Please select the eligibility criteria that correspond to the clinical trial below.
Title: Impact of Azithromycin and Clarithromycin Therapy on Pharyngeal Carriage of Macrolide-Resistant Streptococci Among Healthy Volunteers: A Randomised, Double-Blind, Placebo-Controlled Trial
Brief Summary: Resistance to antibiotics is a major public-health problem and studies linking antibiotic use and resistance have shown an association not a causal effect. Utilizing the newer macrolides, azithromycin and clarithromycin that are commonly prescribed for respiratory infections, we investigated the direct impact of antibiotic exposure on resistance at the individual level.


Options:
A: Inclusion Criteria:

* Diagnosis of asthma
* Age 18-70
* Current smoker
* Duration of symptoms \>1yr with stability for 4 weeks
* Able to maintain asthma without exacerbations during run in period
* Able to wean off other asthma medication

Exclusion Criteria:

* Ex-smokers or never smokers
* Planning to quit smoking during duration of trial
* Patients with unstable asthma
* Patients with current epilepsy, psychosis or history of significant atrial or ventricular tachyarrhythmia
* Corrected QT-interval greater than 450msec in women, 430msec in men
* Low potassium levels. If can be corrected then screening can continue with confirmation of normal levels prior to taking study medication
* Liver disease (ALT and/or AST levels 2 or more times ULN)
* Significant renal disease (Creatinine or urea levels 2 or more times ULN)
* Any previous severe adverse reactions to macrolides
* Patients who are known to have specific IgE sensitivity or skin test positivity to grass pollen and a history of worsening of asthma due to hay fever will not be recruited from mid May to the end of July
* Upper or lower respiratory tract infection in the 4 weeks prior to randomisation. Run in period can be prolonged in this situation to have 4 weeks with no respiratory infection prior to randomisation.
* Patients who require medications known to interact with azithromycin
* On other immunosuppressants or chronic antibiotics
* Weight less than 45kg
* Frequent asthma exacerbations (greater than 4) requiring oral corticosteroids in the year prior to randomisation
* Current or past diagnosis of allergic-bronchopulmonary-aspergillosis
* Pregnancy and breast feeding
* Mental impairment or language difficulties that makes informed consent not possible
B: Inclusion Criteria:

* 12-71 months of age.
* Recurrent significant wheezing in the past year (any of the following):

  * \>3 episodes, ≥1 of which was clinically significant\*; OR
  * \>2 clinically significant\* episodes; OR
  * \>4 months of daily controller therapy AND \>1 clinically significant\* episode.
  * \* Clinically significant episode: requiring any of the following: (1) systemic corticosteroids (oral or injectable), (2) unscheduled physician office visit, (3) ED visit, (4) urgent care visit, or (5) hospitalization.
* Up to date with immunizations, including varicella (unless the subject has already had clinical varicella). If the subject needs varicella vaccine, this will be arranged with the primary care physician and must be received prior to randomization.
* Willingness to provide informed consent by the child's parent or guardian.

Exclusion Criteria:

Participants who meet any of the following criteria are NOT eligible for enrollment, but may be re-enrolled if these exclusion criteria are resolved:

* \>4 courses of systemic corticosteroids in past 12 months.
* More than 1 hospitalization for wheezing illnesses within the preceding 12 months.
* Use of long-term controller medications for asthma, including inhaled corticosteroids, leukotriene modifiers, cromolyn/nedocromil, or theophylline for more than 8 months (cumulative use) in the past 12 months.
* Current use of higher than step 2 NAEPP asthma guideline therapy (e.g. medium-high dose ICS alone or combination therapy of low-medium-high dose ICS + LABA, montelukast, theophylline or cromolyn). NOTE: children who have evidence of well-controlled symptoms immediately preceding study entry while receiving Step 2 controller therapy (presence of self-reported symptoms on average no more than 2 times per week and less than 2 nights per month of nocturnal awakenings, requiring albuterol, during the 4 weeks preceding visit 1) may be enrolled and will have their controller therapy discontinued upon study entry.
* Use of OCS in the past 2 weeks.
* Daily symptoms or \>2 nocturnal awakenings, requiring albuterol, on average in the last 2 weeks.
* Use of antibiotics in the past month.
* Current treatment with antibiotics for diagnosed sinus disease.
* Participation presently or in the past month in another investigational drug trial.
* Evidence that the family may be unreliable or nonadherent, or may move from the clinical center area before trial completion.
* Contraindication of use of systemic corticosteroids or azithromycin.
* Clinically relevant gastroesophageal reflux.
* Concurrent medical conditions other than asthma that are likely to require oral or injectable corticosteroids during the study.
* If receiving allergy shots, change in dose within the past 3 months.

Participants who meet any of the following criteria are NOT eligible for enrollment, and may not be re-enrolled:

* Gestation less than late preterm as defined as birth before 34 weeks gestational age.
* Presence of lung disease other than asthma, such as cystic fibrosis and BPD. Evaluation during the screening process will assure that an adequate evaluation of other lung diseases has been performed.
* Presence of other significant medical illnesses (cardiac, liver, gastrointestinal, endocrine) that would place the study subject at increased risk of participating in the study.
* Immunodeficiency disorders.
* History of respiratory failure requiring mechanical ventilation.
* History of hypoxic seizure.
* History of significant adverse reaction to any study medication ingredient.
* The child has significant developmental delay/failure to thrive, defined as crossing of two major percentile lines during the last year for age and gender. If a child plots less than the 10th percentile for age and gender, a growth chart for the previous year will be obtained from the child's primary care provider.
C: Inclusion Criteria:

* healthy adults (≥ 18 years of age)
* non-pregnant
* free of any respiratory tract infection
* not having been administered any antibiotic at least in the past three months

Exclusion Criteria:

* \<18 years of age
* pregnant
* having a respiratory tract infection
* having been administered any antibiotic at least in the past three months
D: Inclusion Criteria:

* Confirmed COPD diagnosis
* Informed Consent: Patients must give their signed and dated written informed consent to participate
* Gender: Male or female patients
* Age: ≥ 45 years of age at screening
* Produce sputum regularly (produce sputum in at least 3 months of a year)
* Able to complete questionnaires for health status and symptoms and considered able to comply with the dosing regimen.
* Severity of disease: Patients with a measured FEV1\<80% of predicted normal values as determined at screening. An average of three spirometry readings will be taken.

Exclusion Criteria:

* Patients with TB, other chronic respiratory disease (e.g. chronic asthma, bronchiectasis, pulmonary fibrosis), patients with hepatic or renal impairment and patients with prolonged QT interval and other cardiac abnormalities.
* Patients with known hypersensitivity to the antibiotics under evaluation.
* Patients on long term antibiotics for other conditions.
* Patients with uncontrolled hypertension.
* Female patients who are pregnant or planning on becoming pregnant during the study, or are breastfeeding.
* Patients with a history of long QT syndrome or whose QTc measured at Visit 1 is prolonged (\>450 msec for males and females) as confirmed by the ECG assessor.
* Clinically relevant abnormal laboratory values at the screening assessment that could interfere with the objectives of the trial or safety of the volunteer.
* Patient taking clinically significant contraindicated medication, as per the SmPCs

Answer: C