In this prospective observational study of PEx, treatment regimens and durations showed substantial variation. A significant proportion of patients did not reach physician's treatment goals, yet treatment was deemed successful.

Background The Standardized Treatment of Pulmonary Exacerbations (STOP) program has the intent of defining best practices in the treatment of pulmonary exacerbations (PEx) in patients with cystic fibrosis (CF). The objective of this analysis was to describe the clinical presentations of patients admitted for intravenous (IV) antibiotics and enrolled in a prospective observational PEx study as well as to understand physician treatment goals at the start of the intervention. Methods We enrolled adolescents and adults admitted to the hospital for a PEx treated with IV antibiotics. We recorded patient and PEx characteristics at the time of enrollment. We surveyed treating physicians on treatment goals as well as their willingness to enroll patients in various study designs. Additional demographic and clinical data were obtained from the CF Foundation Patient Registry. Results Of 220 patients enrolled, 56% were female, 19% were adolescents, and 71% were infected with P. aeruginosa. The mean (SD) FEV1 at enrollment was 51.1 (21.6) % predicted. Most patients (85%) experienced symptoms for ≥7 days before admission, 43% had received IV antibiotics within the previous 6 months, and 48% received oral and/or inhaled antibiotics prior to IV antibiotic initiation. Forty percent had ≥10% FEV1 decrease from their best value recorded in the previous 6 months, but for 20% of patients, their enrollment FEV1 was their best FEV1 recorded within the previous 6 months. Physicians reported that their primary treatment objectives were lung function recovery (53%) and improvement of symptoms (47%) of PEx. Most physicians stated they would enroll patients in studies involving 10-day (72%) or 14-day (87%), but not 7-day (29%), treatment regimens. Conclusions Based on the results of this study, prospective studies are feasible and physician willingness for interventional studies of PEx exists. Results of this observational study will help design future PEx trials.

Objective To evaluate microbiologic effectiveness, i.e. culture negativity of a non-blinded eradication protocol (Rx) compared to observation (Obs) in clinically stable cystic fibrosis participants with newly positive MRSA cultures. Design This non-blinded trial randomized participants ages 4-45 years with first or early (≤2 positive cultures within 3 years) MRSA positive culture without MRSA-active antibiotics within 4 week 1:1 to Rx or Obs. The Rx protocol was: oral trimethoprim-sulfamethoxazole or if sulfa-allergic, minocycline plus oral rifampin; chlorhexidine mouthwash for two weeks; nasal mupirocin and chlorhexidine body wipes for five days, and environmental decontamination for 21 days. The primary endpoint was MRSA culture status at day 28. Results Between April 1, 2011 to September 2014, forty-five participants (44% female, mean age 11.5 years) were randomized (24 Rx, 21 Obs). At Day 28, 82% (n=18/22) of participants in the Rx-arm compared to 26% (n=5/19) in Obs-arm were MRSA negative. Adjusted for interim monitoring, this difference was 52% (95% CI: 23%, 80%; p<0.001). Limiting analyses to participants who were MRSA positive at the screening visit, 67% (8/12) in the Rx and 13% (2/15) in the Obs-arm were MRSA negative at Day 28, adjusted difference: 49% (95% CI: 22%,71%, p<0.001). Fifty-four percent in the Rx compared to 10% participants in the Obs-arm remained MRSA negative through Day 84. Mild gastrointestinal side effects were higher in the Rx-arm. Conculsions This MRSA eradication protocol for newly acquired MRSA demonstrated microbiologic efficacy with a large treatment effect. Trial Registration www.clinicaltrials.gov NCT01349192

KB001-A was safe and well-tolerated and associated with a modest FEV benefit and reduction in select sputum inflammatory markers (IL-8). KB001-A was not associated with an increased time to need for antibiotics. The lack of efficacy seen with KB001-A may be due, in part, to the low levels of the type III secretion proteins previously reported in sputum of CF patients chronically infected with Pa.

Results from randomized prospective superiority and non-inferiority studies employing mean CRISS and FEV change from treatment initiation should prove compelling to the community. They will need to be large, but appear feasible.