ABSTRACT
Cationic cholic acid derivatives displayed potent and broad-spectrum activity against multidrug-resistant Gram-negative and -positive bacteria. Specific examples were effective permeabilizers of the outer membranes of many strains of multidrug-resistant Gram-negative bacteria and sensitized these to hydrophobic antibiotics. We also prepared a new cholic acid derivative with improved apparent selectivity for prokaryote membranes.
Subject(s)
Anti-Bacterial Agents/pharmacology , Cholic Acid/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Cholic Acid/chemical synthesis , Cholic Acid/chemistry , Drug Resistance, Multiple , Escherichia coli/drug effects , Humans , Microbial Sensitivity Tests , Salmonella typhimurium/drug effects , Staphylococcus aureus/drug effects , Streptococcus pneumoniae/drug effectsABSTRACT
[reaction: see text] Novel cholic acid-derived antimicrobial agents that decompose under mildly basic conditions have been prepared. These compounds range in biological properties from potent antibacterial activity to effective permeabilization of the outer membranes of Gram-negative bacteria.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Cholic Acids/chemical synthesis , Cholic Acids/pharmacology , Anti-Bacterial Agents/pharmacokinetics , Cell Membrane Permeability , Cholic Acids/pharmacokinetics , Drug Stability , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/metabolism , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/metabolism , Microbial Sensitivity Tests , Structure-Activity RelationshipABSTRACT
Little research exists on the outcome of smaller patients who undergo coronary artery bypass graft surgery. The purpose of this study was to evaluate the outcomes of cardiac surgery in smaller patients (males with body surface area of 1.6 square meters or less, and women with 1.5 meters or less). A consecutive series of 4,358 patients undergoing bypass surgery was evaluated. Of these, 246 (5.6%) were classified as small patients. Smaller patients were more likely to be women, older and of Asian ethnicity. They were less likely to have undergone a prior cardiac surgery. Smaller patients were less likely to receive an arterial conduit (74% versus 99%; p<0.00001). Rates of post-surgery complications differed between small and normal size patients, with smaller patients more likely to require prolonged ventilator support (p <0.05), more likely to have acute renal failure (p<0.0001), more transfusions and re-operation for bleeding (p<0.05), higher death rate (5.7% versus 2.6%; p<0.01) and longer length of hospital stay (11.4 versus 8.3 days; p<0.00001). In multivariate analyses evaluating factors related to death, emergent surgery, poor ejection fraction and older patient age were independently related to mortality. Small body surface area was not an independent predictor. The results of this study indicate that smaller patients do have poorer outcomes associated with coronary artery bypass surgery. However, 90% of the smaller patients did have an event-free surgery. Surgeons may need to monitor these patients more closely and anticipate the increased risk and cost that is associated with this group.
Subject(s)
Body Height , Body Weight , Coronary Artery Bypass/methods , Coronary Disease/surgery , Adult , Aged , Body Composition , Cardiac Catheterization , Chi-Square Distribution , Coronary Artery Bypass/mortality , Coronary Disease/diagnosis , Coronary Disease/mortality , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Probability , Prognosis , Retrospective Studies , Risk Assessment , Sampling Studies , Survival Rate , Treatment OutcomeABSTRACT
Compounds in a series of cholic acid derivatives, designed to mimic the activities of polymyxin B and its derivatives, act as both potent antibiotics and effective permeabilizers of the outer membranes of gram-negative bacteria. Some of these compounds rival polymyxin B in antibacterial activity against gram-negative bacteria and are also very active against gram-positive organisms. Other compounds interact synergistically with hydrophobic antibiotics to inhibit bacterial growth.
