Carlos M. Ardila

Antimicrobial Susceptibility of Moxifloxacin Against Gram-Negative Enteric Rods From Colombian Patients With Chronic Periodontitis

BACKGROUND Gram-negative enteric rods were associated with periodontal diseases in several populations. The association between enteric and putative periodontal pathogens has received little attention in the literature. The present investigation determined the occurrence and in vitro antimicrobial susceptibility of isolates of Gram-negative enteric rods from Colombian patients with chronic periodontitis. METHODS Clinical parameters and the in vitro antimicrobial sensitivity of isolates of Gram-negative enteric rods were examined in 76 patients with chronic periodontitis in Medellin, Colombia. Subgingival samples were processed using culture and biochemical tests for the detection of periodontal and superinfecting pathogens. Selected colonies of Gram-negative enteric rods from pure cultures were used to test the susceptibility to amoxicillin/clavulanic acid, ciprofloxacin, and moxifloxacin. Chi-square and Mann-Whitney tests were used to determine differences in clinical variables versus the presence or absence of Gram-negative enteric rods. RESULTS Klebsiella pneumoniae was found in 12 patients, Pseudomonas aeruginosa was found in four patients, and three other species were recovered with a lower prevalence. Men (38.75%) tended to harbor more of the studied organisms than women (17.7%) (P = 0.04). Gram-negative enteric rods in periodontal pockets correlated positively with the presence of Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, and Prevotella intermedia/nigrescens (respectively, r = 0.66, 0.31, and 0.32; P <0.001). All superinfecting organisms demonstrated a high susceptibility to moxifloxacin and ciprofloxacin but exhibited a variable susceptibility to amoxicillin/clavulanic acid. CONCLUSIONS This study found high levels of Gram-negative enteric rods in patients with chronic periodontitis. Moxifloxacin and ciprofloxacin appeared capable of eradicating these organisms from periodontal pockets. Its good activity against Gram-negative enteric rods and periodontopathogens suggests the potential use of moxifloxacin as an adjunctive antibiotic in the treatment of mixed periodontal infections.

Comparison of serum amyloid A protein and C-reactive protein levels as inflammatory markers in periodontitis

Purpose The purpose of this study was to compare serum amyloid A (SAA) protein levels with high-sensitive C-reactive protein (hs-CRP) levels as markers of systemic inflammation in patients with chronic periodontitis. The association of serum titers of antibodies to periodontal microbiota and SAA/hs-CRP levels in periodontitis patients was also studied. Methods A total of 110 individuals were included in this study. Patients were assessed for levels of hs-CRP and SAA. Nonfasting blood samples were collected from participants at the time of clinical examination. The diagnosis of adipose tissue disorders was made according to previously defined criteria. To determine SAA levels, a sandwich enzyme-linked immunosorbent assay was utilized. Paper points were transferred to a sterile tube to obtain a pool of samples for polymerase chain reaction processing and the identification of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Tannerella forsythia. The serum level of IgG1 and IgG2 antibodies to P. gingivalis, A. actinomycetemcomitans, and T. forsythia was also determined. Results SAA and hs-CRP levels were higher in periodontitis patients than in controls (P<0.05). In bivariate analysis, high levels of hs-CRP (>3 mg/L) and SAA (>10 mg/L) were significantly associated with chronic periodontitis (P=0.004). The Spearman correlation analysis between acute-phase proteins showed that SAA positively correlated with hs-CRP (r=0.218, P=0.02). In the adjusted model, chronic periodontitis was associated with high levels of SAA (odds ratio [OR], 5.5; 95% confidence interval [CI], 1.6-18.2; P=0.005) and elevated hs-CRP levels (OR, 6.1, 95% CI, 1.6-23.6; P=0.008). Increased levels of serum IgG2 antibodies to P. gingivalis were associated with high levels of SAA (OR, 3.6; 95% CI, 1.4-8.5; P=0.005) and high concentrations of hs-CRP (OR, 4.3; 95% CI, 1.9-9.8; P<0.001). Conclusions SAA and hs-CRP concentrations in patients with chronic periodontitis are comparably elevated. High serum titers of antibodies to P. gingivalis and the presence of periodontal disease are independently related to high SAA and hs-CRP levels. Graphical Abstract

Adjunctive moxifloxacin in the treatment of generalized aggressive periodontitis patients: clinical and microbiological results of a randomized, triple-blind and placebo-controlled clinical trial

