azlocillin and Respiratory-Tract-Infections

Topics: Adolescent; Adult; Aged; Azlocillin; Bacterial Infections; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Osteomyelitis; Penicillins; Pregnancy; Respiratory Tract Infections; Urinary Tract Infections

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

Azlocillin, an acylureidopenicillin particularly active against Pseudomonas aeruginosa, was used to treat 124 patients, 36 of whom were children, presenting with pulmonary infections (including cystic fibrosis), urinary, genital, intra-abdominal, osteoarticular and skin infections as well as septicaemia, otitis and meningitis. The causative agent in all cases was Ps. aeruginosa either alone or associated with other pathogens. Azlocillin was administered alone in 75% of the cases and in combination with an aminoglycoside in 25%. Dosage was 240 mg/kg/24 h in three intravenous infusions in adults and in children older than 3 months, and 75 to 225 mg/kg/24 h in two intravenous injections in neonates and prematures. The duration of treatment varied according to the site of infection, with a mean of 10 days. One-hundred and eight pathogenic organisms were isolated, including 114 strains of Pseudomonas, 43 of which were carbenicillin-resistant. A satisfactory clinical response was observed in 86.5% of the infections. The bacteriological response was similar to the clinical response, with 76.6% cures, 10% improvements and 13.5% failures. Microbiologically, 77.5% of the germs were eradicated, 7.5% reappeared and 15% persisted. Azlocillin was well tolerated systemically and biochemically and had no detrimental effect on renal function.

Topics: Adult; Azlocillin; Bacterial Infections; Child; Clinical Trials as Topic; Humans; Meningitis; Middle Aged; Otitis Media; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Sepsis; Urinary Tract Infections

Eleven patients with severe bronchopulmonary infection due to Pseudomonas were treated with azlocillin in doses of 250 mg/kg/day. Severe preexisting respiratory diseases, such as bronchopulmonary carcinoma, bronchiectasis or respiratory insufficiency were present in all cases. All patients had been unsuccessfully treated with various antibiotics before they received azlocillin. The pathogenicity of the isolates was assessed by germ counts in sputum. Comparative in vitro sensitivities to carbenicillin and azlocillin were determined by the disc method and by measurement of the minimum inhibitory concentrations in liquid medium. All strains of Pseudomonas aeruginosa isolated were sensitive to azlocillin with minimum inhibitory concentrations of 0.5 to 64 micrograms/ml. When tested against carbenicillin, 4 of the strains were resistant and 1 had intermediate sensitivity. The carbenicillin/azlocillin minimum inhibitory concentrations ratio was usually equal to 4. Clinical results were satisfactory in 7 cases; inadequate response or failure was observed in 4 cases and attributed to the replacement of Pseudomonas by another pathogen (Proteus morganii or Klebsiella pneumoniae). This study suggests that azlocillin is of value in the treatment of bronchopulmonary infections caused by Ps. aeruginosa.

Topics: Adult; Aged; Azlocillin; Carbenicillin; Clinical Trials as Topic; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract 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

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

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; Cefmenoxime; Chromatography, High Pressure Liquid; Humans; Moxalactam; Respiratory Tract Infections; Superinfection

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

Azlocillin is a semisynthetic acylureidopenicillin with increased activity against most strains of Pseudomonas aeruginosa. It was given as the sole antibacterial agent in the treatment of 21 patients with serious pulmonary, wound, bone or joint, or urinary tract infections, endocarditis, or malignant external otitis caused by Pseudomonas sp. In preliminary in vitro tests, azlocillin inhibited 90% of 36 clinical isolates, while carbenicillin and ticarcillin inhibited only 60% and 73%, respectively. Mean MIC of azlocillin against Ps. aeruginosa isolated from the 21 study patients was 9.8 mg/l; more than 50% of the strains were inhibited by a concentration of 6.25 mg/l. Intravenous administration of the antibiotic at a mean dosage of 17 g/day for 6 to 59 days resulted in an excellent or good clinical response in 90% (19) of the patients treated. Pseudomonas sp. was eliminated from the site of infection in 67% (14) of the patients. Azlocillin therapy was well tolerated; in only two patients, both of whom had penicillin-type rashes, was it necessary to discontinue therapy. Azlocillin was a safe and effective antimicrobial agent for the treatment of serious infections caused by strains of Pseudomonas sp., primarily Ps. aeruginosa.

