Biology

Cystic fibrosis is an inherited condition that affects the human body, especially the respiratory and digestive systems. It has an autosomal recessive mode of inheritance with a carrier frequency of about 1 in 22 Caucasians. Cystic fibrosis causes an alteration of the viscosity of the mucus being produced at all the epithelial surfaces. The classical form of the syndrome includes broncho-pulmonary infection and pancreatic insufficiency, with a high sweat sodium and chloride concentration (Kumar  Clark 2006). One of the major results of the viscous intraluminal secretions is the chronic bacterial colonization and resulting infections. Some of the bacterial that can complicate cystic fibrosis includes Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa, Burkholderia cepacia, and Stenotrophomonas maltophilia.

Staphylococcus aureus
Staphylococcus aureus is a gram positive ball-shaped cell arranged in an irregular grape-like cluster. It ferments carbohydrates (especially glucose), forms gray-colored to yellow colonies, and it produces catalase (a major distinguishing factor separating it from all other staphylococci).

According to Marks (1990), Staphylococcus aureus is usually the first bacterial pathogen detected in the respiratory secretions of patients with cystic fibrosis. The ability of S. aureus to infect patients with cystic fibrosis is controlled by the agr-locus, which is auto- induced by a short secreted peptide (auto-inducing peptide AIP), of which four different agr-groups have been described according to the variability of the AIP, accounting for cross-activation within and inhibition between the different agr-groups (Kahl, Becker, Belling, Schuhen, Weber,  Peters 2002). It colonizes the lungs of patients with cystic fibrosis and can be transmitted among the same patients. It survives well in the altered mucous layer and is collected in the small airways of the lungs. The ultimate result is the formation of biofilms which makes it difficult for the penetration of immune cells and antimicrobial agents. It causes the production of resistance to antibiotics.

Haemophilus influenzae
H. influenza belongs to a group of tiny, gram negative, pleomorphic bacteria. It is found usually in the mucous linings of the upper respiratory tract of human beings. In children, it is one of the most important causes of meningitis, and respiratory tract infections in both adults and infants.

It is also a complication of cystic fibrosis in which it colonizes the lungs and infects it. The pathogenesis of this infection has been evaluated. According to a research carried out by Starner, Zhang, Kim, Apicella  McCray (2006), nontypeable strains of H. influenzae formed adherent biofilms on the apical surface airway epithelia with decreased susceptibility to antibiotics, and respiratory cells exhibited inflammatory and host defense responsesevidence of a dynamic hostpathogen interaction. This result is important in the treatment of early colonization in patients with cystic fibrosis.

It is transmitted via the respiratory route and it is an obligate human parasite. It can be grouped on the basis of the antigenic properties of the capsule into six groups a, b, c, d, e, and f, with H. Influenza type b being the most virulent, causing invasive disease in children. It does not produce exotoxins. It can exist in two forms encapsulated and non-encapsulated forms.

Pseudomonas aeruginosa
It is a gram negative, motile, rod-shaped organism which has a dimension of about 0.6 x 2 microns. Usually, P. aeruginosa exists in pairs on short chains. Other characteristics include the fact that it is oxidase positive and does not ferment carbohydrates (glucose). It produces a green fluorescent pigment, called fluorescein, and a blue pigment (pyocyanin).

P. aeruginosa is pathogenic only when introduced into areas devoid of normal defences, for example, when the mucous membranes and skin are disrupted by direct tissue damage when intravenous or urinary catheters are used or when neutropenia is present, as in cancer chemotherapy (Brooks, Carroll, Butel  Morse 2006). In case of cystic fibrosis, because the mucus membrane is impaired, it potentiates the abilities of this organism to colonize and cause infections. Several hypotheses related to the underlying molecular defects in cystic fibrosis have been suggested to explain this high rate of prevalence and these include abnormalities of airway surface liquid leading to impaired mucociliary clearance or malfunction of antibacterial peptides, increased availability of bacterial receptors, reduced ingestion of pathogens by cystic fibrosis cells and impaired defence related to low levels of molecules such as nitric oxide or glutathione (Davis 2002). However, it is well known that once Pseudomonas aeruginosa have become established in the respiratory airway, they possess different properties that enhance their survival and allow them to evade antibiotic therapy and hot defences successfully. Conversion to mucoidy and the formation of biofilms are two of the main mechanisms by which this is achieved (Davis 2002).

