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PubMed1995

Cephalosporin binding sites to human serum albumin and the relation with the N-B transition of this protein.

The binding of some cephalosporins to human serum albumin was studied using probes for the so-called I, II, bilirubin and fatty acids binding sites. The results showed that cephradine and cefsulodin bind to site II, cefaclor, cefamandole, cefsulodin, cephaloglycin and cefadroxil bind to the bilirubin binding site, while cefaclor does it to the fatty acid binding site. No binding of these cephalosporins to site I of albumin was found. The binding produced a perturbation on the N-B equilibrium of albumin, stabilizing the N conformational form, which suggests that the N form of albumin has more affinity with the cephalosporins than the B form. This finding gives support to the assumption that the binding of cephalosporins to site II, bilirubin and fatty acids binding sites affects the N-B transition of albumin.

Bilirubin↗
PubMed1994

[Comparative activity of oral beta-lactam antibiotics against fifty strains of Haemophilus influenzae producing a beta-lactamase according to bacterial inoculum].

Minimal inhibitory concentrations (MICs) of amoxycillin alone and in combination with 2 mg/l or 4 mg/l clavulanic acid, ampicillin alone and in combination with 4 mg/l or 8 mg/l sulbactam, cefuroxime and cefaclor, were determined by the agar dilution method, with bacterial inoculum size ranging from 3 x 10(7) to 3 x 10(9) colony-forming units per ml. As expected, an inoculum effect was observed with cefaclor. In contrast, MICs of amoxycillin in combination with clavulanic acid did not significantly increase with the inoculum size. Ampicillin combined with sulbactam, and cefuroxime were less efficient at the highest bacterial concentration tested.

Anti-Bacterial Agents↗
PubMed1994

[Multicenter evaluation of oral antibiotics: resistance behavior in 5 Swiss centers].

The susceptibility of 2196 fresh clinical isolates to twelve different oral compounds was assessed in five Swiss microbiology institutions during summer 1992. A standardized microdilution system including all other material necessary was employed to assess the antibacterial activity of penicillin G, ampicillin, ampicillin + sulbactam, amoxycillin + clavulanic acid, cefadroxil, cephalexin, cefaclor, cefuroxime, cefetamet, doxycycline, erythromycin and clindamycin. The aminopenicillins (including the beta-lactamase inhibitor combinations) were highly active against the streptococci, in combination with a beta-lactamase inhibitor they covered the majority of the bla+ E. coli and Proteus mirabilis and between 60 to 80% of the Klebsiella spp. and Proteus vulgaris isolates. All the cephalosporins exhibited good activity against the streptococci, they were active against Gram-negative fermentative rods to a varying degree. Cefetamet was also active against many cefaclor and cefuroxime-resistant isolates. A considerable part of the species studied exhibited resistance to doxycycline; the observed resistance of S. agalactia, P. mirabilis, and Morganella morganii agreed with previous findings. Most of the Streptococcus spp. were inhibited by erythromycin and clindamycin. There were only single penicillin resistant S. pneumoniae isolates in the five Swiss centers. Taking account of the above particulars the epidemiology of antimicrobial resistance in Switzerland can be considered satisfactory.

Anti-Bacterial Agents↗
PubMedDate not supplied

In vitro activity of clarithromycin, cefprozil, and other common oral antimicrobial agents against gram-positive and gram-negative pathogens.

Macrolide and beta-lactam antimicrobial agents are frequently used for the treatment of upper and lower respiratory tract infections and skin or skin structure infections. To evaluate the relative in vitro activity of these antimicrobial drugs against organisms commonly involved in these infections, we tested clarithromycin, erythromycin, cefprozil, cefuroxime, cefaclor, cephalexin, amoxicillin, amoxicillin/clavulanate, and doxycycline against 174 gram-positive and gram-negative clinical isolates, including Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, group A beta-hemolytic streptococci, alpha-hemolytic streptococci, Escherichia coli, and Klebsiella pneumoniae. Manual broth microdilution susceptibility testing was used with a standard inoculum of 5 x 10(4) colony-forming units/well at pH of 7.2. Clarithromycin was the most active agent against streptococci. Methicillin-susceptible S aureus exhibited resistance to both clarithromycin and erythromycin, but was susceptible to cefprozil, cefuroxime, amoxicillin/clavulanate, and doxycycline. Cefprozil was at least as active as cefuroxime, cefaclor, and cephalexin against all organisms tested, but was fourfold less active than doxycycline against E coli and 16-fold less active than clarithromycin versus S pneumoniae. The gram-negative isolates tested showed resistance to clarithromycin and erythromycin; however, cefprozil was as active as amoxicillin/clavulanate against K pneumoniae and E coli. These results demonstrate that clarithromycin provides superior in vitro activity against common streptococci, while cefprozil, cefuroxime, amoxicillin/clavulanate, and doxycycline provide greater activity against methicillin-susceptible S aureus, K pneumoniae, and E coli. Prospective clinical trials are needed to determine the clinical significance of these findings.

