tetracycline and Bacteroidaceae-Infections

Both systemic and topical antibiotics are increasingly used in the management of periodontal infections. Whilst these drugs are used mostly on an empirical basis, some contend that rational use of antibiotics should be the norm due to their wide abuse and consequential global emergence of antibiotic resistance organisms. Here we review the rationale and principles of antimicrobial therapy, treatment goals, drug delivery routes and various antibiotics that are used in the management of periodontal diseases. The pros and cons of systemic and local antibiotic therapy are described together with practical guidelines for their delivery. The available data indicate, in general, that mechanical periodontal treatment alone is adequate to ameliorate or resolve the clinical condition in most cases, but adjunctive antimicrobial agents, delivered either locally or systemically, can enhance the effect of therapy in specific situations. This is particularly true for aggressive (early onset) periodontitis, in patients with generalised systemic disease that may affect host resistance and in case of poor response to conventional mechanical therapy. Locally delivered antibiotics together with mechanical debridement are indicated for non-responding sites of focal infection or in localised recurrent disease. After resolution of the periodontal infection, the patient should be placed on an individually tailored maintenance care programme. Optimal plaque control by the patient is of paramount importance for a favourable clinical and microbiological response to any form of periodontal therapy.

Topics: Actinobacillus Infections; Administration, Oral; Administration, Topical; Aggregatibacter actinomycetemcomitans; Anti-Bacterial Agents; Anti-Infective Agents, Local; Bacteroidaceae Infections; Chlorhexidine; Humans; Metronidazole; Periodontitis; Porphyromonas gingivalis; Tetracycline

To investigate mechanisms of reduced susceptibility to commonly used antibiotics in Prevotella cultured from patients with cystic fibrosis (CF), patients with invasive infection and healthy control subjects and to determine whether genotype can be used to predict phenotypic resistance.. The susceptibility of 157 Prevotella isolates to seven antibiotics was compared, with detection of resistance genes (cfxA-type gene, ermF and tetQ), mutations within the CfxA-type β-lactamase and expression of efflux pumps.. Prevotella isolates positive for a cfxA-type gene had higher MICs of amoxicillin and ceftazidime compared with isolates negative for this gene (P < 0.001). A mutation within the CfxA-type β-lactamase (Y239D) was associated with ceftazidime resistance (P = 0.011). The UK CF isolates were 5.3-fold, 2.7-fold and 5.7-fold more likely to harbour ermF compared with the US CF, UK invasive and UK healthy control isolates, respectively. Higher concentrations of azithromycin (P < 0.001) and clindamycin (P < 0.001) were also required to inhibit the growth of the ermF-positive isolates compared with ermF-negative isolates. Furthermore, tetQ-positive Prevotella isolates had higher MICs of tetracycline (P = 0.001) and doxycycline (P < 0.001) compared with tetQ-negative isolates. Prevotella spp. were also shown, for the first time, to express resistance nodulation division (RND)-type efflux pumps.. This study has demonstrated that Prevotella isolated from various sources harbour a common pool of resistance genes and possess RND-type efflux pumps, which may contribute to tetracycline resistance. The findings indicate that antibiotic resistance is common in Prevotella spp., but the genotypic traits investigated do not reflect phenotypic antibiotic resistance in every instance.

Topics: Amino Acid Substitution; Anti-Bacterial Agents; Bacteroidaceae Infections; beta-Lactamases; Case-Control Studies; Ceftazidime; Cephalosporin Resistance; Cystic Fibrosis; Drug Resistance, Microbial; Genes, Bacterial; Genotype; Humans; Microbial Sensitivity Tests; Mutation; Prevotella; Tetracycline; Tetracycline Resistance; United Kingdom

Head-and-neck infections often involve anaerobes such as Prevotella species. Aim of the present study was to assess the evolution and the factors associated with resistance in Prevotella species to penicillin, clindamycin, metronidazole, tetracycline and β-lactams/β-lactamase inhibitors (BL/BLIs). In total, 192 Prevotella strains, isolated from patients with oral and head-and-neck infections, were evaluated. Common isolates were Prevotella intermedia and Prevotella melaninogenica within the pigmented species as well as Prevotella oris and Prevotella oralis group within the non-pigmented species. Overall resistance was 43.2% for penicillin, 10.9% for clindamycin, 0% for metronidazole. Nonsusceptibility to tetracycline was 29.1% without significant differences in resistance rates between pigmented and other species. Penicillin resistant strains were β-lactamase positive. From 2003-2004 to 2007-2009, penicillin resistance rates increased about four-fold (from 15.4% to 60.6%). Clindamycin resistance did not show evolution, whereas tetracycline nonsusceptibility decreased from 43.3% in 2003-2004 to 20.7% in 2007-2009. Except for one (0.5%) P. oralis strain with intermediate susceptibility to BL/BLIs, the other strains were susceptible to the agents. In conclusion, in Prevotella strains from patients with head-and-neck infections, the resistance rate to penicillin increased, that to clindamycin remained stable and the nonsusceptibility rate to tetracycline decreased during the period. Activity against >99% of Prevotella strains was observed with metronidazole and BL/BLIs. The penicillin resistance and tetracycline nonsusceptibility were associated with the year of study, national antibiotic consumption and possibly with previous treatment (for tetracycline). The evolution of penicillin resistance in Prevotella strains was highly dynamic.

