Triclosan Is an Aminoglycoside Adjuvant for Eradication of Pseudomonas aeruginosa Biofilms.

One of the most important clinical obstacles in cystic fibrosis (CF) treatment is antibiotic treatment failure due to biofilms produced by Pseudomonas aeruginosa The ability of this pathogen to survive eradication by tobramycin and pathoadapt into a hyperbiofilm state leading to chronic infections is key to its success. Retrospective studies have demonstrated that preventing this pathoadaptation by improving eradication is essential to extend the lives of CF patients. To identify adjuvants that enhance tobramycin eradication of P. aeruginosa, we performed a high-throughput screen of 6,080 compounds from four drug-repurposing libraries. We identified that the Food and Drug Administration (FDA)-approved compound triclosan, in combination with tobramycin, resulted in a 100-fold reduction of viable cells within biofilms at 6 h, but neither compound alone had significant antimicrobial activity against biofilms. This synergistic treatment significantly accelerated the killing of biofilms compared to that with tobramycin treatment alone, and the combination was effective against 6/7 CF clinical isolates compared to tobramycin treatment alone, including a tobramycin-resistant strain. Further, triclosan and tobramycin killed persister cells, causing a 100-fold reduction by 8 h and complete eradication by 24 h. Triclosan also enhances tobramycin killing of multiple Burkholderia cenocepacia and Staphylococcus aureus clinical isolates grown as biofilms. Additionally, triclosan showed synergy with other aminoglycosides, such as gentamicin or streptomycin. Triclosan is a well-tolerated aminoglycoside adjuvant shown to be safe for human use that could improve the treatment of biofilm-based infections.

Influence of sociodemographics on the health-related quality of life of pediatric patients with asthma and their caregivers.

The relationship between socioeconomic variables and the health-related quality of life (HQL) of children with asthma and their caregivers was examined. The Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and Pediatric Asthma Caregivers Quality of Life Questionnaire (PACQLQ) were administered to 99 pediatric asthmatic patients and caregivers in two specialty clinics. Sociodemographic data was obtained from medical records and additional questions. The relationship between sociodemographic variables and HQL was determined using multiple linear regression. The mean patient age was 12.6+/-2.1 years, more were male and from a minority race. The mean age of caregivers was 41.2+/-8.5 years; most were female and were fom a minority race. Patients tended to rate their asthma severity as mild to moderate, while caregivers tended to rate patients in the moderate to severe category. Based on prescribed medications, most patients had mild to moderate asthma. Household income was consistently associated with patient-perceived HQL. Less consistent associations were seen with other variables. Household income and the caregiver's perception of asthma severity were associated with all caregiver HQL domains. It was concluded that household income was most consistently associated with the HQL of asthmatic pediatric patients and their caregivers.

Hypersensitivity to inhaled TOBI following reaction to gentamicin.

Cystic fibrosis (CF) is the most common autosomal-recessive disease in Caucasians. Colonization with Pseudomonas aeruginosa (P. aeruginosa) of the CF airways causes deterioration of pulmonary status. TOBI (Tobramycin solution for inhalation) is an inhaled antibiotic that can improve the pulmonary disease. We report on a 9-year old boy with CF who developed a rash following a course of IV gentamicin. The rash resolved after its discontinuation. However, the rash returned all over his body, with the start of inhalation of TOBI therapy. We desensitized the patient using escalating doses of inhaled TOBI. He tolerated the procedure well, and continues to be on TOBI 9 months after desensitization on a once-a-day regimen.