• 1

    Davies J. Davies D. Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev 74: 417, 2010.

  • 2

    Percival SL. McCarty S. Hunt JA. et al: The effects of pH on wound healing, biofilms and antimicrobial efficacy. Wound Repair Regen 22: 174, 2014.

  • 3

    World Health Organization: pH in drinking-water: revised background document for development of WHO Guidelines for Drinking-water Quality. Available from: http://www.who.int/water_sanitation_health/publications/2011/dwq_guidelines/en/.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Apelqvist J. Diagnosis and treatment of the diabetic foot. Endocrine 41: 384, 2012.

  • 5

    Lipsky BA. Medical treatment of diabetic foot diseases. Clin Infect Dis 39(suppl 2): S104, 2004.

  • 6

    Gardner SE. Frantz RA. Wound bioburden and infection-related complications in diabetic foot ulcers. Biol Res Nurs 10: 44, 2008.

  • 7

    Cooper RA. Ameen H. Price P. et al: A clinical investigation into the microbiological status of ‘locally infected' leg ulcers. Int Wound J 6: 453, 2009.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Howell-Jones RS. Wilson MJ. Hill KE. et al: A review on the microbiology, antibiotic usage and resistance in chronic skin wounds. J Antimicrob Chemother 55: 143, 2005.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Thomas J. Linton S. Corum L. et al: The effect of pH and bacterial phenotypic state on antibiotic efficacy. Int Wound J 9: 428, 2012.

  • 10

    Dissemond J. Witthoff M. Grabee S. Investigations on pH values in milieus of chronic wounds during modern wound therapy . Paper presented at: World Wound Congress, Paris, 2004.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Shukla VK. Shukla D. Tiwary SK. et al: Evaluation of pH measurement as a method of wound assessment. J Wound Care 16: 291, 2007.

  • 12

    Percival SL. Thomas J. Linton S. et al: The antimicrobial efficacy of silver on antibiotic-resistance bacteria isolated from burn wounds. Int Wound J 9: 488, 2011.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Clinical and Laboratories Standards Institute (CLSI): Performance Standards for Antimicrobial Susceptibility Testing; Twenty Third Information Supplement: M100-S23, Clinical and Laboratories Standards Institute, Wayne, PA, 2013.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Schneider LA. Korber A. Grabbe S. et al: Influence of pH on wound-healing: a new perspective for wound-therapy? Arch Dermatol Res 298: 413, 2007.

  • 15

    Pellizzer G. Strazzabosco M. Presi S. et al: Deep tissue biopsy vs. superficial swab culture monitoring in the microbiological assessment of limb-threatening diabetic foot infection. Diabet Med 18: 822, 2001.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Lister PD. Wolter DJ. Hanson ND. Antibacterial-resistant Pseudomonas aeruginosa: complex regulation of chromosomally encoded resistance mechanisms. Clin Microbiol Rev 22: 582, 2009.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Peters EJ. Lipsky BA. Aragon-Sanchez J. et al: Interventions in the management of infection in the foot in diabetes: a systematic review. Diabetes Metab Res Rev 32(suppl 1): 145, 2016.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Leese G. Dilip N. Young M. et al: Use of antibiotics in people with diabetic foot disease: a consensus statement. Diabet Foot J 12: 62, 2009.

  • 19

    McArdle C. Lagan KM. McDowell DA. The pH of wound fluid in diabetic foot ulcers: the way forward in detecting clinical infection? Curr Diabetes Rev 10: 177, 2014.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    McArdle C. Lagan KM. Spence S. et al: Diabetic foot ulcer wound fluid: the effects of pH on bacteria and infection. J Foot Ankle Res 8(suppl 1): A8, 2015.

  • 21

    Bauer AW. Kirby WM. Sherris JC. et al: Antibiotic susceptibility by standardized single dink method. Am J Clin Pathol 45: 493, 1966.

  • 22

    Emrich NC. Heisig A. Stubbings W. et al: Antibacterial activity of flinafloxacin under different pH conditions against isogenic strains of Escherichia coli expressing combinations of defined mechanisms of fluoroquinolone resistance. J Antimicrob Chemother 65: 2530, 2010.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Falagas ME. McDermott L. Snydman DR. Effect of pH on in vitro antimicrobial susceptibility of Bacteroides fragilis group. Antimicrob Agents Chemother 41: 2047, 1997.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Yang L. Wang K. Li H. et al: The influence of urinary pH on antibiotic efficacy against bacterial uropathogens. Urology 84: 731.e1, 2014.

