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Antimicrobial Agents and Chemotherapy May 1984The efficacy of beta-lactam antibiotics and amikacin alone and in various combinations against Pseudomonas aeruginosa was studied in a rabbit model simulating a... (Comparative Study)
Comparative Study
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.
Topics: Agranulocytosis; Amikacin; Animals; Anti-Bacterial Agents; Azlocillin; Cefotaxime; Cefoxitin; Ceftizoxime; Disease Models, Animal; Drug Combinations; Female; Hydrogen-Ion Concentration; Kanamycin; Microbial Sensitivity Tests; Neutropenia; Penicillins; Protein Binding; Pseudomonas Infections; Rabbits
PubMed: 6329087
DOI: 10.1128/AAC.25.5.545 -
IET Nanobiotechnology Dec 2017In recent years, the problems associated with bacterial resistance to antibiotics caused nanodrugs to be considered as a new way for infectious diseases treatment. The...
In recent years, the problems associated with bacterial resistance to antibiotics caused nanodrugs to be considered as a new way for infectious diseases treatment. The main purpose of this study was to develop a new agent against a very difficult bacterium to treat, based on azlocillin antibiotic and silver nanoparticles (AgNPs). Azlocillin was conjugated with AgNPs by chemical methods and its antimicrobial activity was studied against . using well diffusion agar method. Then, minimum inhibitory concentration and minimum bactericidal concentration of the new conjugate was specified with macro-dilution method. The animal study showed the considerable enhanced antibacterial effect of azlocillin in conjugation with AgNPs against . in comparison with azlocillin alone, AgNPs alone and azlocillin in combination with AgNPs.
Topics: Animals; Anti-Bacterial Agents; Azlocillin; Female; Metal Nanoparticles; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Silver; Spectroscopy, Fourier Transform Infrared
PubMed: 29155393
DOI: 10.1049/iet-nbt.2017.0009 -
Antimicrobial Agents and Chemotherapy Jun 1978The activity of azlocillin and mezlocillin, new semisynthetic ureido penicillins, was investigated and compared with that of other known beta-lactam antibiotics. At a... (Comparative Study)
Comparative Study
The activity of azlocillin and mezlocillin, new semisynthetic ureido penicillins, was investigated and compared with that of other known beta-lactam antibiotics. At a concentration of 25 mug/ml, azlocillin inhibited 74% of Enterobacter, 97% of Proteus mirabilis, 64% of Citrobacter, 91% of Pseudomonas aeruginosa, and 82% of Bacteroides strains tested. Mezlocillin inhibited 86% of Shigella, 96% of Enterobacter, 80% of indole-positive Proteus, 88% of Bacteroides, and 63% of Pseudomonas strains tested. Azlocillin was more active against Pseudomonas than was ticarcillin, carbenicillin, or mezlocillin. Mezlocillin was more active than carbenicillin and ampicillin against Escherichia coli, Klebsiella, Enterobacter, Citrobacter, Acinetobacter, Serratia, and Bacteroides. Azlocillin and mezlocillin were less active than cefazolin against beta-lactamase-producing E. coli and Klebsiella strains but more active than cefazolin against Enterobacter, indole-positive Proteus, Acinetobacter, Citrobacter, and Serratia strains. Both compounds showed activity equivalent to that of cefoxitin against Bacteroides isolates. Both agents were destroyed by many of the beta-lactamases from gram-negative organisms.
Topics: Bacteria; Microbial Sensitivity Tests; Penicillinase; Penicillins; Protein Binding
PubMed: 677860
DOI: 10.1128/AAC.13.6.930 -
Antimicrobial Agents and Chemotherapy Jan 1978Sodium 6{d(-)-alpha(4-hydroxyl-1,5 naphthyridine-3-carboxamido)phenylacetamido} penicillanate (PC-904) is a new semisynthetic penicillin with broad-spectrum activity...
