摘要:

A mathematical multiple dosing model was designed so that human plasma concentration-versus-time curves of β-lactams are reproduced in mouse plasma. The pharmacokinetic parameters of FK037, a new injective cephalosporin, in volunteers and in the mice model were 6,966 and 6,894 ml, respectively, for Vc, 2.592 and 2.698/h for α, 0.2875 and 0.3027/h for β, and 0.9079 and 1.0506 for K21. Therefore, real pharmacokinetics of humans were reproduced in mice by this method. The 8-hour therapeutic efficacy (the decrease of the viable counts in the lung) against pneumonia with Staphylococcus aureus and Pseudomonas aeruginosa in mice was well correlated with the time above MIC value, but not with AUC, Cmax or AUC above MIC. These results indicate that this model was valuable to evaluate the β-lactam antibiotics for predicting their clinical efficacy and that the time above MIC is an important factor in selecting β-lactam agents and determining dosage in pulmonary infec

ISSN:0009-3157    

DOI:10.1159/000239162

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

This multicentre study evaluates the distribution of ciprofloxacin into the tissue structures of the middle ear following multiple dosing of one 500 mg tablet every 12 h. The samples were taken perioperatively from adult patients due to undergo surgery for chronic otitis. Administration of ciprofloxacin was instigated 9 days prior to the operation. The samples were taken at different intervals after the last dose in order to evaluate variations in concentration with time. The average peak concentrations recorded and the time taken to reach these concentrations were as follows: middle ear mucosa (n = 16): 5.54 ± 3.46 μg/g (3-4 h): cortical bone of the mastoid process (n = 21): 1.07 ± 1.29 μg/g (4h). The measurements carried out 12 h after the last dose show that concentrations of ciprofloxacin in the middle ear mucosa were still at least as high as the minimum inhibitory concentration for this antibiotic for most of the pathogens implicated in acute exacerbations of chronic otitis. These results suggest that, administered as an oral dose of 500 mg every 12 h, ciprofloxacin may be an effective agent for the treatment of chronic suppurative otitis. These results now need to be backed up by clinical tri

ISSN:0009-3157    

DOI:10.1159/000239309

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

There is evidence that a variety of anticancer drugs exert their cytotoxic activity by a free-radical-mediated mechanism. These drugs include anthracyclines such as adriamycin, dauno-rubicin, 4-epi-adriblastin as well as bleomycin, procarbazine, vincristin, cyclophosphamide, etoposide and mitomycin C. The aim of this study was to investigate whether cancer patients who underwent polychemotherapy (n = 44) show more signs of oxidative stress in plasma than a group of healthy controls (n = 52). As an index of free radical generation, plasma concentrations of thiobarbituric-acid-reactive substances (TBARS), well-accepted as markers for oxidative stress, were determined by fluorometric detection after separation by high-performance liquid chromatography. In 12 cases, the TBARS were measured both before and after a chemotherapy course. After chemotherapy, 10 of 12 patients showed a marked increase in plasma TBARS concentration compared to values measured before therapy [9.02 ± 1.84 nmol/ml (n = 12) vs. 11.58 ± 2.49 nmol/ml (n = 12); p = 0.002, t-test for paired observations]. Tumor patients in general had significantly larger amounts of TBARS in plasma in comparison with a control group [mean 11.88 ± 3.51 nmol/ml (n = 44) vs. 7.51 ± 2.14 nmol/ml (n = 52); p < 0.001, t test]. Our results are evidence that repetitive polychemotherapy with radical-generating compounds may exceed the antioxidative capacities of cancer patients and may lead to oxidative str