Anti-Bacterial Agents↗
PubMed2003

Modelling and analysing exchangeable binary data with random cluster sizes.

Correlated binary data occur very frequently in cluster sample surveys, dependent repeated cancer screening, teratological experiments, ophthalmologic and otolaryngologic studies, and other clinical trials. The standard methods to analyse these data include the use of beta-binomial models and generalized estimating equations with third and fourth moments specified by 'working matrices'. However, in many applications it is reasonable to assume that the data from the same cluster are exchangeable. When all sampled clusters have equal sizes, Bowman and George introduced maximum likelihood estimates (MLEs) of the population parameters such as the marginal means, moments, and correlations of order two and higher. They also extended their approach to sampled clusters with unequal sizes. It seems that their extension has a gap. This paper points out the source of this gap and shows that estimates introduced by Bowman and George are not the MLEs of the parameters which are used to identify the joint distribution of correlated binary data. We show that the MLEs of the population parameters have no closed form in general and should be calculated by numerical methods. We apply our results and a generalized estimating equation procedure to a data set from a double-blind randomized clinical trial comparing two antibiotics, cefaclor and amoxicillin, used for the treatment of acute otitis media. To see the performance of the MLEs with small or moderate sample sizes, several simulation studies are also conducted.

Amoxicillin↗
PubMed1997

Antimicrobial susceptibility of Streptococcus pneumoniae isolated from pediatric carriers in Spain.

The in vitro activity of several beta-lactam agents, macrolides, and cotrimoxazole was investigated against 53 Streptococcus pneumoniae isolates recovered from healthy children. The rates of resistance to penicillin or amoxicillin, cefaclor, and cefuroxime were 30%, 51%, and 37%, respectively. No cefotaxime-resistant isolates were found. Rates of resistance to erythromycin, clarithromycin, and cotrimoxazole were 22.6%, 13.2%, and 83%, respectively. Pneumococci with divergent antimicrobial susceptibility profiles (susceptible or moderately resistant vs. resistant isolates) coexisted in 32% samples, with divergencies more often involving beta-lactam agents and/or macrolides. In five of these samples, isolates belonged to different serotypes.

Adolescent↗
PubMed1979

[Antibacterial activity of cefotaxim in comparison with seven cephalosporins].

The antibacterial activity of cefotaxim and seven cephalosporins was determined in 1,112 fresh isolates using the microdilution technique. All of the cephalosporins tested were ineffective against enterococci. Cefalotin was the most effective agent against Staphylococcus aureus. Cefaclor was superior to cephalexin against Escherichia coli and Proteus mirabilis, and thus inhibited 20% more Enterobacteriaceae. Cefazolin was as effective as cefamandole against E. coli. Cefuroxime and cefoxitin were almost equally effective against E. coli, Klebsiella and P. mirabilis; more than 95% of the strains were sensitive. Cefuroxime and also cefamandole were much more effective than cefoxitin against Citrobacter and Enterobacter. Cefoxitin on the other hand was superior against Serratia and indol-positive Proteus species. Cefotaxim was by far the most active cephalosporin against Enterobacteriaceae, only 2% of the strains being resistant. More than 90% of the strains of E. coli, Klebsiella, P. mirabilis and Serratia were sensitive to 1 mg/l, the lowest degree of activity being displayed against Enterobacter; 82% of the strains were inhibited by 16 mg/l. Cefotaxim was the only cephalosporin which showed appreciable activity against Pseudomonas.

Bacteria↗
PubMed1988

Comparative in vitro activity of the new quinolone fleroxacin (RO 23-6240).

