Last updated Jan. 13, 2023, by Teresa Carvalho, MS
Ā Fact-checked byĀ JosĆ© Lopes, PhD
What are antibiotics for CF?
Antibiotics are taken to prevent, eliminate, or control respiratory infections caused by bacteria in people with cystic fibrosis (CF).
By stopping or preventing damage caused by lung infections, antibiotics help to maintain lung function and quality of life in CF patients. They also reduce exacerbations ā periods when lung function suddenly declines, usually due to a lung infection.
There is a complex arsenal of antibiotics for CF. They can be classified based on the route of administration, the class of bacteria they target, and their mechanism of action.
Staphylococcus aureus,Ā Haemophilus influenzae,Ā Pseudomonas aeruginosa, andĀ Burkholderia cepaciaĀ are some common bacterial species that can infect CF patients and are the target of the most commonly used antibiotics.
HowĀ do antibiotics work?
CF is caused by mutations in the CFTR gene, which codes for a protein of the same name. This protein functions as a channel and is normally found on the surface of various cells in different parts of the body, such as the lungs, gastrointestinal tract, and reproductive organs.
Specific mutations in CFTR compromise the transport of chloride and water across cell membranes and affect the consistency of mucus. This leads to the accumulation of thick, sticky mucus in organs that presents an ideal culture medium for the growth of bacteria.
Some antibiotics are only effective against certain bacteria. Others, called broad-spectrum antibiotics, attack a wide range of bacteria. They work in two main ways: Antibiotics can stop bacteria from reproducing or kill them, for example by stopping the way they build their cell walls.
Identifying the right combination of antibiotics for a patient early on can help prevent the infection from spreading.
Who can take antibiotics?
Antibiotics can be used to prevent or treat bacterial infections in children and adults with CF.
Intravenous (IV or into the vein) treatment is often required for pulmonary exacerbations in CF patients in addition to inhaled or oral antibiotics.
Inhaled antibiotics should be taken last, after bronchodilators, mucus thinners, and airway clearance techniques are used to clear mucus as much as possible so that antibiotics can reach deep into the lungs. The inhaled form is recommended for people with chronic P.aeruginosa infection to preserve lung function and decrease the need for additional IV treatments.
Oral antibiotics can be taken for chronic bacterial infections or mild exacerbations.
Who should not take antibiotics?
Antibiotics should not be taken for viral infections as they treat only certain infections caused by bacteria. Allergies to antibiotics are common in the CF patient population, which limits the number of antibiotics that can be used.
How are antibiotics administered?
Antibiotics can be taken in several ways: oral, IV, intramuscular (injected into a muscle), or inhaled. They usually take 48 to 72 hours to start working, and it may take a day before patients start to feel better.
Patients should complete the prescribed course of antibiotics to prevent the remaining bacteria from becoming antibiotic-resistant.
Oral antibiotics
Oral antibiotics are available as liquids, tablets, or capsules. Some are administered once daily for a few days, while others can be used for longer periods. Some can be taken with food, while others should be taken on an empty stomach.
Oral antibiotics include:
IV antibiotics
IV antibiotics are delivered directly into the bloodstream through a catheter placed in the arm.
These antibiotics are often given by healthcare professionals in the hospital so that the dosage and potential side effects can be carefully managed. Sometimes the treatment can be self-administered at home after proper training.
IV antibiotics include:
- Gentamicin
- Amikin
- Tetracyclines
- Penicillins
- Quinolones
- Zyvox
Inhaled antibiotics
CF specialists usually determine if a patient needs to take an inhaled antibiotic based on the results of a sputum culture.
Aztreonam and tobramycin inhalation solution are administered via a nebulizer. Typically, the medication is put in a clean nebulizer cup and attached to a small air compressor that blows air through the nebulizer cup. This creates a mist that is inhaled by the patient through a mouthpiece.
Both aztreonam and tobramycin are approved for patients who are infected with P. aeruginosa. Of note, an inhaled form of amikacin, called Arikayce, has been approved for treating infections caused by MycobacteriumĀ avium complex.
Patients usually take one of these antibiotics every other month for 28 days. However, doctors may have patients alternate between antibiotics.
Antibiotics in clinical trials
Several clinical trials have shown the efficacy of antibiotics in eliminating bacterial infections in CF patients.
STOP2 trial
The Phase 4 STOP2 (Standardized Treatment of Pulmonary Exacerbations 2) trial (NCT02781610) was part of the STOP program, which set out to define the best way to treat lung exacerbations in people with CF.Ā The trial assessed the safety and effectiveness of different durations of IV treatment for pulmonary exacerbations in 982 CF patients.
The primary goal was to assess improvement of lung function, as measured by percent predicted forced expiratory volume in one second (ppFEV1) from the start of IV antibiotic treatment until two weeks after the end of treatment. Of note, ppFEV1 is a measure of the amount of air forcibly exhaled.
After seven to 10 days of IV treatment, participants who had lung function improvements and symptom reduction were randomized to receive IV antibiotics for 10 or 14 days; those who did not see improvement were randomized to 14 or 21 days of antibiotics.
The study found that, regarding lung function improvements, responses to 14 days of antibiotic treatment did not differ from 10 days of treatment among participants who responded early to treatment. Likewise, in the remaining participants, 21 days also was not significantly better than 14 days of antibiotic treatment.
Respiratory symptoms eased in all treatment duration groups as measured by the chronic respiratory infection symptom score questionnaire, with no significant differences observed between groups. No significant differences were observed when it comes to the need to be treated again for a lung exacerbation within 30 days, or in the time to the next lung exacerbation.
A sub-analysis of these trials showed that compared to male patients, women reported better lung function at treatment start, but had more severe symptoms.
Ongoing trials
STOP360AG trial
The STOP360AG trial (NCT05548283), also part of the STOP program platform, is an open-label study with patients 6 or older, who are randomly assigned to receive one beta-lactam antibiotic (a class that includes penicillin), or two antibiotics (an aminoglycoside and a beta-lactam). Antibiotic choice will be made by the treating physician.
Eligible participants must have at least oneĀ P. aeruginosa-positive test in the past two years.
The trialās primary goal is to assess the change in ppFEV1 after four weeks of treatment. This study will be conducted in the U.S.
STOP-PEDS trial
A pilot study involving children and adolescents, called STOP-PEDS, is also ongoing. This trial (NCT04608019), which recruited 121 CF patients, ages 6 to 18, will assess whether a subsequent trial is feasible for determining the benefits/risks of starting antibiotics at the first signs of illness.
Early oral antibiotic treatment along with increased airway clearance will be compared to airway clearance alone, with the addition of antibiotics for worsening symptoms or no improvement.
Common side effects of antibiotics
Antibiotics may cause several side effects, including:
- fungal infections of the mouth
- skin rash
- diarrhea
- vomiting
- nausea
- headache
- weakness
Allergic reactions
Regular use of antibiotics to treat chronic infections may cause hypersensitivity, or allergic, reactions in people with CF. These reactions have more commonly been associated with IV antibiotics, and include mild to moderate skin reactions, such as itching and rashes.
Antibiotic resistance
Bacterial species can become antibiotic-resistant, rendering a certain class of antibiotics ineffective. Therefore, higher doses of the same antibiotic or different antibiotics may be needed.
Worsening of cough
As antibiotics break up mucus, coughing may increase, which may make some people feel worse before their symptoms improve.
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