azlocillin and Cystic-Fibrosis

Cross-over studies on volunteers with several doses of azlocillin ranging from 1.0 to 5.0 g have shown that azlocillin is subject to dose dependent pharmacokinetics, the area under the serum curve becoming larger than expected as doses increase. There was also a tendency towards longer serum half-life values and excretion of more unchanged compound as the doses increase. The serum half-life varied between 0.9 h after 1.0 g increasing to 1.5 h after intravenous doses of 5.0 g given to adults. In neonates, values around 2.6 h have been observed, and they were slightly longer in premature babies at approximately twice the value in adults receiving similar doses per kg body weight. In normal adults protein binding lies between 35 and 40% for therapeutic concentrations. Approximately 60-75% of the dose appears as unchanged azlocillin in the urine, increasing with higher doses. Reduced renal function lowers urinary excretion, but concentrations are always above the break point for sensitivity of 32 mg/l in patients with creatinine clearances above 10 ml/min. In anephric subjects T1/2 of 2.5-6 h is observed. Dosage modifications only to one-third of normal are needed for a renal clearance of 10-25 ml/min. The concentrations of active compound are high in the bile in subjects with normal liver function.

Topics: Azlocillin; Cystic Fibrosis; Dose-Response Relationship, Drug; Female; Half-Life; Humans; Infant, Newborn; Intestinal Absorption; Kidney Diseases; Kinetics; Liver Diseases; Penicillins; Pregnancy; Protein Binding; Renal Dialysis

We determined whether a beta-lactam and an aminoglycoside have efficacy greater than a beta-lactam alone in the management of a pulmonary exacerbation in patients with cystic fibrosis.. Azlocillin and placebo or azlocillin and tobramycin were administered to 76 patients with a pulmonary exacerbation caused by Pseudomonas aeruginosa in a randomized double-blind, third-party monitored protocol. Improvement was assessed by standardized clinical evaluation, pulmonary function testing, sputum bacterial density, sputum DNA content, and time to the next pulmonary exacerbation requiring hospitalization.. No significant difference was seen between the 2 treatment groups in clinical evaluation, sputum DNA concentration, forced vital capacity, forced expiratory volume in second 1, or peak expiratory flow rate at the end of treatment (33 receiving azlocillin alone and 43 both antibiotics); adverse reactions were equivalent in each group. Sputum P. aeruginosa density decreased more with combination therapy (P =.034). On follow-up evaluation, an average of 26 days after the end of treatment, all outcome indicators had worsened in both groups. Time to readmission for a new pulmonary exacerbation was significantly longer in the group receiving azlocillin plus tobramycin (P <.001). Treatment-emergent tobramycin resistance occurred in both groups and was more frequent with combination therapy.. We conclude that the combination of a beta-lactam and an aminoglycoside produces a longer clinical remission than a beta-lactam alone and slightly better initial improvement.

Topics: Adolescent; Analysis of Variance; Anti-Bacterial Agents; Azlocillin; Child; Cystic Fibrosis; DNA, Bacterial; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Male; Penicillins; Pseudomonas aeruginosa; Respiratory Function Tests; Sputum; Tobramycin; Vital Capacity

The immunogenicity, allergenicity, and cross-reactivity of aztreonam were investigated in 21 patients with cystic fibrosis (CF) (aged 5 to 39 years) with well-documented histories of allergic systemic reactions (SRs) to penicillin and/or cephalosporin antipseudomonal beta-lactam antibiotics (BLAs). Skin tests (STs) with penicilloyl-polylysine (PPL), penicillin minor determinant mixture, and antipseudomonal BLA were positive in 19 patients (90%). The BLA causing the most recent allergic reaction, minor determinant mixture, or PPL, was positive in 89%, 53%, and 32% of ST-positive patients, respectively. Serum PPL-specific IgE antibodies were not detectable, although PPL-specific IgG antibodies were found in 64% of patients tested. STs to aztreonam reagents were performed and were initially negative in 20 patients. One patient was ST positive to the polylysine conjugate of hydrolyzed aztreonam (SQ 27629), despite no prior exposure to aztreonam, and was not treated. Of 20 patients treated with aztreonam, four were demonstrated to be sensitized by exposure (one had an SR during initial treatment course, two had SRs on reexposure, and one patient was asymptomatic after intravenous desensitization) by positive aztreonam reagent skin responses on repeat testing. Aztreonyl-specific IgE and IgG serum antibodies were not detected in any patients, including patients with allergic reactions to aztreonam. Thus, aztreonam is generally well tolerated in high-risk patients with CF allergic to other BLAs and appears to have reduced immunogenicity by serologic testing. However, caution should be exercised with aztreonam in BLA-allergic patients with CF in light of 5% preexisting ST cross-reactivity and 20% sensitization rates found in this study.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Antibodies, Anti-Idiotypic; Azlocillin; Aztreonam; Ceftazidime; Child; Child, Preschool; Cross Reactions; Cystic Fibrosis; Drug Hypersensitivity; Female; Humans; Immunoglobulin E; Immunoglobulin G; Male; Piperacillin; Skin Tests; Ticarcillin; Tobramycin

The efficacy of aztreonam was compared to that of standard therapy consisting of tobramycin and azlocillin in the treatment of acute pulmonary exacerbations of cystic fibrosis in a randomized, open trial. Fifteen patients were randomized to each treatment. Responses were assessed based on changes in pulmonary and clinical scores, white blood cell counts, pulmonary function tests and quantitative bacteriology of sputum which were performed before, every 5 to 7 days during and on the last day of therapy. Patients in both groups responded to therapy and there were no statistically significant differences in changes in the above indicators of response with therapy between the two groups (P greater than 0.05). The incidence of detection of Pseudomonas aeruginosa isolates resistant to all three study antibiotics increased with therapy. Side effects were limited to transient elevations of liver enzymes (both groups) and rash and fever in one patient treated with azlocillin. Aztreonam represents effective therapy for pulmonary exacerbations of cystic fibrosis associated with susceptible pathogens.

