摘要:

The in vitro distribution of the antimalarial drug halofantrine was measured in drug-preincubated whole blood after separation of the blood cells from the plasma according to their type. In normal blood, halofantrine was mainly associated with plasma (85% of the total drug) and to a lesser degree with erythrocytes (11%). The drug accumulated in lymphocytes to an approximately 250-fold higher concentration than in normal erythrocytes, but this represented only a small fraction (1%) of the total drug. It was not significantly bound to thrombocytes (2%), lymphocytes (1%) or granulocytes (0.3%). The distribution of halofantrine into Plasmodium falciparum-parasitised red blood cells was measured at different parasite stages and with varying serum concentrations. Halofantrine accumulated in P. falciparum-parasitised red blood cells to concentrations up to 60-fold those found in normal erythrocytes. The amount of accumulated drug depended on the parasite stage and presence of serum, since mature parasites showed the highest accumulation, and serum reduced drug accumulation compared to incubation under standard cultivation conditions.

ISSN:0009-3157    

DOI:10.1159/000239337

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The binding of five structurally diverse β-lactam antibiotics to penicillin-binding proteins (PBPs) of two clinical isolates of Streptococcus pneumoniae resistant to penicillin G was compared with that of a susceptible strain. A common feature of the PBP patterns of the resistant strains was the absence of PBP la detected in the susceptible strain. For each β-lactam antibiotic tested, there appeared to be significant decreases in the affinity for BPB 1b, 2a and 2b of the resistant strains. We attempted to evaluate a quantitative correlation between the antibacterial activity of the drugs for three strains and their affinity for the various PBPs. A close correlation was found between the minimum inhibitory concentrations and the affinity for PBP 2a, but not for any of the other PBP

ISSN:0009-3157    

DOI:10.1159/000239338

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Susceptibility to penicillin, vancomycin, imipenem, streptomycin, kanamycin and gentamicin was tested in 130 clinical isolates of Enterococcus 8 mg/l) was only observed among strains of Enterococcus faecium and Enterococcus raffinosus. Thirty-nine percent of the penicillin-resistant enterococci showed low-level resistance to at least one of the three aminoglycosides tested (gentamicin, kanamycin and streptomycin). Six Enterococcus strains (5 E. faecium and 1 E. raffinosus 200 mg/l) were tested. No synergy was observed when penicillin concentrations were below the MICs.

ISSN:0009-3157    

DOI:10.1159/000239339

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We detected a novel protein with [14C]benzylpenicillin (PCG)-binding capacity and a molecular mass of about 60 kD in methicillin-resistant Staphylococcus aureus using a high concentration of [14C]PCG and extending the reaction time. However, the fluorogram showed that the band density of penicillin-binding protein 2′ (PBP2′) decreased gradually with incubation time. The appearance of the 60-kD protein and the reduction of the band density of PBP2′ were stoichiometrically linked, and the binding profiles of β-lactams for PBP2′ and the 60-kD protein corresponded. These results suggested that the 60-kD protein is a degradation product

ISSN:0009-3157    

DOI:10.1159/000239340

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The effects of a subminimal inhibitory concentration (sub-MIC) of cefodizime on the bactericidal activity of phagocytes against encapsulated Klebsiella pneumoniae were studied in an in vitro system using an established mouse macrophage cell line, and in an in vivo system using mice in which many phagocytes were induced in the peritoneal cavity. In the in vitro system, the bactericidal activity of mouse macrophages against K. pneumoniae treated with a sub-MIC of cefodizime was significantly enhanced, and was greater than that of cefotaxime or cefoperazone. Significantly more bacteria treated with a sub-MIC of cefodizime were killed by serum complement than those treated with cefotaxime or cefoperazone. In the in vivo system, cefodizime-treated bacteria were phagocytosed and killed by phagocytes in the mouse peritoneal cavity, whereas, cefotaxime- and cefoperazone-treated and untreated bacteria were hardly phagocytosed at all or killed by phagocytes in the mouse peritoneal cavity, and bacterial regrowth was observed 24 h after bacterial challenge. Furthermore, the virulence of K. pneumoniae in mice was reduced more by treatment with cefodizime than with cefotaxime or cefoperazone. These findings indicate that K. pneumoniae treated with a sub-MIC of cefodizime become more susceptible to the bactericidal activity of phagocytes both in vitro and in vivo. This provides evidence that cefodizime at a sub-MIC may act together with the phagocytes against bacterial infections.

