OBJECTIVEOver the past several decades, there has been a significant increase in allergy and asthma in the world, which correlates with alterations in microflora and widespread use of antibiotics. The authors have developed a mouse model of antibiotics-induced microbiota disruption. In that model, mice were challenged by intranasal exposure to Aspergillus fumigatus allergens to explore the relation of allergic airway response and intestinal microflora disruption.

METHODSSixty female BALB/c mice were divided at random into 6 groups with 10 mice in each. (1) First antibiotic therapy group: the mice were given oral cefoperazone for 7 days, on day 7, mice were inoculated with Candida albicans (10(9)/ml, 50 microl) orally. (2) First control group: the mice were treated as first antibiotic therapy group, but cefoperazone and Candida albicans were replaced by saline. The mice in groups (1) and (2) were sacrificed on day 8, and cecal contents were collected for quantitative analysis of the intestinal bacterial flora. (3) Antibiotic therapy and challenge group: the mice were treated as the first antibiotic therapy group, then challenged (day 9 and 16) by intranasal exposure to Aspergillus fumigatus allergen. (4) Second antibiotic therapy group: the mice were treated as the first antibiotic therapy group, then challenged (day 9 and 16) by intranasal exposure to saline. (5) Challenge group: the mice were treated as the first control group, then challenged (day 9 and 16) by intranasal exposure to Aspergillus fumigatus allergen. (6) Second control group: the mice were treated as the first control group, then challenged (day 9 and 16) by intranasal exposure to saline. The mice in (3) - (6) group were killed for analysis of allergic airway response on day 19.

RESULTSThe quantity of Enterobacteriaceae, Enterococcus, Bifidobacterium and Lactobacillus in first antibiotic therapy group was significantly lower than that in the first control group, the quantity of Candida albicans increased in the first antibiotic therapy group as compared with the first control group. Mice intestinal microflora were disrupted with weight reduction and increased moisture in feces. After challenging with Aspergillus fumigatus allergens via intranasal inhalation, the total cell count, eosinophils, lymphocytes and neutrophils increased in BALF, especially in bronchoalveolar lavage fluid (BALF) from the mice in antibiotic therapy and challenge groups. IL-4 level in BALF from antibiotic therapy and challenge group (45.35 +/- 2.36) pg/ml was higher than that in the second control group (35.32 +/- 2.53) pg/ml. The expression of GATA-3 mRNA in the mice lung tissue (0.569 +/- 0.023) was higher than that in the second control group (0.410 +/- 0.020), and the ratios of T-bet/GATA-3 (0.578 +/- 0.021) decreased as compared with that in the second control group (0.804 +/- 0.035). IFN-gamma level in BALF from any group was not significantly different. In the absence of antibiotics, mice exposed to Aspergillus fumigatus allergen did not develop an allergic response in the airways.

CONCLUSIONSThe allergic (Th2) immune response can be induced by airway challenge with Aspergillus fumigatus allergen in the mice in which the intestinal microflora disruption resulted from antibiotic therapy, this result suggests that the intestinal microflora disruption resulted from antibiotic therapy is a risk factor for allergy and asthma.

Animals ; Anti-Bacterial Agents ; adverse effects ; Antibiosis ; Aspergillus fumigatus ; chemistry ; growth & development ; Asthma ; drug therapy ; microbiology ; Bronchoalveolar Lavage Fluid ; microbiology ; Cefoperazone ; therapeutic use ; Disease Models, Animal ; Eosinophils ; drug effects ; microbiology ; Female ; Hypersensitivity ; drug therapy ; microbiology ; Hypersensitivity, Immediate ; microbiology ; Intestines ; drug effects ; microbiology ; physiopathology ; Lung ; drug effects ; microbiology ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; adverse effects ; immunology ; Respiratory System ; microbiology

A worsening scenario of drug-resistant tuberculosis has increased the need for new treatment strategies to tackle this worldwide emergency. There is a pressing need to simplify and shorten the current 6-month treatment regimen for drug-susceptible tuberculosis. Rifamycins and fluoroquinolones, as well as several new drugs, are potential candidates under evaluation. At the same time, treatment outcomes of patients with drug-resistant tuberculosis should be improved through optimizing the use of fluoroquinolones, repurposed agents and newly developed drugs. In this context, the safety and tolerance of new therapeutic approaches must be addressed.
Animals ; Antitubercular Agents/adverse effects/*therapeutic use ; *Drug Discovery ; *Drug Repositioning ; Drug Resistance, Bacterial ; Drug Therapy, Combination ; Extensively Drug-Resistant Tuberculosis/drug therapy/microbiology ; Humans ; Lung/*drug effects/microbiology ; Mycobacterium tuberculosis/*drug effects/pathogenicity ; Treatment Outcome ; Tuberculosis, Multidrug-Resistant/diagnosis/*drug therapy/microbiology ; Tuberculosis, Pulmonary/diagnosis/*drug therapy/microbiology

