Albert T. Brown

Chlorhexidine prophylaxis for chemotherapy-and radiotherapy-induced stomatitis: A randomized double-blind trial

Patients receiving cytotoxic antineoplastic therapy often have treatment-associated stomatitis. A 0.12% chlorhexidine digluconate mouthrinse was evaluated (15 ml, three times a day) in a prospective, double-blind randomized trial as prophylaxis against cytotoxic therapy-induced damage to oral soft tissues. Seventy subjects, forty inpatients receiving high-dose chemotherapy and thirty outpatients receiving high-dose head and neck radiation therapy, were evaluated. Chlorhexidine mouthrinse significantly reduced the incidence of oral mucositis in the chemotherapy group on day 14 (p less than 0.02) and at 1 week follow-up on day 28 (p less than 0.002). Mucositis in the patients undergoing chemotherapy who received chlorhexidine also resolved more rapidly. Mucositis severity was significantly less compared to the control chemotherapy group on day 14 (p less than 0.03), day 21 (p less than 0.04), and on 1 week follow-up (p less than 0.02). Concomitant trends in the reduction in oral streptococci and yeast were noted in the chemotherapy group receiving chlorhexidine mouthrinse. Although no differences were observed in oral mucositis between the control and chlorhexidine groups of patients undergoing high-dose radiotherapy, similar reductions of oral microflora to those seen in the chemotherapy population were also noted for patients undergoing radiation therapy who received chlorhexidine. Although generally not significant, some increase in gram-negative bacilli was noted in the chlorhexidine-treated patients in both the chemotherapy and radiotherapy groups, but there was no correlation with increased systemic infection. Prophylactic chlorhexidine mouthrinse reduces oral mucositis and microbial burden in patients with cancer undergoing intensive chemotherapy.

Therapeutic use of chlorhexidine in bone marrow transplant patients: Case studies

Patients undergoing cytotoxic chemotherapy and radiation therapy often experience severe oral complications during and after treatment despite supervised oral hygiene and conventional antimicrobial regimens. The antimicrobial compound chlorhexidine is an effective topical prophylactic agent against oral mucositis and candidiasis. Oral mucositis developed in four patients who underwent bone marrow transplantation; the condition was severe enough to prompt use of chlorhexidine. In each case, there was clinical resolution of mucositis and a concomitant decrease in the oral microbial burden 1 week after chlorhexidine use began. This strongly suggests that, in addition to its value in protecting these severely immunocompromised patients from oral infection, chlorhexidine also offers a therapeutic benefit in the resolution of existing oral infections and of mucositis.

OralCandida albicans in bone marrow transplant patients given chlorhexidine rinses: Occurrence and susceptibilities to the agent

The tongue and buccal mucosa of 26 bone marrow transplant recipients given three 0.12% chlorhexidine digluconate (CHX) oral rinses daily for 8 weeks were sampled weekly for oral Candida albicans. Putative C. albicans colony-forming units on selective bismuth sulfite glucose glycine yeast agar plates were identified with the API 20C system. The CHX minimum inhibitory concentrations (MICs) of oral C. albicans isolates obtained at all 8 sample weeks was determined with a microbroth dilution sensitivity assay. The CHX MIC range for yeast isolates selected randomly at all sample weeks was up to 2.5 to up to 20 micrograms/ml (mean MIC less than or equal to 8.5 micrograms/ml). The CHX MIC range for isolates at week 1 was less than or equal to 5 to less than or equal to 10 micrograms/ml (mean MIC less than or equal to 7.9 micrograms/ml) compared with less than or equal to 2.5 to less than or equal to 20 micrograms/ml at week 8 (mean MIC less than or equal to 8.8 micrograms/ml). Therefore the persistence of oral C. albicans in bone marrow transplant recipients using CHX rinses was due neither to low CHX susceptibilities nor to the development of resistance to the agent.

In vitro effect of chlorhexidine and amikacin on oral gram-negative bacilli from bone marrow transplant recipients.

