Eradication of early Pseudomonas aeruginosa infection

Department of Clinical Microbiology 9301, Rigshospitalet, University of Copenhagen, Juliane Maries Vej 22, 2100 Copenhagen, Denmark.
Journal of Cystic Fibrosis (Impact Factor: 3.48). 09/2005; 4 Suppl 2(Suppl 2):49-54. DOI: 10.1016/j.jcf.2005.05.018
Source: PubMed


Chronic pulmonary infection with Pseudomonas aeruginosa is responsible for most of the morbidity and mortality in cystic fibrosis (CF). Once established as a biofilm, chronic P. aeruginosa infection caused by the mucoid phenotype cannot be eradicated. However, a period of intermittent colonization with P. aeruginosa precedes the establishment of the chronic infection. This window of opportunity can be utilized to eradicate P. aeruginosa from the respiratory tract of CF patients by means of oral ciprofloxacin in combination with nebulized colistin for 3 weeks or, even better, for 3 months or by means of inhaled tobramycin as monotherapy for 4 weeks or longer. This early, aggressive eradication therapy has now been used for 15 years without giving rise to resistance to the antibiotics and without serious side effects. The therapeutic results have been very successful and have completely changed the epidemiology in the Danish Cystic Fibrosis Center and a few other centers which have used this strategy for several years. The chronic P. aeruginosa lung infection is not seen in CF infants and children anymore due to the aggressive therapy, and no other bacteria have replaced P. aeruginosa in these young patients. The aggressive therapy has been shown to very cost-effective, and a European Consensus report recommends this approach.

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    • "A number of studies have investigated the consequences of combining various antibiotics with polymyxins. Antimicrobial agents such as miconazole [24], rifampicin [25,26] meropenem, ampicillin-sulbactam, ciprofloxacin, piperacillin-clavulanic acid, imipenem, amikacin, and gentamicin [27] ciprofloxacin [28] trimethoprim, trimethoprim-sulfamethoxazole, and vancomycin [29], to name but a few, have been the focus of studies to assess if they can work synergistically with polymyxins (also see Yahav et. al., for a review of compounds synergistic with polymyxin E [30]). "
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    ABSTRACT: The emergence of bacterial drug resistance encourages the re-evaluation of the potential of existing antimicrobials. Lantibiotics are post-translationally modified, ribosomally synthesised antimicrobial peptides with a broad spectrum antimicrobial activity. Here, we focussed on expanding the potential of lacticin 3147, one of the most studied lantibiotics and one which possesses potent activity against a wide range of Gram positive species including many nosocomial pathogens. More specifically, our aim was to investigate if lacticin 3147 activity could be enhanced when combined with a range of different clinical antibiotics. Initial screening revealed that polymyxin B and polymyxin E (colistin) exhibited synergistic activity with lacticin 3147. Checkerboard assays were performed against a number of strains, including both Gram positive and Gram negative species. The resultant fractional inhibitory concentration (FIC) index values established that, while partial synergy was detected against Gram positive targets, synergy was obvious against Gram negative species, including Cronobacter and E. coli. Combining lacticin 3147 with low levels of a polymyxin could provide a means of broadening target specificity of the lantibiotic, while also reducing polymyxin use due to the lower concentrations required as a result of synergy.
    BMC Microbiology 09/2013; 13(1):212. DOI:10.1186/1471-2180-13-212 · 2.73 Impact Factor
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    • "As P. aeruginosa strains adapt to the CF lung and are able to persist, they establish a chronic infection that is difficult to eradicate (Govan & Deretic, 1996; Høiby et al., 2005; Landry et al., 2006). Both epidemic FCC and non-epidemic "
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    ABSTRACT: Chronic Pseudomonas aeruginosa infection is the leading cause of morbidity and mortality in cystic fibrosis patients. P. aeruginosa isolates undergo significant transcriptomic and proteomic modulations as they adapt to the niche environment of the CF lung and the host defences. This study characterised the in vitro virulence of isogenic strain-pairs of P. aeruginosa epidemic or Frequent Clonal Complexes (FCC) and non-epidemic or Infrequent Clonal Complexes (IFCC) collected five to eight years apart from five chronically infected adult CF patients. Strains showed a significant decrease in virulence over the course of chronic infection using a Caenorhabditis elegans slow kill assay and in phenotypic tests for important virulence factors. This decrease in virulence correlated with numerous differentially expressed genes such as oprG, lasB ,rsaL and lecB. Microarray analysis identified a large genomic island deletion in the IFCC strain-pair that included T3SS effector and fimbrial subunit genes.. This study presents novel in vitro data to examine the transcriptomic profiles of sequentially-collected P. aeruginosa from CF adults. The genes with virulence-related functions identified here present potential targets for new therapies and vaccines against FCC and IFCC.
    Microbiology 09/2013; 159(Pt_11). DOI:10.1099/mic.0.066985-0 · 2.56 Impact Factor
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    • "A study using quantitative PCR (qPCR) to target the oprL gene showed 85% specificity and concluded that qPCR may have a predictive value for impending P. aeruginosa infection for only a limited number of patients.22 The specificity of another developed multiplex PCR was reported as only 45.5%.23 P. aeruginosa from various sources were studied and it was found that the combination of oprl, oprL, 16S rDNA, ETA and fliC genes leads to false positive result because of genetic conservation and it showed difficulties in building up a reliable screening with these targets, however the gyrB and 16S-23S rDNA ITS genes were highly specific.7 "
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    ABSTRACT: Background and Objective: Wound infections are often difficult to treat due to various bacterial pathogens. Pseudomonas aeruginosa is one of the common invaders of open wounds. Precise diagnosis of this etiological agent in wound infections is of critical importance particularly in treatment of problematic cases. The existing diagnostic methods have certain limitations particularly related to specificity. Our objective was to to establish a comprehensive and reliable multiplex PCR to confirm diagnosis of P. aeruginosa. Methods: A multiplex PCR test was developed for rapid and comprehensive identification of P. aeruginosa. Four highly specific genes were targeted simultaneously for detection of genus, species and exotoxin production (16S rDNA, gyrB, oprL and ETA) in P. aeruginosa; additionally one internal control gene (invA) of Salmonella was used. The specificity of the multiplex PCR was confirmed using internal and negative controls. Amplified fragments were confirmed by restriction analysis and DNA sequencing. Results: The developed method was applied on 40 morphologically suspected P. aeruginosa isolates (from 200 pus samples) and 18 isolates were confirmed as P. aeruginosa. In comparison, only 12 could be identified biochemically. Conclusions: Combination of the four reported genes in multiplex PCR provided more confident and comprehensive detection of P. aeruginosa which is applicable for screening of wound infections and assisting treatment strategy.
    Pakistan Journal of Medical Sciences Online 07/2013; 29(4):957-61. DOI:10.12669/pjms.294.3652 · 0.23 Impact Factor
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