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Salem Health: Infectious Diseases & Conditions, 2nd Edition

Cystic Fibrosis Respiratory Infections

by Filip Polenakovik, , BS, Hari Polenakovik, , M.D.

Category: Diseases and conditions

Anatomy or system affected: Lungs, respiratory system, throat, upper respiratory tract

Definition

Cystic fibrosis (CF) is a rare, systemic, life-shortening genetic disease with an autosomal recessive inheritance caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The mutation in the CFTR gene changes the protein (chloride channel) that regulates the movement of salt and water in and out of cells. This results in a build-up of thick, sticky mucus in the respiratory, digestive and reproductive systems, together with increased salt in sweat.

CF is a systemic disease, but its most prominent characteristic is the chronic respiratory infections. These infections are among the main causes of morbidity and mortality in CF. Improved survival of CF individuals to a large extent is due to aggressive antibiotic treatment of these infections. Accumulation starts early; the buildup of thick, sticky mucus in CF airways results in a cycle of infection, inflammation, and mucus buildup. The thick mucus in the sinuses, airways and lungs provides an ideal breeding ground for many viruses, bacteria, mycobacteria and fungi. Many of these microorganisms eventually establish a chronic infection in the airways.

Causes

The main microorganisms believed to be pathogenic in CF are Pseudomonas aeruginosa, Haemophilus influenza, Staphylococcus aureus, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Burkholderia species. More recent microbiological studies, which utilized newer molecular (culture independent) techniques, have demonstrated that the microorganisms of the CF airways are much more diverse, abundant and complex than previously demonstrated by standard culturing methods. Emerging pathogens in the CF airways include anaerobes (especially Prevotella species), Streptococcus anginosus group, other gram negative non-fermentative bacteria such as Pandorea and Ralstonia species, non-tuberculous mycobacteria (NTM) such as Mycobacterium abscessus, Mycobacterium avium complex, and fungi such as Aspergillus fumigatus, Trichosporon mucotoxinivorans, Scedosporium species, and at times Candida species. Many of these emerging pathogens can significantly impact the course of CF lung disease. Differentiation between colonization and infection is very difficult clinically, as co-infection with various microorganisms is common. Moreover, many bacteria form biofilms in the respiratory tract of the CF individuals. It is now believed that the CF lung infections are polymicrobial in nature. The outcome of these infections is greatly influenced by the balance of these microorganisms and the host inflammatory response to these pathogens. In addition, studies have shown that there is not a good correlation between in vitro drug susceptibility profiles of the suspected pathogens with the clinical outcome.

“Jimmy Carter with Tommy Young, Cystic Fibrosis Poster Child” by White House staff photographers. Courtesy of the U.S. National Archives and Records Administration via Wikimedia Commons.

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Symptoms

Chronic infection in the airways often leads to a progressive condition called bronchiectasis, which eventually affects nearly all individuals with CF. Bronchiectasis is a permanent abnormal dilatation of the airways which makes it harder to clear the mucus from the airways and to move air in and out of the lungs. Unless appropriately managed, the lungs become more damaged, leading to a loss of lung function and shortened life. Acute pulmonary exacerbations are often a key part of this progressive condition. CF individuals experience worsening of their respiratory symptoms, including an increase in cough, change in sputum volume, shortness of breath, wheezing, chest pain, and hemoptysis (coughing up blood). In addition, there are systemic symptoms such as decreased exercise tolerance, malaise, fever and weight loss. It’s important to promptly treat acute pulmonary exacerbations to prevent and slow down the progression of bronchiectasis. If left untreated, permanent loss of lung function develops.

Screening and Diagnosis

The CF Foundation and the European CF Society Guidelines Committee recommend that individuals with CF undergo regular respiratory cultures (sputum if able to expectorate or oropharyngeal swab) for bacteria every 3 months and for NTM annually. At times, bronchoalveolar lavage cultures obtained by bronchoscopy may be needed, especially in individuals not responding well to the antimicrobial regimen directed to the pathogens isolated from routine sputum cultures. The diagnosis of acute pulmonary exacerbation is centered around identifying new or worsening respiratory and systemic symptoms, excluding non-infectious causes (e.g., seasonal allergies, allergic bronchopulmonary aspergillosis (ABPA)), recognizing new chest imaging findings and differences in lung function measures (decrease in FEV1), and recovering CF pathogens from respiratory microbiologic specimens.

Treatment

There is no cure for cystic fibrosis but treatment can improve symptoms, reduce complications and prolong the life of the CF individual. Antibiotic therapy of the respiratory infections has been the mainstay therapy of CF ever since their approval for use in humans. Despite over 6 decades of experience, there are no definitive antibiotic studies to guide the decision to treat (or not to treat) the various infections in CF, and the approaches recommended are based on uncontrolled studies and anecdote.