ISSN:0009-3157    

DOI:10.1159/000239341

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Seven amikacin-resistant strains of Enterobacteriaceae isolated in Slovakia and Germany were included in this study. The strains were also resistant in vitro to high levels of gentamicin, tobramycin, netilmicin and isepamicin. Phosphocellulose paper binding assays indicated that resistance to aminoglycosides was due to synthesis of aminoglycoside acetyltransferase AAC(6′)-I in combination with aminoglycoside phosphotransferase APH(2XXX), a mechanism until now only identified in staphylococci and streptococci. This mechanism of aminoglycoside resistance has also been found in two isolates of Klebsiella pneumoniae from Germany. The substrate profile suggested that in addition to AAC(6′)-I and APH(2XXX), several strains also produced AAC(3)-II. Aminoglycoside resistance was found to be transferable to Escherichia coli 3110 rifr in all isolates, and R plasmids of 36-45 MD were detected in donor and transconjugant strains. All isolated plasmids from transconjugants encoded resistance to aminoglycosides by genes encoding the enzymes AAC(6′)-I and APH(

ISSN:0009-3157    

DOI:10.1159/000239342

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

During surveillance studies, a total of 66 strains of gram-negative bacilli (28 Enterobacter cloacae, 20 Serratia marcescens and 18 Pseudomonas aeruginosa) with a reduced susceptibility to third-generation cephalosporins, aztreonam and amikacin were isolated from documented infections. All isolates were highly susceptible to imipenem and sparfloxacin. β-Lactamase activity was demonstrated in all isolates of E. cloacae and S. marcescens, and in 77% of P. aeruginosa isolates. Inducible β-lactamase activity was detected in 80, 65 and 40% of E. cloacae, S. marcescens and P. aeruginosa isolates, respectively, when cefoxitin was used as an inducer. More inducible β-lactamase producers were observed when imipenem was used as an inducer. Isolates of E. cloacae, and to a lesser extent S. marcescens, expressed a wide spectrum of β-lactamase activities. There was a good correlation between baseline β-lactamase activity and the respective MIC of ceftazidime, cefotaxime and ceftriaxone, and to a lesser extent aztreonam in E. cloacae and S. marcescens isolates. Only one isolate of E. cloacae demonstrated an extended β-lactamase activity. The data suggest that the resistance of E. cloacae and S. marcescens isolates to β-lactam antibiotics is largely dependent upon hyperproduction of β-la

ISSN:0009-3157    

DOI:10.1159/000239343

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The in vitro susceptibility of a rare fungal pathogen, Mucor ramosissimus Samutsevitsch, to antimycotics in clinical use was determined. Minimal inhibitory concentrations (MICs) and minimal fungicidal concentrations (MFCs) were (MIC/MFC, μg/ml): amphotericin B, 3.125/25; miconazole, 6.25/ 6.25; clotrimazole, 25/25; fluconazole, 5-fluorocytosine, itraconazole, and ketoconazole, ≥100/100. Our results show that amphotericin B and miconazole are the most effective antimycoti

ISSN:0009-3157    

DOI:10.1159/000239344

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Today Mycobacterium avium and Mycobacterium tuberculosis multidrug resistance are responsible for frequent and severe infections in humans and especially in AIDS patients. Irloxacin is a new quinolone derivate, and shows greater activity with an acid pH. It has a good in vitro antimicrobial spectrum against both gram-positive and gram-negative bacteria. We have compared the in vitro activity of irloxacin against mycobacteria (20 M. tuberculosis, 17 M. avium, 5 Mycobacterium bovis, 5 Mycobacterium chelonae, 5 Mycobacterium fortuitum and 1 Mycobacterium gadium)using the Bactec at pH 6.8 and 5.0, with other quinolones (ofloxacin, ciprofloxacin, pefloxacin and 27753 RP). All quinolones tested showed good activity against mycobacteria at pH 6.8 and 5.0. Irloxacin at pH 5.0 had a greater activity agianst M. avium.

ISSN:0009-3157    

DOI:10.1159/000239345

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Renal scarring, which occurs following refluxing pyelonephritis, is considered to be involved in the development of reflux nephropathy. Prevention of renal scar formation requires immediate initiation of antimicrobial treatment; treatment delay results in renal scarring. We demonstrate that Ebselen, an antioxidant agent, given at a dose of 15 mg/kg twice a day prevents renal scarring in rats following direct renal parenchymal bacterial inoculation. In addition, using an ascending pyelonephritis model, which clinically resembles refluxing pyelonephritis in humans, we show that when initiation of antimicrobial treatment was delayed, coadministration of Ebselen prevents renal scar formation. These results show that Ebselen is effective in preventing renal scarring and suggest that the clinical use of this drug may prevent renal scar formation following pyelonephritis and progression to reflux nephropathy.

ISSN:0009-3157    

DOI:10.1159/000239346

出版商:S. Karger AG    

年代:1995

数据来源: Karger