Treatment approaches for severe Stenotrophomonas maltophilia infections

Abstract

Purpose of review Stenotrophomonas maltophilia is an emerged opportunistic pathogen. Intrinsic multidrug resistance makes treating infections caused by S. maltophilia a great clinical challenge. Herein, we provide an update on the most recent literature on treatment options for severe S. maltophilia infections. Recent findings Trimethoprim-sulfamethoxazole (SXT) is recognized as the first-line therapy for S. maltophilia infections. However, its clinical use is based on good in vitro activity and favorable clinical outcomes, rather than on solid minimum inhibitory concentration (MIC) correlations with pharmacokinetic/pharmacodynamics (PK/PD) and/or clinical outcomes. The same is true for other treatment options like levofloxacin (LVX) and minocycline (MIN). Recent PK/PD studies question the current clinical breakpoints for SXT, LVX, and MIN. Based on this, the latest guidance issued by the Infectious Diseases Society of America (IDSA) recommends using these agents only as part of a combination therapy. Alternatively, novel therapeutic options such as cefiderocol (FDC) and ceftazidime-avibactam plus aztreonam (CZA-ATM) are suggested, based on limited but promising clinical data. Summary PK/PD data and controlled clinical studies are needed to optimize current treatment options. Presently, combination therapy of SXT, LVX, MIN, or FDC, or monotherapy with CZA-ATM are recommended therapeutic options for severe-to-moderate S. maltophilia infections.

Optimizing Antibiotic Therapy for Stenotrophomonas maltophilia Infections in Critically Ill Patients: A Pharmacokinetic/Pharmacodynamic Approach

“…According to our study, while in the U.S., a high level of treatment success is achieved with any of the three dose regimens studied (CFR ≥ 90%), in Europe, even with the highest dose evaluated, the probability of treatment success is much lower (CFR < 75%). In spite of our results, and despite the fact that a recent meta-analysis has shown that the resistance rate of S. maltophilia has increased in recent years [ 24 ], cotrimoxazole remains the first choice for treatment, with the dosing recommendation ranging from 10 to 15 mg/kg/day of trimethoprim q8h and a maximum daily dose of trimethoprim of 960 mg [ 1 , 8 ].…”

“…These results agree with Lasko et al [ 18 ], who demonstrated that cotrimoxazole in monotherapy even at a high dose displays limited activity against cotrimoxazole-susceptible S. maltophilia strains. In fact, several authors have pointed out the necessity of redefining the breakpoints of cotrimoxazole for S. maltophilia [ 8 , 19 , 20 ]. Apart from cotrimoxazole, we detected discrepancies between the breakpoints for the rest of the antibiotics.…”

“…The overexpression of efflux pumps also contributes to resistance to tetracyclines, quinolones, cotrimoxazole (trimethoprim/sulfamethoxazole), tigecycline, and polymyxins. S. maltophilia also acquire genes horizontally that confer resistance to cotrimoxazole ( sul and dfrA ) and beta-lactams ( bla ) [ 4 , 8 ].…”

Deciphering the Coevolutionary Dynamics of L2 β-Lactamases via Deep Learning

“…The prevalence of S. maltophilia infections in the hospital setting has been on the rise, and this bacterium is increasingly recognized as a formidable multidrug-resistant pathogen . Traditionally, S.…”

“… 20 The prevalence of S. maltophilia infections in the hospital setting has been on the rise, and this bacterium is increasingly recognized as a formidable multidrug-resistant pathogen. 21 Traditionally, S. maltophilia has demonstrated resistance to a wide range of β-lactam antibiotics, including penicillins, cephalosporins, and carbapenems. This resistance is primarily attributed to the expression of L1 and L2 β-lactamases.…”