Inhibition of fungal growth by Pseudomonas aeruginosa and Pseudomonas cepacia isolated from patients with cystic fibrosis

This study was undertaken because of the infrequency of infections due to Candida species in patients with cystic fibrosis despite their extensive treatment with broad-spectrum antibiotics. In vitro susceptibility studies revealed significant inhibition of 11 strains of fungi known to infect human beings by 10 strains of Pseudomonas aeruginosa and nine strains of Pseudomonas cepacia isolated from the sputum of patients with cystic fibrosis. The fungi were Candida krusei, Candida keyfr, Candida guillermondii, Candida tropicalis, Candida lusitaniae, Candida parapsilosis, Candida pseudotropicalis, Candida albicans, Torulopsis glabrata, Saccharomyces cerevisiae and Aspergillus fumigatus. Inhibition of fungal growth by Escherichia coli (NCTC 10418), Staphylococcus aureus (NCTC 6571) and Haemophilus influenzae (NCTC 11931) could not be demonstrated. The continued presence in the sputum of patients with cystic fibrosis of strains of P. aeruginosa and P. cepacia, which produce antifungal substances, may inhibit growth of Candida species and so prevent overt Candida infections. A. fumigatus would seem to be the most important fungus causing disease in patients with cystic fibrosis. It is therefore interesting to note that this was the most resistant of all the fungi tested for inhibition by P. aeruginosa and P. cepacia.     

Hyperoxia exaggerates bacterial dissemination and lethality in Pseudomonas aeruginosa pneumonia

Effects of hyperoxia on lethality in mice with Pseudomonas aeruginosa pneumonia were defined, and protective roles of macrolides were examined both in vitro and in vivo. Sub-lethal hyperoxia accelerated lethality of mice with P. aeruginosa pneumonia. Bacterial number was not different in the lungs, but higher in the liver of mice in hyperoxic conditions. Filter-sterilized culture supernatants of bacteria induced loss of viability of alveolar epithelial cells, which was exaggerated in hyperoxia. Metalloprotease blocking by inhibitor or gene-disruption in bacteria resulted in partial reduction of cytotoxic activity in culture supernatants. Co-culture of bacteria with sub-inhibitory concentrations of macrolides, such as azithromycin, reduced cytotoxic activity in the culture supernatants. Azithromycin provided significant survival benefit in hyperoxia–pneumonia model, which was associated with suppression of bacterial dissemination to extra-pulmonary organs. These results suggest that hyperoxia serves as an important cofactor for bacterial dissemination and lethality of P. aeruginosa pneumonia. Our data identify the potential of macrolides to protect individuals with P. aeruginosa pneumonia in the setting of hyperoxia.     

Increased adherence to human epithelial cells of resistant Pseudomonas aeruginosa strains

The adherence of Pseudomonas aeruginosa strains to human epithelial cells from the buccal mucosa, large intestine and urinary tract was studied. Strains resistant to gentamicin and carbenicillin, derived by laboratory training, exhibited enhanced adherence as compared to their sensitive parent strain. The same was found with a strain showing an R-factor acquired resistance to gentamicin. This phenomenon was observed with all epithelial cells tested regardless of their anatomical origin. These results suggest that resistant strains of P. aeruginosa are more likely to colonise mucosal surfaces.     

Effectiveness and safety of colistin for the treatment of multidrug-resistant Pseudomonas aeruginosa infections

Purpose:   

To describe the clinical and microbiological outcomes of patients infected with multidrug-resistant Pseudomonas aeruginosa (MDRP) treated with colistin (colistimethate sodium) and the adverse events observed with this treatment.     

Typing of non-serogroupable Neisseria meningitidis by means of sensitivity to R-type pyocines of Pseudomonas aeruginosa

Thirty-three (66 per cent) of 50 non-serogroupable isolates of Neisseria meningitidis could be typed on the basis of their sensitivities to partially purified rod-type (R-type) pyocines from 13 strains of Pseudomonas aeruginosa. Only seven (11 per cent) of 63 serogroupable meningococci were sensitive to the test pyocines. The pyocine typing method is particularly applicable to the labelling of strains in which autoagglutinability precludes the standard agglutination typing procedure.     

Pseudomonas aeruginosa in a neonatal intensive care unit: molecular epidemiology and infection control measures

Background  

Pseudomonas aeruginosa, a non-fermentative, gram-negative rod, is responsible for a wide variety of clinical syndromes in NICU patients, including sepsis, pneumonia, meningitis, diarrhea, conjunctivitis and skin infections. An increased number of infections and colonisations by P. aeruginosa has been observed in the neonatal intensive care unit (NICU) of our university hospital between 2005 and 2007.     

