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PubMed1994

The pharmacokinetics of once daily gentamicin in neutropenic adults with haematological malignancy.

Seven febrile neutropenic adults with normal renal function were treated with intravenous gentamicin 4.5 mg/kg once a day in combination with azlocillin. Gentamicin serum concentrations 1, 2, 4, 8, and 24 h after a 30 min infusion were 10.9 +/- 0.6, 7.1 +/- 0.4, 4.2 +/- 0.2, 1.8 +/- 0.1 and 0.16 +/- 0.003 mg/L respectively. The pharmacokinetics were best described by a triphasic plot including a distribution phase (about 1/2 h) and two elimination phases, an early and late.

Adolescent↗
PubMed1981

Comparative activity of N-formimidoyl thienamycin with third generation cephalosporins and ureido penicillins against multiple resistant Serratia marcescens.

Twenty multiple resistant clinical isolates were tested with N-formimidoyl thienamycin, moxalactam, cefotaxime, cefoperazone, and the three ureidopenicillins: azlocillin, mezlocillin, and piperacillin. A concentration of less than 0.97 microgram/ml inhibited 100% of organisms for N-f-thienamycin and cefotaxime, 90% for moxalactam, and 60% for cefoperazone. An increase in inoculum from 10(3) to 10(6) cells reduced activity fourfold for 95% of isolates with cefoperazone, 70% with N-formimidoyl thienamycin, 65% for cefotaxime, but only 15% for moxalactam. For ureidopenicillins, 85% of strains tested had MIC's less than or equal to 15.6 micrograms/ml. An inoculum effect was observed in only 35-50%. At 10(3), the cidal concentration was the same or twofold greater than the inhibitory level for N-f-thienamycin and cephalosporins in 70% of strains tested and 65% for penicillins. With 10(6), the 70% value remained for N-f-thienamycin but was reduced to 45% for cefotaxime and 25% for moxalactam; 85% demonstrated greater than eightfold differences with cefoperazone. Single step high-level resistance was observed to moxalactam (20%). Carbenicillin resistant strains were cross-resistant to the ureidopenicillins. N-f-thienamycin and cefotaxime appeared comparable, although important differences between morphological alteration and metabolism may influence their therapeutic effectiveness.

Azlocillin↗
PubMed1982

Estimation of biliary excretion of ureidopenicillins in healthy volunteers using marker dilution technique.

1 Aspiration of duodenal fluid and estimation of recovery by a marker dilution technique was adapted to measure the biliary excretion of two chemically related ureidopenicillins, mezlocillin and azlocillin, in healthy volunteers. 2 The drug was infused intravenously at a constant rate over a period of 6 h during which duodenal fluid was aspirated through the distal opening of a triple-lumen polyvinyl tube. 3 Drug levels in plasma, urine and duodenal fluid were determined by h.p.l.c. 4 Biliary excretion rate was calculated by multiplying the concentration in the duodenal fluid by the dilution factor resulting from the dilution of marker substance infused through the proximal opening of the triple-lumen tube. 5 Since the results obtained by the marker dilution technique are comparable to data obtained by studies in patients with t-tube drainage following biliary surgery, it can be concluded that the method is useful to measure the biliary excretion of drugs in man.

Adult↗
PubMed1987

Changes in serotype caused by cell to cell contact between different Pseudomonas aeruginosa strains from cystic fibrosis patients.

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.

Agglutination Tests↗
PubMed1978

Comparison of the in vitro activity of Bay k 4999 and piperacillin, two new antipseudomonal broad-spectrum penicillins, with other beta-lactam drugs.

Bay k 4999 and piperacillin, two new substituted ampicillins, were compared with other beta-lactam antibiotics, including carbenicillin, azlocillin, mezlocillin, benzylpenicillin, ampicillin, and cefoxitin, against a wide range of gram-positive and -negative organisms. Bay k 4999 and piperacillin were extremely active against Pseudomonas aeruginosa (50% inhibited by 2 mug/ml), being about 16-fold more active than carbenicillin. Bay k 4999 was the most active drug against Escherichia coli (50% inhibited by 0.5 mug/ml) and Klebsiella spp. (50% inhibited by 2 mug/ml). Piperacillin and Bay k 4999 were equally active against Proteus spp., and piperacillin had high activity against Bacteroides fragilis (50% inhibited by between 1 and 2 mug/ml).

