Impact of Oropharyngeal Administration of Colostrum in Preterm Newborns' Oral Microbiome.

The initial colonization of the human microbiota is of paramount importance. In this context, the oropharyngeal administration of colostrum is a safe, viable, and well-tolerated practice even by the smallest preterm infants. Therefore, this study evaluated the effects of oropharyngeal administration of colostrum on the establishment of preterm infants' oral microbiota. A longitudinal observational study was carried out with 20 premature neonates, divided into two groups: one receiving the protocol (Oropharyngeal Administration of Colostrum; OAC) and the other one receiving Standard Caare (SC). Saliva samples were collected from the newborns weekly during the study period (from the day of birth until the 21st day of life) for analysis of oral microbiota through 16S rRNA gene sequencing. We observed that the colonization of the oral microbiota of preterm newborns preseanted a higher relative abundance of Staphylococcus on the 7th day of life, mainly in the OAC group. Additionally, an increased abundance of Bifidobacterium and Bacteroides was observed in the OAC group at the first week of life. Regarding alpha and beta diversity, time was a key factor in the oral modulation of both groups, showing how dynamic this environment is in early life.

Comparative efficacy of honey 12.5% and chlorhexidine 0.2% mouthwashes on the oropharyngeal bacterial colonization in mechanically-ventilated patients: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of honey mouthwash 12.5% and chlorhexidine solution 0.2% to reduce the rate of oropharyngeal bacterial colonization in mechanically-ventilated patients. METHODS: This study was a randomized, single blind, phase Ⅲ controlled clinical trial. Sixty patients newly admitted to internal and trauma Intensive Care Units of the two educational hospitals of Sanandaj city affiliated with Kurdistan University of Medical Sciences were selected by convenience sampling and allocated to two groups of 30 patients using random blocks design. In each group, the mouthwash was applied twice a day for four consecutive days. Swab samples were taken from the mouth and throat of all patients three times a day (pre- intervention, two days, and four days after the intervention) and then the samples were transferred onto the blood agar and eosin methylene blue (EMB) culture plates and investigated for bacterial growth and colonization after 24-48 h. RESULTS: The findings showed that oropharyngeal colonization was not significantly different between the two groups, pre-intervention, two days, and four days after the intervention (P > 0.05). Rinsing with honey mouthwash 12.5% led to the inhibition of Staphylococcus aureus and Pseudomonas aeruginosa on the fourth day of the intervention in all samples. CONCLUSION: None of the studied solutions contributed to the reduction of oropharyngeal bacterial colonization. It seems that the growth inhibition of Staphylococcus aureus and Pseudomonas aeruginosa by the honey 12.5% mouthwash in mechanically-ventilated patients need further investigation.

Evaluating the Alimentary and Respiratory Tracts in Health and disease (EARTH) research programme: a protocol for prospective, longitudinal, controlled, observational studies in children with chronic disease at an Australian tertiary paediatric hospital.

INTRODUCTION: Chronic gastrointestinal and respiratory conditions of childhood can have long-lasting physical, psychosocial and economic effects on children and their families. Alterations in diet and intestinal and respiratory microbiomes may have important implications for physical and psychosocial health. Diet influences the intestinal microbiome and should be considered when exploring disease-specific alterations. The concepts of gut-brain and gut-lung axes provide novel perspectives for examining chronic childhood disease(s). We established the 'Evaluating the Alimentary and Respiratory Tracts in Health and disease' (EARTH) research programme to provide a structured, holistic evaluation of children with chronic gastrointestinal and/or respiratory conditions. METHODS AND ANALYSIS: The EARTH programme provides a framework for a series of prospective, longitudinal, controlled, observational studies (comprised of individual substudies), conducted at an Australian tertiary paediatric hospital (the methodology is applicable to other settings). Children with a chronic gastrointestinal and/or respiratory condition will be compared with age and gender matched healthy controls (HC) across a 12-month period. The following will be collected at baseline, 6 and 12 months: (i) stool, (ii) oropharyngeal swab/sputum, (iii) semi-quantitative food frequency questionnaire, (iv) details of disease symptomatology, (v) health-related quality of life and (vi) psychosocial factors. Data on the intestinal and respiratory microbiomes and diet will be compared between children with a condition and HC. Correlations between dietary intake (energy, macro-nutrients and micro-nutrients), intestinal and respiratory microbiomes within each group will be explored. Data on disease symptomatology, quality of life and psychosocial factors will be compared between condition and HC cohorts.Results will be hypothesis-generating and direct future focussed studies. There is future potential for direct translation into clinical care, as diet is a highly modifiable factor. ETHICS AND DISSEMINATION: Ethics approval: Sydney Children's Hospitals Network Human Research Ethics Committee (HREC/18/SCHN/26). Results will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04071314.

Dimethylaminododecyl methacrylate inhibits Candida albicans and oropharyngeal candidiasis in a pH-dependent manner.

