Review Iain J Abbott , Monica A Slavin

Review
For reprint orders, please contact [email protected]
Stenotrophomonas
maltophilia: emerging
disease patterns and
challenges for treatment
Expert Rev. Anti Infect. Ther. 9(4), 471–488 (2011)
Iain J Abbott†1,
Monica A Slavin1,2,
John D Turnidge3,
Karin A Thursky1,2
and Leon J Worth1
Department of Infectious Diseases,
Peter MacCallum Cancer Centre, East
Melbourne, Victoria, Australia
2
Victorian Infectious Diseases Service,
Royal Melbourne Hospital, Parkville,
Victoria, Australia
3
Division of Laboratory Medicine,
Women’s and Children’s Hospital,
North Adelaide, Australia
†
Author for correspondence:
Tel.: +61 396 561 599
Fax: +61 396 561 185
[email protected]
1
Stenotrophomonas maltophilia is a ubiquitous organism associated with opportunistic infections.
In the immunocompromised host, increasing prevalence and severity of illness is observed,
particularly opportunistic bloodstream infections and pneumonia syndromes. In this article, the
classification and microbiology are outlined, together with clinical presentation, outcomes and
management of infections due to S. maltophilia. Although virulence mechanisms and the genetic
basis of antibiotic resistance have been identified, a role for standardized and uniform reporting
of antibiotic sensitivity is not defined. Infections due to S. maltophilia have traditionally been
treated with trimethoprim–sulfamethoxazole, ticarcillin–clavulanic acid, or fluoroquinolone
agents. The use of combination therapies, newer fluoroquinolone agents and tetracycline
derivatives is discussed. Finally, measures to prevent transmission of S. maltophilia within
healthcare facilities are reported, especially in at-risk patient populations.
Keywords : antibiotic resistance • immunocompromised • opportunistic infection • Stenotrophomonas maltophilia
• trimethoprim–sulfamethoxazole • virulence factors
Classification, microbiology &
identification
The genus Stenotrophomonas is phylogenetically
classified as part of the Gammaproteobacteria
group. Currently, this genus is comprised
of eight species: Stenotrophomonas acidaminiphila, Stenotrophomonas chelatiphaga,
Stenotrophomonas humi, Stenotrophomonas
koreensis, Stenotrophomonas rhizophilia,
Stenotrophomonas terrae, Stenotrophomonas
nitritireducens and Stenotrophomonas maltophilia [1] . S. maltophilia was originally named
as a member of the genus Pseudomonas [2] before
assignment to the Xanthomonas genus [3] and
was recently reclassified as Stenotrophomonas [4] .
The full genomic sequence of two S. maltophilia isolates (K279a, a clinical isolate and
R551–3, an environmental isolate) is now
available [1,5] . Subclassification according to
genomic subtypes has been performed [6–11]
and demonstrates remarkable diversity among
S. maltophilia isolates. One recent study identified a unique strain associated with respiratory
tract specimens from cystic fibrosis (CF) and
intensive care unit (ICU) patients, suggesting
www.expert-reviews.com
10.1586/ERI.11.24
an adaptation to colonization of the airway [11] .
However, a clear relationship with virulence
or other clinical presentations has not been
determined.
Gram-stain, culture and biochemical properties are all used for routine laboratory identification. The features of S. maltophilia are
summarized in B ox 1 and F igur e 1. Although
not widely practiced, molecular diagnostic
techniques may also be used, reducing identification times by 24–48 h. Matrix-assisted
laser desorption ionization-time of flight mass
spectrometry (MALDI-TOF MS) produces
specific mass spectral fingerprints for different
organisms. When compared with multi-locus
sequence ana­lysis (MLSA), which uses partial
genes and 16s rRNA amplified by PCR and
sequenced, MALDI-TOF MS was less expensive and correlated well with MLSA results
[12] . In a comparative study of conventional
identification methods and MALDI-TOF MS,
however, identification failures occurred in
S. maltophilia [13] . Greater clinical experience
with these new diagnostic tests is required
before routine application.
© 2011 Expert Reviews Ltd
ISSN 1478-7210
471
Review
Abbott, Slavin, Turnidge, Thursky & Worth
Box 1. Characteristics of Stenotrophomonas
maltophilia.
Microscopy
• Gram-negative straight, or slightly curved, rod
• Multiple polar flagella
• Motile
Culture
• Blood agar – faint lavender colonies
• Nutrient agar – opaque gray/yellow colonies
• MacConkey agar – nonlactose fermenter
• Koser’s citrate medium – no growth
• Selective culture medium† – colony growth
Biochemical tests
• Oxidase reaction –negative
• Indole – negative
• Acid from – maltose and glucose
• Lysine decarboxylase – positive
• DNase – positive
Selective medium containing vancomycin, imipenem and amphotericin B with a
mannitol/bromothymol blue indicator system [150]. Meropenem may be used in
place of imipenem [151].
†
Febrile neutropenic sepsis and CF pulmonary exacerbations
are two clinical areas where application of these molecular diagnostic techniques could dramatically impact on management.
Given that many first-line empiric antibiotic agents used for the
management of febrile neutropenia do not have activity again
S. maltophilia [14] , the early identification of S. maltophilia from
blood cultures would allow for earlier change of antibiotics to
active agents [15] . In the management of CF pulmonary exacerbations, which can be commonly due to multiple copathogens, the
ability to identify S. maltophilia and detail the bacterial load,
the presence of other copathogens and detect virulence factor
­expression, would direct antibiotic treatment [16] .
Virulence factors & antibiotic resistance
Isolation of S. maltophilia in human specimens may represent
colonization rather than infection. Being an opportunistic pathogen, the relationship between host and organism is important,
with immunocompromised hosts and hospitalized patients being
predisposed to infection.
The ability to survive in biofilms and respond to environmental stressors makes S. maltophilia a persistent and adaptable pathogen. Biofilm production is associated with resistance
to environmental factors by promoting intimate attachment
to ­surfaces, resistance to phagocytic activity and other host
immune factors, shielding from antimicrobial activity and
enhanced spread throughout surfaces via bacterial motility
[17–19] . Biofilm production is caused by the interplay of multiple
contributory virulence factors including the flagella [20–22] , fimbriae, pili and afimbrial adhesin [5,23] and the outer-membrane
lipopoly­saccharide layer [1,5,24,25] . These factors have also been
shown to produce significant immunostimulatory affects that
promote inflammation, especially within the lungs [22,24,25] .
472
Quorum sensing via diffusible signal molecules can influence
the behavior of S. maltophilia populations within biofilms by
intraspecies signaling [26] . Other virulence factors of importance include a positively charged surface [27] , the production
of melanin-like pigment [28] , the production of extracellular
enzymes [5] and growth of small colony variants [29] . These
factors are discussed in detail in Table 1.
An important role for interspecies interactions in bacterial virulence has been demonstrated in CF patients, where S. maltophilia
may protect antibiotic-sensitive strains of Pseudomonas aeruginosa
by degrading antibiotics [30] . P. aeruginosa can also respond to
the signaling system mediated by diffusible signal molecules that
are produced by S. maltophilia, which then promote alteration
of biofilm architecture to increase tolerance to antibiotics [31] .
S. maltophilia has also been implicated as a potential reservoir
of resistance elements leading to transference to other bacteria
[5,32,33] . Resistance plasmid and transposon carriage has been demonstrated in S. maltophilia, as has transmission of these elements
to Escherichia coli, in vitro [34,35] .
Mechanisms of antibiotic resistance may be intrinsic, inducible
or acquired. Functional genomic ana­lysis of S. maltophilia reveals
considerable capacity for drug and heavy metal resistance [5] .
Resistance patterns are largely due to b-lactamases, multidrugefflux pumps, modifying enzymes, outer membrane changes and
target site modification (Table 2) .
b-lactam resistance is via two chromosomal b-lactamases, L1
and L2, that hydrolyze and inactivate these antibiotics [36–38] .
Their expression may be induced by the presence of b-lactam
antibiotics [39,40] . Clavulanic acid is an effective inhibitor of L2,
but not L1 b-lactamase [41] . Resistance to the aminoglycoside class
of antibiotics is seen in a variety of mechanisms including specific aminoglycoside-modifying enzymes that cause intrinsic resistance to all aminoglycoside antibiotics except gentamicin [42,43] .
Resistance by multidrug-efflux pumps affects multiple antibiotic
classes, including fluoroquinolone, tetracycline and macrolide
antibiotics [5,44] . Resistance to trimethoprim–sulfamethoxazole
has more recently been reported owing to modified target genes
sul1 and sul2 [34,45–47] .
Variations in resistance rates have been reported from region
to region, but resistance to trimethoprim–sulfamethoxazole is
generally accepted to be less than 10% in most settings. Data
collected from the Asia–Pacific region, Canada, Europe, Latin
America and the USA showed that the trimethoprim–sulfamethoxazole resistance rates ranged from 2 to 10% (n = 842)
depending on location [48] . The SENTRY Antimicrobial
Surveillance Program (1997–2003) reported a global resistance
rate of 4.7% [49] . This is to be contrasted with a Taiwanese study
of 103 S. maltophilia isolates from hospitalized patients, which
demonstrated 25% trimethoprim–sulfamethoxazole resistance
[45] . Recent data obtained from the SENTRY Antimicrobial
Surveillance Program (1998–2009; 679 S. maltophilia isolates)
suggest that current trimethoprim–sulfamethoxazole resistance rates in the Asia–Pacific region remain less than 10%
(7.8% resistant when applying Clinical Laboratory Standards
Institute, MIC breakpoint) [Turnidge JD, Pers. Comm.] .
Expert Rev. Anti Infect. Ther. 9(4), (2011)
Stenotrophomonas maltophilia: emerging disease patterns & challenges for treatment
Review
Epidemiology
Environment
With adaptability to hostile and nutrientlimited environments, S. maltophilia occurs
ubiquitously and may be isolated from water,
soil, plants, animals (reptiles and aquatic
animals [50–52]), foods (ready-to-eat salads
[53] , raw and microfiltrated milk [54,55]) and
materials used in clinical laboratories and
medical practice.
In hospital environments, S. maltophilia
may survive in dis­infectant solutions containing chlorhexidine–cetrimide or hexamidine [27] and can colonize inanimate
surfaces, including intravenous and urinary catheters. Other healthcare-associated sources of S. maltophilia include
contaminated intravenous fluids, hospital
water and ice supplies, nebulizers, dialysis
machines, ventilator circuits, thermometers, blood gas analyzers, intra-abdominal
balloon pumps and central venous or arterial pressure monitors [56] . Furthermore,
the hands of healthcare workers may be
a potential source of transmission [57] .
Predisposing factors for the acquisition
of S. maltophilia are summarized in Box 2.
Immunocompromised hosts are at highest risk for infection, often with multiple
­contributory risk factors.
Incidence
Figure 1. Laboratory appearance of Stenotrophomonas maltophilia.
(A) Gram stain showing evenly stained Gram-negative straight, or slightly curved, rods.
(B) Culture on MacConkey agar demonstrating lack of lactose fermentation. (C) Culture
on blood agar demonstrating faint lavender-colored colonies. (D) Scanning electron
micrograph of a S. maltophilia biofilm grown at 30°C for 24 h in a flow cell.
Reproduced with permission from the American Society for Microbiology [18] .
