A Surveillance Bacteriological Study of Acute Bacterial Rhinosinusitis in Thailand and the Clinical Responses to the Culture-directed Antibiotics.

OBJECTIVE: To examine: 1) types of bacteria and antimicrobial sensitivity of commonly used antibiotics for acute bacterial rhinosinusitis (ABRS) in Thailand, 2) the effectiveness of using antibiotics according to antimicrobial sensitivity, and 3) the effectiveness of using antibiotics according to the Thai clinical practice guidelines (CPG) of ABRS. MATERIAL AND METHOD: Descriptive & experimental studies were conducted in seven tertiary hospitals in Thailand. The specimens from maxillary sinuses were taken for bacterial cultures either by maxillary sinus tap or endoscopically directed middle meatus swabs in patients with clinically diagnosed ABRS. Antimicrobial sensitivity was performed and antibiotics were prescribed according to the results of antimicrobial sensitivity or the Thai CPG of ABRS. RESULTS: A total of 113 patients were enrolled between August 2006 and April 2007, 104 cases of which were performed for bacteriological study. The incidence of bacterial growth was 60.6% (95% CI 51.0-69.4%). The most common bacteria was H. influenzae (25.0%, 95% CI 16.9-35.3%), followed by S. pneumoniae (14.3%, 95% CI 8.2-23.5%) and S. aureus (9.5%, 95% CI 4.7-17.9%), respectively, whilst M. catarrhalis was found only in 2.4% (95% CI 0.5-7.3%). Eight in 12 S. pneumoniae isolates were tested for the minimal inhibitory concentration of penicillin and found to be penicillin resistant strain in five specimens. Beta-lactamase producing H. influenzae was found in eight out of 20 isolates. H. influenzae had a tendency to be sensitive to amoxicillin/clavulanate, cefuroxime, cefpodoxime, azithromycin, clarithromycin, ofloxacin, levofloxacin and gatifloxacin, whilst S. pneumoniae had a tendency to be sensitive to amoxicillin/clavulanate, cefaclor ampicillin/sulbactam, cefuroxime, ofloxacin, levofloxacin, gatifloxacin, cefpodoxime, cefixime and cefdinir. The effectiveness of antibiotics prescription according to the Thai CPG of ABRS and antimicrobial sensitivity were comparable, 88.5% (95% CI 69.8-97.6%) and 82.2% (95% CI 67.9-92%), respectively. CONCLUSION: H. influenzae is found to be the most common bacteria in Thai ABRS, followed by S. pneumoniae and S. aureus. There is a high incidence of beta-lactamase producing H. influenzae and penicillin non-susceptible S. pneumoniae.

Fungal rhinosinusitis: a retrospective analysis of clinicopathologic features and treatment outcomes at Ramathibodi Hospital.

The objective of this study was to determine the clinicopathologic findings of invasive and non-invasive fungal rhinosinusitis and to compare the features of the two diseases. The medical records of patients with invasive and noninvasive fungal rhinosinusitis at Ramathibodi Hospital between July 1999 and June 2009 were analyzed. The criterion for the diagnosis of fungal rhinosinusitis was the evidence of fungal elements from histopathologic section on sinonasal specimens. The age, gender, clinical manifestations, duration of symptoms, associated diseases, laboratory data, results of mycotic culture and treatment outcomes were analyzed. The relationship between fungal rhinosinusitis and patient characteristics as well as clinical presentations were assessed. The fungus-attributable mortality rate was determined. The study included 43 cases of invasive fungal rhinosinusitis and 68 cases of non-invasive fungal rhinosinusitis. There were 44 male, and 67 female patients. The mean age at diagnosis was 54.6 years (range: 5 to 86 years). A total of 70 (63.1%) were attributed to aspergillosis, 8 (7.2%) to candidiasis, 6 (5.4%) to zygomycosis, 4 (3.6%) to phaeohyphomycosis, 1 (0.9%) to pseudallescheriasis, 1 (0.9%) to entomophthoromycosis and 21 (18.9%) to nonspecific fungi. Cultures from sinonasal tissues were positive for fungus in 37 of 87 cases (42.5%). The clinical presentations of fungal rhinosinusitis included nasal stuffiness (27.9%), nasal discharge (27.9%), facial pain (27.9%), fever (24.3%) and headache (19.8%). One-fifth of cases had an underlying hematologic malignancy. Invasive fungal rhinosinusitis was significantly associated with hematologic malignancy and neutropenia. Fungus-attributable mortality rate was 44.2% in invasive fungal rhinosinusitis. Early antifungal therapy and surgical drainage were associated with a survival advantage.

