Gene/Protein Disease Symptom Drug Enzyme Compound
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The wide and potent in vitro activity of cefixime, a new oral broad spectrum cephalosporin, has been confirmed on a collection of respiratory and urinary pathogens recently isolated in Italy. The new cephem emerged as the most bactericidal of all the comparators tested against several fast as well as slowly-growing gram-negative species including Enterobacteria, Haemophilus and Moraxella, irrespective of their ability to synthetize beta-lactamases. Among the gram-positive species Streptococcus pyogenes and S. pneumoniae were effectively covered. Cefixime activity was not adversely influenced by several important variables such as pH (over the range from 5 to 8), inoculum size (from 10(5) to 10(8) CFU per ml) and the presence of 50% human serum or urine. Time-kill tests confirmed a pronounced bactericidal potency of the drug especially towards common respiratory pathogens (H. influenzae, M. catarrhalis, S. pneumoniae and S. pyogenes). Killing of urinary strains was optimal at cefixime concentrations reached in urine since eradication, except for Proteus mirabilis, was enhanced with increasing levels of the drug. The absence of an untoward paradoxic effect on the rate of cefixime bactericidal action was confirmed by employing a dynamic bladder model simulating the pharmacokinetic parameters of the drug after a single 200 mg daily dosage. Interactions of cefixime with several other drugs that may be employed in combination therapy were generally prone to provide indifference and synergism while antagonism was never observed. Favorable interactions were also registered when cefixime acted with other antibiotics on partially resistant species such as Staphylococci and Pseudomonas. The new cephem seems to provide excellent opportunities for expanding oral cephalosporin therapy to a wide range of infections produced by susceptible pathogens in the adult and pediatric populations.
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PMID:Parameters characterizing the in vitro activity of cefixime, a new oral broad spectrum cephalosporin, against respiratory and urinary pathogens. 151 6

Following determination of MICs and MBCs of spiramycin and trimethoprim by the broth microdilution method for 16 typable (including 13 type b) and 15 nontypable H. influenzae isolates, bactericidal synergy was tested by the chequerboard method and the time-kill curve methods. Nineteen (13 typable and six nontypable) of 31 strains demonstrated synergy by the chequerboard method. Ten strains showed indifference, and two manifested antagonism. In contrast, 12/13 strains tested by the time-kill method showed synergy and 1/13 demonstrated indifference. Of note was the finding that seven isolates that showed indifference by chequerboard method (three typable, four nontypable) manifested synergism by the kill-curve method. Of the two nontypable strains showing antagonism by chequerboard, one manifested synergy and the other indifference by the time-kill method. Our studies show that in-vitro synergy between spiramycin and trimethoprim against H. influenzae strains is frequently demonstrable. In-vivo studies may be helpful in confirming these in-vitro observations.
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PMID:Spiramycin alone and in combination with trimethoprim against Haemophilus influenzae. 326 55

We investigated the combination of teicoplanin and ceftriaxone for its bactericidal activity against Staphylococcus aureus, Haemophilus influenzae type b and Streptococcus pneumoniae isolated from bone and joint infections in children. An increase in bactericidal activity was observed against isolates of S. aureus and H. influenzae when the antibiotics were tested at fractional MICs whereas indifference was observed at their MICs. Similar results were obtained at fractional MICs against S.pneumoniae, but the bactericidal activity fell by more than 1 x log 10 cfu/mL when the antibiotics were tested at or above their MICs.
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PMID:In-vitro activity of teicoplanin and ceftriaxone in combination against pathogens involved in paediatric bone and joint infections. 893 66

The activity of the antiseptic polyhexanide was tested against 250 gram-negative clinical isolates, that is, 50 isolates each of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Moraxella catarrhalis, and Haemophilus influenzae. Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were determined by using a serial broth microdilution technique according to DIN 58940. Time-kill studies were performed for reference stains E. coli ATCC 25922, K. pneumoniae ATCC 4352, P. aeruginosa ATCC 15442, M. catarrhalis ATCC 43617, and H. influenzae ATCC 49247. All tested isolates had MICs and MBCs within a range of 1-32 mg/L and were regarded as susceptible to polyhexanide. The highest values were found for P. aeruginosa and H. influenzae with MICs and MBCs of 32 mg/L. Addition of up to 4% albumin to the test medium did not change MICs and MBCs. Time-kill studies of the reference strains showed reduction rates from 3 log10 colony forming units (CFU)/ml to more than 5 log10 CFU/ml for 200 and 400 mg/L polyhexanide within 5-30 min. Testing of polyhexanide in combination with antibiotics showed indifference with amoxicillin, cefotaxime, imipenem, gentamicin, and ciprofloxacin; no antagonism was found. As no resistance and no antagonism with antibiotics were detected, polyhexanide is regarded as suitable agent for topical eradication of gram-negative bacteria.
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PMID:Activity of the antiseptic polyhexanide against gram-negative bacteria. 2419 97