Retinoic acid induces antimicrobial peptides and cytokines leading to Mycobacterium tuberculosis elimination in airway epithelial cells.

Tuberculosis (TB) is the leading cause of death by a single infectious agent, Mycobacterium tuberculosis (Mtb). Alveolar macrophages and respiratory epithelial cells are the first cells exposed to Mtb during the primary infection, once these cells are activated, secrete cytokines and antimicrobial peptides that are associated with the Mtb contention and elimination. Vitamins are micronutrients that function as boosters on the innate immune system, however, is unclear whether they have any protective activity during Mtb infection. Thus, we investigated the role of vitamin A (retinoic acid), vitamin C (ascorbic acid), vitamin D (calcitriol), and vitamin E (alfa-tocopherol) as inductors of molecules related to mycobacterial infection in macrophages and epithelial cells. Our results showed that retinoic acid promotes the expression of pro- and anti-inflammatory molecules such as Thymic stromal lymphopoietin (TSLP), ß-defensin-2, IL-1ß, CCL20, ß-defensin-3, Cathelicidin LL-37, TGF-ß, and RNase 7, whereas calcitriol, ascorbic acid, and α-tocopherol lead to an anti-inflammatory response. Treatment of Mtb-infected epithelial cells and macrophage-like cells with the vitamins showed a differential response, where calcitriol reduced Mtb in macrophages, while retinoic acid reduced infection in epithelial cells. Thereby, we propose that a combination of calcitriol and retinoic acid supplementation can drive the immune response, and promotes the Mtb elimination by increasing the expression of antimicrobial peptides and cytokines, while simultaneously modulating inflammation.

Spotlight on inhaled ciprofloxacin and its potential in the treatment of non-cystic fibrosis bronchiectasis.

Non-cystic fibrosis bronchiectasis (NCFB) is a severe chronic illness characterized by irreversible dilation of airways and thickening of bronchial walls, chronic inflammation, repeated infections, and progressive obstruction of the airways. In contrast to cystic fibrosis bronchiectasis (CFB), which is a well-defined genetic disorder, NCFB is a heterogeneous disease caused by many different medical entities. Inhaled antibiotics are effective for patients with CFB, but their efficacy in NCFB has not been proven. The main pathogens involved in the colonization of patients with bronchiectasis are Haemophilus influenza, Moraxella catarrhalis, Staphylococcus aureus, and Pseudomonas aeruginosa. The latter is associated with increased morbidity and mortality. In addition, in NCFB, P. aeruginosa strains are frequently more resistant than those in CFB. At present, there are no approved inhaled antibiotic therapies for NCFB patients. Inhaled ciprofloxacin has been under investigation in the last few years. In two phase II randomized, double-blind, placebo-controlled trials, the use of inhaled ciprofloxacin was significantly associated with reduction in sputum bacterial density and greater eradication rates. In four phase III randomized, double-blind, placebo-controlled trials, the results regarding the time of the first exacerbation and the rate of exacerbations were inconsistent. Specifically, ORBIT-4 and RESPIRE-1 trials showed clinical benefit (prolongation of the time of the first exacerbation and reduced rate of exacerbations in the treatment group compared to the placebo group), whereas the ORBIT-3 and RESPIRE-2 failed to achieve their primary endpoints. The RESPIRE-1 was the first trial that examined the 14-days on/off course separate from the standard 28-days on/off regimen, which is based on CFB protocol treatments. The current data on the efficacy of inhaled ciprofloxacin are encouraging, but further evaluation is needed to determine the appropriate target group and the ideal duration of treatment.

[Morpho-functional characteristics of conducting airways and the respiratory portion of rat lung under the conditions of intratracheal infection from the positions of the neuroendocrine regulation of reparative histogeneses].