AIM The aim of the present study was to evaluate the clinical and microbiological efficacy of moxifloxacin (MOX) in one-stage scaling and root planing (SRP) in treating generalized aggressive periodontitis (GAgP). MATERIALS AND METHODS Forty subjects were randomly allocated to two treatment groups. The two treatment groups consisted of SRP combined with systemically administered MOX at the dosage of 400 mg once daily for 7 days or SRP + placebo once daily for 7 days. Subgingival plaque samples were analysed for cultivable bacteria. RESULTS Both groups resulted in significant reduction of probing depth (PD) and clinical attachment level (CAL) compared with baseline (p < 0.0001), and this difference was maintained at 6 months from baseline in both groups. However, subjects receiving MOX showed the greatest improvements CAL, and PD. Subjects in both groups at 6 months displayed the greatest reduction from baseline in frequency of sites with PD ≥ 6 mm (p < 0.001), favouring the MOX group. Adjunctive antibiotic protocol reduced subgingival Aggregatibacter actinomycetemcomitans to undetectable levels, after 3 and 6 months, and there was a significant reduction in the levels of Porphyromonas gingivalis and Tannerella forsythia in the MOX group compared to the placebo group. CONCLUSIONS The results from this study suggest that moxifloxacin as and adjunct to one-stage full-mouth SRP leads to a better clinical and microbiological advantages compared to mechanical treatment.

Tannerella forsythia is associated with increased levels of atherogenic low density lipoprotein and total cholesterol in chronic periodontitis

Background Accumulating evidence suggests that acute and chronic infections with periodontopathogens are associated with an increased risk of cardiovascular disease. The objective of this study was to assess whether Tanerella forsythia and Porphyromonas gingivalis are associated with increased levels of atherogenic low-density lipoprotein (LDL), high-density lipoprotein, total cholesterol (TC), triglycerides and body mass index (BMI) in chronic periodontitis patients. Material and Methods Medical history and clinical and radiographic examination were conducted in 80 chronic periodontitis patients and 28 healthy individuals. Fasting blood samples were drawn for the measurement of the parameters of dyslipidemia. Anthropometric measurements such as height in meters and weight in kilograms were recorded. Both periodontitis and control subjects were asked to answer a questionnaire with regard to their socio-demographic and smoking status. The presence of T. forsythia, and P. gingivalis was detected using primers designed to target the respective 16S rRNA gene sequences. Results The occurrence of T. forsythia and P. gingivalis was higher in the group of subjects with periodontitis. Superior levels of triglycerides were observed in chronic periodontitis patients compared to healthy individuals. High levels of TC in periodontitis persons were significantly associated with increased bleeding on probing. Greater mean levels of TC and LDL were shown in the presence of T. forsythia (P<0.05). Likewise, higher proportions of patients with BMI ≥25 kg/m2 related with T. forsythia (P<0.05). T. forsythia was a significant discriminating factor in the multivariate linear regression model emerging as significant explanatory of increased levels of TC (β=17,879, 95% CI = 4,357-31,401; p=0.01) and LDL (β=17,162, 95% CI= 4,009-30,316; p=0.01). Conclusions Higher levels of serum total cholesterol and LDL were observed in the occurrence of T. forsythia and the presence of this periodontopathogen may increase the atherogenic potency of low-density lipoprotein that may augment the risk for atherosclerosis in periodontal disease patients. Key words:Periodontitis, dyslipidemia, Tannerella forsythia, cardiovascular disease.

Relationship between Gram negative enteric rods, Aggregatibacter actinomycetemcomitans, and clinical parameters in periodontal disease.

Background: The association between Gram negative enteric rods and Aggregatibacter actinomycetemcomitans in periodontal diseases has received little attention in the literature. The objective of this study was to explore the relationship between these organisms and clinical parameters of periodontal disease. Materials and Methods: Clinical parameters and occurrence of Gram-negative enteric rods and A. actinomycetemcomitans were examined in 76 patients with chronic periodontitis. Chi-square and Mann-Whitney tests were used to determine differences in clinical variables versus the presence or absence of both microorganisms. Correlation among both organisms and clinical data were determined using Spearman rank correlation coefficient. Results: Gram-negative enteric rods and A. actinomycetemcomitans were detected in 20 (26.3%) and 18 (23.7%) individuals, respectively. A total of 14 (18.4%) patients harbored both microorganisms studied. There were significantly positive correlations between enteric rods and presence of A. actinomycetemcomitans (r=0.652, P<0.0001). Both microorganisms were significant and positively correlated with probing depth (PD), clinical attachment level, and bleeding on probing (P<0.0001). The mean PD (mm) of the sampled sites was significantly deeper in patients with presence of A. actinomycetemcomitans and Gram-negative enteric rods. Conclusion: The results of the present study suggest a strong positive correlation between Gram-negative enteric rods and A. actinomycetemcomitans in the population studied. This finding must be taken into account when considering the best therapeutic approach, including the utilization of antimicrobials. The adverse clinical outcomes observed in presence of these microorganisms could have implications in the pathogenesis of periodontal disease and a possible impact on outcomes after treatment.

Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans IgG Subclass Antibody Levels as Immunological Risk Indicators of Chronic Periodontitis: A Multilevel Approach

Los niveles de anticuerpos en algunos patogenos periodontales estan asociados con mayores niveles de marcadores inflamatorios. El proposito de este estudio fue examinar la contribucion relativa de inmunoglobulina serica G (IgG) factores de nivel de anticuerpos de subclase y factores locales en la profundidad del sondaje en periodontitis cronica. Se tomaron muestras de suero de 444 pacientes con diagnostico de periodontitis moderada y grave y de 223 sujetos de control. Se determinaron los titulos de anticuerpos IgG subclase a Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa) y Tanerella forsythia (Tf) mediante inmunoensayo indirecto (ELISA). La contribucion relativa de los pacientes, los dientes, y el sitio asociado a los parametros en la profundidad de sondaje fueron evaluados con un modelo multinivel jerarquico. Los resultados indicaron que los pacientes con periodontitis tenian niveles detectables de IgG1 e IgG2. Altos niveles de anticuerpos IgG1 e IgG2 contra Aa fueron observados en 132 y 142 pacientes con periodontitis, respectivamente. Niveles altos de anticuerpos IgG1 e IgG2 contra Pg fueron detectados en 141 y 138 en pacientes con periodontitis respectivamente, y niveles altos de anticuerpos IgG1 e IgG2 contra Tf se produjeron en 121 y 136 pacientes con periodontitis, respectivamente. La mayor parte de la varianza se atribuyo a nivel de sitio (48%). El analisis multinivel asociados a profundidad de sondaje con factores relacionados a los sujetos, anticuerpos (suero IgG1 e IgG2 Aa y Pg), factores de los dientes (tipo) y los factores del sitio (localizacion mesial - distal y sangrado al sondaje). Anticuerpos elevados de suero IgG1 e IgG2 Aa y Pg (factores de los sujetos) reflejan el estado de la enfermedad periodontal destructiva.

Influence of the Socio-Economic Context on Self-Reported Gingival Bleeding in Individuals of Ethnic Minority Groups: A Multilevel Analysis

Introduction: To evaluate the influence of the socio-economic context on self-reported gingival bleeding (SRGB) in individuals of ethnic minority groups (IEG). Methods: Data from the 2007 National Public Health Survey in Colombia were collected. A multiple-stage stratified sampling was used. Data from 34.843 subjects were collected through interviews. The influence of socio-economic factors on SRGB in IEG was investigated with logistic and multilevel regression analyses. Results: Out of 34.843 subjects studied, a total of 6.440 individuals were members of ethnic minority groups. SRGB was observed in approximately 5% of IEG. There was a significant difference between IEG and subjects of the rest of the sample (28.403 subjects) regarding SRGB, elementary and high school education, Gross Domestic Product (GDP), Human Development Index (HDI) and Unmet Basic Needs Index (UBNI) disfavouring IEG (P<0.05). The logistic model showed that SRGB was associated with IEG (P<0.001). This association persisted after controlling for confounders. A total of 33 Colombian states (level 2) and 6.440 members (level 1) of ethnic minority groups were included in the multilevel analisys; this model showed that the variance on SRGB was statistically significant at level 1 and 2. However, the variation at IEG level (35%) was smaller than the variation between states (65%) in the multilevel multivariate model. Conclusions: SRGB was higher in IEG. Also, GDP, HDI and UBNI were unfavourable factors in the members of ethnic minority groups. Considering these detriment factors and the higher variation between states, this study suggests that socio-economic context affects significantly SRGB in IEG.