Sodium 6{d(-)-alpha(4-hydroxyl-1,5 naphthyridine-3-carboxamido)phenylacetamido} penicillanate (PC-904) is a new semisynthetic penicillin with broad-spectrum activity against gram-positive cocci and gram-negative bacilli. At a concentration of 1.56 mug/ml, it inhibited 100% of isolates of Proteus mirabilis, 89% of Pseudomonas aeruginosa, 67% of Escherichia coli, and 45% of Enterobacter spp. At a concentration of 12.5 mug/ml, it inhibited 75% of Klebsiella spp. and 67% of Serratia marcescens. PC-904 failed to inhibit the growth of gram-negative bacilli when large inocula were used. Some differences were noted when organisms were tested in different media or at different hydrogen ion concentrations. It is more active than mezlocillin, azlocillin, ticarcillin, carbenicillin, and amoxicillin against E. coli, Klebsiella spp., and P. aeruginosa.
Topics: Ampicillin; Microbial Sensitivity Tests; Naphthyridines
PubMed: 626486
DOI: 10.1128/AAC.13.1.14 -
African Health Sciences Jun 2021Tuberculosis (TB) sputum culture contaminants make it difficult to obtain pure TB isolates.We aimed to study and identify persistent TB sputum culture contaminants post...
BACKGROUND
Tuberculosis (TB) sputum culture contaminants make it difficult to obtain pure TB isolates.We aimed to study and identify persistent TB sputum culture contaminants post the standard laboratory pre-culture sample decontamination techniques.
METHODS
This was a longitudinal study of TB sputum culture contamination for a cohort of TB patients on standard treatment at: baseline, during TB treatment and post TB treatment. Sputum samples were decontaminated with 1.5%NaOH and neutralized using 6.8 Phosphate buffer solution.Sputum was then inoculated into MGIT (mycobactrial growth indicator tube) supplemented with 0.8ml PANTA. A drop of each positive MGIT culture was sub cultured onto blood agar and incubated for 48 hours at 35 -37OC.Any growth was identified using growth characteristics and colony morphology.
RESULTS
From October 2017 through May 2019;we collected 8645 sputum samples of which 8624(99.8%) were eligible and inoculated into MGIT where 2444(28.3%)samples were TB culture positive and 255(10.4%)were positive for contaminants: 237 none-tuberculosis bacteria, 12 fungi and 6 mixed(none-tuberculous bacteria+fungi). There was no statistically significant difference between none tuberculosis bacteria and fungi in the treatment (OR=1.4,95%CI:0.26-7.47,p=0.690) and the post treatment TB phases(OR=2.02,95%CI:0.38-10.79,p=0.411)Vs baseline.
CONCLUSION
None-tuberculous bacteria and fungi dominate the plethora of TB sputum culture contamination and persist beyond the standard laboratory pre-culture decontamination algorithm.
Topics: Amphotericin B; Anti-Bacterial Agents; Azlocillin; Bacteria; Bacteriological Techniques; Fungi; Humans; Longitudinal Studies; Mycobacterium tuberculosis; Nalidixic Acid; Polymyxin B; Sputum; Trimethoprim; Tuberculosis
PubMed: 34795716
DOI: 10.4314/ahs.v21i2.18 -
Antimicrobial Agents and Chemotherapy Apr 1979The in vitro activities of the newer semisynthetic penicillins azlocillin, mezlocillin, and piperacillin were compared with those of ampicillin and ticarcillin by using... (Comparative Study)
Comparative Study
The in vitro activities of the newer semisynthetic penicillins azlocillin, mezlocillin, and piperacillin were compared with those of ampicillin and ticarcillin by using 290 clinical laboratory isolates. Piperacillin and mezlocillin were the most active against Escherichia coli, Proteus mirabilis, Klebsiella spp., and Enterobacter spp. When Pseudomonas aeruginosa was tested, piperacillin and azlocillin were more active than either mezlocillin or ticarcillin. Streptococcus pneumoniae and Haemophilus influenzae species were highly susceptible to all of the penicillins tested. Ticarcillin had relatively poor activity against enterococci. The rate of bacterial killing with multiples of the minimal inhibitory concentration of azlocillin, ampicillin, or ticarcillin was tested for E. coli, P. mirabilis, P. aeruginosa, and Klebsiella spp. Increasing concentrations increased the bactericidal effect. The effect of combining azlocillin, ampicillin, or ticarcillin with an aminoglycoside was studied by using both killing curves and checkerboards. The isobolograms constructed from the checkerboards showed a synergistic pattern for the organisms tested, which included E. coli, P. aeruginosa, Klebsiella spp., P. mirabilis, and enterococci. However, the rate of killing was increased by the combination only for P. aeruginosa and enterococci.
