Introduction:
Cystic fibrosis is an autosomal recessive disorder that causes sticky, thick, hyper-viscous mucus to build up in the lungs. This mucus secretion is not removed. Instead, the secretions plug up ducts and the airways leading to difficulty breathing and increasing the risk of infections. It is a defect in the cystic fibrosis transmembrane regulator (CFTR) gene. The CFTR is an epithelial anion channel in the alveolar ducts that facilitates the transfer of chloride and bicarbonate ions along with water to pass through it.
How Does the Immune System Detect the Infection?
Bacterial products and components are named pathogen-associated molecular patterns (PAMPS) and are detected by the immune cells' pattern recognition receptors (PRR). The detection of PAMPs and their subsequent activation results in an innate and acquired inflammatory response. One such PRR is the toll-like receptor(TLR), characterized by its ligand specificity.
What Are the Different Bacterial Infections in Cystic Fibrosis?
The most common bacterial infections in cystic fibrosis are:
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Staphylococcal aureus.
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Pseudomonas aeruginosa.
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Burkholderia cepacia complex.
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Nontuberculous mycobacterial infections.
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Haemophilus influenzae.
Cystic fibrosis patients are predominantly infected by specific pathogens, of which Staphylococcal aureus and Pseudomonas aeruginosa are the most prevalent.
Staphylococcal Aureus:
It is the first non-fastidious Gram-positive pathogen to infect and colonize the airways of cystic fibrosis patients, specifically seen in children. It is a co-infective pathogen associated with Pseudomonas aeruginosa. The inflammatory process becomes more intense due to the additive effect of the two pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) has become a major nosocomial pathogen with an increased prevalence in cystic fibrosis patients. MRSA can cause serious infections that usually present multi-resistance to several antibiotics.
Symptoms of MRSA:
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Osteomyelitis- It is an infection of the bone and bone marrow.
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Lung abscess.
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Empyema- Accumulation of pus in between the lung and chest wall.
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Sepsis- It is an infection in the blood.
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Endocarditis - Inflammation of the inner layer of the heart.
If the infection spreads into the body, a person can experience high fever, chills, dizziness, confusion, and body ache.
Lab Diagnosis:
Blood culture is an important tool in the diagnosis of Staphylococcal aureus.
Treatment:
The broad-spectrum anti-MRSA cephalosporins, such as Ceftaroline and Ceftobiprole, have shown a marked ability to limit MRSA biofilm formation.
Pseudomonas Aeruginosa:
It is a non-capsulated, non-sporing oxidase-positive gram-negative motile bacillus that most commonly affects the lower respiratory tract. It is an opportunistic pathogen in cystic fibrosis patients. It is more prevalent in adult cystic fibrosis patients.
Laboratory Investigations:
The standard method for assessing respiratory infections with pseudomonas are:
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Bacterial culture of sputum.
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Oropharyngeal swabs.
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Bronchoalveolar lavage.
Bacterial culture and oropharyngeal swabs are the most frequently used to establish Pseudomonas infection. Bronchoalveolar lavage is an invasive method considered a standard laboratory diagnosis as it reflects colonization of the lower respiratory tract.
Treatment:
The Pseudomonas infections can range in severity from colonization to severe necrotizing bronchopneumonia. The extended-spectrum Penicillins, Aminoglycosides, Cephalosporins, Fluoroquinolones, and Monobactams are the most commonly used. An Aminoglycoside with beta-lactam Penicillin is considered to be the first-line treatment. Nebulised delivery of antipseudomonal antibiotics is thought to prevent recurrent exacerbations, reduce antibiotic usage and maintain lung function, particularly in cystic fibrosis patients.
Burkholderia Cepacia Complex:
It is an aerobic, mesophilic gram-negative bacillus. It is one of the most opportunistic bacterial pathogens of cystic fibrosis patients. It is linked to a more rapid decline in lung function and increases morbidity and mortality.
Symptoms of Burkholderia Are:
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Fever.
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Cough.
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Congestion.
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Shortness of breath.
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Wheezing
Cepacia Syndrome:
If the infection disseminates throughout the body, causing cepacia syndrome, which is characterized by fulminating pneumonic infection along with fever and respiratory failure, and occasional association with septicemia. If left untreated, it can lead to death within weeks.
Lab Investigation:
The best way to confirm Burkholderia infection is to get a sputum culture and a bronchoscopy.
Treatment:
It is highly resistant to antibiotic therapy because its genome is very plastic, shows several mutations, and adapts itself, making it difficult to treat. Isolated pathogenic colonization often loses its characteristic phenotype or growth conditions, leading to difficulty in accurate identification. To overcome this problem, molecular identification is required to distinguish species within the Burkholderia cepacia complex (Bcc). Thorough molecular targets for identification are not reliable when used individually. A multi-target approach is essential to improve the identification of Bcc and non-Bcc organisms. It often requires combination therapy to eradicate the bacteria.
Nontuberculous Mycobacterium (NTM):
It is a group of microorganisms that is common in chronic pulmonary diseases. The most common NTM infecting cystic fibrosis patients is Mycobacterium abscessus. It is particularly resistant to therapy.
Symptoms:
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Persistent cough.
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Fever.
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Night sweats.
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Shortness of breath during activity.
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Weight loss.
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Fatigue.
Lab Diagnosis:
Sputum culture: Rapidly growing medium is an agar-based, selective culture medium designed to isolate nontuberculous Mycobacteria from the sputum of cystic fibrosis patients. Bronchoscopy and imaging tests such as chest X-ray and computed tomography (CT) scans can help confirm the signs of NTM infection.
Treatment:
A combination of three antibiotics is given: Azithromycin, Ethambutol, and Rifampicin.
Haemophilus Influenzae:
It is a gram-negative Coccobacillus that usually infects younger patients between 6-12 years old. This bacterium undergoes hyper mutation making itself resistant to antibiotics and making the treatment more difficult.
Symptoms:
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Cough.
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Fever and chills.
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Excessive fatigue.
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Shortness of breath.
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Muscle pain and headache.
Lab investigation:
Blood culture and spinal fluid, joint fluid, and pleural fluid culture can be done to confirm the presence of the bacteria.
Treatment:
Haemophilus infections are treated with antibiotics such as Cephalosporins, Azithromycin, Amoxicillin, Clarithromycin, and fluoroquinolones.
Conclusion:
Pseudomonas aeruginosa remains the most common pathogen in adults, whereas Staphylococcal aureus is the most common pathogen in children. Expanded culturing and culture-independent molecular methods are used for such polymicrobial respiratory infections. With proper physical examinations along with lab investigation, one can come to a diagnosis in a cystic fibrosis patient.