The prevalence of stomatitis, especially that caused by Candida albicans, has highlighted the need for new antifungal agents. We previously found that a type of quaternary ammonium salts, dimethylaminododecyl methacrylate (DMADDM), incorporated in dental materials inhibited the growth and hyphal development of C. albicans. However, how the quaternary ammonium salts inhibited the fungal pathogens and whether the oral condition, such as salivary pH variation under different diseases, can affect the antimicrobial capacity of quaternary ammonium salts is unknown. This study evaluated the antifungal effects of DMADDM at different pH in vitro and in vivo. A pH-dependent antifungal effect of DMADDM was observed in planktonic and biofilm growth. DMADDM enhanced antifungal activity at alkaline pH. Two pH-regulated genes (PHR1/PHR2) of C. albicans were correlated with the pH-dependent antifungal effects of DMADDM. The PHR1/PHR2 genes and pH values regulated the zeta potential of C. albicans, which then influenced the binding between C. albicans cells and DMADDM. The pH-dependent antifungal activity of DMADDM was then substantiated in a murine oropharyngeal candidiasis model. We directly demonstrated that the antifungal abilities of quaternary ammonium salts relied on the cell zeta potential which affected the binding between fungal cells and quaternary ammonium salts. These findings suggest a new antifungal mechanism of quaternary ammonium under different pH and that DMADDM can be a potential antifungal agent applied in dental materials and stomatitis therapy.Key Points • DMADDM has stronger antifungal activity in alkaline than in acidic pH conditions. • The pH values and pH-regulated genes can affect the zeta potential of fungal cells. • Zeta potential of fungal cells directly affect the binding between DMADDM and cells. Graphical abstract Schematic diagram of the antifungal activities of DMADDM at different pH values.

Bactericidal activity of hexylresorcinol lozenges against oropharyngeal organisms associated with acute sore throat.

OBJECTIVE: For the majority of people with acute sore throat, over-the-counter treatments represent the primary option for symptomatic relief. This study evaluated the in vitro bactericidal activity of lozenges containing the antiseptic hexylresorcinol against five bacteria associated with acute sore throat: Staphylococcus aureus, Streptococcus pyogenes, Moraxella catarrhalis, Haemophilus influenzae and Fusobacterium necrophorum. RESULTS: Hexylresorcinol 2.4 mg lozenges were dissolved into 5 mL of artificial saliva medium. Inoculum cultures were prepared in triplicate for each test organism to give an approximate population of 108 colony-forming units (cfu)/mL. Bactericidal activity was measured by log reduction in cfu. Greater than 3log10 reductions in cfu were observed at 1 min after dissolved hexylresorcinol lozenges were added to S. aureus (log10 reduction cfu/mL ± standard deviation, 3.3 ± 0.2), M. catarrhalis (4.7 ± 0.4), H. influenzae (5.8 ± 0.4) and F. necrophorum (4.5 ± 0.2) and by 5 min for S. pyogenes (4.3 ± 0.4). Hexylresorcinol lozenges achieved a > 99.9% reduction in cfu against all tested organisms within 5 min, which is consistent with the duration for a lozenge to dissolve in the mouth. In conclusion, in vitro data indicate that hexylresorcinol lozenges offer rapid bactericidal activity against organisms implicated in acute sore throat.

Oropharyngeal Bacterial Colonization after Chlorhexidine Mouthwash in Mechanically Ventilated Critically Ill Patients.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Oropharyngeal care with chlorhexidine to prevent ventilator-associated pneumonia is currently questioned, and exhaustive microbiologic data assessing its efficacy are lacking. The authors therefore aimed to study the effect of chlorhexidine mouthwash on oropharyngeal bacterial growth, to determine chlorhexidine susceptibility of these bacteria, and to measure chlorhexidine salivary concentration after an oropharyngeal care. METHODS: This observational, prospective, single-center study enrolled 30 critically ill patients under mechanical ventilation for over 48 h. Oropharyngeal contamination was assessed by swabbing the gingivobuccal sulcus immediately before applying 0.12% chlorhexidine with soaked swabs, and subsequently at 15, 60, 120, 240, and 360 min after. Bacterial growth and identification were performed, and chlorhexidine minimal inhibitory concentration of recovered pathogens was determined. Saliva was collected in 10 patients, at every timepoint, with an additional timepoint after 30 min, to measure chlorhexidine concentration. RESULTS: Two hundred fifty bacterial samples were analyzed and identified 48 pathogens including Streptococci (27.1%) and Enterobacteriaceae (20.8%). Oropharyngeal contamination before chlorhexidine mouthwash ranged from 10 to 10 colony-forming units (CFU)/ml in the 30 patients (median contamination level: 2.5·10 CFU/ml), and remained between 8·10 (lowest) and 3·10 CFU/ml (highest count) after chlorhexidine exposure. These bacterial counts did not decrease overtime after chlorhexidine mouthwash (each minute increase in time resulted in a multiplication of bacterial count by a coefficient of 1.001, P = 0.83). Viridans group streptococci isolates had the lowest chlorhexidine minimal inhibitory concentration (4 [4 to 8] mg/l); Enterobacteriaceae isolates had the highest ones (32 [16 to 32] mg/l). Chlorhexidine salivary concentration rapidly decreased, reaching 7.6 [1.8 to 31] mg/l as early as 60 min after mouthwash. CONCLUSIONS: Chlorhexidine oropharyngeal care does not seem to reduce bacterial oropharyngeal colonization in critically ill ventilated patients. Variable chlorhexidine minimal inhibitory concentrations along with low chlorhexidine salivary concentrations after mouthwash could explain this ineffectiveness, and thus question the use of chlorhexidine for ventilator-associated pneumonia prevention.

