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PubMed1985

Effects of clindamycin in combination with rifampicin on clindamycin-susceptible and clindamycin-resistant Staphylococcus aureus.

The effects of the combination of clindamycin and rifampicin against 21 strains of clindamycin-susceptible and 19 strains of clindamycin-resistant Staphylococcus aureus were studied by the time-kill method. For the clindamycin-susceptible strains, clindamycin prevented the re-growth of Staph. aureus in the presence of rifampicin. For the clindamycin-resistant Staph. aureus strains, indifference was demonstrated against the majority of strains, with only a few strains showing synergism or antagonism.

Clindamycin↗
PubMed1985

Interaction of gentamicin, dibekacin, netilmicin and amikacin with various penicillins, cephalosporins, minocycline and new fluoro-quinolones against Enterobacteriaceae and Pseudomonas aeruginosa.

Thirty strains of Enterobacteriaceae and ten strains of Pseudomonas aeruginosa were selected to study the in-vitro activity of various combinations containing aminoglycosides, by the checkerboard method. The following aminoglycosides: gentamicin, dibekacin, netilmicin and amikacin were used in combination with each of the following: ampicillin, ticarcillin, piperacillin, cefazolin, cefuroxime, ceftazidime, norfloxacin, enoxacin and minocycline. Synergy was not a constant feature of beta-lactam+aminoglycoside combinations. Discrepancies occurred with the same strain submitted to combinations containing different aminoglycosides. The combinations containing new quinolones+aminoglycosides were usually additive, although occasionally synergy occurred. The combination minocycline+aminoglycoside was usually additive but partial antagonism (FIC or FBC index: 1 X 5- less than 2) occurred in 10 to 40% of the strains depending on the aminoglycoside. The combinations of beta-lactams with dibekacin or netilmicin most frequently produced partial or full synergy against strains of Ps. aeruginosa susceptible to all four aminoglycosides tested.

Amikacin↗
PubMed1985

In-vitro study of the activity of ciprofloxacin alone and in combination against strains of Pseudomonas aeruginosa with multiple antibiotic resistance.

Ciprofloxacin appears to have useful activity against Pseudomonas aeruginosa. We have studied its in-vitro activity against ten strains of Ps. aeruginosa with multiple antibiotic resistance. We have confirmed that ciprofloxacin is very active against Ps. aeruginosa with minimal inhibitory concentrations ranging from 0.07 to 0.7 mg/l. Killing curves show ciprofloxacin to be rapidly bactericidal with no regrowth after 24 h. Checkerboard studies with ciprofloxacin in combination with gentamicin, azlocillin and ceftazidime show no consistent interaction. These studies suggest that ciprofloxacin should prove a useful antibiotic in treating infections caused by multiresistant Ps. aeruginosa.

Anti-Bacterial Agents↗
PubMed1986

Resistance to antibiotics at medical centres in different parts of the world.

The diameters of the zones of inhibition of consecutive clinical isolates around antibiotic susceptibility test discs at medical centres in different parts of the world were computer filed and analysed by a series of programs that evaluate test quality and compare results. Percentages of isolates resistant to ampicillin at 18 centres ranged from 16 to 73 for Escherichia coli and from 3 to 56 for Proteus mirabilis. Percentages resistant to chloramphenicol ranged from 2 to 48 for E. coli, from 5 to 52 for Klebsiella pneumoniae, and from 8 to 67 for Serratia marcescens. Gentamicin resistance did not exceed 4% at any of 18 centres and was less than 1 at 14 of them for isolates of E. coli, while K. pneumoniae showed less than 2% resistance at six centres but averaged 22% at another eight. Multi-resistant isolates were ten-fold more frequent at eight centres than at the remaining six. Too few centres were sampled to characterize individual countries except in the United States where resistance seemed generally less prevalent.

Anti-Bacterial Agents↗
PubMed1988

Bactericidal activity and killing rate of serum in volunteers receiving pefloxacin alone or in combination with ceftazidime, piperacillin or mezlocillin against Pseudomonas aeruginosa.

The activity of the combination of pefloxacin with ceftazidime, piperacillin, or mezlocillin was compared to the activity of the same antibiotics given alone, by measurement of serum bactericidal titres and the rate of killing of ten strains of Pseudomonas aeruginosa. Three groups of five volunteers each received pefloxacin (12 mg/kg iv) with or without ceftazidime, piperacillin or mezlocillin (25 mg/kg iv). Serum samples were obtained at the end of the infusion. The mean serum concentration of pefloxacin at this time was 13.9 mg/l (3.2, S.D.). The activity of each of the three combinations was identical to the corresponding activity of the beta-lactam alone. However, the emergence of resistance to pefloxacin was prevented by ceftazidime (five out of five strains), and piperacillin (two out of five strains). We conclude that combinations of pefloxacin with beta-lactam antibiotics may not increase efficacy against P. aeruginosa.