Mycobacterium abscessus (M. abscessus) is the second most common nontuberculous mycobacteria (NTM) in South Korea. Nevertheless, the diagnosis and treatment of M. abscessus lung disease can be problematic. Surgical resection has been tried for patients with localized M. abscessus lung disease refractory to medical treatment. Here, we report on a 25-year-old woman with M. abscessus lung disease who had been diagnosed and treated three times for pulmonary tuberculosis. She was initially diagnosed as having M. intracellulare lung disease; however, M. abscessus was isolated after several months of medication. She had multiple bronchiectatic and cavitary lesions bilaterally, and M. abscessus was repeatedly isolated from her sputa despite prolonged treatment with clarithromycin, ethambutol, moxifloxacin, and amikacin. She improved only after sequential bilateral lung resection. Based on the experience with this patient, we suggest that, if medical treatment fails, surgical resection of a diseased lung should be considered even in patients with bilateral lesions.
Adult ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Female ; Humans ; Lung Diseases/*drug therapy/*microbiology/surgery ; Mycobacteria, Atypical/drug effects/*physiology

Antifungal Agents ; therapeutic use ; Female ; Humans ; Lung ; microbiology ; pathology ; Lung Diseases, Fungal ; drug therapy ; etiology ; Middle Aged ; Schizophyllum ; drug effects ; pathogenicity ; Voriconazole ; therapeutic use

BACKGROUNDIt is recognized that Haemophilus influenzae isolated from patients with otitis media forms biofilms both in vitro and in vivo, suggesting that biofilm formation in vivo might play an important role in the pathogenesis and chronicity of otitis media, but the effect of antibiotics on biofilm has not been well studied. We investigated the impact of ciprofloxacin and azithromycin on bacterial biofilms formed by Haemophilus influenzae in vitro in this study.

METHODSEleven strains of Haemophilus influenzae were isolated from sputum specimens collected from patients with acute exacerbation of chronic obstructive pulmonary diseases. Formation of bacterial biofilm was examined by crystal violet assay and a scanning electron microscope. Alterations of biofilms were measured under varying concentrations of azithromycin and ciprofloxacin.

RESULTSStriking differences were observed among strains with regard to the ability to form biofilm. Typical membrane-like structure formed by bacterial cells and extracellular matrix was detected. Initial biofilm synthesis was inhibited by azithromycin and ciprofloxacin at concentrations higher than two-fold minimal inhibitory concentration. Disruption of mature biofilms could be achieved at relatively higher concentration, and ciprofloxacin displayed more powerful activity.

CONCLUSIONSHaemophilus influenzae is capable of forming biofilm in vitro. Sufficient dosage might control early formation of biofilms. Ciprofloxacin exerts better effects on breakdown of biofilm than azithromycin at conventional concentration in clinics.

Anti-Bacterial Agents ; pharmacology ; Azithromycin ; pharmacology ; Biofilms ; drug effects ; Ciprofloxacin ; pharmacology ; Haemophilus influenzae ; drug effects ; isolation & purification ; Humans ; Lung Diseases, Obstructive ; microbiology ; Microbial Sensitivity Tests ; Microscopy, Electron, Scanning

Adult ; Aged ; Aged, 80 and over ; Anthracosis ; complications ; microbiology ; Anti-Bacterial Agents ; pharmacology ; Drug Resistance, Bacterial ; Humans ; Lung Neoplasms ; complications ; microbiology ; Male ; Middle Aged ; Pseudomonas Infections ; microbiology ; Pseudomonas aeruginosa ; drug effects

A 50-year-old male visited the outpatient clinic and complained of fever, poor oral intake, and weight loss. A chest X-ray demonstrated streaky and fibrotic lesions in both lungs, and chest CT revealed multifocal peribronchial patchy ground-glass opacities with septated cystic lesions in both lungs. Cell counts in the bronchoalveolar lavage fluid revealed lymphocyte-dominant leukocytosis, and further analysis of lymphocyte subsets showed a predominance of cytotoxic T cells and few T helper cells. Video-assisted wedge resection of the left upper lobe was performed, and the histologic examination was indicative of a Pneumocystis jirovecii infection. Trimethoprim-sulfamethoxazole (TMP-SMX) was orally administered for 3 weeks; however, the patient complained of cough, and the pneumonia was aggravated in the follow-up chest X-ray and chest CT. Molecular studies demonstrated mutations at codons 55 and 57 of the dihydropteroate synthase (DHPS) gene, which is associated with the resistance to TMP-SMX. Clindamycin-primaquine was subsequently administered for 3 weeks replacing the TMP-SMX. A follow-up chest X-ray showed that the pneumonia was resolving, and the cough was also alleviated. A positive result of HIV immunoassay and elevated titer of HCV RNA indicated HIV infection as an underlying condition. This case highlights the importance of careful monitoring of patients with P. jirovecii pneumonia (PCP) during the course of treatment, and the molecular study of DHPS mutations. Additionally, altering the anti-PCP drug utilized as treatment must be considered when infection with drug-resistant P. jirovecii is suspected. To the best of our knowledge, this is the first case of TMP-SMX-resistant PCP described in Korea.
Anti-Bacterial Agents/*administration & dosage ; Drug Resistance, Bacterial ; Humans ; Lung/microbiology/radiography ; Male ; Middle Aged ; Pneumocystis jirovecii/*drug effects/genetics/isolation & purification/physiology ; Pneumonia/*drug therapy/immunology/microbiology/radiography ; Sulfamethoxazole/*administration & dosage ; Trimethoprim/*administration & dosage