Topics: Adolescent; Azlocillin; Aztreonam; Child; Cystic Fibrosis; Drug Therapy, Combination; Female; Humans; Liver; Male; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Random Allocation; Respiratory Tract Infections; Sputum; Tobramycin; Transaminases

40 adult patients with cystic fibrosis (CF) were admitted to hospital with acute exacerbations of infection associated with isolation of Pseudomonas aeruginosa from sputum. The patients were randomly allocated (20 per group) to receive intravenous azlocillin 5 g and gentamicin 80 mg, or oral ciprofloxacin 500 mg. Both treatments were given three times a day for 10 days. The patients were assessed on days 1 and 10, and at 6 weeks. There was a significant improvement in lung function between days 1 and 10 in both groups (p less than 0.001). Significant improvement was maintained at 6 weeks after ciprofloxacin but not in the intravenous group. Improvement after ciprofloxacin was superior at day 10. Sputum weight decreased in both groups (p less than 0.001). Patient-recorded symptoms also improved in both groups. There was no serious toxicity or side-effects. Drug resistant organisms were isolated no more frequently after ciprofloxacin than after intravenous therapy. 17 of the ciprofloxacin-treated patients said they preferred oral treatment to intravenous therapy. Oral ciprofloxacin is a useful short-term treatment for patients with CF who are infected with Ps aeruginosa.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Azlocillin; Ciprofloxacin; Clinical Trials as Topic; Cystic Fibrosis; Drug Therapy, Combination; Female; Gentamicins; Humans; Injections, Intravenous; Male; Pseudomonas Infections; Random Allocation; Respiratory Function Tests

Twenty adult patients with cystic fibrosis who were experiencing acute pulmonary exacerbations were enrolled in a randomized, controlled trial comparing oral ciprofloxacin with intravenous tobramycin plus azlocillin. Efficacy of the two treatments was compared based upon changes in clinical status, pulmonary function tests, white blood cell counts, and quantitative bacteriology of sputum. No statistically significant differences were detected in these parameters of response between the two treatment groups (p greater than 0.05). Ciprofloxacin appears to be therapeutically equivalent to intravenous antibiotics in the treatment of adult patients with cystic fibrosis who are experiencing pulmonary exacerbations associated with susceptible bacteria.

Topics: Adult; Anti-Bacterial Agents; Azlocillin; Bacterial Infections; Ciprofloxacin; Clinical Trials as Topic; Cystic Fibrosis; Drug Therapy, Combination; Humans; Lung Diseases; Random Allocation; Therapeutic Equivalency; Tobramycin

Ciprofloxacin, a 4-quinolone bactericidal antimicrobial, has a high activity against a broad spectrum of bacterial microorganisms, including Pseudomonas aeruginosa. The fact that ciprofloxacin can be administered orally would represent a cost-efficient advance in the management of patients with cystic fibrosis, most of whom must be treated frequently with anti-pseudomonal antibiotics. In this study, 11 adult patients received 26 therapeutic courses of ciprofloxacin at a dose of 750 mg orally every 12 hours. In addition, a 13-year-old patient received 500 mg orally every 12 hours. The length of therapy was usually two weeks, but some patients received treatment for up to eight weeks. The mean serum concentration at two to three hours after administration of a dose was 3.68 micrograms/ml (range, 1.85 to 7.25 micrograms/ml). The mean trough level was 0.85 microgram/ml (range, 0.36 to 1.65 micrograms/ml). A comparable group of 11 patients matched by age and severity of disease were treated with conventional doses of tobramycin and azlocillin administered intravenously for at least two weeks. Sputum cultures from all the patients grew P. aeruginosa, except for one patient with Pseudomonas cepacia infection; the minimal inhibitory concentration of ciprofloxacin for these organisms ranged from 0.05 to 1.56 micrograms/ml. The clinical and microbiologic results obtained with these two antimicrobial regimens were similar. A therapeutic failure was noted in the patient infected with P. cepacia whose organism became resistant after one week of therapy (minimal inhibitory concentration greater than 4.58 micrograms/ml). Emergence of resistant strains was not observed in any of the other patients.

Topics: Adolescent; Adult; Azlocillin; Ciprofloxacin; Clinical Trials as Topic; Cystic Fibrosis; Drug Therapy, Combination; Female; Humans; Lung Diseases; Male; Penicillin Resistance; Pseudomonas Infections; Tobramycin

There is great need for an oral agent that could be used to treat pulmonary exacerbations in patients with cystic fibrosis. In this study, the use of oral ciprofloxacin as sole therapy was evaluated in 18 patients with 39 infectious episodes; 13 episodes were classified as severe, 19 were classified as moderate, and seven were classified as mild. Patients ranged in age from eight to 36 years (mean, 23 years). Dosage varied according to severity of disease, body size, and the susceptibility of the Pseudomonas isolate to ciprofloxacin; the dose ranged from 750 to 2,250 mg daily (mean, 1,800 mg). Ten patients received one course of ciprofloxacin, and eight received repeated courses. The overall clinical response rate was 82 percent. There was a response to the initial treatment course in 96 percent of the patients. Those in whom therapy failed had been re-treated with ciprofloxacin and were severely ill. Failure to respond correlated poorly with pretreatment minimal inhibitory concentration (MIC) values (0.6 microgram/ml for failures versus 0.4 microgram/ml for responses). Pseudomonas could not be eradicated from the sputum of any of the patients, although there was a marked reduction in purulence and bacterial counts. In general, patients who did not require re-treatment for three months would again have susceptible organisms. When organisms became resistant to ciprofloxacin (MIC greater than 2 micrograms/ml), they showed no concomitant new aminoglycoside or beta-lactam resistance. No serious toxicity occurred in any of the 39 episodes of treatment. In seven patients treated with combination therapy (tobramycin or azlocillin), the infecting organisms were reduced in number, but eradication of Pseudomonas generally could not be achieved. Increases in MIC occurred during combination therapy. Ciprofloxacin is a major advance in the treatment of bronchopulmonary infection in patients with cystic fibrosis.