Topics: Adult; Anti-Bacterial Agents; Arthritis, Infectious; Azlocillin; Bone Diseases; Humans; Microbial Sensitivity Tests; Penicillins; Pseudomonas Infections; Respiratory Tract Infections; Skin Diseases, Infectious

Clinical studies with azlocillin were conducted in North America and Europe to assess its efficacy and to monitor its safety. The results of studies from these two areas are compared retrospectively. In North America 631 multiple-dose courses were monitored, while 887 were given in Europe. The most frequently administered daily dose was 18 g in North America and 15 g in Europe. In 71% of the courses a Pseudomonas species was the causative infecting organism in the former area and 51% in the latter. Over 60% of the patients were seriously ill, and about a third were over 60 years of age. A satisfactory bacteriological response, as defined by the eradication or a marked reduction of the organism causing infection was obtained in 74% of patients in North America and in 75% in Europe. 89% of the patients in America responded clinically compared to 92% in Europe. Ps. aeruginosa was eradicated in over 70% of instances. Azlocillin, like other penicillins, possesses a low potential for toxicity. Hypersensitivity reactions and gastrointestinal effects were the most common adverse experiences. No serious problems were encountered with impairment of renal or hepatic function, or blood coagulation. Azlocillin was effective for treating serious infections caused primarily by Ps. aeruginosa.

Topics: Adolescent; Adult; Aged; Azlocillin; Bacterial Infections; Child; Child, Preschool; Humans; Infant; Middle Aged; Penicillins; Respiratory Tract Infections; Sepsis; Urinary Tract 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

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

Azlocillin, an acylureido penicillin with bactericidal activity, is particularly effective against Pseudomonas, enterococci and Haemophilus influenzae. It is also very active against E. coli, various Proteus species and Bacteroides. Pharmacokinetic studies were carried out in 138 children of various ages (prematures, newborns, infants, schoolchildren) after administering 50-75-100 mg/kg/ body weight azlocillin via the i.v. or i.m. routes; The constant of elimination and the distribution volumes were calculated besides the serum levels. In prematures and newborns, therapeutically effective serum levels were obtained on administering 50 or 100 mg/kg body weight twice daily. Infants and older children required 100 or 75 mg/kg body weight t.i.d. Determination of azlocillin in the bronchial secretion after i.v. doses of 75 mg/kg body weight showed good elimination. Azlocillin was always identified up to the 5th hour post injectionem. Inspite of parenteral administration, azlocillin was identified in different concentrations in the meconium as well. 39 children were treated with azlocillin, 35 of whom had Pseudomonas infection. Very good results were obtained in infections of the urinary tract, wound infections, conjunctivitis, dacryocystitis and in one case of meningitis. Bronchopulmonary diseases did not take an equally good course, but in these cases the conditions had not been favourable. No serious side effects were revealed by testing several laboratory parameters.

Topics: Azlocillin; Child; Child, Preschool; Conjunctivitis; Dacryocystitis; Humans; Infant; Infant, Newborn; Kinetics; Meconium; Meningitis; Penicillins; Pseudomonas Infections; Respiratory Tract Infections; Surgical Wound Infection; Urinary Tract Infections

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-[(R)-2-(2-Oxo-imidazolidine-1-carboxamido)-2-phenyl-acetamido]-penicillanic acid sodium salt (azlocillin, Securopen), has a special activity against Pseudomonas species besides is broadspectrum character. We confirmed the high in vitro potency of that antibiotic in 200 clinical Pseudomonas isolates. Good penetration of azlocillin into bronchial secretions was found, especially through the inflamed bronchial mucosa, but also in the post-inflammatory phase. In 16 patients with serious Pseudomonas infections of the respiratory tract the good efficacy of azlocillin was shown. There were no tolerance problems.

Topics: Azlocillin; Bronchi; Gentamicins; Humans; Kinetics; Lung Diseases; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Time Factors

This pharmacokinetic study involved school children who were treated with 6-[(R)-2-(2-oxo-imidazolidine-1-carboxamido)-2-phenyl-acetamido]-penicillanic acid sodium walt (azlocillin, Securopen) at doses of 50 mg/kg bodyweight or 75 mg/kg body weight i.v. Kinetics of the first order were found for the concentrations measured at the same time, being proportionate to the administered dose, while there was no dose dependence for the relative distribution volume. The elimination half-life was about 55 min. In 25 children of different age who had to undergo bronchoscopy for diagnositic and therapeutic reasons, the azlocillin concentrations in the bronchial secretions were measured 1 h and 4 h after the administration of 75 mg/kg quantity of bronchial secretion was obtained, azlocillin concentrations of 30 - 240 microgram/g were found. Measurements of azlocillin concentration in the bronchial secretion and in the serum, which were made at the same time, did not show any correlation.

Topics: Adolescent; Aging; Azlocillin; Bronchi; Child; Child, Preschool; Female; Humans; Kinetics; Male; Penicillins; Respiratory Tract Infections