Piperacillin

Indications

Piperacillin is used for: Urinary Tract Infection, Uncomplicated, Community-Acquired Pneumonia, Acute Cholangitis, Uncomplicated Gonorrhea, Pseudomonas Infections, Severe infections, Cystic Fibrosis

Adult Dose

Parenteral Usual Dosage Range IV: 3-4 g/dose q4-6hr; not to exceed 24 g/24hr IM: 2-3 g/dose q6-12hr; not to exceed 24 g/24 hr Urinary Tract, Uncomplicated 6-8 g/day IV/IM (100 to 125 mg/kg/day) divided q6-12 hr Community-Acquired Pneumonia 6-8 g/day IV/IM (100 to 125 mg/kg/day) divided q6-12 hr Acute Cholangitis 4 g IV q6hr Moderate Infections 2-3 g/dose IV/IM q6-12hr; not to exceed 2 g IM/site Severe Infections 3-4 g IV/IM q4-6hr; not to exceed 24 g/24 hr Uncomplicated Gonorrhea 2 g once with 1 g probenecid 30 min before injection Pseudomonas Infections 4 g IV/IM q4hr

Child Dose

Usual Dosage Range Neonates: 100 mg/kg IV/IM q12hr Infants and Children: 200-300 mg/kg/day IV/IM divided q4-6hr Cystic Fibrosis 350-500 mg/kg/day IV/IM divided q4-6hr

Renal Dose

Renal Impairment CrCl 20-40 mL/min: 3-4 g q8hr CrCl <20 mL/min: 3-4 g q12hr

Administration

IV/IM Preparation IV: reconstitute each gram w/ 5 mL SWI, BWI, NS, D5W or other compatible diluents Slight darkening does not indicate potency loss IV/IM Administration Slow direct inj over 3-5 min, OR Intermittent infusion in at least 50 mL over 20-30 min IM: upper outer quadrant of buttock

Contra Indications

Allergy to penicillins, cephalosporins, imipenem

Precautions

Risk of bleeding complications, especially in renal impairment Monitor renal, hepatic & especially hematopoietic functions during prolonged treatment Hypersensitivity reactions reported; discontinue therapy and institute appropriate therapy if allergic reaction occurs Found to be an independent risk factor for renal failure and was associated with delayed recovery of renal function as compared to other beta-lactam antibacterial drugs; if alternative treatment options are inadequate or unavailable, monitor renal function during treatment Combined use of piperacillin/tazobactam and vancomycin may be associated with an increased incidence of acute kidney injury Serious skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome, acute exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms (DRESS) reported; monitor closely if rash develops; discontinue if lesions progress Hematological effects (including bleeding, leukopenia and neutropenia) have occurred. Monitor hematologic tests during prolonged therapy Use may result in fungal or bacterial superinfection; valuate patients for Clostridium difficile if diarrhea occurs Dosage adjustment recommended in patients with renal impairment or receiving hemodialysis Use with caution in patients with history of seizure disorder; high levels, that may result from renal impairment, may increase risk of seizures

Pregnancy-Lactation

Pregnancy Piperacillin and tazobactam cross the placenta in humans; however, there are insufficient data in pregnant women to inform a drug-associated risk for major birth defects and miscarriage; no fetal structural abnormalities observed in rats or mice when piperacillin/tazobactam was administered intravenously during organogenesis at doses 1 to 2 times and 2 to 3 times human dose, respectively, based on body-surface area’ however, fetotoxicity in presence of maternal toxicity was observed in developmental toxicity and peri/postnatal studies conducted in rats (intraperitoneal administration prior to mating and throughout gestation or from gestation day 17 through lactation day 21) at doses less than the maximum recommended human daily dose based on body-surface area Lactation Piperacillin is excreted in human milk; tazobactam concentrations in human milk not studied; no information available on effects of piperacillin and tazobactam on breastfed child or on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal condition.

Interactions

May prolong the neuromuscular blocking effect of vecuronium when used perioperatively. May enhance the anticoagulant effect of vit K antagonists (e.g. warfarin). May increase the risk of methotrexate toxicity. Probenecid may increase the peak serum level of piperacillin.

Adverse Effects

Side effects of Piperacillin : <1% Seizure Rash Hemolytic anemia Postive Coombs reaction Prolonged prothrombin time Interstitial nephritis Hypersensitivity Anaphylaxis Thrombophlebitis Injection site pain Headache Fever Intestinal infection due to pseudomonas

Mechanism of Action

Piperacillin inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins (PBPs) which in turn inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.