The incidence of S. maltophilia ranges from
7.1 to 37.7 cases per 10,000 hospital discharges, depending on the degree and severity of immunocompromise and underlying medical conditions in the population studied
[38] . International reports from tertiary healthcare facilities suggest that these numbers have increased over time [58–60] . Reports
of S. maltophilia bacteremia episodes from England, Wales, and
Northern Ireland demonstrated a 93% increase between the years
2000 and 2006, but then a decrease by 31% in the period 2005–
2009 [301] . Overall, this still accounted for a 30% increase over
the 10-year period of observation. At the MD Anderson Cancer
Center (TX, USA), an increased proportion of S. maltophilia
isolates (from 2 to 7% of Gram-negative bacilli isolates between
1986 and 2002) has been reported, representing an incremental increase in S. maltophilia’s ranking from ninth to fifth most
common Gram-negative organism [59] . S. maltophilia is the third
most common nonfermenting Gram-negative bacilli responsible
for healthcare-associated infections, behind P. aeruginosa and
Acinetobacter spp. [49] . Factors potentially contributing to increased
incidence include: an expansion of at-risk populations, the widespread use of intensive chemotherapy, the prolonged use of central
venous catheters (CVCs) and the selection pressure afforded by the
use of broad-spectrum antibiotics [61] .
www.expert-reviews.com
Special patient groups
Hematological malignancy
Patients with hematological malignancies (e.g., leukemia or
lymphoma) are at risk of colonization and opportunistic infection [62] . Chen et al. examined the epidemiology of bloodstream
infections in patients with hematological malignancies between
2002 and 2006 and found S. maltophilia to account for 6% of
all bloodstream isolates in neutropenic patients [63] . Individual
risk is related to the degree and duration of neutropenia, presence
of indwelling devices and loss of integrity of mucosal and skin
­surfaces. A range of predisposing factors for S. maltophilia infection may be present in the one patient (Box 1) . Severe mucositis
has been identified as an important risk factor [64] .
Cystic fibrosis
Approximately 10–15% of patients with CF are colonized with
S. maltophilia [65,66] . Recent retrospective studies have showed
reductions in the prevalence of P. aeruginosa and Burkholderia
cepacia complex, but an increase in emerging pathogens including S. maltophilia [67,68] . Colonization with S. maltophilia has,
however, not been associated with reduction in lung function or
473
Review
Abbott, Slavin, Turnidge, Thursky & Worth
Table 1. Potential virulence factors for Stenotrophomonas maltophilia infection.
Virulence
factor
Virulence gene(s)/structures
Proposed mechanisms
Ref.
Biofilm formation Interplay of multiple contributory factors: Significantly higher biofilm production at 32°C compared to
flagella, pili/fimbriae, quorum sensing
18°C or 37°C; produced as the bacteria spread and intimately
and outer-membrane LPS
attach to surfaces such as medical implants and venous or
urinary catheters; resist host immune factors and shield from
antimicrobial activity
[17–19,152]
Flagella
Composed of a 38–42-kDa flagellin
subunit (SMFliC)
Stimulates innate immunity and provides enhanced motility;
considerable shared sequence identity to the flagellins of Serratia
marcescens, Escherichia coli, Proteus mirablis, Shigella sonnei and
Pseudomonas aeruginosa
[20–22]
Pili/fimbriae/
adhesins
17-kDa fimbriae subunit, Smf-1, seen as Contributes to adherence, autoaggregration, colonization of
peritrichous semi-flexible fimbriae of
biotic and abiotic surfaces, evasion of the host immune response
5–7 nm under electron microscopy. Also and increased drug resistance
identified are TadE-like pili/fimbrial
genes, type IV pili, afimbrial adhesin,
Hep–Hag family adhesins and two
hemagglutinin/hemolysin family proteins
[5,23]
Outer-membrane SpgM, also known as xanA gene, is a
LPS
phosphoglucomutase and is a
homologue of AlgC in P. aeruginosa that
is associated with LPS and alginate
biosynthesis. Mutations in manA, rmlA
and rmlC affect LPS structure.
Considerable level of variation in
O antigens between isolates, defining
31 serotypes
Forms an integral component of the extracellular matrix of
bacterial biofilms; has a role in resistance of bacteria to
antibiotics; involved in colonization and resistance to
complement-mediated cell killing; immunostimulatory effects,
implicated in airway inflammation, via mechanisms including
TNF-a and IL-8 expression, and polymorphonuclear leukocyte
recruitment. Variations in LPS biosynthetic gene clusters,
particularly the O-antigen moiety, may be implicated in evading
the host immune system
[1,5,24,25]
Intercellular and Uses the Xanthomonas and Xylella
intracellular
signaling system mediated by a diffusible
signaling
signal factor, methyl dodecenoic acid
(quorum sensing)
A cell–cell signaling factor to regulate a number of virulence
traits and antimicrobial resistance (e.g., motility, extracellular
proteases, LPS synthesis, microcolony formation, and tolerance
toward antibiotics and heavy metal ions); likely to be responsive
to environmental cues; interspecies signaling occurs in
polymicrobial infections
[26,31]
Extracellular
enzymes
Produces protease and phospholipases. StmPr1 protease is a
phage-encoded zonula occludens-like toxin enabling
S. maltophilia to degrade human serum and tissue proteins
(e.g., the IgG heavy chain, protein components of collagen,
fibronectin and fibrinogen) and contribute to local tissue damage
and hemorrhage
Characterized by small colony size, slow growth (or no growth)
on agar media compared to wild-type isolates and the inability to
generate in vitro susceptibility results (broth MIC, Kirby-Bauer or
E-test) under standard conditions. May be implicated in latent or
recurrent infections
Resistance to antiseptics and disinfectants that bind with high
affinity to the negatively charged cell walls and membranes
of bacteria
Protects cells from environmental insult. Associated with
resistance to ciprofloxacin and ticarcillin–clavulanic acid antibiotics
SCV
StmPr1, an alkaline serine protease;
plcN1, nonhemolytic phospholipase C;
other enzymes from the phospholipase D
family; other strain-specific extracellular
enzymes include DNase, gelatinase,
hemolysin, lipases and proteinase K
Interference with the dihydrofolate
reductase pathway; prolonged exposure
to antibiotics may select for both the SCV
S. maltophilia phenotype and
trimethoprim–sulfamethoxazole resistance
Positively charged
surface
Melanin-like
pigment
Tyrosinase gene (mel)
[5]
[29]
[27]
[28]
LPS: Lipopolysaccharide; SCV: Small colony variant.
short-term survival [69,70] . Information regarding the impact of
S. maltophilia post-lung transplantation is limited, but unlike
other resistant organisms such as Burkholderia cenocepacia, the
presence of S. maltophilia is not a contraindication to transplantation [71] . Polymicrobial infections are common, especially
with P. aeruginosa as a copathogen. More than one strain of
474
S. maltophilia has been identified in one third of patients with
repeated episodes of S. maltophilia infection or colonization [72] .
Small-colony variant forms of S. maltophilia have been isolated
from the sputa of CF patients. These are significant because
slower growth and increased antibiotic resistance enable persistence in the airway [29] .
Expert Rev. Anti Infect. Ther. 9(4), (2011)
Stenotrophomonas maltophilia: emerging disease patterns & challenges for treatment
ICU patients
Patients requiring ICU support frequently require intubation
and mechanical ventilation and are at risk for development of
ventilator-associated pneumonia (VAP). Between 1993 and 2004,
4.3% of Gram-negative infections in intensive care patients in the
USA were due to S. maltophilia [73] . In ICU patients with nosocomial pneumonia, S. maltophilia has been identified as the cause of
VAP in 6% of cases [74] . Chronic obstructive airway disease and
duration of antibiotic treatment were independent risk factors for
ICU-acquired S. maltophilia in an observational ICU study [75] .
Patient–patient clonal transmission of S. maltophilia within the
ICU environment has been reported [76] .
Review
hospitalized patients (53 cases), 56% had an underlying hematological disorder and the mortality rate was 51% [87] . Neutropenia
and mixed infection with Enterococcus spp. were independent factors associated with mortality. A 10-year audit of 32 S. maltophilia
bacteremia episodes in pediatric patients showed early and effective targeted antimicrobial therapy and early removal of CVC to be
associated with improved outcomes [101] . Bloodstream infections
can be polymicrobial (i.e., S. maltophilia isolated with copathogens) and this finding may indicate underlying catheter-related
bacteremia [91,98,99,102] . In a retrospective study of hematopoietic
stem cell transplant recipients, 11 of 19 patients (58%) had a polymicrobial infection [103] . The most common copathogens were
Acinetobacter baumannii, P. aeruginosa and Enterococcus faecalis.
Other patient groups
Patients with end-stage renal disease receiving both peritoneal dialysis
and maintenance hemodialysis are another at-risk group for S. maltophilia infections [77,78] . These infections are frequently related to the
presence of indwelling dialysis catheters. High mortality rates have
been reported for S. maltophilia pneumonia in this population [79] .
Stenotrophomonas maltophilia is an important cause of respiratory infections in neonates [80,81] , where it has also been detected
in gastric aspirates. Trimethoprim–sulfamethoxazole-resistant
isolates [82] and interpatient transmission have been reported [83]
in neonatal populations.
Lower respiratory tract infection remains a leading cause of
morbidity and mortality following solid organ transplantation,
where S. maltophilia has been implicated as a causative agent [84] .
Following liver transplantation, S. maltophilia bacteremia accounted
for 14.9% of all bacteremic episodes in a single-center cohort [85] .
Stenotrophomonas maltophilia has also been identified as an
opportunistic infection in patients with significant burns [86] . Over
a 9-year period, 14 episodes of S. maltophilia bacteremia were seen
in 13 of 666 patients admitted to a single burn center [86] .
Pneumonia
Clinical presentation
Management of infections
In at-risk patient populations, S. maltophilia may result in a range
of clinical syndromes (Table 3) . Most commonly, bacteremia (usually in the presence of an indwelling venous catheter) [63,77,87–91]
and pneumonia (especially in the setting of mechanical ventilation
or underlying chronic lung disease) [92–95] are observed. Although
predominantly a pathogen that causes infections in hospitalized and immunocompromised patients, community-acquired
S. maltophilia infections have been reported [61] . The attributable
mortality of S. maltophilia infection has been estimated to be
between 26.7 [96] and 37.5% [97] . In a retrospective hospital cohort,
the rate of septic shock associated with S. maltophilia infection was
30% and was an independent risk factor for 14-day mortality [98] .
Susceptibility testing & clinical breakpoints
Bloodstream infections
Approximately 1% of all nosocomial bacteremias are caused by
S. maltophilia [1] . S. maltophilia bacteremia is frequently associated
with an indwelling device, most commonly a CVC, and prognosis
is improved following the removal of the device [99] . Recurrent
bacteremia has been observed in the setting of failure to remove an
infected CVC and neutropenia [88,100] . In a retrospective review of
www.expert-reviews.com
The respiratory system is the most common site from which S. maltophilia is cultured. Pneumonia-causing isolates from the SENTRY
Antimicrobial Surveillance Program (1997–1999) were four-times
more prevalent than bloodstream isolates (3.3% of all respiratory
isolates versus 0.8% of all blood isolates) [48] . Severely debilitated
patients may be colonized asymptomatically with S. maltophilia [95]
and this organism may also be identified with other organisms in
respiratory specimens. It may therefore be difficult to distinguish
between colonization and infection with S. maltophilia. Clinical
and radiological findings will aid in the diagnosis of pneumonia or
VAP. The attributable mortality for S. maltophilia pneumonia has
been estimated to be 20–30%, even in non-neutropenic, non-ICU
patients [104] . Pulmonary hemorrhage is a fatal complication of fulminant S. maltophilia pneumonia and may arise in patients with an
underlying hematological malignancy [94] . In a retrospective study
of 406 patients with S. maltophilia pneumonia, S. maltophilia was
a component of polymicrobial infection in 43.6% of patients and
P. aeruginosa was the most common copathogen [93] .
Universal and standardized methods for the susceptibility testing
and reporting for S. maltophilia are not available. There remain
uncertainties surrounding which antibiotic agents should be tested
and what is the best in vitro methodology to be used. MIC and
disc diffusion zones are affected by both temperature and medium.