With the use of light and electron microscopy and immunohistochemistry, the morpho-functional changes in the lungs, the hypothalamus and the neurohypophysis were studied in 45 outbred albino male rats 1, 3, 7 and 14 days after the intratracheal infusion of Staphylococcus aureus strains either possessing anti-lactoferrin activity (ALfA(+)) or lacking it (ALfA(-)). After the infusion of ALfA(+) bacteria, the bronchial wall and the respiratory portion of the lungs demonstrated the destructive changes of tissues, sclerosis phenomena, disturbances of regeneration processes (polypoid outgrowth, metaplasia), while in the neurohypophysis a delay in the release of neurosecretion into the blood from the terminals of nonapeptidergic neurosecretory cells took place. These phenomena were not observed after the infection with ALfA(-)bacteria. The results obtained indicate the disturbances of the structural-functional homeostasis of pulmonary tissues associated with bacterial ALfa, taking place together with the limitations of the hypothalamic neurosecretion.

Occurrence of the aacA4 gene among multidrug resistant strains of Pseudomonas aeruginosa isolated from bronchial secretions obtained from the Intensive Therapy Unit at University Hospital in Bialystok, Poland.

The aim of this study was to investigate the prevalence of the aacA4 gene in a population of multidrug resistant strains of P. aeruginosa isolated from bronchial secretions obtained from the Intensive Therapy Unit (ITU). Twelve MDR isolates were tested for antibiotic susceptibility and the presence of the aacA4 gene. In this study, 58.3% of the strains contained (6')-Ib' aminoglycoside acetyltransferase gene. All of the studied strains (aacA4-positive and aacA4-negative) were susceptible only to colistine (100%). Among other antibiotics, the lowest resistance rates were those shown against ceftazidime (14.3% to 20%) and imipenem (28.6% to 40%). Our studies frequently revealed the presence of the aacA4 gene as a factor responsible for resistance; it is probable that other mechanisms of resistance to aminoglycoside antibiotics also occurred.

Efficacy of moxifloxacin in the treatment of bronchial colonisation in COPD.

This study was designed to investigate the efficacy of moxifloxacin for the eradication of bacterial colonisation of the airways in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Out of 119 stable patients with COPD screened, 40 (mean age 69 yrs, mean forced expiratory volume in 1 s 50% predicted) were colonised with potentially pathogenic microorganisms (PPMs) and were included in a randomised, double-blind, placebo-controlled trial with moxifloxacin 400 mg daily for 5 days. Eradication rates were 75% with moxifloxacin and 30% with placebo at 2 weeks (p = 0.01). Bacterial persistence at 8 weeks was still higher (not significantly) in the placebo arm (five (25%) out of 20 versus one (5%) out of 20; p = 0.18). The frequencies of acquisition of a new PPM were high and similar in both treatment groups; consequently, the prevalence of colonisation at 8 weeks was also similar between treatment arms. No difference was found in the number of patients with exacerbations during the 5-month follow-up. Only the acquisition of a new PPM during follow-up showed a statistically significant relationship with occurrence of an exacerbation. Moxifloxacin was effective in eradicating PPMs in patients with positive sputum cultures. However, most patients were recolonised after 8 weeks of follow-up. Acquisition of a new strain of bacteria was associated with an increased risk of developing an exacerbation.

[Endocytosymbiosis of microorganisms in mammal eukaryotic cells and factors of its regulation].

Morphofunctional equivalents of the process of long-term intracellular prokaryotes--eukaryotes interaction were studied by light and electron microscopy. The mechanisms for adaptation, elaborated in the course of evolution of bacteria-host interaction, were analysed on the ultrastructural level. A concept on the role of hypothalamic nonapeptides, as factors of regulation of intracellular persistence and symbiosis of prokaryotes, is discussed.

[Approaches to combined therapy of pulmonary tuberculosis in adolescents excreting drug-resistant Mycobacterium tuberculosis]. / Podkhody k kompleksnoi terapii tuberkuleza legkikh u podrostkov, vydeliaiushchikh ustoichivye k khimiopreparatam mikobakterii tuberkuleza.