Topics: Anti-Bacterial Agents; Bacteroidaceae Infections; Bulgaria; Clindamycin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Penicillins; Prevotella; Tetracycline

The recA gene in Porphyromonas gingivalis is involved in DNA repair. To further elucidate the importance of the recA locus in the pathogenesis of P. gingivalis, we assessed its ability for expression in an animal host. The promoterless xa-tetA(Q)2 cassette was used in heterodiploid mutants to study recA promoter activity during infection. P. gingivalis FLL118.1 had the xa-tetA(Q)2 cassette under the control of recA promoter whereas P. gingivalis FLL119 had the cassette in the opposite orientation. xa encodes a bifunctional xylosidase/arabinosidase enzyme (XA) and the tetA(Q)2 gene product confers tetracycline resistance. Intramuscular infection in a mouse model allowed the recovery of the bacteria from inguinal lymph nodes. Infusion of tetracycline in the animals permitted the enrichment P. gingivalis FLL118.1 over the wild-type strain, during a mixed infection. The xylosidase activity of FLL118.1 could be detected on agar plates in the presence of 5-methylumbellifiry-beta-D-xyloside. No such enrichment for xylosidase activity was detected when the mixture of P. gingivalis W83 and P. gingivalis FLL119 was used to infect the mouse or cultured in vitro. These results indicated that recA promoter was transcriptionally active during the infection of the murine host and further support the importance of this locus during the P. gingivalis infection process.

Topics: Animals; Anti-Bacterial Agents; Antiporters; Bacterial Proteins; Bacteroidaceae Infections; Chromosome Mapping; Diploidy; Disease Models, Animal; DNA Repair; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Enzymologic; Glycoside Hydrolases; Lymph Nodes; Mice; Mice, Inbred BALB C; Mutation; Phenotype; Polymerase Chain Reaction; Porphyromonas gingivalis; Promoter Regions, Genetic; Rec A Recombinases; Tetracycline; Tetracycline Resistance; Transcription, Genetic; Virulence; Xylosidases

Gram-negative anaerobes belonging to the genera Fusobacterium, Prevotella and Porphyromonas were investigated for the presence of tetQ and ermF, which have been shown to be spread by conjugal elements. One hundred isolates from either sites of infection or various body sites in healthy subjects were studied. PCR was used to detect tetQ, and DNA-DNA hybridization studies on EcoRI chromosomal digests were undertaken to detect the presence of tetQ and ermF. Antibiotic sensitivity assays were performed on selected isolates to detect tetracycline, erythromycin and penicillin resistance. Twenty Fusobacterium isolates lacked tetQ, and were tetracycline sensitive. Twenty per cent of Prevotella spp. isolates both from clinical specimens and from healthy subjects were found to possess tetQ. Of 20 Porphyromonas isolates tested, one (Porphyromonas levii) from a case of bacterial vaginosis was shown to possess tetQ in the chromosome. The presence of tetQ was always associated with tetracycline resistance. Four isolates of Prevotella melaninogenica and one isolate of Prevotella were ermF-positive, although expression of erythromycin resistance was not consistently associated with detection of this gene. Antibiotic resistance phenotypes of Prevotella isolates were shown to be related to specific chromosomal restriction patterns by hybridization studies: tetracycline resistance and tetracycline/erythromycin resistance are conferred by Bacteroides tetracycline-resistant ERL elements, whereas the tetracycline/penicillin resistance phenotype could be due to spread of elements identified in Prevotella only. Tetracycline/erythromycin-resistant and tetracycline/erythromycin/penicillin-resistant P. melaninogenica isolates were found in this study. It appeared that the presence of tetQ and ermF in Bacteroides and Prevotella contributed to the persistence of antibiotic resistance isolates within the host and to potential spread to other organisms through conjugal elements.

