Phage therapy to control multidrug-resistant Pseudomonas aeruginosa skin infections: in vitro and ex vivo experiments

Vieira, Anabela; Silva, Y. J.; Cunha, Ângela; Gomes, Newton C. M.; Ackermann, Hans-W.; Almeida, Adelaide

doi:10.1007/s10096-012-1691-x

Cited by 80 publications

(54 citation statements)

References 32 publications

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“…In vitro results demonstrate that MDR-bacterial isolates could regrow after 14–16 h of phage therapy; this may be due to emergence of phage resistant strains, as also reported by the Vieira, Kumari, and Andretti groups [54,55]. …”

Section: Discussionsupporting

confidence: 62%

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Isolation and in vitro evaluation of bacteriophages against MDR-bacterial isolates from septic wound infections

et al. 2017

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Multi-drug resistance has become a major problem for the treatment of pathogenic bacterial infections. The use of bacteriophages is an attractive approach to overcome the problem of drug resistance in several pathogens that cause fatal diseases. Our study aimed to isolate multi drug resistant bacteria from patients with septic wounds and then isolate and apply bacteriophages in vitro as alternative therapeutic agents. Pus samples were aseptically collected from Rajiv Gandhi Institute of Medical Science (RIMS), Kadapa, A.P., and samples were analyzed by gram staining, evaluating morphological characteristics, and biochemical methods. MDR-bacterial strains were collected using the Kirby-Bauer disk diffusion method against a variety of antibiotics. Bacteriophages were collected and tested in vitro for lytic activity against MDR-bacterial isolates. Analysis of the pus swab samples revealed that the most of the isolates detected had Pseudomonas aeruginosa as the predominant bacterium, followed by Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli. Our results suggested that gram-negative bacteria were more predominant than gram-positive bacteria in septic wounds; most of these isolates were resistant to ampicillin, amoxicillin, penicillin, vancomycin and tetracycline. All the gram-positive isolates (100%) were multi-drug resistant, whereas 86% of the gram-negative isolates had a drug resistant nature. Further bacteriophages isolated from sewage demonstrated perfect lytic activity against the multi-drug resistant bacteria causing septic wounds. In vitro analysis of the isolated bacteriophages demonstrated perfect lysis against the corresponding MDR-bacteria, and these isolated phages may be promising as a first choice for prophylaxis against wound sepsis, Moreover, phage therapy does not enhance multi-drug resistance in bacteria and could work simultaneously on a wide variety of MDR-bacteria when used in a bacteriophage cocktail. Hence, our results suggest that these bacteriophages could be potential therapeutic options for treating septic wounds caused by P. aeruginosa, S. aureus, K. pneumoniae and E. coli.

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Section: Discussionsupporting

confidence: 62%

“…pneumoniae and S . aureus infections [55] in various disease conditions. Limitations of the present study are following:…”

Section: Discussionmentioning

confidence: 99%

Isolation and in vitro evaluation of bacteriophages against MDR-bacterial isolates from septic wound infections

et al. 2017

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“…Several studies have shown the potential of use of phages to treat infectious diseases in animals 26 and humans 27 , even those caused by multidrugresistant bacteria. 28 The 15 strains of the present study were susceptible to 6 lytic phages isolated from effluents isolated from the same hospital over several months.…”

Section: Discussionmentioning

confidence: 99%

Bacteriophage-antibiotic synergism to control planktonic and biofilm producing clinical isolates of Pseudomonas aeruginosa

