Co-production of AmpC and extended spectrum beta-lactamases in cephalosporin-resistant Acinetobacter baumannii in Egypt

  • Heba Shehta SaidEmail author
  • Abdalbagi Basheer Benmahmod
  • Ramadan Hassan Ibrahim
Original Paper


Acinetobacter baumannii is an opportunistic pathogen that has been held responsible for a lot of infections worldwide. Infections caused by this pathogen are difficult to control because of the widespread of antimicrobial resistance mechanisms. The aim of the present study is to assess the prevalence of extended spectrum β-lactamases (ESBLs) and AmpC β-lactamases among isolates of A. baumannii collected from different clinical sources in Mansoura University Hospitals, Egypt. Antimicrobial susceptibility testing has demonstrated elevated resistance level to β-lactams, quinolones and aminoglycosides. All isolates were sensitive to colistin and polymyxin B. ESBL activity was detected in 86% of the isolates. Among the tested ESBL encoding genes, blaTEM gene was the most prevalent gene as it was detected in 52% of the isolates. While blaPER, blaSHV and blaVEB were detected in 12%, 4%, and 2%, respectively. AmpC activity and blaADC gene were detected in 90% of the tested isolates. Insertion sequence ISAba1 was located 9 bp upstream of blaADC gene in 88.9% of the ADC-expressing isolates providing a potent promoter activity for its expression. To our knowledge this is the first report of loss of intrinsic ADC activity, in 10% of the tested isolates, as a result of insertional inactivation by an element belonging to IS5 family transposase. Co-expression of both ESBLs and AmpC β-lactamases was detected in 78% of the isolates. The study demonstrates high prevalence of resistance to β-lactam antibiotics through ESBLs and AmpC β-lactamases production among A. baumannii clinical isolates. Prevalence of β-lactamases should be detected routinely and reported in hospitals to avoid inappropriate use of antibiotics and therapeutic failure.


Acinetobacter baumannii Beta-lactam resistance ADCs ESBLs ISAba1 IS5 family transposase 



This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11274_2018_2571_MOESM1_ESM.docx (106 kb)
Supplementary material 1 (DOCX 105 KB)


