Which medications in the drug class Antibiotics are used in the treatment of Cystic Fibrosis?

Updated: Oct 22, 2019
  • Author: Girish D Sharma, MD, FCCP, FAAP; Chief Editor: Kenan Haver, MD  more...
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Answer

Antibiotics

Antibiotic treatment may vary from a short course of one antibiotic agent to a continuous course with multiple antibiotics administered via various routes, including oral, intravenous, or inhalation. Antibiotic therapy has been found to be related to the greater likelihood of recovery after acute decline in FEV1. [82]  Because patients with cystic fibrosis have a larger lean body mass, they often have a higher clearance rate for many antibiotics. Achieving effective levels in respiratory secretions is difficult; higher doses of antibiotics and monitoring of aminoglycoside levels are required.

A Cochrane review included four studies (total 328 patients) comparing once-daily dosing of aminoglycosides in the treatment of acute pulmonary exacerbation with thrice-daily dose. There were no significant differences in lung function, weight for height, and body mass index. The creatinine changes significantly favored once-daily treatment in children but not in adults. These findings support the recent trend to use once-daily intravenous aminoglycosides. [83]

Administer aerosolized antibiotics when the airway pathogens are resistant to oral antibiotics or when the infection is difficult to control at home. Aerosolized antibiotics may reduce symptoms by reducing the organism density in the airways. Other advantages include prevention of infection or delay of chronic colonization, treatment of acute infection, and treatment of bacterial colonization in patients following transplantation to prevent infection in the transplanted lungs.

Agents used in the aerosolized form include gentamicin, aztreonam, colistin, and preservative-free high-dose tobramycin especially formulated for inhalation (ie, TOBI). Currently, clinical trials using a powder form of tobramycin and colistin are under way. These preparations use novel delivery devices and shorten the time required for dosage administration. A European study comparing lung function in 380 patients with cystic fibrosis and chronic Pseudomonas aeruginosa infection reported that colistimethate sodium dry powder inhalation was as effective as nebulized tobramycin. [84]

Cephalosporins are effective against staphylococci and Haemophilus influenzae. A small subset of third-generation cephalosporins is effective against Pseudomonas aeruginosa. Generally speaking, moving from first-generation to third-generation cephalosporins gives increasing gram-negative coverage and less gram-positive coverage.

Fluoroquinolones are effective against most gram-positive and gram-negative organisms. They are the only class of oral antibiotics effective against P aeruginosa. The most commonly used medication in this class is ciprofloxacin. No fluoroquinolones are approved for children because of concern regarding their effects on deposition in the cartilage. However, studies from Europe have reported substantial evidence of their safety in patients with CF.

In patients with colonization with P aeruginosa, azithromycin administered orally 3 times per week on a long-term basis has been shown to improve lung function and nutritional status and to reduce acute pulmonary exacerbations. [85] . However, one study reported that azithromycin may interfere with the P aeruginosa, killing the action of inhaled tobramycin in these patients. [86]

Because colonization with P aeruginosa is considered to be an unfavorable event in the clinical course of patients with cystic fibrosis, various regimens have been studied in an attempt to eradicate the organism. A group in Italy compared inhaled tobramycin plus oral ciprofloxacin with inhaled colistin plus oral ciprofloxacin. They reported 62.8% and 65.2% eradication, respectively, thus showing no superiority for either treatment. [87]

Tobramycin inhaled (TOBI, Bethkis, TOBI Podhaler)

Preservative-free high-dose tobramycin especially formulated for oral inhalation (ie, TOBI, Bethkis) has been reported to be safe and effective in patients older than 6 months. The usual dose is 300 mg inhaled via nebulization twice daily administered during alternate months. A dry powder inhaler device is also available (TOBI Podhaler) with a different dosage regimen of 4 capsules (28 mg/cap) inhaled orally BID. Long-term intermittent administration in patients with P aeruginosa infection improves pulmonary function and nutritional status and reduces symptomatic pulmonary exacerbation.

Systemic tobramycin is usually combined with one of the penicillins used to treat pseudomonad infections in patients with CF. It is administered intravenously.

Aztreonam inhalation (Azactam, Cayston)

Aztreonam is a monobactam antibiotic that elicits activity in vitro against gram-negative aerobic pathogens, including P aeruginosa. This agent binds to penicillin-binding proteins of susceptible bacteria, thereby inhibiting bacterial cell wall synthesis, resulting in cell death. Activity is not decreased in the presence of cystic fibrosis lung secretions.

Aztreonam is indicated to improve respiratory symptoms in patients with CF who are infected with P aeruginosa.

Gentamicin

Gentamicin is usually combined with one of the penicillins used to treat pseudomonad infections in patients with CF.

Piperacillin

Piperacillin is effective against most strains of P aeruginosa and H influenzae. It is usually not effective against staphylococci. It is administered intravenously.

Cephalexin (Keflex)

Cephalexin is a first-generation cephalosporin that arrests bacterial growth by inhibiting bacterial cell wall synthesis. It has bactericidal activity against rapidly growing organisms. Its primary activity is against skin flora.

Ceftazidime (Fortaz, Tazicef)

Ceftazidime is a third-generation cephalosporin with broad-spectrum gram-negative activity. It has lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. It arrests bacterial growth by binding to one or more penicillin-binding proteins.

Ciprofloxacin (Cipro XR, Proquin XR)

Ciprofloxacin is a fluoroquinolone with activity against Pseudomonas organisms, streptococci, methicillin-resistant Staphylococcus aureus (MRSA), S epidermidis, and most gram-negative organisms, but with no activity against anaerobes. This agent inhibits bacterial DNA synthesis and, consequently, growth. Oral bioavailability is lower in younger patients with CF (65%) than in those older than 13 years (95%).

Trimethoprim/sulfamethoxazole (Bactrim DS, Septra DS)

The broad spectrum and action of trimethoprim and sulfamethoxazole (TMP-SMZ) against organisms found in patients with CF and the convenience of oral administration make this combination useful for treatment of milder infections on an outpatient basis.

Chloramphenicol

Chloramphenicol is effective against H influenzae and staphylococcal species. It may help treat P aeruginosa infection, for unclear reasons. Oral chloramphenicol is no longer available in the United States.


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