Many isolates grow optimally at 30°C and some isolates grow poorly
(or not at all) at 37°C. Similarly, some S. maltophilia isolates may
appear falsely susceptible at 37°C to many antibiotic classes [105] .
Although there are conflicting reports, disc diffusion and Etest
methods have been reported to be reliable for testing susceptibility to chloramphenicol, doxycycline, gatifloxacin, trimethoprim–
sulfa­methoxazole and ticarcillin–clavulanate [106] . This is in
contrast to testing for polymyxin B and colistin, where a weak
correlation has been found between disc diffusion and agar dilution techniques, likely related to the poor agar diffusion characteristics of colistin [107–110] . A recent study evaluating susceptibility
results obtained by disc diffusion, Etest and reference agar dilution
method, showed disc diffusion and Etest to be unreliable for ticarcillin–clavulanic acid and ciprofloxacin [111] . Given the current
475
476
Resistance to ciprofloxacin, norfloxacin
and tetracycline derivatives
SmrA
Multidrug ATP-binding cassette transporter
Resistance to macrolide class
Resistance to aminoglycoside class,
polymyxin B and fluoroquinolone class
mph(C) gene
SpgM gene encodes a bifunctional enzyme with both
phosphoglucomutase and phosphomannomutase
activities. Mutants lacking spgM gene produce less
lipopolysaccharide and tend to have shorter
O-polysaccharide chains
Resistance to aminoglycoside class
Resistance to tetracycline class,
chloramphenicol, erythromycin and
fluoroquinolone class
SmeDEF (expressed in 33% of S. maltophilia isolates);
loss of function mutations in smeT gene may lead or
contribute to SmeDEF overproduction; additional efflux
system reported include: SmeABC, SmeGH, SmeIJK,
SmeMN, SmeOP, SmeVWX and SmeYZ
Eight tripartite, putative resistant–nodulation–
division efflux pumps that actively extrude organic
solvents, disinfectants and antimicrobials from the
cell
Antibiotic inactivation by direct destruction or
Aminoglycoside-modifying enzymes are a family of
modification of the compound by hydrolysis, group chromosomal genes encoding for
transfer and redox mechanisms
O-nucleotidyltransferase, O-phosphotransferases and
N-acetyltransferase enzymes; aminoglycosideinactivating enzymes AAC(6’)-IIc and APH(3’)Iz
May present low virulence potential in
S. maltophilia, but could spread to
other Gram-negatives
CTX-M-15 and CTX-M-1 b-lactamases
A cephalosporinase. Inhibited by
clavulanic acid
L2 Ambler class A serine-b-lactamases
May act as a reservoir for mobile
b-lactamase genes
Hydrolyzes all b-lactam antibiotics
(penicillins, cephalosporins and
carbapenems) excluding
monobactams. Not inhibited by
clavulanic acid. Carbapenem therapy
shown to induce L1-b-lactamases
Impact upon antimicrobial
therapy
L1 Ambler class B Zn2+ -dependent metallo-b-lactamase
(hometetramer 118 kDa)
Responsible gene(s)
TEM-2 penicillinase (located on an active Tn1-like
transposon)
Changes in the Temperature-dependent changes affecting the
outer membrane fluidity, lipopolysaccharide side chain length and
core phosphate content of the outer membrane
Enzymatic
modification
Efflux systems
Two chromosomal inducible b-lactamases:
L1 and L2. Induced when exposed to b-lactams.
Production controlled by b-lactamase regulator
(AmpR)
b-lactamases
Extended-spectrum b-lactamase
Resistance mechanism
Category
Table 2. Stenotrophomonas maltophilia: mechanisms of antibiotic resistance.
[158]
[157]
[42,43]
[156]
[5,44]
[154,155]
[153]
[36–40]
Ref.
Review
Abbott, Slavin, Turnidge, Thursky & Worth
Expert Rev. Anti Infect. Ther. 9(4), (2011)
[34,45–47]
[34,47]
Trimethoprim–sulfamethoxazole
resistance
Trimethoprim–sulfamethoxazole
resistance
[32,159]
Resistance to fluoroquinolone class
Impact upon antimicrobial
therapy
Ref.
Stenotrophomonas maltophilia: emerging disease patterns & challenges for treatment
Review
controversy, disc diffusion and Etest appear to be most appropriate
for the susceptibility testing of trimethoprim–sulfamethoxazole
in S. maltophilia isolates [112] .
The European Committee on Antimicrobial Susceptibility Testing
(EUCAST) and the British Society for Antimicrobial Chemotherapy
(BSAC) report clinical breakpoint data only for trimethoprim–sulfamethoxazole (resistant: MIC >4 mg/l; zone diameter: <16 mm for
EUCAST, ≤19 mm for BSAC; disc content: 1.25/23.75 µg) [302,303] .
By contrast, a broader range of sensitivities has been reported by the
Clinical Laboratory Standards Institute, including data for trimethoprim–sulfamethoxazole, ceftazidime, ticarcillin–clavulanic acid,
minocycline, levofloxacin and chloramphenicol. EUCAST report
S. maltophilia to be intrinsically resistant to ceftazidime, regardless
of the result of susceptibility testing [304] . This is supported by the
wild-type MIC distribution of S. maltophilia and ceftazidime ranging from clinically achievable values to those well above that which
can be achieved with maximum doses [113] .
www.expert-reviews.com
Sul2
Located on large plasmids; resistance genes are
embedded in a transposon-like structure and can
transfer both intra- and inter-generically
(insertional sequence common region)
Integrase-encoding gene allows site-specific
Sul1
insertion of resistance gene cassettes between two
highly conserved adjacent nucleotide sequences;
located on transposons or plasmids that facilitate
transfer of integrons to other strains and bacterial
species (class 1 intergrons)
Smqnr
Protect DNA gyrase and topoisomerases from
inhibition
Target site
modification
Responsible gene(s)
Resistance mechanism
Category
Table 2. Stenotrophomonas maltophilia: mechanisms of antibiotic resistance.
Recommended antibiotic agents
Current treatment recommendations are based upon historical
evidence, case series, case reports and in vitro susceptibility studies. A summary of treatment options is provided in Table 4. The
recommended first-line agent is trimethoprim–sulfamethoxazole.
Alternative agents include ticarcillin–clavulanic acid, newer fluroquinolone agents (e.g., moxifloxacin) and tetracycline derivatives (e.g., tigecycline and minocycline). Other agents with
documented activity against S. maltophilia include colistin and
chloramphenicol. There are concerns regarding the use of ceftazidime, given high resistance rates and the potential for inducible
resistance. S. maltophilia is intrinsically resistant to carbapenems
and demonstrates high levels of resistance to aminoglycosides and
these agents should not be used as ­therapeutic options.
Trimethoprim–sulfamethoxazole resistance rates are generally
less than 10% [48,49,106,114–116] and high doses are recommended
given its bacteriostatic action [117] . Bone marrow suppression
side effects, among the other side effects of high-dose trimethoprim–sulfamethoxazole, may limit therapy, especially in
patients with underlying hematological malignancies receiving
myelosuppressive chemotherapy.
Ticarcillin–clavulanic acid is the most active b-lactam antibiotic as clavulanic acid is able to inhibit the L2 b-lactamase of
S. maltophilia [41,118] . Increasing resistance, however, has been
reported [49,106,119] . Clavulanic acid can also be used in combination with aztreonam [120] and aztreonam itself has been reported
as an inhibitor of L2 b-lactamase of S. maltophilia [121] .
Another b-lactam, ceftazidime, shows some in vitro activity,
however resistance rates are high [122] . Although clinical success has
been reported, often when used in combination with other active
agents [62] , its use as empirical therapy is not recommended [56] .
Newer fluoroquinolone agents have been proposed as promising
alternative agents. Moxifloxacin demonstrates a post-anti­biotic
effect and activity against biofilms [123,124] . Resistance rates remain
low to the newer fluoroquinolone agents when compared with
ciprofloxacin, however, rapid resistance can emerge on therapy,
limiting their use outside of combination therapy [125–127] .
477
Review
Abbott, Slavin, Turnidge, Thursky & Worth
Box 2. Predisposing factors for Stenotrophomonas
maltophilia infection.
• Compromised immune system
– Malignancy (hematologic/nonhematologic)
– Cytotoxic chemotherapy, or neutropenia (especially if prolonged)
– Solid organ transplantation
– Chronic lung disease (CF/COPD)
– HIV infection
– Hemodialysis
• Indwelling devices
– Intravascular catheters
– Other: indwelling urinary catheters or recent instrumentation;
endotracheal or tracheostomy tubes; neurosurgical devices;
prosthetic cardiac values and pacemaker wires;
ophthalmological lenses; and peritoneal catheters
• Intensive care unit admission
• Mechanical ventilation (or tracheostomy)
• Exposure to broad-spectrum antibiotics
– Especially carbapenems, extended-spectrum cephalosporins
and fluoroquinolones
– Risk increases with duration and the number of antimicrobials
used
• Prolonged hospital inpatient stay
• Mucositis
CF: Cystic fibrosis; COPD: Chronic obstructive pulmonary disease.
The tetracycline derivative, tigecycline, has been reported to
have susceptibility rates equivalent to trimethoprim–sulfamethoxazole, but clinical experience is limited [114] . Colistin has variable
activity against S. maltophilia and may offer another alternative
agent [106,107,109,110,128] .
Combination therapy
Combination therapy may be indicated in specific clinical settings. In practice, combination therapy is most often employed
in the setting of severe sepsis, neutropenia or polymicrobial infections, or when trimethoprim–sulfamethoxazole cannot be used
or tolerated. Because of the bacteriostatic action of most active
drugs, combination therapy has also been promoted to reduce the
risk of developing antibiotic resistance during ­treatment [38,129] .
In vitro synergy of antibiotic agents has been widely reported,
yet the extrapolation of these results for clinical application is
not yet supported by clinical trials [130] . Such synergy has been
reported for trimethoprim–sulfamethoxazole and ticarcillin–clavulanic acid (47–100% displaying synergy in >700 strains tested)
as well as ticarcillin–clavulanic acid and ciprofloxacin (13–75%
displaying synergy in >700 strains tested) combinations [131] . In
an in vitro study comparing trimethoprim–sulfamethoxazole
alone or in combination, all combinations were more active than
mono­therapy [117] . More recently, in vitro synergistic activity was
detected predominantly with trimethoprim–sulfamethoxazole and
ticarcillin–clavulanic acid, and trimethoprim–sulfamethoxazole
and ceftazidime, however, concerns remain regarding the reliability
of susceptibility testing methods [111] . A study of trimetho­prim–sulfamethoxazole-resistant S. maltophilia isolates showed a beneficial
478
role of combination therapy with trimethoprim–sulfamethoxazole
and polymyxin B in vitro, suggesting that significant benefit may
still be gained using antibiotic agents in combination that are inactive alone or only intermediately susceptible [132] . The interaction
of colistin and rifampin and, to a lesser extent, of colistin and trimethoprim–sulfamethoxazole has also been shown to inhibit the
growth in vitro of multidrug-resistant S. maltophilia [133] .
