摘要:

We report the pharmacokinetic parameters of ceftriaxone in 11 patients on hemodialysis with end-stage renal disease (ESRD; creatinine clearance < 5 ml/ min/1.73 m2). The patients were studied during the interdialysis period and during 4h of hemodialysis. The mean age was 53.4 years. After the administration of 1 g of ceftriazone during a constant intravenous infusion over a 30-min period, t½ was 16.6 h, β was 0.0418 ± 0.0106 h-1, VD was 14.5 ± 3.0 liters/1.73 m2 and Clp was 0.40 ± 0.05 liters/h for the interdialysis period. Hemodialysis started 24 h after the infusion. The initial plasma ceftriaxone concentration was 68.6 ± 10.8 μg/ml. This value dropped to 40.4 ± 4.7 μg/ml at the end of the 4th hour, indicating a significant 41% decay in blood levels during hemodialysis (p < 0.001). The t½ decreased to 4.88 h, kel rose to 0.142 ± 0.0250 h-1 and Clp increased to 1.73 ± 0.44 liters/h. All values were highly significantly different (p < 0.001) from those during the interdialysis period. The plasma ceftriaxone concentration of 40.4 ± 4.7 μg/ml at the end of hemodialysis was well within the therapeutic range of the drug. We conclude that ceftriaxone has a moderated increase in t½ in patients with ESRD. Ceftriaxone is significantly dialyz-able, however, the plasma concentrations are in the therapeutic range by the end of a 4-hour hemodialysis, 28 h after the administration of the drug. We propose that 1 g given intravenously before each hemodialysis will be sufficient to keep the patient’s plasma concentrations within the therapeutic range until the next hemodialysis. If the interdialysis period is longer than 48 h an extra dose should

ISSN:0009-3157    

DOI:10.1159/000238578

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The concentrations of azlocillin and mezlocillin in human prostatic tissue obtained by transurethral resection or enucleation were measured after two 2.0-gram doses of either drug. The average plasma concentration of azlocillin and mezlocillin at time of tissue sampling was 64.9 and 36.3 μg/ml, respectively, and tissue concentration at the time of sampling was 22.9 μg/g for azlocillin and 9.4 μg/g for mezlocillin. The plasma/tissue concentration ratio for mezlocillin was 0.25 and for azlocillin 0.35. Concentrations of mezlocillin in tissue obtained by transurethral resection were similar to those obtained by enucleation. Azlocillin and mezlocillin in appropriate doses achieve a concentration in human prostatic tissue above the inhibitory concentration for common bacterial pathoge

ISSN:0009-3157    

DOI:10.1159/000238579

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The rat enteral and rabbit rectal models were utilized to study the effect of Capmul (medium chain glycerides) on the absorption of a selection of β-lactam and aminoglycoside antibiotics. All tested non-orally available β-lactam antibiotics (cefaman-dole, cefotaxime, moxalactam, cefoxitin, mezlocillin, carumonam, penicillin G and am-dinocillin) showed increased absorption enterally in rats and rectally in rabbits when formulated with Capmul. The orally available β-lactam antibiotics, cephalexin and cephradine, were not enhanced in their enteral or rectal absorption by Capmul in the two model systems. Ampicillin absorption was enhanced rectally and enterally by Capmul. Rectal absorption of the aminoglycoside antibiotics, tobramycin and gentamycin, was enhanced by Capmul while enteral absorption was n

ISSN:0009-3157    

DOI:10.1159/000238580

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The pharmacokinetic parameters of chlorproguanil (Lapudrine®) and its active metabolite, chlorcycloguanil, were determined in 6 healthy male volunteers after a single oral dose of 4 Lapudrine tablets (80 mg). The mean maximum plasma chlorproguanil concentration was 36.7 ± (SD)7.9 ng/ml and was reached at 3.8+1.3 h. The chlorproguanil elimination half-life was 17.5 ± 6.7 h and its plasma clearance was 1.28 ± 0.12 1/h/kg. The mean whole blood to plasma ratio was 3.1 at 4 h after dosing. Chlorcycloguanil could not be quantified in plasma and whole blood at the detection limit of 10 ng/ml using a high-performance liquid chromatographic method. An excretion rate-time plot from urine data shows a rapid (t½ = 20 h) and a slow phase (t½ = 51 h) in the elimination of chlorcycloguanil. Our findings suggest that the current prophylactic regimen of chlorproguanil hydrochloride (20 mg weekly) may not be optimal in preventing infections with chloroquine-resistant falciparum ma