  1. Al-Agamy MH, Khalaf NG, Tawfick MM, Shibl AM, El Kholy A (2014) Molecular characterization of carbapenem-insensitive Acinetobacter baumannii in Egypt. Int J Infect Dis 22:49–54CrossRefPubMedGoogle Scholar
  2. Barwa R, Abdelmegeed E, Abd El Galil K (2012) Occurrence and detection of AmpC-lactamases among some clinical isolates of Enterobacteriaceae obtained from Mansoura University Hospitals, Egypt. Afr J Microbiol Res 6:6924–6930CrossRefGoogle Scholar
  3. Bauer AW, Kirby WM, Sherris JC, Turck M (1966) Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol 45:493–496CrossRefPubMedGoogle Scholar
  4. Bonnin RA, Nordmann P, Poirel L (2013) Screening and deciphering antibiotic resistance in Acinetobacter baumannii: a state of the art. Expert Rev Anti Infect Ther 11:571–583CrossRefPubMedGoogle Scholar
  5. Carter MW, Oakton KJ, Warner M, Livermore DM (2000) Detection of extended-spectrum beta-lactamases in klebsiellae with the Oxoid combination disk method. J Clin Microbiol 38:4228–4232PubMedPubMedCentralGoogle Scholar
  6. CLSI (2017) Performance standards for antimicrobial susceptibility testing: 27th ed. CLSI document M100-S27 (ISBN 1-56238-805-3)Google Scholar
  7. Colle JG, Miles RS, Watt B (1996) Tests for identification of bacteria. In: Colle JG, Fraser AG, Marimon BP, Simmon A (ed) Mackie & MacCartney practical medical microbiology, 14th edn. Churchill Livingstone, Edinburgh, pp 151–179Google Scholar
  8. Cortivo GD, Gutberlet A, Ferreira JA, Ferreira LE, Deglmann RC, Westphal GA, França PHCd (2015) Antimicrobial resistance profiles and oxacillinase genes in carbapenem-resistant Acinetobacter baumannii isolated from hospitalized patients in Santa Catarina. Braz Rev Soc Bras Med Trop 48:699–705CrossRefGoogle Scholar
  9. Corvec S, Caroff N, Espaze E, Giraudeau C, Drugeon H, Reynaud A (2003) AmpC cephalosporinase hyperproduction in Acinetobacter baumannii clinical strains. J Antimicrob Chemother 52:629–635CrossRefPubMedGoogle Scholar
  10. Endimiani A, Luzzaro F, Migliavacca R, Mantengoli E, Hujer AM, Hujer KM, Pagani L, Bonomo RA, Rossolini GM, Toniolo A (2007) Spread in an Italian hospital of a clonal Acinetobacter baumannii strain producing the TEM-92 extended-spectrum beta-lactamase. Antimicrob Agents Chemother 51:2211–2214CrossRefPubMedPubMedCentralGoogle Scholar
  11. Esterly JS, Richardson CL, Eltoukhy NS, Qi C, Scheetz MH (2011) Genetic mechanisms of antimicrobial resistance of Acinetobacter baumannii. Ann Pharmacother 45:218–228CrossRefPubMedGoogle Scholar
  12. Gharrah MM, Mostafa El-Mahdy A, Barwa RF (2017) Association between virulence factors and extended spectrum beta-lactamase producing klebsiella pneumoniae compared to nonproducing isolates. Interdiscip Perspect Infect Dis 2017:7279830CrossRefPubMedPubMedCentralGoogle Scholar
  13. Hamidian M, Hall RM (2013) ISAba1 targets a specific position upstream of the intrinsic ampC gene of Acinetobacter baumannii leading to cephalosporin resistance. J Antimicrob Chemother 68:2682–2683CrossRefPubMedGoogle Scholar
  14. Heidari H, Halaji M, Taji A, Kazemian H, Shamsabadi MS, Sisakht MT, Ebrahim-Saraie HS (2018) Molecular analysis of drug-resistant Acinetobacter baumannii isolates by ERIC-PCR. Meta Gene 17:132–135CrossRefGoogle Scholar
  15. Heras J, Dominguez C, Mata E, Pascual V, Lozano C, Torres C, Zarazaga M (2015) GelJ—a tool for analyzing DNA fingerprint gel images. BMC Bioinform 16:270CrossRefGoogle Scholar
  16. Heritier C, Poirel L, Nordmann P (2006) Cephalosporinase over-expression resulting from insertion of ISAba1 in Acinetobacter baumannii. Clin Microbiol Infect 12:123–130CrossRefPubMedPubMedCentralGoogle Scholar
  17. Hujer KM, Hujer AM, Hulten EA, Bajaksouzian S, Adams JM, Donskey CJ, Ecker DJ, Massire C, Eshoo MW, Sampath R, Thomson JM, Rather PN, Craft DW, Fishbain JT, Ewell AJ, Jacobs MR, Paterson DL, Bonomo RA (2006) Analysis of antibiotic resistance genes in multidrug-resistant Acinetobacter sp. isolates from military and civilian patients treated at the Walter Reed Army Medical Center. Antimicrob Agents Chemother 50:4114–4123CrossRefPubMedPubMedCentralGoogle Scholar
  18. Jacoby GA (2009) AmpC beta-lactamases. Clin Microbiol Rev 22:161–182CrossRefPubMedPubMedCentralGoogle Scholar
  19. Jiang X, Zhang Z, Li M, Zhou D, Ruan F, Lu Y (2006) Detection of extended-spectrum beta-lactamases in clinical isolates of Pseudomonas aeruginosa. Antimicrob Agents Chemother 50:2990–2995CrossRefPubMedPubMedCentralGoogle Scholar
  20. Karah N, Jolley KA, Hall RM, Uhlin BE (2017) Database for the AmpC alleles in Acinetobacter baumannii. PLoS ONE 12:e0176695CrossRefPubMedPubMedCentralGoogle Scholar
  21. Livermore DM, Maskell JP, Williams JD (1984) Detection of PSE-2 beta-lactamase in enterobacteria. Antimicrob Agents Chemother 25:268–272CrossRefPubMedPubMedCentralGoogle Scholar
