Activity of cefiderocol on extensively drug-resistant Pseudomonas aeruginosa from burn wound infections in Mansoura, Egypt
,
Abstract
Background and Objectives: Increased Pseudomonas aeruginosa antibiotic resistance limits treatment options and is associated with a higher level of mortality and mordacity. The purpose of this research was to identify class 1 and 2 integrons, carbapenemase, SHV, and TEM genes in extensively drug-resistant (XDR) P. aeruginosa isolated from infected burns and evaluate their in vitro cefiderocol activity.
Materials and Methods: By using the disc diffusion method, the antimicrobial susceptibility of 110 P. aeruginosa isolates collected from infected burns were evaluated. XDR P. aeruginosa were screened phenotypically for carbapenemase and extended spectrum β-lactamases (ESBLs) production. Both MIC Test Strip and disc diffusion were employed to test the cefiderocol susceptibility. PCR was used to assess carbapenemase, SHV and TEM genes and integrons class 1 and 2.
Results: From the 110 P. aeruginosa, 54 isolates (49%) were XDR. TEM gene was detected in 35 isolates. Among XDR isolates, carbapenemase genes were detected in 31.5%, with NDM being predominant Thirty XDR isolates had class1 integrons. All isolates were sensitive to cefiderocol and its MIC50/MIC90 was 0.5/1.5mg/L (range 0.064-1.5mg/L).
Conclusion: Nearly half the P. aeruginosa isolates from burn infections were extensively drug-resistant. Cefiderocol's in vitro activity demonstrated that it is a promising therapy alternative for treating extensively drug-resistant P. aeruginosa in burn patients.
1. Aljanaby AAJ, Aljanaby IAJ. Prevalence of aerobic pathogenic bacteria isolated from patients with burn infection and their antimicrobial susceptibility patterns in Al-Najaf City, Iraq- a three-year cross-sectional study. F1000Res 2018; 7: 1157.
2. Oliver A, Rojo-Molinero E, Arca-Suarez J, Beşli Y, Bogaerts P, Cantón R, et al. Pseudomonas aeruginosa antimicrobial susceptibility profiles, resistance mechanisms and international clonal lineages: update from ESGARS-ESCMID/ISARPAE Group. Clin Microbiol Infect 2024; 30: 469-480.
3. Ghasemian S, Karami-Zarandi M, Heidari H, Khoshnood S, Kouhsari E, Ghafourian S, et al. Molecular characterizations of antibiotic resistance, biofilm formation, and virulence determinants of Pseudomonas aeruginosa isolated from burn wound infection. J Clin Lab Anal 2023; 37(4): e24850.
4. Horcajada JP, Montero M, Oliver A, Sorlí L, Luque S, Gómez-Zorrilla S, et al. Epidemiology and treatment of multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa infections. Clin Microbiol Rev 2019; 32(4): e00031-19.
5. Yin C, Alam MZ, Fallon JT, Huang W. Advances in development of novel therapeutic strategies against multi-drug resistant Pseudomonas aeruginosa. Antibiotics (Basel) 2024; 13: 119.
6. Rahimi E, Asgari A, Azimi T, Soleiman-Meigooni S. Molecular detection of carbapenemases and extended-spectrum β-Lactamases-encoding genes in clinical isolates of Pseudomonas aeruginosa in Iran. Jundishapur J Microbiol 2021; 14(7): e115977.
7. McCreary EK, Heil EL, Tamma PD. New perspectives on antimicrobial agents: cefiderocol. Antimicrob Agents Chemother 2021; 65(8): e0217120.
8. Weber C, Schultze T, Göttig S, Kessel J, Schröder A, Tietgen M, et al. Antimicrobial activity of ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol against multidrug-resistant Pseudomonas aeruginosa recovered at a German University Hospital. Microbiol Spectr 2022; 10(5): e0169722.
9. Soriano MC, Montufar J, Blandino-Ortiz A. New antimicrobial alternatives in the treatment of pneumonia. Rev Esp Quimioter 2022; 35 (Suppl. 1): 31-34.
