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piperacillin (Pipracil)
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 [6]
Dosage:
1) 3-4 g IV every 4-6 hours
2) 2-3 g IM every 6-12 hours
Powder for injection: 2 g, 3 g, 4 g.
Dosage adjustment in renal failure:
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:
1) 70-80% of an IM dose is absorbed
2) well distributed to most body tissues & fluids
a) pleural, peritonal, synovial & wound fluids
b) sputum & bone
c) minimal CSF penetration unless meninges are inflamed; therapeutic concentrations in the CNS may be obtained with inflammed meninges
d) crosses placenta
e) distributes into milk at low concentrations
3) time to peak concentration 30-50 minutes
4) protein-binding 22%
5) elimination 1/2life is 1 hour (3.3-5 hours ESRD)
6) eliminated primarily by the kidney (70%)
7) 10-30% eliminated in the bile
8) dosage adjustment necessary with renal insufficiency
9) 20-50% dializable
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 [6]
Anaerobes
- Actinomyces
- Bacteroides fragilis
- Bacteroides melaninogenicus
- Clostridium difficile
- Clostridium species
- Peptostreptococcus species
Adverse effects:
1) 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)
2) 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 [7]
Drug interactions:
1) probenecid increased concentration & prolongs 1/2life of piperacillin
2) aminoglycosides are inactivated by piperacillin when mixed in same IV bag
Laboratory:
- piperacillin in serum/plasma
Mechanism of action: inhibition of bacterial cell wall synthesis
Interactions
drug interactions
General
4th generation penicillin (extended-spectrum)
Properties
MISC-INFO: elimination route KIDNEY
pregnancy-category B
safety in lactation ?
protein-binding 22%
elimination by hemodialysis +/-
Database Correlations
PUBCHEM correlations
References
- The Pharmacological Basis of Therapeutics, 9th ed.
Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- Harrison's Principles of Internal Medicine, 13th ed.
Companion Handbook. Isselbacher et al (eds),
McGraw-Hill Inc. NY, 1995, pg 161
- Sanford Guide to antimicrobial therapy 1997
- Drug Information & Medication Formulary, Veterans Affairs,
Central California Health Care System, 1st ed., Ravnan et al
eds, 1998
- Kaiser Permanente Northern California Regional Drug
Formulary, 1998
- Deprecated Reference
- Medical Knowledge Self Assessment Program (MKSAP) 19
Board Basics. An Enhancement to MKSAP19.
American College of Physicians, Philadelphia 2022
Component-of
piperacillin tazobactam (Zosyn)