Topics: Adolescent; Adult; Azlocillin; Child; Ciprofloxacin; Clinical Trials as Topic; Cystic Fibrosis; Drug Therapy, Combination; Female; Humans; Lung Diseases; Male; Pseudomonas Infections; Tobramycin

High-dose anti-Pseudomonas chemotherapy is mandatory in the treatment of acute pulmonary exacerbations in patients with advanced cystic fibrosis and Pseudomonas aeruginosa isolated from their sputum. However, neither the regimen itself nor its objective evaluation have been optimized yet. In a prospective controlled evaluation 42 such exacerbations were treated for two weeks with netilmicin combined by randomisation with either azlocillin or ticarcillin. Other aspects of therapy were constant. The two therapy groups were comparable in all aspects. Both regimens produced similar improvements in clinical, radiological, laboratory, bacteriological and pulmonary function measurements. Concentrations of sputum bacteria were significantly reduced; transient eradication was documented in 29% and correlated with antibiotic susceptibility of the initially isolated Pseudomonas strains. The highly dosed antibiotics were well tolerated and emergence of resistance was rarely observed. It is concluded that both antibiotic combinations are beneficial and safe in cystic fibrosis. Monitoring of such intensive hospital treatment must include multiple parameters.

Topics: Adolescent; Adult; Azlocillin; Child; Child, Preschool; Clinical Trials as Topic; Cystic Fibrosis; Drug Combinations; Female; Humans; Lung Diseases; Male; Netilmicin; Penicillins; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Function Tests; Ticarcillin

A randomised controlled open comparison of azlocillin and gentamicin versus carbenicillin and gentamicin was carried out in patients with cystic fibrosis who were chronically infected with Pseudomonas aeruginosa. The clinical response was assessed by measurements of pulmonary function and of the patients' feelings of wellbeing scored on a visual analogue scale. The sputum penetration of the antibiotics used was also studied. The two groups of 10 patients were similar in terms of age, sex, and pulmonary function at entry to the trial. Both regimens produced significant improvement in pulmonary function over 10 days. The mean FEV1 in the azlocillin group increased from 1206 to 1760 ml (p less than 0.001). In the carbenicillin group the mean FEV1 increased from 1116 to 1619 ml (p less than 0.001). Significant improvements in peak expiratory flow rate, forced vital capacity, and score on the visual analogue scale were also seen but there was no significant difference between the antibiotic regimens. Despite high serum concentrations the sputum penetration of the antibiotics was poor.

Topics: Adolescent; Adult; Azlocillin; Carbenicillin; Clinical Trials as Topic; Cystic Fibrosis; Drug Therapy, Combination; Female; Forced Expiratory Volume; Gentamicins; Humans; Lung Diseases; Male; Microbial Sensitivity Tests; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Random Allocation

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

In a randomized, double-blind study, cystic fibrosis patients 11-30 years of age with an acute exacerbation of their pulmonary disease were treated with either ticarcillin-tobramycin, azlocillin-tobramycin, or azlocillin-placebo for 10 days. There was significant improvement in Shwachman scores and pulmonary function tests. Concentrations of sputum bacteria were significantly reduced, but after therapy patients had a mean of 10(7) bacteria/ml of sputum. Pseudomonas was transiently eliminated in only one patient. The three regimens had similar impacts on pulmonary function and sputum bacterial concentration. Antibiotic resistance was noted more frequently in the azlocillin-placebo group, but this trend was not statistically significant. Improvement in pulmonary function did not correlate with bacteriological response. Four weeks after discharge, 62% of the improvement in forced expiratory volume in one second and 75% of the improvement in vital capacity remained, but concentrations of sputum bacteria had returned to pretreatment levels, and antibiotic-resistant bacteria persisted.

Topics: Acute Disease; Adolescent; Adult; Anti-Bacterial Agents; Azlocillin; Child; Clinical Trials as Topic; Cystic Fibrosis; Double-Blind Method; Drug Therapy, Combination; Humans; Lung; Penicillin Resistance; Penicillins; Random Allocation; Ticarcillin; Tobramycin

Patients with cystic fibrosis hospitalized because of deterioration in their pulmonary disease were randomly assigned to receive ten days of intravenous antibiotic therapy with either ticarcillin plus tobramycin (previously the standard regimen at our hospital), azlocillin plus tobramycin or azlocillin plus placebo. Pulmonary function and microbiological responses were similar in the three treatment groups, although patients receiving azlocillin and placebo tended to have a smaller reduction in the concentration of bacteria in the sputum and a greater rate of acquisition of antibiotic-resistant organisms. Overall, in-hospital treatment was associated with a significant improvement in Shwachman score, pulmonary function tests, and PO2. Improvement was noted by day 5 of therapy, continued through day 10, and was partially maintained at follow-up clinic visit one month after discharge. There was also a statistically significant reduction in sputum bacterial concentration, but patients cultured at the conclusion of antibiotic therapy still had a mean of 10(7) cfu/ml in sputum. Pseudomonas aeruginosa, the principal pathogen recovered from sputum cultures in this study, was transiently suppressed to sub-detectable levels in only one patient. There was no correlation between microbiological response and change in any parameter of pulmonary function. By follow-up clinic visit, sputum bacteria had returned to pre-treatment levels, and antibiotic-resistant organisms persisted in all patients from whom they had been recovered during hospitalization.

