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PubMed1985

Comparative in-vitro activities of azlocillin, ticarcillin and ticarcillin plus clavulanic acid against Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa.

Azlocillin (5 g), ticarcillin (5 g) and ticarcillin (5 g) plus clavulanic acid (200 mg) were administered intravenously on separate days to human volunteers. Serum levels 1 h after the infusion were (mean +/- S.E.): 263 +/- 40 mg/1 for azlocillin, 238 +/- 56 mg/l for ticarcillin and 5.5 +/- 1.9 mg/l for clavulanic acid. Serum withdrawn at 0.5 h was titrated against ten strains of Staphylococcus aureus, ten Klebsiella pneumoniae and nine Pseudomonas aeruginosa of which four were resistant to ticarcillin. Against Staph. aureus and K. pneumoniae, median serum bactericidal activity (SBA) and percentage of sera with SBA greater than or equal to 1:8 were greater with ticarcillin plus clavulanic acid (median SBA 1:32 and 85% of sera with SBA greater than or equal to 1:8) than with the other two regimens. There were no differences in activity against Ps. aeruginosa.

Azlocillin↗
PubMed1986

Bactericidal activity of ciprofloxacin alone and in combination with azlocillin in an in-vitro capillary model.

An in-vitro pharmacokinetic model was used to study the bactericidal activity of ciprofloxacin, alone and in combination with azlocillin. Ciprofloxacin alone produced excellent bactericidal activity against highly susceptible strains of Escherichia coli and Klebsiella pneumoniae. Against a strain of Pseudomonas aeruginosa, ciprofloxacin in clinically achievable dosing schedules produced a rapid bactericidal effect, but bacterial regrowth occurred. Azlocillin in combination with ciprofloxacin produced a rapid bacterial kill and regrowth was prevented. Further consideration of the clinical role of this combination is warranted.

Azlocillin↗
PubMed1988

Controlled trial of aztreonam vs. tobramycin and azlocillin for acute pulmonary exacerbations of cystic fibrosis.

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.

Adolescent↗
PubMed1989

A randomised trial of empirical antibiotic therapy in febrile neutropenic patients with hematological disorders: ceftazidime versus azlocillin plus amikacin.

One hundred and two patients with neutropenia (less than 1 x 10(9)/L) secondary to primary hematological disorders or chemotherapy for hematological malignancies were prospectively randomised, upon the development of fever or other signs of infection, to receive empirical antibiotic treatment with either ceftazidime (+/- flucloxacillin) (n = 52) or azlocillin plus amikacin (+/- flucloxacillin) (A&A, n = 50). The two groups were equivalent with respect to clinical and laboratory parameters prior to antibiotic therapy and flucloxacillin was added to approximately 25% of the patients in each group on the clinical suspicion of Gram positive infection. When assessed at 96 hours, the complete response rates were 59.6% for the ceftazidime treated patients and 44% for A&A treated patients. Partial response rates were 17% and 20% respectively. This difference was not statistically significant. Eight patients died whilst on the trial, three of those initially randomised to ceftazidime and five initially randomised to A&A. Moderate to severe hypokalemia was encountered significantly less often in the ceftazidime treated group (p less than 0.01), whilst other parameters of toxicity were equivalent. No primary or acquired resistance to ceftazidime was encountered. Separate analysis of those patients who did not receive flucloxacillin yielded identical results. We conclude that ceftazidime (+/- flucloxacillin) is as efficacious as azlocillin plus amikacin (+/- flucloxacillin) in the empirical antibiotic management of such patients and is associated with a lower incidence of moderate to severe hypokalemia.

Adolescent↗
PubMed1979

Comparison of the activities of the new ureidopenicillins piperacillin, mezlocillin, azlocillin, and Bay k 4999 against gram-negative organisms.

The in vitro activities of the new ureidopenicillins piperacillin, mezlocillin, azlocillin, and Bay k 4999 were compared with those of ampicillin and ticarcillin against 336 Enterobacteriaceae, 109 nonfermenters, 55 Neisseria, and 28 Haemophilus influenzae isolates. Bay k 4999 displayed the largest spectrum of activity and had lower minimal inhibitory concentrations than any of the other penicillins against all of the species tested. Piperacillin showed the same spectrum but was slightly less active than Bay k 4999; it was slightly more effective than mezlocillin against Enterobacteriaceae and fully as active as azlocillin against Pseudomonas. All ureidopenicillins were substantially more active than ampicillin and ticarcillin. Isolates highly resistant to ampicillin or ticarcillin were also less susceptible to the ureidopenicillins.

