Michael T. Brennan

Bacteremia Associated With Toothbrushing and Dental Extraction

Background— Antibiotic prophylaxis recommendations for the prevention of infective endocarditis are based in part on studies of bacteremia from dental procedures, but toothbrushing may pose a greater threat. The purpose of this study was to compare the incidence, duration, nature, and magnitude of endocarditis-related bacteremia from single-tooth extraction and toothbrushing and to determine the impact of amoxicillin prophylaxis on single-tooth extraction. Methods and Results— In this double-blind, placebo-controlled study, 290 subjects were randomized to (1) toothbrushing, (2) single-tooth extraction with amoxicillin prophylaxis, or (3) single-tooth extraction with identical placebo. Blood was drawn for bacterial culturing and identification at 6 time points before, during, and after these interventions. The focus of our analysis was on bacterial species reported to cause infective endocarditis. We identified 98 bacterial species, 32 of which are reported to cause endocarditis. Cumulative incidence of endocarditis-related bacteria from all 6 blood draws was 23%, 33%, and 60% for the toothbrushing, extraction-amoxicillin, and extraction-placebo groups, respectively (P<0.0001). Significant differences were identified among the 3 groups at draws 2, 3, 4, and 5 (all P<0.05). Amoxicillin resulted in a significant decrease in positive cultures (P<0.0001). Conclusions— Although amoxicillin has a significant impact on bacteremia resulting from a single-tooth extraction, given the greater frequency for oral hygiene, toothbrushing may be a greater threat for individuals at risk for infective endocarditis.

Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren’s syndrome

Sjögrens syndrome is a common autoimmune disease (affecting ∼0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjögrens syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (Pmeta = 7.65 × 10−114), we establish associations with IRF5-TNPO3 (Pmeta = 2.73 × 10−19), STAT4 (Pmeta = 6.80 × 10−15), IL12A (Pmeta = 1.17 × 10−10), FAM167A-BLK (Pmeta = 4.97 × 10−10), DDX6-CXCR5 (Pmeta = 1.10 × 10−8) and TNIP1 (Pmeta = 3.30 × 10−8). We also observed suggestive associations (Pmeta < 5 × 10−5) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjögrens syndrome.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life

PurposeThis systematic review aimed to assess the literature for prevalence, severity, and impact on quality of life of salivary gland hypofunction and xerostomia induced by cancer therapies.MethodsThe electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. Two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results and conclusions for each article.ResultsThe inclusion criteria were met by 184 articles covering salivary gland hypofunction and xerostomia induced by conventional, 3D conformal radiotherapy or intensity-modulated radiotherapy in head and neck cancer patients, cancer chemotherapy, total body irradiation/hematopoietic stem cell transplantation, radioactive iodine treatment, and immunotherapy.ConclusionsSalivary gland hypofunction and xerostomia are induced by radiotherapy in the head and neck region depending on the cumulative radiation dose to the gland tissue. Treatment focus should be on optimized/new approaches to further reduce the dose to the parotids, and particularly submandibular and minor salivary glands, as these glands are major contributors to moistening of oral tissues. Other cancer treatments also induce salivary gland hypofunction, although to a lesser severity, and in the case of chemotherapy and immunotherapy, the adverse effect is temporary. Fields of sparse literature included pediatric cancer populations, cancer chemotherapy, radioactive iodine treatment, total body irradiation/hematopoietic stem cell transplantation, and immunotherapy.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact

PurposeThis systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations.MethodsThe electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions.ResultsSeventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer.ConclusionsThere is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.