Topics: Adolescent; Adult; Aged; Azlocillin; Bacterial Infections; Child; Clinical Trials as Topic; Cystic Fibrosis; Double-Blind Method; Drug Therapy, Combination; Humans; Lung Diseases; Middle Aged; Penicillins; Random Allocation; Respiratory Function Tests; Sputum; Ticarcillin; Tobramycin

Azlocillin, a new acylureidopenicillin, has been compared to carbenicillin in a controlled, double-blind study for acute exacerbations of pulmonary infections in 29 patients with cystic fibrosis. Twenty-six patients were valid for final analysis of their therapeutic results; 12 treated with azlocillin (group I) at mean dosage of 252 mg/kg/day for a mean duration of 13.2 days of treatment, and 14 treated with carbenicillin (group II) at mean dosage of 505 mg/kg/day for a median duration of 12.6 days. Except for one patient of group I who had Staphylococcus aureus in sputum culture, the remaining patients all had Pseudomonas aeruginosa of mucoid colonial morphology with or without the same organism of rough variety in their sputum culture. Therapeutic efficacy was evaluated according to our scoring system of ten clinical factors, five radiological and five pulmonary function factors with 5 points each and 100 points total if perfect. The percentage of patients who improved by 20% or greater in clinical scores was found in 91.7% of patients in group I and 64.3% of patients in group II, which was statistically significantly different. The percentage of patients who improved by 20% or greater in total scores was found in 80% of group I and 45.5% of group II patients, which was less significant than the evaluation of clinical scores alone. Azlocillin was well tolerated and safe in the dosage employed. Its optimal dosage for patients with cystic fibrosis should be established.

Topics: Adolescent; Adult; Azlocillin; Bacterial Infections; Carbenicillin; Child; Child, Preschool; Clinical Trials as Topic; Cystic Fibrosis; Double-Blind Method; Female; Humans; Lung Diseases; Male; Microbial Sensitivity Tests; Penicillins; Piperacillin

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azlocillin; Child; Cystic Fibrosis; Female; Humans; Lung Diseases; Male; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Sputum

The purpose of this study was to compare resistance and cross-resistance development in Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients to commonly used antipseudomonal antibiotics. Isolates were repeatedly exposed to subinhibitory concentrations of either azlocillin, tobramycin, ceftazidime or ciprofloxacin. On 10 consecutive occasions, samples were removed from the half-MIC well of a microtitre plate and regrown in drug-free medium to provide the next inoculum for MIC determination. The increase in MIC at the end of the treatment period was significant (p<0.05) for all selecting antibiotics. Cross-resistance to unrelated antibiotics was not observed, but was significant (p<0.05) in all beta-lactams (ticarcillin, piperacillin, ceftazidime and cefsulodin) studied where azlocillin was the selecting antibiotic. The addition of clavulanic acid to ticarcillin and of tazobactam to piperacillin had no effect on cross-resistance. The development of resistance to azlocillin was associated with increased beta-lactamase activity and a change in isoelectric point of the beta-lactamases. The result of this study supports a rotational policy for antipseudomonal antibiotics in CF patients.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azlocillin; Ceftazidime; Cephalosporins; Ciprofloxacin; Cystic Fibrosis; Drug Resistance, Microbial; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

The ability of combinations of azlocillin and tobramycin to prevent or delay resistance development in eight Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients was studied using chequerboard titration and in-vitro serial subculture. No isolate had developed resistance to tobramycin after 12 treatments with the antibiotic combination. Azlocillin resistance had not developed in four isolates after 16 exposures, and was delayed in the other four isolates for at least eight exposures. Beta-lactamase production was responsible for azlocillin resistance in two isolates and occurred to a lesser extent in a third.

Topics: Anti-Bacterial Agents; Azlocillin; Cystic Fibrosis; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

A combination of esterase electrophoretic typing and analysis of the restriction fragment length polymorphism of ribosomal DNA regions (ribotyping) was used to compare 27 Pseudomonas aeruginosa strains isolated before and after two-week courses of anti-pseudomonal treatment in seven cystic fibrosis patients. A total of 12 courses of therapy were studied in which ciprofloxacin, ceftazidime, azlocillin or imipenem were used alone or in combination with tobramycin. Isolates at a count of greater than or equal to 10(6) cfu/ml of sputum were collected when there was evidence of therapeutic failure on the basis of persistence of isolates whether or not they were resistant to the antibiotic used for therapy. Emergence of resistance was observed in ten cases and failure to eradicate sensitive strains in five cases. Among the 27 isolates, eight zymotypes and five ribotypes were identified. With this typing approach, resistant post-therapy isolates were found to be identical to pre-therapy isolates in all cases but one. However, in one case an additional resistant strain was isolated after therapy besides that initially present. In all five cases in which susceptibility was still observed after treatment, pre-therapy and post-therapy isolates were indistinguishable. Using this molecular typing approach, all the strains were typable. Thus combination of esterase typing and ribotyping should improve the analysis of therapeutic failure in cystic fibrosis patients.

Topics: Azlocillin; Bacterial Typing Techniques; Ceftazidime; Ciprofloxacin; Cystic Fibrosis; Drug Resistance, Microbial; Drug Therapy, Combination; Esterases; Humans; Imipenem; Polymorphism, Restriction Fragment Length; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections

The pharmacokinetics of netilmicin was studied in 14 patients with cystic fibrosis, aged 4-21 years (mean 16 years) during treatment of pulmonary exacerbations of pseudomonas infection. The patients received 24 courses of netilmicin (10 mg/kg/day) in combination with azlocillin (600 mg/kg/day), cefsulodin (200 mg/kg/day) or ceftazidime (150 mg/kg/day) for 9-14 days. Seven patients received two or three courses of different combinations. Serum and sputum concentrations of netilmicin were determined on day 2 and 6. Mean (+/- S.E.M.) trough serum values were 1.4 +/- 0.2 mg/l (same on day 2 and 6), peak values at 10 min 13.6 +/- 1.0 and 13.7 +/- 0.9 mg/l, and serum concentration at 1 h 7.5 +/- 0.6 and 7.5 +/- 0.5 mg/l, on days 2 and 6 respectively. The half-life was about 1 h. The pharmacokinetics did not differ on day 2 and 6. Sputum concentrations increased up to 2-3 h after administration, mean (+/- S.E.M.) peak values being 2.6 +/- 0.6 and 1.5 +/- 0.4 mg/l at day 2 and 6, respectively. The study shows that the pharmacokinetics of netilmicin was not influenced by different combinations with beta-lactams. All patients improved clinically, but pseudomonas growth was only reduced in nine courses. In one case transient resistance to netilmicin developed during the treatment. The clinical efficacy and tolerance were good and similar to those seen with combinations with other aminoglycosides.

