1887

Abstract

Treatment of orthopaedic infections remains challenging owing to the inability of antibiotics to eradicate biofilms and prevent their regrowth. The present study characterized the effects of 12 antibiotics on biofilm formed by a representative strain of meticillin-susceptible (MSSA) isolated from a bone infection. Determination of the minimum biofilm eradication concentrations indicated that eradication of 24 h-old biofilms required concentrations up to 51 200 times higher than MICs. The influence of the same panel of antibiotics was also investigated on biofilm formation at concentrations including the breakpoints, by numbering viable cells in the suspensions (individual cells) and the biofilm biomass. Except for fusidic acid, the presence of antibiotics during the initial steps of biofilm formation resulted in significant decreases in the number of sessile viable bacteria at the highest concentrations tested. Ceftarolin, daptomycin, fosfomycin, gentamicin, ofloxacin, rifampicin and vancomycin were the most effective drugs. Confocal microscopy analysis indicated that daptomycin was more efficient at bacteria lysis than gentamicin and vancomycin. However, viable individual cells were still detectable in the assays performed with ceftarolin, fosfomycin, ofloxacin, rifampicin and vancomycin at concentrations for which no sessile cells were detected. Although none of the molecules tested was effective at classical therapeutic concentrations against 24 h-old MSSA biofilms, all except fusidic acid were able to impair biofilm formation at concentrations near the breakpoints. However, presence of viable individual unattached cells could imply a significant risk of microbial dissemination and increased risk of infections.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000125
2015-09-01
2019-12-11
Loading full text...

Full text loading...

/deliver/fulltext/jmm/64/9/1021.html?itemId=/content/journal/jmm/10.1099/jmm.0.000125&mimeType=html&fmt=ahah

