|Year : 2017 | Volume
| Issue : 4 | Page : 469-479
Stenotrophomonas maltophilia: From trivial to grievous
Lipika Singhal1, Parvinder Kaur2, Vikas Gautam3
1 Department of Microbiology, Government Medical College and Hospital, Chandigarh, India
2 Department of Biotechnology, Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial College, Bela, Ropar, Punjab, India
3 Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||1-Feb-2018|
Dr. Vikas Gautam
#229, Department of Medical Microbiology, 1st Floor, Research Block-A, Postgraduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
Stenotrophomonas maltophilia, once regarded as an organism of low virulence, has evolved as a significant opportunistic pathogen causing severe human infections in both hospital and community settings, especially amongst highly debilitated patients. Globally, S. maltophilia ranks third amongst the four most common pathogenic non-fermenting Gram-negative bacilli (NFGNBs), others being Pseudomonas aeruginosa, Acinetobacter baumannii and Burkholderia cepacia complex (Bcc). The worth of accurate identification of S. maltophilia comes to the forefront as it needs to be differentiated from other NFGNBs such as Acinetobacter, P. aeruginosa and Bcc due to its inherently contrasting antibiotic susceptibility pattern. Consequently, its correct identification is essential as no single drug is amply effective against all NFGNBs, which hinders initiation of appropriate empirical treatment resulting in increased morbidity and mortality.
Keywords: Multidrug resistance, Stenotrophomonas maltophilia, virulence
|How to cite this article:|
Singhal L, Kaur P, Gautam V. Stenotrophomonas maltophilia: From trivial to grievous. Indian J Med Microbiol 2017;35:469-79
|How to cite this URL:|
Singhal L, Kaur P, Gautam V. Stenotrophomonas maltophilia: From trivial to grievous. Indian J Med Microbiol [serial online] 2017 [cited 2019 Aug 20];35:469-79. Available from: http://www.ijmm.org/text.asp?2017/35/4/469/224415
| ~ Introduction|| |
Stenotrophomonas maltophilia is a glucose non-fermenting Gram-negative multidrug-resistant organism found extensively distributed in natural and unnatural environments. It has been suggested for bio-remediation of polluted grounds on the basis of its competence to degenerate xenobiotic compounds and metal resistance.,
S. maltophilia, once regarded as an organism of low virulence, has evolved as a significant opportunistic pathogen causing severe human infections, especially amongst highly debilitated patients. Globally, S. maltophilia ranks third amongst the four most common pathogenic non-fermenting Gram-negative bacilli (NFGNBs), others being Pseudomonas aeruginosa, Acinetobacter baumannii and Burkholderia cepacia complex (Bcc).
S. maltophilia causes a variety of infections including respiratory tract infections (pneumonia and acute exacerbations of chronic obstructive pulmonary disease), bloodstream infections (BSIs), bone and joint infections, urinary tract infections, endocarditis and meningitis.,,, In cystic fibrosis (CF) patients, S. maltophilia can account perseverant colonisation and chronic infection.
The inert bio-chemical profile, difficulty in interpretation of phenotypic characteristics and poor laboratory know-how exert challenge to a routine laboratory to identify S. maltophilia. Due to this reason, reports on S. maltophilia infection are less from India though its isolation incidence is booming with increased awareness in clinical settings. The correct identification of S. maltophilia has its significance as it needs to be differentiated from other NFGNBs such as A. baumannii, P. aeruginosa and Bcc due to its inherently contrasting antibiotic susceptibility pattern. Consequently, its correct identification is essential as no single drug is amply effective against all NFGNBs, which hinders initiation of appropriate empirical treatment resulting in increased morbidity and mortality.
| ~ Historical Background and Taxonomy|| |
S. maltophilia was first isolated in 1943 by J. L. Edward and named as 'Bacterium bookeri.' In 1958, Hugh and Ryschenkow isolated a strain from an oral carcinoma patient and named it as Pseudomonas maltophilia; they also reclassified 'B. bookeri' as Pseudomonas maltophilia. In 1981, on the evidence of similar G + C content, comparative enzymology, similar ubiquinones and cellular fatty acid composition, P. maltophilia was re-classified as Xanthomonas maltophilia. Finally, in 1993, after a very long period of debate, Palleroni and Bradbury proposed a genus Stenotrophomonas with only one species S. maltophilia.
At present, the genus Stenotrophomonas is heterogeneous both genetically and phenotypically and encompasses 12 recognised species that include Stenotrophomonas acidaminiphila, Stenotrophomonas chelatiphaga, Shinella daejeonensis, Sphingomonas dokdonensis, Stenotrophomonas ginsengisoli, Stenotrophomonas humi, Stenotrophomonas koreensis, S. maltophilia, Stenotrophomonas nitroreducens, Stenotrophomonas pavanii, Stenotrophomonas rhizophila and Stenotrophomonas terrae. Spirostachys africana, which had been recognised as a new species in 1997, was afterwards found to be similar to S. maltophilia., The clinically significant species of this genus is S. maltophilia which is extensively found in the environment as well as in clinical setting. The term S. maltophilia is derived from Greek and Latin words: Stenos, narrow; trophos, one who feeds; monas, a unit, monad; i.e., a unit feeding on few substrates; and malt, malt; philos, friend; i.e., a friend of malt. S. maltophilia can ferment maltose but not glucose.
| ~ Epidemiology|| |
S. maltophilia is ubiquitous in nature. It exists in various types of environments and extreme geographical regions such as Antarctica. Due to its ubiquitous nature, many fomites and medical devices in the clinical settings may serve as promising reservoirs of infection. It resides in various ecological niches both inside and outside the hospital settings as catheters, contaminated chlorhexidine-cetrimide disinfectant, ventilator inspiratory/expiratory circuits, endoscopes, faucets, showerheads, hand washing soaps, haemodialysis water and dialysate of renal units, hospital suction tubing, nebulisers, tap water and water fountain drains. It also has an ability to form biofilm on any kind of humid surface. The biofilms have been identified in contact lens stock solution, home use nebulisers of CF patients, micro-filtered water dispensers, plant Rhizosphere, river water and water treatment process.
The well-recognised risk factors for S. maltophilia infections are lengthened hospitalisation requiring invasive procedures, admission in an Intensive Care Unit (ICU), indwelling catheters, mechanical ventilation, recent exposure to antibiotics, corticosteroid or immunosuppressant therapy, CF, severe mucositis, underlying malignancy, human immunodeficiency virus infection and organ transplantation.,
| ~ Virulence Factors|| |
Despite its rising incidence, the virulence factors of S. maltophilia have been poorly characterised. Some of the virulence factors are extracellular protease, lipases, exopolysaccharides and lipopolysaccharides, siderophores  and a phage-encoded zonula occludens-like toxin.
Another crucial virulence factor produced by S. maltophilia is its ability to form biofilms on both biotic and abiotic surfaces., A higher level of biofilm formation was demonstrated in multidrug resistance (MDR) isolates in a study that included 70 S. maltophilia clinical isolates (40 MDR and 30 non-MDR isolates). Biofilm formation was found in correlation (P < 0.01) with resistance to aztreonam, cefepime, ceftazidime, piperacillin-tazobactam, ticarcillin-clavulanic acid and gentamicin but not in correlation with resistance to trimethoprim-sulphamethaxazole (TMP-SMX), ciprofloxacin, levofloxacin and meropenem.
