Three Decades of -Lactamase Inhibitors
نویسندگان
چکیده
INTRODUCTION .......................................................................................................................................................161 MECHANISM OF ACTION OF -LACTAM ANTIBIOTICS .............................................................................161 RESISTANCE TO -LACTAM ANTIBIOTICS .....................................................................................................161 -LACTAMASES ........................................................................................................................................................164 Classification ...........................................................................................................................................................164 Class A serine -lactamases .............................................................................................................................164 Class A ESBLs ....................................................................................................................................................164 Class A serine carbapenemases ........................................................................................................................165 Class B metallo-lactamases ...........................................................................................................................165 Class C serine cephalosporinases.....................................................................................................................166 Class D serine oxacillinases ..............................................................................................................................166 -Lactamase Hydrolytic Mechanisms..................................................................................................................166 Class A .................................................................................................................................................................166 Class C .................................................................................................................................................................168 Class D .................................................................................................................................................................168 Class B .................................................................................................................................................................168 CIRCUMVENTING -LACTAMASES ....................................................................................................................169 -Lactamase Inhibitors: Mechanistic Considerations.......................................................................................169 -Lactamase Inhibitors in Clinical Practice ......................................................................................................169 Clavulanic acid, sulbactam, and tazobactam .......................................................................................169 Mechanism of inhibition....................................................................................................................................170 -Lactam– -lactamase inhibitor combinations: clinical use .......................................................................171 (i) Amoxicillin-clavulanate ............................................................................................................................171 (ii) Ticarcillin-clavulanate .............................................................................................................................172 (iii) Ampicillin-sulbactam..............................................................................................................................173 (iv) Piperacillin-tazobactam ..........................................................................................................................173 Inhibitory Activity of Carbapenems .....................................................................................................................174 INHIBITOR-RESISTANT CLASS A -LACTAMASES........................................................................................176 Epidemiology and Detection of -Lactamase Inhibitor Resistance.................................................................176 Substitutions in Class A Enzymes Conferring Inhibitor Resistance...............................................................178 Arginine 244.........................................................................................................................................................179 Methionine 69......................................................................................................................................................179 Asparagine 276 ....................................................................................................................................................179 Serine 130 ............................................................................................................................................................180 Arginine 275.........................................................................................................................................................180 Lysine 234 ............................................................................................................................................................180 THE PROMISE OF NOVEL -LACTAMASE INHIBITORS .............................................................................180 Monobactam Derivatives .......................................................................................................................................180 ATMO Derivatives ..................................................................................................................................................182 Penems .....................................................................................................................................................................182 BRL 42715 and Syn 1012...................................................................................................................................182 BRL 42715 derivatives........................................................................................................................................183 Oxapenems...........................................................................................................................................................184 Tricyclic carbapenems (trinems) ......................................................................................................................184 1-Methylcarbapenems.....................................................................................................................................184 Penicillin and Cephalosporin Sulfone Derivatives.............................................................................................184 C-2/C-3-substituted penicillin and cephalosporin sulfones ..........................................................................185 C-6-substituted penicillin sulfones ...................................................................................................................185
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