Nutritional, microbiological, and therapeutic factors related to mucositis in head and neck cancer patients: a cohort study / Factores nutricionales, microbiológicos y terapéuticos relacionados con el desarrollo de mucositis en pacientes con cáncer de cabeza y cuello: un estudio de cohorte

Purpose: the objective was to demonstrate if treatment modality, nutritional status and oropharyngeal flora contribute to the development of mucositis in radiotherapy-treated head and neck cancer. Methods: single-cohort study of patients with head and neck cancer (H&N) in which radiotherapy was indicated. Nutritional status was evaluated using SGA, BMI, and FFMI. A buccal smear was performed before radiotherapy for cultivation of bacteria and yeasts. Mucositis was evaluated using the WHO grades. Relative risk (RR) and its 95% CI were calculated. Results: the study included 35 patients, 74.3% males, 63.8 (9.9) years of age, and 34.3% malnourished. The diagnoses included larynx (40.0%), oral (25.7%), and pharynx cancer (11.4%). Treatment comprised 66.0 Gy of radiation, chemotherapy (60.0%), and surgery (57.1%). Bacteria were found in 28.6%, including Staphylococcus aureus (8.6%) and Escherichia coli (8.6%). Yeasts (Candida spp.) were found in 35.3%. Mucositis was more frequent in patients with definitive radiotherapy [100% vs. 65%, p = 0.01; RR = 1.54 (CI95% 1.12 to 2.12)]. Neither SGA nor BMI or FFMI were related to the development or severity of mucositis. Positive cultures for bacteria before radiotherapy were related to severe mucositis [44.4% vs. 12%, p = 0.039; RR = 4.17 (CI95% 1.22 to 14.24)], but there was no relationship with the presence of yeasts. Previous surgery was not associated with the appearance of the studied strains of bacteria. Conclusion: bacterial colonization of the oropharynx prior to radiotherapy may be a factor for severe mucositis in H&N patients (AU)

Objetivo: el objetivo fue demostrar si la modalidad de tratamiento, el estado nutricional y la flora orofaríngea contribuyen al desarrollo de mucositis en pacientes con cáncer de cabeza y cuello tratados con radioterapia. Métodos: estudio de cohorte de pacientes con cáncer de cabeza y cuello (CyC) tratados con radioterapia. El estado nutricional se evaluó utilizando VGS, IMC e IMM. Se realizó un frotis bucal antes de la radioterapia para el cultivo de bacterias y levaduras. Se evaluó la mucositis usando los criterios de la OMS. Se calcularon el riesgo relativo (RR) y su IC del 95%. Resultados: el estudio incluyó a 35 pacientes, 74,3% hombres, 63,8 (9,9) años de edad, y 34,3% desnutridos. Los tumores estaban localizados en laringe (40,0%), boca (25,7%) y faringe (11,4%). El tratamiento consistió en 66,0 Gy de radiación, quimioterapia (60,0%) y cirugía (57,1%). Se encontraron bacterias en 28,6%, incluyendo Staphylococcus aureus (8,6%) y Escherichia coli (8,6%). Se encontró Candida spp. en el 35,3%. La mucositis fue más frecuente en los pacientes con radioterapia radical [100% vs. 65%, p = 0,01; RR = 1,54 (IC95% 1,12 a 2,12)]. Ni VGS, IMC ni IMM se relacionaron con el desarrollo o la gravedad de la mucositis. Los cultivos positivos para bacterias antes de la radioterapia se relacionaron con mucositis severa [44,4% vs. 12%, p = 0,039; RR = 4,17 (IC95% 1,22 a 14,24)], pero no hubo ninguna relación con la presencia de levaduras. La cirugía no se asoció con la aparición de las cepas estudiadas de bacterias. Conclusión: la colonización bacteriana de la orofaringe antes de la radioterapia puede ser un factor para la mucositis graves en pacientes con cáncer CyC (AU)

NUTRITIONAL, MICROBIOLOGICAL, AND THERAPEUTIC FACTORS RELATED TO MUCOSITIS IN HEAD AND NECK CANCER PATIENTS: A COHORT STUDY.