Topics: Adolescent; Adult; Azlocillin; Cephalosporins; Child; Child, Preschool; Cystic Fibrosis; Female; Humans; Lung Diseases; Male; Netilmicin; Pseudomonas aeruginosa; Sputum

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.

Topics: Adolescent; Azlocillin; Child; Child, Preschool; Cystic Fibrosis; Drug Therapy, Combination; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Serotyping; Sputum; Time Factors; Tobramycin

Topics: Anti-Bacterial Agents; Azlocillin; Aztreonam; Ciprofloxacin; Cystic Fibrosis; Humans; Tobramycin

Two Pseudomonas aeruginosa strains, one monoagglutinable and one polyagglutinable, isolated from cystic fibrosis patients were grown in mixed culture. The strains were then separated by means of their azlocillin susceptibility and a number of colonies were tested for serotype and phage type. Changes from monoagglutinable to polyagglutinable reaction and vice versa were observed. The monoagglutinable strain was able to perform bacteriophage infection of the polyagglutinable strain, but no free phages were released. If the donor strain was to produce plaques on the receptor strain, the presence of bacteria belonging to the donor strain was essential.

Topics: Agglutination Tests; Azlocillin; Bacteriophage Typing; Bacteriophages; Cystic Fibrosis; DNA, Viral; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Serotyping; Transformation, Genetic

Proteinuria and enzymuria were measured in 27 patients with Cystic Fibrosis before and after tobramycin therapy. Prior to treatment, kidney function was normal in 23 patients. Four patients showed a pathological proteinuria and two haematuria. Renal biopsy in one patient showed segmental basement membrane alterations on electron microscopy; there were no immunoglobulin deposits. During intravenous therapy with tobramycin (10 mg/kg per day) and azlocillin (100 mg/kg per day) mean urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion rose six-fold and mean urinary alaninaminopeptidase excretion increased ten-fold. After cessation of therapy, enzymuria rapidly returned to pretreatment values in all 14 patients. Aerosol tobramycin therapy in four patients did not affect urinary excretion of NAG. It can be concluded that tobramycin did not cause persistent renal damage in our patients, whether given intravenously or as an aerosol.

Topics: Acetylglucosaminidase; Adolescent; Adult; Aminopeptidases; Azlocillin; CD13 Antigens; Child; Child, Preschool; Creatinine; Cystic Fibrosis; Female; Hexosaminidases; Humans; Kidney; Male; Proteinuria; Pseudomonas Infections; Tobramycin

Sputa from 30 patients with cystic fibrosis (CF) were cultured on routine and selective media plus three Mueller-Hinton antibiotic resistance screening plates containing tobramycin (5 micrograms/ml), azlocillin (100 micrograms/ml), and ticarcillin (100 micrograms/ml). In addition to direct semiquantitative plating, samples were homogenized for semiquantitative and quantitative culture. Blood agar plates from direct semiquantitative and homogenized semiquantitative cultures were then replica plated onto the antibiotic screening plates. Homogenized semiquantitative and quantitative cultures both detected more Pseudomonas aeruginosa strains than direct semiquantitative plating (103 versus 85 strains), including more antibiotic-resistant strains. Antibiotic screening media facilitated isolation of resistant strains and decreased detection time by 24 hr. Of the 103 strains on homogenized semiquantitative and quantitative cultures isolated before replica plating, 13 (13%) were tobramycin-resistant, 67 (65%) were ticarcillin-resistant, and 42 (41%) were azlocillin-resistant; 13 of 30 cultures (43%) had at least one tobramycin-resistant organism before replica plating. Replica plating detected an additional seven tobramycin-resistant and nine ticarcillin- or azlocillin-resistant strains in seven patients. Homogenization, antibiotic screening media, and replica plating enhance recognition of antibiotic-resistant strains in CF sputum.

Topics: Anti-Bacterial Agents; Azlocillin; Culture Media; Cystic Fibrosis; Humans; Penicillin Resistance; Pseudomonas aeruginosa; Sputum; Ticarcillin; Tobramycin

Ten patients with cystic fibrosis received 19 therapeutic courses of ciprofloxacin at a dose of 750 mg orally twice daily. The length of therapy ranged from two to five weeks except for one patient who was treated for six weeks. The mean peak serum concentration of ciprofloxacin was 3.41 mg/l and the mean trough level was 1.11 mg/l. For comparison nine patients were treated with the combination of azlocillin at a dose of 350 mg/kg/day in four divided doses and tobramycin at an initial dose of 9 mg/kg/day in three divided doses. All patients were infected with Pseudomonas aeruginosa except for one patient in whom P. cepacia grew in the sputum cultures; the MICs of ciprofloxacin ranged from 0.05 to 1.56 mg/l. The results obtained with these two therapeutic regimens were comparable. The patient treated for P. cepacia infection developed resistance to ciprofloxacin (MIC greater than 6.24 mg/l) during the course of treatment. Ciprofloxacin appears to be an alternative treatment to the use of an aminoglycoside and a penicillin in cystic fibrosis patients.