It is usually a nosocomial pathogen that thrives in moist environments such as water baths, tubs, sinks, and other wet environments.

Burkholderia cepacia
This organism, formerly known as Pseudomonas cepacia, is a gram negative, motile, aerobic rod which is able to grow on plants and animals, in water, in the soil, and on decaying vegetable materials. It is also a nosocomial organism that can be found in the hospital. It has been isolated from a wide variety of water and environmental sources from which it can be transmitted to patients (Brooks et al 2006).

It is not known exactly how this organism is implicated in cystic fibrosis. However, it is important to note that  in general  the species that grow in the lungs of people with cystic fibrosis differ from most of those found in the natural environment (Burkholderia cepacia FAQs 2009). Individuals are usually vulnerable to B. cepacia infection in which they may display an asymptomatic carriage with progressive deterioration within the space of some months. They can also progress to bacteremia and necrotizing pneumonia. Transmission of this organism is by close contact with carriers. On culture media, B cepacia grows on most, especially those used for gram negative organisms. There are however selective media for Burkholderia cepacia. It grows very slowly when compared with other gram negative enteric rods.

Treatment of Burkholderia cepacia infection is difficult. This is due to their resistance to many antibiotics. Standard practices for infection control however can reduce the risk of infection. Burkholderia cepacia poses very little medical risks to healthy people, but some people who have a serious illness (e.g., cancer, AIDS) may be at risk of an infection with this germ (Burkholderia cepacia FAQs 2009).

Stenotrophomonas maltophilia
This organism exists as a free-living, non-fermentative, gram negative bacillus which is found distributed ubiquitously in the environment. Its former name was Pseudomonas maltophilia. It was also grouped previously under the genus Xanthomonas before getting the new name which is still in use. When cultured on blood agar, it forms colonies which have a green to greyish colour. Some of its properties include the fact that it is oxidase negative, and also lysine decarboxylase positive.

It has few virulence properties and predominantly causes colonization of lung parenchyma. It is also important in the aetiology of several nosocomial infections in immunocompromised patients, and those on antimicrobial therapy. In the case of cystic fibrosis, there is no clear pathogenetic association between the condition and the organism. According to a cohort study conducted in 2003, consisting of 20,755 patients with median age at entry of 13.8 years and median follow up time of 3.8 years 2,739 patients (13) were positive at least once for Stenotrophomonas maltophilia and 18,016 (87) were never positive (Goss 2004).

Treatment and Prevention
The major mode of treatment is by the use of antimicrobial agents. These causative agents have different susceptibilities to the antimicrobials. For example, Stenotrophomonas maltophilia is particularly susceptible to trimethoprim-sulfamethoxazole and ticarcillin-clavulanic acid and resistant to other commonly used antimicrobials, including cephalosporins, aminoglycosides, imipenem, and the quinolones (Brooks et al 2006). Also, aztreonam, imipenem, and some of the newer quinolones, such as ciprofloxacin are active against Pseudomonas aeruginosa. In some cases, synergistic combination of therapy can be only the means of killing the causative agents.

Prevention methods include the use of vaccines (in the case of Haemophilus influenzae type b  Haemophilus b conjugate vaccine), paying special attention to wet areas (Pseudomonas aeruginosa), appropriate sterilisation of hospital equipments in order to avaoid hospital-acquired infections (Stenotrophomonas maltophilia), avoiding close contact with carriers (Burkholderia cepacia), and improving the immune status of individuals by good and appropriate feeding, regular exercise, drinking of water, etc. Other methods include maintaining cleanliness, hygiene and proper aseptic management of any lesion, in the case of Staphylococcus aureus.