Salvage Treatment for Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia: Efficacy of Linezolid With or Without Carbapenem

Background. Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with high mortality rates, but no treatment strategy has yet been established. We performed this study to evaluate the efficacy of linezolid with or without carbapenem in salvage treatment for persistent MRSA bacteremia. Methods. All adult patients with persistent MRSA bacteremia for >= 7 days from January 2006 through March 2008 who were treated at Seoul National University Hospital were studied. The results of linezolid salvage therapy with or without carbapenem were compared with those of salvage therapy with vancomycin plus aminoglycosides or rifampicin. Results. Thirty-five patients with persistent MRSA bacteremia were studied. The early microbiological response (ie, negative results for follow-up blood culture within 72 hours) was significantly higher in the linezolid-based salvage therapy group than the comparison group (75% vs 17%; P = .006). Adding aminoglycosides or rifampicin to vancomycin was not successful in treating any of the patients, whereas linezolid-based therapy gave an 88% salvage success rate (P < .001). The S. aureus-related mortality rate was lower for patients treated with a linezolid salvage regimen than for patients continually treated with a vancomycin-based regimen (13% vs 53%; P = .030). Conclusions. Linezolid-based salvage therapy effectively eradicated S. aureus from the blood for patients with persistent MRSA bacteremia. The salvage success rate was higher for linezolid therapy than for vancomycin-based combination therapy.Jenkins TC, 2008, CLIN INFECT DIS, V46, P1000, DOI 10.1086/529190Falagas ME, 2008, LANCET INFECT DIS, V8, P53, DOI 10.1016/S1473-3099(07)70312-2Hawkins C, 2007, ARCH INTERN MED, V167, P1861Kollef MH, 2007, CLIN INFECT DIS, V45, pS191, DOI 10.1086/519470Micek ST, 2007, CLIN INFECT DIS, V45, pS184, DOI 10.1086/519471*CLIN LAB STAND I, 2007, M100S17 CLIN LAB STAHidayat LK, 2006, ARCH INTERN MED, V166, P2138Howden BP, 2006, ANTIMICROB AGENTS CH, V50, P3039, DOI 10.1128/AAC.00422-06Hageman JC, 2006, CLIN INFECT DIS, V43, pE42Jacqueline C, 2006, ANTIMICROB AGENTS CH, V50, P2547, DOI 10.1128/AAC.01501-05Sakoulas G, 2006, CLIN INFECT DIS, V42, pS40Jones RN, 2006, CLIN INFECT DIS, V42, pS13Khatib R, 2006, SCAND J INFECT DIS, V38, P7, DOI 10.1080/00365540500372846Wu VC, 2006, CLIN INFECT DIS, V42, P66Jacqueline C, 2005, ANTIMICROB AGENTS CH, V49, P45, DOI 10.1128/AAC.49.1.45-51.2005*CDCP, 2005, CA MRSA CLIN FAQS CDFowler VG, 2004, J INFECT DIS, V190, P1140Wisplinghoff H, 2004, CLIN INFECT DIS, V39, P309, DOI 10.1086/421946Khosrovaneh A, 2004, CLIN INFECT DIS, V38, P1328Howden BP, 2004, CLIN INFECT DIS, V38, P521KIM SH, 2004, 42 ANN M INF DIS SOC, P142Fowler VG, 2003, ARCH INTERN MED, V163, P2066Kim SH, 2003, CLIN INFECT DIS, V37, P794Moise PA, 2002, J ANTIMICROB CHEMOTH, V50, P1017, DOI 10.1093/jac/dkf215Li JS, 2000, CLIN INFECT DIS, V30, P633You I, 2000, DIAGN MICR INFEC DIS, V36, P37Lowy FD, 1998, NEW ENGL J MED, V339, P520Hiramatsu K, 1997, LANCET, V350, P1670LIBMAN H, 1984, ARCH INTERN MED, V144, P5411

Unprecedented Hydrophobic Amplification in Noncovalent Organocatalysis "on Water": Hydrophobic Chiral Squaramide Catalyzed Michael Addition of Malonates to Nitroalkenes