RO 23-6240 (fleroxacin), pefloxacin, augmentin, cefaclor, cef-uroxime, ceftazidime, vancomycin, piperacillin and amikacin were tested against a wide variety of gram-positive and gram-negative bacteria. The MICs of fleroxacin were very similar to those of pefloxacin. Against all the bacterial groups tested, the quinolones compared favorably with the other antimicrobials tested, particularly against the more resistant species such as Corynebacterium group JK and D2 and methicillin-resistant staphylococci.

Amikacin↗
PubMed1988

Comparative in vitro activity of the new oral cephalosporin cefixime.

Cefixime was 8 to 10 times more active than cefaclor and augmentin against isolates of Escherichia coli, Klebsiella pneumoniae and Salmonella typhi, MIC90 values ranging from 0.06 to 0.25 micrograms/ml. However, none of these three drugs was particularly active against isolates of more resistant gram-negative bacilli such as Enterobacter, Serratia, Citrobacter, Acinetobacter, Providencia and Achromobacter spp. The lowest MIC values for gram-negative bacilli were seen with ciprofloxacin, except for isolates of Acinetobacter, where cotrimoxazole was the most active of the five drugs studied. Augmentin and ciprofloxacin exhibited the lowest MICs for isolates of streptococci and corynebacteria. Although cefixime may be among the most active oral beta-lactam drugs, it does not appear to be useful for treatment of infections caused by more resistant gram-negative bacilli.

Amoxicillin↗
PubMed1992

Killing kinetics of five orally administered antibiotics at clinically achievable concentrations against Moraxella catarrhalis.

Time-kill kinetic studies were used to measure the bactericidal activity of amoxicillin/clavulanic acid (in a new form for pediatric use), cefaclor, cefuroxime, cefixime and erythromycin against 30 beta-lactamase producing Moraxella catarrhalis strains. Antibiotics were tested at the mean maximum serum concentration observed after administration of a standard dose and at 0.5 x Cmax, 0.33 x Cmax and 0.25 x Cmax. A 2 log10 reduction in colony counts was obtained with the Cmax of amoxicillin/clavulanic acid and cefixime after 5 h of incubation. After 24 h of incubation a decrease of 3 and 4 log was observed with cefixime and amoxicillin/clavulanic acid respectively. At 0.5 x Cmax and 0.33 x Cmax, bactericidal activity was obtained only with amoxicillin/clavulanic acid.

Amoxicillin↗
PubMed1988

Surveillance study of resistance in Haemophilus species in Greece.

The results are presented of the first surveillance study in Greece on resistance in strains of Haemophilus influenzae (n = 61) and Haemophilus parainfluenzae (n = 96) to six antibiotics. Strains were isolated in a three-month period in 1987 in most cases from sputum specimens from adult patients with lung infections. The overall rate of resistance to ampicillin was 28.3%, to chloramphenicol 2.7%, to cefaclor 2.7%, to tetracycline 10.6%, to erythromycin 38.1% and to cotrimoxazole 5.3%. It is evident that the resistance rate of Haemophilus spp. is steadily increasing in Greece as in other European countries. Regular surveys of resistance patterns for both older and newer antimicrobial agents are therefore necessary.

Adult↗
PubMed1992

Antibacterial activity of the investigational oral and parenteral cephalosporin BK-218.

BK-218 is a novel cephalosporin with a dual route of administration and spectrum of activity most similar to that of second-generation cephalosporins. BK-218 was active against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis but strains resistant to penicillins had higher MICs. BK-218 had greater activity (8-fold) than cefuroxime or cefaclor against oxacillin-susceptible Staphylococcus spp. Moderate BK-218 activity was observed against Neisseria gonorrhoeae and commonly isolated Enterobacteriaceae such as Escherichia coli (MIC90, 1 mg/l), Klebsiella spp. (MIC90, 2 mg/l), and Proteus mirabilis (MIC90, 2 mg/l). The following organisms were generally BK-218-resistant (MIC90, greater than 16 mg/l): Bacteroides fragilis, Pseudomonas spp., Acinetobacter spp., Xanthomonas maltophilia, Citrobacter spp., Enterobacter spp., indole-positive Proteus, Serratia spp., enterococci and oxacillin-resistant staphylococci.

Cefaclor↗
PubMed1990

Prevalence of antimicrobial resistance in Haemophilus influenzae in Greece, Israel, Lebanon and Morocco.