Clinical data supporting combination therapy is very limited and
although there are case reports detailing the use of many different
antibiotics combinations, clinical evidence for one combination over
another is lacking. In a recent review of 40 hematology patients with
S. maltophilia bacteremia, the most frequent combination therapy
used was trimethoprim–sulfamethoxazole or ceftazidime with ciprofloxacin [62] . Other reported combination regimes include: trimethoprim–sulfamethoxazole and amikacin in the treatment of an
infected pacemaker and epicardial electrodes [134] ; trimethoprim–
sulfamethoxazole and ciprofloxacin for bacteremia in a hemodialysis
patient with a long-term CVC [90]; trimethoprim–sulfamethoxazole
and ciprofloxacin for S. maltophilia meningitis in a preterm neonate
after neurosurgery [135]; trimethoprim–sulfamethoxazole and tobramycin for prosthetic mitral value S. maltophilia endocarditis [136] ;
trimethoprim–sulfa­methoxazole, ticarcillin–clavulanic acid and
aztreonam in an allogeneic bone marrow transplant recipient, who
developed myositis with S. maltophilia [137] ; and trimethoprim–sulfamethoxazole and ciprofloxacin for distal necrosis of the fingers
caused by a community-acquired S. maltophilia [138] .
The need for combination therapy becomes more apparent
when the use of trimethoprim–sulfamethoxazole is contraindicated, either due to allergic reaction or intolerance. In a systematic review examining therapeutic options for S. maltophilia
infections beyond trimethoprim–sulfamethoxazole, Falagas et al.
found the most common combinations to include ciprofloxacin,
­ticarcillin–clavulanic acid and ceftazidime [139] . More recently, a
case report of recurrent S. maltophilia VAP, which failed initial
trimethoprim–sulfamethoxazole therapy, was successfully treated
with intravenous doxycycline and aerosolized colistin [92] .
Prevention
Stenotrophomonas maltophilia may be identified infrequently, as part
of an outbreak, or as an endemic pathogen. In the setting of an outbreak, review of hospital infection control measures, consideration
of environmental reservoirs and improved ­antimicrobial stewardship
may be required.
Outbreaks of S. maltophilia infection within healthcare facilities
have been reported. For example, contaminated water supply has
been identified as a source of infection [57,83,140] . Transmission of
S. maltophilia among CF patients is uncommon but may occur [72] .
Within the ICU, clonal spread of S. maltophilia between patients
has been reported [76] .
Infection control
The beneficial role of hand hygiene in prevention of transmission
of S. maltophilia has been demonstrated in patients with CF [141]
and patients in ICU environments [76] . Although the potential role
for aerosolized transmission has been identified in patients with
Expert Rev. Anti Infect. Ther. 9(4), (2011)
Stenotrophomonas maltophilia: emerging disease patterns & challenges for treatment
Review
Table 3. Clinical syndromes associated with Stenotrophomonas maltophilia infection.
System
Syndrome
Clinical details
Associated factors
Cardiovascular
Bacteremia
Polymicrobial infections may be seen in
children or in the presence of an
infected CVC
CVC; hematological malignancy;
ICU patients; hemodialysis
Endocarditis
Subannular abscess has been reported
Prosthetic valve
Pacemaker infection
Delayed infection may occur
Ref.
[63,77,87–91]
[160–166]
[134]
Respiratory tract Pneumonia
New or progressive pulmonary infiltrate
on chest imaging
Ear, nose and
throat
Rhinosinusitis
May present as chronic refractory
rhinosinusitis
Gingivitis
Acute necrotizing ulcerative gingivitis
ALL
[169]
Epiglottitis
Necrotizing epiglottitis
Neutropenia; CMV disease
[170]
CLL
[171]
Otitis externa
Skin, soft tissue
and bone
Cellulitis
Chronic lung disease (CF and
COPD); intubation and mechanical
ventilation (VAP)
[92–95]
[167,168]
[172]
Hematogenous spread (in 58%), primary
cellulitis (in 23%) and ecthyma
gangrenosum (in 17%)
[137,138,173–175]
Deep soft tissue/myositis Acute upper airway obstruction caused
by infection of mucocutaneous and soft
tissues of the neck; distal necrosis of the
fingers reported
Neurological
Intra-abdominal
[176–179]
Septic arthritis and
bursitis
Detected by 16S rRNA gene analysis
from synovial fluid
HIV/AIDS
Osteomyelitis
Vertebral osetomyelitis and
spondylodiscitis
Post-discectomy; chronic hepatitis
B infection; post-renal
transplantation
[180,181]
Neurosurgical procedures
[182,183]
Meningitis
Brain abscess
Secondarily infected spontaneous lobar
cerebral hemorrhage
Enteritis
Chronic diarrhea; malabsorption; failure
to thrive
Cholangitis
[184]
Cerebral amyloid angiopathy
[185]
[186]
Hepatobiliary malignancy; biliary
tract obstruction; biliary tract
instrumentation
HIV; nephrostomy
[187–190]
Peritonitis
Peritoneal dialysis
[78,191]
Renal
Urinary tract infection
Obstructive uropathy; surgery of
urinary tract; neutropenia; urinary
tract structural abnormalities;
neonates
Opthalmic
Conjunctivitis/orbital
cellulitis/keratitis
Component of polymicrobial infection
Endophthalmitis
Acute endophthalmitis; endogenous
endopthalmitis; infected scleral buckle
Intra-abdominal
collection
Infected necrotic pancreatic collection;
liver abscess; superinfection of
perinephric abscess
[192–194]
[61,195,196]
Cataract and retinal reattachment
surgery; contaminated rinsing
solution; penetrating eye injuries
[197–200]
ALL: Acute lymphocytic leukemia; CF: Cystic fibrosis; CLL: Chronic lymphocytic leukemia; CMV: Cytomegalovirus; COPD: Chronic obstructive pulmonary disease;
CVC: Central venous catheter; ICU: Intensive care unit; VAP: Ventilator-associated pneumonia.
www.expert-reviews.com
479
Review
Abbott, Slavin, Turnidge, Thursky & Worth
Table 4. Treatment options for Stenotrophomonas maltophilia infection.
Antibiotic agent or
class
In vitro
Details
susceptibility (%)
Ref.
Trimethoprim–
sulfamethoxazole
>90†
Bacteriostatic, therefore high doses are recommended (trimethoprim
component ≥15 mg/kg per day). Therapy may be limited by side effects
(including cutaneous reactions, hepatotoxicity, myelosuppression, renal and
electrolyte disorders). Resistance may emerge during treatment
Ticarcillin–clavulanic
acid
45.3 to >70
Bacteriostatic. Aztreonam–clavulanic acid (2:1 or 1:1) also demonstrates
in vitro activity. Emergence of resistance reported. Other combinations such
as ticarcillin–sulbactam, piperacillin–tazobactam and ampicillin–sulbactam do
not have good activity
[34,114–116]
[48,49,
106,116,119,
120,201]
Newer fluoroquinolones 85–95
(e.g., clinafloxacin,
gatifloxacin,
moxifloxacin, sitafloxacin
and trovafloxacin)
Bacteriocidal. Newer agents show superior in vitro activity compared to earlier [123–127,202]
fluoroquinolones, such as ciprofloxacin. Moxifloxacin shown to produce a
post-antibiotic effect with daily dosing and decreased adhesion and biofilm
formation. Rapid emergence of resistance may emerge during treatment,
especially if used as monotherapy
Tetracycline derivatives
(minocycline and
tigecycline)
80–100
Limited clinical experience. Tigecycline may overcome the usual tetracycline
resistance mechanisms and has been found to be active against
trimethoprim–sulfamethoxazole-resistant isolates
[114,201–
204]
Colistin/polymyxin B
72.4–79
Variable activity found. Etest susceptibility testing preferred over disc
diffusion. Compared with agar dilution, however, broth microdilution, Etest
and disc diffusion can all give high rates of false susceptibility. Synergistic
activity reported when used in combination
[106,107,109,
110,128,133]
Fourth-generation
cephalosporins (e.g.,
ceftazidime)
0–53
Some in vitro activity, however, resistance rates are high. Combination
with b-lactamase inhibitors does not demonstrate activity in vitro.
EUCAST reports S. maltophilia to be intrinsically resistant to ceftazidime even
if in vitro sensitivity testing suggests the isolate to be sensitive.
Clinical success has been reported when ceftazidime is used in
combination therapy
[62,116,122]
Chloramphenicol
11.5–81.4
Some in vitro activity. Clinical experience is extremely limited and concern
regarding potential myelotoxicity may limit use
[106]
Stenotrophomonas maltophilia demonstrates intrinsic resistance to penicillin G, cefazolin, cefoxitin, cefamandole, cefuroxime, glycopeptides, fusidic acid, macrolides,
lincosamides, streptogramins, rifampicin, daptomycin and linezolid, a feature common to other nonfermentative Gram-negative bacteria [304].
†
Excluding reports from cystic fibrosis or patients from Taiwan, where higher resistance rates have been reported.
EUCAST: European Committee on Antimicrobial Susceptibility Testing.
CF [142] , respiratory isolation precautions are not routinely recommended for healthcare workers caring for patients with pneumonia due to S. maltophilia. Water filtration has been used to reduce
contamination of nebulizer equipment in this population [143] .
Environmental reservoirs
If an increased number of infections are observed within a healthcare facility, environmental sampling may be indicated to identify
a common source. Taps, nebulizers, sinks, portable water and contaminated hand moisturizer solutions have all been identified as
sites for S. maltophilia colonization in ward environments [144,145] .
Targeted environmental cleaning may be necessary in a commonsource outbreak. Recently, hydrogen peroxide and peracetic acid
have been reported to have activity against S. maltophilia [146] .
Antibiotic stewardship
Given the association of S. maltophilia acquisition with the use of
broad-spectrum antibiotic agents, measures to minimize the indiscriminate use of broad-spectrum antimicrobial therapy should be
encouraged [147,148] . Data analyzed across 39 German ICUs found
480
a significant positive correlation between total antibiotic use, carbapenem, ceftazidime, glycopeptide and fluoro­quinolone administration and the isolation of S. maltophilia [149] . It is plausible that
improved antibiotic stewardship could impact upon the incidence
of S. maltophilia isolates and reduce the development of induced
resistance to some antibiotic classes (e.g., fluoroquinolone agents).
Expert commentary
Being an opportunistic pathogen, it is necessary that careful clinical evaluation be performed in all patients in whom S. maltophilia
is isolated. The finding of S. maltophilia in blood or other sterile
sites is generally considered significant. However, nonsterile site
isolates may represent colonization or infection and evaluation of
underlying immunocompromise and clinical findings is necessary.
Patients with hematological malignancy represent an important at-risk population. In this group, the presence of indwelling
devices, administration of broad-spectrum antibiotic therapy and
loss of integrity of gut mucosa means that patients often have
multiple risk factors for acquisition of S. maltophilia. Molecular
or rapid diagnostic techniques would be of considerable benefit,
Expert Rev. Anti Infect. Ther. 9(4), (2011)
Stenotrophomonas maltophilia: emerging disease patterns & challenges for treatment
allowing earlier commencement of targeted therapy, with ­potential
to improve clinical outcomes.
Patients with chronic lung disease, particularly CF, represent
another at-risk population, with challenges regarding diagnosis.
In this group, long-term colonization of the airways by S. maltophilia is common. As a contributing pathogen in lower respiratory
tract infection, it is important that all clinical parameters are carefully evaluated: the presence of fever, change in respiratory function and radiological findings. Clinical challenges include the fact
that copathogens may be recovered from respiratory specimens in
patients with CF and the pathogenicity of individual isolates may
be difficult to ascertain. This same challenge may be faced in prolonged, mechanically ventilated patients.