10. Hegazy EE, Zahra SW, Shoeib SM, Taha MS. Evaluation of in vitro activity of cefiderocol and ceftolozane-tazobactam against extended-spectrum β-lactamase–producing coliform and multidrug resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Egypt J Med Microbiol 2022; 31: 123-129.
11. Vos P, Garrity GM, Jones D, Krieg NR, Ludwig W, Rainey FA, et al. (2009). Bergey’s Manual of Systematic Bacteriology. In: Volume three: the Firmicutes. 2nd ed. https://link.springer.com/book/10.1007/978-0-387-68489-5
12. Kresken M, Korte-Berwanger M, Gatermann SG, Pfeifer Y, Pfennigwerth N, Seifert H, et al. In vitro activity of cefiderocol against aerobic Gram-negative bacterial pathogens from Germany. Int J Antimicrob Agents 2020; 56: 106128.
13. Magiorakos A-P, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pan drug resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18: 268-281.
14. Morris CP, Bergman Y, Tekle T, Fissel JA, Tamma PD, Simner PJ. Cefiderocol antimicrobial susceptibility testing against multidrug-resistant gram-negative bacilli: a comparison of disk diffusion to broth microdilution. J Clin Microbiol 2020; 59(1): e01649-20.
15. Laudy AE, Rog P, Smolińska-Krol K, Cmiel M, Søoczyńska A, Patzer J, et al. Prevalence of ESBL-producing Pseudomonas aeruginosa isolates in Warsaw, Poland, detected by various phenotypic and genotypic methods. PLoS One 2017; 12(6): e0180121.
16. Dashti AA, Jadaon MM, Abdulsamad AM, Dashti HM. Heat treatment of bacteria: A simple method of DNA extraction for molecular techniques. Kuwait Med J 2009; 41: 117-122.
17. Poirel L, Walsh TR, Cuvillier V, Nordmann P. Multiplex PCR for detection of acquired carbapenemase genes. Diagn Microbiol Infect Dis 2011; 70: 119-123.
18. Zaniani FR, Meshkat Z, Naderi Nasab M, Khaje-Karamadini M, Ghazvini K, Rezaee A, et al. The prevalence of TEM and SHV genes among extended-spectrum beta-lactamases producing Escherichia coli and Klebsiella pneumoniae. Iran J Basic Med Sci 2012; 15: 654-660.
19. Khosravi AD, Motahar M, Abbasi Montazeri E. The frequency of class1 and 2 integrons in Pseudomonas aeruginosa strains isolated from burn patients in a burn center of Ahvaz, Iran. PLoS One 2017; 12(8): e0183061.
20. Hammoudi Halat D, Ayoub Moubareck C. The Intriguing carbapenemases of Pseudomonas aeruginosa: Current Status, Genetic Profile, and Global Epidemiology. Yale J Biol Med 2022; 95: 507-515.
21. Mendes Pedro D, Paulo SE, Santos CM, Fonseca AB, Melo Cristino J, Pereira ÁA, et al. Extensively drug-resistant Pseudomonas aeruginosa: clinical features and treatment with ceftazidime/avibactam and ceftolozane/tazobactam in a tertiary care university hospital center in Portugal – A cross-sectional and retrospective observational study. Front Microbiol 2024; 15: 1347521.
22. Nasirmoghadas P, YadegariS, Moghim S, Esfahani BN, Fazeli H, Poursina F, et al. Evaluation of biofilm formation and frequency of multidrug-resistant and extended drug-resistant strain in Pseudomonas aeruginosa isolated from Burn patients in Isfahan. Adv Biomed Res 2018; 7: 61.
23. Basha AM, El-Sherbiny GM, Mabrouk MI. Phenotypic characterization of the Egyptian isolates “extensively drug-resistant Pseudomonas aeruginosa” and detection of their metallo-β-lactamases encoding genes. Bull Natl Res Cent 2020; 44: 117.
24. Saderi H, Owlia P. Detection of multidrug resistant (MDR) and extremely drug resistant (XDR) P. aeruginosa isolated from patients in Tehran, Iran. Iran J Pathol 2015; 10: 265-271.
