Uglier than “syn”

I want to understand why I hear so much shade thrown at Piperacillin/Tazobactam or Zosyn, which I will now call PipTaz. The googles tell me there is a significant risk of liver injury. Is that it? On Epocrates and other googles, it seems to be about $20 a dose. Is that accurate? Is that why it gets hate? Please tell me or just point me in the right direction. I’m getting a lot of Indian pharmacy websites. I did find this in an article from the International Journal of Infectious Diseases that "economic analyses have shown that generic antibiotic treatments during a 5-day hospitalization cost on average US$ 45.5–98.2, while the use of innovators can cost US$ 106.2–463.7."

Down to brass tacks or tax, I never know. Piperacillin is, guess what? A penicillin which means it has the good old beta-lactam mechanism of action. Disrupting the peptidoglycan wall by binding to the PBP and causing the cell to lyse. It is enhanced to allow entry into gram negative bacteria, something about a polar side chain but that is above my pay grade, and is commonly used against Pseudomonas. In the past we talked about beta-lactamase, the arch nemesis to beta-lactam antibiotics, the kryptonite to beta-lactam superman, the fire to the beta-lactam straw. You get the idea. 

So in bursts tazobactam which runs defense for the piperacillin telling the beta-lactamase to get off his lawn like Clint Eastwood in Grand Torino. This allows for a sort of pass against typical resistance to beta-lactamase producing microbes. Which expands its use. From Antimicrobe.org, PipTaz covers "Staphylococcus aureus (methicillin susceptible), Coagulase negative Staphylococci, Streptococcus pneumoniae (penicillin susceptible), Streptococcus spp., Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitides, Neisseria gonorrhoeae, Enterobacteriaceae, E. coli, Pseudomonas aeruginosa."

PipTaz is commonly given for PID, cellulitis and sepsis to name a few and is not the only combination antibiotic out there. Amoxicillin/clavulanate is one. Cefepime/Enmetazobactam is another. The last one is touted in a trial of 1034 complicated UTIs comparing the cefepime/enmetazobactam to PipTaz. Of course the new one is better (insert sarcasm). I do not know how much it will cost but being a novel combo, probably a billion dollars, a kidney, your soul, and first born child. So is it that much better? We will have to see, but I always am a bit skeptical given how much these can cost when new. Not saying that if it is that great we should sacrifice patient outcomes, but it is a cost/benefit analysis. 

Thats pip/taz for you from my strange mind and some journals. Again, please tell me why there is so much hate for the Zosyn. I want to know these things or else I will make bad jokes about it and my jokes are already bad enough with subjects I understand. Imagine if I was ignorant. 

References 

An unusual case of piperacillin-tazobactam-induced fever, eosinophilia, thrombocytopenia and liver damage

 from the European Journal of Hospital Pharmacy 2021 by Jawed et al.

Effect of Cefepime/Enmetazobactam vs Piperacillin/Tazobactam on Clinical Cure and Microbiological Eradication in Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis: A Randomized Clinical Trial from JAMA Network October 2022 by Kaye et al.

Image of P. Aeruginosa from Wikipedia.

Results of the effectiveness of two piperacillin–tazobactam molecules in the real world from the International Journal of Infectious Diseases by Machado-Alba et al. in 2018.

The super duper reliable Wikipedia, from Wikipedia and whoever wanted to write that article. Yay.