The data are presented on 138 adolescents with active, advanced tuberculosis. M. tuberculosis were detected in the sputum and bronchial lavage of 75(54.3%) adolescents. 32 patients had M. tuberculosis resistant to drugs. 28 untreated patients demonstrated primary drug resistance (37.5%). Intensive combined treatment with consideration of bacterial resistance, administration of reserve drugs, wide spectrum medicines bring about positive results, but in patients with drug resistance positive dynamics is slow.

[Changes in the intrabronchial microflora of patients with chronic bronchitis after inhaling mineral water]. / Izmeneniia intrabronkhial'noi mikroflory u bol'nykh khronicheskim bronkhitom posle ingaliatsii s mineral'noi vodoi.

The authors' investigations show that inhalations of sodium chloride bromine-iodine water given in spray modify intrabronchial microflora of patients with chronic bronchitis reducing the number of the pathogenic bacteria and elevating the number of bacteria typical for physiological composition of the bronchial mucus.

Effectiveness of antimicrobial mouthrinses on aerosols produced by an air polisher.

PURPOSE: The purpose of this examiner-blind investigation was to study the effect of two antimicrobial mouthrinses on the quantity and potential respiratory-penetrating ability of microorganisms generated by an air-abrasive polisher. METHODS: Forty-five adult subjects were randomly assigned to one of three groups and asked to rinse for 30 seconds with 15 ml of either a 0.12% chlorhexidine rinse, an essential oil mouthrinse, or water prior to air polishing. Prior to treatment, microbes in ambient air were collected for five minutes using an Andersen air sampler. This device simulates the human respiratory system and collects airborne microbes by means of blood agar plates stacked in a cascade impact system. Bacteria found at stages two, four, and six--representing the pharynx, bronchi, and alveoli-were collected and counted in this study. During three minutes of air-abrasive instrumentation and two minutes immediately following, airborne microbes were again collected. Agar plates removed from the sampler were incubated for 24 hours at 37 degrees C. Colony-forming units per cubic foot of air (CFUs/ft(3)) were enumerated using a Lab Line colony counter. Data were analyzed using a two-factor repeated measure ANOVA and Dunn's multiple mean comparison techniques. RESULTS: Results showed no significant effect of prerinsing among treatment groups. An increase in CFUs/ft(3) was found at each sequential stage of the air sampler, resulting in a statistically significant within-group effect (p< or =.05). Additionally, a significant interaction was found between prerinse treatment and respiratory stage (p< or =.05) . CONCLUSION: While the air-abrasive polisher produced significant amounts of deeply penetrating bacterial aerosol, differences in CFUs/ft(3) generated following the antimicrobial prerinsing tested are of little clinical significance.

Bronchoscopy versus empirical therapy in HIV-infected patients with presumptive Pneumocystis carinii pneumonia. A decision analysis.

The outcomes of alternative strategies for the management of pulmonary complications in patients infected with the human immunodeficiency virus (HIV) and with suspected Pneumocystis carinii pneumonia were compared using a decision analysis model. A decision tree was constructed using baseline probabilities derived from published data and expert opinion. The case scenario analyzed was that of a patient not currently receiving anti-Pneumocystis prophylaxis who presents with moderate pulmonary symptoms and fulfills the Centers for Disease Control (CDC) criteria for presumptive P. carinii pneumonia. Two strategies were compared: (1) early bronchoscopy with appropriate therapy based on the results, and (2) empiric treatment for P. carinii (trimethoprim/sulfamethoxazole or pentamidine, and steroids) with delayed bronchoscopy in those not responding to 5 days of empiric therapy. The expected 1-month survival rate (with and without quality of life adjustment) was found to be essentially the same for the two strategies using the baseline probabilities, and the decision remained a toss-up within the clinically relevant range of published probabilities for P. carinii pneumonia in patients fulfilling the CDC criteria. Because early bronchoscopy does not offer any additional survival benefits and is associated with greater costs and disutility, empiric therapy would appear to be the superior management strategy in this scenario.

