Biomedical subjects
Publications and source records attributed to H Knothe.
Framycetin was tested against a variety of isolates of grampositive and gramnegative bacteria. The in-vitro activity of Framycetin against Staphylococcus aureus, Enterobacteriaceae, Pseudomonas aeruginosa as well as Pseudomonas fluorescens is today still favourable.
The always growing number of cephalosporins constitutes a significant part of the betalactam antibiotics. Depending on antibacterial spectrum and in vitro activity, different groups, e.g. the "cefuroxime-group" and the "cefotaxime-group" have been defined. Based on epidemiologic and comparative in vitro data, the present review offers some guidance where the less expensive cephalosporins of the "cefuroxime-group" may still be clinically useful.
It is often proposed that the indiscriminate use of antimicrobial agents in the veterinary field leads to increased resistance in bacteria pathogenic to humans. Although for human medicine there is some potential danger behind the use of antimicrobial agents in animals, very few species (such as Staphylococci, Salmonella, Escherichia coli, Yersinia and Campylobacter) isolated in animals, which are also pathogenic to man, have been mentioned in the literature. The present paper analyzes the areas and bacteria where the clinician faces problems in the treatment of infection in man.
Cefodizime is a bactericidal cephem with the typical broad spectrum activity of an aminothiazolyl cephalosporin, including both gram-positive and gram-negative bacteria: its MIC90 is 0.125 mg/l for Streptococcus pneumoniae, Streptococcus pyogenes and other streptococci; and 0.05 mg/l for Haemophilus spp., Neisseria meningitidis, Neisseria gonorrhoeae and Moraxella catarrhalis; while beta-lactamase positive strains of M. catarrhalis require 1 mg/l. Less than 1 mg/l is needed for Escherichia coli, Klebsiella spp., Proteus spp. and Shigella spp. The MIC90 is 4 mg/l for methicillin-sensitive Staphylococcus aureus, Morganella morganii, Providencia spp. and most strains of Serratia marcescens, Citrobacter spp. and Enterobacter spp. Staphylococcus epidermidis, Enterococcus faecalis and most strains of Pseudomonas spp. and Acinetobacter spp. are considered cefodizime-resistant. Cefodizime is unaffected by plasmid-mediated beta-lactamases, but it is hydrolyzed by some chromosomally mediated enzymes, thus resembling other third-generation cephalosporins. Cefodizime has high affinity for PBP 3 and PBP IA and IB (Escherichia coli); in S. aureus it shows the highest affinity for PBP 1.
Cefodizime has been shown to possess high in vivo antibacterial activity in a variety of experimental infection models involving different body systems and animal species: systemic infections, pneumonia and urinary tract infections in normal mice, intrauterine infections in normal rats, and meningitis in normal rabbits, as well as systemic infections in immunosuppressed animals. Most investigations found that the therapeutic efficacy of cefodizime frequently exceeded the one expected from its in vitro values and in many cases compared favorably with those of other cephems, even when the in vitro susceptibility of the infecting organism to these drugs was markedly higher. These findings have been attributed either to the superior kinetic profile of cefodizime--prolonged serum half-life and excellent tissue penetration with long-lasting levels--or to a synergy between its high bactericidal activity and host defence mechanisms. The parallel consideration of the MIC90 values of cefodizime and the pharmacokinetic profile of this agent in humans indicate that the vast majority of the relevant respiratory and urinary pathogens are covered by once-a-day cefodizime dosage regimens of either 1 or 2 g.
The effect of single and multiple 2 g doses of i.v. cefpirome on pharyngeal and faecal flora was studied in ten male volunteers. There was no effect on pharyngeal flora. After a single dose, cefpirome had no effect on faecal flora but numbers of Escherichia coli were reduced below the detection limit during multiple dose treatment. No strains of Clostridium difficile were selected in this study and only a slight increase in the numbers of Candida spp. were found. Cefpirome, therefore, has little, if any, effect on faecal or pharyngeal flora.
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The antibacterial activity of the oxacephalosporin flomoxef was evaluated in comparison to cefpirome, cefuzoname, cefotaxime, ceftazidime, and imipenem against fresh clinical isolates. Flomoxef is an antibiotic with strong antibacterial activity against staphylococci including methicillin-resistant strains and streptococci with the exception of Enterococcus faecalis and Enterococcus faecium. It is very active against gram-negative cocci and rods including gram-positive and gram-negative anaerobes. Against Pseudomonas sp. flomoxef has no activity.
