Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q96DG6 (Pseudomonas)
 76,258 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The combined effect of sisomicin and 6-[(R)-2-[3-methylsulfonyl-2-oxo-imidazolidine-1-carboxamido]-2-phenyl-acetamido-a1-penicillanic acid sodium salt (mezlocillin, Baypen) was studied against 50 bacterial strains, including Pseudomonas aeruginosa, Proteus spp. Klebsiella-Enterobacter, E. coli and Staphylococcus aureus. No antagonism or indifference was detected with the strains studied. Both antibiotics were synergistic against 62% of the strains, and partially synergistic against 38%. Out of the bacteria studied, Staphylococcus aureus was the most susceptible to the combined action of sisomicin and mezlocillin.
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PMID:Synergistic action between sisomicin and mezlocillin against gram-negative bacteria and Staphylococcus aureus. 54 94

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

We determined the effect of the combination of rifampin and fleroxacin against Enterobacteriaceae and streptococcal species. None of the 65 isolates tested by checkerboard assay demonstrated synergy, 12% of isolates showed an additive effect; 86.7% were indifferent, and only 1 isolate showed antagonism. The mean FIC was 1.2. When using 2 and 8 micrograms/ml of rifampin, fleroxacin MICs of 285 isolates of Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenzae, staphylococci, streptococci, Bacteroides, and Clostridium were not increased, but synergy was not demonstrated. Time-kill studies against Escherichia coli, P. aeruginosa, Enterobacter cloacae, Staphylococcus aureus, and Enterococcus faecalis failed to show increased killing when the two agents were present at one-half the MBC. The fleroxacin-rifampin interaction is one of indifference but provides coverage for species not adequately inhibited by fleroxacin.
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PMID:Fleroxacin combined with rifampin. 190 34

Antimicrobial combinations are frequently needed for the successful treatment of serious infections. Generally, the same dosing schedules are employed irrespective of whether the drugs are used singly or in combination. A postantibiotic effect (PAE) has been described for all antibiotics used singly against Gram-positive cocci, but only for non-beta-lactams against Gram-negative bacilli with the exception of carbapenems against Pseudomonas aeruginosa. The major clinical relevance of the PAE pertains to its impact on antimicrobial dosing, where agents inducing a long PAE may be administered with longer dosing intervals than currently employed, without loss of efficacy. The purpose of this study was to examine whether PAEs induced by drug combinations differed from the PAEs induced by the drugs alone, and whether a pattern of synergism, addition or antagonism could be defined in this regard. The study organisms, 7 strains of Staphylococcus aureus, 4 strains of Escherichia coli, 4 strains of Klebsiella pneumoniae and 6 strains of Ps. aeruginosa, were exposed to several beta-lactams, aminoglycosides, rifampin and ciprofloxacin singly and in combination. The antimicrobial combinations used against S. aureus affected the PAE in either an additive or an indifferent manner when compared to the PAEs induced by the drugs as single agents. Enhancement of PAEs against Gram-negative bacilli was primarily dependent on the ability of each individual drug to induce a PAE. Thus, for a combination of drugs where both agents induced a PAE individually, the final PAE was a rough mathematical sum of the individual PAEs (addition). When only one of the agents induced a PAE, the final result was similar to the PAE of that particular drug (indifference). Ciprofloxacin seemed to be an exception to this rule, since it did not increase the PAE of a PAE producing drug, despite exhibiting a PAE itself. Rifampin was unique in that it prolonged the PAE in a marked synergistic fashion, when employed with one or more other PAE-producing agents. Further studies in vivo are clearly needed to confirm these observations, but they could have significant impact on the design of dosing regimens for antimicrobial combinations.
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PMID:The postantibiotic effect induced by antimicrobial combinations. 212 68

