cefsulodin and Cystic-Fibrosis

Cephalosporins modified at the C-3 and C-7 positions of the cephem-nucleus have high antimicrobial activity and are safe. With evolution through first, second, and third generations, they have gained increasing gram-negative activity, but often at the expense of potency against gram-positive organisms. All third-generation cephalosporins have some intrinsic anti-Pseudomonas activity, indicating their potential benefit in the treatment of acute pulmonary exacerbations in patients with cystic fibrosis. Rational therapy in this clinical setting requires recognition of the pharmacodynamic and pharmacokinetic idiosyncrasies intrinsic to this patient population. When these priorities are recognized, only two of the available agents, cefsulodin and ceftazidime, appear to be of any therapeutic value. Both agents have been evaluated extensively in the treatment of acute pulmonary exacerbation in cystic fibrosis, and both have been found to be safe and effective.

Topics: Cefsulodin; Ceftazidime; Cephalosporins; Clinical Trials as Topic; Cystic Fibrosis; Humans; Kinetics; Lung Diseases; Pseudomonas Infections; Structure-Activity Relationship

A modified chocolate blood agar medium incorporating cefsulodin, a semi-synthetic cephalosporin, was developed and compared with non-selective chocolate blood agar and selective haemin-bacitracin blood agar for the routine isolation of Haemophilus influenzae from the respiratory secretions of patients with cystic fibrosis. The results showed that cefsulodin chocolate blood agar improved the recovery rate of H. influenzae in this group of patients. The medium was stable on storage for 10 days at 4 degrees C.

Topics: Agar; Bacitracin; Blood; Cacao; Cefsulodin; Cephalosporins; Culture Media; Cystic Fibrosis; Haemophilus Infections; Haemophilus influenzae; Hemin; Humans; Inhalation; Respiratory Tract Infections; Sputum

Cephalosporins modified at the C-3 and C-7 positions of the cephem-nucleus have high antimicrobial activity and are safe. With evolution through first, second, and third generations, they have gained increasing gram-negative activity, but often at the expense of potency against gram-positive organisms. All third-generation cephalosporins have some intrinsic anti-Pseudomonas activity, indicating their potential benefit in the treatment of acute pulmonary exacerbations in patients with cystic fibrosis. Rational therapy in this clinical setting requires recognition of the pharmacodynamic and pharmacokinetic idiosyncrasies intrinsic to this patient population. When these priorities are recognized, only two of the available agents, cefsulodin and ceftazidime, appear to be of any therapeutic value. Both agents have been evaluated extensively in the treatment of acute pulmonary exacerbation in cystic fibrosis, and both have been found to be safe and effective.

Topics: Cefsulodin; Ceftazidime; Cephalosporins; Clinical Trials as Topic; Cystic Fibrosis; Humans; Kinetics; Lung Diseases; Pseudomonas Infections; Structure-Activity Relationship

Cefsulodin sodium is a narrow-spectrum cephalosporin with marked in vitro activity against clinical isolates of Pseudomonas aeruginosa. We have studied the antibiotic in a clinical trial in 10 patients admitted to the Pediatric Ward of the University of Virginia Medical Center with cystic fibrosis and recurrent acute lower respiratory tract infections with P. aeruginosa isolated from their sputa. The patients received 500 to 1,500 mg of cefsulodin every 6 hours by intravenous infusion for 10 to 22 days. Mean peak drug levels in plasma after 500, 1,000, and 1,500 mg were 46, 71, and 90 micrograms/ml, respectively, and the mean minimal inhibitory concentration of all organisms was 7.5 micrograms/ml. Detectable levels of cefsulodin in sputa were found in approximately half of the random samples and ranged from 2 to 5 micrograms/ml. The clinical response was satisfactory in nine (90%) of the patients. One patient gained weight and had improved pulmonary function tests but showed no reduction in sputum production and no improvement in arterial blood gas values. In pulmonary function tests, four of five patients tested showed an average 43% increase in forced vital capacity after initiation of therapy and five of five had an average 51% increase in forced expired volume in 1 s. No adverse effects were observed.

Topics: Adolescent; Adult; Cefsulodin; Cephalosporins; Clinical Trials as Topic; Cystic Fibrosis; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Sputum

