Abstract
D
The authors state that they made the assumption that the metronidazole was infused over 30 minutes and imply that they considered appropriate timing only if infusion was completed at the time of incision. This is not consistent with the published literature in which every article I can find on antibiotic timing that actually reports this in detail only reports the time of initiation of the infusion [10,11] or presents the data in a way that implies this [12–19]. Most studies reporting on antibiotic timing do so from the medical record where the standard throughout the country is to record the time of initiation of the infusion and does not record the duration. After an extensive search I have been unable to find any references explaining why a long infusion time would be necessary for metronidazole. An online Baxter/FDA label [20] says that for prophylaxis 15 mg/kg (1,005 mg in a 70-kg patient) can be infused over 30 to 60 minutes. This would equal 500 mg in 15 to 30 minutes. I have found seven articles reporting on the infusion at the rate of 500 mg in 20 minutes without any report of side effects [21–28]. One of these also implies infusion of 2 g in 20 minutes to some of the subjects [21], and two others report giving 1 g in 30 minutes that would be equivalent to 500 mg in 15 minutes [29,30]. But the real refutation of the need for slow administration comes from the two recent reports from Basel, Switzerland in which more than 884 patients have received a combination of 1.5 g of cefuroxime mixed in an intravenous bag with 500 mg of metronidazole in two to five minutes, and 91 patients received 3 g of cefuroxime plus 1 g of metronidazole without untoward side effects [1,31]. This is a practice that continues at that institution and has been followed for years involving thousands of patients (written personal communication [email], Walter Weber, MD, 2018). In addition, I have polled the anesthesiologists in my own institution (University of Washington Medical Center, Seattle, Washington) where for many years we have given our colorectal patients a pre-mixed bag of cefazolin 2 g plus metronidazole 1 g in rapid fashion in the operating room before incision. The average duration of infusion reported by my anesthesiology colleagues (but not documented, as only the start of infusion is entered into the electronic medical record) is 5 to 15 minutes. In the past year we have changed our standard to 2 g of cefazolin plus 500 mg of metronidazole because of a recent metronidazole shortage.
This gets us to the final point regarding prophylaxis with cefazolin (or other cephalosporins) plus metronidazole. Metronidazole is compatible in solution with essentially all cephalosporins, and because of this our operating room pharmacy has provided us with pre-mixed intravenous bags as described above and similar to those used in Basel [1], which I lightheartedly refer to as “cefanidazole.” There is extensive literature confirming the safety of this practice [32–39]. An advantage of this combination in one intravenous bag is the efficiency that it provides for the anesthesia team, which is faced with a multitude of important tasks affecting patient safety as the preparation for a major operation proceeds and antimicrobial prophylaxis is only one of those. This eases the burden on the anesthesia team and provides optimal prophylaxis for the patient. Dr. Danan and her team can continue to give their patients the preferred antibiotic agents and avoid the now ineffective second-generation cephalosporins while making administration easier in the operating room and stop worrying about prolonged infusions.