  • 25

    Bowler PG. Welsby S. Towers V. et al: Multi-resistant organisms, wounds and topical antimicrobial protection. Int Wound J 9: 387, 2012.

  • 26

    Wu S. Driver VR. Wrobel JS. et al: Foot ulcers in the diabetic patient, prevention and treatment. Vasc Health Risk Manag 3: 65, 2007.

  • 27

    Santy J. Recognising infection in wounds. Nurs Stand 23: 53, 2008.

  • 28

    Lipsky BA. Berendt AR. Cornia PB. et al: 2102 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 54: e132, 2012.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Game F. Jeffcoate W. MRSA and osteomyelitis of the foot in diabetes. Diabet Med 21(suppl 4): 16, 2004.

  • 30

    Gillings MR. Evolutionary consequences of antibiotic use for the resistome, mobilome and microbial pangenome. Front Microbiol 4: 4, 2013.

  • 31

    Greener B. Hughes AA. Bannister, NP. et al: Proteases and pH in chronic wounds. J Wound Care 14: 59, 2005.

  • 32

    Gethin GT. Cowman S. Conroy RM. The impact of Manuka honey dressings on the surface pH of chronic wounds. Int Wound J 5: 185, 2008.

  • 33

    Shi L. Ramsay S. Ermis R. et al: pH in the bacteria-contaminated wound and its impact on Clostridium histolyticum collagenase activity: implications for the use of collagenase wound debridement agents. J Wound Ostomy Continence Nurs 38: 514, 2011.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

Effects of pH on the Antibiotic Resistance of Bacteria Recovered from Diabetic Foot Ulcer Fluid

An In Vitro Study

Carla D. McArdle Queen Margaret University, Health Sciences, Musselburgh, Edinburgh, Scotland.

Search for other papers by Carla D. McArdle in
Current site
Google Scholar
PubMed
Close
 PhD
,
Katie M. Lagan Centre for Rehabilitation and Health Sciences, Ulster University, Newtownabbey, County Antrim, Ireland.

Search for other papers by Katie M. Lagan in
Current site
Google Scholar
PubMed
Close
 PhD
, and
David A. McDowell Centre for Rehabilitation and Health Sciences, Ulster University, Newtownabbey, County Antrim, Ireland.

Search for other papers by David A. McDowell in
Current site
Google Scholar
PubMed
Close
 PhD

Background:

This study investigated the resistance of bacteria isolated from diabetic foot ulcers (DFUs) to antibiotics frequently used in the management of the diabetic foot infections, at a range of pH values (pH 6.5, 7.5, and 8.5) known to exist in DFU wound fluid. This study aimed to determine whether changes (or atypical stasis) in wound fluid pH modulate the antibiotic resistance of DFU isolates, with potential implications in relation to the suppression/eradication of bacterial infections in DFUs.

Methods:

Thirty bacterial isolates were recovered from DFU wound fluid, including Staphylococcus spp, Staphylococcus aureus, Escherichia coli, Streptococcus spp, Pseudomonas spp, and Pseudomonas aeruginosa. The resistances of these isolates to a panel of antibiotics currently used in the treatment of infected or potentially infected DFUs, ie, ciprofloxacin, amoxicillin-clavulanate, doxycycline, and piperacillin-tazobactam, at the previously mentioned pH values were determined by a modification of the Kirby-Bauer assay.

Results:

The resistance of DFU isolates to clinically relevant antibiotics was significantly affected by the pH levels in DFU wound fluid.

Conclusions:

These findings highlight the importance of a more comprehensive understanding of the conditions in DFUs to inform clinical decision making in the selection and application of antibiotics in treating these difficult-to-heal wounds. The scale of the differences in the efficacies of antibiotics at the different pH values examined is likely to be sufficient to suggest reconsideration of the antibiotics of choice in the treatment of DFU infection.

Corresponding author: Carla D. McArdle, Queen Margaret University, Health Sciences, Queen Margaret Drive, Musselburgh, Edinburgh, EH21 6UU Scotland. (E-mail: cmcardle@qmu.ac.uk)
Save