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Improved Outcomes Via Integrated Molecular Diagnostics and Biofilm Targeted Therapeutics

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Culture Negative Orthopedic Biofilm Infections

Part of the book series: Springer Series on Biofilms ((BIOFILMS,volume 7))

Abstract

Molecular diagnostics are validated clinical tools available today for most all clinicians. Given the expanded microbial census they elucidate with DNA-level certainty, a new microbial reality has emerged making interpretation pivotal to advancing outcomes. Regarding chronic infection, there is little consensus for interpretation, even from traditional culture. To advance outcomes, the authors propose an escalating chronic infection protocol leveraging multiple concurrent strategies. A pivotal aspect, directing multiple legs of the protocol, is the diagnostic objectivity and accuracy of molecular diagnostics.

Using the combination of polymerase chain reaction and pyrosequencing (PCR:PSEQ) applied to chronic wounds, clinical outcomes are highlighted in a chronic infection example. Absolute healing rates for microbial DNA guided topical treatments including antibiotics and antibiofilm agents were approximately twice that of culture directed therapy (p<0.001). Further, median days to closure were 177 days for culture directed therapy versus 28days for microbial DNA guided topical treatments (p<0.001).

Absent of cultivation biases and limitations, PCR:PSEQ accurately identifies all known bacteria, yeast, and fungi. While the utility of PCR:PSEQ has become relatively established for chronic wounds, the use of these methods for any chronic infection is warranted whenever the comprehensive microbial contribution is clinically relevant to interventional strategy.

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References

  • Chakraborti C, Le C, Yanofsky A (2010) Sensitivity of superficial cultures in lower extremity wounds. J Hosp Med 5(7):415–420

    Article  PubMed  Google Scholar 

  • del Pozo JL, Patel R (2007) The challenge of treating biofilm-associated bacterial infections. Clin Pharmacol Ther 82:204–209

    Article  PubMed  Google Scholar 

  • Dowd SE, Wolcott R (2010) Molecular diagnosis: a new era in wound care. Today’s Wound Clinic 2:24–27

    Google Scholar 

  • Dowd SE, Wolcott RD, Sun Y et al (2008a) Polymicrobial nature of chronic diabetic foot ulcer biofilm infections determined using bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP). PLoS One 3:e3326

    Article  PubMed  Google Scholar 

  • Dowd SE, Sun Y, Secor PR et al (2008b) Survey of bacterial diversity in chronic wounds using Pyrosequencing, DGGE, and full ribosome shotgun sequencing. BMC Microbiol 8:43

    Article  PubMed  Google Scholar 

  • Dowd SE, Wolcott RD, Kennedy J, Jones C, Cox SB (2011) Molecular diagnostics and personalised medicine in wound care: assessment of outcomes. J Wound Care 20:232–239

    PubMed  CAS  Google Scholar 

  • El-Azizi M, Rao S, Kanchanapoom T, Khardori M (2005) In vitro activity of vancomycin, quinupristin/dalfopristin, and linezolid against intact and disrupted biofilms of staphylococci. Ann Clin Microbiol Antimicrob 4:2

    Article  PubMed  Google Scholar 

  • Gardner SE, Frantz RA, Doebbeling BN (2001) The validity of the clinical signs and symptoms used to identify localized chronic wound infection. Wound Repair Regen 9:178–186

    Article  PubMed  CAS  Google Scholar 

  • Kennedy JP (2011) Molecular enabled personalized medicine for chronic infection. Chronic orthopaedic infection conference, Center for Genomic Sciences, Allegheny-Singer Research Institute, Pittsburgh, PA, May 2011

    Google Scholar 

  • Lazăr V, Chifiriuc MC (2010) Medical significance and new therapeutically strategies for biofilm associated infections. Roum Arch Microbiol Immunol 69:125–138

    PubMed  Google Scholar 

  • Rennie RP, Jones RN, Mutnick AH (2003) Occurrence and antimicrobial susceptibility patterns of pathogens isolated from skin and soft tissue infections: report from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 2000). Diagn Microbiol Infect Dis 45:287–293

    Article  PubMed  CAS  Google Scholar 

  • Sun Y, Smith E, Wolcott R, Dowd SE (2009) Propagation of anaerobic bacteria within an aerobic multispecies chronic wound biofilm model. J Wound Care 18:426–431

    PubMed  CAS  Google Scholar 

  • Wolcott RD, Rhoads DD (2008) A study of biofilm-based wound management in subjects with critical limb ischaemia. J Wound Care 17:145–155

    PubMed  CAS  Google Scholar 

  • Wolcott RD, Gontcharova V, Sun Y, Dowd SE (2009) Evaluation of the bacterial diversity among and within individual venous leg ulcers using bacterial tag-encoded FLX and titanium amplicon pyrosequencing and metagenomic approaches. BMC Microbiol 9:226

    Article  PubMed  Google Scholar 

  • Wolcott RD, Cox SB, Dowd SE (2010a) Healing and healing rates of chronic wounds in the age of molecular pathogen diagnostics. J Wound Care 19:272–281

    PubMed  CAS  Google Scholar 

  • Wolcott RD, Rumbaugh KP, James G, Schultz G, Phillips P, Yang Q, Watters C, Stewart PS, Dowd SE (2010b) Biofilm maturity studies indicate sharp debridement opens a time-dependent therapeutic window. J Wound Care 19:320–328

    PubMed  CAS  Google Scholar 

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Correspondence to John P. Kennedy .

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Kennedy, J.P., Jones, C.E. (2012). Improved Outcomes Via Integrated Molecular Diagnostics and Biofilm Targeted Therapeutics. In: Ehrlich, G., DeMeo, P., Costerton, J., Winkler, H. (eds) Culture Negative Orthopedic Biofilm Infections. Springer Series on Biofilms, vol 7. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-29554-6_4

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