First-line therapy for S. maltophilia infections is generally
with trimethoprim–sulfamethoxazole, although the beneficial
role for combination therapy requires further evaluation. Newer
antibiotic agents (e.g., tigecycline and moxifloxacin) also require
additional clinical evaluation. Future research endeavors validating antibiotic susceptibility reporting will directly assist in
the defining of roles for newer agents and combination therapies.
Review
malignancy, solid organ transplantation, chronic lung disease, endstage renal failure and neonatal populations. It will be necessary for
the further development of rapid and molecular diagnostic testing
and for this to be adopted within routine clinical practice.
The relationship between genotypic and phenotypic characteristics of S. maltophilia is not well established, meaning that
future research agendas must focus upon clinical outcomes.
There is an ongoing need for clinically relevant interpretation of
antibiotic susceptibility testing. Translational research, including
functional genomic analyses of S. maltophilia, may reveal alternative targets for new antimicrobial agents or novel mechanisms of
action (e.g., inhibition of quorum sensing or cell–cell signaling).
Given the ubiquitous nature of this organism, it is not likely
that eradication of healthcare facility-associated infections will
be achieved. Nonetheless, control may be achieved by environmental decontamination and optimizing hand hygiene practices.
Collaborative multicenter investigation of longitudinal data is
required to demonstrate the beneficial impact of antibiotic stewardship programs in reducing the incidence of S. maltophilia infections
and modifying antibiotic susceptibility profiles of S. maltophilia
isolates in healthcare facilities.
Five-year view
Over the last decade, increased prevalence of S. maltophilia infections has been reported in immunocompromised and hospitalized
patient populations. During this period, a greater understanding
of pathogenicity, including the genetic basis for disease, has been
gained. Molecular diagnostic methods have also been introduced.
Approaches to management, however, have remained largely
unchanged, with trimethoprim–sulfamethoxazole generally used
as first-line therapy for S. maltophilia infections.
Within the next 5 years, it is likely that disease burden related
to S. maltophilia infections will become increasingly significant if
enlarged immunocompromised patient populations are managed by
current healthcare services – for example, patients with hematological
Acknowledgements
Denis Spelman and Cameron Jeremiah (Department of Microbiology, The
Alfred Hospital, Melbourne, Australia) are acknowledged for the provision
of Gram-stain and culture images in Figure 1.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial conflict with
the subject matter or materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or options, expert
testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues
• Stenotrophomonas maltophilia has emerged as an opportunistic pathogen of increasing relevance to immunocompromised and
hospitalized patient populations. Examples of at-risk populations include patients in intensive care environments and patients with
hematologic disorders or cystic fibrosis.
• Biofilm production by S. maltophilia is an important virulence mechanism contributing to enhanced surface spread and adhesion,
resistance to phagocytosis and shielding from antimicrobial activity. A focus upon biofilm disruption is required for newer therapies,
especially for infections associated with indwelling medical devices.
• Molecular diagnostic techniques for S. maltophilia have the potential to improve clinical outcomes. However, further validation and
investigation of clinical correlates (viable bacterial load, antibiotic susceptibility profiles, virulence factor expression and clinical
outcomes) is required before routine application.
• Intrinsic, inducible and acquired mechanisms of resistance are well described for S. maltophilia. However, standardization is required for
reporting susceptibility of clinical isolates.
• The recommended first-line therapy for S. maltophilia infection is trimethoprim–sulfamethoxazole, supported by a high rate of in vitro
susceptibility (>90%) to this agent.
• Alternative therapies include ticarcillin–clavulanic acid and newer fluoroquinolone agents, which may be used as components of
combination regimens. Tigecycline and colistin have also been used in therapy for trimethoprim–sulfamethoxazole-resistant isolates,
although a more defined therapeutic role for these agents is yet to be established. Controversy remains regarding the use of
ceftazidime – the European Committee on Antimicrobial Susceptibility Testing reports S. maltophilia to be intrinsically resistant to
ceftazidime even if in vitro testing suggests susceptibility.
• In clinical practice, combination antibiotic therapy is generally reserved for severe sepsis and patients with neutropenia, or when
trimethoprim–sulfamethoxazole is contraindicated. However, compelling clinical evidence for combination therapies is lacking.
www.expert-reviews.com
481
Review
Abbott, Slavin, Turnidge, Thursky & Worth
References
10
Gould VC, Avison MB. SmeDEF-mediated
antimicrobial drug resistance in
Stenotrophomonas maltophilia clinical
isolates having defined phylogenetic
relationships. J. Antimicrob. Chemother.
57(6), 1070–1076 (2006).
11
Kaiser S, Biehler K, Jonas D. A
Stenotrophomonas maltophilia multilocus
sequence typing scheme for inferring
population structure. J. Bacteriol. 191(9),
2934–2943 (2009).
•
Comprehensive genetic subgroup
classification based on a multilocus
sequence typing scheme.
12
Svensson L, Gomila M, Mihaylova S,
Erhard M, Moore E. New genotypic and
phenotypic analyses of clinically-relevant
Gram-negative, non-fermenting bacteria:
MALDITOFMS as a rapid, high-resolution
method for identifying and typing
micro-organisms. Presented at: 20th
European Congress of Clinical Microbiology
and Infectious Diseases. Vienna, Austria,
10–13 April 2010.
Papers of special note have been highlighted as:
• of interest
•• of considerable interest
1
Ryan RP, Monchy S, Cardinale M et al.
The versatility and adaptation of bacteria
from the genus Stenotrophomonas. Nat. Rev.
Microbiol. 7(7), 514–525 (2009).
•• Excellent review of Stenotrophomonas
maltophilia phylogenetics and potential
pathogenic mechanisms.
2
Hugh R, Ryschenkow E. Pseudomonas
maltophilia, an Alcaligenes-like species. J.
Gen. Microbiol. 26(1), 123–132 (1961).
3
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) comb. nov. Int. J. Syst.
Bacteriol. 33(2), 409–413 (1983).
4
5
Palleroni NJ, Bradbury JF.
Stenotrophomonas, a new bacterial genus for
Xanthomonas maltophilia (Hugh 1980)
Swings et al. 1983. Int. J. Syst. Bacteriol.
43(3), 606–609 (1993).
Crossman LC, Gould VC, Dow JM et al.
The complete genome, comparative and
functional analysis of Stenotrophomonas
maltophilia reveals an organism heavily
shielded by drug resistance determinants.
Genome Biol. 9(4), R74 (2008).
•• Detailed analysis of the S. maltophilia
genome including genetic determinants of
antibiotic resistance.
6
7
8
9
13
Ferreira L, Vega S, Sanchez-Juanes F et al.
Identifying bacteria using a matrix-assisted
laser desorption ionization time-of-flight
(MALDI-TOF) mass spectrometer.
Comparison with routine methods used in
clinical microbiology laboratories. Enferm.
Infecc. Microbiol. Clin. 28(8), 492–497
(2010).
19
Pompilio A, Crocetta V, Confalone P et al.
Adhesion to and biofilm formation on
IB3-1 bronchial cells by Stenotrophomonas
maltophilia isolates from cystic fibrosis
patients. BMC Microbiol. 10, 102 (2010).
20
de Oliveira-Garcia D, Dall’Agnol M,
Rosales M, Azzuz AC, Martinez MB,
Giron JA. Characterization of flagella
produced by clinical strains of
Stenotrophomonas maltophilia. Emerg.
Infect. Dis. 8(9), 918–923 (2002).
21
Chhibber S, Zgair AK. Involvement of
Stenotrophomonas maltophilia flagellin in
bacterial adhesion to airway biotic surfaces:
an in vitro study. Am. J. Biomed. Sci. 1(3),
188–195 (2009).
22
Zgair AK, Chhibber S. Stenotrophomonas
maltophilia flagellin induces a
compartmentalized innate immune
response in mouse lung. J. Med. Microbiol.
59(Pt 8), 913–919 (2010).
23
de Oliveira-Garcia D, Dall’Agnol M,
Rosales M et al. Fimbriae and adherence of
Stenotrophomonas maltophilia to epithelial
cells and to abiotic surfaces. Cell. Microbiol.
5(9), 625–636 (2003).
24
Waters VJ, Gomez MI, Soong G, Amin S,
Ernst RK, Prince A. Immunostimulatory
properties of the emerging pathogen
Stenotrophomonas maltophilia. Infect.
Immun. 75(4), 1698–1703 (2007).
25
Di Bonaventura G, Pompilio A, Zappacosta
R et al. Role of excessive inflammatory
response to Stenotrophomonas maltophilia
lung infection in DBA/2 mice and
implications for cystic fibrosis. Infect.
Immun. 78(6), 2466–2476 (2010).
14
Minkwitz A, Berg G. Comparison of
antifungal activities and 16S ribosomal
DNA sequences of clinical and
environmental isolates of Stenotrophomonas
maltophilia. J. Clin. Microbiol. 39(1),
139–145 (2001).
Bal AM, Gould IM. Empirical
antimicrobial treatment for
chemotherapy-induced febrile
neutropenia. Int. J. Antimicrob. Agents
29(5), 501–509 (2007).
15
26
Coenye T, Vanlaere E, LiPuma JJ,
Vandamme P. Identification of genomic
groups in the genus Stenotrophomonas
using gyrB RFLP analysis. FEMS
Immunol. Med. Microbiol. 40(3), 181–185
(2004).
Xu J, Moore JE, Millar BC et al. Improved
laboratory diagnosis of bacterial and fungal
infections in patients with hematological
malignancies using PCR and ribosomal
RNA sequence analysis. Leuk. Lymphoma
45(8), 1637–1641 (2004).
Fouhy Y, Scanlon K, Schouest K et al.
Diffusible signal factor-dependent cell–
cell signaling and virulence in the
nosocomial pathogen Stenotrophomonas
maltophilia. J. Bacteriol. 189(13),
4964–4968 (2007).
16
Rogers GB, Hoffman LR, Whiteley M,
Daniels TWV, Carroll MP, Bruce KD.
Revealing the dynamics of polymicrobial
infections: implications for antibiotic
therapy. Trends Microbiol. 18(8), 357–364
(2010).
27
17
Hoštacká A, ižnár I, Štefkovičová M.
Temperature and pH affect the production
of bacterial biofilm. Folia Microbiologica
55(1), 75–78 (2010).
Grare M, Dibama HM, Lafosse S et al.
Cationic compounds with activity against
multidrug-resistant bacteria: interest of a
new compound compared with two older
antiseptics, hexamidine and chlorhexidine.
Clin. Microbiol. Infect. 16(5), 432–438
(2010).
28
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 35(2), 126–130 (2010).
29
Anderson SW, Stapp JR, Burns JL, Qin X.
Characterization of small-colony-variant
Stenotrophomonas maltophilia isolated from
Gould VC, Okazaki A, Howe RA, Avison
MB. Analysis of sequence variation among
smeDEF multi drug efflux pump genes and
flanking DNA from defined 16S rRNA
subgroups of clinical Stenotrophomonas
maltophilia isolates. J. Antimicrob.
Chemother. 54(2), 348–353 (2004).
Gould VC, Okazaki A, Avison MB.
b-lactam resistance and b-lactamase
expression in clinical Stenotrophomonas
maltophilia isolates having defined
phylogenetic relationships. J. Antimicrob.
Chemother. 57(2), 199–203 (2006).
482
18
Briandet R, Lacroix-Gueu P, Renault M
et al. Fluorescence correlation spectroscopy
to study diffusion and reaction of
bacteriophages inside biofilms. Appl.