Anti-Bacterial Agents↗
PubMed1988

Microbiological properties of teicoplanin.

Teicoplanin is a glycopeptide antibiotic structurally related to vancomycin. Both agents achieve their effect by binding to acyl-D-alanyl-D-alanine in the bacterial cell wall. The spectrum of activity of teicoplanin, like that of vancomycin, is restricted to Gram-positive aerobic and anaerobic bacteria. However, the activity of the two agents is not identical: teicoplanin is generally more active than vancomycin against streptococci and Gram-positive anaerobes; the two agents exhibit similar activity against Staphylococcus aureus (including methicillin-resistant strains); and vancomycin is more active than teicoplanin against some strains of coagulase-negative staphylococci. Inoculum size influences the activity of teicoplanin, and variations in activity against some strains of coagulase-negative staphylococci have been observed with different culture media. Resistance to teicoplanin and vancomycin is difficult to induce under laboratory conditions and the small increment in resistance that may develop is lost when the organisms are subcultured in the absence of the drugs.

Anti-Bacterial Agents↗
PubMed1989

In-vitro activity of ciprofloxacin combined with either fusidic acid or rifampicin against Staphylococcus aureus.

Killing kinetic experiments were performed with ciprofloxacin, fusidic acid and rifampicin alone and with ciprofloxacin combined with either fusidic acid or rifampicin against ten strains of Staphylococcus aureus. The strains were all clinical isolates and two strains were methicillin-resistant. The antibiotic concentrations tested were in the range obtainable in the serum with recommended doses. The early bactericidal effect of ciprofloxacin alone was substantially greater than that of fusidic acid or rifampicin; thus the extent of killing after 6 h exposure to these antibiotics was 3.4 log10, 0.8 log10 and 0.6 log10, respectively. Fusidic acid as well as rifampicin antagonized the bactericidal activity of ciprofloxacin. Each combination killed 2 log10 cfu less than ciprofloxacin alone. For each combination the mean decrease in the number of organisms was comparable to that achieved with fusidic acid or rifampicin used alone.

Ciprofloxacin↗
PubMed1989

The prevalence of antibiotic resistance in Haemophilus influenzae in Ireland.

From January to April 1988, 36 clinical microbiology laboratories in Northern Ireland and Eire took part in a survey to determine the prevalence of antibiotic resistance in Haemophilus influenzae. All isolates were collected and despatched to a coordinating laboratory where identification was confirmed and antibiotic sensitivity tests repeated. One thousand seven hundred and ninety strains were available for analysis. Of these, 10.9% were resistant to ampicillin (10.2% being beta-lactamase producers), 0.4% to amoxycillin-clavulanate, 2.1% to cefaclor, 3.7% to chloramphenicol, 2.6% to erythromycin, 4.1% to tetracycline, 2.6% to sulphonamide and 5.1% to trimethoprim. One hundred and nine strains (6.3%) were resistant to two or more of the antibiotics tested and 31 (1.7%) exhibited combined resistance to ampicillin, chloramphenicol and tetracycline. The prevalence of resistance to ampicillin and chloramphenicol was higher than had been previously recorded in largescale studies conducted on the British mainland.

Anti-Bacterial Agents↗
PubMed1993

Effects of betaines and urine on the antibacterial activity of aminoglycosides.

Urine has long been known to inhibit the activity of aminoglycosides against urinary tract pathogens. Glycine betaine which is present in urine confers resistance against high osmolarity to Gram-negative organisms. We postulated that glycine betaine might contribute to the aminoglycoside resistance found in hypertonic urine. Escherichia coli became extremely resistant to gentamicin (40 x MIC in 0.9 M sodium chloride) when cultured in minimal medium supplemented with 10(-4) M glycine betaine and 0.1-1.0 M sodium chloride. Resistance was increased in the presence of high glucose concentrations but to a lesser extent (3 x MIC in 1.0 M glucose). This effect was not produced by other polyols or urea. These results suggest the observed synergism is mediated by the osmoprotective effects of glycine betaine and the inhibitory effect of sodium chloride or glucose against the aminoglycoside. Other betaines tested had a less marked effect. The betaines in urine permit the expression of increased resistance to aminoglycosides in concentrated urine.