Ampicillin↗
PubMed1982

In vitro comparison of N-formimidoyl thienamycin (MK0787) and Azlocillin with three aminoglycosides and ticarcillin against Pseudomonas aeruginosa.

The activities of N-formimidoyl thienamycin and azlocillin were compared with those of tobramycin, gentamicin, amikacin, and ticarcillin against 175 Pseudomonas aeruginosa isolates, including 24 strains with known mechanisms of resistance to aminoglycosides. The 50% mean inhibitory concentration for azlocillin was lower than for ticarcillin, but the 90% mean inhibitory concentration was similar for both drugs. All susceptible and multidrug-resistant strains were susceptible to N-formimidoyl thienamycin.

Amikacin↗
PubMed1983

High-pressure liquid chromatographic quantitation of azlocillin.

We describe a rapid, precise, and simple procedure for the quantitation of azlocillin in serum and in aqueous solutions by high-pressure, reverse-phase liquid chromatography. This method uses a single precipitation step, detection by dual-wavelength monitoring (220 and 254 nm), and quantitation by comparison with an internal standard. The 10-micron C18 muBondapak column was eluted with 45% (vol/vol) methanol-65% (vol/vol) phosphate buffer. The precision was 4.2 and 5.6% at 50 and 10 micrograms/ml, respectively. The assay was linear up to concentrations of 100 micrograms/ml, with recoveries of 90.4 to 110.5% from serum. The assay was sensitive to 0.4 micrograms of azlocillin per ml. The short turnover time (14 min) and small serum sample size (20 microliters) make the assay ideal for therapeutic drug monitoring and clinical pharmacokinetic studies.

Azlocillin↗
PubMed1984

Comparison of azlocillin, ceftizoxime, cefoxitin, and amikacin alone and in combination against Pseudomonas aeruginosa in a neutropenic-site rabbit model.

The efficacy of beta-lactam antibiotics and amikacin alone and in various combinations against Pseudomonas aeruginosa was studied in a rabbit model simulating a closed-space infection in a locally neutropenic site. Six strains of P. aeruginosa were studied in semipermeable chambers placed subcutaneously in rabbits. Therapy was begun 4 h after inoculation of 5 X 10(4) CFU of bacteria per ml of pooled rabbit serum into the chambers. Antibiotics were administered intramuscularly every 6 h for 16 doses. Quantitative bacteriology was measured at the start of therapy and at 20, 44, and 92 h thereafter. Antibiotic concentrations were measured in blood and chamber fluid. Results were compared with in vitro tests of susceptibility and synergy. No single-agent therapy eradicated any of the six test organisms. Azlocillin (100 mg/kg per dose) plus amikacin (20 mg/kg per dose) eliminated five of six organisms by 92 h, and ceftizoxime (100 mg/kg per dose) plus amikacin (20 mg/kg per dose) eliminated three of six test strains. Azlocillin plus ceftizoxime (each 100 mg/kg per dose) failed to eliminate any of the six strains. To eliminate P. aeruginosa in this model, two drugs were required, with one being an aminoglycoside. In vitro susceptibility tests of synergy were predictive of successful therapy whenever the antibiotic concentrations (free and total) at the infection site exceeded the MBC for both the aminoglycoside alone and the beta-lactam when tested in combination with amikacin.

Agranulocytosis↗
PubMed1984

Effect of aztreonam in combination with azlocillin or piperacillin on Pseudomonas aeruginosa.

Aztreonam, a synthetic monobactam antimicrobial agent specifically active against aerobic, gram-negative microorganisms, was studied in combination with the extended-spectrum penicillins azlocillin and piperacillin against 46 strains of Pseudomonas aeruginosa. Of these strains, 4.3% were synergistically inhibited, and 19.7% showed evidence for an additive effect of the antibiotics. All other strains showed indifference. The addition of cefoxitin to these combinations increased the MICs of azlocillin and piperacillin by two to three tubes, whereas zero- to one-tube increases were noted for aztreonam MICs. Attempts to block cefoxitin-induced beta-lactamase production by using clindamycin were unsuccessful even at high clindamycin concentrations.

