Trimethoprim-Sulfamethoxazole Versus Levofloxacin for Stenotrophomonas maltophilia Infections: A Retrospective Comparative Effectiveness Study of Electronic Health Records from 154 US Hospitals

Abstract

Background Trimethoprim-sulfamethoxazole (TMP/SMX) is considered first-line therapy for Stenotrophomonas maltophilia infections based on observational data from small studies. Levofloxacin has emerged as a popular alternative due to tolerability concerns related to TMP/SMX. Data comparing levofloxacin to TMP/SMX as targeted therapy are lacking. Methods Unique adult inpatient encounters between January 1 st 2005 and December 31 st 2017 with growth of S. maltophilia in blood and/or lower respiratory cultures (including as part of polymicrobial growth) were identified in the Cerner Healthfacts™ database. Patients receiving targeted therapy with either levofloxacin or TMP/SMX and without other S. maltophilia-active agents were included. Propensity-scores were generated and overlap weighting was used to balance groups and simulate randomization followed by downstream weighted regression. The primary outcome was adjusted odds ratio (aOR) for in-hospital mortality or discharge to hospice. The secondary outcome was number of days from index S. maltophilia culture to hospital discharge. Results Among 1,581 patients with S. maltophilia infections, 758 received TMP/SMX and 823 received Levofloxacin. Levofloxacin displayed statistically similar mortality risk (aOR 0.76 [95% CI 0.58-1.01], p=0.06) compared to TMP/SMX. Levofloxacin (versus TMP/SMX) use was associated with a lower aOR of death in the prespecified subgroup of patients with LRTI (n=1,452) (aOR 0.73 [95%CI 0.54-0.98, p=0.03) and among those in whom the agent was initiated empirically (n=89) (aOR 0.16 (0.03-0.95, p=0.04). Compared to the TMP/SMX cohort, the levofloxacin cohort had fewer hospital days between index culture collection and discharge (weighted median[IQR] days 7 [4,13] vs. 9 [6,16]; p<0.0001). Conclusions Based on observational evidence, levofloxacin is a reasonable alternative to TMP/SMX in the treatment of bloodstream and lower respiratory tract infections caused by S. maltophilia.

In vitro Antibacterial Activity and Resistance Prevention of Antimicrobial Combinations for Dihydropteroate Synthase-Carrying Stenotrophomonas maltophilia

“…Based on observational evidence, levofloxacin and moxifloxacin are reasonable alternatives to SXT for the treatment of bloodstream and lower respiratory tract infections caused by S maltophilia. 10,[29][30][31] It is reported that sul-carrying S. maltophilia were more susceptible to moxifloxacin than levofloxacin in in vitro experiments, and moxifloxacin can inhibit the biofilm they form on the surface of the respiratory tract or intubation tubes. 9,[32][33][34] Therefore, moxifloxacin has a high clinical value as a therapeutic option for sul-carrying S. maltophilia.…”

The Contribution of Efflux Systems to Levofloxacin Resistance in Stenotrophomonas maltophilia Clinical Strains Isolated in Warsaw, Poland

“…Levofloxacin, along with trimethoprim/sulfamethoxazole, is the main drug used in the treatment of S. maltophilia infection [ 9 , 10 , 11 ]. However, an increase in the number of resistant strains or strains with reduced susceptibility to this fluoroquinolone has been observed worldwide in the last two decades [ 9 , 12 , 13 ].…”

“…Other therapeutic options include the use of fluoroquinolones, minocycline, and ticarcillin/clavulanate. Recently, it has been revealed that fluoroquinolones, an alternative treatment, are equally as effective as trimethoprim/sulfamethoxazole [ 9 , 10 , 11 ]. Levofloxacin was most frequently used among fluoroquinolones (187 of 331, 56.5%), followed by ciprofloxacin (114 of 331, 34.4%) [ 10 ].…”

Overcoming Stenotrophomonas maltophilia Resistance for a More Rational Therapeutic Approach

“…The lack of sufficient PK/PD data combined with diagnostic hurdles specific to S maltophilia impedes the optimization of antimicrobial therapy and makes it difficult for clinical laboratories to provide useful actionable information to clinicians [ 21 ]. As most S maltophilia infections occur in the respiratory tract and human epithelial lining fluid is known to have an acidic pH [ 22 ], drug concentrations and antibacterial activity at the site of infection must be considered. This creates additional challenges given the considerable PK variability among the limited number of available treatment options for S maltophilia , such as between-class differences in pulmonary penetration (~24% for cefiderocol vs >100% for levofloxacin) and within-class differences in activity at acidic pH among the fluoroquinolones [ 23–25 ].…”

“…Finally, discrepancies between in vitro and in vivo activity and clinical efficacy are common owing in part to its slow growth rate and high mutation frequency [ 29 ]. Together these issues challenge the ability to maximize drug efficacy and minimize toxicity, leading to the low cure and high mortality rates observed in S maltophilia infections [ 22 ]. Although TMP-SMX is typically considered a preferred agent for S maltophilia , there is no established PK/PD index or target threshold for efficacy or toxicity, severely impairing the ability to optimize its clinical use.…”