Combination therapy respiratory system

A combination of trimethoprim-sulfamethoxazole is effective treatment for a wide variety of infections including P jiroveci pneumonia, shigellosis, systemic salmonella infections, urinary tract infections, prostatitis, and some nontuberculous mycobacterial infections. It is active against most Staphylococcus aureus strains, both methicillin-susceptible and methicillin-resistant, and against respiratory tract pathogens such as the pneumococcus, Haemophilus sp, Moraxella catarrhalis, and Klebsiella pneumoniae (but not Mycoplasma pneumoniae). However, the increasing prevalence of strains of E coli (up to 30% or more) and pneumococci that are resistant to trimethoprim-sulfamethoxazole must be considered before using this combination for empirical therapy of upper urinary tract infections or pneumonia. 

Pulmonary administration of medicines currently has the primary objective to achieve local effects in the respiratory tract of patients with chronic diseases like asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). For half a century, inhalation therapy has been the cornerstone in the management of these diseases and the often life-time therapies aim to suppress inflammatory processes and bacterial infection in order to reduce hospitalisations and to improve the patient s quality of life. They also give relief to the patient in moments of bronchoconstriction. The advantages of pulmonary administration of medicines for local treatment are well known. The active substances are delivered directly to the site of action which leads to a faster response than via the systemic route. It may also result in higher local active substance concentrations and this could reduce the total dose by as much as a factor 10 compared to oral or intravenous administration. This has the advantage that systemic side effects are reduced and in combination with being a non-invasive method of administration, inhalation therapy may lead to better patient compliance. 

The use of the combination of intestinal and oropharyngeal decontamination still did not significantly reduce the overall incidence of respiratory tract infections (27), because a large proportion of respiratory tract infections occurred within the first 4 days of mechanical ventilation, before decontamination was established. These cases of early-onset pneumonia were caused by pathogens that had already contaminated patients lower respiratory tract in the period shortly before, or after, ICU admission, and therefore could not be eradicated by intestinal and oropharyngeal decontamination. Addition of 3 to 7 days (28) of systemic prophylaxis to the SDD regimen resulted in a further reduction of the early-onset infections (27), presumably as a result of preemptive therapy of incubating pneumonia. 

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