25. Khosravi AD, Taee S, Dezfuli AA, Meghdadi H, Shafie F. Investigation of the prevalence of genes conferring resistance to carbapenems in Pseudomonas aeruginosa isolates from burn patients. Infect Drug Resist 2019; 12: 1153-1159.
26. Mirzaei B, Bazgir ZN, Goli HR, Iranpour F, Mohammadi F, Babaei R. Prevalence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) phenotypes of Pseudomonas aeruginosa and Acinetobacter baumannii isolated in clinical samples from Northeast of Iran. BMC Res Notes 2020; 13: 380.
27. Elmosallamy WA, Tabl HA, Ghanem MA, Abd Elhamid HS. Detection of efflux pumps in carbapenem resistant Pseudomonas aeruginosa isolated from Benha University Hospitals. Egypt J Med Microbiol 2024; 33: 11-18.
28. Chimi LY, Noubom M, Bisso BN, Singor Njateng GS, Dzoyem JP. Biofilm formation, pyocyanin production, and antibiotic resistance profile of Pseudomonas aeruginosa isolates from wounds. Int J Microbiol 2024; 2024: 1207536.
29. Valzano F, La Bella G, Lopizzo T, Curci A, Lupo L, Morelli E, et al. Resistance to ceftazidime-avibactam and other new β-lactams in Pseudomonas aeruginosa clinical isolates: a multi-center surveillance study. Microbiol Spectr 2024; 12(8): e0426623.
30. Tenover FC, Nicolau DP, Gill CM. Carbapenemase-producing Pseudomonas aeruginosa–an emerging challenge. Emerg Microbes Infect 2022; 11: 811-814.
31. Alatoom A, Alattas M, Alraddadi B, Moubareck CA, Hassanien A, Jamal W, et al. Antimicrobial resistance profiles of Pseudomonas aeruginosa in the Arabian Gulf Region Over a 12-Year Period (2010–2021). J Epidemiol Glob Health 2024; 14: 529-548.
32. Hsueh SC, Lee YJ, Huang YT, Liao CH, Tsuji M, Hsueh PR. In vitro activities of cefiderocol, ceftolozane/tazobactam, ceftazidime/avibactam and other comparative drugs against imipenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, and Stenotrophomonas maltophilia, all associated with bloodstream infections in Taiwan. J Antimicrob Chemother 2019; 74: 380-386.
33. Weber C, Schultze T, Göttig S, Kessel J, Schröder A, Tietgen M, et al. Antimicrobial activity of ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol against multidrug-resistant Pseudomonas aeruginosa recovered at a German University Hospital. Microbiol Spectr 2022; 10(5): e0169722.
2. Oliver A, Rojo-Molinero E, Arca-Suarez J, Beşli Y, Bogaerts P, Cantón R, et al. Pseudomonas aeruginosa antimicrobial susceptibility profiles, resistance mechanisms and international clonal lineages: update from ESGARS-ESCMID/ISARPAE Group. Clin Microbiol Infect 2024; 30: 469-480.
3. Ghasemian S, Karami-Zarandi M, Heidari H, Khoshnood S, Kouhsari E, Ghafourian S, et al. Molecular characterizations of antibiotic resistance, biofilm formation, and virulence determinants of Pseudomonas aeruginosa isolated from burn wound infection. J Clin Lab Anal 2023; 37(4): e24850.
4. Horcajada JP, Montero M, Oliver A, Sorlí L, Luque S, Gómez-Zorrilla S, et al. Epidemiology and treatment of multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa infections. Clin Microbiol Rev 2019; 32(4): e00031-19.
5. Yin C, Alam MZ, Fallon JT, Huang W. Advances in development of novel therapeutic strategies against multi-drug resistant Pseudomonas aeruginosa. Antibiotics (Basel) 2024; 13: 119.