[Use ciprofloxacin in children with mucoviscidosis]. / Opyt primeneniia tsiprofloksatsina u detei, bol'nykh mukovistsidozom.

Ciprofloxacin was used in treatment of 13 children aged 6 to 18 years with mucoviscidosis and exacerbation of the bronchopulmonary process. The dose of the drug was 20 to 30 mg/kg a day when administered orally or 15 mg/kg a day when administered at first intravenously and then orally. The treatment course averaged 14 days. The indications to the drug use were: severe processes of mucoviscidosis and chronic colonization of the bronchial mucosa and lung tissues with Pseudomonas aeruginosa (mucoid or nonmucoid form) sensitive to ciprofloxacin and resistant to other antibiotics. The trials showed that ciprofloxacin was highly efficient: the state of the patients improved and the inflammation index of the total blood count normalized. However, eradication of P. aeruginosa from the respiratory tracts was not observed. The drug allergy in 1 patient and a transient increase in the level of transaminases in 5 patients as the adverse reactions were recorded.

Safety and efficacy of using high-dose topical and nebulized anesthesia to obtain endobronchial cultures.

We evaluated the safety and efficacy of high-dose topical and nebulized airway anesthesia in normal volunteers and in patients undergoing diagnostic fiberoptic bronchoscopy. Lidocaine solution (4 percent) was used for gargling, for spraying the palate and oropharynx with an atomizer, and for nebulization with an air-powered nebulizer (mean total dose, 1,682 mg) and 2 percent lidocaine (Xylocaine) jelly for anesthetizing nasal passages. In six normal subjects and in eight patients, lidocaine blood levels were measured at baseline, after gargling, after spraying, after nebulization, and then at 5, 10, 15, 30, and 60 min; 19 normal subjects and ten patients underwent the same anesthesia protocol but had no blood drawn. Fiberoptic bronchoscopy was performed in 21 normal volunteers and in 18 patients and cultures obtained using the protected specimen brush. Additional endobronchial lidocaine (mean 256 mg) was given to the 18 patients after collecting the microbiology specimens. Peak lidocaine blood levels remained below 6 micrograms/ml in all cases. Cough and discomfort during bronchoscopic examination was absent or minimal in 17 of 21 normal subjects (80 percent) and in 14 of 18 patients (77 percent) and was severe in only one instance (5 percent). There were no related complications. Using only topical and nebulized anesthesia is safe and effective for performing fiberoptic bronchoscopy, especially when bacterial cultures are to be obtained and endobronchial instillation of lidocaine must be avoided.

Identification of contaminants during primary isolation of mycobacteria in the BACTEC system with the antimicrobial supplement PACT.

1500 sputum specimens and bronchial washings were cultured for mycobacteria. One half of the specimen was treated with N-acetyl-L-cysteine--sodium hydroxide (3%) (NALC) and the other with sodium dodecyl (lauryl) sulfate--sodium hydroxide (1%) (SDS). The different species of contaminants found with each pretreatment method with the BACTEC radiometric system were identified. Contamination occurred in 6% by using SDS and in 10% by using NALC. The SDS method was more effective against Bacillus ssp. and Streptomyces ssp., the major contaminants. However, the growth of Pseudomonas ssp. was a problem in both methods.

A cluster of Mycobacterium gordonae isolates from bronchoscopy specimens.

During a 2.5-year period, 52 patients at Yale-New Haven Hospital had Mycobacterium gordonae recovered from specimens obtained by suction at bronchoscopy; 2 of them also had smears positive for acid-fast bacilli. Almost all of the isolates came from patients bronchoscoped by the same physician, one of 4 who performed the procedure during that period. Only this physician added one drop of green dye, stored in a 100-ml bottle, to the cocaine used for topical anesthesia during the procedure; cultures of the dye yielded Mycobacterium gordonae. Contamination with this organism, a cause of positive acid-fast smears, may result in an initial inappropriate diagnosis of Mycobacterium tuberculosis.