Topics: Anti-Bacterial Agents; Bacteroidaceae Infections; Drug Resistance, Microbial; Erythromycin; Fusobacterium; Fusobacterium Infections; Genes, Bacterial; Humans; Microbial Sensitivity Tests; Nucleic Acid Hybridization; Penicillins; Polymerase Chain Reaction; Porphyromonas; Prevotella; Tetracycline; Tetracycline Resistance

A study of the predominant microflora in active sites of noma (cancrum oris) lesions was carried out in eight noma patients 3-15 years of age in Sokoto State in northwestern Nigeria. Paper point sampling and conventional anaerobic microbiologic techniques were used. Fusobacterium necrophorum was recovered from 87.5% of the noma lesions. Oral microorganisms included Prevotella intermedia, alpha-hemolytic streptococci, and Actinomyces spp. which were isolated from 75.0%, 50.0%, and 37.5% of the patients, respectively. Peptostreptococcus micros, Veillonella parvula, Staphylococcus aureus, and Pseudomonas spp. were each recovered from one lesion. The F. necrophorum and P. intermedia isolates were tested for antibiotic sensitivity to clindamycin, tetracycline, metronidazole, and penicillin using the E-test, and all strains were observed to be sensitive to all of the antibiotics tested with the exception of one strain of P. intermedia, which showed resistance to penicillin. The first reported isolation from human noma lesions of F. necrophorum, a pathogen primarily associated with animal diseases, may have important etiologic and animal transmission implications.

Topics: Adolescent; Anti-Bacterial Agents; Bacteroidaceae Infections; Child; Child, Preschool; Clindamycin; Culture Media; Drug Resistance, Microbial; Fusobacterium Infections; Fusobacterium necrophorum; Humans; Metronidazole; Microbial Sensitivity Tests; Nigeria; Noma; Nutrition Disorders; Penicillins; Prevotella intermedia; Tetracycline

Tissue remodeling is a dynamic state in which a balance is achieved between the proteolytic breakdown and synthesis of the extracellular matrix. Type I collagen is a major component of the gingival connective tissue (GCT) and the periodontal ligament (PDL) throughout development, while type XII collagen has been found in the mature forms of these tissues. The purpose of this study was to investigate the effects of periodontitis on the expression of type I and XII collagen and subsequently to investigate the effects of doxycycline (DOXY) and chemically modified non-antimicrobial tetracycline (CMT-1) on the expression of these molecules in this model. Adult barrier-raised male Sprague-Dawley rats were inoculated with Porphyromonas gingivalis obtained from humans to create the experimental periodontitis. The animals with the P. gingivalis-induced periodontitis were then split into the following groups: Group A served as infected untreated controls (PGI group); group B was treated with doxycycline (DOXY group); and group C was treated with chemically modified tetracycline-1 (CMT-1 group). Group D contained uninfected animals that served as uninfected controls (NIC group). The expression of type I and XII collagen mRNAs was examined by in situ hybridization in each group, with the co-expression of these molecules representing mature and functional gingival connective tissue. In the NIC group, cells hybridized with digoxygenine-labeled cDNA probes encoding rat alpha2(I) or alpha1(XII) collagens were found distributed uniformly throughout the periodontal connective tissue. The PGI group showed little hybridization in the areas of infection, while both the DOXY and CMT-1 groups showed co-expression of the alpha2(I) and alpha1(XII) probes in the GCT and coronal part of the PDL. This study demonstrates that doxycycline and CMT-1 moderate or reduce the inhibitory effects of periodontal infection on the expression of type I and type XII collagen mRNAs. These results suggest that doxycycline and a form of non-antimicrobial tetracycline, chemically modified tetracycline-1, can reduce periodontal destruction by reversing the inhibitory effect of periodontal infection on collagen synthesis.

Topics: Affinity Labels; Animals; Anti-Bacterial Agents; Bacteroidaceae Infections; Collagen; Connective Tissue; Digoxigenin; Disease Models, Animal; DNA Probes; DNA, Complementary; Doxycycline; Extracellular Matrix; Gene Expression Regulation; Gingiva; In Situ Hybridization; Male; Matrix Metalloproteinase Inhibitors; Periodontal Ligament; Periodontitis; Porphyromonas gingivalis; Protease Inhibitors; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tetracycline

Topics: Animals; Bacteroidaceae Infections; Bone Resorption; Collagenases; Doxycycline; Enzyme Activation; Gelatinases; Gingiva; Male; Matrix Metalloproteinase Inhibitors; Metalloendopeptidases; Pancreatic Elastase; Periodontitis; Porphyromonas gingivalis; Rats; Rats, Sprague-Dawley; Tetracycline