Topics: Aminoglycosides; Ampicillin; Anti-Bacterial Agents; Drug Interactions; Enterobacteriaceae; Microbial Sensitivity Tests; Penicillinase; Penicillins; Pseudomonas aeruginosa; Ticarcillin
PubMed: 111616
DOI: 10.1128/AAC.15.4.540 -
Antimicrobial Agents and Chemotherapy Oct 1981The activities of azlocillin, cefotaxime, and amikacin alone and in combination were evaluated in in vitro checkerboard studies, in infected neutropenic mice, and in... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The activities of azlocillin, cefotaxime, and amikacin alone and in combination were evaluated in in vitro checkerboard studies, in infected neutropenic mice, and in human volunteers. The combination of cefotaxime plus amikacin was more synergistic in vitro than the others against the Enterobacteriaceae tested, and the combination of azlocillin plus amikacin was more synergistic against Pseudomonas aeruginosa and Staphylococcus aureus. Survival of neutropenic mice infected with Escherichia coli and Klebsiella pneumoniae, respectively, was greater with azlocillin plus amikacin (24 of 40 and 11 of 40) and with cefotaxime plus amikacin (21 of 40 and 17 of 40) than with azlocillin plus cefotaxime (22 of 40 and 3 of 40; P less than 0.05). Median serum bactericidal activity in volunteers receiving these antibiotics alone and in combination was greater than or equal to 1:8 with most agents and with all combinations tested against 10 strains each of E. coli, K. pneumoniae, P. aeruginosa, and S. aureus. These data suggest that clinical trials with combinations of azlocillin or cefotaxime plus amikacin deserve further study in febrile neutropenic patients.
Topics: Amikacin; Animals; Anti-Bacterial Agents; Azlocillin; Cefotaxime; Enterobacteriaceae; Escherichia coli; Escherichia coli Infections; Humans; In Vitro Techniques; Klebsiella; Klebsiella Infections; Mice; Mice, Inbred BALB C; Penicillins; Pseudomonas aeruginosa; Serratia; Staphylococcus aureus
PubMed: 6282192
DOI: 10.1128/AAC.20.4.463 -
Antimicrobial Agents and Chemotherapy Sep 1984Azlocillin (AZL) and cefonicid (CFD) penetration into rabbit humerus and scapula was evaluated with and without concomitantly administered probenecid. Groups of animals...
Azlocillin (AZL) and cefonicid (CFD) penetration into rabbit humerus and scapula was evaluated with and without concomitantly administered probenecid. Groups of animals received either 70 mg of AZL intravenously or 20 mg of CFD intramuscularly per kg of body weight; other groups were pretreated with 40 mg of probenecid per kg before the administration of antibiotics. Peak levels of AZL in the sera of animals not receiving probenecid were 76.0 micrograms/ml at 30 min and declined to 7.7 micrograms/ml by 2.0 h. Maximum concentrations in bone were 2.7 micrograms/g in the humerus and 7.1 micrograms/g in the scapula at 1 h. Pretreatment with probenecid significantly elevated levels of AZL in both serum and bone while increasing the half-life in serum from 0.44 to 0.65 h. Maximum drug concentrations in bones of probenecid-pretreated animals were 3.9 and 11.7 micrograms/g in the humerus and scapula, respectively, with detectable levels persisting in bone for up to 4 h. The peak level of CFD alone in serum was 36.7 micrograms/ml at 30 min and declined to 0.86 micrograms/ml at 8 h. Maximum concentrations in bone were 0.66 micrograms/g in the humerus at 1 h and 1.8 micrograms/g in the scapula at 2 h. Pretreatment with probenecid significantly elevated levels of CFD in both serum and bone while increasing the half-life in serum from 1.4 to 2.94 h. Pretreatment with probenecid achieved maximum concentrations of 1.7 and 2.8 micrograms/g in the humerus and scapula, respectively. Detectable levels of CFD persisted in the humerus for up to 4 h and in the scapula for 8 h.