PURPOSE: the objective was to demonstrate if treatment modality, nutritional status and oropharyngeal flora contribute to the development of mucositis in radiotherapy- treated head and neck cancer. METHODS: single-cohort study of patients with head and neck cancer (H&N) in which radiotherapy was indicated. Nutritional status was evaluated using SGA, BMI, and FFMI. A buccal smear was performed before radiotherapy for cultivation of bacteria and yeasts. Mucositis was evaluated using the WHO grades. Relative risk (RR) and its 95% CI were calculated. RESULTS: the study included 35 patients, 74.3% males, 63.8 (9.9) years of age, and 34.3% malnourished. The diagnoses included larynx (40.0%), oral (25.7%), and pharynx cancer (11.4%). Treatment comprised 66.0 Gy of radiation, chemotherapy (60.0%), and surgery (57.1%). Bacteria were found in 28.6%, including Staphylococcus aureus (8.6%) and Escherichia coli (8.6%). Yeasts (Candida spp.) were found in 35.3%. Mucositis was more frequent in patients with definitive radiotherapy [100% vs. 65%, p = 0.01; RR = 1.54 (CI95% 1.12 to 2.12)]. Neither SGA nor BMI or FFMI were related to the development or severity of mucositis. Positive cultures for bacteria before radiotherapy were related to severe mucositis [44.4% vs. 12%, p = 0.039; RR = 4.17 (CI95% 1.22 to 14.24)], but there was no relationship with the presence of yeasts. Previous surgery was not associated with the appearance of the studied strains of bacteria. CONCLUSION: bacterial colonization of the oropharynx prior to radiotherapy may be a factor for severe mucositis in H&N patients.

Objetivo: el objetivo fue demostrar si la modalidad de tratamiento, el estado nutricional y la flora orofaríngea contribuyen al desarrollo de mucositis en pacientes con cáncer de cabeza y cuello tratados con radioterapia. Métodos: estudio de cohorte de pacientes con cáncer de cabeza y cuello (CyC) tratados con radioterapia. El estado nutricional se evaluó utilizando VGS, IMC e IMM. Se realizó un frotis bucal antes de la radioterapia para el cultivo de bacterias y levaduras. Se evaluó la mucositis usando los criterios de la OMS. Se calcularon el riesgo relativo (RR) y su IC del 95%. Resultados: el estudio incluyó a 35 pacientes, 74,3% hombres, 63,8 (9,9) años de edad, y 34,3% desnutridos. Los tumores estaban localizados en laringe (40,0%), boca (25,7%) y faringe (11,4%). El tratamiento consistió en 66,0 Gy de radiación, quimioterapia (60,0%) y cirugía (57,1%). Se encontraron bacterias en 28,6%, incluyendo Staphylococcus aureus (8,6%) y Escherichia coli (8,6%). Se encontró Candida spp. en el 35,3%. La mucositis fue más frecuente en los pacientes con radioterapia radical [100% vs. 65%, p = 0,01; RR = 1,54 (IC95% 1,12 a 2,12)]. Ni VGS, IMC ni IMM se relacionaron con el desarrollo o la gravedad de la mucositis. Los cultivos positivos para bacterias antes de la radioterapia se relacionaron con mucositis severa [44,4% vs. 12%, p = 0,039; RR = 4,17 (IC95% 1,22 a 14,24)], pero no hubo ninguna relación con la presencia de levaduras. La cirugía no se asoció con la aparición de las cepas estudiadas de bacterias. Conclusión: la colonización bacteriana de la orofaringe antes de la radioterapia puede ser un factor para la mucositis graves en pacientes con cáncer CyC.

Development of antimicrobial resistance in the normal anaerobic microbiota during one year after administration of clindamycin or ciprofloxacin.

Thirty healthy subjects (15 males and 15 females) were randomly assigned in three groups and clindamycin (150 mg qid) or ciprofloxacin (500 mg bid) or placebo was given for a 10-day period. Skin, nasal, saliva, faeces samples were collected at day - 1, day 11, 1 month, 2 months, 4 months and 12 months post administration for microbiological analysis. Ciprofloxacin or clindamycin had no impact on the anaerobic skin microbiota and the proportions of antibiotic resistant anaerobic bacteria were similar as in the placebo group. Ciprofloxacin had impact on the Propionibacterium acnes in the nasal microbiota that normalized after 1 month, however, ciprofloxacin-resistant P. acnes strains increased at month 2 and month 12. Clindamycin had no impact on the nasal microbiota. In the oropharyngeal microbiota, a higher proportion of ciprofloxacin resistant Veillonella was found, it lasting up to 12 months post dosing. In the clindamycin group, clindamycin-resistant Prevotella spp. were found in increased proportions compared to placebo at various time points except month 4 in the saliva samples. The relative proportion of ciprofloxacin-resistant Bifidobacteria increased in the faecal samples on day 11, 1 month, 4 months and 12 months post dosing compared to placebo. The proportion of clindamycin-resistant Bacteroides spp. increased at 1, 2, 4 and 12 months post dosing compared to placebo in the faecal samples. No Clostridium difficile was recovered from any of the samples from any of the volunteers at any visit. The concentrations of ciprofloxacin or clindamycin in the faeces were higher than the MICs for most of the organisms present in the normal microbiota. No obvious correlation between the groups in resistant patterns for anaerobic bacteria was observed. In conclusion, based on the microbiological data of the microbiota as well as the results of the bioassays for ciprofloxacin and clindamycin concentrations in the faecal samples, oral administration of ciprofloxacin and clindamycin has an impact on the anaerobic microbiota and may have a long-term effect on the development and persistence of antibiotic-resistant anaerobes in the normal microbiota.

