Stenotrophomonas maltophilia

INTRODUCTION — Stenotrophomonas (Xanthomonas) maltophilia is a multidrug-resistant gram-negative bacillus that is an opportunistic pathogen [1-4], particularly among hospitalized patients. S. maltophilia infections have been associated with high morbidity and mortality in severely immunocompromised and debilitated individuals.

The clinical features and management of S. maltophilia infections are discussed here. The general approach to gram-negative bacillary bacteremia, catheter-associated bloodstream infections, and hospital-acquired pneumonia are discussed elsewhere. (See "Gram-negative bacillary bacteremia in adults" and "Intravascular non-hemodialysis catheter-related infection: Treatment" and "Treatment of hospital-acquired and ventilator-associated pneumonia in adults".)

MICROBIOLOGY — S. maltophilia is a ubiquitous, aerobic, nonfermentative, gram-negative bacillus that is closely related to the Pseudomonas species [5].

The organism was first isolated in 1943 and, at the time, was named Bacterium bookeri. It was later classified within the genus Pseudomonas, then Xanthomonas, and then finally Stenotrophomonas in 1993 [4,6,7]. The name signifies "a unit feeding on few substrates," based on the Greek roots stenos (narrow), trophos (one who feeds), and monas (a unit). Maltophilia means "affinity for malt," based on the Greek roots maltum (malt) and philia (affinity).

S. maltophilia is the only species of Stenotrophomonas known to infect humans; its closest genetic relatives are plant pathogens [7,8]. It is frequently isolated from soil, water, animals, plant matter, and hospital equipment [4,9-21].

S. maltophilia has an inherent ability to adhere to foreign materials and form a biofilm, rendering protection from host defenses as well as antimicrobial agents [18,19,22-26]. Factors contributing to this behavior include its positively charged surface and fimbrial adhesions [7,22-24,26-28].

In addition, S. maltophilia has intrinsic or acquired resistance mechanisms to several antibiotic classes. Resistance to beta-lactams, carbapenems, and aztreonam is conferred by two inducible beta-lactamases: a zinc-containing penicillinase (L1) and a cephalosporinase (L2) [21,29-34]. Aminoglycoside resistance occurs due to an acetyl-transferase mechanism as well as temperature-dependent changes in the outer membrane lipopolysaccharide (LPS) structure [18,35-45]. In addition, many strains of S. maltophilia possess efflux pumps, which confer further resistance to multiple antibacterial classes [41,46-49].

There are uncertainties regarding the optimal approach to in vitro susceptibility testing given discrepancies between results of various methods [50-53]. The United States Clinical and Laboratory Standards Institute (CLSI) has published minimal inhibitory concentration (MIC) breakpoints for trimethoprim-sulfamethoxazole, minocycline, levofloxacin, ticarcillin-clavulanic acid, ceftazidime, cefiderocol, and chloramphenicol [18,51,54,55]. There are no MIC interpretive criteria for tetracycline or tigecycline, although susceptibility to tigecycline is assumed using interpretive criteria for Enterobacteriaceae [56]. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) has only published breakpoint criteria for trimethoprim-sulfamethoxazole [57].

EPIDEMIOLOGY — The reported incidence of S. maltophilia infections ranges from 7.1 to 37.7 cases per 10,000 discharges [4,41,50,58]. The incidence seems to be increasing as the population of patients at risk increases [1,4,51,59-61]. Specifically, the increased incidence is probably due to advances in the treatment of malignancy, increased use of invasive devices, and widespread use of broad-spectrum antibiotics.

Risk factors associated with S. maltophilia infection include admission to an intensive care unit (ICU), malignancy, cystic fibrosis, neutropenia, mechanical ventilation, central venous catheters, recent surgery, trauma, HIV infection, and previous therapy with broad-spectrum antibiotics [1,2,4,20,21,50,59,60,62]. S. maltophilia infections are typically hospital-acquired; even in community-acquired infections, most affected individuals have significant health care exposure or predisposing comorbidities (eg, prior trauma, an immunocompromising condition, indwelling devices) [63].

A number of outbreaks of S. maltophilia have been described involving adult ICU patients [64-66], hematologic malignancy and bone marrow transplant recipients [67,68], hemodialysis patients [69], and neonates [70,71]. Patient exposure to contaminated tap water, ice machines, or soap has been the suspected etiology in many outbreaks [66,68,70,72]. In addition, a number of outbreaks and pseudo-outbreaks have been associated with failures in endoscope reprocessing [73-79].