ISSN:0009-3157    

DOI:10.1159/000239163

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The antimicrobial susceptibility and in vitro growth curve of 4 nonencapsulated and 4 encapsulated isolates of Bacteroides fragilis were determined for clindamycin. The MIC of the non-encapsulated isolates was 1-2 dilutions less (0.062-0.25 μg/ml) than the MIC for their encapsulated counterparts (0.25-0.5 μg/ ml). No difference was noted in the bacterial growth of the nonencapsulated or encapsulated isolates when incubated without clindamycin. The decline in the number of nonencapsulated isolates was significantly lower (p < 0.05) as compared to the encapsulated isolates when incubated with 0.1 or 0.4 μg/ml of clindamycin. These results illustrate the higher susceptibility of nonencapsulated B. fragilis isolates to clindamycin as compared to their encapsulated counterparts. Since B. fragilis becomes more encapsulated during the infectious process, this finding underscores the advantage of early antimicrobial prophylaxis and thera

ISSN:0009-3157    

DOI:10.1159/000239164

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

There is a need to identify alternative agents to vancomycin for the treatment of infections with methicillin-resistant Staphylococcus aureus (MRSA). One candidate is the l isomer of ofloxacin (DR-3355). We tested 520 frozen MRSA isolates, 248 fresh MRSA isolates, and 375 fresh methicillin-susceptible S. aureus (MSSA) isolates from Minnesota, and 600 clinical isolates of S. aureus (150 MRSA and 450 MSSA) from Illinois. Over 90% of the MRSA strains were resistant to 32 μg/ml of oxacillin. Of the 520 frozen MRSA, 24% were susceptible to ≤ 2 μg/ml ofloxacin, and an additional 74% were susceptible to ofloxacin between 8 and 16 μg/ml. More than 98% of all strains were susceptible to ≤ 16 μg/ml ofloxacin or l-ofloxacin. All the quinolones had a bimodal distribution of in vitro activity, but for only ofloxacin and l-ofloxacin was activity confined to a very narro

ISSN:0009-3157    

DOI:10.1159/000239165

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Over a 12-month period, 56 patients with acute exacerbations of chronic sinusitis were included in this study. The mean age of the patients was 48.6 ± 10.1 years. The period between the onset of sinus symptoms and inclusion in the study was 10.1 ± 12.1 years and the exacerbation had lasted 2.4 ± 4.4 months. Patients were given 500 mg ciprofloxacin twice daily for 9 days. Bacteriological specimens taken at inclusion were positive in 53.6% of cases, 25 Gram-positive and 16 Gram-negative pathogens being isolated. At the end of the treatment, rhinor-rhoea, which was the main criterion for evaluation of the efficacy of treatment, had disappeared in 46/54 (85%) patients who were examined. Of the 30 patients whose sinusitis was confirmed by bacteriological test, the bacteria were eradicated in 90% of cases. At the end of a 4-week follow-up period after the end of treatment, the clinical success rate was 74.5%, the partial success rate 21.2% and the failure rate 4.3%. There were no bacteriological recurrences. Ten adverse events were observed in seven patients and in four (7%) of these treatment had to be withdrawn. This study showed ciprofloxacin to be an effective and well tolerated treatment for exacerbations of chronic sinusitis treated in non-hospital practi

ISSN:0009-3157    

DOI:10.1159/000239313

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The incidence of methicillin-resistant Staphylococcus aureus (MRSA) is on the rise, especially in nosocomial and intravenous-drug-abuse-related infections, with a concomitant increase in morbidity, mortality and health care costs. At present the drug of choice, vancomycin, which must be administered intravenously, is expensive and can cause serious side effects in vancomycin-intolerant patients. Recently, minocycline has received much attention as an antibiotic to combat the increasing frequency of MRSA-related infections. We tested 102 recent clinical isolates of MRSA from tertiary-care patients and found none to be resistant to minocycline, with minimum inhibitory concentrations of < 1-2 μg/ml. The only other drug that inhibited all the strains was vancomycin, followed by ciprofloxacin (87%), clindamycin (55%) and chloramphenicol (52%). Gentamicin, β-lactams, tetracycline and trimethoprim-sulfamethoxazole had little or no activity against our isolates of MRS

