Resumen de Antibiotic Resistance in Human Chronic Periodontitis Microbiota
Background: Patients with chronic periodontitis (CP) may yield multiple species of putative periodontal bacterial pathogens that vary in their antibiotic drug susceptibility. This study determines the occurrence of in vitro antibiotic resistance among selected subgingival periodontal pathogens in patients with CP.
Methods: Subgingival biofilm specimens from inflamed deep periodontal pockets were removed before treatment from 400 adults with CP in the United States. The samples were cultured, and selected periodontal pathogens were tested in vitro for susceptibility to amoxicillin at 8 mg/L, clindamycin at 4 mg/L, doxycycline at 4 mg/L, and metronidazole at 16 mg/L, with a post hoc combination of data for amoxicillin and metronidazole. Gram-negative enteric rods/pseudomonads were subjected to ciprofloxacin disk-diffusion testing.
Results: Overall, 74.2% of the patients with CP revealed subgingival periodontal pathogens resistant to at least one of the test antibiotics. One or more test species, most often Prevotella intermedia/nigrescens, Streptococcus constellatus, or Aggregatibacter actinomycetemcomitans, were resistant in vitro to doxycycline, amoxicillin, metronidazole, or clindamycin, in 55%, 43.3%, 30.3%, and 26.5% of the patients with CP, respectively. Fifteen percent of patients harbored subgingival periodontal pathogens resistant to both amoxicillin and metronidazole, which were mostly either S. constellatus (45 individuals) or ciprofloxacin-susceptible strains of Gram-negative enteric rods/pseudomonads (nine individuals).
Conclusions: Patients with CP in the United States frequently yielded subgingival periodontal pathogens resistant in vitro to therapeutic concentrations of antibiotics commonly used in clinical periodontal practice. The wide variability found in periodontal pathogen antibiotic-resistance patterns should concern clinicians empirically selecting antibiotic treatment regimens for patients with CP.
During the past 35 years, the issue of systemic antibiotics in periodontal therapy has evolved from initial research and controversy1,2 to a scientific consensus recognizing their beneficial impact in the treatment of both aggressive (AgP) and chronic (CP) forms of human periodontitis.3-9 However, many aspects related to the selection and administration of systemic periodontal antibiotic therapy remain unresolved.4 At present, most systemic periodontal antibiotic treatment regimens appear to be empirically prescribed by clinicians without guidance from a microbiologic analysis of subgingival bacterial biofilm populations,10 although patients with periodontitis frequently yield multiple species of periodontal pathogens that potentially vary in their antibiotic drug resistance.5 One of the risks of this approach is that an antibiotic drug may be selected to which the targeted periodontal pathogens are intrinsically resistant or poorly susceptible, compromising the efficacy of the antimicrobial therapy and increasing the likelihood of a clinical treatment failure. A position paper of the American Academy of Periodontology5 expressed concern about this potential adverse outcome and advocated evaluation of antimicrobial susceptibility patterns of suspected periodontal pathogens before administration of systemic periodontal antibiotic therapy. In contrast, a European workshop on antimicrobial agents in periodontics concluded that, �Since the antimicrobial profiles of most putative periodontal pathogens are quite predictable, antimicrobial susceptibility testing seems to have no benefit.�11 Relative to this, recent data document antibiotic resistance to be rare among fresh subgingival clinical isolates of periodontal pathogens tested from patients with periodontitis residing in northern European countries, where antibiotic usage is generally restricted and infrequent.12 However, markedly higher levels of periodontal pathogen antibiotic resistance have been reported in other geographic regions of the world, such as in Spain in southern Europe and Columbia in South America, where there are less controlled antibiotic access and greater non-supervised consumption of these drugs than in northern Europe.13,14 In the United States, relatively little recent data exist on the extent to which antibiotic resistance occurs among subgingival periodontal pathogens in patients with periodontitis.15 As a result, it is not clear whether patients with periodontitis in the United States harbor subgingival periodontal pathogens with predictable antimicrobial susceptibility profiles or, instead, present with a more variable occurrence of sensitivity and resistance to antibiotics. To address this issue, the purpose of this study is to examine the occurrence of in vitro antibiotic resistance of selected periodontal pathogens in patients with CP in the United States to therapeutic antibiotic breakpoint concentrations of clindamycin, doxycycline, amoxicillin, and metronidazole, as well as to both amoxicillin and metronidazole.
