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Treating S. maltophilia Infections
Treatment Considerations for Stenotrophomonas maltophilia Infections

Released: February 22, 2023

Expiration: February 21, 2024

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Key Takeaways
  • Stenotrophomonas maltophilia is one of the most common carbapenem-resistant, gram-negative pathogens causing bloodstream infections and pneumonia in hospitalized patients.
  • Preferred treatment options include trimethoprim/sulfamethoxazole and minocycline. Combination therapy may be considered in patients with moderate to severe infections and those who do not respond clinically to monotherapy.

Stenotrophomonas maltophilia is an environmental gram-negative bacterium that is increasingly implicated in healthcare-acquired infections and, to a lesser extent, community-acquired infections. Some of its traits, including avid biofilm formation and intrinsic resistance to carbapenems, make it especially suitable for survival in the hospital environment. Risk factors for infection by S. maltophilia include prolonged hospital stay, presence of indwelling devices, and exposure to antibiotic therapy, among others. The 2 common clinical presentations are bloodstream infections and pneumonia.

S. maltophilia is now the most common carbapenem-resistant, gram-negative bacteria causing bloodstream infections in the United States. Intrinsic resistance to carbapenems (due to production of L1 β-lactamase) and many of the commonly used β-lactam agents (due to production of L2 β-lactamase) pose a challenge in selecting therapy. 

In this commentary, we will review a patient case and discuss key considerations for treating infections caused by S. maltophilia. 

Case Details
A 53-year-old man is admitted to the hospital with severe COVID-19 pneumonia. He is treated with remdesivir, dexamethasone, and baricitinib, as well as empiric vancomycin and ceftriaxone, but his clinical status worsens, and extracorporeal membrane oxygenation (ECMO) is initiated. Several days later, his tracheal aspirate grows Enterobacter cloacae, and ceftriaxone is changed to meropenem.

He remains critically ill on ECMO. Two weeks later, 2 sets of blood cultures drawn from a central venous catheter and a peripheral vein as part of fever workup grow S. maltophilia. Upon susceptibility testing, the strain is susceptible to trimethoprim (TMP)/sulfamethoxazole (SMX) and minocycline and resistant to levofloxacin. How would you manage him at this point?

Therapeutic Considerations
In this case, the diagnosis is straightforward: The patient has a central line‒associated bloodstream infection. 

For pneumonia, establishing the diagnosis can be more nuanced because a positive respiratory culture does not always indicate infection, and polymicrobial cultures also are common, in which case S. maltophilia could represent a bystander rather than a true pathogen. 

In terms of treatment, S. maltophilia is intrinsically resistant to carbapenems, as well as commonly used broad-spectrum β-lactam agents including piperacillin/tazobactam and cefepime. Among β-lactams, ticarcillin/clavulanate and ceftazidime previously had reasonable activity against S. maltophilia, but they are less commonly used because of increased rates of resistance. Instead, TMP/SMX and minocycline are the preferred agents in the 2022 Infectious Diseases Society of America (IDSA) treatment guidance for mild infections. Other options include tigecycline, levofloxacin, and cefiderocol. 

TMP/SMX
TMP/SMX is active against S. maltophilia, and—despite its use over the years—resistance remains uncommon to date. Comparative effectiveness studies with other agents are scarce. Nonetheless, it is considered the first-line treatment given its robust activity and long history of clinical use.

Minocycline
Tetracycline derivatives generally are active against S. maltophilia, and minocycline is the most active among these. Minocycline also has the advantage of having a susceptibility breakpoint established by the Clinical and Laboratory Standards Institute. Resistance may be increasing, but the majority of isolates remain susceptible. 

The large volume of distribution and consequent low serum level of minocycline make it less favorable for the treatment of bloodstream infections, as in this case.

Levofloxacin
Levofloxacin also has been used for the treatment of S. maltophilia infection, and observational data suggest that it is as effective as TMP/SMX—however, resistance is increasing, and susceptibility cannot be assumed in the absence of susceptibility testing. Development of resistance while receiving prolonged therapy also is a potential concern.

Cefiderocol
Cefiderocol is a newly developed siderophore cephalosporin and has excellent activity against S. maltophilia. Despite being a cephalosporin, it is stable against hydrolysis by L1 and L2 β-lactamases produced by the bacteria. Clinical experience is extremely limited; thus, cefiderocol remains on the reserve list of alternative options at this time. 

Back to the Case
The patient was switched from meropenem to TMP/SMX. His bacteremia was cleared when he came off ECMO and the drive lines could be removed. He eventually was discharged to a rehabilitation facility on hemodialysis.

Combination Therapy
As this case illustrates, patients who develop S. maltophilia infection typically are very ill to begin with. Would such patients then be better off with combination therapy, that is, 2 active agents given together? Although in vitro studies have suggested the presence of synergy for certain combinations, the clinical benefit is uncertain. 

For moderate to severe S. maltophilia infections, the IDSA guidance recommends 3 different approaches. Combination therapy with TMP/SMX and minocycline is the preferred approach, followed by initiation of TMP/SMX monotherapy with the addition of a second agent (eg, minocycline, tigecycline, levofloxacin, or cefiderocol) if there is a delay in clinical improvement. The third option includes combining ceftazidime/avibactam and aztreonam. The rationale is that avibactam, a potent β-lactamase inhibitor, protects aztreonam from L1 β-lactamase, allowing aztreonam, which is stable against L2 β-lactamase on its own, to exert its activity.

Of course, we can try to reduce the incidence of S. maltophilia infection through measures such as proper management and early removal of indwelling catheters when possible and avoidance of excessive carbapenem use that may select for this pathogen.

Your Thoughts?
How would you have managed this patient? Do you routinely use combination therapy in treating S. maltophilia infection? Join the discussion by leaving a comment.