Topics: Adolescent; Adult; Azlocillin; Ciprofloxacin; Cystic Fibrosis; Drug Therapy, Combination; Humans; Pseudomonas; Pseudomonas aeruginosa; Pseudomonas Infections; Sputum; Tobramycin

Large amounts of free granulocyte elastase (GE), an enzyme capable of mediating airway damage, have been found in bronchial secretions of patients with cystic fibrosis who are infected with Pseudomonas aeruginosa. This finding indicates an imbalance between GE and its antiproteases, alpha 1-proteinase inhibitor (alpha 1-PI) and bronchial mucosal inhibitor (BMI), in the airways of these individuals. The effect of intravenous antimicrobial treatment against P. aeruginosa on activity and concentration of GE, BMI, and alpha 1-PI was evaluated in 30 treatment courses of 20 patients with cystic fibrosis. Although sputum volume and level of immunoreactive GE decreased and concentrations of alpha 1-PI and BMI increased significantly (P less than .05), a high level of free GE persisted. No active alpha 1-PI and BMI were detectable after treatment. High levels of GE correlated with a poor pulmonary condition (rs = .98, P less than .001). In vitro, elastolytic activity of bronchial secretions from patients with cystic fibrosis was significantly inhibited by eglin C and an oxidation-resistant variant of alpha 1-PI, both compounds currently produced by recombinant DNA technology.

Topics: alpha 1-Antitrypsin; Anti-Bacterial Agents; Azlocillin; Blood Proteins; Bronchi; Cystic Fibrosis; Granulocytes; Humans; Netilmicin; Pancreatic Elastase; Protease Inhibitors; Proteins; Pseudomonas Infections; Serpins; Sputum; Ticarcillin

The pharmacokinetic characteristics of azlocillin were compared in 7 children with cystic fibrosis (CF) and 6 children without this disease who were all treated for infectious diseases. Azlocillin was administered as intravenous bolus injections in doses of 200 mg/kg. The serum concentrations were somewhat lower in CF than in non-CF as reflected by total areas under the serum concentration curves of 594 and 677 mg h/1, and serum levels after 8 hrs of 10.7 mg/1 in non-CF vs. a concentration below the detection limit in CF. The CF children had a lower serum half-life (1.1 hrs) than the children without this disease (3.3 hrs). The difference is explained by higher total body clearance in CF (12.7 1/h) than the non-CF group (8.4 1/h). The dose interval should either be shorter, or the doses increased, when azlocillin is administered to patients with CF.

Topics: Adolescent; Azlocillin; Bacterial Infections; Child; Child, Preschool; Cystic Fibrosis; Female; Humans; Kinetics; Male

Nine adult patients with cystic fibrosis, nearly a quarter of the 38 patients with this disease who were treated with piperacillin (59 courses in all) during 1981-3 at the Brompton Hospital, developed a swinging pyrexia after a mean of 13.5 days' treatment with this antibiotic. The fever resolved shortly after the piperacillin treatment was stopped, as did the widespread rashes in the two patients who developed them. Three of four patients who had probable reactions to azlocillin may have been sensitised by piperacillin. As piperacillin does not appear to be any more effective than other antipseudomonal penicillins in cystic fibrosis, it is no longer used at the hospital for treating bronchopulmonary exacerbations in such patients.

Topics: Adult; Azlocillin; Carbenicillin; Cystic Fibrosis; Female; Fever; Humans; Male; Piperacillin; Pseudomonas Infections; Respiratory Tract Infections

From April, 1980 to December, 1981 ten children aged from 2 to 14 years presenting with cystic fibrosis were admitted to hospital for exacerbation of their chronic bronchial infection. Mucous Pseudomonas aeruginosa was present in sputum. Seven of the 10 strains isolated were susceptible to azlocillin and 3 were classified as intermediate. Eight children were treated with azlocillin alone in doses of 200-300 mg/kg/day and two with combined azlocillin 300 mg/kg/day and amikacin 16 and 23 mg/kg/day respectively. In both groups the antibiotics were administered 8-hourly by short (30 min) intravenous infusions and the duration of treatment ranged from 8 to 21 days (mean 14 days). Both drugs were well tolerated. Antibacterial activity was assessed as "cure" when Pseudomonas could not be isolated in sputum for at least 2 weeks after the end of the treatment, as "relapse" when that organism reappeared in sputum within the same period of time, and as "failure" when it persisted in sputum. On this account, among the 8 children treated with azlocillin alone 3 were cured, one relapsed and 4 failed. One of the two children treated with the azlocillin-amikacin association was cured, the other failed. Clinical results correlated roughly with antibacterial activity. Five distinct improvements were observed: 2 were associated with bacteriological cure, 2 with transient eradication followed by relapse and 1 occurred although the responsible organism persisted in bronchial secretions. Two children showed poor clinical results; 2 with failure and 1 with bacteriological cure. In two other children treatment was ineffective both clinically and bacteriologically. This study confirms that high parenteral doses of azlocillin have a beneficial effect on exacerbations with Ps. aeruginosa of chronic bronchial infection in cystic fibrosis. Clinical improvement usually correlates with antibacterial activity when the organism is eliminated, even temporarily, from bronchial secretions. The synergistic azlocillin-aminoglycoside association should probably be recommended, at least to reduce the risk of emergence of resistant strains.

Topics: Adolescent; Amikacin; Azlocillin; Child; Child, Preschool; Cystic Fibrosis; Drug Therapy, Combination; Female; Humans; Male; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Sputum

Single-dose pharmacokinetics of azlocillin, cefoperazone and ceftazidime were studied in 17 patients with cystic fibrosis (CF). All patients had broncho-pulmonary infections caused by Pseudomonas aeruginosa. Three groups of five, six, and six patients were treated with azlocillin, cefoperazone, or ceftazidime, respectively. The size of the single dose was 133 mg/kg for azlocillin, 66.7 mg/kg for ceftazidime and 66.7 mg/kg for cefoperazone. The clearance values for the three antibiotics calculated from the single-dose data were, on the average, higher than the values previously reported for normal subjects. After the first dose, the patients received a repeated-dose treatment with the same antibiotic. During the first 5 days of therapy, a complement postural drainage of sputum was obtained four times a day for each patient. Cefoperazone could be measured in 47 (39.2%) of the 120 sputum samples assayed while ceftazidime was shown to be present in all 120 sputum samples examined. Azlocillin was not detected in any of the 100 sputum samples assayed.

