piperacillin (Pipracil)

Introduction

Tradename: Pipracil. 4th generation penicillin.

Indications

• treatment of serious bacterial infections cause by susceptible gram-negative organisms:
  • infectious arthritis, osteomyelitis
  • skin or soft tissue infection
  • urogenital infection
    • gonorrhea
  • urinary tract infection
  • lower respiratory tract infection
  • intra-abdominal infection
  • bacteremia
• indicated for infections caused by Pseudomonas aeruginosa & Enterobacteriaceae
• use in combination with an aminoglycoside or quinolone
• prophylaxis for perioperative infection
  • gastrointestinal surgery
  • cesarean section
  • hysterectomy

Dosage

• 3-4 g IV every 4-6 hours
• 2-3 g IM every 6-12 hours

Powder for injection: 2 g, 3 g, 4 g.

Dosage adjustment in renal failure

Table

Creatinine clearance	mild-moderate infection	serious infection
> 40 mL/min	3-4 g IV every 8 hours	3-4 g IV every 6 hours
20-39 mL/min*	3-4 g IV every 12 hours	3-4 g IV every 8 hours
< 19 mL/min#	3 g IV every 12 hours	3-4 g IV every 12 hours

* same dose for continuous arteriovenous hemofiltration

# dose after hemodialysis

Pharmacokinetics

• 70-80% of an IM dose is absorbed
• well distributed to most body tissues & fluids
  • pleural, peritonal, synovial & wound fluids
  • sputum & bone
  • minimal CSF penetration unless meninges are inflamed; therapeutic concentrations in the CNS may be obtained with inflammed meninges
  • crosses placenta
  • distributes into milk at low concentrations
• time to peak concentration 30-50 minutes
• protein-binding 22%
• elimination 1/2life is 1 hour (3.3-5 hours ESRD)
• eliminated primarily by the kidney (70%)
• 10-30% eliminated in the bile
• dosage adjustment necessary with renal insufficiency
• 20-50% dializable

elimination via kidney

protein binding = 22 %

elimination by hemodialysis = +/-

Antimicrobial activity

Gram positive

• Streptococcus
  • Streptococcus group A
  • Streptococcus group B
  • Streptococcus group C
  • Streptococcus group G
  • Streptococcus pneumonia
  • Streptococcus viridans, milleri
• Enterococcus faecalis (+/-)
• Enterococcus faecium (+/-)
• Listeria monocytogenes

Gram negative

• Neisseria gonorrhoeae
• Neisseria meningitidis
• Moraxella catarrhalis (+/-)
• Haemophilus influenzae (+/-)
• Escherichia coli
• Klebsiella species
• Enterobacter species
• Salmonella species
• Shigella species
• Proteus mirabilis
• Proteus vulgaris
• Providencia species
• Morganella species
• Citrobacter species
• Aeromonas species
• Pseudomonas aeruginosa
• Xanthomonas maltophilia
• Yersinia enterocolitica
• Pasteurella multocida
• Acinetobacter

Anaerobes

• Actinomyces
• Bacteroides fragilis
• Bacteroides melaninogenicus
• Clostridium difficile
• Clostridium species
• Peptostreptococcus species

Adverse effects

• uncommon (< 1%)
  • thrombophlebitis, convulsions, confusion, drowsiness, fever, rash, electrolyte imbalance, hemolytic anemia, positive direct antiglobulin test (Coomb's test, DAT), myoclonus, acute interstitial nephritis*, Jarisch-Herxheimer reaction, hypersensitivity reactions, anaphylaxis, abnormal platelet aggregation, prolonged prothrombin time (high doses)
• other
  • diarrhea
  • rare blood dyscrasias
  • increased serum transaminases
  • increased BUN & creatinine
  • seizures (rare)

* generally complete recovery of renal function (may take months) if piperacillin discontinued immediately after onset of acute kidney injury

Drug interactions

• probenecid increased concentration & prolongs 1/2life of piperacillin
• aminoglycosides are inactivated by piperacillin when mixed in same IV bag

• drug interaction(s) anticonvulsants with anti-bacterial agents
• drug interaction(s) of antibiotics with warfarin

Laboratory

• piperacillin in serum/plasma

Mechanism of action

inhibition of bacterial cell wall synthesis

More general terms

• 4th generation penicillin (extended-spectrum)

Component of

• piperacillin tazobactam (Zosyn)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=43672
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=73246
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=73757
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=474871
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4834
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=43066
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=656513