Clinical Factors Influencing the Efficacy of Systemic Moxifloxacin in the Therapy of Patients With Generalized Aggressive Periodontitis: A Multilevel Analysis From a Clinical Trial

Background: It has been reported that clinical results of mechanical periodontal treatment could differ between subjects and among different sites of the tooth in the patient. The objective of this multilevel analysis is to investigate clinical factors at subject and sites of the tooth that influence variations in clinical attachment (CAL) increase and probing depth (PD) diminution of adjunctive moxifloxacin (MOX) at six months post-treatment in generalized aggressive periodontitis. Methods: This clinical trial included 40 patients randomly distributed to two therapy protocols: scaling and root planing alone or combined with MOX. Multilevel linear models for continuous variables were formulated to evaluate the clinical impact of the hierarchical configuration of periodontal data. Results: Six months following therapy, the divergences between both protocols were statistically significant in PD diminution and CAL increase, favouring the MOX therapy (p<0.001). Besides, the multilevel analysis revealed that adjunctive MOX at the subject level, non-molar and the interaction non-molar x MOX at the tooth level, interproximal sites and the interaction interproximal sites x MOX at the site level, were statistically significant factors in determining CAL increase and PD diminution. Conclusions: The main cause of variability in CAL gain and PD reduction following adjunctive MOX was attributable to the tooth level. Adjunctive MOX and their interactions with non-molar and interproximal sites showed higher clinical benefits at the tooth and site levels which could be essential for PD reduction and CAL gain in generalized aggressive periodontitis subjects.

Benefits of adjunctive moxifloxacin in generalized aggressive periodontitis: a subgroup analyses in Aggregatibacter actinomycetemcomitans-positive/negative patients from a clinical trial

AIM The aim of the present study was to evaluate the influence of the baseline detection of Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) on the clinical outcomes of moxifloxacin (MOX) as an adjunct to full-mouth scaling and root planing (SRP) in generalized aggressive periodontitis (GAgP). METHODS Forty patients were randomly distributed to two therapy protocols: SRP + placebo or SRP combined with MOX. A. actinomycetemcomitans was detected using culture methods. The significance of the treatment option (MOX or SRP + placebo) on the dependent variables (probing depth [PD] and clinical attachment level [CAL]), considering the interaction with the baseline detection of A. actinomycetemcomitans, was estimated. RESULTS MOX therapy led to a higher significant PD reduction and CAL gain in A. actinomycetemcomitans-positive patients at baseline. In A. actinomycetemcomitans-positive patients, the reduction of sites ≥5 mm was higher in the MOX group. A. actinomycetemcomitans was not present in sites with PD ≥6 mm in the MOX group. The interactions of A. actinomycetemcomitans and MOX were significantly associated with CAL gain and PD reduction at 6 months. CONCLUSIONS Adjunctive MOX trended toward better clinical responses in A. actinomycetemcomitans-positive patients at baseline. These results suggest that A. actinomycetemcomitans at baseline might modify the effect of adjunctive MOX in GAgP.

Association between immunoglobulin G1 against Tannerella forsythia and reduction in the loss of attachment tissue

Purpose To evaluate whether the levels of immunoglobulin G (IgG) antibody to Tanerella forsythia are associated with periodontal status. Methods Patients with a diagnosis of chronic periodontitis were considered candidates for the study; thus 80 chronic periodontitis patients and 28 healthy persons (control group) were invited to participate in this investigation. The presence of T. forsythia was detected by polymerase chain reaction (PCR) analysis using primers designed to target the respective 16S rRNA gene sequences. Peripheral blood was collected from each subject to identify the IgG1 and IgG2 serum antibodies against T. forsythia. All microbiological and immunological laboratory processes were completed blindly, without awareness of the clinical status of the study patients or of the periodontal sites tested. Results The bivariate analysis showed that lower mean levels of clinical attachment level (CAL) and probing depth were found in the presence of the IgG1 antibody titers against whole-cell T. forsythia; however, only the difference in CAL was statistically significant. In the presence of the IgG2 antibody titers against whole-cell T. forsythia, the periodontal parameters evaluated were higher but they did not show statistical differences, except for plaque. The unadjusted linear regression model showed that the IgG1 antibody against whole-cell T. forsythia in periodontitis patients was associated with a lower mean CAL (β=-0.654; 95% confidence interval [CI], -1.27 to -0.28; P<0.05). This statistically significant association remained after adjusting for possible confounders (β=-0.655; 95% CI, -1.28 to -0.29; P<0.05). On the other hand, smoking was a statistically significant risk factor in the model (β=0.704; 95% CI, 0.24 to 1.38; P<0.05). Conclusions Significantly lower mean levels of CAL were shown in the presence of the IgG1 antibody titers against whole-cell T. forsythia in periodontitis patients. Thus, the results of this study suggest that IgG1 antibody to T. forsythia may have been a protective factor from periodontitis in this sample. Graphical Abstract