CLINICAL SYNDROMES — Pneumonia and bacteremia are the most common manifestations of infection [2,4,41,51,52,80-83].

Pulmonary infection — S. maltophilia pneumonia is usually hospital-acquired and most frequently occurs in mechanically ventilated patients. Antecedent exposure to extended-spectrum penicillin or carbapenem antibiotics is associated with increased risk of ventilator-associated S. maltophilia pneumonia [84]. Compared with pulmonary colonization, infection is more commonly associated with underlying immunosuppression [85]. Clinical and radiographic findings are generally similar to those seen with other infectious causes of hospital-acquired pneumonia. However, in patients with hematologic malignancies, a syndrome of rapidly progressive and frequently fatal hemorrhagic pneumonia associated with S. maltophilia infection has been increasingly reported [9,86,87].

S. maltophilia is a recognized pathogen for cystic fibrosis patients in the United States, with overall prevalence rates similar to those of nontuberculous mycobacteria [88]. S. maltophilia infection correlates with decline in lung function in adult and pediatric cystic fibrosis patients, although causality has not been determined [89,90]. (See "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection", section on 'Other pathogens'.)

Bacteremia — Most cases of S. maltophilia bacteremia are associated with central venous catheters [3,91,92]. As an example, in a study of 207 oncology patients with a central venous catheter and S. maltophilia bloodstream infection, 73 percent of infections were deemed to be catheter-related, 22 percent were secondary (mainly from a pulmonary source), and 5 percent were thought to be primary and noncatheter related [91]. Many catheter-related S. maltophilia bloodstream infections are polymicrobial. Relapse of catheter-associated bacteremia, even up to 200 days after treatment of the initial infection, is also described and has been associated with prolonged neutropenia and catheter retention [93].

Bacteremia can also be secondary to other types of infections, such as soft tissue infections, urinary tract infections, or severe mucositis in patients with profound neutropenia [81,91,94,95].

Other syndromes — Less common manifestations of S. maltophilia infections include endocarditis, mastoiditis, peritonitis, meningitis, soft tissue infection, wound infection, urinary tract infection, and ocular infection [2,4,41,51,52,81-83,95,96]. Stenotrophomonas can also cause cutaneous manifestations, which may reflect metastatic infiltration or localized infection [97,98]. Reported skin manifestations include cellulitis, infected ulcers, and ecthyma gangrenosum.

MICROBIOLOGIC DIAGNOSIS — S. maltophilia grows well on commonly used laboratory media, including blood and MacConkey agars, and can be reliably identified in the laboratory using standard biochemical tests (it is lactose nonfermenting, oxidase-negative, and catalase-positive). In addition, it is accurately identified by commercially available automated identification systems [4]. Other techniques for identification include matrix-assisted laser desorption/ionization (MALDI) and nucleic acid amplification, but these tests are not yet standard for many microbiology laboratories.

The diagnostic evaluation for the specific clinical syndromes caused by S. maltophilia are discussed in detail elsewhere. (See "Clinical presentation and diagnostic evaluation of ventilator-associated pneumonia", section on 'Diagnostic evaluation' and "Intravascular non-hemodialysis catheter-related infection: Clinical manifestations and diagnosis", section on 'Diagnosis'.)

CONSIDERATIONS PRIOR TO SELECTING AN ANTIBIOTIC REGIMEN

Differentiating colonization from infection — S. maltophilia can be readily identified on culture of relevant clinical specimens. However, differentiating colonization from true infection can be difficult and depends on the anatomic site from which the culture sample was obtained and the patient's clinical presentation.

●Cultures from sterile sites – Growth of the organism from normally sterile sites (eg, blood, pleural fluid, peritoneal fluid, cerebrospinal fluid) should be interpreted as a true infection.

●Cultures from nonsterile sites – Clinical evaluation of the patient is necessary to determine whether a positive culture from a nonsterile site represents true infection. Colonization should not be treated because inappropriate antibiotic use can cause adverse effects and select for resistant organisms.