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Six strains of P. aeruginosa, resistant to IMI, CTZ and/or AZA, or to two of these drugs even to all three antibiotics, have been analysed by transduction by standard transducing phages F116 and G101, propagated on these strains, as well by a wildtype phage isolated from one of P. aeruginosa strains resistant to CTZ and AZA. Analysis of occurrence of resistance determinants in individual sets of transductants allows us to conclude that all three antibiotic-resistance determinants are separable by transduction and, thus, the resistance to any of these three antibiotics is genetically governed by independent determinants. None strain, resistant to these antibiotics, could hydrolyse any of these drugs, with an exception of slow hydrolysis of IMI, observed also by other investigators [8]. In contrast, strains hydrolysed classical, first-generation cephalosporins as well as Cefoxitin, and transferability of these two determinants could be proved by transfers, to Enterobacteriaceae (P. aeruginosa are naturally resistant to these two antibiotics). Thus, resistance to IMI, CTZ and/or AZA, is not co-transferred, with determinants of resistance to more classical cephalosporins.
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Lomefloxacin (1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4- oxoquinoline-3-carboxylic acid monohydrochloride, SC-47111) is a broad-spectrum antibiotic of the 4-quinolone group. In this comparative study the antimicrobial in-vitro activity of lomefloxacin was tested against 863 gram-negative and 415 gram-positive strains from fresh clinical isolates. As comparative agents ciprofloxacin, norfloxacin and ofloxacin were used. The minimal inhibitory concentrations were determined by means of a serial dilution with the agar-dilution procedure. Lomefloxacin showed an antibacterial efficacy comparable to other quinolones. Ciprofloxacin in general was two-fold dilutions more active. No cross-resistance with beta-lactamase producing-methicillin resistant or aminoglycoside-, tetracycline-, chloramphenicol- and co-trimoxacol-resistant strains could be found. Lomefloxacin showed in this study a broad antimicrobial activity. The clinical utilities of this new fluoroquinolone will depend on the pharmacokinetic properties and the adverse event profile.
The safety, tolerance, and influence on the faecal flora of volunteers of fleroxacin was studied following a daily dose of 800 mg for seven days. A major reduction was seen in the numbers of Escherichia coli, but there was no change in anaerobic bacteria or the faecal streptococci. Ophthalmological examinations and laboratory evaluations revealed no untoward effect. Reduced appetite and flatulence were observed in one volunteer each, two reported loose stools, and five complained of sleep disturbances. All volunteers completed the study.
The aim of this randomised controlled study was to investigate the effect of a preoperative, single dose, intravenous injection of ceftriaxone 2g and cefotaxime 2g in 2 groups of 30 patients who underwent vaginal hysterectomy. The parameters were: efficacy and tolerance; impact on the aerobic bowel and vaginal flora; and serum concentrations. There were no significant differences in efficacy, haematology or clinical chemistry parameters. In the ceftriaxone group 2 patients had exanthemas, 2 had diarrhoea. In the cefotaxime group no such side effects occurred. Serum concentrations were 9.75 and 0.07 mg/L for ceftriaxone and cefotaxime, respectively, after 24 and 12 hours, respectively. Ceftriaxone had a pronounced and continuous effect on the bowel flora: Streptococcus faecium and Candida spp. increased, reaching counts of 10(8) and 10(7) organisms/g faeces, respectively, at day 10. Under cefotaxime no dramatic alteration was determined and growth of Candida spp. was not influenced. Growth of Escherichia coli and other bacteria of the vaginal flora was not influenced by either drug. Overgrowth of Candida spp. under ceftriaxone was significant (p less than 0.05) compared with that under cefotaxime. The results of this study indicate that the high biliary excretion of ceftriaxone (45%) and its long acting properties are responsible for the high selection pressure and overgrowth of Candida. Cefotaxime, a drug with low biliary excretion (5%) and shorter action, had only a negligible effect on the microflora with quick normalisation. The observed overgrowth of Candida spp., even after a single injection of ceftriaxone, could cause problems when this drug is being used for surgical prophylaxis or treatment. This applies especially to immunocompromised patients.
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407 strains of pseudomonas aeruginosa form in-patients and out-patients were serotyped according to Habs' schema. 11.3% of the isolates were non-typable and among the other strains serotypes 6 and 10 were the most prevalent (20.4 and 14.0%, respectively). Type 14 was not observed. Most of the strains isolated from sputum were non-typable, whereas serotype 6 predominated in specimens from urine, wounds and ears. The susceptibility of the isolates to antipseudomonal agents was estimated: 4.7% of the isolates (mainly serotypes 2, 4, and 11) were resistant to gentamicin and among these strains parallel resistance to tobramycin and netilmicin was observed in 47.4%.
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