Dosing
CrCl > 80: 2.5 - 4.5 iv q 6 - 8 h. Probably best to dose q 8 with a 4-hour infusion. It decreases mortality (PubMed).
CrCl 80-50: 2.5 - 4.5 iv q 6 - 8 h.
CrCl 50-10: ?
CrCl < 10: ?
Hemodialysis:
Peritoneal dialysis:
Important side effects
Important drug interactions
Methotrexate, probenecid, vecuronium.
When added to vancomycin it is associated with acute kidney injury (PubMed) (PubMed). One article is entitled (PubMed) "Increasing Evidence of the Nephrotoxicity of Piperacillin/Tazobactam and Vancomycin Combination Therapy—What Is the Clinician to Do?" How about not give that combination? Duh. How hards can it be to, oh, I don't know, think about the disease and give something else? Hard it appears.
A meta-analysis suggests an odds ratio of 3 for AKI (PubMed) when combined with vancomycin.
Rants and Screeds
The use of this antibiotic in sepsis empirically is associated with increased mortality rates compared to other agents, especially if the mic is in the high end of 'sensitive', greater than 2 ug/ml.
Funny how we had a piperacillin shortage (inexpensive) but plenty of pip/tazo (expensive). Wonder why?
Pearls
Beta-lactamase inhibitor combinations are problematic with some gram-negative rods, depending on the strain and the type of beta-lactamase. Clavulanate can be antagonistic for ticarcillin (PubMed) and other beta-lactam antibiotics (PubMed). This is less of a problem with tazobactam, maybe occurring 1% of the time (PubMed).
"Clinicians must remember that the addition of tazobactam does not always increase the susceptibility of P. aeruginosa and other Gram-negative bacilli expressing AmpC β-lactamases. However, tazobactam does extend piperacillin's activity against most β-lactamase producing strains of Enterobacteriaceae, H. influenzae, N. gonorrhoeae, and M. catarrhalis and has the potential to lower MICs against these strains expressing ESBLs (PubMed)."
Treatment of choice
In my opinion? Nothing. I do not believe I have ever used the drug.
Use for
Like all beta-lactamase inhibitor combination, I can't find a use for them. It is approved for appendicitis, cellulitis, cutaneous abscesses, diabetic foot infection, diverticulosis/itis, endometritis, Escherichia coli infections, gynecologic infections, intraabdominal infections, neutropenic fever, PID, peritonitis, pneumonia.
Don't use for
Class
Penicillin.
Curious Cases
Relevant links to my Medscape blog
Last update 11/30/19