Assessment by Time-Kill Methodology of the Synergistic Effects of Oritavancin in Combination with Other Antimicrobial Agents against
 Staphylococcus aureus

Belley, Adam; Neesham-Grenon, Eve; Arhin, Francis F.; McKay, Geoffrey A.; Parr, Thomas; Moeck, Greg

doi:10.1128/aac.00361-08

Cited by 71 publications

(53 citation statements)

References 21 publications

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“…Our results also show that the concentrations at which these effects are measured were critical and that favorable effects with rifampin may only clearly appear when the drug is used at suboptimal concentrations. Our observation that the combination of oritavancin with other antistaphylococcal drugs is systematically favorable is in line with observations made with S. aureus strains with various resistance phenotypes when they are exposed to combinations of oritavancin with gentamicin, vancomycin, or rifampin (6,7,18). A second key observation is that the combination of rifampin with oritavancin was markedly and almost always synergistic, with a global effect suggesting that near eradication of an intracellular SCV strain could be obtained.…”

Section: Vol 53 2009 Effect Of Combined Antibiotics On S Aureus Scsupporting

confidence: 74%

“…We may, however, speculate that the systematically favorable effects seen with oritavancin could be related (i) to its intense bactericidal effect, probably due to membrane-destabilizing properties (11,17) that may favor access to target for other antibiotics (6), and/or (ii) to the high concentration that oritavancin reaches in the phagolysosomes (28) where SCV strains also locate (21). The negative effect exerted by all antistaphylococcal drugs, except oritavancin, toward rifampin when tested at high concentrations also requires further explanation.…”

Section: Vol 53 2009 Effect Of Combined Antibiotics On S Aureus Scmentioning

confidence: 99%

“…In the first instance, antibiotics were combined as follows: (i) at their respective static concentrations (i.e., the extracellular concentration causing no apparent change in the intracellular CFU count compared to the postphagocytosis inoculum [C s ], as obtained from previous dose dependence experiments with each antibiotic [see Table 1 in this paper for values and Table 2 in reference 21 for pharmacological descriptions of concentration-effect relationships]) and (ii) at an extracellular concentration corresponding to the maximal serum concentration (total drug) observed in patients after administration of conventional doses of the corresponding antibiotic to humans ([C max ]see Table 2 in this paper for individual values and Table 1 in reference 21 for references). To check that the increases in activity seen when antibiotics are combined at their C max values were not due to a carryover effect upon plating of cell lysates containing high intracellular concentrations of antibiotics, we compared bacterial counts from cultures exposed to cell lysates incubated for 24 h with antibiotics at their C max values; samples were then either left untreated or treated with an equal volume of 25 mg/ml activated charcoal suspension (6). No difference was seen between samples treated with charcoal or left untreated or between samples exposed to cell lysates challenged by antibiotics or to unchallenged lysates, ruling out that any carryover effect could take place under our experimental conditions.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Intracellular Activity of Antibiotics in a Model of Human THP-1 Macrophages Infected by a Staphylococcus aureus Small-Colony Variant Strain Isolated from a Cystic Fibrosis Patient: Study of Antibiotic Combinations

Nguyen

Denis

Vergison

et al. 2009

Antimicrob Agents Chemother

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In a companion paper (H. A. Nguyen et al., Antimicrob. Agents Chemother. 53:1434-1442, 2009), we showed that vancomycin, oxacillin, fusidic acid, clindamycin, linezolid, and daptomycin are poorly active against the intracellular form of a thymidine-dependent small-colony variant (SCV) strain isolated from a cystic fibrosis patient and that the activity of quinupristin-dalfopristin, moxifloxacin, rifampin, and oritavancin remains limited (2-to 3-log CFU reduction) compared to their extracellular activity. Antibiotic combination is a well-known strategy to improve antibacterial activity, which was examined here against an intracellular SCV strain using combinations with either rifampin or oritavancin. Time-kill curve analysis using either concentrations that caused a static effect for each antibiotic individually or concentrations corresponding to the maximum concentration in human serum showed largely divergent effects that were favorable when antibiotics were combined with rifampin at low concentrations only and with oritavancin at both low and high concentrations. The nature of the interaction between rifampin, oritavancin, and moxifloxacin was further examined using the fractional maximal effect method, which allows categorization of the effects of combinations when dose-effect relationships are not linear. Rifampin and oritavancin were synergistic at all concentration ratios investigated. Oritavancin and moxifloxacin were also synergistic but at high oritavancin concentrations only. Rifampin and moxifloxacin were additive. This approach may help in better assessing and improving the activity of antibiotics against intracellular SCV strains.Small-colony variant (SCV) strains of Staphylococcus aureus are notoriously difficult to eradicate with most commonly used antistaphylococcal agents (30). Failures favor both selection and acquisition of antibiotic resistance because SCV strains are hypermutators (8). In the companion paper (21), we compared the intracellular activity of a series of 13 antibiotics against a methicillin-susceptible thymidinedependent SCV strain isolated from a cystic fibrosis (CF) patient. We showed that most of these antibiotics are poorly active, with only moxifloxacin, rifampin, and oritavancin able to decrease the intracellular inoculum to less than 1% of the initial value.Antibiotic combination is a well-known strategy both to prevent the emergence of resistant organisms and to increase activity against extracellular organisms thanks to additive, and even sometimes synergistic, effects between coadministered drugs (12,23). Available data suggest that combining antibiotics can improve intracellular activity against both normal and SCV phenotypes of S. aureus strains (2-4). These studies, however, used only a limited number of antibiotics and fixed concentrations, making it difficult to appreciate the exact nature of interactions between combined drugs. We therefore undertook to reexamine this issue by including a series of commonly used antibiotics. These were combined with either rifamp...

