[Antibiotic therapy in cystic fibrosis. II Antibiotic strategy]. / L'antibiothérapie dans la mucoviscidose. II. Stratégie antibiotique.

Antibiotherapy is one of the main treatments of cystic fibrosis, contributing to a better nutritional and respiratory status and a prolonged survival. The choice of antibiotics depends on quantitative and qualitative analysis of sputum, bacteria resistance phenotypes and severity of infection. Haemophilus influenzae infection can be treated orally with the association of amoxicillin-clavulanic acid or a cephalosporin. Staphylococcus aureus generally remains sensitive to usual antibiotics; in case of a methicillin-resistant strain, an oral bitherapy or a parenteral cure can be proposed. Treatment of Pseudomonas aeruginosa is different in case of first colonization or chronic infection: in first colonization, parenteral antibiotherapy (beta-lactams-aminoglycosids) followed by inhaled antibiotherapy may eradicate the bacteria; in chronic infections, exacerbations require parenteral bi-antibiotherapy (beta-lactams or quinolons and aminoglycosids) for 15 to 21 days, inhaled antibiotics between the cures being useful to decrease the number of exacerbation. A careful monitoring of antibiotherapy is necessary because of possible induction of bacterial resistance, nephrotoxicity and ototoxicity of aminosids and allergy to beta-lactams.

[Antibiotic therapy in cystic fibrosis. I. Pharmacologic specifics of antibiotics]. / L'antibiothérapie dans la mucoviscidose. I. Particularités pharmacologiques des antibiotiques.

Antibiotherapy is one of the main treatment in cystic fibrosis. Antibiotic administration schedules are different from normal patients because of pharmacokinetic and pharmacodynamic particularities. In moderate disease, the digestive resorption of antibiotics is delayed and their half-life is reduced due to an increase in total clearance. In severe disease, the volume of distribution of antibiotics is increased due to the higher proportion of lean mass in these malnourished patients. Other particularities limit the action of antibiotics such as thick sputum, which limits drug penetration; the property of Pseudomonas aeruginosa to be surrounded by a biofilm; alteration of local antibacterial defense; and inhibition of antibiotics by local factors. Systematic prescription of a biotherapy beta-lactam-aminoglycoside and obtaining high antibiotic concentration in situ might limit this antagonism. In spite of particular therapeutic schedules such as single daily dose for aminoglycoside and continuous infusion for beta-lactams, the intervals between administrations must be narrowed for time-dependent antibiotics, and the total daily dose increased by 20 to 30% for concentration-dependent antibiotics.

In vitro susceptibilities to amphotericin B, itraconazole, and miconazole of filamentous fungi isolated from patients with cystic fibrosis.

The antimicrobial activities of amphotericin B, itraconazole, and miconazole against 101 filamentous fungi from patients with cystic fibrosis were tested by a reproducible microdilution method. Itraconazole was very active against Aspergillus species and Scedosporium species (MIC at which 90% of the isolates were inhibited [MIC90], 0.06 to 0.5 mg/liter), whereas amphotericin B was less effective (MIC90, 0.5 to 8 mg/liter).

[Severe colitis in mucoviscidosis]. / Colite grave au cours d'une mucoviscidose.

We report the association of severe indeterminate colitis with cystic fibrosis in a 21 year old woman, with mild pulmonary involvement, and without digestive or pancreatic symptoms or pancreatic enzyme preparation. Ten cases of inflammatory bowel disease associated with a cystic fibrosis have been reported. Most fit with the diagnostic criteria of Crohn's disease. Although this case was compatible with this diagnosis, we have retained the diagnosis of "severe indeterminate colitis" because of the lack of specific histological features of Crohn's disease. The association between inflammatory bowel disease and cystic fibrosis is probably not fortuitous, although the pathophysiological link between the two diseases is unknown.

[Pneumococcal meningitis in children: should probabilistic antibiotherapy of infectious meningitis be modified?]. / Méningites à pneumocoque de l'enfant: faut-il modifier l'antibiothérapie probabiliste des méningites communautaires?