ISSN:0009-3157    

DOI:10.1159/000238581

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Twelve clinical isolates of Pseudomonas aeruginosa of distinct pyocin type varied in susceptibility to 14 of 17 antimicrobial drugs. The 2 x MIC concentrations of 16 antimicrobial drugs combined with 55% (v/v) of fresh, defibrinated human blood yielded additive effects. Additive effects were noted with blood plus the MIC concentrations of all drugs tested except cefoperazone, gentamicin, and netilmicin. Blood combined with subinhibitory (1/2 MIC) concentrations of aztreonam, ceftazidime, ciprofloxacin, fleroxacin, imipenem, and tobramycin, respectively, yielded additive effects; indifferent effects were observed with the remaining 10 blood plus 1/2 MIC drug combinations. The following drug combinations additively augmented the antibacterial activity of 65% (v/v) of human blood against two selected isolates of P. aeruginosa: tobramycin (1 μg/ml) plus the MIC or 2 x MIC concentrations of azlocillin, aztreonam, ceftazidime, ciprofloxacin, imipenem, norfloxacin, ofloxacin, piperacillin, and ticarcil-lin, respectively. Imipenem (8 μg/ml) combined with ceftazidime, cefoperazone, and piperacillin, but not aztreonam, enhanced the bactericidal activity of human blood. Rifampin (2 μg/ml) plus tobramycin (0.5–1 μg/ml) combined with 8 or 16 μg/ml of azlocillin, aztreonam, cefoperazone, ceftazidime, imipenem, and piperacillin, respectively, enhanced blood-mediated killing of three representative multiple-drug-resistant P. aeruginosa isolates. Additional effective triple-drug combinations with human blood were rifampin + tobramycin + polymyxin B, rifampin + ciprofloxacin + imipenem, and rifampin + amikacin + imipenem. Ciprofloxacin (2 μg/ml) was the most potent intra-phagocytic bactericidal drug of 16 tested agents ( ≥ 2 x MBC concentrations) against P. aeruginosa control strain A

ISSN:0009-3157    

DOI:10.1159/000238582

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The in vitro activities of A56619 (difloxacin) and A-56620, two newer quinolones, have been compared with the activities of ciprofloxacin, ofloxacin, ceftazidime and netilmicin. A total of 782 clinical, bacterial isolates were employed. Minimal inhibitory concentrations (MICs) were determined under standard conditions with all isolates and, for 100 isolates against difloxacin and A-56620, with variation of agar pH and bacterial inoculum size. On a weight-for-weight basis, ciprofloxacin and A-56620 were the most active agents against Enterobacteriaceae (MIC90 = 0.03 and 0.12 mg/l, respectively). Difloxacin was the least active quinolone, particularly against Proteus, Morga-nella and Providencia spp. Except for ceftazidime, all agents were highly active against staphylococci, but difloxacin and ofloxacin were somewhat less active against Staphylococcus saprophytics. The streptococcal isolates were moderately sensitive to the quinolones, difloxacin being least active. Haemophilus influenzae and Neisseria gonorrhoeae were extremely susceptible to all the quinolones; nearly all isolates were inhibited by the lowest concentrations of the agents that were employed in the study (0.03 mg/l). The quinolones all showed moderate activity against Bacteroides fragilis. The activities of difloxacin and A-56620 were affected little by inoculum size. Difloxacin showed lower activity against most isolates at pH 8.0 as compared to the activity at pH 7.4 and 6.8. A-56620 was minimally influenced by pH variation.