Finally, a cell–cell signalling factor has been determined, which controls the expression of virulence genes and antimicrobial resistance through a two-component regulatory system.
| ~ Global Problem Statement|| |
With a worldwide occurrence, the incidence and fatality rate due to S. maltophilia have been reported from various countries. A high mortality rate ranging from 23.0% to 77.0%,,,, and 21.0% to 62.0%,,, was found associated with pneumonia and bacteraemia, respectively, caused by S. maltophilia. A study during 1993–2004, based on data recovered from multiple hospitals in US, reported S. maltophilia accounted for 4.3% of total 74,394 GNB isolates causing infections in patients admitted to the ICU. In another US study, an increased incidence rate of S. maltophilia from 6.7% to 12.0% was observed among CF patients. A worldwide study as a part of SENTRY Antimicrobial Surveillance Program during 1997–2008 reported 3.1% incidence rate of S. maltophilia among the hospitalised patients suffering from pneumonia. With respect to age group, S. maltophilia isolation rate among respiratory infections was found to be 3.0% higher in patients of age group 16–25 years than in patients with age >25 years. In paediatric patients, S. maltophilia ranked amongst the top 15 pathogens in Europe, Latin America and North America. A German study carried out in ICUs reported S. maltophilia amongst the top 13 most common pathogens causing nosocomial infections.
| ~ Stenotrophomonas Maltophilia-Associated Infections|| |
Recently, S. maltophilia has arisen as a crucial nosocomial pathogen responsible for high mortality rate. The most common infections caused by S. maltophilia include pneumonia, BSI and wound and urinary tract infections.,,, Other less common infections associated with S. maltophilia include meningitis, endocarditis, eye infections, epididymitis, arthritis, sinusitis, mastoiditis, cholangitis, peritonitis and osteochondritis.,,, Very less reports are documented on community-acquired S. maltophilia infections. These occur mostly in patients with pre-existing comorbidities (chronic obstructive pulmonary disease, trauma, malignancy or immunosuppression) and include bacteraemia, respiratory tract infections, ocular infections, otitis, conjunctivitis, wound/soft tissue infections, urinary tract infections and cellulitis.
Respiratory tract infections
In majority of the cases, S. maltophilia isolated from respiratory tract represents colonisation and indicates an immunocompromised state of the patient. S. maltophilia has also evolved as one of the most common bacteria isolated from the airway of CF patients.,
S. maltophilia is usually collaterally isolated along with other pathogens of respiratory tracts, which creates problem in proper interpretation of the colonisation. One of the studies conducted in a tertiary care hospital reported 30 cases of nosocomial pneumonia, 27 cases of ventilator-associated pneumonia and 3 cases of pneumonia in non-ventilated patients by S. maltophilia. The symptoms developed by S. maltophilia pneumonia patients are non-specific, which include fever, cough and dyspnoea. Pulmonary infiltrates on examination by radiology appear lobular-shaped and unusual pleural effusions. In one of the retrospective studies carried out to analyse the effect of inhalation of tobramycin for the treatment of P. aeruginosa infections in CF patients, they showed that this treatment was lesser effective in patients who were also colonised with S. maltophilia. Various studies have reported the high mortality rates with S. maltophilia pneumonia ranging from 23% to 77% with maximum rates observed amongst cancer and bacteraemia patients.,,,,,
S. maltophilia isolates have been implicated in increasing inflammatory response that includes increase in expression of interleukin-8 and tumour necrosis factor (TNF)-α in airway epithelial cells and macrophages, respectively, contributing to airway inflammation. In a study, S. maltophilia isolates from CF patients showed higher level of inflammatory response during murine lung infection model. Moreover, in CF patients with chronic S. aureus cultures, co-infection with S. maltophilia is independent risk factor for worse lung function. Air-borne transmission of S. maltophilia is known to occur by aerosols generated from cough of CF patients.
S. maltophilia from blood culture should be properly assessed to demarcate between contamination, colonisation and true BSI. The most common source of bacteraemia by S. maltophilia is central venous line. Catheter-related BSIs are usually polymicrobial and prognosis can be improved by removal of infected catheter.S. maltophilia has been found in relation with advanced bacteraemia in patients suffering from haematological malignancies.,
Various studies reported the high mortality rate ranging from 22% to 62% with BSI by S. maltophilia.,,,, Increased disease severity and high mortality were associated with hospital-acquired S. maltophilia bacteraemia as compared with community-onset bacteraemia by S. maltophilia.
| ~ Indian Scenario|| |
Various case studies on S. maltophilia infections in India such as endophthalmitis, tropical pyomyositis, neonatal sepsis, unilateral conjunctival ulcer, non-healing leg ulcer  and meningitis  have been reported. In one study from a tertiary care hospital in Karnataka, the isolation rate of S. maltophilia was found to be 2.5% (5 isolates) out of 193 NFGNBs collected from various clinical samples. Another study also from Karnataka region reported 1.8% (15 isolates) isolation rate of S. maltophilia out of 830 NFGNBs from respiratory samples. A tertiary care super-speciality hospital from North India has reported a rise in number of cases due to S. maltophilia over the last decade. It is currently the fourth most common NFGNB in septicaemic patients after A. baumannii, P. aeruginosa and Bcc obtained from blood cultures.,,
| ~ Laboratory Diagnosis|| |
The ancient saying that 'the eyes do not see what the mind does not know' holds very true for S. maltophilia. Only with awareness and suspicion can this organism be identified instead of being reported as just NFGNB or more incorrectly as some Pseudomonas spp. by a routine microbiology laboratory where automation facilities for identification do not exist.
S. maltophilia is a Gram-negative, motile, non-lactose-fermenting bacillus. It is an obligate aerobe. The optimal temperature for its growth is 35°C and no growth occurs below 5°C and above 40°C. It produces lavender-green colonies with ammonical odour on blood agar plates, non-pigmented tiny colonies on MacConkey agar plates and tiny cream colonies on Muller-Hinton agar plates after 24 h of incubation at 37°C [Figure 1]a,[Figure 1]b,[Figure 1]c.
|Figure 1: (a) Colonies of Stenotrophomonas maltophilia on blood agar plate. (b) Colonies of Stenotrophomonas maltophilia on MacConkey agar plate. (c) Colonies of Stenotrophomonas maltophilia on Mueller-Hinton agar plate|
Click here to view
Initially, for the isolation of S. maltophilia, X. maltophilia selective medium (XMSM) was used. After 2 days of incubation, S. maltophilia produces orange colonies with yellow halo. Because of complexity in its preparation, time consumption and high cost, XMSMs are unattractive for S. maltophilia isolation.
S. maltophilia is usually co-isolated with other microorganisms. Thus, for better isolation of clinical and environmental isolates, vancomycin, imipenem and amphotericin B (VIA) medium was developed. It contains vancomycin to inhibit imipenem-resistant Enterococcus faecium, amphotericin B as an antifungal agent, mannitol agar base to distinguish non-fermenting S. maltophilia from fermenting bacteria and bromothymol blue as an indicator dye. S. maltophilia produces greenish colonies with a blue halo. This medium is more selective and less inhibitory to S. maltophilia than XMSM. In few reports, the use of VIA medium has been demonstrated for the isolation of S. maltophilia from bottled water, salads, sputa, hospital and domestic settings; however, these studies failed to provide specificity in isolation of S. maltophilia from environmental samples.,,,,
S. maltophilia can be differentiated from other bacterial species present in mixed culture samples on the basis of their selective fermentation of sugars. For example, S. maltophilia can produce acid from maltose but not from glucose; on the other hand, P. aeruginosa utilises glucose but not maltose.