Impact of Amoxicillin Prophylaxis on the Incidence, Nature, and Duration of Bacteremia in Children After Intubation and Dental Procedures

Background—Controversy exists about the impact of prophylactic antibiotics on bacteremia after invasive dental procedures. The purpose of this double-blind, randomized, placebo-controlled study was to determine the impact of amoxicillin prophylaxis on the incidence, nature, and duration of bacteremia from nasotracheal intubation and dental procedures in children. Methods and Results—Children were randomly assigned before surgery to the American Heart Association (AHA)–recommended dose of amoxicillin or to a placebo. Aerobic and anaerobic blood cultures were drawn at 8 specific time points after intubation, dental restorative and cleaning procedures, and before, during, and after dental extraction(s), to include blood drawings up to 45 minutes after the last extraction. Aerobic and anaerobic blood culture results were used to determine the incidence, nature, and duration of bacteremia from these procedures. For the 100 children enrolled (mean age, 3.5 years), the overall incidence of positive blood cultures, defined as at least 1 positive culture of the 8, was significantly higher in the placebo (84%) than the amoxicillin group (33%) (P <0.0001). Bacteremia occurrence rates after intubation and after dental restorations and cleaning were 18% and 20% in the placebo group and 4% and 6% in the amoxicillin group (P =0.05 and P =0.07, respectively). At 1.5 minutes after the initiation of dental extractions, bacteremia occurred in 76% of the placebo group versus 15% of the amoxicillin group (P <0.001). The majority of the 152 positive cultures and of the 29 different bacteria identified were Gram-positive cocci. Bacteremia persisted longer in the placebo group. Conclusions—Bacteremia from these procedures occurs more often, from a wider variety of bacterial species, and for a longer duration after dental extractions than previously reported in any age group. Amoxicillin has a significant impact on the incidence, nature, and duration of bacteremia after nasal intubation, dental restorative and cleaning procedures, and dental extractions.

Molecular Analysis of Oral and Respiratory Bacterial Species Associated with Ventilator-Associated Pneumonia

ABSTRACT Trauma intensive care unit (TICU) patients requiring mechanical respiratory support frequently develop ventilator-associated pneumonia (VAP). Oral and oropharyngeal bacteria are believed to be responsible for many cases of VAP, but definitive evidence of this relationship is lacking. Earlier studies used conventional culture-based methods for identification of bacterial pathogens, but these methods are insufficient, as some bacteria may be uncultivable or difficult to grow. The purpose of this study was to use a culture-independent molecular approach to analyze and compare the bacterial species colonizing the oral cavity and the lungs of TICU patients who developed VAP. Bacterial samples were acquired from the dorsal tongue and bronchoalveolar lavage fluid of 16 patients. Bacterial DNA was extracted, and the 16S rRNA genes were PCR amplified, cloned into Escherichia coli, and sequenced. The sequencing data revealed the following: (i) a wide diversity of bacterial species in both the oral and pulmonary sites, some of them novel; (ii) known and putative respiratory pathogens colonizing both the oral cavity and lungs of 14 patients; and (iii) a number of bacterial pathogens (e.g., Dialister pneumosintes, Haemophilus segnis, Gemella morbillorum, and Pseudomonas fluorescens) in lung samples that had not been reported previously at this site when culture-based methods were used. Our data indicate that the dorsal surface of the tongue serves as a potential reservoir for bacterial species involved in VAP. Furthermore, it is clear that the diversity of bacterial pathogens for VAP is far more complex than the current literature suggests.

A systematic review of dental disease in patients undergoing cancer therapy

IntroductionThis purpose of this systematic review was to evaluate the literature and update our current understanding of the impact of present cancer therapies on the dental apparatus (teeth and periodontium) since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies.Review methodA systematic literature search was conducted with assistance from a research librarian in the databases MEDLINE/PubMed and EMBASE for articles published between 1 January 1990 and 31 December 2008. Each study was independently assessed by two reviewers. Taking into account predetermined quality measures, a weighted prevalence was calculated for the prevalence of dental caries, severe gingival disease, and dental infection. Data on DMFT/dmft, DMFS/dmfs, plaque, and gingival indexes were also gathered. The level of evidence, recommendation, and guideline (if possible) were given for published preventive and management strategies.ResultsSixty-four published papers between 1990 and 2008 were reviewed. The weighted overall prevalence of dental caries was 28.1%. The overall DMFT for patients who were post-antineoplastic therapy was 9.19 (SD, 7.98; n = 457). The overall plaque index for patients who were post-antineoplastic therapy was 1.38 (SD, 0.25; n = 189). The GI for patients who were post-chemotherapy was 1.02 (SD, 0.15; n = 162). The weighted prevalence of dental infections/abscess during chemotherapy was reported in three studies and was 5.8%.ConclusionsPatients who were post-radiotherapy had the highest DMFT. The use of fluoride products and chlorhexidine rinses are beneficial in patients who are post-radiotherapy. There continues to be lack of clinical studies on the extent and severity of dental disease that are associated with infectious complications during cancer therapy.