Anti-Bacterial Agents↗
PubMed1989

Pharmacokinetic comparison of 5 g of azlocillin every 8 h and 4 g every 6 h in healthy volunteers.

To compare the multiple-dose pharmacokinetics of two dosage regimens of azlocillin, we studied 12 healthy volunteers via a randomized, crossover design with a 2-week washout phase between regimens. Serum and urine samples were collected for 8 h following the fifth dose of a regimen of 4 g every 6 h and the fourth dose of a regimen of 5 g every 8 h. Data for concentrations in serum were fitted to a two-compartment open model by nonlinear regression. Statistically significant differences (P less than 0.05) were observed in the following parameters (mean +/- standard deviation) for the 4- and 5-g regimens, respectively: area under the serum concentration-time curve during the dosing interval, 592 +/- 140 versus 772 +/- 151 micrograms.h/ml; terminal elimination rate constant, 0.5364 +/- 0.0912 versus 0.4758 +/- 0.0486 h-1; renal clearance, 87.6 +/- 16.1 versus 76.1 +/- 13.5 ml/min; maximum drug concentration in serum, 381 +/- 89 versus 473 +/- 90 micrograms/ml; and minimum drug concentration in serum, 19 +/- 10 versus 8 +/- 4 micrograms/ml. No significant differences were seen in the following parameters: V1, V beta, k10, k12, k21, total systemic clearance, and nonrenal clearance. These data support the presence of saturable renal elimination of azlocillin, as well as the feasibility of an 8-h dosing interval.

Adult↗
PubMed1982

Azlocillin, a ureido penicillin active against Pseudomonas aeruginosa: interpretive zone standards and quality control parameters for tests with 75-mu g disks.

A nine-laboratory coordinated study was performed to establish tentative control limits for 75-mu g azlocillin disks tested against the standard control strain of Pseudomonas aeruginosa (ATCC 27853). Control limits for individual tests were 24 to 30 mm (25 to 29 mm for means of five separate tests). To establish interpretive zone standards for 75-mu g azlocillin disks, three separate laboratories each tested 93 strains of P. aeruginosa or related species. Geometric mean minimal inhibitory concentrations (MICs) were plotted against arithmetic mean zone diameters. Regression analyses were performed with zone diameter as the independent variable and also with MIC as the independent variable. The following interpretive categories were recommended: resistant, less than or equal to 14 mm (MIC, greater than 128 mu g/ml); intermediate, 15 to 17 mm (MIC, 128 mu g/ml); and susceptible, greater than or equal to 18 mm (MIC, less than or equal to 64 mu g/ml).

Azlocillin↗
PubMed1984

Azlocillin compared with carbenicillin in the treatment of bronchopulmonary infection due to Pseudomonas aeruginosa in cystic fibrosis.

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.

Adolescent↗
PubMed1984

Fosfomycin, piperacillin, azlocillin. Correlation between therapeutic response of mice infected with Pseudomonas aeruginosa and in vitro data.

Intramuscular infections of mice with eight different strains of Pseudomonas aeruginosa were treated with three doses each of fosfomycin, piperacillin and azlocillin. The therapeutic response (measured as decrease in colony-forming units in the homogenized infected tissue) was compared with the 'aggregate suprainhibitory time' (the time for which the serum concentration exceeds the minimal inhibitory concentration of the infecting bacteria during the whole treatment period). The therapeutic response improved with increasing aggregate suprainhibitory time. The correlation was better for fosfomycin than for piperacillin and, especially, azlocillin.

Animals↗
PubMed1986

In vivo efficacy of azlocillin and amikacin versus ciprofloxacin with and without amikacin in experimental right-sided endocarditis due to Pseudomonas aeruginosa.

