Samuel L. Aitken, PharmD, MPH: Lessons Learned From a Stenotrophomonas maltophilia Case Study

Segment Description: Samuel L. Aitken, PharmD, MPH, clinical pharmacy specialist in infectious disease at The University of Texas MD Anderson Cancer Center, shares the lessons learned from a case study presented at IDWeek 2019 on a patient with Stenotrophomonas maltophilia infection.

Interview transcript (modified slightly for readability):

Dr. Aitken: I gave a presentation on a patient that we had at MD Anderson with a very serious disseminated Stenotrophomonas maltophilia infection who's an immunocompromised patient with a refractory leukemia, who had been neutropenic for about a month actually before developing a cellulitis with this organism. Unfortunately, over the course of treatment, [the patient] basically failed treatment with the first-line agent, which is trimethoprim-sulfamethoxazole. And really, it left us with a sort of a conundrum as to what to do clinically because the patient was in a very bad way, it was a terrible infection that was worsening, and we had just lost our drug of choice for that. And so we started looking through the literature to see what might be [some] possibilities.

Unfortunately, the literature with Stenotrophomonas treatment is quite limited. Even looking at the literature that led to trimethoprim-sulfa becoming the drug of choice, that was really not necessarily because it was anything good; it was just because that was the drug that existed when patients started getting infected with this organism. And so, since then, there have been several retrospective studies looking at alternatives to it. Levofloxacin, for example, is frequently active in vitro against the organism. Minocycline [and] tygocyclin are frequently active against the organism. There have been studies looking at these and they generally come to the conclusion that there's no difference, but with a major caveat for those. Unfortunately, because this literature is so limited in retrospective, there's a lot of confounding by indication in that the patients who get these alternative agents are likely not nearly as sick as the patients getting trimethoprim-sulfa. The other issue with them is that Stenotrophomonas causes a very heterogeneous group of infections with a very high associated mortality and essentially no associated mortality and anything ranging in between, so it's really difficult to sort of tease out what the drug effect might actually be there. You're really left with a very limited body of literature [for] what to do for this organism.

We did use those options. Levofloxacin was resistant, as the patient had been on prophylaxis with that beforehand. Then we ended up giving minocycline as well as ceftazidime, which were active in vitro. And unfortunately, those drugs also failed to treat the patient's infection adequately. Then we were really sort of stuck with what to do, so that led us to do some more digging in terms of the literature for this organism and really sort of understand the mechanistic basis for why this organism becomes so drug-resistant. When compared to other gram-negative organisms that we commonly encounter—especially the Enterobacteriaceae, where resistance is predominantly associated with acquisition of resistance elements—Stenotrophomonas is more along the lines of Acinetobacter and Pseudomonas in that it has everything it needs right there in its own genome to become resistant to essentially everything we have.

In addition to the 2 probably most well-known mechanisms in Stenotrophomonas are 2 beta-lactamases known as L1 and L2. The L1 beta-lactamase is a metallo-beta-lactamase; it's very similar to other metallos, such as NDM or VIM, in that it hydrolyzes essentially all beta-lactams we have with the exception of aztreonam and it is not inhibited by any of the commercially available beta-lactamase inhibitors. L2 is a class A cephalosporinase and that has a substrate profile of basically everything other than carbapenems, but it is inhibited by commercially available beta-lactamase inhibitors, especially clavulanate and avibactam. That led us to explore the possibility of synergy between aztreonam, which would not be hydrolyzed by the L1, and ceftazidime/avibactam, which would inhibit that other beta-lactamase. It turned out there actually was in vitro synergy for this organism. We did use that combination to try to treat the patient but, unfortunately, the infection progressed and the patient ultimately passed away.

Really the other lesson that we took from this is that in immunocompromised patients, particularly those of hematologic malignancy, Stenotrophomonas can be an absolutely devastating infection. And even if you have a bunch of antimicrobials that are active in vitro, even if you use them, use them appropriately, use them early...unfortunately, the host conditions might not necessarily allow for the infection to clear, as was the case here. So it really just is a good lesson [that] just because a drug is active in vitro doesn't necessarily mean it'll work in a patient. And it is also a good lesson to sort of call for a better understanding of these infections and risk factors for it so we can prevent them from happening and avoid these issues of potentially having to treat an untreatable infection.