Unlike P. aeruginosa, S. maltophilia lacks easily discernable phenotypic characteristics. It closely relates to Bcc in its pattern of infections. Identification and differentiation of these two lysine decarboxylase-positive NFGNBs are important. To overcome problem of their identification in routine clinical laboratories, we standardised simple five conventional biochemical tests including oxidase, triple sugar iron, lead acetate paper strip for hydrogen sulphide production and aerobic low peptone medium slants containing ammonium salts with glucose, lysine and ornithine decarboxylase and arginine dihydrolase.S. maltophilia can be differentiated from Bcc, as majority of isolates are oxidase negative and positive for H2S production on lead acetate strips [Table 1] though it has been reported by Carmody et al. that some of the S. maltophilia isolates may be oxidase positive.
|Table 1: Simplified identification table for lysine-positive non-fermenting Gram-negative bacilli|
Click here to view
Molecular approach based on 23S rRNA gene amplification completes identification schemes. Whitby et al. designed primers SM1 and SM4 based on species level signature sequences in 23S rRNA. This polymerase chain reaction (PCR) is highly selective for S. maltophilia and has proved negative for all other organisms. This PCR showed sensitivity and specificity of 100% for clinical and environmental isolates.,,
Previous studies reported considerable heterogeneity among S. maltophilia isolates using different typing approaches that included enterobacterial repetitive intergenic consensus sequence-PCR (ERIC-PCR), ribotyping, random-amplified polymorphic DNA and pulsed-field gel electrophoresis., These results revealed large amount of genetic diversity among the clinical isolates of S. maltophilia and also indicated that cross-transmission among patients may not be occurring. Multilocus sequencing typing (MLST) has proven to be a reliable mean for inter- and intra-species delineation of Stenotrophomonas spp. and a highly portable standard for strain characterisation. Such analysis is appropriate to identify the nosocomial or community origin of infections, serving to detect outbreaks and allowing a study of the population structure of the pathogen that is important for molecular epidemiology. Kaiser et al. framed up MLST for S. maltophilia on the basis of partial sequences (444–558 bp) of seven housekeeping genes. Nearby 40–55 alleles have been deposited for each of seven targeted genes and 56 sequence types (ST) in online database though this number is quite less when compared to the other databases available for other bacteria (http://pubmlst.org/smaltophilia/). In an MLST-based study by Cho et al. of 33 clinical isolates of S. maltophilia collected over a period of 1 year at a university hospital in Korea, 26 different STs were found where 23 were new STs and 3 were previously discovered STs.
| ~ Matrix-Assisted Laser Desorption Ionisation Time-Of-Flight Mass Spectrometry for the Identification of Stenotrophomonas Maltophilia|| |
Until recently, identification of microbes in clinical diagnostic laboratories has mainly been dependent on conventional biochemical (phenotypic) and gene sequencing-based techniques. The introduction of matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) devices has transformed the routine identification of microorganisms in clinical diagnostic laboratories. Vasileuskaya-Schulz et al. described the use of MALDI-TOF MS BioTyper system in concordance with MLST for the analysis of 21 strains of different species and showed good consistency between the two techniques. Seng et al. misidentified seven S. maltophilia isolates as Pseudomonas hibiscicola, an invalid name for S. maltophilia entered into the BioTyper database. We tested 50 clinical isolates of S. maltophilia that were confirmed by species-specific PCR. The concordance rate of MALDI-TOF MS was 100% for the genus and 50% (25/50) for the correct species identification. An increase in species identification to 70% (35/50) was noted when altered cut-off ≥1.9 was considered. No isolate was however misidentified by MALDI-TOF. MALDI-TOF MS is emerging as an efficient, accurate and cost-effective alternative tool in microbial identification.
| ~ Treatment of Stenotrophomonas Maltophilia Infections|| |
S. maltophilia is intrinsically resistant to aminoglycosides and commonly used carbapenems. The contrasting susceptibility, high intrinsic resistance and the notable capacity to develop resistance to essentially all commonly used antibiotics including the anti-pseudomonal drugs and dilemma over in vitro susceptibility testing poses a great challenge to clinicians in selecting suitable antimicrobial regimen for the treatment of S. maltophilia infections. In literature, there are limited data available on clinical trials of various treatment regimes. The present-day recommendations for the treatment of S. maltophilia infections are based on previous evidence, case reports and case series and in vitro susceptibility studies. Drug susceptibility among S. maltophilia isolates in routine microbiology laboratory should be determined by Kirby-Bauer disk diffusion test against the following recommended antimicrobial agents (TMP-SMX, 1.25/23.75 μg; minocycline, 30 μg; levofloxacin, 5 μg) according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. As per the CLSI guidelines only, minimum inhibitory concentration (MIC) is determined against ticarcillin-clavulanate (sensitive, S ≤16/2: resistant, R ≥128/2), ceftazidime (S ≤8: R ≥32), minocycline (S ≤4: R ≥16), levofloxacin (S ≤2: R ≥8), TMP-SMX (S ≤2/38: R ≥4/76) and chloramphenicol (S ≤8: R ≥32) (CLSI, 2016).
| ~ Antimicrobial Resistance in Stenotrophomonas Maltophilia|| |
Various antimicrobial resistance mechanisms reported in S. maltophilia include efflux pumps, low outer membrane permeability, antibiotic-inactivating enzymes and β-lactamases [Table 2]. Horizontal transfer of resistance genes present on plasmids, transposing and integrons may also lead to antibiotic resistance in S. maltophilia.
|Table 2: Various antibiotic resistance mechanisms in Stenotrophomonas maltophilia|
Click here to view
In S. maltophilia, resistance to antimicrobials is also contributed by the activity of multidrug efflux pumps, which are basically made up of membrane fusion protein, an energy-dependent transporter and an outer membrane protein. Stenotrophomonas multiple efflux (sme) smeDEF operon was cloned, sequenced and expressed in Escherichia More Details coli, which indicated that operon smeDEF encodes a multidrug efflux pump, which is responsible for resistance to β-lactams, tetracyclines, erythromycin, quinolones, chloramphenicol and aminoglycosides.
Another operon smeABC was also identified in S. maltophilia, which was encoded by smeA, smeB and smeC genes, respectively. Expression of smeABC efflux pump has been reported as important for the fluoroquinolone (ciprofloxacin and levofloxacin) and meropenem resistance.
Integrons are non-self mobilisable elements, which contain an integrase enzyme for the insertion of antibiotic resistance genes at specific sites. As integrons lack enzymes for transposition, their movement is usually facilitated by plasmids and transposons. Their role has been discussed below.
TMP-SMX is a first line drug for the treatment of S. maltophilia infections owing to its good susceptibility and clinical outcomes in the treated patients. TMP-SMX is a mixture of two antimicrobial agents, which function synergistically and inhibit enzymes involved in synthesis of tetrahydrofolate.
On the background of in vitro data, TMP-SMX is bacteriostatic against S. maltophilia. A high dose of TMP-SMX (15 mg/kg) has been suggested to treat S. maltophilia infections, which is similar in amount used to treat Pneumocystis jirovecii pneumonia.In vitro studies proved that TMP-SMX suppresses the liberation of TNF-α from peripheral blood monocytes that have been induced by S. maltophilia, but further clinical investigation on this observation is required. However, this drug has side effects such as intolerance and hypersensitivity, which may limit its use.
Reports are now emerging relating to the resistance to TMP-SMX throughout the world that ranges from 1.1% in Europe, 2.4% in North America, 4.5% in Latin America and 9.2% in Asian-Pacific regions. It has been reported that increased MIC values of TMP-SMX for clinical isolates of S. maltophilia is due to class 1 integrons. Transposition events transfer the class 1 integrons present in transposons to plasmids or chromosomal DNA. The resistance to TMP-SMX has been attributed to two allelic forms of sul genes (sul1 and sul2). These genes have been found in association with class 1 integrons and insertion sequence common region elements. However, there are also reports on the absence of sul1 gene as a part of class 1integron., On the other hand, sul2 gene has been found located on plasmids and as part of chromosomal DNA.