  22. Manchanda V, Singh NP (2003) Occurrence and detection of AmpC beta-lactamases among gram-negative clinical isolates using a modified three-dimensional test at Guru Tegh Bahadur Hospital, Delhi, India. J Antimicrob Chemother 51:415–418CrossRefPubMedGoogle Scholar
  23. Naas T, Bogaerts P, Bauraing C, Degheldre Y, Glupczynski Y, Nordmann P (2006) Emergence of PER and VEB extended-spectrum beta-lactamases in Acinetobacter baumannii in Belgium. J Antimicrob Chemother 58:178–182CrossRefPubMedGoogle Scholar
  24. Naas T, Namdari F, Reglier-Poupet H, Poyart C, Nordmann P (2007) Panresistant extended-spectrum beta-lactamase SHV-5-producing Acinetobacter baumannii from New York City. J Antimicrob Chemother 60:1174–1176CrossRefPubMedGoogle Scholar
  25. Peleg AY, Seifert H, Paterson DL (2008) Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev 21:538–582CrossRefPubMedPubMedCentralGoogle Scholar
  26. Perez F, Hujer AM, Hujer KM, Decker BK, Rather PN, Bonomo RA (2007) Global challenge of multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother 51:3471–3484CrossRefPubMedPubMedCentralGoogle Scholar
  27. Poirel L, Karim A, Mercat A, Le Thomas I, Vahaboglu H, Richard C, Nordmann P (1999a) Extended-spectrum beta-lactamase-producing strain of Acinetobacter baumannii isolated from a patient in France. J Antimicrob Chemother 43:157–158CrossRefPubMedGoogle Scholar
  28. Poirel L, Naas T, Guibert M, Chaibi EB, Labia R, Nordmann P (1999b) Molecular and biochemical characterization of VEB-1, a novel class A extended-spectrum beta-lactamase encoded by an Escherichia coli integron gene. Antimicrob Agents Chemother 43:573–581CrossRefPubMedPubMedCentralGoogle Scholar
  29. Poirel L, Menuteau O, Agoli N, Cattoen C, Nordmann P (2003) Outbreak of extended-spectrum beta-lactamase VEB-1-producing isolates of Acinetobacter baumannii in a French hospital. J Clin Microbiol 41:3542–3547CrossRefPubMedPubMedCentralGoogle Scholar
  30. Poirel L, Bonnin RA, Nordmann P (2011) Genetic basis of antibiotic resistance in pathogenic Acinetobacter species. IUBMB Life 63:1061–1067CrossRefPubMedGoogle Scholar
  31. Potron A, Munoz-Price LS, Nordmann P, Cleary T, Poirel L (2011) Genetic features of CTX-M-15-producing Acinetobacter baumannii from Haiti. Antimicrob Agents Chemother 55:5946–5948CrossRefPubMedPubMedCentralGoogle Scholar
  32. Potron A, Poirel L, Nordmann P (2015) Emerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter baumannii: mechanisms and epidemiology. Int J Antimicrob Agents 45:568–585CrossRefPubMedGoogle Scholar
  33. Rodriguez-Martinez JM, Nordmann P, Ronco E, Poirel L (2010) Extended-spectrum cephalosporinase in Acinetobacter baumannii. Antimicrob Agents Chemother 54:3484–3488CrossRefPubMedPubMedCentralGoogle Scholar
  34. Rudant E, Courvalin P, Lambert T (1997) Loss of intrinsic aminoglycoside resistance in Acinetobacter haemolyticus as a result of three distinct types of alterations in the aac (6′)-Ig gene, including insertion of IS17. Antimicrob Agents Chemother 41:2646–2651CrossRefPubMedPubMedCentralGoogle Scholar
  35. Segal H, Garny S, Elisha BG (2005) Is IS(ABA-1) customized for Acinetobacter? FEMS Microbiol Lett 243:425–429CrossRefPubMedGoogle Scholar
  36. Shahid M, Malik A, Agrawal M, Singhal S (2004) Phenotypic detection of extended-spectrum and AmpC beta-lactamases by a new spot-inoculation method and modified three-dimensional extract test: comparison with the conventional three-dimensional extract test. J Antimicrob Chemother 54:684–687CrossRefPubMedGoogle Scholar
  37. Tian GB, Adams-Haduch JM, Taracila M, Bonomo RA, Wang HN, Doi Y (2011) Extended-spectrum AmpC cephalosporinase in Acinetobacter baumannii: ADC-56 confers resistance to cefepime. Antimicrob Agents Chemother 55:4922–4925CrossRefPubMedPubMedCentralGoogle Scholar
  38. Turton JF, Woodford N, Glover J, Yarde S, Kaufmann ME, Pitt TL (2006) Identification of Acinetobacter baumannii by detection of the blaOXA-51-like carbapenemase gene intrinsic to this species. J Clin Microbiol 44:2974–2976CrossRefPubMedPubMedCentralGoogle Scholar
  39. Versalovic J, Koeuth T, Lupski R (1991) Distribution of repetitive DNA sequences in eubacteria and application to finerpriting of bacterial enomes. Nucleic Acids Res 19:6823–6831CrossRefPubMedPubMedCentralGoogle Scholar
  40. Vila J, Pachon J (2008) Therapeutic options for Acinetobacter baumannii infections. Expert Opin Pharmacother 9:587–599CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Heba Shehta Said
    • 1
    Email author
  • Abdalbagi Basheer Benmahmod
    • 1
  • Ramadan Hassan Ibrahim
    • 1
  1. 1.Department of Microbiology and Immunology, Faculty of PharmacyMansoura UniversityMansouraEgypt

Personalised recommendations