In cases in which the distinction between infection and colonization is uncertain, we recommend initiation of treatment for S. maltophilia until additional clinical information is available. After 48 to 72 hours, we re-evaluate the need for continued S. maltophilia therapy. Treatment recommendations are discussed below. (See 'Suggested antibiotic regimens' below.)

•Respiratory isolates – The ability of S. maltophilia to adhere to the surfaces of the upper airway and large bronchi can make it especially difficult to differentiate respiratory colonization from infection.

Patients with clinical evidence of pneumonia (eg, new pulmonary infiltrate, decreased oxygenation, and fever and/or leukocytosis) whose respiratory culture grows S. maltophilia (with or without other concurrent respiratory pathogens) should be considered to have true infection.

In the absence of consolidation on chest radiography and other clinical signs of pulmonary infection, a positive respiratory tract isolate of Stenotrophomonas probably represents colonization rather than invasive disease. In a retrospective review of 92 patients presenting with acute respiratory symptoms and subsequently found to have respiratory cultures positive for S. maltophilia, there was no measurable impact of antibiotic therapy in patients who did not have chest radiograph consolidation [99].

•Nonrespiratory isolates – As with respiratory samples, clinicians should use caution when interpreting culture data obtained from other nonsterile sites. Given the organism's propensity to colonize foreign material, cultures from indwelling urinary catheters, surgical drains, and vascular catheter hubs are especially likely to represent colonization.

It is critical to assess for clinical evidence of infection, such as fever, leukocytosis, or localized symptoms. In the absence of such findings, the culture findings may be presumed to reflect colonization rather than infection. For example, asymptomatic bacteruria should not be treated in most individuals. (See "Asymptomatic bacteriuria in adults".)

Indications for empiric therapy — We suggest covering Stenotrophomonas as part of empiric therapy in certain situations. Primarily, we provide empiric therapy to patients with moderate to severe infection (eg, ventilator-associated pneumonia) who have had prior cultures at the site of infection that grew S. maltophilia. In such cases, we treat with agents that were active against the prior isolates. If the organism ultimately grows from culture, we continue treatment and alter our regimen once susceptibility results return, as described below. (See 'Suggested antibiotic regimens' below.)

Assessing the severity of infection — Clinical judgement is necessary when categorizing a patient's severity of illness. We typically divide infections in one of two categories:

●Mild infections – In general, mild infections are those that have good source control and no evidence of severe sepsis or septic shock. Examples include cystitis and tracheitis. Select cases of pneumonia may be categorized as mild if no systemic symptoms (eg, fever >100.5°F/38°C, tachycardia, tachypnea), decrease in baseline oxygenation, or other concerning features are present.

●Moderate to severe infection – These infections include any infection for which heightened clinical concern is present or the criteria for mild infection are not met. Examples include more severe cases of pneumonia, severe sepsis or septic shock, undrained abscesses, and catheter-related bloodstream infections for which the catheter has not been removed.

SUGGESTED ANTIBIOTIC REGIMENS — Infections should be treated promptly because a delay in appropriate treatment can contribute to significant mortality. In addition, removal of potential sources of infection (eg, catheter removal or wound debridement) is recommended, if possible [93].

In general, our recommendations are in accordance with those of expert guidance [34].

Antibiotic options for treatment of S. maltophilia infections are limited due to high rates of resistance (see 'Microbiology' above). Our preferred antibiotic is trimethoprim-sulfamethoxazole. We favor it for monotherapy and as the backbone component of combination therapy. Alternatives include minocycline and levofloxacin. Other less favorable options include tigecycline and cefiderocol. Detailed regimens and their efficacy are discussed below. (See 'Mild infections in immunocompetent patients' below and 'Moderate to severe infections and infections in immunocompromised hosts' below and 'Antibiotic efficacy and safety' below.)

In general, we select antibiotic regimens based on the severity of illness and immune status of the patient (algorithm 1).

Mild infections in immunocompetent patients — For mild infections in immunocompetent patients, we typically suggest monotherapy based on the results of the isolate's antibiotic susceptibility testing.

Treatment options include the following (doses listed are for patients with normal renal function) (algorithm 1) [34]:

●Trimethoprim-sulfamethoxazole (preferred)

For infections other than cystitis, the typical dose is 8 to 12 mg/kg/day of the trimethoprim component intravenously in 2 or 3 divided doses, with a maximum dose of 960 mg of trimethoprim component per day. An equivalent oral dosage is two double-strength tablets every 12 hours for a patient who weighs 70 kg.