Enigmatic question of early reactive arthritis disclosed after researches of mycoplasmas, Chlamydia trachomatis and enteropathogens following the holistic vision of human being.

An HLA-B27 genetic profile patient is fully investigated by molecular analyses after an anamnestic assessment of multi-site ecosystems, following the holistic vision of human being.VDRL and Widal-Wright (WWR) resulted positive, showing at Wright’s reaction a title of 1:40. Of all the enzymatic activities measured, only the ALP enzymatic pool activities showed a low increasing value of 297 U/L. Of all later acute phase proteins, Only C3 c protein value (127 mg/dL) and fibrinogen (376 mg/dL) were altered. Cultural and molecular oropharyngeal ecosystem investigation resulted significantly positive to Mycoplasmas(Mhand Uu) and Chlamydia trachomatis(Ct) together with a spread of saprophytic flora. From an accurate anamnesis, several and severe uro-genital clinical symptomatology emerged from birth until the beginning of rheumatologic symptomatologies that were confirmed by oldest Mh, Uu and Ctsilent chronic infections between these ecosystems. The molecular HPV research was negative, while the Thin prep pap-test was indicative of vaginosis and cellular reactive changes associated with inflammation. Parasitological research resulted positive for presence of 5-7 newly-formed G. lambliacysts for microscopic field, while digestibility test was positive for presence of several free fatty acid crystals. The remarkable presence of indigested meat fibre and several mucous dense filaments were observed. The pH value was 6.5, while blood faecal test was positive. The values observed were: ferritin 12 microg/L (10-120), total iron-binding capacity (TIBC) 310 &mgr;g/dL (300+-20), unsaturated iron-binding capacity (UIBC) 286 microg/dL (200-220) and iron seric level 24 microg/dL (60-130). Faecal research highlighted a very scarce presence of E. coli, resulting in 102 UFC/g of stool. Of all enteroinvasive pathogens, researched by molecular analyses, only Yersinia spp. was positive. After several specific cycles of antibiotic and antinflammatory therapies, the patient improved its general health condition considerably and showed almost complete regression of aching inguinal lymph node inflammation. In a picture of a worsening inflammatory process, produced by pathogens like Mycoplasmas, chronic silent or low grade inflammation atypical agents, in young HLA-B27 positive patient, VDRL test resulted positive. This value represents the first non-specific unique spy to reveal the precocious immunological signal in order to register the beginning of early innate immune system decay, keeping in mind that mycoplasmal and chlamydial infections are the triggering of cancer in patients genetically susceptible.

Oral health promotion interventions on oral reservoirs of staphylococcus aureus: a systematic review.

The oral cavity serves as a reservoir of Staphylococcus aureus for infection of the lower respiratory tract and cross-infection to other patients. This systematic review was designed to examine the effectiveness of oral health promotion interventions on this pathogen. The PubMed, ISI Web of Science, and Cochrane Library databases were searched for clinical trials assessing the effect of oral health promotion interventions on oral and oropharyngeal carriage of S. aureus. Oral health promotion interventions on oral reservoirs of S. aureus in both systemically healthy and medically compromised groups consisted of oral hygiene interventions only. There was a lack of evidence pertaining to the effectiveness of mechanical oral hygiene interventions against this pathogen. Chlorhexidine delivered in oral hygiene products such as mouthrinses, gels, and sprays appeared to have some utility against S. aureus, although some studies found equivocal effects. There was a dearth of studies investigating the efficacy of other chemical agents. Although many chemical agents contained in oral hygiene products have proven in vitro activity against S. aureus, their clinical effectiveness and potential role as adjuncts or alternative therapies to conventional treatment remain to be confirmed by further high-quality randomized controlled trials.

Topical curcumin can inhibit deleterious effects of upper respiratory tract bacteria on human oropharyngeal cells in vitro: potential role for patients with cancer therapy induced mucositis?

