1887

Abstract

The therapeutic options to treat infections are very limited.

Our aim was to evaluate the activity of sulbactam combined directly with avibactam or the ampicillin-sulbactam/ceftazidime-avibactam combination against extensively drug-resistant isolates.

Extensively drug-resistant isolates (=127) collected at several South American hospitals were studied. Synergy with the sulbactam/avibactam combination was assessed in all isolates using the agar dilution method. Avibactam was used at a fixed concentration of 4 mg l. A disc diffusion synergy test was also performed. Synergy by a time-kill experiment was performed in a selected isolate.

Synergy with sulbactam/avibactam was demonstrated in 124 isolates and it showed MIC values ≤4 mg l. This synergy was not detected in the three New Delhi metallo-β-lactamase-harbouring isolates. Similar results were observed with the disc diffusion synergy test of ampicillin-sulbactam/ceftazidime-avibactam. In the time-kill experiments, sulbactam/avibactam showed a rapid synergistic and bactericidal activity in ampicillin-sulbactam-resistant isolates.

This study demonstrated that the sulbactam/avibactam combination displayed synergistic activity against isolates. This synergy was observed when both inhibitors were also used as part of the commercially available combinations: ampicillin-sulbactam and ceftazidime-avibactam.

Funding
This study was supported by the:
  • Angela Famiglietti , Secretaria de Ciencia y Tecnica, Universidad de Buenos Aires , (Award UBACyT 20020130100167BA)
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001211
2020-06-25
2020-10-24
Loading full text...

Full text loading...

References

  1. Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev 2008; 21:538–582 [CrossRef][PubMed]
    [Google Scholar]
  2. Rodríguez CH, Nastro M, Famiglietti A. Carbapenemases in Acinetobacter baumannii. Review of their dissemination in Latin America. Rev Argent Microbiol 2018; 50:327–333 [CrossRef][PubMed]
    [Google Scholar]
  3. Cai Y, Chai D, Wang R, Liang B, Bai N. Colistin resistance of Acinetobacter baumannii: clinical reports, mechanisms and antimicrobial strategies. J Antimicrob Chemother 2012; 67:1607–1615 [CrossRef][PubMed]
    [Google Scholar]
  4. Karaiskos I, Lagou S, Pontikis K, Rapti V, Poulakou G. The "Old" and the "New" Antibiotics for MDR Gram-Negative Pathogens: For Whom, When, and How. Front Public Health 2019; 7:151 [CrossRef][PubMed]
    [Google Scholar]
  5. Piperaki E-T, Tzouvelekis LS, Miriagou V, Daikos GL. Carbapenem-Resistant Acinetobacter baumannii: in pursuit of an effective treatment. Clin Microbiol Infect 2019; 25:951–957 [CrossRef][PubMed]
    [Google Scholar]
  6. Higgins PG, Wisplinghoff H, Stefanik D, Seifert H. In vitro activities of the beta-lactamase inhibitors clavulanic acid, sulbactam, and tazobactam alone or in combination with beta-lactams against epidemiologically characterized multidrug-resistant Acinetobacter baumannii strains. Antimicrob Agents Chemother 2004; 48:1586–1592 [CrossRef][PubMed]
    [Google Scholar]
  7. Yang Y, Xu Q, Li T, Fu Y, Shi Y et al. OXA-23 is a prevalent mechanism contributing to sulbactam resistance in diverse Acinetobacter baumannii clinical strains. Antimicrob Agents Chemother 2019; 63: [CrossRef][PubMed]
    [Google Scholar]
  8. Mataracı Kara E, Yılmaz M, Özbek Çelik B. In vitro activities of ceftazidime/avibactam alone or in combination with antibiotics against multidrug-resistant Acinetobacter baumannii isolates. J Glob Antimicrob Resist 2019; 17:137–141 [CrossRef][PubMed]
    [Google Scholar]
  9. Álvarez-Buylla A, Culebras E, Picazo JJ. Identification of Acinetobacter species: is Bruker Biotyper MALDI-TOF mass spectrometry a good alternative to molecular techniques?. Infect Genet Evol 2012; 12:345–349 [CrossRef][PubMed]
    [Google Scholar]
  10. Pournaras S, Gogou V, Giannouli M, Dimitroulia E, Dafopoulou K et al. Single-locus-sequence-based typing of bla OXA-51-like genes for rapid assignment of Acinetobacter baumannii clinical isolates to international clonal lineages. J Clin Microbiol 2014; 52:1653–1657 [CrossRef][PubMed]
    [Google Scholar]
  11. Turton JF, Gabriel SN, Valderrey C, Kaufmann ME, Pitt TL. Use of sequence-based typing and multiplex PCR to identify clonal lineages of outbreak strains of Acinetobacter baumannii . Clin Microbiol Infect 2007; 13:807–815 [CrossRef][PubMed]
    [Google Scholar]
  12. Rodríguez CH, Balderrama Yarhui N, Nastro M, Nuñez Quezada T, Castro Cañarte G et al. Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii in South America. J Med Microbiol 2016; 65:1088–1091 [CrossRef]
    [Google Scholar]
  13. Woodford N, Ellington MJ, Coelho JM, Turton JF, Ward ME et al. Multiplex PCR for genes encoding prevalent OXA carbapenemases in Acinetobacter spp. Int J Antimicrob Agents 2006; 27:351–353 [CrossRef][PubMed]
    [Google Scholar]
  14. Poirel L, Walsh TR, Cuvillier V, Nordmann P. Multiplex PCR for detection of acquired carbapenemase genes. Diagn Microbiol Infect Dis 2011; 70:119–123 [CrossRef][PubMed]
    [Google Scholar]
  15. Clinical and Laboratory Standards Institute Performance standards for antimicrobial susceptibility testing. Twenty-fifth Informational Supplement M100–S28 Wayne. PA: CLSI; 2018
    [Google Scholar]
  16. Rodriguez CH, De Ambrosio A, Bajuk M, Spinozzi M, Nastro M et al. In vitro antimicrobials activity against endemic Acinetobacter baumannii multiresistant clones. J Infect Dev Ctries 2010; 4:164–167 [CrossRef][PubMed]
    [Google Scholar]
  17. Han M-L, Liu X, Velkov T, Lin Y-W, Zhu Y et al. Comparative metabolomics reveals key pathways associated with the synergistic killing of colistin and sulbactam combination against multidrug-resistant Acinetobacter baumannii . Front Pharmacol 2019; 10:754 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001211
Loading
/content/journal/jmm/10.1099/jmm.0.001211
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error