For cystitis, one double-strength tablet every 12 hours is appropriate. An equivalent parenteral dose is 160 mg (trimethoprim component) intravenously every 12 hours.

●Minocycline 200 mg intravenously or orally every 12 hours (alternative). Minocycline is not recommended as monotherapy for UTIs or bacteremia due to low concentrations in the blood and urine. (See 'Alternative antibiotics' below.)

●Levofloxacin 750 mg intravenously or orally once daily (alternative)

If none of the above three agents is an option due to resistance or intolerance, options include tigecycline (200 mg intravenously for one dose, then 100 mg intravenously every 12 hours) or cefiderocol (2 g intravenously every eight hours). Tigecycline is not recommended as monotherapy for UTIs or bacteremia due to low concentrations in the blood and urine, and it is not recommended for monotherapy for hospital-acquired pneumonia due to data suggesting worse outcomes (algorithm 1) [100]. (See 'Alternative antibiotics' below.)

Discussion of the safety and efficacy of these regimens is found below. (See 'Antibiotic efficacy and safety' below.)

Moderate to severe infections and infections in immunocompromised hosts — Consistent with the Infectious Diseases Society of America (IDSA) guidelines, we generally suggest initial combination therapy for moderate to severe infections and infections in immunocompromised hosts, though clinical outcomes data comparing monotherapy to combination therapy are limited and have conflicting results [59,101]. In one prospective study of patients with S. maltophilia bacteremia, receipt of two or more of trimethoprim-sulfamethoxazole (TMP-SMX), a third generation cephalosporin, and an extended-spectrum penicillin was associated with lower mortality rates compared with receipt of just one agent [59]. In contrast, a retrospective study of 252 patients with S. maltophilia pneumonia found no difference in outcomes with combination therapy versus monotherapy [101]. The evidence for combination therapy resides predominantly in in vitro studies that have reported in vitro synergy for TMP-SMX plus a second agent (including minocycline, fluoroquinolones, and cefiderocol, as well as other agents) [102-109].

The choice of agents is based on the results of the isolate's susceptibility testing and factors specific to the clinical scenario including any known antibiotic intolerances, patient-specific antibiotic risk assessment, and need for concomitant antibacterial coverage for other infections. Consultation with an expert in these infections is advised (algorithm 1).

●Preferred regimens for combination therapy – For combination therapy, we prefer to include TMP-SMX if the isolate is susceptible and there are no contraindications.

Our preferred combination is TMP-SMX plus minocycline. If minocycline is not an option, then levofloxacin, tigecycline, or cefiderocol may be added to TMP-SMX as second agents. Dosages are the same as those described above for mild infections. (See 'Mild infections in immunocompetent patients' above.)

●Regimens if trimethoprim-sulfamethoxazole is not an option – For these situations, we favor a combination of minocycline and levofloxacin, if the isolate is susceptible to both agents. Dosages are listed above. (See 'Mild infections in immunocompetent patients' above.)

If the combination of minocycline and levofloxacin is not an option, and TMP-SMX can't be administered because the patient has an immunoglobulin (Ig)E-mediated hypersensitivity reaction, we favor rapid desensitization to TMP-SMX if the isolate is susceptible [110]. After desensitization, we choose one of the TMP-SMX-based regimens listed above. The technique for desensitizing patients is discussed in detail elsewhere [7,110]. (See "Rapid drug desensitization for immediate hypersensitivity reactions" and "Sulfonamide allergy in HIV-uninfected patients", section on 'Desensitization'.)

If neither the combination of minocycline and levofloxacin nor TMP-SMX desensitization are options, then other combinations of minocycline, levofloxacin, cefiderocol, and tigecycline may be selected, depending on the site of infection and patient-specific factors. Once appropriate clinical response has occurred, we narrow the antibiotic regimen to a single active agent.

In the rare event that none of the above options can be used, limited in vitro and in vivo data indicate the combination of ceftazidime-avibactam plus aztreonam may be effective and may be trialed as a salvage regimen (algorithm 1) [111-115].

Discussion of the safety and efficacy of these regimens is found below. (See 'Antibiotic efficacy and safety' below.)