Acetylcarnitine↗
PubMed1996

In-vitro activity of teicoplanin and ceftriaxone in combination against pathogens involved in paediatric bone and joint infections.

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.

Bacterial Infections↗
PubMed1996

Resistance to bismuth among gram-negative bacteria is dependent upon iron and its uptake.

Bismuth antimicrobial action is poorly understood. Many trivalent metals possess antibacterial activity, especially under low iron conditions. Protection of bacteria from the deleterious effects of bismuth and other trivalent metals was demonstrated in iron-fortified media. Near-equimolar quantities of Fe3+ neutralized the growth-inhibitory effects of 250 microM Bi3+. Resistance to bismuth action also depended on the production of virulence-related siderophores. Escherichia coli, Aeromonas hydrophila or Pseudomonas aeruginosa producing aerobactin, amonabactin or pyoverdin respectively, were most resistant to Bi3+. Enterochelin or pyochelin producers were less resistant to Bi3+, but more resistant than strains lacking siderophores. Purified pyoverdin restored Bi3+ resistance in a mutant lacking this siderophore, but not in one lacking the pyoverdin receptor. Bismuth-treated bacteria exhibited unique outer membrane proteins, similar in size to iron-repressible proteins. Thus, resistance to the inhibitory action of Bi3+ among Gram-negative bacteria is inversely related to iron concentration and strongly dependent on iron transport mechanisms. The data suggest that bismuth action is largely a nonspecific, competitive interference with iron-transport, related primarily to atomic valence Furthermore, resistance to Bi3+ among bacteria is predictive of virulence.

Bacterial Outer Membrane Proteins↗
PubMed1999

The effects of NorA inhibition on the activities of levofloxacin, ciprofloxacin and norfloxacin against two genetically related strains of Staphylococcus aureus in an in-vitro infection model.

NorA is a membrane-associated multidrug efflux protein that can decrease susceptibility to fluoroquinolones in Staphylococcus aureus. We have previously determined that NorA inhibition can increase fluoroquinolone killing activity and post-antibiotic effect. In the current investigation, we studied the killing activity and development of resistance for levofloxacin, ciprofloxacin and norfloxacin with or without the H+/K+ ATPase inhibitor omeprazole, in a wild-type strain of S. aureus (SA-1199) and its NorA hyperproducing mutant (SA-1199-3) in an in-vitro pharmacodynamic model with infected fibrin-platelet matrices. Each drug was administered every 12-24 h for 72 h and human pharmacokinetics were simulated. Levofloxacin was the most potent fluoroquinolone against both strains and its activity was not significantly affected by combination with omeprazole. The addition of omeprazole to ciprofloxacin significantly lowered colony counts at all time-points against both strains and decreased the time to 99.9% kill from 72.2 h to 33.8 h against SA-1199. The addition of omeprazole minimally increased norfloxacin activity against both strains. Omeprazole decreased the frequency of ciprofloxacin resistance nearly 100-fold at the 24 h time-point, but the frequency of resistance was not significantly different for any of the fluoroquinolone regimens after this time-point. No resistance was detected during levofloxacin regimens. The hydrophobic fluoroquinolones such as levofloxacin appear to circumvent NorA efflux, which may contribute to their better activity and decreased resistance rates against staphylococci. More durable and potent NorA inhibitor compounds are needed that can improve killing activity and prevent resistance.

Anti-Infective Agents↗
PubMed2000

In vitro susceptibility studies of Cryptococcus neoformans isolated from patients with no clinical response to amphotericin B therapy.

The in vitro activities of three antifungal drugs alone and in combination were evaluated against five isolates of Cryptococcus neoformans using time-kill curves (TKC). The isolates were from AIDS patients who had either died or had failed to show a clinical response during amphotericin B (AMB) treatment. AMB, fluconazole (FCZ) and flucytosine (5FC), and combinations of the drugs (AMB plus 5FC, AMB plus rifampicin (RIF) and FCZ plus 5FC), were evaluated. With all five isolates AMB did not show fungicidal activity; instead, a persistent or tolerant effect was observed. Combinations of AMB plus 5FC and AMB plus RIF showed a clear synergic effect, except for one isolate tested with AMB plus RIF. In contrast, the FCZ plus 5FC combination did not inhibit growth of any isolate.

Acquired Immunodeficiency Syndrome↗