BACKGROUND: Since a significant proportion of Streptococcus pneumoniae strains is now resistant to penicillin and sometimes to third-generation cephalosporin, it is necessary to reevaluate the initial therapy of bacterial meningitis proposed before identification of the organism and its susceptibility pattern. POPULATION: From 1 January 1992 to 31 March 1994, nine children with acute S pneumoniae meningitis were treated with ceftriaxone plus aminoglycoside as conventional initial therapy. Eight children were less than 1 year-old (five from 3 to 6 months). Five S pneumoniae strains were penicillin-resistant; four had a ceftriaxone minimal inhibitory concentration (MIC) of 0.047 to 0.094 mg/L and one of 1.5 mg/L. Ceftriaxone was given intravenously at doses of 50 mg/kg twice a day to patients less than 12 months old and 100 mg/kg once a day to patients older than 12 months. Intravenous amikacin (7.5 mg/kg twice daily) or netilmicin (3 mg/kg twice daily) were administered in combination. Dexomethasone was given to all children as adjunctive therapy. Follow-up lumbar puncture was performed after 24 to 36 hours of treatment. RESULTS: For each of the nine patients, cerebrospinal fluid was sterile with normal glucose level. After 2 or 4 days, initial therapy had been modified according to antibiogram and MIC. Monotherapy with ceftriaxone was continued in five children. Rifampicin was associated with initial bitherapy in one case. In two other patients, initial empiric therapy was stopped and changed to chloramphenicol. CONCLUSION: No case of bacteriological failure was noted in our patients but evolution of epidemiology and emergence of decreased penicillin sensibility in S pneumoniae strains (55% in our study) suggests that a third antibiotic (vancocin or rifampicin) should be associated with the standard first-line drug when S pneumoniae is suspected.

Correlation between activity of beta-lactam agents in vitro and bacteriological outcome in acute pulmonary exacerbations of cystic fibrosis.

A study was conducted to determine whether a direct relationship exists between beta-lactam and/or aminoglycoside activity measured in vitro and bacteriological outcome in acute pulmonary exacerbations of cystic fibrosis. Twenty-seven patients, aged between 6 months and 24 years (mean age 10 1/2 years), were included in the study and received 41 i.v. courses of a beta-lactam agent combined with an aminoglycoside. A total of 63 Pseudomonas aeruginosa strains were found in sputum taken on admission at densities exceeding 10(6) cfu/g of sputum. For each episode, the serum inhibitory quotient (SIQ) and the serum bactericidal quotient (SBQ) of the beta-lactam agent and of the aminoglycoside administered were determined for the Pseudomonas aeruginosa isolate(s). The SIQs and SBQs were calculated by dividing the average peak serum levels achievable in the patients by the minimal inhibitory concentrations and minimal bactericidal concentrations, respectively. The SIQs and SBQs were compared to bacteriological outcome. Bacteriological success was defined as a decrease of 2 log10 counts or more in the Pseudomonas aeruginosa density in sputum between days 0 and 7 of therapy. The SIQ and SBQ of beta-lactam agents were good predictors of bacteriological outcome: SIQs of < 1:16 were 100% predictive of failure (chi 2 28; p < 0.001) and of > or = 1:64 were 92.9% predictive of success (chi 2 35.68; p < 0.001); SBQs of < 1:8 were 100% predictive of failure (chi 2 42.78; p < 0.001) and of > or = 1:32 were 95.8% predictive of success (chi 2 31.5; p < 0.001). Aminoglycoside SIQs and SBQs were not predictive of outcome.

[Infectious complication after lung transplantation for cystic fibrosis]. / Complications infectieuses après transplantation pulmonaire pour mucoviscidose.

The infectious complications after lung transplantation have been studied in 26 patients suffering from mucoviscidosis who had transplants in the Ile-de-France between July 1987 and October 1990. We counted 99 infections (74 bacterial infections, 23 viral infections and two fungal infections) during a cumulative observation period of 127 months. The majority of the infections (48%) were localised to the grafted lung. These infections were responsible for 61% of deaths (50% secondary to bacterial infections and 11% to viral infections). The risk of infection remains even after a considerable time after transplantation in this series. These studies underline the importance of infectious complications in the mortality and morbidity of lung transplant patients suffering from mucoviscidosis.

Cerebrospinal fluid penetration of amikacin in children with community-acquired bacterial meningitis.

The penetration of amikacin into the cerebrospinal fluid (CSF) was studied with 16 children (mean age, 1 year and 9 months; range, 4 months to 8 years) with community-acquired bacterial meningitis. Amikacin was given intravenously at a dose of 7.5 mg/kg of body weight twice daily. CSF was collected on day 1, at the expected peak concentration of amikacin in CSF. The mean (standard deviation) concentration of amikacin in CSF was 1.65 (1.6) mg/liter. Concentrations of amikacin in CSF correlated significantly with CSF glucose levels on admission. The mean concentrations of amikacin in CSF were 2.9, 1.1, and 0.20 mg/liter in patients with CSF glucose levels of < 1, 1 to 2, and > 2 mmol/liter, respectively. Thus, amikacin penetrates the blood-brain barrier substantially in children with bacterial meningitis and achieves particularly high concentrations when CSF glucose level is < 1 mmol/liter on admission.