Prophylactic use of chlorhexidine (CHX) mouthrinses has been shown to benefit the oral health status of bone marrow transplant recipients and other immunosuppressed persons and to reduce systemic complications of oral origin. However, a problem that often emerges with these patients is oropharyngeal and lower respiratory tract colonization by opportunistic aerobic or facultative gram-negative bacilli (GNB). Trends in four studies indicated that CHX rinses may predispose these persons to oral colonization by GNB such as the enterobacteria, Klebsiella pneumoniae and Enterobacter cloacae. Since GNB are generally susceptible to broad-spectrum aminoglycoside antibiotics such as amikacin, the in vitro sensitivities of K. pneumoniae, E. cloacae, Pseudomonas aeruginosa, and Escherichia coli ATCC reference strains and K. pneumoniae and E. cloacae oral clinical isolates to combinations of CHX and amikacin were determined by means of a disk diffusion sensitivity assay on Mueller-Hinton agar. The amikacin minimum inhibitory concentrations for all GNB tested were much lower (less than or equal to 4.69 to less than or equal to 9.37 micrograms/ml) than those for CHX (less than or equal to 18.75 to less than or equal to 300 micrograms/ml), and combinations of CHX and amikacin gave larger growth inhibition zones than CHX alone. No antibacterial antagonism between CHX and amikacin was found, and their solubilities were compatible. Therefore use of topical amikacin in conjunction with CHX rinses may reduce oral colonization by GNB in severely immunocompromised patient populations.

Oral Gram-negative Bacilli in Bone Marrow Transplant Patients Given Chlorhexidine Rinses

Fifteen bone marrow transplant (BMT) patients who received three 0.12% chlorhexidine digluconate (CHX) mouthrinses daily for eight weeks were monitored weekly for the occurrence of oral opportunistic Gram-negative bacilli (GNB). Tongue and buccal mucosa were sampled with use of Culturette swabs that were streaked on plates containing selective MacConkey agar. After incubation, colony-forming units were scored and putative GNB classified with use of the API 20E rapid identification system and supplemental biochemical tests. After identification, the susceptibilities of all GNB to CHX were determined by means of a disk diffusion sensitivity assay. Sixty-seven percent (10) of the BMT subjects had at least one GNB-positive tongue culture, and 53% (8) had GNB in samples taken from the buccal mucosa. Of 218 samples taken, 26% and 24% from the tongue and buccal mucosa, respectively, were GNB-positive. The predominant clinical GNB isolates were Enterobacter cloacae (46%) and Klebsiella pneumoniac (30%). Their respective CHX minimum inhibitory concentrations (MICs) were similar to those of ATCC reference strains. Although the CHX MIC values of the clinical GNB isolates were high (≤37.5 to ≤300 μg/mL), they were not dependent upon length of exposure to the agent. Therefore, changes in sensitivity or resistance to CHX did not appear to occur. The results suggest that the mouths of BMT patients - and perhaps of other immunosuppressed individuals - should be routinely monitored for GNB, as are other clinically important sites, such as the throat and the urinary and gastro-intestinal tracts.

Apparent Synergism between the Interaction of Saccharin, Acesulf ame K, and Fluoride with Hexitol Metabolism by Streptococcus mutans

Acesulfame, a structural analogue of saccharin, like the parent compound, markedly decreased the sorbitol- and mannitol-dependent growth rate and growth yield of Streptococcus mutans

Interaction of Saccharin with Hexitol Metabolism by Streptococcus mutans

Saccharin markedly decreased the sorbitol- and mannitol-dependent growth rate and growth yield of Streptococcus mutans NCTC 10449 and also decreased the amount of acid produced from these hexitols by the organism. In addition, saccharin increased both the lag phase when glucose-grown cells were placed in a medium which contained sorbitol or mannitol as the primary energy source and to also increase the diauxie portion of the growth-response curve when glucose-grown cells were placed in a medium which contained a mixture of glucose and sorbitol or mannitol as fermentable energy sources. One mechanism by which saccharin may exert its negative effect upon hexitol catabolism by S. mutans is through inhibiting the activity of two inducible NAD-dependent oxidoreductases, sorbitol-6-phosphate dehydrogenase and mannitol-1-phosphate dehydrogenase which are found at high specific activities in extracts obtained from sorbitol- or mannitol-adapted cells respectively. Saccharin exerted a negative effect upon the enzymes by competitively inhibiting their interaction with both their oxidized and reduced coenzymes, NAD and NADH. In contrast, the inhibitor had no effect on the interaction of the enzymes with their respective substrates, mannitol-1-phosphate and sorbitol-6-phosphate.

Regulation of Lactic Acid Production by Leptotrichia buccalis

Two lactate dehydrogenase (EC 1.1.1.27) species were separated by agarose A 0.5 M molecular exclusion column chromatography from cell-free extracts obtained from Leptotrichia buccal

A Proposed Mechanism for the Effects of Saccharin on Glucose Metabolism by Streptococcus mutans

Saccharin inhibited the rate of growth, the amount of acid produced, and glucose utilization by Streptococcus mutans NCTC 10449. One possible mechanism by which saccharin mediates i