A patient on urinary catheter - catheter tip culture shown extended spectrum b-lactamase +ve Klebsiella. Which of the following drug you can give?
(B) pH + b-lactamaseoKlebsiella infection at any site can produce bacteremia.[?]Extended-spectrum b-Lactam agents:-Enhanced activity against G- and some G+ bacteria; E.g., 3rd and 4th generation cephalosporins, carboxy- and ureidopenicillinsoExtended-spectrum b-Lactamases (ESBLs)-Enzymes produced by GNR that destroy certain extended-spectrum b-lactam agents, including 3rd generation cephalosporins.[?]Important resistance mechanisms to ft-lactam antibiotics:[?]b-lactamase resistance:oMany bacteria produce enzymes that are capable of destroying the b-lactam ring of penicillin, these enzymes are referred to as penicillinases or beta-lactamases, & make bacteria that possess them resistant to many penicillins. Clavulanic acid is a chemical that inhibits beta- lactamase enzymes, thereby increasing the longevity of beta-lactam antibiotics in the presence of penicillinase - producing bacteria.oClavamox is a combination of Amoxicillin & Clavulanate & is marketed under the trade name Augmentin.oZosyn, a similar combination of the beta-lactamase inhibitor Tazobactam & Piperacillin.oDrug of Choice: UTI: Cortimoxazole, Augmentin, Nitrofuration, levofloxacin/ ciprofloxacin-Other Serious infections:-Carbapenems:-Imipenem, Meropenem, Ertapenem (reliable activity vs ESBL-producing Enterobac-teriaceae). Fluoroquinolone + Aminoglycoside[?]ESBL-Producing Enterobacteriaceae:oExtended-spectrum beeta-lactamases: Any bacterial enzymes that are capable of inactivating third generation cephalosporins.-ESBL are Generally regarded as resistant to Penicillins & CephalosporinsFOUR MAIN TYPES OF RESISTANCE MECHANISMS IN GRAM NEGATIVE BACILLIDrug inactivationEnzymatic deactivation of beta lactam antibiotics by beta lactamases and deactivation of aminoglycosides by varios enzymes; beta -lactam/beta - lactamase inhibitor combination drugs have the potential to overcome some, but not all, beta-lactamasesAlteration of target siteAlteration of the DNA gyrase-bidning site for fluoroquinolones (Quinolone resistance-determing region)Reduced drug accumulation within the bacterial cellReduced drug permeability (via, for E.g., altering levels of outer membrane protein channels (porins) that are responsible for passive diffusion) and/or increased active efflux of the drugs across the cell surface.Alteration of metabolic pathwayPlasmid-encoded, drug-resistant dihydropteroate synthetase bypasses the chromosomal-encoded enzyme inhibited by sulfa drugs so the organism can still synthesize folic acid from para-aminobenzoic acid.[?]Effects of Acidic conditions on activities of Seven beta-lactamases:oTEM-1 (class A), KOXY (class A), IMP-1 (class B), AmpC (class C), MOX-1 (class C), OXA-5 (class D), and PSE-2 (class D)-& their inhibitors were measured.oEnzymatic activities of KOXY, IMP-1, and MOX-1 at pH 5.8 were slightly lower than those at pH 7.5.oActivities of PSE-2 & OXA-5 were greatly reduced at pH 5.8.oAll of the beta-lactamase inhibitors tested had poorer inhibitory activities at pH 5.8 than at pH 7.5 except clavulanic acid for TEM-1.
Ceftriaxone
pH + b-lactamase
Aminoglycoside
Tetracycline (Vancomycin)
Infection