Topics: Animals; Azlocillin; Bone and Bones; Cefamandole; Cefonicid; Half-Life; Probenecid; Rabbits
PubMed: 6508259
DOI: 10.1128/AAC.26.3.292 -
Antimicrobial Agents and Chemotherapy Jun 1994Time-survival studies were conducted to estimate the effects of azlocillin and tobramycin on Pseudomonas aeruginosa NCIMB 8295 (in the exponential phase of growth) at...
Time-survival studies were conducted to estimate the effects of azlocillin and tobramycin on Pseudomonas aeruginosa NCIMB 8295 (in the exponential phase of growth) at concentrations ranging from one-quarter to twice the MIC. The effects of the individual agents and their combinations were determined by measuring the viable counts (CFU per milliliter) over a 24-h period. The typical pattern observed from the plot of the logarithm of the CFU per milliliter against time was an initial rapid killing; this was followed by a period of stasis and regrowth. Initial rates of killing by tobramycin were concentration dependent, whereas this was not the case with azlocillin. From the time-survivor plots, the area under the curve for viable bacteria was also calculated. It offered a useful method of interpreting the results of time-kill studies, taking the overall pattern of killing and regrowth into consideration. The area under the curve for viable bacteria was concentration dependent for both antibiotics. A 2(2) factorial experimental design was used to analyze the joint effects of azlocillin and tobramycin. In such a factorial experiment, an interaction between two factors, in this case, azlocillin and tobramycin concentrations, is shown by a change in the slope of the plot when the concentration of the interactant is changed. Analysis of variance showed that the combination was synergistic at low concentrations, but this was not significant when the concentration of either interactant was increased.
Topics: Azlocillin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Tobramycin
PubMed: 8092825
DOI: 10.1128/AAC.38.6.1271 -
Antimicrobial Agents and Chemotherapy Mar 1979The anti-pseudomonas activities of azlocillin and mezlocillin were compared with that of ticarcillin. We measured the minimal inhibitory and minimal bactericidal... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The anti-pseudomonas activities of azlocillin and mezlocillin were compared with that of ticarcillin. We measured the minimal inhibitory and minimal bactericidal concentrations of the three drugs against 20 different strains of Pseudomonas aeruginosa and found significantly lower values for azlocillin than for the other two drugs. We then infused 5 g of each drug into 10 volunteers on three consecutive days and determined the serum levels of the three antibiotics at 1-h intervals from 1 to 6 h after injection. The levels of azlocillin were significantly higher than those of mezlocillin and ticarcillin (at 1 h: 236.55 mug/ml +/- 12.9 for azlocillin, 192.45 mug/ml +/- 28.8 for mezlocillin, and 131.5 mug/ml +/- 10.9 for ticarcillin). The inhibitory and bactericidal activities of the sera obtained 1 and 6 h after the injection against the same 20 strains of P. aeruginosa demonstrated a significantly greater anti-pseudomonas activity of azlocillin when compared with mezlocillin and ticarcillin; mezlocillin and ticarcillin had approximately the same activity. The mean values for bactericidal activity against the strains tested were 1/32 for azlocillin, 1/8 for mezlocillin, and 1/8 for ticarcillin. Azlocillin thus appears to be a promising anti-pseudomonas drug and should be tested in clinical trials.
Topics: Humans; Microbial Sensitivity Tests; Penicillins; Pseudomonas Infections; Pseudomonas aeruginosa; Ticarcillin; Time Factors
PubMed: 111610
DOI: 10.1128/AAC.15.3.396