Nouraldin

Baddour²,

Harfoush³

et al. 2016

Alexandria Journal of Medicine

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Introduction: Pseudomonas aeruginosa (P. aeruginosa) is a highly resistant opportunistic pathogen and is capable of forming biofilms on medical devices. Bacterial biofilms, which are micro-colonies encased in extracellular polysaccharide material are so difficult to be treated by conventional antibiotics. During the last decade, P. aeruginosa phages have been extensively examined as an alternative to antimicrobial agents. The aim of the study was to assess bacteriophageantibiotic combination on planktonic and biofilm states of P. aeruginosa isolates. Materials: In this study, we isolated 6 lytic phages, from hospital effluents, they were tested against 50 P. aeruginosa strains, isolated from different clinical specimens delivered to the Diagnostic Microbiology Laboratories, Faculty of Medicine, Alexandria University. Results: Out of the 50 isolates, 15 were susceptible to these phages. So the biofilm forming capacity of these 15 isolates was investigated. The results showed that 14 isolates (93.33%) produced detectable biofilm. The minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) assays were used to evaluate the antibiotic sensitivity patterns of these P. aeruginosa isolates in their planktonic and biofilm phases to amikacin and meropenem. Also, the effects of phage on the planktonic and biofilm states of isolates at different multiplicities of infections (MOI) were tested. On the planktonic state, the amikacin-phage combination showed synergistic effect (P = 0.001), and the meropenem-phage combination showed synergistic effect (P = 0.003). On the biofilm state, the amikacin-phage combination showed biofilm eradication Please cite this article in press as: Nouraldin AAM et al. Bacteriophage-antibiotic synergism to control planktonic and biofilm producing clinical isolates of Pseudomonas aeruginosa, Alex J Med (2015), http://dx.doi.org/10.1016/j.ajme.2015.05.002in 50% of the isolates (P = 0.003). On the other hand, the meropenem-phage combination showed biofilm eradication in 14.3% of the strains. Conclusion: The combination of phage and antibiotics could have potentially more benefits on P. aeruginosa planktonic and biofilm states than just using phages or antibiotics alone.

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“…New phages are continuously isolated for P. aeruginosa, and their capacity to target various clinical strains is tested in vitro and in animal models [10], [54], [55]. Our first attempt to obtain phages that could lyse strains that do not support pyophage infection led in part to the isolation of phages which belong to different species or genera.…”

Section: Discussionmentioning

confidence: 99%

The Susceptibility of Pseudomonas aeruginosa Strains from Cystic Fibrosis Patients to Bacteriophages

Essoh

Blouin

Loukou³

et al. 2013

PLoS ONE

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Phage therapy may become a complement to antibiotics in the treatment of chronic Pseudomonas aeruginosa infection. To design efficient therapeutic cocktails, the genetic diversity of the species and the spectrum of susceptibility to bacteriophages must be investigated. Bacterial strains showing high levels of phage resistance need to be identified in order to decipher the underlying mechanisms. Here we have selected genetically diverse P. aeruginosa strains from cystic fibrosis patients and tested their susceptibility to a large collection of phages. Based on plaque morphology and restriction profiles, six different phages were purified from “pyophage”, a commercial cocktail directed against five different bacterial species, including P. aeruginosa. Characterization of these phages by electron microscopy and sequencing of genome fragments showed that they belong to 4 different genera. Among 47 P. aeruginosa strains, 13 were not lysed by any of the isolated phages individually or by pyophage. We isolated two new phages that could lyse some of these strains, and their genomes were sequenced. The presence/absence of a CRISPR-Cas system (Clustered Regularly Interspaced Short Palindromic Repeats and Crisper associated genes) was investigated to evaluate the role of the system in phage resistance. Altogether, the results show that some P. aeruginosa strains cannot support the growth of any of the tested phages belonging to 5 different genera, and suggest that the CRISPR-Cas system is not a major defence mechanism against these lytic phages.

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Phage therapy to control multidrug-resistant Pseudomonas aeruginosa skin infections: in vitro and ex vivo experiments

Cited by 80 publications

References 32 publications

Isolation and in vitro evaluation of bacteriophages against MDR-bacterial isolates from septic wound infections

Isolation and in vitro evaluation of bacteriophages against MDR-bacterial isolates from septic wound infections

Bacteriophage-antibiotic synergism to control planktonic and biofilm producing clinical isolates of Pseudomonas aeruginosa

The Susceptibility of Pseudomonas aeruginosa Strains from Cystic Fibrosis Patients to Bacteriophages

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