摘要:

This study elucidates the routes of elimination of ciprofloxacin and its metabolites in two groups of 5 subjects each, one of healthy volunteers, the other of patients with severe renal failure having a creatinine clearance of 12 ml/min (range 8–16 ml/min). Each subject received one dose of 200 mg ciprofloxacin infused intravenously over 30 min. In an effort to recover the total dose administered, all urine and faeces were collected for the 7 days following dosing. Blood was collected at set intervals after dosing. Serum, urine, and faeces were assayed by high-pressure liquid chromatography for ciprofloxacin and metabolites. The ciprofloxacin serum half-life in healthy volunteers was 3.9 ± 0.4 h and in patients with marked renal failure 11.2 + 2.5 h. The total amount of ciprofloxacin recovered in urine fell by a multiple of 3.4 from ± 10.7% in healthy subjects to 19.0 ± 15.9% in patients with renal failure, and the metabolites from 12.2 ± 2.3% in the former group to 5.8 ± 5.1% in the latter. In contrast, the amount of ciprofloxacin eliminated in faeces increased, by a similar factor, from ± 2.6% in healthy subjects to 37.2 ± 12.5 % in patients with renal failure. The amount of metabolites in faeces increased analogously from 7.3 ± 1.6 to 26.2 ± 6.5%. Since ciprofloxacin was administered intravenously and biliary elimination of the drug and its metabolites is negligible, we propose that elimination by faeces is due primarily to transintestinal elimination. This study demonstrates that transintestinal elimination of ciprofloxacin serves as an extrarenal safety factor compensating for reduced elimination by the r

ISSN:0009-3157    

DOI:10.1159/000238751

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Clindamycin phosphate becomes biologically active only with cleavage of the phosphate ester bond. A rat model was used to examine the amount of biologically active clindamycin attainable in the dialysate and in the blood during peritoneal dialysis. Intravenous administration of 10 mg/kg clindamycin phosphate alone without peritoneal dialysis produced peak blood levels of 15–20 μg/ml. With peritoneal dialysis, blood levels of less than 5 μg/ml were achieved. When clindamycin phosphate was added to the dialysis fluid at an initial concentration of 10 mg/ml, less than 5 μg/ml of the active antibiotic can be detected in the dialysis return fluids. Even in rats with induced peritonitis, less than 15 μg/ml could be found in the dialysis returns. With or without peritonitis, less than 5 μg/ml of active clindamycin was attained in blood from peritoneal installation alone. The conversion of the ester to the active compound appears to be the major problem. It is recommended that in those clinical situations in which the patient requires peritoneal dialysis, an alternate antimicrobial agent be used in place of clindamycin to avoid infections in the abdominal cavity or the blood while under t

ISSN:0009-3157    

DOI:10.1159/000238752

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The effects of ‘third-generation’ cephalosporins and penicillin analogues on the concentrations of total unconjugated bilirubin, unbound bilirubin and erythrocyte-bound bilirubin were determined in blood samples. This study was performed, in vitro, at two bilirubin/albumin molar ratios and at various concentrations of antibiotics. The most effective displacers, considering the three methods, were antibiotics tightly bound to albumin: ceftriaxone and cefotetan. Cefoperazone, which is bound to albumin as tightly as these two antibiotics, caused no significant increase in unbound bilirubin but should be considered as a displacer drug on the basis of the variations of erythrocyte-bound bilirubin and total bilirubin. We suggest that drug interaction on bilirubin-albumin binding be investigated by several meth

ISSN:0009-3157    

DOI:10.1159/000238753

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Postoperative infection is among the most common complications in patients with cerebrospinal fluid shunt placement. Nafcillin is often used for prophylaxis but no pharmacokinetic data are available perioperatively in pediatric patients. The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal concentrations of nafcillin. Ten patients (mean age 8.0 ± 5.6 years) received three doses of intravenous nafcillin, 50 mg/kg every 6 h; the first dose was administered 1 h prior to surgery. Multiple blood samples were collected during and after surgery and the cerebrospinal fluid sample was obtained at the time of shunt insertion. Urine samples were collected for 24 h after initiation of nafcillin. Nafcillin was analyzed with an HLPC method. The peak serum concentrations ranged from 22 to 107 μg/ml; cerebrospinal fluid concentrations ranged from 0.02 to 0.30 (mean 0.16 ± 0.11) μg/ml. The mean total clearance, renal clearance, apparent volume of distribution, and elimination half-life were 0.90 ± 0.55 1/kg/h, 0.12 ± 0.04 1/kg/h, 0.70 ± 0.52 1/kg, and 0.5 ± 0.1 h, respectively. 16% of total nafcillin dose was excreted in the urine. A 4-fold variability in total clearance and a 10-fold variation in cerebrospinal fluid concentrations of nafcillin was observed in these patients. Further, the concentrations of nafcillin attained in the cerebrospinal do not appear to be adequate, based on its minimum inhibitory concentration of 0.5 μ.g/ml against very susceptible staphylococci. These data, in addition to the fact that an increasing number of staphylococci are becoming resistant to nafcillin, question the usefulness of prophylactic nafcillin in pediatric patients undergoing shunt pr