We have investigated the effectiveness of seven new beta-lactam antibiotics, azlocillin, piperacillin, ceftazidime, cefsulodin, cefoperazone, latamoxef (moxalactam), and cefotaxime, against acute pulmonary exacerbations caused by Pseudomonas aeruginosa in cystic fibrosis. Three hundred and fifty-five strains of Ps aeruginosa isolated from 310 sputum cultures (190 cystic fibrosis patients) were tested for susceptibility to the drugs by determination of minimal inhibitory concentrations (MIC). The highest activity was shown by ceftazidime (6% resistant strains) followed by cefsulodin and piperacillin (15 and 16% resistant strains); very low activity was found for cefotaxime and latamoxef (moxalactam). Ceftazidime was the most active drug against 32 pseudomonas isolates that were resistant to both carbenicillin and aminoglycosides (78% susceptible). A randomized, double-blind trial of azlocillin, piperacillin, ceftazidime, cefsulodin or cefoperazone was performed in 111 cystic fibrosis patients with predominant and susceptible pseudomonas in their sputum. Results were evaluated by a clinical, radiological and bacteriological scoring system: the best results were obtained with ceftazidime, followed by cefsulodin and piperacillin. However, pseudomonas was eradicated in only 22 (23%) of the cases with the most active drugs and persisted or reappeared in all the cases 1 to 3 months later. Ceftazidime always eradicated Staph. aureus and Haemophilus influenzae associated with pseudomonas. Similar eradication occurred nearly always with cefsulodin but rarely with the other drugs. No serious drug reaction occurred but a later fever and rash with piperacillin, transient diarrhoea with cefoperazone, vomiting with cefsulodin, and very frequent eosinophilia with ceftazidime should be mentioned. These five drugs offer, in varying degree, alternatives to traditional anti pseudomonas antibiotics in cystic fibrosis pulmonary infections, but they should be used only against well-proven resistant strains. Ceftazidime is best and cefotaxime and latamoxef (moxalactam) least useful.

Topics: Adolescent; Alcohol Deterrents; Anti-Bacterial Agents; Azlocillin; Cefoperazone; Cefotaxime; Cefsulodin; Ceftazidime; Cephalosporins; Child; Clinical Trials as Topic; Cystic Fibrosis; Double-Blind Method; Eosinophilia; Humans; Moxalactam; Penicillins; Piperacillin; Pseudomonas Infections; Random Allocation; Respiratory Tract Infections

The steady-state renal clearance of cefsulodin was studied in 6 patients with cystic fibrosis and 8 healthy controls. The drug was administered by constant rate infusion to obtain 2 values of plasma concentration, 2 and 30 mg/L. As an estimate of the glomerular filtration rate, the renal clearance of inulin was measured simultaneously. The results showed the figures for inulin clearance to be approximately 30% higher in cystic fibrosis patients than in healthy controls at both concentrations, and a corresponding increase in the renal clearance of cefsulodin was seen in patients over controls. The ratio between the renal clearances of the 2 substances was on average 0.9 in both groups. The correlation found between the 2 renal clearances (r = 0.75; p less than 0.001) indicates that glomerular filtration rate has considerable influence on the renal elimination of cefsulodin. This finding emphasises the importance of glomerular filtration rate for the renal clearance of drugs in cystic fibrosis.

Topics: Adolescent; Adult; Cefsulodin; Cystic Fibrosis; Female; Glomerular Filtration Rate; Humans; Insulin; Kidney; Male; Metabolic Clearance Rate

Cefsulodin is a third generation cephalosporin with specific antipseudomonas activity. We used cefsulodin in combination with aminoglycosides in 15 cystic fibrosis patients treatments. There were 13 children or adolescents, 4 to 19 years old with chronic Pseudomonas aeruginosa lung infections: 9 patients had acute exacerbations of infection with occasionally important respiratory insufficiency and 5 patients had a regimen of regular treatment every 3 months. Cefsulodin was given after record of bacterial sensitivity to antibiotics, at the mean posology of 100 mg/kg, IV, tid. The combination with aminoglycosides was systematic: tobramycin (6 mg/kg/day), netilmicin (6 mg/kg/day) or amikacin (30 mg/kg/day). Duration of treatment was 9 to 15 days.. --clinical improvement in all patients, important in 13 patients and moderate in 2 patients;--respiratory function improvement in 11 patients;--pulmonary radiography improvement in 10 patients;--Pseudomonas were eradicated in 8 patients but temporarily and were found after treatment in 7 patients, 5 with lower number, 2 with higher number. Clinical and biological tolerance was excellent. The present study shows the interest of cefsulodin use in combination with aminoglycosides in this pathology.

Topics: Adolescent; Adult; Aminoglycosides; Anti-Bacterial Agents; Cefsulodin; Child; Child, Preschool; Cystic Fibrosis; Drug Therapy, Combination; Female; Humans; Lung Diseases; Male; Pseudomonas Infections; Superinfection

The aim of this study was to evaluate the in vitro effect of five antibiotics at sub-inhibitory concentrations on the adhesive and haemagglutinating properties of Pseudomonas aeruginosa isolated from cystic fibrosis sputa. Eleven isolates (mucoid and non-mucoid) from cystic fibrosis, and four isolates (mucoid and non-mucoid) from other chronic respiratory infections were tested. The adhesion test was performed on human lymphoblastoid cell-lines; the haemagglutination test used human O+ and guinea-pig erythrocytes. The antibiotics were tested at six sub-inhibitory concentrations, from MIC/2 to MIC/64. Among the five antibiotics, cefsulodin and pefloxacin were the most active in decreasing the adhesive properties: this effect was statistically significant at MIC/2 and MIC/4 for cefsulodin and at all sub-inhibitory concentrations for pefloxacin. No differences appeared between mucoid and non-mucoid strains, and no correlation was noted with their clinical origins. The three other antibiotics (ceftazidime, latamoxef and imipenem) had no significant effect on the adhesion of all the strains tested, but their effect was rather strain-dependent. This fact and the heterogeneity found in adherence and haemagglutinating activity of each strain suggest that the adhesins and the haemagglutinins of P. aeruginosa are very complex structures.