Between 40 and 43 Haemophilus influenzae isolates obtained from Greece, Lebanon, Israel and Morocco respectively (a total of 167 strains) were analysed for prevalence of resistance to six different drugs. Of these isolates 12.6% produced beta-lactamase and were resistant to ampicillin. All isolates, except a single strain from Greece, were susceptible to cefaclor. The frequency of resistance to chloramphenicol and tetracycline was below 2%. The frequency of isolates susceptible and resistant to erythromycin and cotrimoxazole varied from country to country.

Ampicillin Resistance↗
PubMed1989

Comparative antibacterial activity of the new cephalosporin cefcanel against anaerobic bacteria.

The activity of cefcanel against anaerobic cocci, Clostridium perfringens, Bacteroides fragilis, Bacteroides spp. and fusobacteria was determined by the agar dilution method and compared with the activity of cefaclor, cephalexin, cefadroxil, phenoxymethylpenicillin and ampicillin. Cefcanel showed good activity against Clostridium perfringens, Bacteroides spp. and fusobacteria (MIC90 = 1-4 mg/l). Against anaerobic cocci its MIC90 value was 16 mg/l, and against Bacteroides fragilis, 32 mg/l. Cefcanel has an antibacterial activity that warrants investigation in clinical trials.

Ampicillin↗
PubMed1991

Antimicrobial activity of RU29246 (HR916 metabolite) compared with four other oral beta-lactams tested against more than 5000 clinical isolates.

The activity of RU29246, the active metabolite of the oral cephalosporin ester HR916, was compared in a multicenter study with that of the four oral beta-lactam antibiotics cephalexin, cefaclor, cefixime and amoxicillin/clavulanate (amoxicillin/CA). RU29246 was generally 2- to 8-fold more active than the other oral cephalosporins and comparable to amoxicillin/CA against staphylococci, and was the most active cephalosporin against group B streptococci. All four cephalosporins were ineffective against enterococci. RU29246 was the only cephalosporin consistently active against Acinetobacter, but all beta-lactam antibiotics had poor activity against Pseudomonas spp. and Xanthomonas maltophilia. RU29246 was comparable to cefixime and more active than the other cephalosporins against members of the family Enterobacteriaceae. However, all of the antibiotics had poor activity against Enterobacter cloacae and Serratia marcescens. Quality control reference ranges for the quality control organisms Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 are proposed for the broth dilution method based on data derived from this multicenter study.

Amoxicillin↗
PubMed1994

Comparative studies of cefprozil in the management of skin and soft-tissue infections.

Six multicenter clinical trials comparing cefprozil with cefaclor, amoxicillin-clavulanate or erythromycin in the management of skin and soft-tissue infections caused by susceptible bacteria demonstrate that cefprozil, given once or twice daily, is an effective chemotherapeutic agent in this context. Its pharmacokinetic behavior is compatible with once-daily or twice-daily administration, with a probability of improved patient compliance. Safety and tolerability compare favorably with other agents used in skin and soft-tissue infections.

Adolescent↗
PubMed1991

The inhibitory effect of anti-tumor drugs on phosphatidylcholine synthesis and its reversal by geranylgeranylacetone in the isolated guinea pig gastric glands.

To clarify the mechanism by which the administration of anti-tumor drugs, antibiotics or hypoglycemic agents causes gastric mucosal injury, the effects of these drugs on phosphatidylcholine synthesis in isolated guinea pig gastric glands were examined in vitro. Anti-tumor drugs such as tegafur, cyclophosphamide, and mitomycin C decreased [3H]choline incorporation into phosphatidylcholine. Furthermore, tegafur at 0.4 mg/ml decreased [3H]choline incorporation in the glands that had been pulsed with [3H]choline incorporation, suggesting that tegafur exerts its effect by inhibiting late step of phosphatidylcholine synthesis in the stomach. On the other hand, cefaclor and glibenclamide had no effect on [3H]choline incorporation. Geranylgeranylacetone, an anti-ulcer drug partially restored tegafur-induced reduction of [3H]choline incorporation into phosphatidylcholine. These results suggest that the anti-tumor drug-induced gastric mucosal injury may be due to drug-induced decrease in phosphatidylcholine synthesis, which the restoration of phosphatidylcholine synthesis by geranylgeranylacetone may explain its anti-ulcer action on drug-induced gastric mucosal lesions in vivo.

Animals↗