Synergy resulting from the combination of ciprofloxacin and an antipseudomonal penicillin has been reported for 20%-50% of isolates of Pseudomonas aeruginosa. A similar effect has also been reported for the combination of ciprofloxacin and fosfomycin. In contrast, the combination of quinolones and aminoglycosides rarely showed synergy when tested against P. aeruginosa. Most studies have shown that the combination of beta-lactams or aminoglycosides with quinolones is indifferent against Escherichia coli, Klebsiella species, Enterobacter species, Citrobacter species, and Serratia species. The combination of ciprofloxacin and chloramphenicol can be antagonistic against E. coli. In general, the combination of quinolone antibiotics with other drugs tested against staphylococci, enterococci, and anaerobic species has shown indifference. The neutropenic mouse model of infection has demonstrated the synergistic effect of ciprofloxacin plus antipseudomonal penicillins; the combination of ciprofloxacin and rifampin has been superior to single agents in experimental Staphylococcus aureus osteomyelitis. Ciprofloxacin has been the quinolone studied most thoroughly, and few data are available about the combination of other quinolones with other antimicrobial agents. Overall, the occurrence of synergy when quinolones are combined with other antimicrobial agents is infrequent, and clinical studies that demonstrate the clinical relevance of data from in vitro and animal models of infection are not available. However, data from in vitro and animal model studies indicate that the combination of a quinolone with other antimicrobial agents rarely results in antagonism.
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PMID:Synergy of fluoroquinolones with other antimicrobial agents. 250 55

The in vitro activity of the new aminoglycoside dactimicin in comparison to amikacin was tested alone and in combination with piperacillin, mezlocillin and ceftazidime against freshly isolated clinical pathogens. Dactimicin was more active than amikacin against Enterobacter cloacae, Providencia rettgeri and Salmonella spp., and less active than amikacin against Escherichia coli, Pseudomonas aeruginosa and Acinetobacter anitratus. Using the checkerboard technique, the combination of either dactimicin or amikacin with the other drugs was shown to result in synergistic interaction against most of the 23 strains tested. Dactimicin-ceftazidime and amikacin-ceftazidime were the most effective combinations, demonstrating synergism against 91% and 95% of the isolates respectively. Antagonism was not encountered. Using the time-kill method, synergism was seen in most cases, indifference rarely being seen; antagonism was not observed. Dactimicin induced a post-antibiotic effect which ranged from 1 h for Enterobacter cloacae to 2.4 h for Escherichia coli. An average post-antibiotic effect of 0.6 h was also seen when dactimicin was combined with piperacillin, mezlocillin and ceftazidime. The findings indicate that dactimicin compares favorably in vitro with amikacin and suggest that clinical trials with this drug alone or in combination are warranted.
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PMID:Dactimicin, a new aminoglycoside: in vitro activity, post-antibiotic effect and interaction with other antibiotics. 250 28

The bacteriolytic combination effect of cefminox (a potent bactericidal cephamycin) and piperacillin (a broad spectrum ureidopenicillin) was investigated using turbidimetry and expressed as a measure of the combination effect by the relative ratios of bacteriolytic area under the growth curves. Against 20 strains of Gram-positive and -negative bacteria, simultaneous treatment of both antibiotics showed synergy (five strains), indifference (15 strains) and no antagonistic effect. Pretreatment with piperacillin for 1 h followed by combined treatment with cefminox showed a profound enhancement of the bacteriolytic activity against 12 out of 20 strains, especially against Serratia, Enterobacter and Pseudomonas species. In contrast, pretreatment with cefminox against seven strains gave mainly an indifferent effect (four strains). The turbidimetric method gave results comparable with those obtained from the chequerboard method (FIC index), as far as Gram-positive and some of the Gram-negative bacteria (E. coli, K. pneumoniae, M. morganii) were concerned. For Serratia, Enterobacter and Pseudomonas sp., the turbidimetric method showed synergy or indifference in many cases, whereas the chequerboard method showed antagonism. Marked enhancement of lysis by the combination was ascribed at least partly to the D-amino acid side-chain of cefminox.
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PMID:Bacteriolytic combination effect of cefminox and piperacillin evaluated by turbidimetry. 263 Feb 52