beta-defensins possess a broad spectrum of antimicrobial activity. In this study its in vivo antibacterial effect was evaluated by using gene transfer. Rat beta-defensin-2 (rBD2) recombinant pBK-CMV-rBD2 and pCD-NA-3, 1-Myc-His(+)-rBD2 were constructed. Then, by use of liposome agent, the recombinants were delivered into rat airway via tracheal injection. The rBD-2 mRNA expression was detected in the trachea by RT-PCR and its protein expression was determined in the lungs by the tag His immunostaining, 24 hours after inoculation via trachea, the count of P. areuginosa in the lung of rat transfected with pBK-CMV-rBD2 markedly decreased, compared with the control (n = 8, P = 0.003). The data presented in this study provide evidence that airway beta-defensin-2-gene transfer can protect the rat against bacterial infection in vivo, suggesting the beta-defensins as part of the innate host defense system can be of potential applicability.
Animals ; Bacteria ; drug effects ; Lung ; microbiology ; physiology ; Plasmids ; genetics ; Rats ; Rats, Wistar ; Respiratory Tract Infections ; prevention & control ; Transfection ; beta-Defensins ; genetics ; pharmacology ; therapeutic use

OBJECTIVETo analyze the condition of early (≤ 30 d) postoperative pulmonary infection in children after living donor liver transplantation (LDLT).

METHODThe clinical data of 36 cases undergoing LDLT in Children's Hospital of Chongqing Medical University were analyzed retrospectively from June 2006 to December 2009.

RESULTOf 36 cases without preoperative respiratory disease, 17 were boys, 19 were girls. Their age ranged from 2 months to 14 years. Pulmonary infection developed in 24 patients, of whom 4 cases died (17%) and 3 deaths were related to pulmonary infection. Pulmonary infection occurred in 17 of 20 infants (85%) and 10 of 11 cases (91%) with liver function of Child-Pugh grade C. Twenty cases (83%) developed pulmonary infection within first 2 weeks after LDLT. Totally 65 pathogenic strains of microorganisms were isolated, in which Gram-negative bacteria, Gram-positive bacteria and fungi were 46 strains, 5 strains, 14 strains respectively. The most frequently isolated bacteria were Pseudomonas aeruginosa (14 strains), Klebsiella pneumoniae (8 strains) and Acinetobacter baumannii (8 strains). Pseudomonas aeruginosa showed a resistance rate of almost 100% to cotrimoxazole, tetracycline, chloramphenicol, ampicillin, the first, the second and some of the third generation cephalosporins. Klebsiella pneumoniae producing extended spectrum beta-lactamase had a resistance rate of almost 100% to beta-lactams except carbapenems. Acinetobacter baumannii was exquisitely susceptible to carbapenems, but showed a high resistance to penicillins and cephalosporins. Candida albicans, which was the most common fungus, showed a susceptibility rate of 100% to amphotericin B. In the LDLT recipients of pulmonary infection, cytomegalovirus (CMV) infections occurred in 2 patients and Epstein Barr virus (EBV) infection in 1 patient.

CONCLUSIONThe incidence of early postoperative pulmonary infection was high in children undergoing LDLT, especially in infants. And the mortality should not be ignored. The high risk period for infection was within the first 2 weeks after operation. The pathogens were mainly Gram-negative bacteria, which showed high and multidrug resistance.

Adolescent ; Anti-Bacterial Agents ; therapeutic use ; Antifungal Agents ; therapeutic use ; Bacterial Infections ; drug therapy ; etiology ; microbiology ; Child ; Child, Preschool ; Drug Resistance, Bacterial ; Female ; Gram-Negative Bacteria ; drug effects ; isolation & purification ; Gram-Positive Bacteria ; drug effects ; isolation & purification ; Humans ; Infant ; Liver Transplantation ; Living Donors ; Lung Diseases ; drug therapy ; etiology ; microbiology ; Male ; Postoperative Complications ; drug therapy ; epidemiology ; etiology ; Retrospective Studies ; Risk Factors

Adult ; Aged ; Aged, 80 and over ; Coal Mining ; Humans ; Lung Neoplasms ; complications ; microbiology ; Male ; Methicillin Resistance ; Microbial Sensitivity Tests ; Middle Aged ; Pneumoconiosis ; complications ; microbiology ; Staphylococcus aureus ; drug effects ; isolation & purification