Phage-induced efflux down-regulation boosts antibiotic efficacy.

The interactions between a virus and its host vary in space and time and are affected by the presence of molecules that alter the physiology of either the host or the virus. Determining the molecular mechanisms at the basis of these interactions is paramount for predicting the fate of bacterial and phage populations and for designing rational phage-antibiotic therapies. We study the interactions between stationary phase Burkholderia thailandensis and the phage ΦBp-AMP1. Although heterogeneous genetic resistance to phage rapidly emerges in B. thailandensis, the presence of phage enhances the efficacy of three major antibiotic classes, the quinolones, the beta-lactams and the tetracyclines, but antagonizes tetrahydrofolate synthesis inhibitors. We discovered that enhanced antibiotic efficacy is facilitated by reduced antibiotic efflux in the presence of phage. This new phage-antibiotic therapy allows for eradication of stationary phase bacteria, whilst requiring reduced antibiotic concentrations, which is crucial for treating infections in sites where it is difficult to achieve high antibiotic concentrations.

Combination Therapy with Ciprofloxacin and Pentamidine against Multidrug-Resistant Pseudomonas aeruginosa: Assessment of In Vitro and In Vivo Efficacy and the Role of Resistance-Nodulation-Division (RND) Efflux Pumps.

The aim of this work was to (i) evaluate the efficacy of a combination treatment of pentamidine with ciprofloxacin against Galleria mellonella larvae infected with an MDR strain of P. aeruginosa and (ii) determine if pentamidine acts as an efflux-pump inhibitor. Resistant clinical isolates, mutant strains overexpressing one of three RND efflux pumps (MexAB-OprM, MexCD-OprJ, and MexEF-OprN), and a strain with the same three pumps deleted were used. MIC assays confirmed that the clinical isolates and the mutants overexpressing efflux pumps were resistant to ciprofloxacin and pentamidine. The deletion of the three efflux pumps induced sensitivity to both compounds. Exposure to pentamidine and ciprofloxacin in combination resulted in the synergistic inhibition of all resistant strains in vitro, but no synergy was observed versus the efflux-pump deletion strain. The treatment of infected G. mellonella larvae with the combination of pentamidine and ciprofloxacin resulted in enhanced efficacy compared with the monotherapies and significantly reduced the number of proliferating bacteria. Our measurement of efflux activity from cells revealed that pentamidine had a specific inhibitory effect on the MexCD-OprJ and MexEF-OprN efflux pumps. However, the efflux activity and membrane permeability assays revealed that pentamidine also disrupted the membrane of all cells. In conclusion, pentamidine does possess some efflux-pump inhibitory activity, in addition to a more general disruptive effect on membrane integrity that accounts for its ability to potentiate ciprofloxacin activity. Notably, the enhanced efficacy of combination therapy with pentamidine and ciprofloxacin versus MDR P. aeruginosa strains in vivo merits further investigation into its potential to treat infections via this pathogen in patients.

Linguistic adaptation and psychometric properties of the health literacy questionnaire in serbian language among people with chronic diseases.

OBJECTIVE: To translate the Health Literacy Questionnaire (HLQ) to Serbian language and examine its psychometric characteristics. METHODS: This cross-sectional study was conducted among 295 people with chronic diseases from the Foca region (Republic of Srpska, Bosnia and Herzegovina). The HLQ was translated according to the translation integrity procedure. Construct validity was tested using confirmatory factor analysis (CFA) using the maximum likelihood estimator and reliability was estimated using the α and ω coefficients. RESULTS: Minor linguistic differences in 17 items were observed between the original and the initial forward translation and were corrected. The parameters of one-factor CFA on domains 3 and 8 fitted well. The parameters of the CFA for domains 1, 2, 4, 5, 6, 7 and 9 were acceptable after modification using residuals' correlation. The α and ω coefficients for all domains were good to excellent (>0.80). CONCLUSION: Each domain of the HLQ in Serbian has acceptable construct validity and overall good reliability. This study adds to the growing evidence that the HLQ is a useful tool to provide in-depth multidimensional information on health literacy to improve researchers and policymakers understanding of the health literacy strengths, needs and preferences across cultures and languages.

Self-confidence and clinical skills: the case of students who study medicine in English in a non-English speaking setting.

BACKGROUND: An increasing number of international students has been enrolling in medical studies in the English language offered by the countries of Eastern Europe. Development of practical skills is likely more challenging when students learn in the English language, while their patients are non-English speaking persons. AIMS: To evaluate self-perception of practical skills of medical students in the English language program. METHODS: From December 2016 to December 2017, a total of 52 students from the Studies in English program of two universities in Serbia were included in the study. Data were obtained by a previously validated questionnaire. RESULTS: Participants were most confident when measuring blood pressure, checking the arterial pulse, and taking history. Students were the least confident when placing urinary catheters, performing rectal examinations, and suturing wounds. Male students reported higher confidence in "Major interventions" compared to females (p = 0.004), and no difference between male and female students was found in the total skill score of "knowledge of Serbian language" (p = 0.339). Adjusted analysis showed that a higher grade point average remains associated with a more confident perception of one's practical skills (B 26.48, 95% confidence interval 8.98-43.98). Rasch analysis showed that because the scores were distributed around the mean value between "not confident at all" and "quite confident," the majority of students had similar perceptions of their skills. CONCLUSION: Active supervision by teaching staff is also recommended in an attempt to rectify the lack of confidence at performing a range of clinical procedures which is present among international students.

Reliability of health utility measures and a test of values clarification.

This study examines the test-retest reliability of two methods of establishing health preference weights and assesses the effectiveness of a brief values-clarification exercise. Survey participants were randomly allocated to one of two groups and received either a standard protocol for eliciting health preferences (comparison group) or an augmented protocol designed to encourage reflection and deliberation (intervention group). Preferences were elicited on three occasions over 5 weeks. The results show that the two valuation methods each had acceptable levels of test-retest reliability. No significant differences were found in preference weights over time or between intervention and comparison groups. The values-clarification exercise had some impact on individual answers, but the changes cancelled each other out at the group level. There was no discernable intervention effect at the group level. It is premature to draw conclusions from one study about why, or even how, a person's valuations might change over time, but our results support the use of current valuation techniques for group-level analyses.