ISSN:0009-3157    

DOI:10.1159/000238754

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Staphylococcus epidermidis has been established as the common pathogen causing cerebrospinal fluid shunt infections. In addition, clinical isolates of S. epidermidis from infected shunts are typically resistant to methicillin. Vancomycin is often used for neurosurgical prophylaxis due to its excellent in vitro activity against methicillin-resistant staphylococci. Limited data are available about the pharmacokinetics and cerebrospinal fluid concentrations of vancomycin in pediatric patients intraoperatively. The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal fluid concentrations of vancomycin. Eight patients (mean age 8.3 ± 7.0 years) received three doses of intravenous vancomycin, 15 mg/kg every 6 h. The first dose was administered 1 h prior to surgery. Blood samples were collected at 0, 0.5, 1, 2, 4, and 5 h after the end of the infusion. A cerebrospinal fluid sample was collected at the time of shunt insertion. Urine samples were collected over a 24-hour period. Vancomycin was measured with a fluorescence polarization immunoassay. The peak serum concentrations ranged from 15.6 to 33.7 μg/ml; cerebrospinal fluid concentrations ranged from < 0.6 to 0.8 μg/ml. The mean total clearance, renal clearance, apparent volume of distribution, and elimination half-life were 0.11 ± 0.05 1/h/kg, 0.07 ± 0.02 1/h/kg, 0.54 ± 0.151/kg, and 4.8 ± 4.0 h, respectively. Approximately 70% of total vancomycin dose was excreted in the urine. A 2- to 5-fold variation in total clearance and a 2.5-fold variability in renal clearance were observed. Low cerebrospinal fluid concentrations of vancomycin were present at the time of shunt insertion in these pediatric patients. The cerebrospinal fluid concentrations attained were inadequate based upon the minimum inhibitory concentration of methicillin-resistant staphylococci. Two of 9 patients developed moderate to severe adverse reactions during the vancomycin infusion. Thus, studies are needed to evaluate alternative agents to vancomycin for prevention of CSF shunt infe

ISSN:0009-3157    

DOI:10.1159/000238755

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The dual-action antibacterial R 23-9424 (desacetylcefotaxime linked to the quinolone fleroxacin) is a new antibacterial agent with excellent in vitro activity. It was evaluated for in vivo efficacy in comparison with the cephalosporin cefotaxime and the quinolone component, fleroxacin. Ro 23-9424 demonstrated significant activity against all strains tested in systemic infections, including those strains resistant in vivo to cefotaxime (Staphylococcus aureus 753, Serratia marcescens SM and Pseudomonas aeruginosa 8780) and fleroxacin (Streptococcus pneumoniae 6301 and Streptococcus pyogenes 4). In prophylactic studies, Ro 23-9424 compared favorably with fleroxacin against Escherichia coli and with cefotaxime against S. pyogenes, but Ro 23-9424 was considerably more active than cefotaxime against E. coli and more active than fleroxacin against S. pyogenes. In a murine pneumonia model, Ro 23-9424 was equivalent in activity to cefotaxime against S. pneumoniae and more active than cefotaxime against Klebsiella pneumoniae. Fleroxacin was inactive against S. pneumoniae and about 20-fold more active than Ro 23-9424 against K. pneumoniae. In a murine meningitis infection caused by S. pneumoniae, Ro 23-9424 was 3 times as active as cefotaxime, while fleroxacin was inactive. When meningitis was induced by K. pneumoniae, Ro 23-9424 was as active as the quinolone, while cefotaxime was inactive. In a neutropenic (immunocompromised) model, Ro 23-9424 was more active than cefotaxime against P. aeruginosa and 5-fold less active than fleroxacin. In the control normal (immunocompetent) mouse infection, Ro 23-9424 was 3-fold more active than cefotaxime, but 10-fold less active than fleroxacin.

