Why we use Zosyn instead of Ampicillin and Gentamicin at Tulane-Lakeside

Posted on December 16, 2010. Filed under: policy rationales |

Our NICU switched its first choice antibiotic cocktail from ampicillin and gentamicin to Zosyn monotherapy on Jan. 1st 2010. There were a lot of reasons and I am going to detail them here so that the next time some one asks me I can just sit them down and have them read this.

First – gentamicin is the source of most drug errors in the NICU. Because of this we have to draw a lot of blood to check it’s drug levels. In small babies this means we are taking blood out, which means gentimicin dosing translates into a greater need for transfusions. With the recent revelation that there is a real association between late transfusions and NEC, the impetus to get rid of things that promote transfusions is strong.

Second – gentamicin is ototoxic. This has been overblown. If used correctly, the risk of hearing loss is low. But in some states, like Louisiana, the concern about gentimicin ototoxicity has resulted in some policies that are a bit questionable. For example, in Louisiana, if an infant spends more than 24 hours in the NICU, they should have a high level hearing screen done by a trained audiologist every six month until they are 3 years of age. That’s a little excessive for infants who often only get 48 hours of gentimicin during a rule out that proves to be negative. With Zosyn it is even more questionable and some of you may have noticed that we have a “canned” statement in all of our discharge statements letting parents and primary care providers know that most of our NICU graduates are never exposed to gentamicin and thus these state recommendations should discussed and a care plan tailored as they think appropriate.

Third – there is recent evidence that many of drugs we use early in neonatal life keep the ductus arterious open. In general, we like to let this vessel close, preferrably ALL BY ITSELF, without the help of a surgeon and even without the use of additional drugs when possible. It turns out that gentimicin is a potent vasodilator of the ductus (as is amikacin, a close relative of gentamicin sometimes used as an alternative to gentamicin). The data for this is from Jeff Reese’s seminal work (CLICK HERE).

Fourth – because ampicillin is being used by obstetricians to treat group B strep, we are seeing more and more ampicillin resistant E Coli in newborns. Gentamicin creates stasis, but often does not kill this organism by itself. The bug has a nasty tendency to hide out in the CNS and re-emerge once initial antibiotics are stopped. So ampicillin is not the wunder drug it used to be. Our primary reason for keeping it in the rotation all these years is to cover Lysteria.

Fifth – Zosyn has been used of decades. Is known to be safe. It covers Lysteria and basically everything else that ampicillin and gentamicin cover together. It has recently been studied in a preliminary multicenter PK study at the doses we are using (that study is likely to be expanded in the near future). While we made the switch as a categorical change in policy, we did so at roughly the same time as Wesley Medical Center (University of Kansas) in Witchita and the two centers will be performing a combined before and after analysis of outcomes at the end of 2010. The primary purpose of this analysis is quality improvement, to see if we really do reduce blood transfusions and other complications associated with anemia.

Finally, because Zosyn is not used often in the adult population, we are unlikely to acquire resistance in infants. Obviously, this will be one of the outcomes we are watching for in our quality improvement analysis.

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