ANTIBIOTIC EFFICACY AND SAFETY — Inherent and acquired resistance limits the number of antimicrobial options for S. maltophilia. Clinical data are limited regarding optimal therapy, and most available data are derived from observational and in vitro studies.

Trimethoprim-sulfamethoxazole as the preferred option — The preferred antibiotic for treatment of S. maltophilia infections is trimethoprim-sulfamethoxazole (TMP-SMX). Specific TMP-SMX-based regimens for treatment of S. maltophilia are found elsewhere. (See 'Suggested antibiotic regimens' above.)

There is extensive clinical experience with TMP-SMX, and observational studies and case series report somewhat favorable clinical outcomes [59,116-120]. In observational studies, in-hospital or 30-day mortality rates ranged between 21 and 31 percent with monotherapy with TMP-SMX [59,116,117]. Outcomes were similar when compared with other antimicrobials.

This agent has the most reliable in vitro activity against S. maltophilia [121-124]. As an example, in a surveillance study of gram-negative organisms isolated from patients hospitalized with pneumonia between 2009 and 2012, susceptibility to TMP-SMX was documented for 96 percent of the 302 S. maltophilia isolates from United States hospitals and 98 percent of the 192 isolates from European hospitals [121]. However, in vitro resistance to TMP-SMX among S. maltophilia isolates has been increasingly reported, particularly in patients with cystic fibrosis [51,80,125,126].

Resistance to TMP-SMX can develop during therapy. In observational studies, the rates of resistance at the end of therapy with TMP-SMX ranged from 7 to 10 percent [116,119]. Although concerning, these rates are not as high as with other agents such as fluoroquinolones.

Some patients are unable to tolerate TMP-SMX due to hypersensitivity reaction, drug toxicity, or another adverse reaction. In some situations, desensitization may allow the administration of TMP-SMX, as discussed above. (See 'Moderate to severe infections and infections in immunocompromised hosts' above and "Sulfonamide allergy in HIV-uninfected patients".)

Alternative antibiotics — Tetracycline derivatives (ie, minocycline and tigecycline) and fluoroquinolones (ie, levofloxacin) are favored for infections for which TMP-SMX is not an option or for combination therapy with TMP-SMX.

●Tetracycline derivatives – Minocycline and tigecycline are alternatives to trimethoprim-sulfamethoxazole for treatment of S. maltophilia. We favor minocycline over tigecycline due to minocycline's more favorable in vitro data, availability of an oral formulation, standardized breakpoints for reporting susceptibility, and better tolerability. Specific regimens for treatment of S. maltophilia are found elsewhere. (See 'Suggested antibiotic regimens' above.)

For treatment of bloodstream infections and urinary tract infections, we only use these agents as part of combination therapy because both minocycline and tigecycline achieve suboptimal drug levels in the blood and urine [34]. For hospital-acquired pneumonia, tigecycline monotherapy is not advised due to concerns about higher mortality rates compared with other agents [100].

Minocycline and tigecycline have both been shown in small retrospective studies to be associated with clinical outcomes that are comparable to those with TMP-SMX [117,118,127]. In one study of 93 hospitalized patients with S. maltophilia infection treated with minocycline, 17 (18 percent) experienced clinical failure, defined as death within 30 days or clinical deterioration [127]. In another study of 19 hospitalized patients treated with tigecycline, six (32 percent) had clinical failure [117].

The majority of S. maltophilia isolates are susceptible to both minocycline and tigecycline [121,122,128]. For example, in a surveillance study of 494 isolates of S. maltophilia from patients hospitalized with S. maltophilia pneumonia between 2009 and 2012 in the United States and Europe, susceptibility to minocycline was 99 percent [121]. In a separate study of 80 clinical isolates, 67 (84 percent) were susceptible to tigecycline [109]. Most isolates that were resistant to TMP-SMX retained susceptibility to minocycline and tigecycline.

Clinical data are scarce for eravacycline, another tetracycline derivative with low minimal inhibitory concentrations (MICs) when tested against S. maltophilia [129]. Omadacycline has limited in vitro activity against S. maltophilia. These agents are not recommended for treatment of S. maltophilia infections at this time.

