scholarly journals Focused review: The role of drug combinations for the control of coccidiosis in commercially reared chickens

2022 ◽  
Author(s):  
H. David Chapman ◽  
Thilak Rathinam
Keyword(s):  
Drug Combinations

scholarly journals Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)–based mutagenesis screen: high efficacy of drug combinations

Blood ◽  
2006 ◽  
Vol 108 (7) ◽  
pp. 2332-2338 ◽  
Author(s):  
Heather A. Bradeen ◽  
Christopher A. Eide ◽  
Thomas O'Hare ◽  
Kara J. Johnson ◽  
Stephanie G. Willis ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Novel Mutation ◽  
Kinase Domain ◽  
Drug Combinations ◽  
Cross Resistance ◽  
Abl Kinase ◽  
Drug Concentrations ◽  
Trough Levels ◽  
Maximal Suppression

Abstract BMS-354825 (dasatinib) and AMN107 (nilotinib) are potent alternate Abl inhibitors with activity against many imatinib mesylate–resistant BCR-ABL kinase domain (KD) mutants, except T315I. We used N-ethyl-N-nitrosourea (ENU)–exposed Ba/F3-p210BCR-ABL cells to compare incidence and types of KD mutants emerging in the presence of imatinib mesylate, dasatinib, and nilotinib, alone and in dual combinations. Although ENU is expected to induce mutations in multiple proteins, resistant clones were almost exclusively BCR-ABL KD mutant at relevant concentrations of nilotinib and dasatinib, consistent with a central role of KD mutations for resistance to these drugs. Twenty different mutations were identified with imatinib mesylate, 10 with nilotinib (including only 1 novel mutation, E292V) and 9 with dasatinib. At intermediate drug levels the spectrum narrowed to F317V and T315I for dasatinib and Y253H, E255V, and T315I for nilotinib. Thus, cross-resistance is limited to T315I, which is also the only mutant isolated at drug concentrations equivalent to maximal achievable plasma trough levels. With drug combinations maximal suppression of resistant clone outgrowth was achieved at lower concentrations compared with single agents, suggesting that such combinations may be equipotent to higher-dose single agents. However, sequencing uniformly revealed T315I, consistent with the need for a T315I inhibitor, to completely block resistance.

Molecular targeted treatments for fungal infections: the role of drug combinations

2003 ◽  
Vol 9 (6) ◽  
pp. 269-276 ◽  
Author(s):  
Antonella Lupetti ◽  
Peter H. Nibbering ◽  
Mario Campa ◽  
Mario Del Tacca ◽  
Romano Danesi
Keyword(s):  
Fungal Infections ◽  
Drug Combinations ◽  
Targeted Treatments

scholarly journals Role of Antifungal Combinations in Difficult to Treat Candida Infections

2021 ◽  
Vol 7 (9) ◽  
pp. 731
Author(s):  
Roxana G. Vitale
Keyword(s):  
Combination Therapy ◽  
Therapeutic Strategy ◽  
Immune Status ◽  
Drug Combinations ◽  
Significant Shift ◽  
Eye Infections ◽  
Life Threatening ◽  
Candida Infections ◽  
Prevalent Species

Candida infections are varied and, depending on the immune status of the patient, a life-threatening form may develop. C. albicans is the most prevalent species isolated, however, a significant shift towards other Candida species has been noted. Monotherapy is frequently indicated, but the patient’s evolution is not always favorable. Drug combinations are a suitable option in specific situations. The aim of this review is to address this problem and to discuss the role of drug combinations in difficult to treat Candida infections. A search for eligible studies in PubMed and Google Scholar databases was performed. An analysis of the data was carried out to define in which cases a combination therapy is the most appropriate. Combination therapy may be used for refractory candidiasis, endocarditis, meningitis, eye infections and osteomyelitis, among others. The role of the drug combination would be to increase efficacy, reduce toxicity and improve the prognosis of the patient in infections that are difficult to treat. More clinical studies and reporting of cases in which drug combinations are used are needed in order to have more data that support the use of this therapeutic strategy.

scholarly journals In VitroCombination of Anti-Cytomegalovirus Compounds Acting through Different Targets: Role of the Slope Parameter and Insights into Mechanisms of Action

2013 ◽  
Vol 58 (2) ◽  
pp. 986-994 ◽  
Author(s):  
Hongyi Cai ◽  
Arun Kapoor ◽  
Ran He ◽  
Rajkumar Venkatadri ◽  
Michael Forman ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Target Identification ◽  
Mek Inhibitor ◽  
Drug Combinations ◽  
Slope Parameter ◽  
Viral Dna ◽  
Multikinase Inhibitor ◽  
Molecular Weights ◽  
First Line Therapy