ISSN:0009-3157    

DOI:10.1159/000239166

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Over a period of 18 months 76 patients presenting with acute exacerbations of chronic otitis were enrolled in this study. The mean age of the patients was 46.4 ± 16.8 years, the interval between the onset of symptoms of otitis and enrolment in the study was 22.1 ± 19.4 years and the infective episode had been developing for 36.4 ± 72.4 days. The patients received either 500 or 750 mg ciprofloxacin twice daily for a period of 9 days with no topical antibiotic treatment. The bacteriological specimen taken at enrolment was positive in 93% of the patients and led to the isolation of 85 microorganisms, 65% of which were Pseudomonas aeruginosa, Staphylococcus aureus or Proteus mirabilis. At the end of the treatment period, discharge from the ears (the primary clinical evaluation criterion) had ceased in 44/69 (64%) patients examined. The clinical cure rate was 23/39 (59%) for patients treated with 500 mg ciprofloxacin twice daily and 21/30 (70%) for those treated with 750 mg twice daily (difference was not statistically significant). At the end of a 4-week post-treatment follow-up, the clinical relapse rate was 7%. There was no relapse in the patients with chronic otitis which had been bacteriologically documented. Eight adverse effects were observed in five patients and treatment had to be discontinued in one case. This study shows ciprofloxacin to be an effective and safe agent for use in the treatment of acute exacerbations of chronic otitis treated in general practice. In certain cases, however, additional treatment with a topical antibiotic may be desirab

ISSN:0009-3157    

DOI:10.1159/000239314

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The postantibiotic effect (PAE), the postantibiotic sub-MIC effect (PA SME), and the sub-MIC effect (SME) of a new oral quinolone, sparfloxacin, were determined for different strains of gram-negative bacteria. A PAE was induced by 10 x MIC of sparfloxacin for 2 h and the antibiotic was then eliminated by washing and dilution. The PA SME was studied by adding different sub-MICs during the postantibiotic phase, and the SME by exposing the controls to the sub-MICs alone. Growth curves were followed for 20 h by continuous monitoring of optical density in an automatic incubator. Sparfloxacin induced a PAE of 0.9-2.4 h for all strains except two clinical strains of Entero-bacter cloacae. In accordance with earlier experiments with sparfloxacin and gram-positive bacteria, this study showed a PA SME that was nearly equal to the PAE plus the effect of the subinhibitory concentration alone (SME).

ISSN:0009-3157    

DOI:10.1159/000239167

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Malignant external otitis is a serious infection most frequently caused by Pseudomonas aeruginosa. Because of its antipseu-domonal activity and good tissue penetration, ciprofloxacin is an antibiotic which should, in theory, be effective in the treatment of this type of infection. Publications on the use of ciprofloxacin in the treatment of malignant external otitis are analysed below. This paper analyses 84 clinical case studies collected from 13 publications: ciprofloxacin, administered for the most part orally, was given in a dosage of 750 mg twice daily, apart from three studies where a lower dosage of 500 mg twice daily was used. When the drug was administered parenterally, the dosage was 200 mg b.i.d. In one publication, ciprofloxacin was used in combination with rifampicin. The average duration of treatment was 3 months. Ps. aeruginosa was isolated in 82 patients and sensitivity tests were carried out on 47 strains, none of which was resistant to ciprofloxacin. The clinical cure rate was 96.4% (84 patients). The rate of bacteriological eradication was close to 100% in the 76 evaluable patients. Long-term follow-up (between 2 and 44 months) showed that clinical and bacteriological cure was maintained in all but two patients. Ciprofloxacin thus seems to be a particularly useful antibiotic for the treatment of malignant external otitis, both because of its clinical and bacteriological efficacy and because it is well tolerated.

ISSN:0009-3157    

DOI:10.1159/000239315

出版商:S. Karger AG    

年代:1994

数据来源: Karger