ISSN:0009-3157    

DOI:10.1159/000238756

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Twenty Pseudomonas maltophilia isolates were examined for susceptibility to β-lactam antibiotics, including carbapenems, and for β-lactamase production. All the isolates were resistant to imipenem (MICs 64–512 mg/l) and to a lesser extent, to meropenem (MICs 16–256 mg/l). None of the isolates produced significant amounts of β-lactamase without induction. Among the β-lactams studied imipenem proved to be the most potent inducer; meropenem was a weaker inducer. Interestingly, 6-amino-penicil-lanic acid, even in concentrations up to 100 mg/l, entirely lacked induction activity. In any case enzyme production was drug concentration dependent and transient. Isoelectric focusing revealed 6 different enzymes distinguished by their different isoelectric points (pH 6.2, 8.3, 8.5, 9.0, 9.2 and 9.4). This suggested the lack of a unique β-lactamase profile in P. maltophilia. Addition of 5 mM cyclic AMP (cAMP) or 0.5 mM cAMP-N6, O2-dioctanoyl (a lipophilic derivative) resulted in a marked drop of β-lactamase induction by imipenem as compared to the control assay. Monitoring of carbapenem hydrolysis by cell-free supernatants revealed inactivation of both carbapenems. Meropenem was inactivated about 5 times more rapidly than imipenem. Our studies revealed that β-lactamase production in P. maltophilia as well as growth kinetics were influenced to a considerable extent by the nutrient mediu

ISSN:0009-3157    

DOI:10.1159/000238757

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Twenty-four antimicrobial drugs were examined for rapidity of onset and magnitude of bactericidal activity against selected strains of Clostridium perfringens. Ceftriaxone, imipenem, metronidazole, mezlocillin, penicillin G, piperacillin, and teicoplanin reduced colony counts by at least 3 logio units within 2–4 h after exposure. Clindamycin, fluoroquinolones, josamycin, and tetracycline caused delayed kill (≥99.9% reduction of viable counts at 4–22 h after exposure). Chloramphenicol and rifampin lacked bactericidal activity against 2 of 4 strains, whereas erythromycin, fusidic acid, and fosfomycin (with added glucose-6-phosphate) were merely inhibitory for all 4 strains. Imipenem and penicillin G were combined with 9 and 12 antimicrobial drugs, respectively. Essentially all drug combinations yielded indifferent effects; only penicillin G plus doxycycline resulted in an antagonistic effect against C. perfringen

ISSN:0009-3157    

DOI:10.1159/000238758

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The in vitro activity of daptomycin against 297 clinical isolates of Staphylococcus aureus and S. epidermidis sensustrictu was compared with the activities of cephalothin, dicloxacillin, tobramycin, and vancomycin. Minimal inhibitory concentrations (MICs) were determined by an agar dilution method. Cephalothin and dicloxacillin showed the highest activity against S. aureus on a weight-for-weight basis, all isolates being inhibited by 0.5 mg/l or less of either agent. Cephalothin was somewhat more active against S. epidermidis than was dicloxacillin. Daptomycin and vancomycin exhibited high and similar activity against both S. aureus and S. epidermidis (MIC90% = 1 and 2 mg/l, respectively). Tobramycin was highly active against S. aureus, but the activity against S. epidermidis was greatly variable (MIC range ≤0.03 – ≥ 16 mg/l). The activity of daptomycin was markedly influenced by the test medium; the MICs were generally 32 times higher when the isolates were tested on Iso-Sensitest agar than on Mueller-Hin-ton agar. Supplementation of Iso-Sensitest agar with increasing concentrations of calcium potentiated the activity of daptomycin substantially, the results obtained on Iso-Sensitest agar supplemented with 20 mg Ca2+/1 being similar to those obtained on Mueller-Hinton

ISSN:0009-3157    

DOI:10.1159/000238759

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

A multicenter study aimed at assessing the in vitro activity of sulbactam/ ampicillin against a wide range of bacterial pathogens was performed using 2,209 clinical strains, all recently collected from inpatients in seven Italian centers and preliminarily screened as being ampicillin-resistant and β-lactamase producers. In comparative disk diffusion trials using 8 large-spectrum antimicrobials, the percentage of resistance to sulbactam/ampicillin in staphylococci was similar to the percentage of resistance to netilmicin and lower than to the other antibiotics; with gram-negative bacteria, only netilmicin, ofloxacin, and, less consistently, cefotetan showed lower incidences of resistance. The minimal inhibitory concentrations (MICs) of ampicillin alone and sulbactam/ampicillin together were determined using the agar dilution method. The Enterobacteriaceae strains which shifted to ampicillin susceptibility in the presence of sulbactam averaged 68 %, but values significantly above or below average were observed in some genera of this family. The percentage of strains which the presence of sulbactam rendered ampicillin-susceptible in vitro reached 97% in Haemophilus strains and 100% in branhamellae and gonococci. High percentages were also recorded in staphylococci, with a peak of 100% in oxacillin-susceptible Staphylococcus aureus strains. In general, center-to-center differences were relatively limited

ISSN:0009-3157    

DOI:10.1159/000238760

出版商:S. Karger AG    

年代:1990

数据来源: Karger