Insulin responses to intravenous glucose and the hyperglycemic clamp in cystic fibrosis patients with different degrees of glucose tolerance.

The relationship between altered insulin secretion and impaired glucose tolerance was studied in 32 cystic fibrosis patients, 16 men and 16 women, aged 8-26 y, using oral and i.v. glucose tolerance tests and a hyperglycemic glucose clamp (10 mmol/L). Seven of these subjects were already being treated with insulin; seven had fasting blood glucose levels below 7.2 mmol/L but satisfied diabetic criteria at the oral glucose tolerance test; glucose tolerance was impaired in 13 subjects and normal in five. The insulin responses to the two i.v. glucose stimuli were inversely correlated with the plasma glucose levels (60 and 120 min) and the area under the curve of the oral glucose tolerance test. However, the acute insulin response to i.v. glucose was severely altered in patients with impaired glucose tolerance, whereas plasma insulin levels during the hyperglycemic clamp did not differ from those of healthy subjects. The responses to the two stimuli were dramatically low in the diabetic patients. These results suggest that cystic fibrosis patients with normal or impaired glucose tolerance retain their capacity to secrete insulin. Alterations in the acute phase of glucose-stimulated insulin secretion seem to be principally responsible for the early impairment in glucose tolerance.

Concentrations of ceftriaxone in cerebrospinal fluid of children with meningitis receiving dexamethasone therapy.

The penetration of ceftriaxone into cerebrospinal fluid (CSF) was studied with 11 children (mean age: 2 years, 4 months; range: 4 months to 8 years) with meningitis, receiving dexamethasone (0.15 mg/kg of body weight intravenously four times daily) as adjunctive therapy. Ceftriaxone was given intravenously at doses of 50 mg/kg twice daily to patients < 18 months old and 100 mg/kg once daily to patients > or = 18 months old. CSF was collected after 1 day of treatment at the expected peak concentration of ceftriaxone in CSF. Concentrations of ceftriaxone in CSF ranged from 0.7 to 9.2 mg/liter, with a mean value of 4.0 (standard deviation [SD], 2.9) mg/liter. Values were significantly higher for patients with CSF glucose levels of < 1 mmol/liter on admission to the hospital than for patients with CSF glucose levels of > or = 1 mmol/liter (mean values of 7.1 [SD, 2.2] mg/liter versus 2.2 [SD, 1.1] mg/liter; P < 0.001). After 1 day of treatment, ceftriaxone concentrations in the CSF of children receiving dexamethasone are similar to the mean values reported for children not treated with dexamethasone.

[Amiloride hydrochloride nebulized by oxygen in the treatment of mucoviscidosis]. / Etude d'un nébulisat de chlorhydrate d'amiloride véhiculé par de l'oxygène dans la mucoviscidose.

Bronchial inhalation of amiloride chlorhydrate has been suggested for a number of years in the treatment of the pulmonary disease in cystic fibrosis. However, physiotherapy remains invaluable in the struggle in containing pulmonary infections in this disorder. Physiotherapy may lead to a transient fall in the arterial oxygen as can sessions of nebuliser therapy which precedes physiotherapy. The originality of the system studied and proposed here for the administration of medication depends on an electronic control which guarantees that there is the nebulisation of a constant volume of medication with each inspiration. Triggered by inspiration the active principle nebulised is perfectly co-ordinated to the inspiratory cycle. A comparative chromatography carried out in this slides of silica-gel have enabled us to verify the absence of any degradation of the active principle contained in the nebuliser solution during the ten minutes period of aerosol therapy. Thus a quantification of the administered dose of Amiloride Chlorhydrate is made possible. In association with oxygen it enables an efficacious preparation of respiratory physiotherapy to children. As the expiratory tubing ends in a filter the fraction of the oxygen inhaled by the patient remains very high; 80% (V/V) of the medication is emitted in the form of liquid particles whose diameter lies between 0.5 and 5 micrometers. In practice in order to humidify the sputum and to restore the oximetry before the physiotherapy sessions, it seemed to us an interesting possibility to administer Amiloride Chlorhydrate and oxygen simultaneously. This is achieved in hospital by using wall-mounted oxygen (at a gas pressure of 3.5 bars).(ABSTRACT TRUNCATED AT 250 WORDS)