Updated: Sep 17, 2019
Dear Medical Colleagues,
I think it’s time to branch out and show a little more creativity in our initial antibiotic selection. I get it – the patients in front of you look really sick, you aren’t quite sure what’s wrong with them yet, and you want to make sure they’re covered for every pathogenic bacterium under the sun…and maybe some that live where the sun don’t shine (enteric organisms? ID joke? Why aren’t you laughing?). So, you scorch the proverbial earth with the venerated one-two punch of vancomycin and ZOSYN® - hereafter referred to simply as V/Z. “In all things, CYA” sounds like good advice in our current era of medicine, but V/Z is a whole lot of coverage. It’s probably faster to list the bacteria that this heavy-handed combo doesn’t cover. Let’s see – Legionella, Mycoplasma, rickettsial infections, most bacterial zoonoses, most VRE and a handful of really resistant Gram negatives…oh, and mycobacteria, but those really shouldn’t crack the list of likely pathogens for the overwhelming majority of patients presenting with sepsis. It just seems…crude – akin to removing dead trees by burning down the whole forest. Collateral damage produces consequences, and it’s past time to start thinking more about the ripple effect of our cavalier treatment approaches.
It’s pretty amazing that we’ve gotten away with it for this long. ZOSYN® was approved in the US in 1993 and quickly became the antibiotic workhorse of inpatient facilities. Vancomycin has been around since 1954, but its use didn’t really take off until community-acquired MRSA started sweeping the country in the 1980s. By the late 1990s, most US hospitals had realized that the V/Z combination is good for what ails you, and prescribing is still going strong 20 years later. A lot has changed during this time, however – rates of MRSA infection are actually declining significantly, and highly-resistant Gram negatives are on the rise. Minimum inhibitory concentrations (MICs) for vancomycin against MRSA have crept upward, associated with increased risk of vancomycin treatment failure. Likewise, ZOSYN® has been at least partly responsible for driving an increase in extended spectrum beta-lactamase (ESBL)-producing organisms. Perhaps more telling is the number of Gram negative organisms I now see with isolated ZOSYN® resistance. In the grand scheme of bacterial mutation, however, resistance to the components of V/Z has been developing at a glacial pace, but we do have other, more compelling reasons to be judicious in our antibiotic selection.
Remember what I said about collateral damage? Consider Clostridioides (formerly Clostridium) difficile – the scourge of healthcare in resource-rich countries. While we can’t pin the problem squarely on the “Z” component of V/Z, it certainly doesn’t help. Vancomycin is also no help to you here because it doesn’t cross the gut barrier from the bloodstream. Generally speaking, the broader the antibiotic spectrum, the higher the risk of C diff, and I already told you that ZOSYN® is a scorched-earth antibiotic. Even if you don’t get C diff, your kidneys may get burned in the process – several large, retrospective studies in recent memory have found increased rates of acute kidney injury in patients receiving the V/Z combo versus either agent alone or another antibiotic. I know there are some skeptics out there, but I am personally convinced that vancomycin monotherapy can be nephrotoxic in its own right. Combine that with the sizable sodium load of ZOSYN® (just over 1 gram per day at 4.5 gm Q6H dosing), and you have a recipe for unhappy kidneys – potentially unhappy hearts as well – and a longer hospital stay. Lastly, and perhaps most importantly to our patients, these two drugs are just no fun to take. Vancomycin frequently causes itching, flushing and phlebitis during infusion, and a single dose is typically run in over 90 minutes or more, potentially tethering patients to an IV pole for hours a day. ZOSYN® doses run faster, but they have to be given four times a day, so, between the two drugs, there isn’t much time each day that patients aren’t tied up to an infusion pump. Oh and, by the way, ZOSYN® is also known for causing antibiotic-associated diarrhea in the absence of C diff infection in more than 10% of patients – just in case you needed one more reason to ease up on prescribing it.
When it comes to antibiotic prescribing, a little common sense goes a long way. The 65-year-old presenting with her first-ever bout of pneumonia after a 30-year run with no hospitalizations is highly unlikely to have a multidrug-resistant (MDR) organism – just use ceftriaxone/azithromycin or maybe levofloxacin. This false distinction we call “HCAP” (healthcare-associated pneumonia) is falling out of favor as people realize that there’s nothing magical about 90 days out of the hospital. In fact, a majority of patients returning with pneumonia after a stay in a healthcare facility will still have a fairly susceptible organism. Cellulitis is another area with major potential for improvement in stewardship and a pet peeve of mine – if it’s not purulent, it’s not MRSA. There are, of course, exceptions to every rule, but this one is quite consistent. The overwhelming majority of non-purulent cellulitis is due to either beta-hemolytic Strep (groups A, B, C, F and G) or MSSA, and cefazolin should be your go-to in the hospital. In my opinion, Gram negative coverage is generally not necessary for cellulitis except in select cases of chronic wounds and immunosuppressed patients. If that makes you nervous, remember that cefazolin actually covers a lot of the more susceptible varieties of E coli, Klebsiella and Proteus. If you still feel the need to add a second agent because “the patient is sick” (aren’t they all?), then clindamycin is a reasonable addition for its antitoxin (protein synthesis-inhibiting) effects. Look back at previous culture results – has the patient grown any resistant organisms before? If not, you can feel better about keeping a narrower spectrum, since, in my experience, if resistant organisms are present, they will show up in cultures at some point.
If all of that still doesn’t convince you to be more selective in your antibiotic choices, know that it causes your ID consultants mental anguish and maybe even a little physical pain to witness the indiscriminate decimation of all bodily bacteria when there are more sensible options available. Besides, V/Z is just unimaginative, and healthcare providers are supposed to be a thoughtful, creative bunch. There are over 100 different antibacterials available for use in US hospitals, so don’t limit yourself to two. Even a modicum of discernment is appreciated by those of us in infectology – maybe keep the vanc but substitute ceftriaxone for ZOSYN® in a patient with no known history of MDR organisms. Wander off the beaten path and try something new like cefadroxil – it’s closely related to cephalexin but with even higher oral bioavailability. You’ll know you’ve ventured far enough when you can no longer pronounce the generic name. In that case, call me.