Azlocillin↗
PubMed1984

In vitro activities of ureidopenicillins alone and in combination with amikacin and three cephalosporin antibiotics.

The MIC and MBC activity of mezlocillin alone and in combination with two concentrations of ceftizoxime, moxalactam, and amikacin and a single concentration of cefoxitin was studied in a broth microdilution partial checkerboard against 472 strains of aerobic gram-negative and gram-positive bacteria. Azlocillin was tested alone and in the same combinations against Pseudomonas aeruginosa. Of the gram-negative bacilli tested, 38% were gentamicin resistant. Antagonism (less than or equal to a fourfold ureidopenicillin MIC increase) was observed frequently with combinations of ureidopenicillins plus cefoxitin and sporadically with ureidopenicillins plus ceftizoxime or moxalactam. Partial synergism (less than or equal to a fourfold ureidopenicillin MIC decrease) was evident with both combinations of ureidopenicillins plus amikacin and ureidopenicillins plus ceftizoxime or moxalactam, the percentage being dependent upon the individual species and combinations.

Amikacin↗
PubMed1984

Hydroxylamine technique for in vitro prevention of penicillin inactivation of tobramycin.

Hydroxylamine was evaluated and found to be a highly effective agent for the in vitro prevention of penicillin inactivation of tobramycin. This inactivation reaction resulted in an underestimation of tobramycin concentrations and was dependent on time, temperature, amount and type of penicillin, and amount of tobramycin. Plasma samples containing tobramycin and three clinically relevant concentrations of ticarcillin, carbenicillin, azlocillin, or piperacillin were incubated with and without hydroxylamine, and tobramycin concentrations were monitored at 0, 12, 24, 48, and 72 h. The inactivation reaction was found to be completely inhibited by hydroxylamine (1 mg/ml) compared with a 27 to 50% loss of measured tobramycin concentration in the unprotected tobramycin-penicillin samples. Hydroxylamine did not interfere with the Emit enzyme immunoassay (Syva Co.) at either high or low tobramycin concentrations. Hydroxylamine was effective in inhibiting the tobramycin inactivation at both room and refrigerator temperatures and was 100% effective in protecting tobramycin on a 1:1 molar basis.

Azlocillin↗
PubMed1991

Invalidity for Pseudomonas aeruginosa of an accepted model of bacterial permeability to beta-lactam antibiotics.

The accepted model for the penetration of beta-lactam antibiotics into gram-negative bacteria is that proposed by Zimmermann and Rosselet (Antimicrob. Agents Chemother. 12:368-372, 1977). The model assumes (i) that diffusion of the antibiotic molecules across the outer membrane obeys Fick's law and can be characterized by a permeability constant for any given combination of organism and drug, (ii) that drug hydrolysis within the periplasm obeys Michaelis-Menten kinetics, and (iii) that a steady state is rapidly attained between drug uptake and hydrolysis. The model has allowed accurate prediction of antibiotic MICs for Escherichia coli strains from a knowledge of their beta-lactamase production and permeability characteristics. It has been suggested that the model is inappropriate for Pseudomonas aeruginosa, but attempts to confirm this have been bedevilled by experimental difficulties in estimating permeability coefficients for this species. In the present study, we tested a prediction of the model that the overall resistance of P. aeruginosa transconjugants containing a plasmid-encoded beta-lactamase should continue to depend partly on permeability. Transconjugants with PSE-4 beta-lactamase were constructed in host strains with widely different levels of intrinsic, presumably impermeability-determined resistance. Contrary to the prediction of the model, all the transconjugants developed identical overall levels of resistance to substrate beta-lactams, such as azlocillin and cefoperazone, irrespective of the initial levels of intrinsic resistance of the recipient strains. We conclude that the model is inappropriate for P. aeruginosa, and possible explanations for the organism's behavior are discussed.

