In this article an infectious diseases pharmacist discusses five things to know about Stenotrophomonas maltophilia.
Authored by: Hunter O. Rondeau, Pharm.D
Article posted 9 July 2022
I remember the first time hearing the name Stenotrophomonas. At first, I thought a discussion about a Greek philosopher or new dinosaur was taking place. The medical team was struggling to determine what and how to approach the clinical conundrum that is Stenotrophomonas maltophilia. So who is “Stenotrophomonas”, and why are discussions surrounding them filled with many “well, it depends”?
Species of Stenotrophomonas are Gram negative, non-lactose fermenting bacteria. Stenotrophomonas are ubiquitous in the environment, primarily due to their role in the nitrogen and sulfur cycle. The most common species of the genus is Stenotrophomonas maltophilia, and is the only known pathogenic species. Name changes have occurred a few times in the last century, with at one point in its history being called Pseudomonas maltophilia. Interestingly, Pseudomonas aeruginosa and Stenotrophomonas maltophilia have been frequently recovered from hospital sinks upon performing environmental testing. In clinical practice, Stenotrophomonas maltophilia is somewhat affectionately referred to as “Steno”for short.
When I said ubiquitous, I mean this organism seems to be everywhere. Steno has been recovered in soil, plant roots, water treatment centers, dialysate solution, tap water, bottled water, ice machines – you name it. Steno’s ability to form biofilms allows it to adhere to and colonize medical equipment quickly and frequently.
Due to Steno’s ubiquitous presence and biofilm capabilities, it is associated with many types of infections. Reports of osteomyelitis, endocarditis, and meningitis exist, but more often Steno appears where there is hardware to cling to. Think of urinary recovery in the presence of a urinary catheter, bacteremia in the presence of a central line catheter, and sputum recovery in the presence of an endotracheal tube.
Mortality associated with Steno infections can be incredibly high. In bacteremic patients, up to 69% mortality has been observed. High mortality is especially seen in immunocompromised patients. A lung infection due to Steno can be fatal, as the pathogen can create proteins that allow for tissue necrosis and hemorrhage of pulmonary tissue. The question of: “Is the Steno present because they are critically ill, or did the Steno cause them to become critically ill?” – makes the decision to treat Steno more challenging, as the few antibiotic options we have available can be limited by their tolerability.
One of the most challenging obstacles when encountering Steno is its impressive antibiotic resistance profile. Due to it’s harboring of two β-lactamases, L1 (metallo-β-lactamase) and L2 (cephalosporinase), Steno is unphased by common broad-spectrum regimens like vanc–zosyn, vanc-cefepime or vanc-meropenem. Even newer therapies like TOL/TAZ, CAZ/AVI and MERO/VAB are no match for this combination of β-lactamases. Intrinsic resistance to aminoglycosides and macrolides is also seen. Without diving into the rest of its mechanisms of resistance, the frontline antibiotics with the most data to support their use are TMP/SMX, levofloxacin and minocycline. Even with these agents, Steno has proven it can develop resistance to all of them, albeit, some more quickly than others.
In this article, I will identify and discuss 5 key questions health care practitioners should ask when encountering Stenotrophomonas maltophilia in clinical practice….
Question #1: Is this a Stenotrophomonas infection or a Stenotrophomonas colonization?
Just because you recover a bacteria in culture, does not always mean you have an infection.
Remember that Steno LOVES to colonize hardware. You can frequently find Steno in cultures where catheters are involved, especially central lines. A frequently discussed risk factor for Stenotrophomonas infection and mortality is the use, and failure to remove a central venous catheter.
Question #2:. Should I use TMP/SMX to treat Stenotrophomonas? What dose and formulation should I use?
TMP/SMX is the preferred agent, but there are many issues that may prevent its use. Hyperkalemia, bone marrow suppression, hepatotoxicity and nephrotoxicity at Steno treating doses (i.e., higher than your average UTI doses) are more common.