The efficacy of azlocillin + amikacin was compared to ciprofloxacin (with and without amikacin) in 96 rabbits with right-sided endocarditis due to Pseudomonas aeruginosa. Animals received either: no therapy (controls); amikacin (15 mg/kg/day) + azlocillin (400 mg/kg/day); ciprofloxacin (80 mg/kg/day) or amikacin + ciprofloxacin (above dosages). All three antibiotic regimens were significantly more effective than no therapy in reducing mortality (p less than 0.0005), preventing pulmonary infarction (p less than 0.0005) and reducing mean vegetation titers of P. aeruginosa (p less than 0.0005). Also, the three therapy regimens were equivalent in preventing bacteriologic relapse after discontinuing therapy. No development of antibiotic resistance in vivo was observed.

Amikacin↗
PubMed2004

[Azlocillin plus amikacin: an alternative therapy for sepsis caused by resistant staphylococci?].

OBJECTIVE: To assess the effectiveness of combined therapy with azlocillin and amikacin in a group of neonates with sepsis caused by multiresistant staphylococci who were hospitalized in the neonatal intensive care unit of Hospital Ginecobstétrico "America Arias" in Havana, Cuba, from 1998 to 2000. METHODS: A retrospective study was carried out of the clinical and laboratory results obtained in 15 patients with sepsis caused by multiresistant staphylococci who received combined therapy with azlocillin and amikacin, according to hospital guidelines on the use of antibiotics. We used a broth microdilution method to study the patterns of resistance shown by isolated strains to 10 of the antibiotics in use. In vitro synergy tests, specifically the checkerboard technique with microtitration plates, were used to observe the effects of treatment in 8 patients. RESULTS: Twelve coagulase-negative staphylococci and three Staphylococcus aureus isolates showed five different patterns of resistance on the basis of their sensitivity to oxacillin, three aminoglycosides, and vancomycin. Six of the synergy tests showed a considerable synergistic effect, with an average three-fold reduction in the minimum inhibitory concentrations (MIC) of the two antibiotics used to treat the patients. No antagonistic effects were noted, and the combined antibiotics showed an overall clinical effectiveness of 91.7%. CONCLUSIONS: The test showed that the therapeutic combination used was effective, but further studies are needed before conclusive results are obtained.

Amikacin↗
PubMed1986

Impact of azlocillin on the colon microflora.

To evaluate the impact of parenteral azlocillin therapy on human colon microflora, faecal specimens were taken from 6 patients before, during and after therapy for analysis of the microflora. In 2 patients major changes took place. Thus the numbers of streptococci, Escherichia coli, anaerobic cocci, lactobacilli, clostridia and bacteroides decreased markedly during therapy. One of these patients was colonized with azlocillin-resistant Enterobacter cloacae. The other 4 patients had only minor changes in the microflora. Variations between patients seem to exist. Pronounced alterations in the colonic flora may have clinical implications.

Adult↗
PubMed1982

Clinical experience with azlocillin in the treatment of urinary tract infections with Pseudomonas aeruginosa.

27 patients, aged 19-23 yr, with symptomatic urinary tract infection or epididymitis due to Pseudomonas aeruginosa were treated with azlocillin. All pseudomonas strains were sensitive to azlocillin. The microorganism was eradicated in 25/26 evaluable patients. 25/27 patients were clinically cured. Bacteriological relapse occurred in 11 patients. No serious drug reactions were noted.

Adult↗
PubMed1982

Azlocillin, mezlocillin, and piperacillin: new broad-spectrum penicillins.

Three new broad-spectrum penicillins--azlocillin, mezlocillin, and piperacillin--will soon be available for clinical use. Azlocillin and piperacillin are more active than carbenicillin or ticarcillin against Pseudomonas aeruginosa. Piperacillin and mezlocillin demonstrate significant activity against the Enterobacteriaceae, including many strains of Klebsiella pneumoniae against which the older penicillins carbenicillin, ticarcillin, and ampicillin are ineffective. All three new drugs show substantial activity against anaerobes and ampicillin-susceptible gonococci and Haemophilus influenzae. Because these agents are inactivated by various beta-lactamases, most Staphylococcus aureus isolates and a number of gram-negative organisms, including some important nosocomial pathogens, will be resistant to these antibiotics. The new penicillins appear to be relatively safe and have been used successfully to treat patients with various infections; however, comparative trials have not yet established the superiority of these drugs over conventional therapeutic agents.

Azlocillin↗