Anti-Bacterial Agents↗
PubMed1984

Measurement of levels of aminoglycosides and vancomycin in serum in the presence of new beta-lactam antibiotics.

We evaluated the effect of new beta-lactam antibiotics (azlocillin, mezlocillin, piperacillin, cefotaxime, moxalactam, and cefoperazone) on assays for aminoglycosides and vancomycin. These antibiotics produced no interference in an immunoassay for gentamicin and tobramycin. The new penicillins produced no interference in a bioassay of amikacin and vancomycin with penicillinase incorporated into the assay agar. Bioassay in the presence of the cephalosporins required predigestion with cephalosporinase. We describe a method for accurate bioassay in the presence of the available cephalosporins, with the exception of moxalactam.

Aminoglycosides↗
PubMed1998

Effects of decontamination methods and culture conditions on viability of Mycobacterium ulcerans in the BACTEC system.

We used the BACTEC system to evaluate the effects of several decontamination methods and the addition of antibiotics on the viability of Mycobacterium ulcerans. The effects of polyoxyethylene stearate or egg yolk as supplements were also evaluated to determine their impact on the growth of M. ulcerans. Strains of different geographic origins were subjected to Petroff, reversed Petroff, oxalic acid, and mild HCI treatments. After treatment, the viability of each strain was assessed in the BACTEC system. All of the decontamination methods tested adversely affected bacterial viability. Treatment with mild HCl gave the best results, allowing better growth rates with some strains and causing a delay in growth with others, depending on the geographic origin of the strain. A mixture of polymyxin B, amphotericin B, nalidixic acid, trimethoprim, and azlocillin did not significantly inhibit growth. Supplementing BACTEC medium with egg yolk markedly improved the recovery of M. ulcerans following the use of each of the decontamination methods. Our findings demonstrate a detrimental impact on the viability of M. ulcerans by all of the decontamination methods currently in common use. This explains, at least in part, the difficulty often experienced in cultivating this organism from clinical specimens. Egg yolk should be added to enhance the rate of successful primary cultivation of M. ulcerans in the BACTEC system.

Amphotericin B↗
PubMed2002

Reduction of contamination of mycobacterial growth indicator tubes with a modified antimicrobial combination.

Culture in the fluorimetric Mycobacteria Growth Indicator Tube (MGIT) treated with a combination of vancomycin, amphotericin B, and nalidixic acid (VAN) showed growth of most strains of 31 mycobacterial species with a less-than-1-day delay. The results were similar to those in the MGIT with polymyxin B, amphotericin B, nalidixic acid, trimethoprim, and azlocillin, but with respiratory specimens, the MGIT with VAN showed a lower contamination rate with no change in the detection rate or time.

Amphotericin B↗
PubMed1989

Treatment of pseudomonas aeruginosa colonisation in cystic fibrosis.

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.

Adolescent↗
PubMed1985

Adverse reactions to piperacillin in adults with cystic fibrosis.

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.

Adult↗
PubMed1989

Effect of antibiotics on laser-induced thrombus formation in rat mesenteric arterioles.

Antibiotics were tested in a thrombosis model, in which thrombi are produced in small rat mesenteric arterioles. An interference contrast system based on a Leitz Orthoplan microscope, was used to visualize thrombus formation. Vascular lesions were produced with a Coherent CR-2 supergraphite ion laser (argon laser) in arterioles of 25-35 microns diameter. Cefmenoxim, cefotaxim (i.v.) and cephalexin orally at doses of 20 and 40 mg/kg and gentamycin 10 and 20 mg/kg (i.v.) had a marked and significant antithrombotic effect. Even more effective were cefoperazon and lamoxactam 20 and 40 mg/kg (i.v.) and tobramycin 10 and 20 mg/kg (i.v.). Azlocillin, cefoxitin, mezlocillin or spectinomycin (20 mg/kg i.v.) and penicillin or piperacillin (50 mg/kg i.v.) also showed a significant antithrombotic effect, which, however, disappeared on doubling of the applied dose.