Effect of genetic background on the response to bacterial sinusitis in mice.

OBJECTIVE: To study the importance of ongoing allergen exposure and TH1/TH2 genetic background in augmented bacterial and inflammatory responses in allergic and infected mice. DESIGN: BALB/c and C57BL/6 mice were made allergic to ovalbumin. After 1 day of intranasal allergen exposure, they were inoculated intranasally with Streptococcus pneumoniae. The numbers of bacteria and inflammatory cells in the sinuses were determined, and nasal responsiveness to histamine was assessed. RESULTS: Infected BALB/c and C57BL/6 mice that received ongoing ovalbumin challenge following intraperitoneal sensitization showed significantly greater bacterial load and phagocyte level compared with the infected-only mice. Differences were diminished after the allergen challenge was stopped. Allergic and infected C57BL/6 mice showed fewer bacteria and phagocytes compared with the allergic and infected BALB/c mice. Surprisingly, in contrast to the nonallergenic C57BL/6 mice, the infected BALB/c mice showed a larger number of bacteria 28 days after infection. CONCLUSIONS: Ongoing allergic reaction augments bacterial load in both BALB/c and C57BL/6 mice and induces nasal hyperreactivity to histamine. Allergic and infected C57BL/6 mice show less allergic inflammation and bacterial load compared with allergic and infected BALB/c mice. Stopping allergen exposure reduces the response. Infected BALB/c mice, which favor a TH2 response, were less able to clear infection than C57BL/6 mice, which favor a TH1 response. Inflammation and bacterial load are affected by genetic background of mice and ongoing allergen stimulation.

Successful myoblast transplantation in rat tongue reconstruction.

BACKGROUND: Controversy exists regarding the success of myoblast transplantation. The purpose of this study was to determine the survival of transplanted myoblasts in a rat tongue reconstruction model by using fluorescently labeled myoblasts and surgical stains to mark the location of the pocket into which transplanted cells were delivered. We evaluated tongue histology after myoblast transplantation under the hypothesis that myoblast transplantation will promote muscle regeneration and result in minimal scar tissue formation. METHODS: Sterile solutions of 1:10 India ink, 1% methylene blue, and 1% crystal violet were applied to the inner lining of a left-sided mucosa-sparing hemiglossectomy pocket. After air-drying, the hemiglossectomy defect was filled with collagen gel and closed. The tongues were evaluated histologically at 6 weeks. Next, myoblasts were cultured and labeled with three commercially available fluorescent dyes, 5-chloromethyl-fluorescein diacetate (CMFDA), chloromethylbenzamido (CM-DiI), and fluorescently labeled microspheres (FLMs), to determine which would optimally label myoblasts in a tongue reconstruction model. Next, Lewis rats underwent left hemiglossectomy, and the created pockets were coated with 1:10 India ink. Control animals received collagen gel alone, whereas experimental animals received labeled myoblast/collagen constructs into the tongue defect. Tongues were harvested at intervals to determine the presence of labeled fluorescent cells, the relative numbers of viable myoblasts, and the degree of scarring. RESULTS: India ink coating of the hemiglossectomy pocket caused minimal inflammation and lasted longer than the other tested dyes. CMFDA and FLMs both successfully label myoblasts for transplantation. In vivo, donor cells were observed in all specimens at week 0 with increasing numbers of cells and muscle formation, determined by desmin immunofluorescence, after 6 weeks. There was less scar tissue contracture in the experimental group and a significant increase in the amount of desmin-stained muscle in the surgical defect. CONCLUSIONS: India ink is an appropriate vehicle for intra-operative marking of a hemiglossectomy cavity. The introduction of myoblast/collagen constructs into the rat hemiglossectomy defect increases the amount of regenerated muscle, results in less scar contracture, and may increase meaningful tongue function.

The effect of treatment with moxifloxacin or azithromycin on acute bacterial rhinosinusitis in mice.

