A 50-year-old woman comes to the emergency department due to fever and abdominal pain. The patient has a history of type 2 diabetes mellitus. Her temperature is 38.3 C (101 F). Abdominal examination is notable for right upper quadrant tenderness to palpation that is worsened by deep inspiration. Laboratory studies show leukocytosis. An ultrasound of the abdomen reveals multiple gallstones and gallbladder wall thickening with pericholecystic fluid. Blood cultures are drawn, and surgical consultation is requested. The patient is initiated on intravenous piperacillin combined with tazobactam. Which of the following is the most likely reason to use this drug combination in this patient?

Question

A 50-year-old woman comes to the emergency department due to fever and abdominal pain.  The patient has a history of type 2 diabetes mellitus.  Her temperature is 38.3 C (101 F).  Abdominal examination is notable for right upper quadrant tenderness to palpation that is worsened by deep inspiration.  Laboratory studies show leukocytosis.  An ultrasound of the abdomen reveals multiple gallstones and gallbladder wall thickening with pericholecystic fluid.  Blood cultures are drawn, and surgical consultation is requested.  The patient is initiated on intravenous piperacillin combined with tazobactam.  Which of the following is the most likely reason to use this drug combination in this patient?

Quizplus · Accepted Answer

This patient's fever, leukocytosis, right upper quadrant pain with positive Murphy sign, and ultrasound findings (eg, gallstones, wall thickening, pericholecystic fluid) indicate acute cholecystitis. Antibiotic therapy is often administered to prevent secondary infection (eg, Escherichia coli, Klebsiella) due to biliary stasis, particularly in patients who have diabetes mellitus or immunodeficiency. The penicillin family of antibiotics (eg, piperacillin) contains a beta-lactam ring, which inhibits peptidoglycan cross-linking and causes bacterial cell wall disruptions. Resistance is often due to beta-lactamase, a bacterial enzyme that hydrolyzes and inactivates the beta-lactam ring. The coadministration of a beta-lactamase inhibitor such as tazobactam prevents beta-lactamase producing organisms from inactivating penicillins, which extends their spectrum of activity (broadens the range of microbes that can be treated). Some penicillin-derivative antibiotics (eg, late-generation cephalosporins, carbapenems) have beta-lactam rings with additional chemical components, which make them partially or completely resistant to beta-lactamases. (Choice B) Probenecid, a uricosuric agent used for hyperuricemia with gout, blocks the renal tubular excretion of penicillins and cephalosporins and is sometimes used to increase their serum level or prolong their half-life. (Choice C) Aminoglycosides inhibit bacterial protein synthesis by blocking the 30S ribosomal subunit. Penicillins are often coadministered with aminoglycosides to aid in their entry into the cell (penicillins disrupt the cell wall, which allow aminoglycosides to penetrate the bacteria). (Choice D) Piperacillin is always administered intravenously so bioavailability is 100%. Tazobactam inhibits beta-lactamase; it does not alter piperacillin metabolism or excretion. (Choice E) Additive antimicrobial activity occurs when 2 different antibiotic classes are used in combination, such as a fluoroquinolone (DNA gyrase inhibitor) with vancomycin (cell wall synthesis inhibitor). Beta-lactamase inhibitors block an enzyme that destroys penicillins; they do not independently provide antimicrobial activity so they are always used in combination with penicillin-class agents. Educational objective: Beta-lactamase inhibitors (eg, clavulanic acid, sulbactam, tazobactam) prevent beta-lactamase from inactivating penicillin class drugs, which extends the spectrum of their activity.

A 50-Year-Old Woman Comes to the Emergency Department Due to Fever