Early detection using qPCR of Pseudomonas aeruginosa infection in children with cystic fibrosis undergoing eradication treatment.

BACKGROUND: Infection with Pseudomonas aeruginosa (Pa) with a chronic phenotype is associated with antibiotic eradication therapy (AET) failure. Our objective was to determine whether higher levels of Pa (detected using qPCR) prior to culture positivity were associated with AET failure in pediatric CF patients. METHODS: Pa-specific qPCR was performed on stored sputa prior to culture positivity in pediatric CF patients with new-onset culture-positive Pa infections undergoing AET with a 28-day course of tobramycin-inhaled solution (TIS). DNA concentrations were compared in patients in whom AET was successful (Eradicated) to those with persistently positive sputum cultures (Persistent). RESULTS: Forty-seven patients were included. AET was successful in 32 cases (68%), but failed in 15 cases (32%). Median sputum Pa-specific DNA concentration preceding the positive sputum culture was 2.2 × 10-6 µg/mL in Eradicated cases compared to 3 × 10-5 µg/mL in Persistent cases (p = 0.14). There was no significant difference in DNA concentration in the last sputum sample prior to culture positivity, nor in maximal DNA values. There was also no difference in sputum Pa DNA concentrations in patients who had a mucoid (compared to non-mucoid) Pa infection. CONCLUSIONS: Pediatric CF patients with new-onset Pa infections have detectable Pa-specific DNA in the year preceding a positive culture, however, there is no significant difference in Pa DNA concentrations between patients in whom AET is successful compared to those in whom it fails. Therefore, early molecular detection of Pa may not lead to improved eradication success rates.

Effectiveness of a stepwise Pseudomonas aeruginosa eradication protocol in children with cystic fibrosis.

INTRODUCTION: Antibiotic eradication therapy (AET) for initial Pseudomonas aeruginosa (Pa) infection is standard of care in children with cystic fibrosis (CF), but information is limited on treatment for patients who fail initial AET. The aim of this study was to evaluate the effectiveness of a multi-step protocol for AET for new-onset Pa infections in children with CF. METHODS: A three-step AET protocol which includes: (step 1) 28days of tobramycin inhalation solution (TIS) for new-onset Pa infection; (step 2) a second course of TIS for patients with positive respiratory tract culture after step 1; (step 3) 14days of intravenous antibiotics followed by 28days of TIS for patients with a subsequent positive culture. We conducted a retrospective review of all pediatric CF patients who underwent the eradication protocol between January 2010 and December 2015. The success rate of each step and of the overall protocol was recorded. RESULTS: During the study period, 128 patients had a total of 213 new-onset Pa infections. Of 195 asymptomatic episodes, 150 (76.9%, 95% CI 70.4; 82.6) cleared after step 1 and 12 cleared after step 2 (33.3% (95% CI 18.6; 50.9) stepwise success rate and 87.1% (95% CI 77.1; 88.1) cumulative success rate). Intravenous antibiotics followed by 28days of TIS were administered in 24 episodes; this was successful in 10 episodes (41.7%; 95% CI 22.1; 63.4). The regimen in asymptomatic patients failed in fourteen episodes (7.5%; 95% CI 4.2; 12.3) then considered chronically infected with Pa. Overall, the cumulative success rate of the asymptomatic arm was 88.2% (95% CI 82.8; 92.4). CONCLUSION: The first step of the AET protocol led to the greatest eradication success. Subsequent eradication attempts have a success rate below 50%. Prospective studies of eradication protocols for this population are needed to determine the most effective treatment strategy.

Effect of pulmonary exacerbations treated with oral antibiotics on clinical outcomes in cystic fibrosis.

BACKGROUND: Despite extensive knowledge regarding the effect of pulmonary exacerbations treated with intravenous antibiotics on clinical outcomes in cystic fibrosis (CF), there is little known about the role of milder pulmonary exacerbations treated with oral antibiotics (oPEx). METHODS: This was a retrospective cohort study of patients with CF followed at the Hospital for Sick Children and St. Michael's Hospital from 2009 to 2014. We evaluated the effect of oPEx on short-term clinical outcomes as the proportion of oPEx events in which 100% or 90% of baseline FEV1% predicted was recovered at the end of treatment. We then examined the association of the number of oPEx events in the past 12 months on lung function (FEV1% predicted) and nutritional status (body mass index (BMI) z-score) using a mixed-effects model. RESULTS: There were a total of 2608 oPEx events in 570 subjects during the study period. In over half (53.4%) of oPEx events, lung function was already at 90% or higher of baseline FEV1 at the initiation of oral antibiotic therapy and 82% were at 90% or higher of baseline FEV1 at follow-up. In individuals with CF, one or more oPex events in the previous 12 months were associated with decreased FEV1 compared with 12 months periods without oPex events. When the cumulative effect of oPExs on lung function was examined over the entire study period, patients with six or more oPEx events had the steepest rate of FEV1 decline. oPEx events were not associated with changes in BMI. CONCLUSIONS: oPEx events are associated with short-term loss of FEV1 and have a negative effect on lung function over time.

STAR™ ankle: long-term results.

BACKGROUND: There has been a resurgence of interest in total ankle replacement (TAR) due to improved results with newer prostheses. However, long-term survivorship data has been limited. The STAR™ Ankle prosthesis is the first three-part prosthesis approved for use in the United States. MATERIALS AND METHODS: Eighty-four total ankle replacements were performed in 80 patients using the STAR™ Ankle prosthesis and followed prospectively. Postoperatively, patients were evaluated with the AOFAS score for pain and function, and serial radiographs were evaluated for stability and alignment of the prosthesis. Implant failure, secondary procedures, and complications were recorded. RESULTS: Ninety-one percent of prostheses remain implanted at an average followup of 9.1 years. The probability of implant survival was 96% at 5 years and 90% at 10 years. An average 39-point improvement in the AOFAS ankle-hindfoot score was noted, from a mean of 43 to a mean of 82 points. We noted a statistically significant increase in both average pain and function sub-scores. Postoperative range of motion averaged 4.5 degrees of dorsiflexion and 35 degrees of plantarflexion. Ninety-two percent of the patients were satisfied with their outcome. Ten patients (13%) developed concerning osteolytic lesions. Change in prosthetic alignment and adjacent joint arthritis were similar to previous reports. We report 21 complications, which included 14 additional surgical procedures. CONCLUSION: The first U.S. prospective long-term survivorship data with the STAR™ Ankle prosthesis found it to be an excellent long-term option for the treatment of ankle arthritis.

Distraction of skeletal muscle: evolution of a rat model.

To better study the effects of limb lengthening on skeletal muscle, the authors developed a rat model that uses a miniature external skeletal fixator applied to the tibia of an adult Sprague-Dawley rat. The mounting and lengthening protocols follow the principles developed by Ilizarov. With the initial version of the fixator, the rats had progressive equinus contractures develop because the calf muscles resisted elongation. By incorporating a footplate in the distraction apparatus, tibial lengthening can be achieved without concomitant equinus.