carbenicillin; carindacillin (Geocillin)

Introduction

Tradename: Geocillin. 4th generation penicillin. (carbenicillin indanyl sodium)

Indications

• treatment of bacterial infections due to susceptible organisms
  • treatment of upper & lower urinary tract infections
  • asymptomatic bacteriuria
  • prostatitis

Contraindications

• severe renal impairment (creatinine clearance < 10 mL/min)

pregnancy category = b

safety in lactation = ?

Dosage

• urinary tract infection: 382-764 mg PO QID for 10 days or longer
• prostatitis 764 mg QID for 2-4 weeks or longer
• children:
  • 30-50 mg/kg/day divided QID
  • maximum 2-3 g/day
• take with water; tablet have bitter taste

Tabs: 382 mg. (23 mg of Na+/tab) Dose adjustment in renal failure:

creatinine clearance	dosage
10-50 mL/min	dose every 12-24 hours
< 10 mL/min	avoid use

Pharmacokinetics

• oral absorption: 30-40%
• distribution
  • crosses placenta
  • small amounts appear in breast milk
  • distributes into the bile
  • low concentrations in CSF
• protein binding 50%
• 1/2 life 1-1.5 hours (adults), prolonged in patients with renal insufficiency
• time to peak concentration: 0.5-2 hours
• 80-85% excreted unchanged in the urine
• serum concentrations insufficient for treatment of systemic infections
• moderately dializable (20-50%)

elimination via kidney

1/2life = 1.1 hours

protein binding = 50 %

elimination by hemodialysis = +/-

Antimicrobial activity

• Pseudomonas aeruginosa
• Providencia
• Morganella morganii
• Escherichia coli
• Proteus
• Enterococcus
• Enterobacter

Adverse effects

• common (> 10%)
  • diarrhea
• less common (1-10%)
  • nausea/vomiting, taste disturbance, flatulence, glossitis
• uncommon (< 1%)
  • headache, skin rash, urticaria, anemia, thrombocytopenia, leukopenia, neutropenia, eosinophilia, hyperthermia, itchy eyes, vaginitis, hypokalemia, hematuria, thrombophlebitis

Drug interactions

• give at least 1 hour prior to aminoglycosides

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

Test interactions

• false positive urine protein
• serum protein
• false positive urine glucose (clinitest)

Laboratory

• specimen:
  • serum, plasma (heparin, EDTA)
  • stable in solution for 15 days at 5 degrees C
• methods: MB, HPLC

More general terms

• 4th generation penicillin (extended-spectrum)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2560
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=20933
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=20824
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2559
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=28415
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=657287
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=93184
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=33554