Environ. Microbiol. 74(7), 2135–2143
(2008).
Expert Rev. Anti Infect. Ther. 9(4), (2011)
Stenotrophomonas maltophilia: emerging disease patterns & challenges for treatment
the sputum specimens of five patients with
cystic fibrosis. J. Clin. Microbiol. 45(2),
529–535 (2007).
30
31
32
33
34
•
35
36
Kataoka D, Fujiwara H, Kawakami T,
Tanaka Y, Tanimoto A, Ikawa S. The
indirect pathogenicity of Stenotrophomonas
maltophilia. Int. J. Antimicrob. Agents
22(6), 601–606 (2003).
Ryan RP, Fouhy Y, Garcia BF et al.
Interspecies signalling via the
Stenotrophomonas maltophilia diffusible
signal factor influences biofilm formation
and polymyxin tolerance in Pseudomonas
aeruginosa. Mol. Microbiol. 68(1), 75–86
(2008).
Gordon NC, Wareham DW. Novel variants
of the Smqnr family of quinolone resistance
genes in clinical isolates of Stenotrophomonas
maltophilia. J. Antimicrob. Chemother. 65(3),
483–489 (2010).
Sanchez MB, Hernandez A, RodriguezMartinez JM, Martinez-Martinez L,
Martinez JL. Predictive analysis of
transmissible quinolone resistance indicates
Stenotrophomonas maltophilia as a potential
source of a novel family of Qnr
determinants. BMC Microbiol. 8, 148
(2008).
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. 13(4), 559–565 (2007).
Genetic basis of trimethoprim–
sulfamethoxazole resistance in
S. maltophilia.
De Gelder L, Williams JJ, Ponciano JM,
Sota M, Top EM. Adaptive plasmid
evolution results in host-range expansion of
a broad-host-range plasmid. Genetics
178(4), 2179–2190 (2008).
Sanchez MB, Hernandez A, Martinez JL.
Stenotrophomonas maltophilia drug
resistance. Future Microbiol. 4, 655–660
(2009).
•• In-depth discussion of therapeutic options
for S. maltophilia infections.
39
40
41
42
38
Avison MB, Higgins CS, Ford PJ, von
Heldreich CJ, Walsh TR, Bennett PM.
Differential regulation of L1 and L2
b-lactamase expression in Stenotrophomonas
maltophilia. J. Antimicrob. Chemother.
49(2), 387–389 (2002).
Nicodemo AC, Paez JI. Antimicrobial
therapy for Stenotrophomonas maltophilia
infections. Eur. J. Clin. Microbiol. Infect.
Dis. 26(4), 229–237 (2007).
www.expert-reviews.com
Okazaki A, Avison MB. Induction of L1 and
L2 b-lactamase production in
Stenotrophomonas maltophilia is dependent
on an AmpR-type regulator. Antimicrob.
Agents Chemother. 52(4), 1525–1528 (2008).
Lin CW, Hu RM, Huang SC, Hsiao YJ,
Yang TC. Induction potential of clavulanic
acid toward L1 and L2 b-lactamases of
Stenotrophomonas maltophilia. Eur. J. Clin.
Microbiol. Infect. Dis. 27(12), 1273–1275
(2008).
Okazaki A, Avison MB. Aph(3’)-IIc, an
aminoglycoside resistance determinant
from Stenotrophomonas maltophilia.
Antimicrob. Agents Chemother. 51(1),
359–360 (2007).
43
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. 51(4), 803–811 (2003).
44
Hernandez A, Mate MJ, Sanchez-Diaz PC,
Romero A, Rojo F, Martinez JL. Structural
and functional analysis of SmeT, the
repressor of the Stenotrophomonas
maltophilia multidrug efflux pump
SmeDEF. J. Biol. Chem. 284(21),
14428–14438 (2009).
45
46
Chang LL, Lin HH, Chang CY, Lu PL.
Increased incidence of class 1 integrons in
trimethoprim/sulfamethoxazole-resistant
clinical isolates of Stenotrophomonas
maltophilia. J. Antimicrob. Chemother.
59(5), 1038–1039 (2007).
Song JH, Sung JY, Kwon KC et al.
Analysis of acquired resistance genes in
Stenotrophomonas maltophilia. Korean J.
Lab. Med. 30(3), 295–300 (2010).
47
Enne VI, Livermore DM, Stephens P, Hall
LMC. Persistence of sulphonamide
resistance in Escherichia coli in the UK
despite national prescribing restriction.
Lancet 357(9265), 1325–1328 (2001).
48
Gales AC, Jones RN, Forward KR, Linares
J, Sader HS, Verhoef J. 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.
32(Suppl. 2), S104–S113 (2001).
•• Excellent review of mechanisms of
antibiotic resistance in S. maltophilia
including clinical correlates.
37
Lin CW, Huang YW, Hu RM, Chiang
KH, Yang TC. The role of AmpR in
regulation of L1 and L2 b-lactamases in
Stenotrophomonas maltophilia. Res.
Microbiol. 160(2), 152–158 (2009).
Review
49
Sader HS, Jones RN. Antimicrobial
susceptibility of uncommonly isolated
non-enteric Gram-negative bacilli. Int. J.
Antimicrob. Agents 25(2), 95–109 (2005).
50
Hejnar P, Kolar M, Sauer P. Antibiotic
resistance of Stenotrophomonas maltophilia
strains isolated from captive snakes. Folia
Microbiol. (Praha) 55(1), 83–87 (2010).
51
Geng Y, Wang KY, Chen DF, Huang XL.
Isolation, identification and phylogenetic
analysis of a pathogenic bacterium in
channel catfish. Wei Sheng Wu Xue Bao
46(4), 649–652 (2006).
52
Diaz MA, Cooper RK, Cloeckaert A,
Siebeling RJ. Plasmid-mediated high-level
gentamicin resistance among enteric
bacteria isolated from pet turtles in
Louisiana. Appl. Environ. Microbiol. 72(1),
306–312 (2006).
53
Qureshi A, Mooney L, Denton M, Kerr
KG. Stenotrophomonas maltophilia in salad.
Emerg. Infect. Dis. 11(7), 1157–1158
(2005).
54
Rasolofo EA, St-Gelais D, LaPointe G, Roy
D. Molecular analysis of bacterial
population structure and dynamics during
cold storage of untreated and treated milk.
Int. J. Food Microbiol. 138(1–2), 108–118
(2010).
55
Delbes C, Ali-Mandjee L, Montel MC.
Monitoring bacterial communities in raw
milk and cheese by culture-dependent and
-independent 16S rRNA gene-based
analyses. Appl. Environ. Microbiol. 73(6),
1882–1891 (2007).
56
Senol E. Stenotrophomonas maltophilia: the
significance and role as a nosocomial
pathogen. J. Hosp. Infect. 57(1), 1–7
(2004).
57
Park YS, Kim SY, Park SY et al.
Pseudooutbreak of Stenotrophomonas
maltophilia bacteremia in a general ward.
Am. J. Infect. Control 36(1), 29–32 (2008).
58
Rolston KV, Kontoyiannis DP, Yadegarynia
D, Raad II. Nonfermentative Gramnegative bacilli in cancer patients:
increasing frequency of infection and
antimicrobial susceptibility of clinical
isolates to fluoroquinolones. Diagn.
Microbiol. Infect. Dis. 51(3), 215–218
(2005).
59
Safdar A, Rolston KV. Stenotrophomonas
maltophilia: changing spectrum of a serious
bacterial pathogen in patients with cancer.
Clin. Infect. Dis. 45(12), 1602–1609
(2007).
60
Tan CK, Liaw SJ, Yu CJ, Teng LJ, Hsueh
PR. Extensively drug-resistant
Stenotrophomonas maltophilia in a tertiary
483
Review
61
•
62
63
•
64
65
66
67
68
69
70
Abbott, Slavin, Turnidge, Thursky & Worth
care hospital in Taiwan: microbiologic
characteristics, clinical features, and
outcomes. Diagn. Microbiol. Infect. Dis.
60(2), 205–210 (2008).
71
Lease ED, Zaas DW. Complex bacterial
infections pre- and posttransplant. Semin.
Respir. Crit. Care Med. 31(2), 234–242
(2010).
Falagas ME, Kastoris AC, Vouloumanou
EK, Dimopoulos G. Community-acquired
Stenotrophomonas maltophilia infections: a
systematic review. Eur. J. Clin. Microbiol.
Infect. Dis. 28(7), 719–730 (2009).
72
Marzuillo C, De Giusti M, Tufi D et al.
Molecular characterization of
Stenotrophomonas maltophilia isolates from
cystic fibrosis patients and the hospital
environment. Infect. Control Hosp.
Epidemiol. 30(8), 753–758 (2009).
Assessment of therapeutic options in
S. maltophilia infections.
Chaplow R, Palmer B, Heyderman R,
Moppett J, Marks DI. Stenotrophomonas
maltophilia bacteraemia in 40 haematology
patients: risk factors, therapy and outcome.
Bone Marrow Transplant. 45(6), 1109–1110
(2010).
73
74
Chen CY, Tsay W, Tang JL et al.
Epidemiology of bloodstream infections in
patients with haematological malignancies
with and without neutropenia. Epidemiol.
Infect. 138(7), 1044–1051 (2010).
Large epidemiological study
demonstrating the disease burden of
S. maltophilia in hematology patients.
Apisarnthanarak A, Mayfield JL, Garison T
et al. Risk factors for Stenotrophomonas
maltophilia bacteremia in oncology patients:
a case–control study. Infect. Control Hosp.
Epidemiol. 24(4), 269–274 (2003).
Steinkamp G, Wiedemann B, Rietschel E
et al. Prospective evaluation of emerging
bacteria in cystic fibrosis. J. Cyst. Fibros.
4(1), 41–48 (2005).
Valenza G, Tappe D, Turnwald D et al.
Prevalence and antimicrobial susceptibility
of microorganisms isolated from sputa of
patients with cystic fibrosis. J. Cyst. Fibros.
7(2), 123–127 (2008).
Spicuzza L, Sciuto C, Vitaliti G, Di Dio G,
Leonardi S, La Rosa M. Emerging pathogens
in cystic fibrosis: ten years of follow-up in a
cohort of patients. Eur. J. Clin. Microbiol.
Infect. Dis. 28(2), 191–195 (2009).
Razvi S, Quittell L, Sewall A, Quinton H,
Marshall B, Saiman L. Respiratory
microbiology of patients with cystic fibrosis
in the United States, 1995 to 2005. Chest
136(6), 1554–1560 (2009).
Goss CH, Mayer-Hamblett N, Aitken ML,
Rubenfeld GD, Ramsey BW. Association
between Stenotrophomonas maltophilia and
lung function in cystic fibrosis. Thorax
59(11), 955–959 (2004).
Goss CH, Otto K, Aitken ML, Rubenfeld
GD. Detecting Stenotrophomonas
maltophilia does not reduce survival of
patients with cystic fibrosis. Am. J. Respir.
Crit. Care Med. 166(3), 356–361 (2002).
484
75
76
77
78
82
Basu S, Das P, Roy S, De S, Singh A.
Survey of gut colonisation with
Stenotrophomonas maltophilia among
neonates. J. Hosp. Infect. 72(2), 183–185
(2009).
83
Gulcan H, Kuzucu C, Durmaz R.
Nosocomial Stenotrophomonas maltophilia
cross-infection: three cases in newborns.
Am. J. Infect. Control 32(6), 365–368
(2004).
84
Bonatti H, Pruett TL, Brandacher G et al.