6. Rahimi E, Asgari A, Azimi T, Soleiman-Meigooni S. Molecular detection of carbapenemases and extended-spectrum β-Lactamases-encoding genes in clinical isolates of Pseudomonas aeruginosa in Iran. Jundishapur J Microbiol 2021; 14(7): e115977.
7. McCreary EK, Heil EL, Tamma PD. New perspectives on antimicrobial agents: cefiderocol. Antimicrob Agents Chemother 2021; 65(8): e0217120.
8. Weber C, Schultze T, Göttig S, Kessel J, Schröder A, Tietgen M, et al. Antimicrobial activity of ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol against multidrug-resistant Pseudomonas aeruginosa recovered at a German University Hospital. Microbiol Spectr 2022; 10(5): e0169722.
9. Soriano MC, Montufar J, Blandino-Ortiz A. New antimicrobial alternatives in the treatment of pneumonia. Rev Esp Quimioter 2022; 35 (Suppl. 1): 31-34.
10. Hegazy EE, Zahra SW, Shoeib SM, Taha MS. Evaluation of in vitro activity of cefiderocol and ceftolozane-tazobactam against extended-spectrum β-lactamase–producing coliform and multidrug resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Egypt J Med Microbiol 2022; 31: 123-129.
11. Vos P, Garrity GM, Jones D, Krieg NR, Ludwig W, Rainey FA, et al. (2009). Bergey’s Manual of Systematic Bacteriology. In: Volume three: the Firmicutes. 2nd ed. https://link.springer.com/book/10.1007/978-0-387-68489-5
12. Kresken M, Korte-Berwanger M, Gatermann SG, Pfeifer Y, Pfennigwerth N, Seifert H, et al. In vitro activity of cefiderocol against aerobic Gram-negative bacterial pathogens from Germany. Int J Antimicrob Agents 2020; 56: 106128.
13. Magiorakos A-P, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pan drug resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18: 268-281.
14. Morris CP, Bergman Y, Tekle T, Fissel JA, Tamma PD, Simner PJ. Cefiderocol antimicrobial susceptibility testing against multidrug-resistant gram-negative bacilli: a comparison of disk diffusion to broth microdilution. J Clin Microbiol 2020; 59(1): e01649-20.
15. Laudy AE, Rog P, Smolińska-Krol K, Cmiel M, Søoczyńska A, Patzer J, et al. Prevalence of ESBL-producing Pseudomonas aeruginosa isolates in Warsaw, Poland, detected by various phenotypic and genotypic methods. PLoS One 2017; 12(6): e0180121.
16. Dashti AA, Jadaon MM, Abdulsamad AM, Dashti HM. Heat treatment of bacteria: A simple method of DNA extraction for molecular techniques. Kuwait Med J 2009; 41: 117-122.
17. Poirel L, Walsh TR, Cuvillier V, Nordmann P. Multiplex PCR for detection of acquired carbapenemase genes. Diagn Microbiol Infect Dis 2011; 70: 119-123.
18. Zaniani FR, Meshkat Z, Naderi Nasab M, Khaje-Karamadini M, Ghazvini K, Rezaee A, et al. The prevalence of TEM and SHV genes among extended-spectrum beta-lactamases producing Escherichia coli and Klebsiella pneumoniae. Iran J Basic Med Sci 2012; 15: 654-660.
19. Khosravi AD, Motahar M, Abbasi Montazeri E. The frequency of class1 and 2 integrons in Pseudomonas aeruginosa strains isolated from burn patients in a burn center of Ahvaz, Iran. PLoS One 2017; 12(8): e0183061.
20. Hammoudi Halat D, Ayoub Moubareck C. The Intriguing carbapenemases of Pseudomonas aeruginosa: Current Status, Genetic Profile, and Global Epidemiology. Yale J Biol Med 2022; 95: 507-515.
21. Mendes Pedro D, Paulo SE, Santos CM, Fonseca AB, Melo Cristino J, Pereira ÁA, et al. Extensively drug-resistant Pseudomonas aeruginosa: clinical features and treatment with ceftazidime/avibactam and ceftolozane/tazobactam in a tertiary care university hospital center in Portugal – A cross-sectional and retrospective observational study. Front Microbiol 2024; 15: 1347521.