A systematic review of oral fungal infections in patients receiving cancer therapy

PurposeThe aims of this systematic review were to determine, in patients receiving cancer therapy, the prevalence of clinical oral fungal infection and fungal colonization, to determine the impact on quality of life and cost of care, and to review current management strategies for oral fungal infections.MethodsThirty-nine articles that met the inclusion/exclusion criteria were independently reviewed by two calibrated reviewers, each using a standard form. Information was extracted on a number of variables, including study design, study population, sample size, interventions, blinding, outcome measures, methods, results, and conclusions for each article. Areas of discrepancy between the two reviews were resolved by consensus. Studies were weighted as to the quality of the study design, and recommendations were based on the relative strength of each paper. Statistical analyses were performed to determine the weighted prevalence of clinical oral fungal infection and fungal colonization.ResultsFor all cancer treatments, the weighted prevalence of clinical oral fungal infection was found to be 7.5% pre-treatment, 39.1% during treatment, and 32.6% after the end of cancer therapy. Head and neck radiotherapy and chemotherapy were each independently associated with a significantly increased risk for oral fungal infection. For all cancer treatments, the prevalence of oral colonization with fungal organisms was 48.2% before treatment, 72.2% during treatment, and 70.1% after treatment. The prophylactic use of fluconazole during cancer therapy resulted in a prevalence of clinical fungal infection of 1.9%. No information specific to oral fungal infections was found on quality of life or cost of care.ConclusionsThere is an increased risk of clinically significant oral fungal infection during cancer therapy. Systemic antifungals are effective in the prevention of clinical oral fungal infection in patients receiving cancer therapy. Currently available topical antifungal agents are less efficacious, suggesting a need for better topical agents.

Radiation-Induced trismus in head and neck cancer patients

PurposeTo determine the incidence of trismus in patients who had previously received curative doses of radiation therapy (RT) for head and neck cancer. In addition, we assessed if trismus was associated with quality of life deficits and radiation toxicity.Methods and materialsBetween February, 2005 and December, 2006, 40 patients with histologically confirmed head and neck cancer who had received curative doses of RT to the area(s) of the masticatory muscles and/or the ligaments of the temporomandibular joint (TMJ) were enrolled in this study. Differences in trismus incidence were compared between cancer treatment modalities [i.e., RT vs RT/chemotherapy (CT) and conventional RT vs intensity modulated RT]. Quality of life (QOL) was measured by using four questions from the EORTC QLQ-C30 that address pain and difficulty opening the jaw. Scores regarding impaired eating as a result of decreased range of motion of the mouth were derived from the Modified Common Toxicity Criteria (CTCAE Version 3.0).ResultsTrismus was identified in 45% of subjects who had received curative doses of RT. No differences were noted in the incidence of trismus between RT and RT/CT or between conventional RT and intensity modulated RT (IMRT). Those with trismus demonstrated more QOL deficits than the non-trismus group.ConclusionsCurative doses of RT for head and neck cancer result in trismus in a high percentage of patients, independent of other treatment modalities. Trismus has a negative impact on quality of life in this population.

Diagnosis and treatment of xerostomia (dry mouth)

Xerostomia (dry mouth) is a common complaint with widespread implications such as impaired quality of life, oral pain, and numerous oral complications. There are a variety of salivary and nonsalivary causes of xerostomia, the most frequent being medication side effects and systemic disorders. A systematic approach should be employed to determine the etiology of this condition, with distinctions made between patients with subjective complaints of xerostomia alone and those with measurable salivary gland dysfunction. Management is multidisciplinary and multimodal. This review summarizes the current literature on the etiology, diagnosis, and complications of xerostomia, and on the management of patients with xerostomia.