Pneumonia in solid organ recipients:
spectrum of pathogens in 217 episodes.
Transplant. Proc. 41(1), 371–374 (2009).
85
Shi SH, Kong HS, Xu J et al. Multidrug
resistant Gram-negative bacilli as
predominant bacteremic pathogens in liver
transplant recipients. Transpl. Infect. Dis,
11(5), 405–412 (2009).
86
Tsai WP, Chen CL, Ko WC, Pan SC.
Stenotrophomonas maltophilia bacteremia in
burn patients. Burns 32(2), 155–158
(2006).
87
Barchitta M, Cipresso R, Giaquinta L et al.
Acquisition and spread of Acinetobacter
baumannii and Stenotrophomonas
maltophilia in intensive care patients. Int. J.
Hyg. Environ. Health 212(3), 330–337
(2009).
Araoka H, Baba M, Yoneyama A. Risk
factors for mortality among patients with
Stenotrophomonas maltophilia bacteremia in
Tokyo, Japan, 1996–2009. Eur. J. Clin.
Microbiol. Infect. Dis. 29(5), 605–608
(2010).
88
Gnanasekaran I, Bajaj R. Stenotrophomonas
maltophilia bacteremia in end-stage renal
disease patients receiving maintenance
hemodialysis. Dial. Transplant. 38(1),
30–32 (2009).
Lai CH, Wong WW, Chin C et al. Central
venous catheter-related Stenotrophomonas
maltophilia bacteraemia and associated
relapsing bacteraemia in haematology and
oncology patients. Clin. Microbiol. Infect.
12(10), 986–991 (2006).
89
Paez JG, Levin AS, Basso M et al. Trends
in Stenotrophomonas maltophilia
bloodstream infection in relation to usage
density of cephalosporins and
carbapenems during 7 years. Infect.
Control Hosp. Epidemiol. 29(10), 989–990
(2008).
90
Kara IH, Yilmaz ME, Sit D, Kadiroglu
AK, Kokoglu OF. Bacteremia caused by
Stenotrophomonas maltophilia in a dialysis
patient with a long-term central venous
catheter. Infect. Control Hosp. Epidemiol.
27(5), 535–536 (2006).
Lockhart SR, Abramson MA, Beekmann
SE 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. 45(10), 3352–3359 (2007).
Weber DJ, Rutala WA, Sickbert-Bennett
EE, Samsa GP, Brown V, Niederman MS.
Microbiology of ventilator-associated
pneumonia compared with that of
hospital-acquired pneumonia. Infect. Control
Hosp. Epidemiol. 28(7), 825–831 (2007).
Nseir S, Di Pompeo C, Brisson H et al.
Intensive care unit-acquired
Stenotrophomonas maltophilia: incidence,
risk factors, and outcome. Crit. Care 10(5),
R143 (2006).
Tzanetou K, Triantaphillis G, Tsoutsos D
et al. Stenotrophomonas maltophilia
peritonitis in CAPD patients: susceptibility
to antibiotics and treatment outcome: a
report of five cases. Perit. Dial. Int. 24(4),
401–404 (2004).
79
Wakino S, Imai E, Yoshioka K et al.
Clinical importance of Stenotrophomonas
maltophilia nosocomial pneumonia due to
its high mortality in hemodialysis patients.
Ther. Apher. Dial. 13(3), 193–198 (2009).
91
80
Xu XF, Ma XL, Chen Z, Shi LP, Du LZ.
Clinical characteristics of nosocomial
infections in neonatal intensive care unit in
eastern China. J. Perinat. Med. 38(4),
431–437 (2010).
Kagen J, Zaoutis TE, McGowan KL, Luan
X, Shah SS. Bloodstream infection caused
by Stenotrophomonas maltophilia in
children. Pediatr. Infect. Dis. J. 26(6),
508–512 (2007).
92
81
Abbassi MS, Touati A, Achour W et al.
Stenotrophomonas maltophilia responsible
for respiratory infections in neonatal
intensive care unit: antibiotic susceptibility
and molecular typing. Pathol. Biol. (Paris)
57(5), 363–367 (2009).
Wood GC, Underwood EL, Croce MA,
Swanson JM, Fabian TC. Treatment of
recurrent Stenotrophomonas maltophilia
ventilator-associated pneumonia with
doxycycline and aerosolized colistin. Ann.
Pharmacother. 44(10), 1665–1668 (2010).
Expert Rev. Anti Infect. Ther. 9(4), (2011)
Stenotrophomonas maltophilia: emerging disease patterns & challenges for treatment
93
Tseng CC, Fang WF, Huang KT et al. Risk
factors for mortality in patients with
nosocomial Stenotrophomonas maltophilia
pneumonia. Infect. Control Hosp. Epidemiol.
30(12), 1193–1202 (2009).
94
Ortin X, Jaen-Martinez J, Rodriguez-Luaces
M, Alvaro T, Font L. Fatal pulmonary
hemorrhage in a patient with myelodysplastic
syndrome and fulminant pneumonia caused
by Stenotrophomonas maltophilia. Infection
35(3), 201–202 (2007).
95
Pathmanathan A, Waterer GW.
Significance of positive Stenotrophomonas
maltophilia culture in acute respiratory
tract infection. Eur. Respir. J. 25(5),
911–914 (2005).
96
Senol E, DesJardin J, Stark PC, Barefoot L,
Snydman DR. Attributable mortality of
Stenotrophomonas maltophilia bacteremia.
Clin. Infect. Dis. 34(12), 1653–1656
(2002).
97
Falagas ME, Kastoris AC, Vouloumanou
EK, Rafailidis PI, Kapaskelis AM,
Dimopoulos G. Attributable mortality of
Stenotrophomonas maltophilia infections: a
systematic review of the literature. Future
Microbiol. 4, 1103–1109 (2009).
•
Focused report on the mortality of
S. maltophilia infections.
98
Paez JI, Tengan FM, Barone AA, Levin AS,
Costa SF. Factors associated with mortality
in patients with bloodstream infection and
pneumonia due to Stenotrophomonas
maltophilia. Eur. J. Clin. Microbiol. Infect.
Dis. 27(10), 901–906 (2008).
99
100
101
102
103
Boktour M, Hanna H, Ansari S et al.
Central venous catheter and
Stenotrophomonas maltophilia bacteremia in
cancer patients. Cancer 106(9), 1967–1973
(2006).
Hanna H, Afif C, Alakech B et al. Central
venous catheter-related bacteremia due to
Gram-negative bacilli: significance of
catheter removal in preventing relapse.
Infect. Control Hosp. Epidemiol. 25(8),
646–649 (2004).
Wu PS, Lu CY, Chang LY et al.
Stenotrophomonas maltophilia bacteremia in
pediatric patients – a 10-year analysis. J.
Microbiol. Immunol. Infect. 39(2), 144–149
(2006).
Lai CH, Chi CY, Chen HP et al. Clinical
characteristics and prognostic factors of
patients with Stenotrophomonas maltophilia
bacteremia. J. Microbiol. Immunol. Infect.
37(6), 350–358 (2004).
Yeshurun M, Gafter-Gvili A, Thaler M,
Keller N, Nagler A, Shimoni A. Clinical
characteristics of Stenotrophomonas
www.expert-reviews.com
Review
maltophilia infection in hematopoietic stem
cell transplantation recipients: a single
center experience. Infection 38(3), 211–215
(2010).
113
Turnidge J, Paterson DL. Setting and
revising antibacterial susceptibility
breakpoints. Clin. Microbiol. Rev. 20(3),
391–408 (2007).
104
Aisenberg G, Rolston KV, Dickey BF,
Kontoyiannis DP, Raad II, Safdar A.
Stenotrophomonas maltophilia pneumonia in
cancer patients without traditional risk
factors for infection, 1997–2004. Eur. J. Clin.
Microbiol. Infect. Dis. 26(1), 13–20 (2007).
114
105
King A. Recommendations for
susceptibility tests on fastidious organisms
and those requiring special handling. J.
Antimicrob. Chemother. 48(Suppl. 1),
77–80 (2001).
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. 54(6), 2735–2737 (2010).
115
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.
20(1), 38–42 (2008).
116
Jones RN, Sader HS, Beach ML.
Contemporary in vitro spectrum of activity
summary for antimicrobial agents tested
against 18569 strains non-fermentative
Gram-negative bacilli isolated in the
SENTRY Antimicrobial Surveillance
Program (1997–2001). Int. J. Antimicrob.
Agents 22(6), 551–556 (2003).
•
Large population-based study of in vitro
susceptibilty of S. maltophilia isolates.
117
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. 51(1), 39–43 (2005).
•
In vitro analysis of antibiotic combination
regimens for S. maltophilia infections.
118
Hejnar P, Kolar M, Chmela Z. Doubledisk synergy test positivity in
Stenotrophomonas maltophilia clinical
strains. Folia Microbiol. (Praha) 49(1),
71–74 (2004).
119
Barbier-Frebour N, Boutiba-Boubake I,
Nouvello M, Lemelan J. Molecular
investigation of Stenotrophomonas
maltophilia isolates exhibiting rapid
emergence of ticarcillin–clavulanate
resistance. J. Hosp. Infect. 45(1), 35–41
(2000).
120
Garcia Sanchez JE, Vazquez Lopez ML,
Blazquez de Castro AM et al. Aztreonam/
clavulanic acid in the treatment of serious
infections caused by Stenotrophomonas
maltophilia in neutropenic patients: case
reports. J. Chemother. 9(3), 238–240
(1997).
121
Kataoka D, Tanaka Y. The combination of
aztreonam and cefozopran against
Stenotrophomonas maltophilia. J. Infect.
Chemother. 10(1), 62–64 (2004).
106
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. 53(4), 604–608 (2004).
•
Reviews laboratory antimicrobial
susceptibility techniques when evaluating
S. maltophilia isolates.
107
Galani I, Kontopidou F, Souli M et al.
Colistin susceptibility testing by Etest and
disk diffusion methods. Int. J. Antimicrob.
Agents 31(5), 434–439 (2008).
108
109
Gomez-Garces JL, Aracil B, Gil Y.
Comparison between agar dilution and
three other methods for determining the
susceptibility of 228 clinical isolates of
non-fermenting Gram-negative rods.
Enferm. Infecc. Microbiol. Clin. 27(6),
331–337 (2009).
Moskowitz SM, Garber E, Chen Y et al.
Colistin susceptibility testing: evaluation of
reliability for cystic fibrosis isolates of
Pseudomonas aeruginosa and
Stenotrophomonas maltophilia. J. Antimicrob.
Chemother. 65(7), 1416–1423 (2010).
110
Somily AM. Comparison of E-test and disc
diffusion methods for the in vitro
evaluation of the antimicrobial activity of
colistin in multi-drug resistant Gramnegative bacilli. Saudi Med. J. 31(5),
507–511 (2010).
111
Gulmez D, Cakar A, Sener B, Karakaya J,
Hascelik G. Comparison of different
antimicrobial susceptibility testing
methods for Stenotrophomonas maltophilia
and results of synergy testing. J. Infect.
Chemother. 16(5), 322–328 (2010).
112
Tatman-Otkun M, Gurcan S, Ozer B,
Aydoslu B, Bukavaz S. The antimicrobial
susceptibility of Stenotrophomonas
maltophilia isolates using three different
methods and their genetic relatedness.
BMC Microbiol. 5, 24 (2005).
485
Review
Abbott, Slavin, Turnidge, Thursky & Worth
122
Travassos LH, Pinheiro MN, Coelho FS,
Sampaio JL, Merquior VL, Marques EA.