●Fluoroquinolones – These agents, in particular levofloxacin, are potential alternatives to TMP-SMX [122]. Specific levofloxacin-based regimens for treatment of S. maltophilia are found elsewhere. (See 'Suggested antibiotic regimens' above.)

Retrospective studies, including one that evaluated over 1500 patients from 154 United States hospitals, have suggested similar clinical outcomes (microbiologic cure, clinical success, and short-term mortality rates) in S. maltophilia infection with fluoroquinolone versus TMP-SMX monotherapy [116,119,120,130,131]. Furthermore, a systematic review and meta-analysis that included 663 patients treated either with TMP-SMX or fluoroquinolone monotherapy found comparable effects on mortality between the two groups [116,119,120,132,133].

Baseline susceptibility rates of S. maltophilia to levofloxacin vary from 30 to 80 percent in surveillance studies [56,103,109,121]. In addition, in vitro and observational studies raise concern about emergence of resistance during treatment with fluoroquinolones [116,119,132,133]. In clinical observational studies, 19 to 27 percent of patients treated with fluoroquinolones had fluoroquinolone-resistant isolates at the end of therapy [116,119].

Although data suggest that moxifloxacin may have similar in vitro activity as levofloxacin against S. maltophilia [134], there are no Clinical and Laboratory Standards Institute (CLSI)-defined breakpoints for moxifloxacin or ciprofloxacin. Therefore, it is our practice to preferentially use levofloxacin rather than other fluoroquinolones for treatment of S. maltophilia infections.

Other antibiotic options

●Cefiderocol – Preclinical data suggest that cefiderocol appears to have reliable in vitro activity against S. maltophilia, but clinical data are limited [103,135]. In a trial of cefiderocol for the treatment of multidrug-resistant gram-negative bacilli infections, only five patients with S. maltophilia infection (pneumonia) were included, and S. maltophilia-specific outcomes were not reported [136,137].

●Combination therapy with ceftazidime-avibactam and aztreonam – Ceftazidime-avibactam is a novel beta-lactam/beta-lactamase inhibitor that has limited in vitro activity against S. maltophilia. However, the avibactam component of the drug is able to overcome the resistance mechanism to aztreonam, rendering aztreonam effective against many S. maltophilia isolates [111,112,138-140]. The combination has been reported to lead to successful clinical outcomes in a few case reports [113-115].

Antibiotics that should not be used — S. maltophilia is intrinsically resistant to a number of antibiotics that are commonly used to treat multidrug-resistant gram-negative bacilli, including traditional beta-lactam antibiotics (eg, ampicillin-sulbactam, piperacillin-tazobactam, ceftriaxone, ceftazidime), aztreonam monotherapy, carbapenems, aminoglycosides, fosfomycin, and other novel agents (eg, omadacycline, ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, plazomicin) [34,141].

Although some isolates of S. maltophilia are reported to be susceptible to ceftazidime and carbapenems, intrinsic resistance mechanisms are felt to render these agents ineffective [121,122,129]. In vitro data suggest that ceftazidime is unable to control growth of the organism [109]. Expert panels suggest that ceftazidime and carbapenems should not be used to treat S. maltophilia infections, even if the isolate is reported as susceptible by the microbiology laboratory [34,142,143].

Polymyxins (eg, colistin sulfate) have variable rates of in vitro activity against S. maltophilia. In the United States, no CLSI criteria exist to determine polymyxin susceptibility in microbiology labs, and the accuracy and reliability of polymyxin MICs are uncertain [34,144-146]. Given these concerns, we do not use polymyxins to treat S. maltophilia infections.

Ticarcillin-clavulanic acid resistance is common (up to 55 percent) [18,41,147], and the drug is unavailable in most countries, including the United States and Canada.

DURATION OF THERAPY — In general, the duration of therapy for S. maltophilia infections is the same as that for other gram-negative bacilli.

The duration primarily depends on the site of infection. For bacteremia, we favor 14 days of therapy. Although studies have suggested that shorter courses are similarly effective for gram-negative bacillary bacteremia, S. maltophilia was not well represented in those studies. Further discussion of gram-negative bacteremia is found elsewhere. (See "Gram-negative bacillary bacteremia in adults", section on 'Duration and route of therapy'.)

PROGNOSIS — S. maltophilia infections have been associated with high morbidity and mortality in severely immunocompromised and debilitated individuals.

