Phage Therapy of Pseudomonas aeruginosa Infection in a Mouse Burn Wound Model

Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 07/2007; 51(6):1934-8. DOI: 10.1128/AAC.01028-06
Source: PubMed


Mice compromised by a burn wound injury and subjected to a fatal infection with Pseudomonas aeruginosa were administered a single dose of a Pseudomonas aeruginosa phage cocktail consisting of three different P. aeruginosa phages by three different routes: the intramuscular (i.m.), subcutaneous (s.c.), or intraperitoneal (i.p.) route. The results
of these studies indicated that a single dose of the P. aeruginosa phage cocktail could significantly decrease the mortality of thermally injured, P. aeruginosa-infected mice (from 6% survival without treatment to 22 to 87% survival with treatment) and that the route of administration
was particularly important to the efficacy of the treatment, with the i.p. route providing the most significant (87%) protection.
The pharmacokinetics of phage delivery to the blood, spleen, and liver suggested that the phages administered by the i.p.
route were delivered at a higher dose, were delivered earlier, and were delivered for a more sustained period of time than
the phages administered by the i.m. or s.c. route, which may explain the differences in the efficacies of these three different
routes of administration.

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    • "Intraperitoneal route provides 87% protection. The pharmacokinetics of bacteriophages suggests that dose delivered to blood, spleen, and liver by intraperitoneal route were delivered earlier, and were delivered for more sustained period of time than doses given by intramascular or subcutaneous route (Catherine et al., 2007). "
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    ABSTRACT: The evolution of antibiotic-resistant in bacteria has aggravated curiosity in development of alternative therapy to conventional drugs. One of the emerging drugs that can be used alternative to antibiotics is bacteriophage therapy. The use of living phages in the cure of lethal infectious life threatening diseases caused by Gram positive and Gram negative bacteria has been reported. Another development in the field of bacteriophage therapy is the use of genetically modified and non replicating phages in the treatment of bacterial infection. Genetically engineered bacteriophages can be used as adjuvant along with antibiotic therapy. Phages encoded with lysosomal enzymes are also effectual in the treatment of infectious diseases.
    Pakistan journal of pharmaceutical sciences 01/2015; 28(1):265-270. · 0.68 Impact Factor
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    • "Phages were shown to be able to rescue burned mice from infection caused by P. aeruginosa and Klebsiella pneumonia [9] [10]. In 1990, in Egypt, 30 patients with burn wounds were treated during 5-17 days with between 15 and 45 phage-saturated dressings [11]. "
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    ABSTRACT: Antibiotic resistance has become a major public health problem and the antibiotics pipeline is running dry. Bacteriophages (phages) may offer an 'innovative' means of infection treatment, which can be combined or alternated with antibiotic therapy and may enhance our abilities to treat bacterial infections successfully. Today, in the Queen Astrid Military Hospital, phage therapy is increasingly considered as part of a salvage therapy for patients in therapeutic dead end, particularly those with multidrug resistant infections. We describe the application of a well-defined and quality controlled phage cocktail, active against Pseudomonas aeruginosa and Staphylococcus aureus, on colonized burn wounds within a modest clinical trial (nine patients, 10 applications), which was approved by a leading Belgian Medical Ethical Committee. No adverse events, clinical abnormalities or changes in laboratory test results that could be related to the application of phages were observed. Unfortunately, this very prudent 'clinical trial' did not allow for an adequate evaluation of the efficacy of the phage cocktail. Nevertheless, this first 'baby step' revealed several pitfalls and lessons for future experimental phage therapy and helped overcome the psychological hurdles that existed to the use of viruses in the treatment of patients in our burn unit.
    International Journal of Burns and Trauma 10/2014; 4(2):66-73.
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    • "In almost all cases, the colonized patient is considered as a major reservoir for the epidemic strains (5, 17). It has been estimated that at least 50% of all deaths caused by burns are the result of infection, and untreatable infections have become a tragically frequent morbidity in patients infected with P. aeruginosa (18). Eradication of MDRPA from hospital burn wards is a demanding task; therefore, the detection of metallo-beta-lactamase (MBL) producing P. aeruginosa is necessary for controlling the spread of resistant strains as well as developing new therapeutic guidelines and prophylactic strategies to control the bacterial infection in patients with burn wounds. "
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    ABSTRACT: Background:Metallo-beta-lactamase (MBL) producing Pseudomonas aeruginosa in the burn patients is a leading cause of morbidity and mortality and remains a serious health concern among the clinicians.Objectives:The aim of this study was to detect MBL-producing P. aeruginosa in burn patients and determine multidrug-resistant (MDR) strains, and respective resistance patterns.Patients and Methods:In this cross-sectional study, 270 strains of P. aeruginosa were isolated from the burn patients referred to Ghotbeddin Burn Hospital, Shiraz, Iran. Among them, 55 MBL-producing P. aeruginosa strains were isolated from 55 patients hospitalized in burn unit. Minimum inhibitory concentrations (MICs) and MBLs were determined by the E-test method.Results:Of the 55 burn cases, 29 (53%) were females and 26 (47%) males. Injured burn patients’ ages ranged from 16 to 87 years, with maximum number of cases in the age group of 16 to 36 years (n, 40; 72.7%). Overall, 32 cases were accidental (60%), and 22 were suicidal burns (40%). Of the 55 burn patients, 17 cases were expired (30%). All deaths were due to chemical exposures. In antibiotic susceptibility testing by E-test method, ceftazidime was the most effective one and 35 isolates (63.5%) were resistant to all the 11 tested antibiotics.Conclusions:Routine microbiological surveillance and careful in vitro testing of antibiotics prior to prescription and strict adherence to hospital antibiotic policy may help to prevent, treat, and control MDR and pandrug-resistant (PDR) P. aeruginosa strains in burn units.
    06/2014; 3(2). DOI:10.5812/atr.18182
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