OBJECTIVE: Acute bacterial rhinosinusitis, which is a major health problem, is treated with antibiotics. We developed a mouse model of acute bacterial rhinosinusitis to gain a better understanding of the pathophysiology of the disease. Our goal was to investigate the response to acute rhinosinusitis when treated with either a bactericidal or a bacteriostatic antibiotic. METHODS: C57BL/6 mice were infected intranasally with Streptococcus pneumoniae. One day after inoculation, the mice were treated with either moxifloxacin (bactericidal) or azithromycin (bacteriostatic). Different groups were euthanized during the first five days post-inoculation. Bacterial counts from nasal lavage culture and the cell markers GR1, CD11b, CD3, CD4, and CD8 in sinus tissue were evaluated by flow cytometry. RESULTS: Azithromycin led to rapid clearance of the bacteria and of the inflammation in contrast to placebo. Surprisingly, moxifloxacin showed a limited effect. Investigations of this limited effect of moxifloxacin suggested a high metabolic clearance, a low concentration at the site of infection, and low persistent post-antibiotic effects of moxifloxacin in mice. CONCLUSION: Our animal model of acute sinusitis has great utility for studying the disease, but the difference between mice and man must always be considered in making extrapolations from animal experiments to the human experience.

Evaluation of importance of Toll-like receptor 4 in acute Streptococcus pneumoniae sinusitis in mice.

OBJECTIVES: To investigate the effect of RC-527, a synthetic toll-like receptor 4 (TLR4) agonist, on stimulating the immune response before acute Streptococcus pneumoniae sinusitis in a mouse model, and to determine the importance of TLR4 in modulating the response to S. pneumoniae. Toll-like receptor 4 agonists have been shown to induce protective innate immune responses when administered before some bacterial or viral challenges in mice. DESIGN: We intranasally inoculated BALB/c, TLR4 complex-deficient C3H/HeJ, and wild-type C3H/HeOuJ mice with S. pneumoniae 24 hours after treatment with 10 or 1 microg of RC-527 or vehicle. Bacterial counts from nasal lavage culture and the cell markers GR1, CD11b, CD3, CD4, and CD8 in sinus tissue were quantified at postinoculation days 2, 5, and 14. MAIN OUTCOME MEASURE: Immune response induced by RC-527. RESULTS: Treatment with RC-527 induced an immune response through TLR4, as demonstrated by recruitment of phagocytes in uninfected wild-type C3H/HeOuJ mice, but not in TLR4 complex-deficient C3H/HeJ mice. The immune response was also demonstrated by a significant increase of CD3+, CD4+, and CD8+ T cells in infected and uninfected wild-type C3H/HeOuJ mice, but not in TLR4 complex-deficient C3H/HeJ mice. However, the enhancement of the immune response induced by the TLR4 agonist showed a limited effect on bacterial clearance. CONCLUSIONS: Our studies in mice suggest that stimulation of TLR4 plays a minor role in the overall response to S. pneumoniae infection of the upper airway, and stimulating this receptor before infection does not significantly enhance the immune response of immunocompetent mice to clear S. pneumoniae infection.

Acute bacterial rhinosinusitis causes hyperresponsiveness to histamine challenge in mice.

OBJECTIVES: To develop a physiologic test of nasal responsiveness in mice and to evaluate whether mice with acute bacterial sinusitis develop nasal hyperresponsiveness. DESIGN: Several experimental studies will be described. The first was a titration pilot study. The second was a randomized, placebo-controlled study. The remainder were before-and-after trials. SPECIES: BALB/c or C57BL/6 mice. INTERVENTIONS: For these experiments, we exposed mice to histamine intranasally, then counted the number of sneezes and nose rubs as the primary outcome measure of nasal responsiveness. First, we constructed a dose-response curve. Second, we treated the mice with desloratadine, a histamine 1 receptor antagonist, prior to histamine exposure. Third, we challenged, with intranasal histamine, mice made allergic using 2 techniques. Fourth, we infected mice with Streptococcus pneumoniae to determine whether acute sinusitis causes nasal hyperresponsiveness to histamine exposure. RESULTS: Nasal histamine challenge led to a reproducible, dose-dependent increase in sneezing and nose rubs. The response to histamine exposure was blocked by desloratadine (P < or = .05). Allergic mice had a significant increase in responsiveness (P < or = .05) over baseline after exposure to antigen. Mice with acute sinusitis had a sustained increase in responsiveness, although less severe than after allergy, compared with baseline values that lasted 12 days after infection (P < or = .05). CONCLUSIONS: Nasal challenge with histamine is a physiologic test of nasal responsiveness. The hyperresponsiveness of allergic mice to histamine exposure parallels the response to nonspecific stimuli during the human allergic reaction. In addition, we showed that acute bacterial sinusitis causes nasal hyperresponsiveness in mice.