References

  1. Aggarwal V. K., Bakhshi H., Ecker N. U., Parvizi J., Gehrke T., Kendoff D.. ( 2014;). Organism profile in periprosthetic joint infection: pathogens differ at two arthroplasty infection referral centers in Europe and in the United States. J Knee Surg 27: 399–406 [CrossRef] [PubMed].
    [Google Scholar]
  2. Bui L. M. G., Hoffmann P., Turnidge J. D., Zilm P. S., Kidd S. P.. ( 2015;). Prolonged growth of a clinical Staphylococcus aureus strain selects for a stable small-colony-variant cell type. Infect Immun 83: 470–481 [CrossRef] [PubMed].
    [Google Scholar]
  3. Cha J. O., Park Y. K., Lee Y. S., Chung G. T.. ( 2011;). In vitro biofilm formation and bactericidal activities of methicillin-resistant Staphylococcus aureus clones prevalent in Korea. Diagn Microbiol Infect Dis 70: 112–118 [CrossRef] [PubMed].
    [Google Scholar]
  4. CLSI ( 2013;). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Third Informational Supplement M100-S23. Wayne, PA: Clinical and Laboratory Standards Institute;.
  5. Darouiche R. O.. ( 2004;). Treatment of infections associated with surgical implants. N Engl J Med 350: 1422–1429 [CrossRef] [PubMed].
    [Google Scholar]
  6. Del Pozo J. L., Patel R.. ( 2009;). Clinical practice. Infection associated with prosthetic joints. N Engl J Med 361: 787–794 [CrossRef] [PubMed].
    [Google Scholar]
  7. Donlan R. M., Costerton J. W.. ( 2002;). Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 15: 167–193 [CrossRef] [PubMed].
    [Google Scholar]
  8. Edwards A. M.. ( 2012;). Phenotype switching is a natural consequence of Staphylococcus aureus replication. J Bacteriol 194: 5404–5412 [CrossRef] [PubMed].
    [Google Scholar]
  9. Evans D. J., Brown M. R., Allison D. G., Gilbert P.. ( 1990;). Susceptibility of bacterial biofilms to tobramycin: role of specific growth rate and phase in the division cycle. J Antimicrob Chemother 25: 585–591 [CrossRef] [PubMed].
    [Google Scholar]
  10. Kaplan J. B., Izano E. A., Gopal P., Karwacki M. T., Kim S., Bose J. L., Bayles K. W., Horswill A. R.. ( 2012;). Low levels of β-lactam antibiotics induce extracellular DNA release and biofilm formation in Staphylococcus aureus. MBiol 3: e00198-0012 [CrossRef] [PubMed].
    [Google Scholar]
  11. Mah T. F., Pitts B., Pellock B., Walker G. C., Stewart P. S., O'Toole G. A.. ( 2003;). A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance. Nature 426: 306–310 [CrossRef] [PubMed].
    [Google Scholar]
  12. Meije Y., Almirante B., Del Pozo J. L., Martín M. T., Fernández-Hidalgo N., Shan A., Basas J., Pahissa A., Gavaldà J.. ( 2014;). Daptomycin is effective as antibiotic-lock therapy in a model of Staphylococcus aureus catheter-related infection. J Infect 68: 548–552 [CrossRef] [PubMed].
    [Google Scholar]
  13. Miró J. M., Entenza J. M., Del Río A., Velasco M., Castañeda X., Garcia de la Mària C., Giddey M., Armero Y., Pericàs J. M., other authors. ( 2012;). High-dose daptomycin plus fosfomycin is safe and effective in treating methicillin-susceptible and methicillin-resistant Staphylococcus aureus endocarditis. Antimicrob Agents Chemother 56: 4511–4515 [CrossRef] [PubMed].
    [Google Scholar]
  14. Ng M., Epstein S. B., Callahan M. T., Piotrowski B. O., Simon G. L., Roberts A. D., Keiser J. F., Kaplan J. B.. ( 2014;). Induction of MRSA biofilm by low-dose β-lactam antibiotics: specificity, prevalence and dose-response effects. Dose Response 12: 152–161 [CrossRef] [PubMed].
    [Google Scholar]
  15. Nguyen D., Joshi-Datar A., Lepine F., Bauerle E., Olakanmi O., Beer K., McKay G., Siehnel R., Schafhauser J., other authors. ( 2011;). Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria. Science 334: 982–986 [CrossRef] [PubMed].
    [Google Scholar]
  16. Odenholt I.. ( 2001;). Pharmacodynamic effects of subinhibitory antibiotic concentrations. Int J Antimicrob Agents 17: 1–8 [CrossRef] [PubMed].
    [Google Scholar]
  17. Siala W., Mingeot-Leclercq M. P., Tulkens P. M., Hallin M., Denis O., Van Bambeke F.. ( 2014;). Comparison of the antibiotic activities of daptomycin, vancomycin, and the investigational fluoroquinolone delafloxacin against biofilms from Staphylococcus aureus clinical isolates. Antimicrob Agents Chemother 58: 6385–6397 [CrossRef] [PubMed].
    [Google Scholar]
  18. Singh R., Ray P., Das A., Sharma M.. ( 2010;). Penetration of antibiotics through Staphylococcus aureus and Staphylococcus epidermidis biofilms. J Antimicrob Chemother 65: 1955–1958 [CrossRef] [PubMed].
    [Google Scholar]
  19. Stewart P. S., Costerton J. W.. ( 2001;). Antibiotic resistance of bacteria in biofilms. Lancet 358: 135–138 [CrossRef] [PubMed].
    [Google Scholar]
  20. Suci P. A., Mittelman M. W., Yu F. P., Geesey G. G.. ( 1994;). Investigation of ciprofloxacin penetration into Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 38: 2125–2133 [CrossRef] [PubMed].
    [Google Scholar]
  21. Titécat M., Senneville E., Wallet F., Dezèque H., Migaud H., Courcol R. J., Loïez C.. ( 2013;). Bacterial epidemiology of osteoarticular infections in a referent center: 10-year study. Orthopaedics Traumatol Surg Res 99: 653–658 [CrossRef] [PubMed].
    [Google Scholar]
  22. Zhang L., Mah T. F.. ( 2008;). Involvement of a novel efflux system in biofilm-specific resistance to antibiotics. J Bacteriol 190: 4447–4452 [CrossRef] [PubMed].
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.000125
Loading
/content/journal/jmm/10.1099/jmm.0.000125
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error