With the IV formulation, TMP/SMX requires a large amount of diluent with D5W which can be 1.5 liters per day. You can easily fluid overload a patient with high doses of IV TMP/SMX if not careful! Also, beware it has a short expiration date after mixing, making each dose an acute task for the inpatient pharmacy team. Some institutions cap individual doses at 500 mg as a result of the fluid volume and short stability once mixed in the pharmacy.
The annually updated IDSA guidelines for treating resistant Gram negative rods discusses TMP/SMX in detail, as well as the more recent, lower dose recommendation of 8-12mg/kg/day divided q8-q12h (previously 15-20mg/kg/day).
While IV or PO is recommended, using the oral formulation should be considered when four key criteria are met:
i. The Steno isolate is susceptible to TMP/SMX
ii. The patient is hemodynamically stable
iii. Reasonable source control has been achieved / the patient’s clinical trajectory is acceptable for oral therapy
iv. The patient can absorb orally administered medications
Question #3: When should I not use SMX/TMP for Stenotrophomonas? What drug should I use instead?
If resistance or other issues prevent SMX/TMP use, alternative agents such as levofloxacin, tetracyclines or cefiderocol may be considered for mild infections. Ceftazidime-avibactam and aztreonam together are recommended by the IDSA guidelines for moderate to severe infections when TMP/SMX or minocycline cannot be used, as this combination is able to inhibit both β-lactamases (avibactam inhibits L2 to allow aztreonam to inhibit L1). Minocycline, at higher than typical doses, has limited, but promising results. Cefiderocol has very limited clinical data, but can be considered for use alone for mild therapy, or as an adjunctive for moderate to severe infections.
No RCT’s have been completed in this area, and most of the knowledge of Steno comes from small study populations of retrospective data. However, one of the largest studies about Steno was published earlier this year, finding comparable outcomes between TMP/SMX and levofloxacin for bacteremias and pneumonia. Be careful with using levofloxacin, as Stenotrophomonas exposed to fluoroquinolones can cause resistance to not only fluoroquinolones, but other frontline agents, like sulfonamides and tetracyclines.
Ceftazidime is no longer recommended for Stenotrophomonas, as the breakpoints likely do not accurately represent the impact of the β-lactamases in vivo. It could be argued that Steno “infections” treated “successfully” with ceftazidime were likely colonizations and not true infections.
Question #4: How am I going to get source control?
As previously mentioned, Steno LOVES to colonize medical equipment.
Change your catheters unless you want Steno to keep waving hello every time you collect a culture culture.
Question #5: How long do I treat Stenotrophomonas infections for?
Trials evaluating durations with Steno hav not been conducted and there is a lot of uncertainty in the duration of therapy, as patients commonly receive “longer” courses of therapy (i.e., >14 days). Steno often appears as a consequence of excessive antibiotic use, so even more antibiotics seem counterintuitive. Based on the location of the infection, respective guidelines can help guide durations (e.g., 7-10 days for HAP/VAP and 7-14 days for bacteremia).
Are you walking away with more questions than answers? As with many things in the ID world, black and white answers are very uncommon. As Stenotrophomonas is one of the organisms included in the annually updated IDSA’s resistant GNR guidelines, so be on the lookout for updates there!
Stenotrophomonas Readings and Resources
Additional Suggested Reading:
Heil EL, Bork JT, Abbo LM, et al. Optimizing the Management of Uncomplicated Gramnegative Bloodstream Infections: Consensus Guidance Using a Modified Delphi Process [In press]. Open Forum Infect Dis 2021; 8: ofab434.
ABOUT THE AUTHOR
Hunter O. Rondeau, Pharm.D is a Kansan native who received their Pharm.D.from the University of Kansas (Wichita, KS) in 2021. He currently is a PGY-2 pharmacy resident at the University of MN Medical Center – M Health Fairview in Minneapolis, MN. His interests include antimicrobial stewardship, Gram negative resistance, and teaching infectious diseases through FOAMed.
In his spare time, he creates specialty cocktails.
You can find him on Twitter @Floralquinolone.
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