Animals↗
PubMed1984

Effect of different penicillin derivatives on complement components in human serum.

The effect of different penicillin derivatives on the human complement system has been studied in vitro. Four penicillins tested (benzylpenicillin, oxacillin, methicillin, azlocillin) were found to inactivate total hemolytic complement dose dependently. This effect is caused by direct inactivation of C2, C5 and one or more of the components C6-9 as well as by activation of the alternative pathway. At relatively high concentrations, penicillins induce a conformational change in C3 and C4, leading to the C3b-like or C4b-like forms of these molecules, respectively. Prominent effects on the complement system occur at penicillin concentrations exceeding those achieved in plasma under regular therapeutic use. However, a synergism of penicillins with drugs acting similarly on the complement system, such as iodinated radiographic contrast media, may be expected.

Azlocillin↗
PubMed1980

Clinical pharmacology of a new ureidopenicillin: Bay K 49999.

A new semisynthetic ureidopenicillin (Bay K 4999) demonstrates favorably in vitro antibacterial efficacy against human-pathogenic gram-negative rods in comparison to mezlocillin and azlocillin. A comparative paramcokinetic study was done with 10 test subjects after 30 min intravenous infusion of 4.0 g of Bay K and mezlocillin, respectively. The serum concentration course during a period of 10 h showed an open three-compartment model for both antibiotics. The urine recovery of Bay K 4999 during 24 h was only 32.6 +/- 4.3% of the applied dose. In three test subjects with normal renal function, the average renal clearance of Bay K was 61.0, the total serum clearance was 409.2 ml/min/1.73 m2. 31 patients were treated with a daily dose of 3 x 1.0--2.0 g Bay K for severe bronchopulmonary, UTI and cholangiogenic infections. The therapeutic results were good; the relatively high number of side effects should be further investigated in animal studies and require more clinical experience.

Adult↗
PubMed1980

In vitro evaluation of new penicillins and cephalosporins upon P. aeruginosa and their interaction with mecillinam.

The in vitro activity of the new semisynthetic ureidopenicillins azlocillin (AZ) and mezlocillin (MZ), and of the new cephalosporin cefsulodin (CEF) were determined against 50 carbenicillin-sensitive (CARs) and 50 carbenicillin-resistant (CARr) P. aeruginosa clinical isolates. In the CARs group the most active antibiotics are AZ and CEF with MICs between 0.5 and 8 microgram/ml. Ticarcillin (TIC) and MZ showed more activity than CAR with MICs from 2 to 32 mu/ml. In this group there is a predominance of pyocine-type groups 1 and 3. In the CARr group, AZ is the most active antibiotic at low concentrations. At 64 microgram/ml of CEF, 72% of strains are inhibited as compared to 70% with AZ, 62% with MZ and 50% with TIC. In this group there is predominance of non-typeable strains. Interaction with mecillinam (MEC) and these antibiotics was studied on three different culture media (MH, NIH and DST). There were few cases of synergism with MEC and TIC combinations, mostly on DST medium. No appreciable synergism was found with other combinations of antibiotics.

Amdinocillin↗
PubMed1983

Pseudomonas aeruginosa and Acinetobacter calcoaceticus: in vitro susceptibility of 150 clinical isolates to five beta-lactam antibiotics and tobramycin.

The in vitro activities of azlocillin, carbenicillin, ceftriaxone, piperacillin, N-formimidoyl thienamycin (N-f thienamycin) and tobramycin have been compared against clinical isolates of Pseudomonas aeruginosa (n = 100) and Acinetobacter calcoaceticus (n = 50). An agar dilution method was employed for measurement of minimal inhibitory concentration (MIC). Tobramycin was the most active drug against P. aeruginosa (MIC less than or equal to 2 mg/l). Of the beta-lactam antibiotics, N-f thienamycin and tobramycin were highly active against A. calcoaceticus (MIC less than or equal to 2 mg/l), although one isolate was resistant to tobramycin (MIC greater than 16 mg/l). The other drugs were only moderately active against A. calcoaceticus.

Acinetobacter↗