Clinafloxacin, gatifloxacin, moxifloxacin, levofloxacin and sitafloxacin represent better in vitro activity than previous quinolones. In an in vitro study, the activities of ciprofloxacin and levofloxacin were compared and results revealed more susceptibility of S. maltophilia isolates to levofloxacin (85.5%) than ciprofloxacin (58.9%). In another study, susceptibility rate was reported to be higher than 95% for newer fluoroquinolones.
The genome analysis of S. maltophilia strain K279a revealed the presence of Smqnr genes that encode for proteins, which are homologous to quinolone protection proteins (Qnr) found in Enterobacteriaceae. The genes encode for pentapeptide repeat proteins that provide protection to DNA gyrase and topoisomerases from quinolones. The qnr genes are thought to have originated from chromosome of aquatic or environmental bacteria, which are transferred to plasmids by horizontal transfer of integrons and other mobile genetic elements carrying qnr genes. It has been reported that plasmid-mediated quinolone resistance may be responsible for stabilising and selecting mutations in DNA gyrase and topoisomerase, which provides high-level resistance to quinolones.
It has been reported that in S. maltophilia, Smqnr genes on chromosomes are responsible for much defined activity because when plasmid carrying qnr genes were provided in wild-type and Smqnr mutants, the resistance to quinolones increased in both the cases.
S. maltophilia exhibits high intrinsic resistance rates towards penicillins, cephalosporins and carbapenems. However, the combination of clavulanic acid, a β-lactamase inhibitor, with these antimicrobials may improve their activity against S. maltophilia. Ticarcillin-clavulanic acid has been prescribed as the second drug of choice owing to its in vitro activity for treating S. maltophilia infections in patients on which TMP-SMX failed to work. The addition of ticarcillin to combination of aztreonam with clavulanic acid (2/1 or 1/1) further enhanced the in vitro activity of combination against S. maltophilia.,, Although favourable treatment in selected cases has been reported, pharmacokinetics of aztreonam and clavulanate are different, which inhibits the clinical use of combination.,
In S. maltophilia resistance to β-lactam antibiotics is due to two inducible β-lactamases, L1 and L2, which are chromosomally encoded. The β-lactamase L1, a homotetramer of 118 kDa, belongs to an Ambler class B Zn + dependent metalloenzyme. It hydrolyses all the classes of β-lactams except monobactams. The β-lactamase L2 belongs to an Ambler class A serine active site β-lactamases and is inhibited by clavulanic acid. Cephalosporins of higher class such as ceftazidime, cefoperazone and cefepime exhibit some in vitro activity and ceftazidime has been successfully used as monotherapy in few cases. The inconsistent occurrence of inducible β-lactamases inhibits their activity and is responsible for high resistance rate to this group of antibiotics. Moreover, few studies have reported that the exposure to ceftazidime and cefepime further increases the chances of S. maltophilia infections., The combinations of cephalosporins with β-lactamase inhibitors, such as cefepime-clavulanic acid, ceftazidime-clavulanic and ceftazidime-sulbactam, did not show any in vitro activity.,
Minocycline, doxycycline and tigecycline have revealed good in vitro activity, but the absence of clinical studies on efficiency of these drugs limits their use in the treatment of S. maltophilia infections. Tigecycline, the broad-spectrum antibiotic, was found effective in TMP-SMX resistant S. maltophilia, and moreover, it can surmount the resistance mechanism of efflux pumps and ribosomal target modifications.,
The presence of high intrinsic rate of resistance to aminoglycosides limits their use in the treatment of S. maltophilia infections. In S. maltophilia, resistance to aminoglycosides is attributed to temperature-dependent resistance due to outer protein changes, aminoglycoside-modifying enzymes and efflux pumps. Genes located on chromosomes encode for aminoglycoside acetyltransferase aac (6L')-Iz and aminoglycoside phosphotransferase aph (3L')-IIc and are responsible for lowering down susceptibility to amikacin, kanamycin, neomycin, netilmicin, paromomycin and tobramycin.,,S. maltophilia at different temperatures undergoes changes in the size of the O-polysaccharide and phosphate content of lipopolysaccharides due to which it shows variable amount of resistance to aminoglycosides, more at 30°C than at 37°C. These experimental results explain the susceptibility of S. maltophilia clinical isolates to aminoglycosides at 37°C and resistance at 30°C.
In the past few years, there has been an increase in the use of polymyxins in the treatment of infections caused by NFGNB. In case of S. maltophilia, high susceptibility rate against colistin and polymyxin B has been reported; however, there is uncertainty about the in vitro clinical data, which creates problem in susceptibility testing of these antibiotics. The resistance to polymyxin B has been found in association with lipopolysaccharide present in outer membrane.
The high level of intrinsic resistance, increasing incidence of acquired resistance and the bacteriostatic activity of TMP-SMX are the stimulants for combination therapy for treating S. maltophilia infections. In case, where TMP-SMX fails to treat S. maltophilia infections, combination of two or more antimicrobials might prove boon, but there is lack of clinical data about combination therapy. The design of combination therapy depends upon the enhanced activity of combination of drugs when compared to single drugs even in case where one or both of antimicrobials are resistant to bacteria. The recommendations for such combinations of antimicrobials for treatment depends upon clinical trials; however, instead of these limitations, the use of combination therapy has been recommended in patients suffering from bacteraemia, endocarditis and osteomyelitis with high rate of resistance to TMP-SMX.,,,, And, examples in which combination therapy proved successful include S. maltophilia early prosthetic-aortic-valve endocarditis and osteomyelitis., It has been suggested that inclusion of TMP-SMX in a combination therapy is a better choice and combinations of TMP-SMX with ticarcillin-clavulanic acid, moxifloxacin, ceftazidime and tobramycin have shown synergy.,,, Chloramphenicol in combination with sulphonamide and gentamicin has proved successful in treating meningitis caused by S. maltophilia.
In India, 13.4% resistance to TMP-SMX was observed from Karnataka. The analysis of antimicrobial susceptibility of 125 clinical isolates of S. maltophilia isolated over 5 years (2007–2012) from North India showed that minocycline and levofloxacin exhibited the highest susceptibility rate followed by TMP-SMX (83%). A more recent study from the same region, conducted on 106 S. maltophilia isolates, demonstrated similar susceptibility rate for minocycline and levofloxacin; however, a decreased susceptibility rate was found for mainstay antibiotic TMP-SMX (77.4%). Twenty-four isolates (out of 106) were found resistant to TMP-SMX and these resistant isolates sustained relatively higher percentage of TMP-SMX resistance gene sul2 than sul1 gene. Moreover, sul1 gene was not found in association with class 1 integrase gene in majority of TMP-SMX-resistant isolates. This decrease in susceptibility may be due to increased antibiotic usage in clinical settings and resulting into TMP-SMX-resistant S. maltophilia strains, which further warrants its judicious use in future.
| ~ Conclusion|| |
S. maltophilia has risen from being a trivial environmental organism used in bioremediation to being a grievous opportunistic pathogen during the last two decades. It is not only resistant to multiple antibiotics but can also degrade and use antibiotics as food, which is of great concern especially in nosocomial infections. It further reinforces the need to look into this aspect of the bacterium. The present scenario requires that clinical microbiology laboratories should correctly identify S. maltophilia. To understand better about this bacterium, there is a great need to gather epidemiological data of clinical S. maltophilia isolates in India. Moreover, hospitals should also perform surveillance on S. maltophilia-associated infections.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| ~ References|| |
Chien CC, Hung CW, Han CT. Removal of cadmium ions during stationary growth phase by an extremely cadmium-resistant strain of Stenotrophomonas
sp. Environ Toxicol Chem 2007;26:664-8.
Lee EY, Jun YS, Cho KS, Ryu HW. Degradation characteristics of toluene, benzene, ethylbenzene, and xylene by Stenotrophomonas maltophilia
T3-c. J Air Waste Manag Assoc 2002;52:400-6.