22. Nasirmoghadas P, YadegariS, Moghim S, Esfahani BN, Fazeli H, Poursina F, et al. Evaluation of biofilm formation and frequency of multidrug-resistant and extended drug-resistant strain in Pseudomonas aeruginosa isolated from Burn patients in Isfahan. Adv Biomed Res 2018; 7: 61.
23. Basha AM, El-Sherbiny GM, Mabrouk MI. Phenotypic characterization of the Egyptian isolates “extensively drug-resistant Pseudomonas aeruginosa” and detection of their metallo-β-lactamases encoding genes. Bull Natl Res Cent 2020; 44: 117.
24. Saderi H, Owlia P. Detection of multidrug resistant (MDR) and extremely drug resistant (XDR) P. aeruginosa isolated from patients in Tehran, Iran. Iran J Pathol 2015; 10: 265-271.
25. Khosravi AD, Taee S, Dezfuli AA, Meghdadi H, Shafie F. Investigation of the prevalence of genes conferring resistance to carbapenems in Pseudomonas aeruginosa isolates from burn patients. Infect Drug Resist 2019; 12: 1153-1159.
26. Mirzaei B, Bazgir ZN, Goli HR, Iranpour F, Mohammadi F, Babaei R. Prevalence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) phenotypes of Pseudomonas aeruginosa and Acinetobacter baumannii isolated in clinical samples from Northeast of Iran. BMC Res Notes 2020; 13: 380.
27. Elmosallamy WA, Tabl HA, Ghanem MA, Abd Elhamid HS. Detection of efflux pumps in carbapenem resistant Pseudomonas aeruginosa isolated from Benha University Hospitals. Egypt J Med Microbiol 2024; 33: 11-18.
28. Chimi LY, Noubom M, Bisso BN, Singor Njateng GS, Dzoyem JP. Biofilm formation, pyocyanin production, and antibiotic resistance profile of Pseudomonas aeruginosa isolates from wounds. Int J Microbiol 2024; 2024: 1207536.
29. Valzano F, La Bella G, Lopizzo T, Curci A, Lupo L, Morelli E, et al. Resistance to ceftazidime-avibactam and other new β-lactams in Pseudomonas aeruginosa clinical isolates: a multi-center surveillance study. Microbiol Spectr 2024; 12(8): e0426623.
30. Tenover FC, Nicolau DP, Gill CM. Carbapenemase-producing Pseudomonas aeruginosa–an emerging challenge. Emerg Microbes Infect 2022; 11: 811-814.
31. Alatoom A, Alattas M, Alraddadi B, Moubareck CA, Hassanien A, Jamal W, et al. Antimicrobial resistance profiles of Pseudomonas aeruginosa in the Arabian Gulf Region Over a 12-Year Period (2010–2021). J Epidemiol Glob Health 2024; 14: 529-548.
32. Hsueh SC, Lee YJ, Huang YT, Liao CH, Tsuji M, Hsueh PR. In vitro activities of cefiderocol, ceftolozane/tazobactam, ceftazidime/avibactam and other comparative drugs against imipenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, and Stenotrophomonas maltophilia, all associated with bloodstream infections in Taiwan. J Antimicrob Chemother 2019; 74: 380-386.
33. Weber C, Schultze T, Göttig S, Kessel J, Schröder A, Tietgen M, et al. Antimicrobial activity of ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol against multidrug-resistant Pseudomonas aeruginosa recovered at a German University Hospital. Microbiol Spectr 2022; 10(5): e0169722.
| Files | ||
| Issue | Vol 17 No 2 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v17i2.18384 | |
| Keywords | ||
| Pseudomonas aeruginosa; Extended detection and response; NDM; Carbapenemase; Burn | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
El-Mahdy R, Mostafa A, El-Tantawy N, Shrief R. Activity of cefiderocol on extensively drug-resistant Pseudomonas aeruginosa from burn wound infections in Mansoura, Egypt. Iran J Microbiol. 2025;17(2):246-252.
