Dotage Schedules and Duration of Tteatment
It is widely agreed that antibiotic therapy is beneficial in the treatment of exacerbations of pulmonary infections in patients with cystic fibrosis (CF). Frequent antibiotic treatments have been shown to increase patient survival. Randomized, double-blind, crossover trials, which have shown the benefit of antibiotic therapy in acute exacerbations in patients with chronic obstructive pulmonary disease, have usually been considered unethical in CF. Difficulties in eradicating the colonizing microorganism from the lower respiratory tract have led to interest being focused on the dosages of antibiotics or special characteristics of the bacteria involved, but little attention has been devoted to the characteristics of the internal environment of the bronchi in the patients. …Read the rest of this article
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Dotage Schedules and Duration of Tteatment
It is recommended that future studies of aerosolized antibiotics address the following topics: (1) pharmacologic and safety testing of other antipseu-domonal antibiotics alone or in combination; (2) efficacy trials to determine the effect of aerosolized antibiotics when used to treat pulmonary exacerbations; (3) long-term suppression trials to determine if bacteriologic and clinical effect are maintained; (4) prospective controlled trials to determine the efficacy of aerosolized antimicrobial therapy to prevent or delay chronic P aeruginosa infection. review
4. At present, there are no microbiological indications to discontinue treatment with aerosolized antibiotics. The emergence of resistant P aeruginosa or acquisition of intrinsically antibiotic-resistant organisms such as B cepacia and S maltophilia does not preclude the continued use of nebulized agents intermittently (consensus grade II-2).
Comment: Several previously published studies have shown transient emergence of resistant P aeruginosa during therapy with aerosolized antibiotics that reverted to a susceptible phenotype with discontinuation of treatment with the nebulized agent. This supports the practice of alternate on and off months of therapy and may suggest that more prolonged suspension of aerosol treatment could be useful. Reading here
Recommendations for Addressing Microbiological Implications of Aerosolized Antibiotics
1. It is strongly recommended that all efforts be made to define a breakpoint to correlate in vitro susceptibility with in vivo efficacy for antibiotics delivered by the aerosol route, because at present, there are inadequate data to establish this breakpoint (consensus grade I to III).
Comment: The National Committee for Clinical Laboratory Standards defines MIC breakpoints for parenteral tobramycin as follows: > 4 ^g/mL, susceptible; 8 ^g/mL, intermediate; and > 16 ^g/mL. resistant. These levels are derived from an assessment of clinically achievable antibiotic concentration in serum, the relatively narrow therapeutic index* needed to avoid nephrotoxicity and ototoxicity, and studies of clinical efficacy. …Read the rest of this article
To define a breakpoint for resistance to aerosolized tobramycin, efforts to correlate the MIC of P aeruginosa isolates and clinical efficacy were made in the preservative-free tobramycin study. There was no significant difference in clinical response among patients with isolates with MICs < vs > 64 ^g/mL. Unfortunately, too few patients had high-level resistance (defined as MIC > 128 ^g/mL) to correlate a breakpoint with clinical efficacy. Ongoing studies of this group of patients may enable definition of a new breakpoint for resistance when using aerosolized tobramycin. …Read the rest of this article
What Are the Microbiological Implications of Aerosolized Antibiotics?
There is understandable concern that prolonged use of aerosolized antibiotics could lead to the development of significant antibiotic resistance in P aeruginosa and that intrinsically resistant bacterial and fungal pathogens could emerge during therapy.
Development of Resistance in P aeruginosa While Receiving Aerosolized Antibiotics
Several studies of antibiotic resistance following aerosolized antibiotics in CF patients have been published. In some, the use of aerosolized antibiotics has not been associated with the emergence of resistance and in others, aerosolized antibiotics were associated with the emergence of resis-tance that appeared to be transient as organisms became susceptible after antibiotic treatment was discontinued. In these latter studies, the emergence of resistance did not appear to have clinical consequences. …Read the rest of this article
4. Monitoring for eighth nerve toxicity should include an audiogram (500 to 8,000 Hz range) after two to four courses of IV therapy or 180 accumulated days of aerosol therapy (consensus grade III).
5. The initial dose of a newly prescribed aerosolized antibiotic should be given in the presence of an appropriately trained health-care provider to monitor for wheezing, respiratory distress, and to instruct in proper technique. Patients should be trained to monitor themselves for potential bronchospasm and to immediately stop taking the medication and administer a bronchodilator if indicated (consensus grade III). …Read the rest of this article