LiPuma JJ, CB, Lum GD, Vandamme PA. Burkholderia, Stenotrophomonas, Ralstonia, Cupriavidus, Pandoraea, Brevundimonas, Comamonas
. In: Murray PR, Baron EJ, Jorgensen JH, Landry ML, Pfaller MA, editors. Manual of Clinical Microbiology. 9th
ed. Ch. 9. Washington, D.C.: ASM Press; 2007. p. 749-69.
Denton M, Kerr KG. Microbiological and clinical aspects of infection associated with Stenotrophomonas maltophilia
. Clin Microbiol Rev 1998;11:57-80.
Falagas ME, Valkimadi PE, Huang YT, Matthaiou DK, Hsueh PR. Therapeutic options for Stenotrophomonas maltophilia
infections beyond co-trimoxazole: A systematic review. J Antimicrob Chemother 2008;62:889-94.
Looney WJ, Narita M, Mühlemann K. Stenotrophomonas maltophilia
: An emerging opportunist human pathogen. Lancet Infect Dis 2009;9:312-23.
Brooke JS. Stenotrophomonas maltophilia
: An emerging global opportunistic pathogen. Clin Microbiol Rev 2012;25:2-41.
Hugh R, Leifson E. A description of the type strain of Pseudomonas maltophilia
. Int Bull Bacteriol Nomencl Taxon 1963;13:133-8.
Swings J, De Vos P, Van den Mooter M, De Ley J. Transfer of Pseudomonas maltophilia
Hugh 1981 to the genus Xanthomonas
as Xanthomonas maltophilia
(Hugh 1981). Int J Syst Bacteriol 1983;33:409-13.
Palleroni NJ, Bradbury JF. Stenotrophomonas
, a new bacterial genus for Xanthomonas maltophilia
(Hugh 1980) Swings et al
. 1983. Int J Syst Bacteriol 1993;43:606-9.
Drancourt M, Bollet C, Raoult D. Stenotrophomonas
africana sp. Nov. an opportunistic human pathogen in Africa. Int J Syst Bacteriol 1997;47:160-3.
Coenye T, Vanlaere E, Falsen E, Vandamme P. Stenotrophomonas
africana Drancourt et al
. 1997 is a later synonym of Stenotrophomonas maltophilia
(Hugh 1981) Palleroni and Bradbury 1993. Int J Syst Evol Microbiol 2004;54:1235-7.
Vazquez SC, Rios Merino L, MacCormack WP, Fraile ER. Protease-producing psychrotrophic bacteria isolated from Antarctica. Polar Biol 1995;15:131-5.
Al-Anazi KA, Al-Jasser AM. Infections caused by Stenotrophomonas maltophilia
in recipients of hematopoietic stem cell transplantation. Front Oncol 2014;4:232.
Huang X, Liu J, Ding J, He Q, Xiong R, Zhang K, et al
. The investigation of nematocidal activity in Stenotrophomonas maltophilia
G2 and characterization of a novel virulence serine protease. Can J Microbiol 2009;55:934-42.
García CA, Passerini De Rossi B, Alcaraz E, Vay C, Franco M. Siderophores of Stenotrophomonas maltophilia
: Detection and determination of their chemical nature. Rev Argent Microbiol 2012;44:150-4.
Hagemann M, Hasse D, Berg G. Detection of a phage genome carrying a zonula occludens like toxin gene (zot) in clinical isolates of Stenotrophomonas maltophilia
. Arch Microbiol 2006;185:449-58.
Passerini de Rossi B, Calenda M, Vay C, Franco M. Biofilm formation by Stenotrophomonas maltophilia
isolates from device-associated nosocomial infections. Rev Argent Microbiol 2007;39:204-12.
Pompilio A, Piccolomini R, Picciani C, D'Antonio D, Savini V, Di Bonaventura G, et al
. Factors associated with adherence to and biofilm formation on polystyrene by Stenotrophomonas maltophilia
: The role of cell surface hydrophobicity and motility. FEMS Microbiol Lett 2008;287:41-7.
Liaw SJ, Lee YL, Hsueh PR. Multidrug resistance in clinical isolates of Stenotrophomonas maltophilia
: Roles of integrons, efflux pumps, phosphoglucomutase (SpgM), and melanin and biofilm formation. Int J Antimicrob Agents 2010;35:126-30.
Fouhy Y, Scanlon K, Schouest K, Spillane C, Crossman L, Avison MB, et al
. Diffusible signal factor-dependent cell-cell signaling and virulence in the nosocomial pathogen Stenotrophomonas maltophilia
. J Bacteriol 2007;189:4964-8.
Morrison AJ Jr., Hoffmann KK, Wenzel RP. Associated mortality and clinical characteristics of nosocomial Pseudomonas maltophilia
in a university hospital. J Clin Microbiol 1986;24:52-5.
Elsner HA, Dührsen U, Hollwitz B, Kaulfers PM, Hossfeld DK. Fatal pulmonary hemorrhage in patients with acute leukemia and fulminant pneumonia caused by Stenotrophomonas maltophilia
. Ann Hematol 1997;74:155-61.
Vartivarian SE, Anaissie EJ, Kiwan EN, Papadakis KA. The clinical spectrum of Stenotrophomonas
respiratory infection. Semin Respir Crit Care Med 2000;21:349-55.
Hanes SD, Demirkan K, Tolley E, Boucher BA, Croce MA, Wood GC, et al
. Risk factors for late-onset nosocomial pneumonia caused by Stenotrophomonas maltophilia
in critically ill trauma patients. Clin Infect Dis 2002;35:228-35.
Aisenberg G, Rolston KV, Dickey BF, Kontoyiannis DP, Raad II, Safdar A, et al
. Stenotrophomonas maltophilia
pneumonia in cancer patients without traditional risk factors for infection, 1997-2004. Eur J Clin Microbiol Infect Dis 2007;26:13-20.
Muder RR, Harris AP, Muller S, Edmond M, Chow JW, Papadakis K, et al
. Bacteremia due to Stenotrophomonas (Xanthomonas) maltophilia
: A prospective, multicenter study of 91 episodes. Clin Infect Dis 1996;22:508-12.
Senol E, DesJardin J, Stark PC, Barefoot L, Snydman DR. Attributable mortality of Stenotrophomonas maltophilia
bacteremia. Clin Infect Dis 2002;34:1653-6.
Wang WS, Liu CP, Lee CM, Huang FY. Stenotrophomonas maltophilia
bacteremia in adults: Four years' experience in a medical center in Northern Taiwan. J Microbiol Immunol Infect 2004;37:359-65.
Garazi M, Singer C, Tai J, Ginocchio CC. Bloodstream infections caused by Stenotrophomonas maltophilia
: A seven-year review. J Hosp Infect 2012;81:114-8.
Lockhart SR, Abramson MA, Beekmann SE, Gallagher G, Riedel S, Diekema DJ, et al
. Antimicrobial resistance among Gram-negative bacilli causing infections in intensive care unit patients in the United States between 1993 and 2004. J Clin Microbiol 2007;45:3352-9.
Emerson J, McNamara S, Buccat AM, Worrell K, Burns JL. Changes in cystic fibrosis sputum microbiology in the United States between 1995 and 2008. Pediatr Pulmonol 2010;45:363-70.
Jones RN. Microbial etiologies of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. Clin Infect Dis 2010;51 Suppl 1:S81-7.
Millar FA, Simmonds NJ, Hodson ME. Trends in pathogens colonising the respiratory tract of adult patients with cystic fibrosis, 1985-2005. J Cyst Fibros 2009;8:386-91.
Fedler KA, Biedenbach DJ, Jones RN. Assessment of pathogen frequency and resistance patterns among pediatric patient isolates: Report from the 2004 SENTRY Antimicrobial Surveillance Program on 3 continents. Diagn Microbiol Infect Dis 2006;56:427-36.
