Publicação
Strategies to combat infections of Acinetobacter baumannii biofilms
| Resumo: | Acinetobacter baumannii has been emerging as a serious nosocomial pathogen in Portugal and worldwide, being implicated in many opportunistic infections such as ventilator-associated pneumonia, bacteremia, meningitis and urinary tract infections. The development of resistance by this microorganism to most classes of antibiotics, and its high mortality rate (19-54 %) makes A. baumannii outbreaks frightening for both patients and healthcare providers. With this in perspective, the main objective of this work was to find strategies to combat A. baumannii infections, particularly those involving biofilms, using antibiotics and bacteriophages (phages). Three antibiotics (Ampicillin, Kanamycin and Ciprofloxacin) were tested, with the determination of the minimum inhibitory concentration (MIC) and minimum biofilm eradication concentrations (MBEC) against A. baumannii. The phage Aba1 was also evaluated at different multiplicities of infection (1 and 10) and periods of time (4 h and 24 h) on biofilms. Then, a recent therapy – the Phage-Antibiotic combination – was applied, to evaluate possible synergic effects with the antibiotics. Additionally, a new strategy was evaluated to fight A. baumannii biofilms, consisting on the stepwise addition of antibiotics and/or phages. In this work, Ciprofloxacin was the most effective of the antibiotics tested against A. baumannii biofilms, according to the MBEC values obtained. Furthermore, the addition of phage Aba1 did not have any effect on the activity of this antibiotic, contrarily to the synergic effect obtained with Ampicillin or Kanamycin, opening new possibilities for the application of these antibiotics. The novel treatment strategies here evaluated had its best results with Kanamycin. In biofilms, the addition of Kanamycin at 0h, 12h and 24h resulted in a 5 log reduction of the biofilm cells, and the use of phage at 0h followed by Kanamycin at 12h and 24h resulted in a 3 log reduction. Similar results were obtained for planktonic cells. The promising results of the novel strategy here presented should be further explored for the combat of A. baumannii infections. Indeed, with the impressive capacity of A. baumannii to acquire resistance to new antibiotics, it is crucial to develop innovative strategies for the efficient application of old antibiotics. |
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| Autores principais: | Macedo, João Manuel Novais de Castro |
| Ano: | 2015 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Acinetobacter baumannii has been emerging as a serious nosocomial pathogen in Portugal and worldwide, being implicated in many opportunistic infections such as ventilator-associated pneumonia, bacteremia, meningitis and urinary tract infections. The development of resistance by this microorganism to most classes of antibiotics, and its high mortality rate (19-54 %) makes A. baumannii outbreaks frightening for both patients and healthcare providers. With this in perspective, the main objective of this work was to find strategies to combat A. baumannii infections, particularly those involving biofilms, using antibiotics and bacteriophages (phages). Three antibiotics (Ampicillin, Kanamycin and Ciprofloxacin) were tested, with the determination of the minimum inhibitory concentration (MIC) and minimum biofilm eradication concentrations (MBEC) against A. baumannii. The phage Aba1 was also evaluated at different multiplicities of infection (1 and 10) and periods of time (4 h and 24 h) on biofilms. Then, a recent therapy – the Phage-Antibiotic combination – was applied, to evaluate possible synergic effects with the antibiotics. Additionally, a new strategy was evaluated to fight A. baumannii biofilms, consisting on the stepwise addition of antibiotics and/or phages. In this work, Ciprofloxacin was the most effective of the antibiotics tested against A. baumannii biofilms, according to the MBEC values obtained. Furthermore, the addition of phage Aba1 did not have any effect on the activity of this antibiotic, contrarily to the synergic effect obtained with Ampicillin or Kanamycin, opening new possibilities for the application of these antibiotics. The novel treatment strategies here evaluated had its best results with Kanamycin. In biofilms, the addition of Kanamycin at 0h, 12h and 24h resulted in a 5 log reduction of the biofilm cells, and the use of phage at 0h followed by Kanamycin at 12h and 24h resulted in a 3 log reduction. Similar results were obtained for planktonic cells. The promising results of the novel strategy here presented should be further explored for the combat of A. baumannii infections. Indeed, with the impressive capacity of A. baumannii to acquire resistance to new antibiotics, it is crucial to develop innovative strategies for the efficient application of old antibiotics. |
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