PURPOSE: Curcumin exerts its anti-inflammatory activity via inhibition of nuclear factor κB. Oropharyngeal epithelia and residing bacteria closely interact in inflammation and infection. This in vitro model investigated the effects of curcumin on bacterial survival, adherence to, and invasion of upper respiratory tract epithelia, and studied its anti-inflammatory effect. We aimed to establish a model, which could offer insights into the host-pathogen interaction in cancer therapy induced mucositis. METHODS: Moraxella catarrhalis (Mcat) and the oropharyngeal epithelial cell line Detroit 562 were used. Time-kill curves assessed the inhibition of bacterial growth and adherence assays and gentamicin protection assays determined the effect of curcumin-preincubated cells on bacterial adherence and invasion. Curcumin-mediated inhibition of pro-inflammatory activation by Mcat was determined via interleukin-8 concentrations in the supernatants. The synergistic role of secretory IgA (sIgA) on adherence was investigated. RESULTS: Curcumin was bactericidal at concentrations >50 µM. Preincubation of Detroit cells for 60 min demonstrated that concentrations >100 µM inhibited bacterial adherence. Together with sIgA, curcumin inhibited adherence at concentrations ≥50 µM. Both 100 and 200 µM curcumin significantly inhibited Mcat cell invasion. Finally, curcumin inhibited Mcat-induced pro-inflammatory activation by strongly suppressing IL-8 release. At a concentration of 200 µM, 10 min of curcumin exposure inhibited IL-8 release significantly, and complete suppression required a pre-exposure time of ≥45 min. CONCLUSION: Curcumin, in clinically relevant concentrations for topical use, displayed strong antibacterial effect against a facultative upper respiratory tract pathogen by inhibiting bacterial growth, adherence, invasion, and pro-inflammatory activation of upper respiratory tract epithelial cells in vitro.

Correlation of the MIC and dose/MIC ratio of fluconazole to the therapeutic response of patients with mucosal candidiasis and candidemia.

We report on the correlation of the outcomes for two cohorts of patients who had been treated for candidemia (126 episodes) or oropharyngeal candidiasis (110 episodes) with various doses of fluconazole and the MIC of fluconazole obtained by using the EUCAST standard for fermentative yeasts. Of 145 episodes caused by an isolate with a fluconazole MIC < or =2 mg/liter, 93.7% (136 of 145) responded to fluconazole treatment. The response for those infected with a strain with a MIC of 4 mg/liter was 66% but reached 100% when the dose was greater than 100 mg/day, whereas the response for those infected with strains with MICs > or =8 mg/liter was only 12%. Hence, a MIC of 2 mg/liter or 4 mg/liter was able to predict successful treatment. A cure rate of 93.9% (140 of 149) was achieved when the dose/MIC ratio was > or =100 but fell to 14.6% (16 of 109) when the ratio was less. The dose/MIC required to achieve a response rate of 50% (the 50% effective concentration) was 43.7 for the cohort of patients with oropharyngeal candidiasis. Classification and regression analysis indicated that a dose/MIC of 35.5 was the threshold for the prediction of cure or failure. However, an increase in exposure above this threshold further increased the probability of cure, and all patients were cured when the dose/MIC exceeded 100. Monte Carlo simulations showed a probability of target attainment of 99% at MICs < or =2 mg/liter and a pharmacodynamic target of a dose/MIC ratio of 100, which was equivalent to an unbound fraction of the fluconazole area under the curve versus the MIC of 79.

Emergence of quinolone resistance among viridans group streptococci isolated from the oropharynx of neutropenic peripheral blood stem cell transplant patients receiving quinolone antimicrobial prophylaxis.

In neutropenic patients receiving quinolone prophylaxis, bacteremia with viridans group streptococci resistant to quinolones is a known complication. The frequency of occurrence of quinolone-resistant organisms colonizing the oropharynx during antibacterial prophylaxis with a quinolone is not well defined. In 48 patients undergoing hematopoietic stem cell transplantation, the prevalence of quinolone resistance in viridans group streptococci colonizing the oropharynx before and during antibacterial prophylaxis with gatifloxacin or moxifloxacin (most with concomitant penicillin) was determined. For quinolone-resistant isolates, mutations in the genes gyrA and parC, which confer resistance to quinolones, were analyzed. Seventy-four isolates before and 27 isolates during quinolone use were recovered from patients' oropharynxes. The numbers of susceptible isolates recovered before versus during quinolone use were as follows: 52 (70%) versus three (11%) for ciprofloxacin, 66 (89%) versus eight (30%) for levofloxacin, 66 (89%) versus ten (37%) for gatifloxacin, and 67 (91%) versus 11 (41%) for moxifloxacin (p<0.0001). Mutations in gyrA and/or parC were detected in quinolone-resistant isolates. Quinolone-resistant viridans group streptococci are frequently found in the oropharynx of neutropenic patients after a brief (median, 8 days) exposure to gatifloxacin or moxifloxacin.