ISSN:0009-3157    

DOI:10.1159/000238583

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The quinolone class of compounds was studied for conditions which might affect susceptibility results. These compounds included amifloxacin, ciprofloxacin, di-floxacin, enoxacin, norfloxacin, ofloxacin, and RO 23–6240. Ciprofloxacin, a representative quinolone, was found to have rapid bactericidal activity, equivalent to that of gen-tamicin, in contrast to the slower activity of a cephalosporin, cefotaxime. Test conditions that might affect susceptibility test results included divalent magnesium and calcium cation concentrations and pH. For strains of Staphylococcus aureus, Enterobacteriaceae, and enterococcus, the effects were not large. A pH of 5.0 in general increased the minimum inhibitory concentrations (MICs) for the organisms against most carboxy-quinolones, up to 8-fold, as compared to that at pH 7.4. In comparison, a similar lowering of pH caused an increased in MIC of 32-fold for gentamicin and no change for cefotaxime. Increasing the concentrations of divalent cations increased the MICs on the average of only 4-fold. Of the quinolones, difloxacin was the least affected by change in concentration of divalent cations and by pH. Such changes are not expected to greatly affect the efficacy of therapy of those members of Enterobacteriaceae which have MICs much less than 0.1 μg/ml, but might diminish therapeutic efficacy for those organisms such as Streptococcus aureus with MICs of 1.0 μg/ml or hig

ISSN:0009-3157    

DOI:10.1159/000238584

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The in vitro activities of six quinolone derivatives, rosoxacin, pefloxacin, ofloxacin, ciprofloxacin, A-56619 and A-56620, were compared with those of penicillin, cefotaxime, spectinomycin, chloramphenicol, tetracycline and erythromycin against 50 nonpenicillinase-producing and 15 penicillinase-producing Neisseria gonorrhoeae strains. Ciprofloxacin was the most active compound in vitro (MIC50, 0.004 mg/l) followed by ofloxacin and A-56620 (MIC50, 0.008 mg/l), A-56619 and cefotaxime (MIC50, 0.016 mg/l). The six quinolones are highly active against all the strains tested but 2, with decreased sensitivity.

ISSN:0009-3157    

DOI:10.1159/000238585

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The beta-lactamase inhibitory properties of 6-acetylmethylene penicillanic acid (6-AMPA) were investigated and compared with those of other beta-lactamase inhibitors. 6-AMPA inhibited the TEM-1, TEM-2, SHV-1, PSE-1, PSE-2, PSE-3, PSE-4, OXA-2, OXA-3, and Staphylococcus aureus beta-lactamases. It also inhibited the chromosomally-mediated beta-lactamases of the Richmond-Sykes type la, Ic and Id type and the type IV Klebsiella enzymes. Beta-lactamases of Branhamellacatarrhalis and Bacteroides fragilis were inhibited. The 6-AMPA I50 values for various enzymes were < 0.01 μg/ml TEM-1 and PSE-4, and 0.01 μg/ml SHV-1, 0.02 μg/ml S. aureus, 0.04 μg/ml Proteus vulgaris, 0.04 μg/ml K. oxytoca, 6.8 μg/ml P99, and 9.7 μg/ml Sa-bath-Abraham Pseudomonas enzyme. With isolated beta-lactamases 6-AMPA was a more potent inhibitor than clavulanate or sulbactam. 6-AMPA was an irreversible inhibitor of beta-lactamases. The penetration index for Escherichia coli JT4 was 23 compared to 3 for clavulanate. 6-AMPA at 10 μg/ml acted synergistically with ampicillin against beta-lactamase containing bacteria, but it was less active than clavulanate and did not act synergistically with ampicillin against Enterobacter, Citrobacter or Pseudomonas. Although 6-AMPA has excellent beta-lactamase inhibitory properties with isolated enzymes, it is less useful with intact or

ISSN:0009-3157    

DOI:10.1159/000238586

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The antimicrobial sensitivity of Campylobacter jejuni isolated in Bangladesh from patients with diarrhoea, asymptomatic carriers and domestic animals was performed. All isolates were sensitive to erythromycin, gentamicin, furazolidone and kanamycin. Seven percent isolates were resistant to tetracycline, 8% to nalidixic acid, 37% to ampicillin and 100% to sulfamethoxazole-trimethoprim and cephalothin. Tetracycline resistance was observed to be plasmid mediated. No plasmid band(s) coding for ampicillin, sulfamethoxazole-trimethoprim or cephalothin resistance were observed, possibly indicating chromosomally located resistance. No significant differences in the susceptibility patterns of C. jejuni isolated from the different sources was observed. However, 10 patients’ isolates showed low molecular weight (2–3, 7 Mdal-tons) plasmid band(s) which were completely absent in isolates from asymptomatic carriers and anim

ISSN:0009-3157    

DOI:10.1159/000238587

出版商:S. Karger AG    

年代:1988

数据来源: Karger