In this study, water was demonstrated to be an exceptionally efficient reaction medium for the noncovalent, hydrogen-bonding-promoted enantioselective Michael addition of malonates to diverse nitroolefins using cinchona-based squaramide catalysts. A significant increase in the reaction rate was observed when the reaction was performed "on water" rather than in the conventional organic solvents, because of the hydrophobic hydration effect. This hydrophobic amplification was significantly dependent upon the hydrophobicity of the C3-substituent (vinyl or ethyl) of cinchona-based catalysts. Thus, the use of more hydrophobic catalyst with an ethyl group at the C3-position, even a highly challenging Michael donor such as dimethyl methylmalonate was also smoothly converted to the desired adduct. Furthermore, because of the remarkable rate acceleration under "on water" conditions, the catalyst loading also significantly decreased. Thus, in the case of beta-ketoesters, even 0.01 mol % of catalyst loading was enough to complete the reaction at room temperature, affording the corresponding Michael adducts with perfect diastereo- and enantioselectivity (up to >99:1 d.r., up to 99% ee). The developed "on water" protocol was successfully applied for the scalable syntheses of an antidepressant (S)-rolipram and an anticonvulsant (S)-pregabali

Cinchona-based Sulfonamide Organocatalysts: Concept, Scope, and Practical Applications

Cinchona-based bifunctional catalysts have been extensively employed in the field of organocatalysis due to the incorporation of both hydrogen-bonding acceptors (quinuclidine) and hydrogen-bonding donors (e.g., alcohol, amide, (thio)urea and squaramide) in the molecule, which can simultaneously activate nucleophiles and electrophiles, respectively. Among them, cinchona-derived (thio)urea and squaramide catalysts have shown remarkable application potential by using their bifurcated hydrogen bonding donors in activating electrophilic carbonyls and imines. However, due to their bifunctional nature, they tend to aggregate via inter- and intramolecular acid-base interactions under certain conditions, which can lead to a decrease in the enantioselectivity of the reaction. To overcome this self-aggregation problem of bifunctional organocatalysts, we have successfully developed a series of sulfonamide-based organocatalysts, which do not aggregate under conventional reaction conditions. Herein, we summarize the recent applications of our cinchona-derived sulfonamide organocatalysts in highly enantioselective methanolytic desymmetrization and decarboxylative aldol reactions. Immobilization of sulfonamide-based catalysts onto solid supports allowed for unprecedented practical applications in the synthesis of valuable bioactive synthons with excellent enantioselectivities

Organocatalytic enantioselective decarboxylative aldol reaction of malonic acid half thioesters with aldehydes

Copycat: A highly enantioselective biomimetic aldol reaction of malonic acid half thioesters with a variety of aldehydes affords optically active ??-hydroxy thioesters by employing the cinchona-derived sulfonamide organocatalyst 1. The synthetic utility of this protocol was demonstrated by performing formal syntheses of the antidepressants (R)-fluoxetine, (R)-tomoxetine, (-)-paroxetine, and (R)-duloxetine

Hydrogen bonding mediated enantioselective organocatalysis in brine: significant rate acceleration and enhanced stereoselectivity in enantioselective Michael addition reactions of 1,3-dicarbonyls to beta-nitroolefins

Brine provides remarkable rate acceleration and a higher level of stereoselectivity over organic solvents, due to the hydrophobic hydration effect, in the enantioselective Michael addition reactions of 1,3-dicarbonyls to beta-nitroolefins using chiral H-donors as organocatalysts

Asymmetric Synthesis of α‑Fluoro-β-Amino-oxindoles with Tetrasubstituted C–F Stereogenic Centers via Cooperative Cation-Binding Catalysis

Biologically relevant chiral 3,3-disubstituted oxindole products containing a β-fluoroamine unit are obtained in high yields and with excellent stereoselectivity (up to 99% ee, dr >20:1 for <i>syn</i>) through the organocatalytic direct Mannich reaction of 3-fluoro-oxindoles as fluoroenolate precursors and α-amidosulfones as the bench-stable precursors of sensitive imines by using a chiral oligoethylene glycol and KF as a cation-binding catalyst and base, respectively. This protocol can be easily scaled without compromising the asymmetric induction. Furthermore, this protocol was also successfully extended to generate tetrasubstituted C–Cl and C–Br stereogenic centers