不同疾病标本中铜绿假单胞菌分离鉴定与多重耐药性分析

目的 了解不同疾病铜绿假单胞菌的感染状况以及该菌对不同抗菌药物的耐药性。方法 采用VITEK-2 Compact全自动细菌鉴定仪联合GN卡和16S RNA基因PCR对不同疾病标本中铜绿假单胞菌进行分离鉴定。分别采用VITEK-2 Compact仪联合AST-GN卡K-B纸片扩散法对铜绿假单胞菌分离株进行药物敏感试验。结果 仅检出铜绿假单胞菌199例病人所患主要疾病为下呼吸道感染(χ²=24.8,P<0.05),病人以≥60男性为主(χ²=26.1,P<0.05)且主要来自重症监护病房(ICU)和普外科(χ²=17.7,P<0.05)。临床常用抗菌药物中,铜绿假单胞菌分离株对氨苄西林、头孢唑林和头孢曲松耐药率较高(耐药率95.48%～98.99%),但对哌拉西林、庆大霉素和左旋氧氟沙星相对敏感(敏感率70.51%～88.44%)。55.3%铜绿假单胞菌分离株(110/199)株多重耐药,优势多重耐药模式为青霉素+头孢菌素+碳青霉烯类(30.9%,34/110)和菌株对青霉素+头孢菌素+碳青霉烯+喹诺酮类(39.1%,43/110)耐药(P<0.05)。结论 铜绿假单胞菌是不同感染性疾病常见病原体,老年男性是该菌感染高危人群。临床标本中分离的铜绿假单胞菌有较强的耐药性,尤其对多种临床常用抗菌药物呈现多重耐药。     

Epidemiology of Pseudomonas aeruginosa infection in cystic fibrosis and the use of strain genotyping

We describe a study of the epidemiology of Pseudomonas aeruginosa (PA) infection in a group of adults with cystic fibrosis who attended a week-long summer camp in the U.K. Sputum samples were collected from 17 patients at the beginning and at the end of the holiday period. Examination of previous sputum samples had identified 11 patients who were chronically colonised with PA. They shared accommodation during the holiday. The sputum samples from these 11 patients were analysed so as to identify the strains of PA by their genotypic characters. All patients were colonised by unique strains before the beginning of the holiday, with the exception of two pairs of patients whose isolates were indistinguishable. After the holiday, eight of the 11 patients harboured strains of the same genotype as was found in their pre-holiday specimens. In three patients, a strain present post-holiday was different from that found in the pre-holiday specimen. In addition, in the case of one patient, two different genotypes were found in the pre-holiday specimen, only one of which was present after the holiday. Evidence of cross-infection of PA during the holiday was not found. Even so, evidence of person-to-person transmission of PA both within the hospital environment and through social contact is presented and discussed.     

Interaction of Depressive and Anxiety Symptoms on the Mortality of Patients with COPD: A Preliminary Study

Background: Depressive and anxiety symptoms increase the risk of death in patients with Chronic Obstructive Pulmonary Disease (COPD), but the combined effects of the two factors are unknown. Purpose: To assess the possible interactive effects of depressive and anxiety symptoms on the death of patients with COPD. Methods: Prospective data for 7787 Chinese patients with COPD was analyzed and the deaths were recorded. Depressive and anxiety symptoms were evaluated using the Hospital Anxiety and Depression Scale. A product of depressive and anxiety symptoms was added to the logistic regression model to evaluate the multiplicative interaction, and relative excess risk of interaction (RERI), attributable proportion (AP) of interaction, and synergy index (S) were applied to evaluate the additive interaction of the two factors. Bootstrap was used to calculate 95% confidence intervals (CIs) of RERI, AP and S. RERI > 0, AP > 0, or S > 1 indicated biological interaction. Results: After 4 years’ follow-up, the cumulative mortality was 20.0%, and the percentages of deaths in patients with depressive and anxiety symptoms were 28.5% and 30.9%, respectively. When adjusting for variables such as age, sex, disease duration, marital status, income, education level, co-morbidity, smoke status, biomass smoke, 6MWD, MRC, BMI and FEV1. the RERI, AP, and S (with 95% CIs) resulted in depression and anxiety scores of 6.54 (1.23–13.79), 0.54 (0.18–0.83), and 2.64 (1.33–4.75) respectively. Conclusion: Interaction effects were found between depressive and anxiety symptoms on the death of patients with COPD. Patients with both depressive and anxiety symptoms have an increased risk of death from COPD.     