ABSTRACTConventional therapy for human cytomegalovirus (CMV) relies on inhibition of the viral DNA polymerase. Ganciclovir (GCV) is the first-line therapy, but when GCV-resistant strains emerge, alternative therapies are extremely limited and are associated with significant toxicities. Combination of anti-CMV agents that act on different targets or stages of virus replication has not been well studied, mostly because of the limited number of anti-CMV agents. We report our investigation of combinations of agents that inhibit CMV by targeting the viral DNA polymerase, cellular kinases, or other cell/virus mechanisms yet to be discovered. The selected compounds differed by the slopes of their dose-response curve: compounds with a slope of 1 (GCV) representing one target or noncooperativity and compounds with high slopes indicating positive cooperativity. Analysis of anti-CMV drug combinations using the Bliss model (which accounts for the slope parameter) distinguished between combinations with synergistic, antagonistic, and additive activities. The combination of GCV and foscarnet was slightly synergistic; strong synergism was found when GCV was used with artemisinin-derived monomers or dimers or the MEK inhibitor U0126. The combination of GCV and cardiac glycosides (digoxin, digitoxin, and ouabain) was additive. The monomeric artemisinin artesunate was synergistic when combined with U0126 or the multikinase inhibitor sunitinib. However, the combination of artemisinin-derived dimers (molecular weights, 606 and 838) and U0126 or sunitinib was antagonistic. These results demonstrate that members of a specific drug class show similar patterns of combination with GCV and that the slope parameter plays an important role in the evaluation of drug combinations. Lastly, antagonism between different classes of CMV inhibitors may assist in target identification and improve the understanding of CMV inhibition by novel compounds.

scholarly journals The Potential Role of Sulbactam and Cephalosporins Plus Daptomycin Against Daptomycin-Nonsusceptible VISA and H-VISA Isolates: An in Vitro Study

Antibiotics ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 184 ◽  
Author(s):  
Lai ◽  
Chen ◽  
Lu ◽  
Lin ◽  
Chen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Synergistic Effect ◽  
Potential Role ◽  
In Vitro Study ◽  
Drug Combinations ◽  
The Other ◽  
In Vitro Activity ◽  
Almost All

This study assesses the synergistic effect of the combination of cephalosporins and sulbactam with daptomycin against daptomycin-nonsusceptible, vancomycin-intermediate resistant Staphylococcus aureus (VISA) or heterogeneous vancomycin-intermediate S. aureus (h-VISA) isolates. The in vitro activity of daptomycin against daptomycin-nonsusceptible VISA/h-VISA isolates after adding cephalosporins with or without sulbactam was evaluated. The MIC of daptomycin against the VISA/h-VISA isolates was reduced after adding cephalosporins to daptomycin. Except for one VISA and two h-VISA isolates, the other VISA/h-VISA isolates became daptomycin-susceptible (MICs 1 mg/L). After adding sulbactam to each daptomycin/cephalosporin combination, the MIC of daptomycin against the VISA/h-VISA isolates decreased for 5 (33.3%), 6 (40.0%), 6 (40.0%), and 6 (40.0%) isolates with the cefazolin, cefmetazole, cefotaxime, and cefepime combinations, respectively. Synergism using the checkerboard method was noted in 100% of cefazolin and cefotaxime combinations and 87% and 80% of cefmetazole and cefepime combinations for all the VISA and h-VISA isolates. With the addition of sulbactam, synergism was noted in 100% of cefazolin, cefmetazole, and cefotaxime combinations and 93% of the cefepime combinations for all the VISA and h-VISA isolates. Almost all the FICs for the three-drug combinations were lower than those for the two-drug combinations. Using time-killing methods, a synergistic effect against five h-VISA isolates was observed. A synergistic effect of daptomycin, sulbactam, and each cephalosporin was observed for all VISA isolates. In conclusion, the activity of daptomycin against daptomycin-nonsusceptible VISA/h-VISA isolates can be enhanced by adding cephalosporins, and partially further promoted by sulbactam.

Identification of Optimal Combinations for Empirical Dual Antimicrobial Therapy of Pseudomonas aeruginosa Infection: Potential Role of a Combination Antibiogram

2006 ◽  
Vol 27 (4) ◽  
pp. 413-415 ◽  
Author(s):  
Mari Mizuta ◽  
Darren R. Linkin ◽  
Irving Nachamkin ◽  
Neil O. Fishman ◽  
Mark G. Weiner ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Therapy ◽  
Antimicrobial Therapy ◽  
Potential Role ◽  
Drug Combinations ◽  
Fine Tuning ◽  
Pseudomonas Aeruginosa Infection

To better determine the optimal combinations for empirical dual antimicrobial therapy of Pseudomonas aeruginosa infection, we evaluated the utility of a novel combination antibiogram. Although the combination antibiogram allowed modest fine-tuning of choices for dual antibiotic therapy, selections based on the 2 antibiograms did not differ substantively. Drug combinations with the broadest coverage were consistently composed of an aminoglycoside and a β-lactam.

Role of dactinomycin in the improved survival of children with Wilms' tumor

JAMA ◽  
1966 ◽  
Vol 195 (12) ◽  
pp. 1005-1009 ◽  
Author(s):  
D. J. Fernbach
Keyword(s):  
Wilms Tumor
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