Topics: Adolescent; Adult; Aged; Azlocillin; beta-Lactamases; Cefoperazone; Ceftazidime; Child; Child, Preschool; Cystic Fibrosis; Female; Humans; Kinetics; Male; Middle Aged; Pseudomonas Infections; Sputum

The pharmacokinetics of azlocillin were studied in 10 cystic fibrosis patients, ranging in age from 11 to 28 years. The patients received a 9- to 23-day course of 350 mg of azlocillin per kg in four or six divided daily doses in combination with am aminoglycoside. Blood and urine samples were collected at specified times after the last dose of the course of azlocillin therapy and then assayed for azlocillin content. Pharmacokinetic parameters were determined by noncompartmental analysis. Mean values for serum half-life (1.74 h), disposition constant (0.41 h-1), total body clearance (123 ml/kg per h), and renal clearance (58 ml/kg per h) were determined. All patients exhibited improvement with respect to clinical and laboratory parameters and displayed no adverse reactions. The pharmacokinetic analysis offers further evidence of the dose-dependent nature of azlocillin elimination, but elimination did not appear to be altered in cystic fibrosis patients.

Topics: Adolescent; Adult; Azlocillin; Child; Cystic Fibrosis; Female; Half-Life; Humans; Infusions, Parenteral; Kinetics; Male; Penicillins; Pseudomonas Infections

The minimal inhibitory concentration of azlocillin for Pseudomonas aeruginosa is appreciably reduced when combined with the mucolytic agent mesna (Mistabron) because of an independent bacteriostatic effect of mesna. Bactericidal activity of azlocillin is unaltered by mesna. Mesna inhalations alone or combined with azlocillin may benefit cystic fibrosis patients with pseudomonas lung infections.

Topics: Azlocillin; Cystic Fibrosis; Drug Therapy, Combination; Humans; Mercaptoethanol; Mesna; Penicillins; Pseudomonas Infections

The combination of azlocillin and gentamicin or tobramycin, in the treatment of lower respiratory tract infection due to Pseudomonas aeruginosa in patients with cystic fibrosis, was evaluated. Twenty patients, 10 boys and 10 girls (mean age 13 1/2 years) who had lower respiratory tract infection with positive sputum culture for P. aeruginosa, were given azlocillin i.v. 20 mg/kg every 8 hours for 10 to 12 days. In addition, either gentamicin, 2.5 to 4 mg/kg i.v. every 12 hours, or tobramycin, 4 to 5 mg/kg i.v. every 8 hours, was given. The antibiotics were given in short-term infusions (20 minutes). Besides the antibiotic treatment, the patients received inhalation therapy, pulmonary physiotherapy, and pancreatic enzymes. Pharmacokinetic studies showed that azlocillin concentrations in serum were within therapeutic levels, and in sputum they inhibited 75% of all P. aeruginosa strains. However, in only 12 of the 52 treatment courses was Pseudomonas eliminated from the sputum.

Topics: Adolescent; Adult; Azlocillin; Child; Child, Preschool; Cystic Fibrosis; Drug Therapy, Combination; Female; Gentamicins; Humans; Male; Penicillins; Pseudomonas Infections; Respiratory Tract Infections; Tobramycin

A comparative study was made on tobramycin combined with either carbenicillin (500 mg/kg/day) or one of the new penicillins: azlocillin or piperacillin (both 300 mg/kg/day) in 50 cystic fibrosis patients with chronic Pseudomonas aeruginosa infection. Average 2-h levels of penicillins in serum were 46 micrograms/ml (piperacillin), 88 micrograms/ml (azlocillin) and 66 micrograms/ml (carbenicillin). The Pseudomonas strains were significantly more sensitive to piperacillin and azlocillin than to carbenicillin (minimal inhibitory concentrations 1.9, 2.3 and 4.2 micrograms/ml). In 21 of 54 treatment course temporary eradication of Pseudomonas was achieved. Improved ventilatory capacity and diminished proteolytic activity in sputum were seen in most patients with or without bacteriological treatment success. Resistant strains - often belonging to other types - appeared in the patients with treatment failure. With increased number of precipitating antibodies against Pseudomonas and with increased minimal inhibitory concentrations, the chance of eradication was smaller. Seven out of 20 treated with azlocillin and 14 out of 30 treated with piperacillin developed fever and exanthema by the end of treatment. Our experience suggests caution in the use of the new penicillins.

Topics: Anti-Bacterial Agents; Azlocillin; Carbenicillin; Cystic Fibrosis; Drug Therapy, Combination; Humans; Penicillins; Piperacillin; Pseudomonas aeruginosa; Pseudomonas Infections; Recurrence; Tobramycin

The retrospective bacteriological results of 322 courses of anti-Pseudomonas aeruginosa chemotherapy in a cohort of 57 cystic fibrosis (CF) patients are reported. Tobramycin given as mono-therapy eradicated P. aeruginosa from the lungs of CF patients in 9% of the courses, whereas a combination therapy consisting of carbenicillin + tobramycin eradicated P. aeruginosa in 55% of the courses. However, the efficacy of the chemotherapy diminished successively when repeated courses of treatment were given. The efficacy of the carbenicillin + tobramycin combination in eradicating P. aeruginosa from the lungs of CF patients was compared with the efficacy of azlocillin + tobramycin and piperacillin + tobramycin in a prospective study. P. aeruginosa was eradicated in 78% of CF patients treated with carbenicillin + tobramycin, in 28% of CF patients treated with azlocillin + tobramycin, and in 33% of CF patients treated with piperacillin + tobramycin. However, the two latter groups of patients had on an average significantly higher numbers of P. aeruginosa precipitins in serum, indicating more severe infections. In CF patients where P. aeruginosa was not eradicated, a significant increase of MIC against carbenicillin, azlocillin and piperacillin was observed. There was a significant improvement of lung function and laboratory parameters reflecting diminished inflammation as a result of the treatment. 40% of the CF patients treated with azlocillin or piperacillin developed serum sickness-like symptoms.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azlocillin; Carbenicillin; Child; Child, Preschool; Chronic Disease; Cystic Fibrosis; Humans; Microbial Sensitivity Tests; Penicillins; Piperacillin; Pseudomonas aeruginosa; Pseudomonas Infections

