Is There a Better Choice Than TMP-SMX to Treat Stenotrophomonas maltophilia Infections?

Stenotrophomonas maltophilia is an aerobic, nonfermenting, gram-negative bacillus that is ubiquitously found in water, soil, and plants and is closely related to Pseudomonas.^1,2 S maltophilia is an opportunistic pathogen and typically causes hospital-acquired infections, particularly bacteremia and pneumonia, among patients with heavy health care exposures, malignancy, cystic fibrosis, neutropenia, mechanical ventilation, central venous catheters, recent surgery, trauma, or recent broad-spectrum antimicrobials.^3-5 The incidence of S maltophilia ranges from 7.1 to 37.7 cases per 10,000 discharges and has increased in recent years, suggesting it is an increasingly emergent iatrogenic threat.⁶ Prior iatrogenic outbreaks, felt to be related to tap water, have been well described in intensive care and inpatient hematologic malignancy and bone marrow transplant settings.^7,8

Because of high-level intrinsic resistance to multiple other antibiotic classes, traditionally trimethoprim-sulfamethoxazole (TMP-SMX) has been perceived as the antimicrobial treatment of choice. Duration of therapy is usually 7 to 14 days, depending on the site of infection and the host immune status.⁹ However, in recent years, the management of S maltophilia infections has become more difficult as the organism becomes increasingly resistant to TMP-SMX.¹⁰ As such, it is of increasing importance to identify which antimicrobials, particularly those besides TMP-SMX, are available to treat S maltophilia infections.¹¹

The recent manuscript “Clinical outcomes of Stenotrophomonas maltophilia infection treated with trimethoprim/sulfamethoxazole, minocycline, or fluoroquinolone monotherapy” by Junco et al explored this issue by assessing clinical outcomes of S maltophilia infection treated with a variety of antimicrobials. The authors completed a retrospective study of adult patients at an 1882-bed multihospital health system in Orlando, Florida, who received monotherapy for S maltophilia infection from January 1, 2010, to January 31, 2016. The antimicrobial agents assessed included TMP-SMX, a fluoroquinolone, or minocycline. The primary outcome was clinical failure, which included isolation of S maltophilia from the same culture site after 48 hours of therapy, alteration of treatment after at least 48 hours of therapy due to an adverse event of concern for clinical failure, and 30-day in-hospital all-cause mortality. Patients were excluded if they had less than 48 hours of monotherapy, a S maltophilia resistant to initial monotherapy, cystic fibrosis, or been treated for S maltophilia infection within the past 12 months.

The authors screened 490 patients, with 284 meeting inclusion criteria. Of those 284 patients, 217 (76.4%) were treated with TMP-SMX, 28 (9.9%) with a fluoroquinolone (either moxifloxacin, ciprofloxacin, or levofloxacin), and 39 (13.7%) with minocycline. Baseline characteristics were reflective of an older population (mean age [SD], 60 [18.0] years) that was severely ill, with an average Acute Physiologic Assessment and Chronic Health Evaluation II score of 19 (corresponding to an approximate in-hospital mortality rate of 25%)¹²; 56% of patients required mechanical ventilation, and 22% required vasopressor support.

However, there were notable differences in demographics and baseline characteristics between groups, including 3.5 days to initiate effective antimicrobial therapy in the minocycline group versus 2.9 and 2.4 days in the TMP-SMX and fluoroquinolone groups, respectively (P=.005), as well as 131 (60.4%) patients requiring mechanical ventilation in the TMP-SMX group versus 8 (28.6%) and 19 (48.7%) in the fluoroquinolone and minocycline groups, respectively (P=.004). Additionally, 101 (46.5%) patients had an acute kidney injury at any point during treatment in the TMP-SMX group versus 21 (75.0%) and 29 (74.4%) patients in the fluoroquinolone and minocycline groups, respectively (P=.002).

For the primary outcome, 97 (34.2%) patients met criteria for clinical failure, and after propensity score weighting was performed, clinical failure was similar at 77 (35.5%), 8 (28.6%), and 12 (30.8%) in the TMP-SMX, fluoroquinolone, and minocycline treatment groups, respectively (P =.69). After performing inverse probability–weighted regression adjustment, 30-day mortality was significantly lower at 5.5% in the minocycline group versus 15.0% in the TMP-SMX group (P=.011), but not significantly lower at 9.9% in the fluoroquinolone group (P=.41).

The study had several limitations. Notably, out of the initial 490 patients with S maltophilia on monotherapy, 206 (42.0%) were excluded, suggesting there may be uncontrolled bias in the study population. Also, the fluoroquinolone and minocycline groups were small at 28 (9.9%) and 39 (13.7%) patients respectively, so there is a significant risk of confounding. The study was retrospective and occurred over 5 years, introducing the possibility of confounders in treatment selection and outcome. Lastly, the antimicrobial treatment groups were not compared to β-lactam antimicrobials such as cefepime, which are often used in the treatment of S maltophilia, so the picture is not yet entirely complete.

However, this was the largest study to date comparing TMP-SMX with other antimicrobial monotherapies in the treatment of S maltophilia infections in a real-world setting. The investigators demonstrated that fluoroquinolones and minocycline displayed similar outcomes to TMP-SMX. Although 30-day mortality was lower in the minocycline arm, the low numbers and retrospective nature of the study preclude statements about superiority. This important study reveals the need for further, prospective, randomized investigations to determine optimal antimicrobial monotherapy and explore the role of combination therapy. Equally important would be further data to identify which patients with S maltophilia in cultures need no treatment at all. In its role as a harbinger of the multidrug resistant iatrogenic infections that will become increasingly impactful in the decades ahead, S maltophilia presents a clinical dilemma that demandsmore pragmatic clinical trial data.

References

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