Pseudomonas aeruginosa: Mannose Sensitive Hemagglutinin Inhibits the Growth of Human Hepatocarcinoma Cells via Mannose-Mediated Apoptosis

A vaccine derived from the outer membrane proteins of the Gram-negative bacterium Pseudomonas aeruginosa has been shown to have immune modulatory properties. An inactivated mutant strain of P. aeruginosa with mannose sensitive hemagglutinin fimbria (PA-MSHA) has been used for adjuvant therapy for malignant cancer. In this study, the growth of human hepatocellular carcinoma Hep G2 and BEL-7402 cells is inhibited by PA-MSHA, but not by mannose-cleaved PA-MSHA. PA-MSHA-treated cells arrested in the S phase of the cell cycle and underwent apoptosis. We hypothesize that apoptosis induced by treatment of Hep G2 and BEL-7402 cells with PA-MSHA is mediated by the mannose residues of PA-MSHA and is propagated through the extrinsic apoptosis pathway directly through caspase-8. These data provide mechanistic details for the potential application of PA-MSHA-based treatment of hepatocellular carcinoma.     

Predictors of Mortality in Patients with Stable COPD

OBJECTIVES  To determine which easily available clinical factors are associated with mortality in patients with stable COPD and if health-related quality of life (HRQoL) provides additional information. DESIGN  Five-year prospective cohort study. SETTING  Five outpatient clinics of a teaching hospital. PARTICIPANTS  Six hundred stable COPD patients recruited consecutively. MEASUREMENTS  The variables were age, FEV_1%, dyspnea, previous hospital admissions and emergency department visits for COPD, pack-years of smoking, comorbidities, body mass index, and HRQoL measured by Saint George’s Respiratory Questionnaire (SGRQ), Chronic Respiratory Questionnaire (CRQ), and Short-Form 36 (SF-36). Logistic and Cox regression models were used to assess the influence of these variables on mortality and survival. RESULTS  FEV_1%(OR: 0.62, 95% CI 0.5 to 0.75), dyspnea (OR 1.92, 95% CI 1.2 to 3), age (OR 2.41, 95% CI 1.6 to 3.6), previous hospitalization due to COPD exacerbations (OR 1.53, 1.2 to 2) and lifetime pack-years (OR 1.15, 95% CI 1.1 to 1.2) were independently related to respiratory mortality. Similarly, these factors were independently related to all-cause mortality with dyspnea having the strongest association (OR 1.54, 95% CI 1.1 to 2.2). HRQoL was an independent predictor of respiratory and all-cause mortality only when dyspnea was excluded from the models, except scores on the SGRQ were associated with all-cause mortality with dyspnea in the model. CONCLUSIONS  Among patients with stable COPD, FEV_1% was the main predictor of respiratory mortality and dyspnea of all-cause mortality. In general, HRQoL was not related to mortality when dyspnea was taken into account, and CRQ and SGRQ behaved in similar ways regarding mortality. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Sources of support: Grant no. 97/0326 from the Fondo de Investigación Sanitaria. Research Committee of Galdakao-Usansolo Hospital.     

Pseudomonas aeruginosa bloodstream infections: risk factors and treatment outcome related to expression of the PER-1 extended-spectrum beta-lactamase

Background  

Bloodstream infection (BSI) due to Pseudomonas aeruginosa (Pa) has relevant clinical impact especially in relation to drug resistance determinants. The PER-1 extended-spectrum beta-lactamase (ESBL) is a common enzyme conferring high-level resistance to anti-pseudomonal cephalosporins. Risk factors and treatment outcome of BSI episodes caused by PER-1-positive Pa (PER-1-Pa) strains were compared to those caused by ESBL-negative Pa isolates (ESBL-N-Pa).     

A low concentration of azithromycin inhibits the mRNA expression of N-acyl homoserine lactone synthesis enzymes, upstream of lasI or rhlI, in Pseudomonas aeruginosa

Low-dose macrolides are effective therapy in patients with chronic lung infections, but the mechanisms of action are unclear. In this study, we performed DNA microarray analysis of Pseudomonas aeruginosa after treatment with a low concentration of azithromycin. We found that a sub-MIC of azithromycin didn't change mRNA expression of quorum-sensing related genes (lasI, lasR, rhlI, rhlR, vft, rsaL), but lowered expression of most N-acyl homoserine lactone (AHL) synthesis enzymes upstream of lasI and rhlI. We propose that small down regulation of these enzymes cumulatively resulted in a larger decrease of AHL production and inhibition of quorum-sensing in P. aeruginosa.