Tratamiento de la micosis orofaríngea con dosis única de fluconazol. Análisis descriptivo / Treatmetn of oropharyngeal mycosis with a single dose of fluconazole. A descriptive analysis

Antecedentes: la candidiasis orofaríngea es frecuente en pacientes terminales. Los tratamientos habituales son nistatina oral y fluconazol en pautas largas. Se ha sugerido que una pauta con dosis única de fluconazol podría ser igualmente efectiva, lo cual supondría una mayor comodidad posológica y un menor coste del tratamiento. Objetivos: describir la experiencia de nuestro servicio en el tratamiento de la candidiasis orofaríngea en pacientes con enfermedad oncológica avanzada con una dosis única de 150 mg de fluconazol. Analizar la frecuencia y posibles factores asociados con la aparición de candidiasis orofaríngea en estos pacientes. Método: se estudiaron retrospectivamente todos los pacientes oncológicos terminales atendidos por un servicio de Cuidados Paliativos Domiciliario durante el año. Se recogieron datos de la historia clínica sobre el diagnóstico (según criterios clínicos), tratamiento y eficacia. Resultados: se incluyeron 96 de 102 pacientes. 24 pacientes (25%) tuvieron al menos un episodio de candidiasis orofaríngea. Un caso se consideró como ineficacia del tratamiento al tener un nuevo episodio en menos de 7 días. Todos los pacientes cumplieron adecuadamente el tratamiento. Como factores asociados con la aparición de candidiasis orofaríngea se detectó el uso de corticoides (p = 0,03) y la linfopenia (p = 0,04). Conclusiones: la dosis única de 150 mg de fluconazol parece eficaz para el tratamiento de la candidiasis orofaríngea en pacientes oncológicos terminales. Se precisan ensayos clínicos que comparen esta pauta con otros tratamientos empleados habitualmente. Los factores asociados con la aparición de candidiasis orofaríngea detectados en nuestro estudio fueron el tratamiento con corticoides y la linfopenia (AU)

Introduction: oropharyngeal candidiasis is a frequent infection inpatients receiving palliative care for advanced cancer. Most common treatments include oral nystatin and fluconazole for one or two weeks. It has been suggested that a single dose of fluconazole may also be effective, which would mean an easier dosage and lower costs. Objectives: to describe our department's experience with the the use of single doses (150 mg) of fluconazole in advanced cancer patients. To establish the prevalence of oropharyngeal candidiasis, and to find potentially related factors. Methods: all advanced cancer patients followed by a home palliative care team during 2002 were retrospectively studied. Information on diagnosis, treatment, and treatment effectiveness was obtained from patient follow-up records. Results: ninety-six of 102 patients were included. Twenty-four of them (25%) had at least one episode of oropharyngeal candidiasis. In one case treatment was considered ineffective because of the development of a new episode in less than 7 days. All patients completed their treatment appropriately. Use of steroids (p = 0.03) and lymphopenia (p = 0.04) were detected as factors related to oropharyngeal candidiasis. Conclusions: A single dose of fluconazole (150 mg) seems effective for the treatment of oropharyngeal candidiasis in advanced cancer patients. Further clinical trials are needed to compare this regimen with other treatments available. Use of steroids and lymphopenia were recognized as factors related to oropharyngeal candidiasis in these patients (AU)

In vitro activities of levofloxacin and comparable agents against middle ear fluid, nasopharyngeal, and oropharyngeal pathogens obtained from Costa Rican children with recurrent otitis media or failing other antibiotic therapy.

This study analyzes the in vitro activities of levofloxacin and other commonly used antimicrobials against middle ear fluid, nasopharyngeal, and oropharyngeal pathogens obtained from children with otitis media at risk of having a resistant pathogen. Levofloxacin proved to be very active against these pathogens and had intermediate activity against Streptococcus pyogenes.

Antimicrobial susceptibility of bacterial pathogens in the oropharynx of healthy school children in Turkey.

BACKGROUND & OBJECTIVES: Information on oropharyngeal carriage rates of Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes and Moraxella catarrhalis and their resistance pattern in healthy school children in Turkey is lacking. The present study was undertaken to determine the carriage rates and antimicrobial resistance of these bacterial pathogens in such children aged 6-14 yr in Manisa, Turkey. METHODS: A total of 1022 children were included from nine schools selected randomly from 32 schools. Throat swabs were cultured for bacteria which were identified using standard microbiological methods. Antimicrobial susceptibility was determined as per National Committee for Clinical Laboratory Standards guidelines. RESULTS: Of the 1022 children 240 (23.4%) harboured S. pneumoniae, 162 (15.8%) H. influenzae, 30 (2.9%) S. pyogenes and 82 (8%) M. catarrhalis in their oropharynx. For S. pneumoniae overall 17.9 per cent of the isolates were intermediately and 7 per cent were resistant to penicillin and resistance to erythromycin trimethoprim-sulphamethoxasole (TMP/SMX), and chloramphenicol was 13.7, 9.1 and 1.6 per cent, respectively. Ampicillin resistance observed in 20.9 per cent of H. influenzae isolates was associated with the presence of beta-lactamase, except two isolates interpreted as beta-lactamase-negative ampicillin resistant strains. Resistance of H. influenzae to TMP/SMX, chloramphenicol, azithromycin, cefaclor and amoxicillin/clavulanic acid was 14.2, 2.4, 1.8, 1.2 and 1.2 per cent, respectively. M.catarrhalis isolates produced beta-lactamase in 80.5 per cent of the cases and all were susceptible to macrolides and clavulanic acid/amoxicillin combination; the highest rate of resistance of 17 per cent was for TMP/SMX. One (3.3%) isolate of S. pyogenes was resistant to macrolides tested. INTERPRETATION & CONCLUSION: Our data shows that upper respiratory tract of about 50 per cent children was colonized with respiratory pathogens. There is a need for surveillance of nasopharyngeal carriage of resistant strains in healthy school children.

