1.
Sachu A, David A. Ceftazidime-avibactam activity against Escherichia coli and Klebsiella pneumoniae. Iran J Microbiol. 2025;17(1):19-24.
