No

Antibiotic, Penicillin

Treatment of infections caused by susceptible gram-negative aerobic bacilli ( Klebsiella, Proteus, Escherichia coli, Enterobacter, Pseudomonas aeruginosa, Serratia) involving the skin and skin structure, bone and joint, respiratory tract, urinary tract, gastrointestinal tract, as well as, septicemia

B

Hypersensitivity to mezlocillin, any component, or penicillins

If bleeding occurs during therapy, mezlocillin should be discontinued; dosage modification required in patients with impaired renal function; use with caution in patients with renal impairment or biliary obstruction, or history of allergy to cephalosporins

1% to 10%: Gastrointestinal: Nausea, diarrhea

<1%: Fever, seizures, dizziness, headache, rash, exfoliative dermatitis, hypokalemia, hypernatremia, vomiting, eosinophilia, leukopenia, neutropenia, thrombocytopenia, agranulocytosis, hemolytic anemia, prolonged bleeding time, positive Coombs' [direct], hepatotoxicity, elevated liver enzymes, hematuria, elevated BUN/serum creatinine, interstitial nephritis, serum sickness-like reactions

Symptoms of penicillin overdose include neuromuscular hypersensitivity (agitation, hallucinations, asterixis, encephalopathy, confusion, and seizures) and electrolyte imbalance with potassium or sodium salts, especially in renal failure

Hemodialysis may be helpful to aid in the removal of the drug from the blood, otherwise most treatment is supportive or symptom directed

Aminoglycosides (synergy), probenecid (decreased clearance), vecuronium (increased duration of neuromuscular blockade), heparin (increased risk of bleeding); possible decrease in effectiveness of oral contraceptives; bacteriostatic action of tetracycline may impair bactericidal effects of the penicillins

Reconstituted solution is stable for 48 hours at room temperature and 7 days when refrigerated; for I.V. infusion in NS or D₅W solution is stable for 48 hours at room temperature, 7 days when refrigerated or 28 days when frozen; after freezing, thawed solution is stable for 48 hours at room temperature or 7 days when refrigerated; if precipitation occurs under refrigeration, warm in water bath (37°C) for 20 minutes and shake well

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin binding proteins (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

Absorption: I.M.: 63%

Distribution: Into bile, heart, peritoneal fluid, sputum, bone; does not cross the blood-brain barrier well unless meninges are inflamed; crosses the placenta; distributes into breast milk at low concentrations

Protein binding: 30%

Metabolism: Minimal

Half-life: Dose dependent:

Neonates: <7 days: 3.7-4.4 hours; >7 days: 2.5 hours

Children 2-19 years: 0.9 hour

Adults: 50-70 minutes, increased in renal impairment

Time to peak serum concentration:

I.M.: 45-90 minutes after administration

I.V. infusion: Within 5 minutes

Elimination: Principally as unchanged drug in urine, also excreted via bile

I.M., I.V.:

less than or equal to 7 days, less than or equal to 2000 g: 75 mg/kg every 12 hours

less than or equal to 7 days, >2000 g: Same as above

>7 days, less than or equal to 2000 g: 75 mg/kg every 8 hours

>7 days, >2000 g: 75 mg/kg every 6 hours

Children: 300 mg/kg/day divided every 4-6 hours; maximum: 24 g/day

Adults: Usual: 3-4 g every 4-6 hours

Uncomplicated urinary tract infection: 1.5-2 g every 6 hours

Serious infections: 200-300 mg/kg/day in 4-6 divided doses

Dosing interval in renal impairment:

Cl_cr 10-30 mL/minute: Administer every 6-8 hours

Cl_cr <10 mL/minute: Administer every 8 hours

Hemodialysis: Moderately dialyzable (20% to 50%)

Dosing adjustment in hepatic impairment: Reduce dose by 50%

Observe for signs and symptoms of anaphylaxis during first dose

False-positive direct Coombs'; false-positive urinary or serum protein; may inactivate aminoglycosides in vitro

May cause dizziness; penicillins reported to cause apprehension, illusions, hallucinations, depersonalization, agitation, encephalopathy, and insomnia

May cause leukopenia; use caution with clozapine and carbamazepine

No information available to require special precautions

Prolonged use of penicillins may lead to development of oral candidiasis

This medication can only be administered by infusion or injection. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). Small frequent meals, frequent mouth care, and adequate fluids may reduce incidence of nausea or vomiting. If diabetic, drug may cause false tests with Clinitest® urine glucose monitoring; use of glucose oxidase methods (Clinistix®) or serum glucose monitoring is preferable. This drug may interfere with oral contraceptives; an alternate form of birth control should be used. Report difficulty breathing, acute diarrhea, systemic rash, fever, white plaques in mouth, or mouth sores. Breast-feeding precautions: Consult prescriber if breast-feeding.

Administer at least 1 hour prior to aminoglycosides

Powder for injection, as sodium: 1 g, 2 g, 3 g, 4 g, 20 g

Donowitz GR and Mandell GL, "Beta-Lactam Antibiotics," N Engl J Med, 1988, 318(7):419-26 and 318(8):490-500.

Meyers BR, Mendelson MH, Srulevitch-Chin E, et al, "Pharmacokinetic Properties of Mezlocillin in Ambulatory Elderly Subjects," J Clin Pharmacol, 1987, 27(9):678-81.

Odio C, Threlkeld N, Thomas ML, et al, "Pharmacokinetic Properties of Mezlocillin in Newborn Infants," Antimicrob Agents Chemother, 1984, 25(5):556-9.

Prober CG, Stevenson DK, and Benitz WE, "The Use of Antibiotics in Neonates Weighing Less Than 1200 Grams," Pediatr Infect Dis J, 1990, 9(2):111-21.

Rohde B, Werner U, Hickstein H, et al, "Pharmacokinetics of Mezlocillin and Sulbactam Under Continuous Veno-Venous Hemodialysis (CVVHD) in Intensive Care Patients With Acute Renal Failure," Eur J Clin Pharmacol, 1997, 53(2):111-5.

Wright AJ, "The Penicillins," Mayo Clin Proc, 1999, 74(3):290-307.

Yoshikawa TT, "Antimicrobial Therapy for the Elderly Patient," J Am Geriatr Soc, 1990, 38(12):1353-72.