Antimicrobial agent effective against ESBL producing microorgansims is
Beta lactam plus beta lactamase inhibitor
Ampicillin
Ceftriaxone
Aztreonam
(A) Beta lactam plus beta lactamase inhibitorAntimicrobial Agents that must not be reported as susceptibleOrganismESBL - producing K. pneumoniae, K oxytoca, E. coli & P mirabilis1st & 2nd generation cephalosporins, cephamycins & aminoglycosidesSalmonell spp., Shegella spp.Penicillins, beta lactam / beta lactamase inhibitor combinations, cephems & carbapenemsOxacillin - resistant Staphylococcus spp.Aminoglycosides (except high concentrations), cephalosporins, Clindamycin & trimethoprim sulfamethoxazoleEnterococcus spp.#Important resistance mechanisms to beta lactam antibiotics:Beta lactamase Resistance:Many bacteria produce enzymes that are capable of destroying the beta-lactam ring of penicillin, these enzymes are referred to as penicillinases or beta-lactamases and they make the bacteria that possess them resistant to many penicillins.Clavulanic acid is inhibits beta-lactamase enzymes, thereby increasing the longevity of beta-lactam antibiotics in the presence of penicillinase-producing bacteria.Clavamox is a combination of amoxicillin and clavulanate.Combination of the beta-lactamase inhibitor tazobactam and piperacillin.Summary of beta lactam / beta lactamase inhibitor on treatment of ESBL - producing organisms:Limited clinical information:Class A ESBLs are susceptible to clavulanate & tazobactam in vitro, nevertheless many producers are resistant to beta lactamase inhibitor due to:-Hyperproduction of the ESBLs - overwhelm inhibitor.-Co-production of inhibitor-resistant penicillinases (E.g., OXA-1) or AmpC enzyme.-Relative impermeability of the host strain.Beta-lactam/beta lactamase inhibitor should not be used not be used to treat serious infections with ESBL producing organisms.Beta lactamase inhibitors:Almost all have weak antibacterial activitiy.Important in combination with penicillins sensitive to beta lactamase degradation.Clavulanic acid is the first one of this class.Natural product from streptomyces.Has a powerful & irreversible inhibition of beta lactamase enzymes because it will covalently bind to two positions in the active site.Normally used in combination with amoxicillin & other beta lactamase sensitive penicillins.Extended Spectrum Beta Lactamase (ESBL):Enzymes that are produced by Gram negative bacteria.Confer resistance to Cephalosporins, Penicillins & Monobactam (Aztreonam) by opening the beta lactam ring inactivating the antibiotic.Cannot attack Cephamycins (cefoxitin, cefotetan) or the carbapenems (imipenem, meropenem, ertapenem, doripe- nem).Generally susceptible to beta-lactamase inhibitors (Tazobactam)Plasmid mediated TEM, SHV, CTX-M beta lactamases are the most common.Therapy for ESBL producing gram negative rods:Carbapenems: Imipenem, Macropenem, Doripenem, ErtapenemPiperacillin / Tazobactam - Tazobactam blocks beta lactamase action.Beta lactam / beta lactamase inhibitor on treatment of ESBL - producing organisms:Most ESBLs are susceptible to clavulanate & tazobactam in vitro.Nevertheless some ESBL producers are resistant to beta lactamase inhibitor due to:Hyperproduction of the ESBLs - overwhelm inhibitor.Co-production of inhibitor - resistent penicillinases or AmpC enzyme.Relative impermeability of the host strain.Beta lactam/beta lactamase inhibitor should not be used to treat serious infections with ESBL - producing organisms
Anti Microbial