The bactericidal activity of dactimicin, a novel aminoglycoside, has been tested in vitro in combination with piperacillin, mezlocillin and ceftazidime against freshly isolated Gram-negative and Gram-positive aerobes and compared with that of amikacin. Using the checkerboard test, the combination of dactimicin and amikacin with the other drugs resulted in a synergistic interaction with the Enterobacteriaceae strains analysed in 36 out of 39 and 37 out of 39 cases, respectively. Antagonism was never encountered. With the Pseudomonas isolates, indifference prevailed with dactimicin, whereas synergism was observed with amikacin in combination with the other drugs. No case of antagonism was encountered. When the time-kill system was employed, synergism prevailed, indifference was a rare case, and antagonism was not observed. In experiments carried out with dactimicin-susceptible staphylococcal and enterococcal isolates, a synergistic outcome was obtained employing both methods. Dactimicin induced a post-antibiotic effect (PAE) which ranged from about 1 h with Enterobacter cloacae to 3 h with Escherichia coli after exposure of the bacteria for 1 h to 4 x MIC. The PAE was also evaluated employing several drug associations. An average of 0.6 h PAE was apparent when dactimicin was combined with piperacillin, mezlocillin and ceftazidime, and the bacteria were exposed for 1 h to drug concentrations corresponding to one-half their MICs.
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PMID:In vitro bactericidal activity and post-antibiotic effect of dactimicin, a new aminoglycoside, alone and in combination with other antibiotics. 275 11

FCE 22101 is a penem antibiotic with broad in-vitro activity similar to that of imipenem, although less active against Pseudomonas aeruginosa. Combinations of FCE 22101 with ciprofloxacin or gentamicin against methicillin-resistant Staphylococcus aureus and methicillin-resistant Staph. epidermidis resulted in addition or indifference by the chequerboard method. The combination of FCE 22101 and gentamicin against Streptococcus faecalis was usually additive. Against Enterobacter cloacae FCE 22101 had MICs of 16 mg/l whilst in combination with gentamicin (0.25-0.12 mg/l) the MICs were reduced to less than 2 mg/l. Ciprofloxacin and FCE 22101 showed only addition against Enterobacter spp. similar results were obtained with the combinations of FCE 22101 and gentamicin or ciprofloxacin tested against Citrobacter freundii. With Serratia spp. FCE 22101 and gentamicin showed synergy, but FCE 22101 and ciprofloxacin showed indifference. Similar results were obtained with strains of Escherichia coli and Klebsiella, Proteus, and Providencia spp. FCE 22101 plus gentamicin, or aztreonam, against Ps. aeruginosa usually showed indifference, but with ciprofloxacin addition was the rule. In general the combination of FCE 22101 with other agents resulted in an additive rather than a synergistic effect.
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PMID:In-vitro activity of FCE 22101 and synergy studies with other antimicrobial agents. 278 20

Combinations of ciprofloxacin with azlocillin, piperacillin and ticarcillin were tested in vitro against clinical isolates. Azlocillin plus ciprofloxacin showed synergy against 30% of Pseudomonas aeruginosa isolates; it was either synergistic or additive against 78% of all isolates tested even those resistant to the beta-lactam. Synergism was rarely noted for Klebsiella pneumoniae, Escherichia coli, Enterobacter spp. or Branhamella spp. isolates. Minimum inhibitory concentrations of ciprofloxacin plus azlocillin, plus piperacillin and plus ticarcillin against Pseudomonas spp. were reduced 4 or 2 fold, respectively. However, the combination azlocillin plus ciprofloxacin showed primarily indifference against gram-positive strains. Neutropenic mice infected with a lethal challenge of Pseudomonas spp. were protected by a combination of azlocillin and ciprofloxacin. Its additive and/or synergistic effects and expanded spectrum of activity against streptococci, methicillin-resistant staphylococci and JK corynebacteria may provide an alternative to traditional therapy.
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PMID:Synergy of ciprofloxacin and azlocillin in vitro and in a neutropenic mouse model of infection. 293 45


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