Meyer E, Schwab F, Gastmeier P, Rueden H, Daschner FD, Jonas D, et al
. Stenotrophomonas maltophilia
and antibiotic use in German intensive care units: Data from project SARI (Surveillance of Antimicrobial Use and Antimicrobial Resistance in German Intensive Care Units). J Hosp Infect 2006;64:238-43.
Sattler CA, Mason EO Jr., Kaplan SL. Nonrespiratory Stenotrophomonas maltophilia
infection at a children's hospital. Clin Infect Dis 2000;31:1321-30.
Gales AC, Jones RN, Forward KR, Liñares J, Sader HS, Verhoef J, et al
. Emerging importance of multidrug-resistant Acinetobacter
species and Stenotrophomonas maltophilia
as pathogens in seriously ill patients: Geographic patterns, epidemiological features, and trends in the SENTRY Antimicrobial Surveillance Program (1997-1999). Clin Infect Dis 2001;32 Suppl 2:S104-13.
Rolston KV, Kontoyiannis DP, Yadegarynia D, Raad II. Nonfermentative gram-negative bacilli in cancer patients: Increasing frequency of infection and antimicrobial susceptibility of clinical isolates to fluoroquinolones. Diagn Microbiol Infect Dis 2005;51:215-8.
Weber DJ, Rutala WA, Sickbert-Bennett EE, Samsa GP, Brown V, Niederman MS, et al
. Microbiology of ventilator-associated pneumonia compared with that of hospital-acquired pneumonia. Infect Control Hosp Epidemiol 2007;28:825-31.
Libanore M, Bicocchi R, Pantaleoni M, Ghinelli F. Community-acquired infection due to Stenotrophomonas maltophilia
: A rare cause of meningitis. Int J Infect Dis 2004;8:317-9.
Pompilio A, Pomponio S, Crocetta V, Gherardi G, Verginelli F, Fiscarelli E, et al
. Phenotypic and genotypic characterization of Stenotrophomonas maltophilia
isolates from patients with cystic fibrosis: Genome diversity, biofilm formation, and virulence. BMC Microbiol 2011;11:159.
Vidigal PG, Dittmer S, Steinmann E, Buer J, Rath PM, Steinmann J, et al
. Adaptation of Stenotrophomonas maltophilia
in cystic fibrosis: Molecular diversity, mutation frequency and antibiotic resistance. Int J Med Microbiol 2014;304:613-9.
Pathmanathan A, Waterer GW. Significance of positive Stenotrophomonas maltophilia
culture in acute respiratory tract infection. Eur Respir J 2005;25:911-4.
Davies JC, Rubin BK. Emerging and unusual gram-negative infections in cystic fibrosis. Semin Respir Crit Care Med 2007;28:312-21.
Fujita J, Yamadori I, Xu G, Hojo S, Negayama K, Miyawaki H, et al
. Clinical features of Stenotrophomonas maltophilia
pneumonia in immunocompromised patients. Respir Med 1996;90:35-8.
Di Bonaventura G, Pompilio A, Zappacosta R, Petrucci F, Fiscarelli E, Rossi C, et al
. Role of excessive inflammatory response to Stenotrophomonas maltophilia
lung infection in DBA/2 mice and implications for cystic fibrosis. Infect Immun 2010;78:2466-76.
Pompilio A, Crocetta V, Scocchi M, Pomponio S, Di Vincenzo V, Mardirossian M, et al
. Potential novel therapeutic strategies in cystic fibrosis: Antimicrobial and anti-biofilm activity of natural and designed α-helical peptides against Staphylococcus aureus, Pseudomonas aeruginosa
, and Stenotrophomonas maltophilia
. BMC Microbiol 2012;12:145.
Wainwright CE, France MW, O'Rourke P, Anuj S, Kidd TJ, Nissen MD, et al
. Cough-generated aerosols of Pseudomonas aeruginosa
and other gram-negative bacteria from patients with cystic fibrosis. Thorax 2009;64:926-31.
Lai CH, Wong WW, Chin C, Huang CK, Lin HH, Chen WF, et al
. Central venous catheter-related Stenotrophomonas maltophilia
bacteraemia and associated relapsing bacteraemia in haematology and oncology patients. Clin Microbiol Infect 2006;12:986-91.
Micozzi A, Venditti M, Monaco M, Friedrich A, Taglietti F, Santilli S, et al
. Bacteremia due to Stenotrophomonas maltophilia
in patients with hematologic malignancies. Clin Infect Dis 2000;31:705-11.
Gopalakrishnan R, Hawley HB, Czachor JS, Markert RJ, Bernstein JM. Stenotrophomonas maltophilia
infection and colonization in the intensive care units of two community hospitals: A study of 143 patients. Heart Lung 1999;28:134-41.
Chang YT, Lin CY, Lu PL, Lai CC, Chen TC, Chen CY, et al
. Stenotrophomonas maltophilia
bloodstream infection: Comparison between community-onset and hospital-acquired infections. J Microbiol Immunol Infect 2014;47:28-35.
Das T, Deshmukh HS, Mathai A, Reddy AK. Stenotrophomonas maltophilia
endogenous endophthalmitis: Clinical presentation, sensitivity spectrum and management. J Med Microbiol 2009;58:837-8.
Thomas J, Prabhu VN, Varaprasad IR, Agrawal S, Narsimulu G. Stenotrophomonas maltophilia
: A very rare cause of tropical pyomyositis. Int J Rheum Dis 2010;13:89-90.
Viswanathan R, Singh AK, Ghosh C, Basu S. Stenotrophomonas maltophilia
causing early onset neonatal sepsis. Indian Pediatr 2011;48:397-9.
Mahendradas P, Avadhani K, Anandula V, Shetty R. Unilateral conjunctival ulcer due to Stenotrophomonas maltophilia
infection. Indian J Ophthalmol 2012;60:134-6.
] [Full text]
Nag F, De A, Banerjee K, Chatterjee G. Non healing leg ulcer infected with Stenotrophomonas maltophilia
:First reported case from India. Int Wound J 2013;10:356-8.
Sood S, Vaid VK, Bhartiya H. Meningitis due to Stenotrophomonas maltophilia
after a neurosurgical procedure. J Clin Diagn Res 2013;7:1696-7.
Malini A, Deepa E, Gokul B, Prasad S. Nonfermenting gram-negative bacilli infections in a tertiary care hospital in Kolar, Karnataka. J Lab Physicians 2009;1:62-6.
] [Full text]
Chawla K, Vishwanath S, Munim FC. Nonfermenting gram-negative bacilli other than Pseudomonas aeruginosa
spp. Causing respiratory tract infections in a tertiary care center. J Glob Infect Dis 2013;5:144-8.
Arora S, Gautam V, Ray P. Changing susceptibility patterns of nonfermenting gram-negative bacilli. Indian J Med Microbiol 2012;30:485-6.
] [Full text]
Gautam V, Kumar S, Kaur P, Deepak T, Singhal L, Tewari R, et al
. Antimicrobial susceptibility pattern of Burkholderia cepacia
complex & Stenotrophomonas maltophilia
over six years (2007-2012). Indian J Med Res 2015;142:492-4.
] [Full text]
Kaur P, Gautam V, Tewari R. Distribution of class 1 integrons, sul1 and sul2 genes among clinical isolates of Stenotrophomonas maltophilia
from a tertiary care hospital in North India. Microb Drug Resist 2015;21:380-5.
Juhnke ME, des Jardin E. Selective medium for isolation of Xanthomonas maltophilia
from soil and rhizosphere environments. Appl Environ Microbiol 1989;55:747-50.