Topics: Animals; Anti-Bacterial Agents; Bacterial Adhesion; Cefsulodin; Ceftazidime; Cystic Fibrosis; Guinea Pigs; Hemagglutination; Humans; Imipenem; Microscopy, Electron; Moxalactam; Pefloxacin; Pseudomonas aeruginosa; Sputum

The pharmacokinetic characteristics of cefsulodin have been studied in 7 patients suffering from cystic fibrosis (CF) and compared to the findings in 6 children without CF. They were given intravenous bolus doses (3 min) of 40 mg/kg. The antibiotic concentrations were assayed by high-pressure liquid chromatography. The serum concentrations were lower in the CF group as reflected by the mean total area under the serum concentration curves of 180 vs. 309 mg h/1, and the serum concentrations after 8 hours which were below the detection limit in the CF patients compared to 4.7 mg/l in the non-CF. The patients with cystic fibrosis had a not significantly lower total body clearance (5.8 vs. 7.0 1/h). The serum half-life was slightly shorter in patients with CF (1.2 vs. 1.4 hours). Consequently, given microbes of the same MIC's, patients with CF should receive higher doses than those recommended for patients without cystic fibrosis.

Topics: Adolescent; Cefsulodin; Child; Child, Preschool; Cystic Fibrosis; Female; Humans; Infant; Kinetics; Male; Respiratory Tract Infections; Urinary Tract Infections

The single-dose pharmacokinetics of cefsulodin were evaluated in 12 patients with cystic fibrosis. Each patient received 3 g of cefsulodin intravenously over 30 min. Multiple plasma and urine samples were obtained during the 6-h study period for the determination of cefsulodin. Pharmacokinetic parameters were determined by model-independent methods. Mean values for t1/2, Vss, and CLp were 1.53 h, 0.242 liters/kg, and 117.3 ml/min per 1.73 m2, respectively. Six-hour urine recovery revealed 73.2% of the administered dose with a corresponding cefsulodin urinary clearance of 75.1 ml/min. These pharmacokinetic data in patients with cystic fibrosis appear consistent with data reported for unaffected individuals.

Topics: Adolescent; Adult; Cefsulodin; Cephalosporins; Child; Cystic Fibrosis; Female; Humans; Injections, Intravenous; Kinetics; Male

During the period 1971-75, 51 cystic fibrosis (CF) patients who contracted chronic P. aeruginosa infection were treated at the Danish CF centre with anti-pseudomonas chemotherapy only when their clinical condition deteriorated considerably. During the period 1976-80, 58 CF patients who contracted chronic P. aeruginosa infection were treated at the Danish CF centre with anti-pseudomonas chemotherapy on a regular basis every 3 months. Each routine 24 day-course of chemotherapy consisted of tobramycin in combination with carbenicillin or other beta-lactam antibiotics with activity against P. aeruginosa. In case of allergy or resistant strains monotherapy with tobramycin was used. The 5-year survival of CF patients from the time of the onset of the chronic P. aeruginosa infection increased from 54% in the first period to 82% in the second period (p less than 0.05), and lung function (peak expiratory flow rate) also improved significantly. It is concluded that intensive "maintenance" chemotherapy against P. aeruginosa improves survival and quality of life of CF patients although permanent eradication of P. aeruginosa is not accomplished.

Topics: Adult; Anti-Bacterial Agents; Carbenicillin; Cefsulodin; Cephalosporins; Cystic Fibrosis; Drug Therapy, Combination; Female; Humans; Male; Peak Expiratory Flow Rate; Pseudomonas Infections; Tobramycin

Topics: Adolescent; Adult; Cefsulodin; Cephalosporins; Cystic Fibrosis; Female; Glomerular Filtration Rate; Humans; Inulin; Kidney; Male

20 patients with cystic fibrosis and chronic pulmonary Pseudomonas aeruginosa infection underwent a total of 23 courses of treatment with a new cephalosporin, cefsulodin. The patients were given 100-150 mg/kg/day in 3 divided doses for 14 days, alone or in combination with tobramycin. Maximum serum levels were around 150 microgram/ml and 6-h levels above 5 micrograms/ml. 90% of the infecting strains were sensitive to 5 micrograms/ml in vitro. Apart from discomfort in direct relation to intravenous bolus injection the drug was well tolerated. Clinical improvement was pronounced, and in 5 cases. P. aeruginosa disappeared from bronchial secretions. Patients allergic to carbenicillin tolerated cefsulodin without signs of allergy. Cefsulodin thus appears to be an effective alternative to carbenicillin in the treatment of severe P. aeruginosa infections.

Topics: Adolescent; Adult; Cefsulodin; Cephalosporins; Child; Cystic Fibrosis; Drug Evaluation; Female; Humans; Lung Diseases; Male; Pseudomonas aeruginosa; Pseudomonas Infections