SUMMARY To test whether early treatment could postpone the chronic colonisation of the respiratory tract with mucoid strains of Pseudomonas aeruginosa in patients with cystic fibrosis, we performed a pilot study in 28 patients aged 2 to 18 years. A two week course of azlocillin (150 mg/kg/day) and tobramycin (10 to 15 mg/kg/day) was given after a mean duration of P aeruginosa colonisation of five months (range one to 11 months). Weight for height increased significantly by 3-5% (SEM 0.7%) of the predicted normal after chemotherapy. The eradication of P aeruginosa that was achieved in 18 children directly after hospital treatment was only temporary. Samples from only 10 and five patients remained negative three and six months after treatment, respectively. Five children remained free from P aeruginosa for a prolonged period of 14 to 32 months.We conclude that, apart from the clinical improvement in all patients, some children might benefit from early antipseudomonas treatment with respect to the bacteriological outcome. Most children, however, experience only a temporary reduction in colonisation. Further investigations in form of controlled clinical trials seem justified.Pulmonary infection is the primary cause of morbidity in patients with cystic fibrosis. Pseudomonas aeruginosa acts as the main bacterial pathogen that causes a persisting lung infection. ' The P aeruginosa strains are usually of the mucoid, alginate producing variant, whose presence is usually a diagnostic feature of the disease.2 The chronic colonisation with mucoid P aeruginosa is associated with an appreciable clinical deterioration of the patient. This poses a serious therapeutic problem as the eradication of mucoid P aeruginosa from sputum by antibacterial chemotherapy is virtually impossible.Several reports suggest that the appearance of mucoid P aeruginosa in patients with cystic fibrosis is preceded by an asymptomatic period of colonisation of the upper respiratory tract with non-mucoid P aeruginosa strains.4 A clinical trial with intravenous antipseudomonas treatment during the initial phase of P aeruginosa colonisation has not been reported.Therefore we performed an open study to test the hypothesis as to whether early antipseudomonas treatment can eradicate P aeruginosa for a prolonged period of time, thereby postponing the chronic stage of P aeruginosa colonisation in patients with cystic fibrosis. Patients and methods PATIENTSAll patients with cystic fibrosis attending the cystic fibrosis outpatient centre at the Hanover Medical School were regularly examined for P aeruginosa in the respiratory tract. The patients were included in the study according to the following criteria: (a) primary growth of P aeruginosa in the sputum or deep throat swabs, (b) demonstration of a second P aeruginosa positive specimen four to eight weeks after the initial positive sample, and (c) treatment at our centre for at least 12 months before the initial demonstration of P aeruginosa. Out of the 34
In 9 patients, who underwent lumbar drainage after transsphenoidal surgery for pituitary adenoma, we collected 69 samples of CSF and plasma, respectively. The concentration of ofloxacin was measured bacteriologically. Considering the ofloxacin CSF and plasma levels related to time some aspects of pharmacokinetics are discussed. With maximum CSF concentrations coming up to 40% of plasma levels liquor penetrability is quite good. Ofloxacin seems to be able to prevent (postoperative) meningitis, even with grampositive Cocci.
Following a 400 mg preoperative oral dose, ofloxacin concentrations were measured preoperatively in serum and at the time of tissue removal in serum, gall bladder fluid, the gall bladder wall, liver tissue, muscle, fascia, subcutaneous fat and skin. Serum values were more or less constantly above 3 mg/l at all times. The highest intraoperative ofloxacin concentration was 11.85 mg/l in the gall bladder fluid. In the gall bladder wall, liver and muscle, concentrations were slightly higher than in the serum, whereas concentrations in the fascia, subcutaneous fat and skin were clearly lower than serum concentrations. Good activity was observed with regard to the MIC90 of the pathogens most commonly encountered in surgical wards.
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