Antibiotic therapy in CF individuals can be divided into 4 groups: antibiotic prophylaxis against infection, eradication of early infection (especially Pseudomonas aeruginosa or PA), suppression of chronic infection, and the treatment of acute pulmonary exacerbations. Antibiotic prophylaxis against infection is not commonly used now because of the increased recognition of antimicrobial resistance and adverse effects of the antibiotics. Eradication of early infection is a commonly used approach in PA infections. The CF Foundation strongly recommends the use of inhaled tobramycin for 28 days to treat initial or new growth of PA from a respiratory culture. For persons intolerant to tobramycin, inhaled aztreonam or inhaled colistin can be used. This recommendation is based on the belief that the easiest time to eradicate PA is most likely when it is first cultured, before it becomes entrenched in the airways. The widespread implementation of therapy to eradicate initial PA acquisition has lead to decreased prevalence of PA in CF individuals. Similar strategy can be used with other pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), but this remains controversial. This is because it is not possible to determine which CF individuals will clear spontaneously and which will progress to chronic MRSA infection. Suppression of chronic infection has mostly been studied in chronic PA infections. Alternating monthly cycles of inhaled tobramycin, aztreonam or colistin and use of oral azithromycin are commonly employed strategies. The most important use of systemic antibiotics is in the treatment of acute pulmonary exacerbations. Typically oral antibiotics are given for mild exacerbations and intravenous antibiotics for moderate to severe exacerbations. The choices of antibiotics, their duration (10, 14 or 21 days) and best site for treatment (home or hospital) are highly influenced by the CF individual (severity of underlying lung disease, pre-existing CF pathogens, drug allergies, social factors, their wishes) and clinical response to the previous treatments. Many combinations of oral and intravenous antibiotics can be utilized to target particular combinations of positive bacterial culture results. Antimicrobial susceptibility testing is not always helpful in predicting response to treatment.

Most recently, use of the new CFTR mutation-specific targeted therapies medications called ivacaftor (Kalydeco), ivacaftor-tezacaftor (Symdeko) for select individuals with CF have been shown to improve lung function, increase weight, and reduce the risk of acute pulmonary exacerbations.

Prevention

Increased awareness and adherence to infection prevention and control (IPC) strategies in various healthcare settings have stabilized or decreased the prevalence of common CF pathogens such as MRSA and Burkholderia species amongst CF individuals. These include: use of contact precautions (i.e., wearing a gown and gloves) for all CF individuals regardless of their pathogen status; use of surgical mask by CF individuals when in health care settings (hospitals and clinics) to reduce the risk of transmission or acquisition of CF pathogens; a minimum six-foot (2 meters) distance between CF individuals to reduce the risk of droplet transmission of CF pathogens (this does not apply to members of the same household); adequate cleaning and disinfection of pulmonary function testing lab and environmental surfaces with regular audits on adherence.

Segregation of CF individuals is another strategy used outside healthcare setting to decrease direct or indirect person-to-person transmission of common CF pathogens.

Further Reading

1 

LiPuma, John J. “The changing microbial epidemiology in cystic fibrosis.” Clinical microbiology reviews 23, no. 2 (2010): 299-323.

2 

Filkins, Laura M., and George A. O’Toole. “Cystic fibrosis lung infections: polymicrobial, complex, and hard to treat.” PLoS pathogens 11.12 (2015): e1005258.

3 

O'Toole, George A. “Cystic Fibrosis Airway Microbiome: Overturning the Old, Opening the Way for the New.” Journal of bacteriology 200.4 (2018): e00561-17.

4 

Salsgiver, Elizabeth L., et al. “Changing epidemiology of the respiratory bacteriology of patients with cystic fibrosis.” Chest 149.2 (2016): 390-400.

5 

Caverly, Lindsay J., Jiangchao Zhao, and John J. LiPuma. “Cystic fibrosis lung microbiome: opportunities to reconsider management of airway infection.” Pediatric pulmonology 50.S40 (2015): S31-S38.

6 

Chmiel, James F., et al. “Antibiotic management of lung infections in cystic fibrosis. I. The microbiome, methicillin-resistant Staphylococcus aureus, gram-negative bacteria, and multiple infections.” Annals of the American Thoracic Society 11.7 (2014): 1120-1129.

7 

Chmiel, James F., et al. “Antibiotic management of lung infections in cystic fibrosis. II. Nontuberculous mycobacteria, anaerobic bacteria, and fungi.” Annals of the American Thoracic Society 11.8 (2014): 1298-1306.

8 

Saiman, Lisa, et al. “Infection prevention and control guideline for cystic fibrosis: 2013 update.” Infection Control & Hospital Epidemiology 35.S1 (2014): s1-s67.

Web Sites of Interest

American Lung Association

https://www.lung.org/lung-health-and-diseases/lung-disease-lookup/cystic-fibrosis/

Cystic Fibrosis Foundation

https://www.cff.org/What-is-CF/About-Cystic-Fibrosis/

See also: Bacterial infections; Bronchitis; Bronchiolitis; Common cold; Contagious diseases; Immunization; Influenza; Outbreaks; Pneumonia; Public health; Transmission routes; Viral infections; Whooping cough.

Citation Types

Type
Format
MLA 9th
Polenakovik, Filip, and Hari Polenakovik. "Cystic Fibrosis Respiratory Infections." Salem Health: Infectious Diseases & Conditions, 2nd Edition, edited by H. Bradford Hawley, Salem Press, 2020. Salem Online, online.salempress.com/articleDetails.do?articleName=Infect2e_0154.
APA 7th
Polenakovik, F., & Polenakovik, H. (2020). Cystic Fibrosis Respiratory Infections. In H. B. Hawley (Ed.), Salem Health: Infectious Diseases & Conditions, 2nd Edition. Salem Press. online.salempress.com.
CMOS 17th
Polenakovik, Filip and Polenakovik, Hari. "Cystic Fibrosis Respiratory Infections." Edited by H. Bradford Hawley. Salem Health: Infectious Diseases & Conditions, 2nd Edition. Hackensack: Salem Press, 2020. Accessed September 16, 2025. online.salempress.com.