Kerr KG, Denton M, Todd N, Corps CM, Kumari P, Hawkey PM, et al
. A new selective differential medium for isolation of Stenotrophomonas maltophilia
. Eur J Clin Microbiol Infect Dis 1996;15:607-10.
Wilkinson FH, Kerr KG. Bottled water as a source of multi-resistant Stenotrophomonas
species for neutropenic patients. Eur J Cancer Care (Engl) 1998;7:12-4.
Denton M, Hall MJ, Todd NJ, Kerr KG, Littlewood JM. Improved isolation of Stenotrophomonas maltophilia
from the sputa of patients with cystic fibrosis using a selective medium. Clin Microbiol Infect 2000;6:397-8.
Denton M, Rajgopal A, Mooney L, Qureshi A, Kerr KG, Keer V, et al
. Stenotrophomonas maltophilia
contamination of nebulizers used to deliver aerosolized therapy to inpatients with cystic fibrosis. J Hosp Infect 2003;55:180-3.
Qureshi A, Mooney L, Denton M, Kerr KG. Stenotrophomonas maltophilia
in salad. Emerg Infect Dis 2005;11:1157-8.
Gautam V, Ray P, Vandamme P, Chatterjee SS, Das A, Sharma K, et al
. Identification of lysine positive non-fermenting gram negative bacilli (Stenotrophomonas maltophilia
and Burkholderia cepacia
complex). Indian J Med Microbiol 2009;27:128-33.
] [Full text]
Carmody LA, Spilker T, LiPuma JJ. Reassessment of Stenotrophomonas maltophilia
phenotype. J Clin Microbiol 2011;49:1101-3.
Whitby PW, Carter KB, Burns JL, Royall JA, LiPuma JJ, Stull TL, et al
. Identification and detection of Stenotrophomonas maltophilia
by rRNA-directed PCR. J Clin Microbiol 2000;38:4305-9.
Giordano A, Magni A, Trancassini M, Varesi P, Turner R, Mancini C, et al
. Identification of respiratory isolates of Stenotrophomonas maltophilia
by commercial biochemical systems and species-specific PCR. J Microbiol Methods 2006;64:135-8.
Foster NF, Chang BJ, Riley TV. Evaluation of a modified selective differential medium for the isolation of Stenotrophomonas maltophilia
. J Microbiol Methods 2008;75:153-5.
Hauben L, Vauterin L, Moore ER, Hoste B, Swings J. Genomic diversity of the genus Stenotrophomonas
. Int J Syst Bacteriol 1999;49 Pt 4:1749-60.
Valdezate S, Vindel A, Martín-Dávila P, Del Saz BS, Baquero F, Cantón R, et al
. High genetic diversity among Stenotrophomonas maltophilia
strains despite their originating at a single hospital. J Clin Microbiol 2004;42:693-9.
Kaiser S, Biehler K, Jonas D. A Stenotrophomonas maltophilia
multilocus sequence typing scheme for inferring population structure. J Bacteriol 2009;191:2934-43.
Cho SY, Kang CI, Kim J, Ha YE, Chung DR, Lee NY, et al
. Can levofloxacin be a useful alternative to trimethoprim-sulfamethoxazole for treating Stenotrophomonas maltophilia
bacteremia? Antimicrob Agents Chemother 2014;58:581-3.
Vasileuskaya-Schulz Z, Kaiser S, Maier T, Kostrzewa M, Jonas D. Delineation of Stenotrophomonas
spp. By multi-locus sequence analysis and MALDI-TOF mass spectrometry. Syst Appl Microbiol 2011;34:35-9.
Seng P, Drancourt M, Gouriet F, La Scola B, Fournier PE, Rolain JM, et al
. Ongoing revolution in bacteriology: Routine identification of bacteria by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Clin Infect Dis 2009;49:543-51.
Gautam V, Sharma M, Singhal L, Kumar S, Kaur P, Tiwari R, et al
. MALDI-TOF mass spectrometry: An emerging tool for unequivocal identification of non-fermenting gram-negative bacilli. Indian J Med Res 2017;145:665-72.
] [Full text]
Clinical and Laboratory Standards Institute: Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Sixth Informational Supplement. CLSI document M100-S26. Wayne, PA: Clinical and Laboratory Standards Institute; 2016.
Avison MB, Higgins CS, von Heldreich CJ, Bennett PM, Walsh TR. Plasmid location and molecular heterogeneity of the L1 and L2 beta-lactamase genes of Stenotrophomonas maltophilia
. Antimicrob Agents Chemother 2001;45:413-9.
al Naiemi N, Duim B, Bart A. A CTX-M extended-spectrum beta-lactamase in Pseudomonas aeruginosa
and Stenotrophomonas maltophilia
. J Med Microbiol 2006;55:1607-8.
Mett H, Schacher B, Wegmann L. Ultrasonic disintegration of bacteria may lead to irreversible inactivation of beta-lactamase. J Antimicrob Chemother 1988;22:293-8.
Akova M, Bonfiglio G, Livermore DM. Susceptibility to beta-lactam antibiotics of mutant strains of Xanthomonas maltophilia
with high- and low-level constitutive expression of L1 and L2 beta-lactamases. J Med Microbiol 1991;35:208-13.
Alonso A, Martínez JL. Cloning and characterization of smeDEF, a novel multidrug efflux pump from Stenotrophomonas maltophilia
. Antimicrob Agents Chemother 2000;44:3079-86.
Chang LL, Chen HF, Chang CY, Lee TM, Wu WJ. Contribution of integrons, and SmeABC and SmeDEF efflux pumps to multidrug resistance in clinical isolates of Stenotrophomonas maltophilia
. J Antimicrob Chemother 2004;53:518-21.
Barbolla R, Catalano M, Orman BE, Famiglietti A, Vay C, Smayevsky J, et al
. Class 1 integrons increase trimethoprim-sulfamethoxazole MICs against epidemiologically unrelated Stenotrophomonas maltophilia
isolates. Antimicrob Agents Chemother 2004;48:666-9.
Toleman MA, Bennett PM, Bennett DM, Jones RN, Walsh TR. Global emergence of trimethoprim/sulfamethoxazole resistance in Stenotrophomonas maltophilia
mediated by acquisition of sul genes. Emerg Infect Dis 2007;13:559-65.
Gordon NC, Wareham DW. Novel variants of the Smqnr family of quinolone resistance genes in clinical isolates of Stenotrophomonas maltophilia
. J Antimicrob Chemother 2010;65:483-9.
Sánchez MB, Martínez JL. Regulation of Smqnr expression by SmqnrR is strain-specific in Stenotrophomonas maltophilia
. J Antimicrob Chemother 2015;70:2913-4.
Wareham DW, Gordon NC, Shimizu K. Two new variants of and creation of a repository for Stenotrophomonas maltophilia
quinolone protection protein (Smqnr) genes. Int J Antimicrob Agents 2011;37:89-90.
Crossman LC, Gould VC, Dow JM, Vernikos GS, Okazaki A, Sebaihia M, et al
. The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia
reveals an organism heavily shielded by drug resistance determinants. Genome Biol 2008;9:R74.
Toleman MA, Bennett PM, Walsh TR. ISCR elements: Novel gene-capturing systems of the 21st
century? Microbiol Mol Biol Rev 2006;70:296-316.
Kalkut G. Sulfonamides and trimethoprim. Cancer Invest 1998;16:612-5.
Zelenitsky SA, Iacovides H, Ariano RE, Harding GK. Antibiotic combinations significantly more active than monotherapy in an in vitro
infection model of Stenotrophomonas maltophilia
. Diagn Microbiol Infect Dis 2005;51:39-43.
Vartivarian S, Anaissie E, Bodey G, Sprigg H, Rolston K. A changing pattern of susceptibility of Xanthomonas maltophilia
to antimicrobial agents: Implications for therapy. Antimicrob Agents Chemother 1994;38:624-7.
