Antimicrobial agent effective against ESBL producing microorgansims is
(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
Beta lactam plus beta lactamase inhibitor
Ampicillin
Ceftriaxone
Aztreonam
Anti Microbial