Effect of oral zinc supplementation on agents of oropharyngeal infection in patients receiving radiotherapy for head and neck cancer.

We aimed to investigate the effect of zinc supplementation on oropharyngeal infections in immunocompromised patients. Thirty patients receiving radiotherapy for head and neck cancer received 150 mg/day zinc or placebo, orally, during radiotherapy and for a further 6 weeks. None received antibiotics during this period. Oropharyngeal samples were collected 1 day before the first course and 1 day after the last course of radiotherapy, and 1 week and 6 weeks after radiotherapy. Samples were cultured and pathogens identified using microbial diagnostic and gas chromatography methods. Coagulase-positive and -negative staphylococci, group A beta-haemolytic streptococci, Streptococcus pneumoniae, and Candida species were detected in both groups, but some infections, especially with Candida species and staphylococci, were prevented by zinc supplementation. We therefore suggest use of low-dose antibiotics and oral zinc supplementation in patients with these infections. No effects of zinc supplementation were observed on group A beta-haemolytic streptococci and Streptococcus pneumoniae, making it essential to start antimicrobial chemotherapy before radiotherapy.

Efficacy of CS-758, a novel triazole, against experimental fluconazole-resistant oropharyngeal candidiasis in mice.

The therapeutic efficacy of CS-758, a novel triazole, was evaluated against experimental murine oropharyngeal candidiasis induced by Candida albicans with various susceptibilities to fluconazole. Against infections induced by strains with various susceptibilities to fluconazole, the efficacy of fluconazole was strongly correlated with the MIC of fluconazole, as measured by the NCCLS method, and agreed with the NCCLS interpretive breakpoints, suggesting that the efficacies of new drugs could be predicted by using this model. The results of the fungal burden study corresponded with the results of the histopathological study. CS-758 exhibited potent in vitro activity (MICs, 0.004 to 0.06 micro g/ml) against the strains used in this murine model including fluconazole-susceptible dose-dependent and fluconazole-resistant strains (fluconazole MICs, 16 to 64 micro g/ml). CS-758 exhibited excellent efficacy against the infections induced by all the strains including a fluconazole-resistant strain, and the reductions in viable cell counts were significant at 10 and 50 mg/kg of body weight/dose. Fluconazole was not effective even at 50 mg/kg/dose against infections induced by a fluconazole-resistant strain (fluconazole MIC, 64 micro g/ml). These results suggest that CS-758 is a promising compound for the treatment of oropharyngeal candidiasis including fluconazole-refractory infections.

Clinical and mycological responses to fluconazole and fluconazole MIC in oropharyngeal candidiasis in HIV-infected patients.

INTRODUCTION: OPC is a common opportunistic infection in HIV-infected patients. Although some patients are asymptomatic, progression of the disease may occur leading to esophageal candidiasis. Fluconazole resistant candidiasis has been reported in several international studies. OBJECTIVES: This study aimed to test the MICs (minimal inhibitory concentrations) to fluconazole of Candida species isolated from mouthwash specimens of 54 HIV positive patients with oral candidiasis. Clinical and mycological responses to fluconazole were also assessed in 16 patients. MATERIAL AND METHOD: This was a prospective study. Mouthwash specimens were cultured on sabouraud dextrose agar twice. Candida species identification was performed and MICs for fluconazole were obtained using NCCLS guidelines. Clinical and mycological responses were assessed on day 14 and 42 in 16 patients who received a 14-day course of fluconazole. RESULTS: 48/54 patients (88.89%) were found to carry pure C. albicans. The other 6 patients (11.11%) had mixed Candida species on cultures. Among these 6 patients, 5 patients had mixed C. albicans and C. glabrata, and 1 patient had C. albicans and C. krusei. Fluconazole MICs of C. albicans, C. glabrata, and C. krusei ranged from 0.125-32 (median=0.250), 4-64 (median=2), and 8 g/L respectively. This study showed that the MICs to fluconazole of oropharyngeal Candida was a good predictor of the therapeutic responses.