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Section: Vol 53 2009 Effect Of Combined Antibiotics On S Aureus Scsupporting

confidence: 74%

Section: Vol 53 2009 Effect Of Combined Antibiotics On S Aureus Scmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Intracellular Activity of Antibiotics in a Model of Human THP-1 Macrophages Infected by a Staphylococcus aureus Small-Colony Variant Strain Isolated from a Cystic Fibrosis Patient: Study of Antibiotic Combinations

Nguyen

Denis

Vergison

et al. 2009

Antimicrob Agents Chemother

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“…Synergy between oritavancin and gentamicin, linezolid, or rifampin against 1 methicillin-susceptible strain and 2 MRSA strains (1 VISA and 1 VRSA strain) has been described (8). In this study, we examined the in vitro activities of oritavancin and comparators against 200 recent MRSA isolates.…”

mentioning

confidence: 99%

Antistaphylococcal Activity of Oritavancin and Its Synergistic Effect in Combination with Other Antimicrobial Agents

Lin

Pankuch

Appelbaum

et al. 2014

Antimicrob Agents Chemother

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Oritavancin exhibited in vitro activity against 169 strains of vancomycin-susceptible, methicillin-resistant Staphylococcus aureus (MRSA) with MICs ranging from 0.03 to 1 g/ml and against vancomycin-intermediate MRSA (VISA; n ‫؍‬ 29), heterogeneous vancomycin-intermediate MRSA (hVISA; n ‫؍‬ 5), and vancomycin-resistant MRSA (n ‫؍‬ 5) strains, with MICs ranging from 0.12 to 4 g/ml. For 10 MRSA isolates comprising 5 VISA and 5 hVISA strains, synergy between oritavancin and gentamicin, linezolid, or rifampin was observed against most of the strains tested using a time-kill method.

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“…Furthermore, comparison of results between them is not possible due to variations in techniques and the criteria to classify the interactions. 6,37,38) It should be noted that the checkerboard method assesses bacteriostatic activity only, while time-kill studies test both bacteriostatic and bactericidal activities. This discrepancy has been documented by different investigators.…”

Section: Resultsmentioning

confidence: 99%

Cooperative Behavior of Fluoroquinolone Combinations against Escherichia coli and Staphylococcus aureus

Vitorino

Becerra

Barrera

et al. 2017

Biological & Pharmaceutical Bulletin

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The effects of different combinations of ciprofloxacin (CIP) and norfloxacin (NOR) against Escherichia coli and Staphylococcus aureus were studied using checkerboard, fractional inhibitory concentration (FIC) and time-kill analysis methods. Results obtained by the checkerboard method showed that the more effectives combinations against Escherichia coli were 0.0009 µg/mL CIP 0.0312 µg/mL NOR and 0.0037 µg/mL CIP 0.0075 µg/mL NOR with a FIC index of 0.62. For Staphylococcus aureus, the combination of 0.0625 µg/mL CIP 0.2500 µg/mL NOR showed a synergistic effect, with a FIC index of 0.50. The results of the time-kill method demonstrated either indifference or additivity of the combinations 0.0009 µg/mL CIP 0.0312 µg/mL NOR, 0.0018 µg/mL CIP 0.0312 µg/mL NOR, 0.0037 µg/mL CIP 0.0075 µg/mL NOR and 0.0037 µg/mL CIP 0.0156 µg/mL NOR at 24 h against E. coli. The combination 0.0037 µg/mL CIP 0.0312 µg/mL NOR showed synergistic activity. All the analyzed combinations evidenced bactericidal effects at 4 h. The combinations 0.0625 µg/mL CIP 0.2500 µg/mL NOR and 0.0625 µg/mL CIP 0.0625 µg/mL NOR showed indifference or additivity against S. aureus. None of them generated bactericidal effect at 4 h. Moreover, this last equimolecular combination (equivalent to 1/4 minimum inhibitory concentration (MIC) CIP 1/16 MIC NOR) generated higher reduction of nitro blue tetrazolium than drugs alone. By another way, combinations not equimolecular of CIP and NOR assayed, generated less levels of reactive oxygen species (ROS) than the components alone.

show abstract

Assessment by Time-Kill Methodology of the Synergistic Effects of Oritavancin in Combination with Other Antimicrobial Agents against Staphylococcus aureus

Cited by 71 publications

References 21 publications

Intracellular Activity of Antibiotics in a Model of Human THP-1 Macrophages Infected by a Staphylococcus aureus Small-Colony Variant Strain Isolated from a Cystic Fibrosis Patient: Study of Antibiotic Combinations

Intracellular Activity of Antibiotics in a Model of Human THP-1 Macrophages Infected by a Staphylococcus aureus Small-Colony Variant Strain Isolated from a Cystic Fibrosis Patient: Study of Antibiotic Combinations

Antistaphylococcal Activity of Oritavancin and Its Synergistic Effect in Combination with Other Antimicrobial Agents

Cooperative Behavior of Fluoroquinolone Combinations against <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>

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