Azlocillin, 200 mg/kg bodyweight every 8 h, and gentamicin, 2.5-4 mg/kg bodyweight every 12 h, in combination were given intravenously to 10 patients with cystic fibrosis for at least 10 days. The patients were colonized with Pseudomonas aeruginosa and were hospitalized due to symptoms of lower respiratory tract infections. Using an agar well diffusion method the antibiotic concentrations were followed in serum and sputum. The individual sputum concentration of azlocillin varied during 4 h after administration from less than 1.5 to 38 micrograms/ml. The sputum concentration of gentamicin varied from 0.3 to 1.1 micrograms/ml. P. aeruginosa was apparently eliminated in 3 patients. The concentration of the antibiotics in sputum could not predict the outcome of treatment. All patients improved subjectively. No adverse effect was seen.

Topics: Adolescent; Adult; Azlocillin; Child; Cystic Fibrosis; Female; Gentamicins; Humans; Male; Penicillins; Pseudomonas Infections; Respiratory Tract Infections; Sputum; Time Factors

Nine patients with cystic fibrosis have been treated with azlocillin alone and later with azlocillin combined with an aminoglycoside (gentamicin or tobramycin) for 50 treatment courses. In the initial series when azlocillin was employed alone, a gradual increase in MIC during successive courses was observed in Pseudomonas aeruginosa. When the beta-lactam antibiotic was combined with an aminoglycoside, the MIC was either maintained or reduced. Objective criteria like peak expiratory flow, erythrocyte sedimentation rate, fever, body weight or bacterial cultures could not clearly identify the combination therapy as better clinically than azlocillin monotherapy. However, the patients subjective and our clinical impression is that the combination therapy was better. The clinical course and the lack of increased resistance on combination therapy make a combination of azlocillin and an aminoglycoside preferable to the beta-lactam alone.

Topics: Aminoglycosides; Anti-Bacterial Agents; Azlocillin; Child; Cystic Fibrosis; Drug Therapy, Combination; Female; Humans; Male; Penicillin Resistance; Penicillins; Respiratory Tract Infections

Inadequate therapeutic results in the treatment of bacterial infections in patients with Cystic Fibrosis prompted a reevaluation of pharmacokinetic parameters of orally and parenterally administered drugs in these patients. Gentamicin, Azlocillin and Ticarcillin are eliminated faster in patients with Cystic Fibrosis. Serum concentrations show a rapid decrease over 60 to 90 minutes and surpass MIC values of Pseudomonas isolates for a maximum of only 60 minutes. 70% to 90% of the administered amount of drug is eliminated within two hours in the urine. Concomitantly determined clearance rates for creatinine didn't show abnormalities, however they pointed towards an additional tubular secretion of Gentamicin which is not seen in healthy controls. Cephalexin, Epicillin and both components of Cotrimoxazol show a delay in oral absorption. The renal elimination of Cephalexin and Trimethoprim is unaltered, but the excretion of Epicillin and Sulfametrol is enhanced again. This is seen by a delay and decrease in the maximal serum concentration (Cmax), but increased urine recovery. Doubling of the dose of gentamicin administered as i. v. infusion over 45 to 60 minutes results in smooth serum curve, the MIC values of most encountered organisms are surpassed for 3 hours and more. The clinical applicability of this recommendation however awaits further investigations concerning efficacy and safety.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azlocillin; Child; Cystic Fibrosis; Gentamicins; Humans; Metabolic Clearance Rate; Penicillins; Sulfanilamides; Ticarcillin; Trimethoprim

In 5 children with cystic fibrosis, 13 courses of lower respiratory infections due to Pseudomonas aeruginosa were treated with azlocillin, 100--200 mg/kg body weight intravenously every 8 h for 10--15 days. The clinical course during azlocillin treatment was more favourable than had been the case previously in the same patients when treated with combinations of carbenicillin and aminoglycosides. No side effects ascribable to azlocillin were observed, although one allergic reaction occurred, but this was probably elicited by another allergen. Upon repeated courses of treatment, the minimum inhibitory concentration of the infecting organisms increased steadily against both azlocillin and carbenicillin. It is concluded that azlocillin represents an important alternative in the treatment of lower respiratory tract infections due to P. aeruginosa in patients with cystic fibrosis.

Topics: Adolescent; Azlocillin; Child; Child, Preschool; Cystic Fibrosis; Female; Humans; Male; Penicillins; Pseudomonas Infections; Respiratory Tract Infections

6-E1(R)-2-(oxo-imidazolidine-1-carboxamido)-2-phenyl-acetamido]-penicillanic acid sodium salt (azlocillin, Securopen) was given in doses of 100 and 200 mg/kg body weight to children with cystic fibrosis. After intravenous bolus infections, the serum half-life was 0.82 +/- 0.12 h after the lower dose and 0.98 +/- 0.18 h after the higher dose. This was consequent to a dose limited elimination kinetics due to limitation in both renal and non-renal processes of elimination. Upon doubling of the dose from 100 to 200 mg/kg, the total body clearance dropped from 13.93 to 5.10 1/h. Evaluation of data presented in other publications indicate that a dose limited elimination kinetics is the normal situation for azlocillin. Besides, the serum concentrations of patients with cystic fibrosis were considerably lower than seen in the healthy state. The reason is faster elimination by the renal route in cystic fibrosis.

Topics: Adolescent; Azlocillin; Child; Child, Preschool; Cystic Fibrosis; Dose-Response Relationship, Drug; Female; Half-Life; Humans; Kinetics; Male; Penicillins; Time Factors