Vickers IE, Smikle MF. The immunomodulatory effect of antibiotics on the secretion of tumour necrosis factor alpha by peripheral blood mononuclear cells in response to Stenotrophomonas maltophilia
stimulation. West Indian Med J 2006;55:138-41.
Farrell DJ, Sader HS, Jones RN. Antimicrobial susceptibilities of a worldwide collection of Stenotrophomonas maltophilia
isolates tested against tigecycline and agents commonly used for S. Maltophilia
infections. Antimicrob Agents Chemother 2010;54:2735-7.
Gündoǧdu A, Long YB, Vollmerhausen TL, Katouli M. Antimicrobial resistance and distribution of sul genes and integron-associated intI genes among uropathogenic Escherichia coli
in Queensland, Australia. J Med Microbiol 2011;60:1633-42.
Nicodemo AC, Paez JI. Antimicrobial therapy for Stenotrophomonas maltophilia
infections. Eur J Clin Microbiol Infect Dis 2007;26:229-37.
Gesu GP, Marchetti F, Piccoli L, Cavallero A. Levofloxacin and ciprofloxacin in vitro
activities against 4,003 clinical bacterial isolates collected in 24 Italian laboratories. Antimicrob Agents Chemother 2003;47:816-9.
Valdezate S, Vindel A, Loza E, Baquero F, Cantón R. Antimicrobial susceptibilities of unique Stenotrophomonas maltophilia
clinical strains. Antimicrob Agents Chemother 2001;45:1581-4.
Shimizu K, Kikuchi K, Sasaki T, Takahashi N, Ohtsuka M, Ono Y, et al
. Smqnr, a new chromosome-carried quinolone resistance gene in Stenotrophomonas maltophilia
. Antimicrob Agents Chemother 2008;52:3823-5.
Poirel L, Villa L, Bertini A. Extended-spectrum β-lactamase and plasmid-mediated quinolone resistance. Emerg Infect Dis 2007;13:803-5.
Poirel L, Cattoir V, Nordmann P. Is plasmid-mediated quinolone resistance a clinically significant problem? Clin Microbiol Infect 2008;14:295-7.
Sanchez MB, Hernandez A, Martinez JL. Stenotrophomonas maltophilia
drug resistance. Future Microbiol 2009;4:655-60.
Muñoz Bellido JL, Muñoz Criado S, García García I, Alonso Manzanares MA, Gutiérrez Zufiaurre MN, García-Rodríguez JA, et al
activities of beta-lactam-beta-lactamase inhibitor combinations against Stenotrophomonas maltophilia
: Correlation between methods for testing inhibitory activity, time-kill curves, and bactericidal activity. Antimicrob Agents Chemother 1997;41:2612-5.
García-Rodríguez JA, García Sánchez JE, García García MI, García Sánchez E, Muñoz Bellido JL. Antibiotic susceptibility profile of Xanthomonas maltophilia
activity of beta-lactam/beta-lactamase inhibitor combinations. Diagn Microbiol Infect Dis 1991;14:239-43.
García-Rodríguez JA, García Sánchez JE, Muñoz Bellido JL, García García MI, García Sánchez E. Kinetics of antimicrobial activity of aztreonam/clavulanic acid (2:1) against Xanthomonas maltophilia
. J Antimicrob Chemother 1991;27:552-4.
García Sánchez JE, Vazquez López ML, Blazquez de Castro AM, Perez Simon JA, Gutierrez NG, Martin IT, et al
. Aztreonam/clavulanic acid in the treatment of serious infections caused by Stenotrophomonas maltophilia
in neutropenic patients: Case reports. J Chemother 1997;9:238-40.
del Toro MD, Rodríguez-Bano J, Herrero M, Rivero A, García-Ordoñez MA, Corzo J, et al
. Clinical epidemiology of Stenotrophomonas maltophilia
colonization and infection: A multicenter study. Medicine (Baltimore) 2002;81:228-39.
Lecso-Bornet M, Bergogne-Bérézin E. Susceptibility of 100 strains of Stenotrophomonas maltophilia
to three beta-lactams and five beta-lactam-beta-lactamase inhibitor combinations. J Antimicrob Chemother 1997;40:717-20.
Galles AC, Jones RN, Sader HS. Antimicrobial susceptibility profile of contemporary clinical strains of Stenotrophomonas maltophilia
isolates: Can moxifloxacin activity be predicted by levofloxacin MIC results? J Chemother 2008;20:38-42.
Sader HS, Jones RN, Dowzicky MJ, Fritsche TR. Antimicrobial activity of tigecycline tested against nosocomial bacterial pathogens from patients hospitalized in the intensive care unit. Diagn Microbiol Infect Dis 2005;52:203-8.
Insa R, Cercenado E, Goyanes MJ, Morente A, Bouza E.In vitro
activity of tigecycline against clinical isolates of Acinetobacter baumannii
and Stenotrophomonas maltophilia
. J Antimicrob Chemother 2007;59:583-5.
Lambert T, Ploy MC, Denis F, Courvalin P. Characterization of the chromosomal aac(6')-iz gene of Stenotrophomonas maltophilia
. Antimicrob Agents Chemother 1999;43:2366-71.
Li XZ, Zhang L, McKay GA, Poole K. Role of the acetyltransferase AAC (6')-iz modifying enzyme in aminoglycoside resistance in Stenotrophomonas maltophilia
. J Antimicrob Chemother 2003;51:803-11.
Okazaki A, Avison MB. Aph(3')-IIc, an aminoglycoside resistance determinant from Stenotrophomonas maltophilia
. Antimicrob Agents Chemother 2007;51:359-60.
McKay GA, Woods DE, MacDonald KL, Poole K. Role of phosphoglucomutase of Stenotrophomonas maltophilia
in lipopolysaccharide biosynthesis, virulence, and antibiotic resistance. Infect Immun 2003;71:3068-75.
Landman D, Georgescu C, Martin DA, Quale J. Polymyxins revisited. Clin Microbiol Rev 2008;21:449-65.
Nicodemo AC, Araujo MR, Ruiz AS, Gales AC.In vitro
susceptibility of Stenotrophomonas maltophilia
isolates: Comparison of disc diffusion, Etest and agar dilution methods. J Antimicrob Chemother 2004;53:604-8.
Landrum ML, Conger NG, Forgione MA. Trimethoprim-sulfamethoxazole in the treatment of Stenotrophomonas maltophilia
osteomyelitis. Clin Infect Dis 2005;40:1551-2.
Muder RR. Optimizing therapy for Stenotrophomonas maltophilia
. Semin Respir Crit Care Med 2007;28:672-7.
Safdar A, Rolston KV. Stenotrophomonas maltophilia
: Changing spectrum of a serious bacterial pathogen in patients with cancer. Clin Infect Dis 2007;45:1602-9.
Sanioǧlu S, Sokullu O, Yavuz SS, Kut MS, Palaz FK, Bilgen FS, et al
. Stenotrophomonas maltophilia
endocarditis treated with moxifloxacin-ceftazidime combination and annular wrapping technique. Anadolu Kardiyol Derg 2008;8:79-80.
Poulos CD, Matsumura SO, Willey BM, Low DE, McGeer A.In vitro
activities of antimicrobial combinations against Stenotrophomonas (Xanthomonas) maltophilia
. Antimicrob Agents Chemother 1995;39:2220-3.
Zhanel GG, DeCorby M, Nichol KA, Wierzbowski A, Baudry PJ, Karlowsky JA, et al
. Antimicrobial susceptibility of 3931 organisms isolated from intensive care units in Canada: Canadian National Intensive Care Unit Study, 2005/2006. Diagn Microbiol Infect Dis 2008;62:67-80.
[Table 1], [Table 2]