Overall, mortality estimates range from 21 to 69 percent [60,148-150]. However, the actual mortality attributed to these infections when controlling for other variables is unclear.

Retrospective analyses have reported the following risk factors for increased mortality: admission to an intensive care unit (ICU), delay in appropriate treatment, hematologic malignancy, and immunosuppression [2,59].

INFECTION CONTROL AND PREVENTION — Infection control and antibiotic stewardship measures are important to minimize the incidence of S. maltophilia infections and for reducing emergence of resistant strains. These measures include appropriate use of antibiotics, avoidance of prolonged or unnecessary use of foreign devices, and adherence to hand hygiene practices. Strict hand hygiene and contact isolation procedures have been utilized to reduce clonal spread in the intensive care unit (ICU) setting [151]. (See "Infection prevention: Precautions for preventing transmission of infection".)

SUMMARY AND RECOMMENDATIONS

●Microbiology – Stenotrophomonas maltophilia is a multidrug-resistant gram-negative bacillus that is an opportunistic pathogen. (See 'Microbiology' above.)

●Risk factors – Infection typically occurs in severely immunocompromised and debilitated individuals. Specific risk factors include admission to an intensive care unit (ICU), HIV infection, malignancy, cystic fibrosis, neutropenia, mechanical ventilation, central venous catheter, recent surgery, trauma, and previous therapy with broad-spectrum antibiotics. (See 'Epidemiology' above.)

●Clinical syndromes – Pneumonia (usually hospital-acquired) and bacteremia (often associated with an indwelling catheter) are the most common manifestations of S. maltophilia infection. Less common manifestations include endocarditis, mastoiditis, peritonitis, meningitis, soft tissue infection, wound infection, urinary tract infection, and ocular infection. (See 'Clinical syndromes' above.)

●Diagnosis and differentiating colonization from infection – Growth of S. maltophilia from normally sterile sites (eg, blood, pleural fluid, peritoneal fluid) should be interpreted to represent true infection. In patients with clinical evidence of pneumonia, cultures growing S. maltophilia from respiratory sites should be interpreted as consistent with infection. Similarly, culture data obtained from other nonsterile sites (eg, indwelling catheters or drains) must consider patients' clinical findings to differentiate colonization from infection. (See 'Differentiating colonization from infection' above.)

●Antibiotic therapy – The selection of antibiotic regimens depends primarily on the severity of illness and immune status of the patient (algorithm 1).

•Mild infections in immunocompetent individuals – For empiric and directed therapy of mild S. maltophilia infections, we suggest monotherapy with trimethoprim-sulfamethoxazole (TMP-SMX) (Grade 2C). If TMP-SMX is not an option, appropriate alternatives include minocycline or levofloxacin. TMP-SMX is preferred because it has the most clinical experience and most reliable in vitro activity (algorithm 1). (See 'Mild infections in immunocompetent patients' above.)

•Moderate to severe infections and infections in immunocompromised patients – For these patients, we suggest initial combination therapy with a TMP-SMX plus minocycline (Grade 2C). If minocycline can't be used (eg, because of intolerance or resistance), levofloxacin is an alternative to use with TMP-SMX. Data for combination therapy are very limited, but some studies suggest that it may be associated with lower mortality (algorithm 1). (See 'Moderate to severe infections and infections in immunocompromised hosts' above.)

Other antibiotic options with activity against S. maltophilia include tigecycline, cefiderocol, or the combination of ceftazidime-avibactam plus aztreonam; clinical data are limited for these agents (algorithm 1). (See 'Suggested antibiotic regimens' above.)

Certain infections may warrant additional interventions, such as catheter removal or wound debridement. (See 'Assessing the severity of infection' above.)

●Duration of therapy – In general, the duration of therapy for S. maltophilia infections is the same as that for other gram-negative bacilli. The duration primarily depends on the site of infection. For bacteremia, we suggest 14 days of therapy rather than shorter durations (Grade 2C). (See 'Duration of therapy' above.)

●Infection control and prevention – To minimize the incidence of S. maltophilia infections and reduce the emergence of resistant strains, judicious use of antibiotics, avoidance of prolonged or unnecessary use of foreign devices, and adherence to hand hygiene practices are necessary. (See 'Infection control and prevention' above and "Infection prevention: Precautions for preventing transmission of infection".)