Phenotypic properties, drug susceptibility
and genetic relatedness of Stenotrophomonas
maltophilia clinical strains from seven
hospitals in Rio de Janeiro, Brazil. J. Appl.
Microbiol. 96(5), 1143–1150 (2004).
132
Munoz JL, Garcia MI, Munoz S, Leal S,
Fajardo M, Garcia-Rodriguez JA. Activity of
trimethoprim/sulfamethoxazole plus
polymyxin B against multiresistant
Stenotrophomonas maltophilia. Eur. J. Clin.
Microbiol. Infect. Dis. 15(11), 879–882
(1996).
123
Korakianitis I, Mirtsou V, Gougoudi E,
Raftogiannis M, Giamarellos-Bourboulis
EJ. Post-antibiotic effect (PAE) of
moxifloxacin in multidrug-resistant
Stenotrophomonas maltophilia. Int. J.
Antimicrob. Agents 36(4), 387–389 (2010).
133
124
Pompilio A, Catavitello C, Picciani C et al.
Subinhibitory concentrations of
moxifloxacin decrease adhesion and biofilm
formation of Stenotrophomonas maltophilia
from cystic fibrosis. J. Med. Microbiol.
59(Pt 1), 76–81 (2010).
Giamarellos-Bourboulis EJ, Karnesis L,
Giamarellou H. Synergy of colistin with
rifampin and trimethoprim/
sulfamethoxazole on multidrug-resistant
Stenotrophomonas maltophilia. Diagn.
Microbiol. Infect. Dis. 44(3), 259–263
(2002).
125
126
127
128
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. 47(2),
816–819 (2003).
Weiss K, Restieri C, De Carolis E,
Laverdiere M, Guay H. Comparative
activity of new quinolones against 326
clinical isolates of Stenotrophomonas
maltophilia. J. Antimicrob. Chemother.
45(3), 363–365 (2000).
Garrison MW, Anderson DE, Campbell
DM et al. Stenotrophomonas maltophilia:
emergence of multidrug-resistant strains
during therapy and in an in vitro
pharmacodynamic chamber model.
Antimicrob. Agents Chemother. 40(12),
2859–2864 (1996).
Gales AC, Jones RN, Sader HS. Global
assessment of the antimicrobial activity of
polymyxin B against 54 731 clinical isolates
of Gram-negative bacilli: report from the
SENTRY antimicrobial surveillance
programme (2001–2004). Clin. Microbiol.
Infect. 12(4), 315–321 (2006).
129
Mendoza DL, Darin M, Waterer GW,
Wunderink RG. Update on
Stenotrophomonas maltophilia infection in
the ICU. Clin. Pulm. Med. 14(1), 17–22
(2007).
130
Looney WJ, Narita M, Muhlemann K.
Stenotrophomonas maltophilia: an emerging
opportunist human pathogen. Lancet
Infect. Dis. 9(5), 312–323 (2009).
131
San Gabriel P, Zhou J, Tabibi S, Chen Y,
Trauzzi M, Saiman L. Antimicrobial
susceptibility and synergy studies of
Stenotrophomonas maltophilia isolates from
patients with cystic fibrosis. Antimicrob.
Agents Chemother. 48(1), 168–171 (2004).
486
134
Rostoff P, Paradowski A, Gackowski A
et al. Stenotrophomonas maltophilia
pacemaker endocarditis in a patient with
d-transposition of the great arteries after
atrial switch procedure. Int. J. Cardiol.
145(3), e92–e95 (2009).
135
Rojas P, Garcia E, Calderon GM, Ferreira
F, Rosso M. Successful treatment of
Stenotrophomonas maltophilia meningitis in
a preterm baby boy: a case report. J. Med.
Case Reports 3, 7389 (2009).
136
Kim JH, Kim SW, Kang HR et al. Two
episodes of Stenotrophomonas maltophilia
endocarditis of prosthetic mitral valve:
report of a case and review of the literature.
J. Korean Med. Sci. 17(2), 263–265 (2002).
137
138
Downhour NP, Petersen EA, Krueger TS,
Tangella KV, Nix DE. Severe cellulitis/
myositis caused by Stenotrophomonas
maltophilia. Ann. Pharmacother. 36(1),
63–66 (2002).
Pereira O, Velho GC, Lopes V, Mota F,
Santos C, Massa A. Acral necrosis by
Stenotrophomonas maltophilia. J. Eur. Acad.
Dermatol. Venereol. 15(4), 334–336 (2001).
143
Woodhouse R, Peckham DG, Conway SP,
Denton M. Water filters can prevent
Stenotrophomonas maltophilia
contamination of nebuliser equipment used
by people with cystic fibrosis. J. Hosp.
Infect. 68(4), 371–372 (2008).
144
Denton M, Rajgopal A, Mooney L et al.
Stenotrophomonas maltophilia
contamination of nebulizers used to deliver
aerosolized therapy to inpatients with cystic
fibrosis. J. Hosp. Infect. 55(3), 180–183
(2003).
145
Klausner JD, Zukerman C, Limaye AP,
Corey L. Outbreak of Stenotrophomonas
maltophilia bacteremia among patients
undergoing bone marrow transplantation:
association with faulty replacement of
handwashing soap. Infect. Control Hosp.
Epidemiol. 20(11), 756–758 (1999).
146
Sacchetti R, De Luca G, Zanetti F. Control
of Pseudomonas aeruginosa and
Stenotrophomonas maltophilia
contamination of microfiltered water
dispensers with peracetic acid and
hydrogen peroxide. Int. J. Food Microbiol.
132(2–3), 162–166 (2009).
147
McGowan JE Jr. Resistance in
nonfermenting Gram-negative bacteria:
multidrug resistance to the maximum. Am.
J. Med. 119(6 Suppl. 1), S29–S36;
discussion S62–S70 (2006).
148
Hanes SD, Demirkan K, Tolley E et al.
Risk factors for late-onset nosocomial
pneumonia caused by Stenotrophomonas
maltophilia in critically ill trauma patients.
Clin. Infect. Dis. 35(3), 228–235 (2002).
149
Meyer E, Schwab F, Gastmeier P, Rueden
H, Daschner FD, Jonas D.
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. 64(3), 238–243
(2006).
139
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. 62(5), 889–894 (2008).
140
Sakhnini E, Weissmann A, Oren I.
Fulminant Stenotrophomonas maltophilia
soft tissue infection in
immunocompromised patients: an
outbreak transmitted via tap water. Am. J.
Med. Sci. 323(5), 269–272 (2002).
150
Kerr KG, Denton M, Todd N, Corps CM,
Kumari P, Hawkey PM. A new selective
differential medium for isolation of
Stenotrophomonas maltophilia. Eur. J. Clin.
Microbiol. Infect. Dis. 15(7), 607–610
(1996).
141
Zuckerman JB, Zuaro DE, Prato BS et al.
Bacterial contamination of cystic fibrosis
clinics. J. Cyst. Fibros. 8(3), 186–192 (2009).
151
142
Wainwright CE, France MW, O’Rourke P
et al. Cough-generated aerosols of
Pseudomonas aeruginosa and other
Gram-negative bacteria from patients with
cystic fibrosis. Thorax 64(11), 926–931
(2009).
Foster NF, Chang BJ, Riley TV. Evaluation
of a modified selective differential medium
for the isolation of Stenotrophomonas
maltophilia. J. Microbiol. Methods. 75(1),
153–155 (2008).
152
Pompilio A, Piccolomini R, Picciani C,
D’Antonio D, Savini V, Di Bonaventura G.
Factors associated with adherence to and
biofilm formation on polystyrene by
Expert Rev. Anti Infect. Ther. 9(4), (2011)
Stenotrophomonas maltophilia: emerging disease patterns & challenges for treatment
Stenotrophomonas maltophilia: the role of
cell surface hydrophobicity and motility.
FEMS Microbiol. Lett. 287(1), 41–47
(2008).
153
154
155
156
157
158
159
160
161
162
163
Avison MB, von Heldreich CJ, Higgins CS,
Bennett PM, Walsh TR. A TEM-2blactamase encoded on an active Tn1-like
transposon in the genome of a clinical isolate
of Stenotrophomonas maltophilia. J. Antimicrob.
Chemother. 46(6), 879–884 (2000).
Lavigne JP, Gaillard JB, Bourg G, Tichit
C, Lecaillon E, Sotto A. Extendedspectrum b-lactamases-producing
Stenotrophomonas maltophilia strains:
CTX-M enzymes detection and virulence
study. Pathol. Biol. (Paris) 56(7–8),
447–453 (2008).
al Naiemi N, Duim B, Bart A. A CTX-M
extended-spectrum b-lactamase in
Pseudomonas aeruginosa and
Stenotrophomonas maltophilia. J. Med.
Microbiol. 55(Pt 11), 1607–1608 (2006).
Al-Hamad A, Upton M, Burnie J.
Molecular cloning and characterization of
SmrA, a novel ABC multidrug efflux pump
from Stenotrophomonas maltophilia. J.
Antimicrob. Chemother. 64(4), 731–734
(2009).
Matsuoka M, Sasaki T. Inactivation of
macrolides by producers and pathogens.
Curr. Drug Targets Infect. Disord. 4(3),
217–240 (2004).
McKay GA, Woods DE, MacDonald KL,
Poole K. Role of phosphoglucomutase of
Stenotrophomonas maltophilia in
lipopolysaccharide biosynthesis, virulence,
and antibiotic resistance. Infect. Immun.
71(6), 3068–3075 (2003).
Sanchez MB, Martinez JL. SmQnr
contributes to intrinsic resistance to
quinolones in Stenotrophomonas
maltophilia. Antimicrob. Agents Chemother.
54(1), 580–581 (2010).
Katayama T, Tsuruya Y, Ishikawa S.
Stenotrophomonas maltophilia endocarditis
of prosthetic mitral valve. Intern. Med.
49(16), 1775–1777 (2010).
Ucak A, Goksel OS, Inan K et al.
Prosthetic aortic valve endocarditis due to
Stenotrophomonas maltophilia complicated
by subannular abscess. Acta Chir. Belg.
108(2), 258–260 (2008).
Muller-Premru M, Gabrijelcic T, Gersak B
et al. Cluster of Stenotrophomonas
maltophilia endocarditis after prosthetic
valve replacement. Wien. Klin. Wochenschr.
120(17–18), 566–570 (2008).
Bayle S, Rovery C, Sbragia P, Raoult D,
Brouqui P. Stenotrophomonas maltophilia
www.expert-reviews.com
Stenotrophomonas maltophilia soft tissue
infection. Scand. J. Infect. Dis. 37(10),
734–737 (2005).
prosthetic valve endocarditis: a case report.
J. Med. Case Reports 2, 174 (2008).
164
Lopez Rodriguez R, Lado Lado FL,
Sanchez A et al. Endocarditis caused by
Stenotrophomonas maltophilia: report of a
case and review of literature. An. Med.
Interna. 20(6), 312–316 (2003).
Review
176
Siala M, Gdoura R, Fourati H et al.
Broad-range PCR, cloning and sequencing
of the full 16S rRNA gene for detection of
bacterial DNA in synovial fluid samples of
Tunisian patients with reactive and
undifferentiated arthritis. Arthritis Res.
Ther. 11(4), R102 (2009).
165
Crum NF, Utz GC, Wallace MR.
Stenotrophomonas maltophilia endocarditis.
Scand. J. Infect. Dis. 34(12), 925–927
(2002).
177
166
Mehta NJ, Khan IA, Mehta RN, Gulati A.
Stenotrophomonas maltophilia endocarditis
of prosthetic aortic valve: report of a case
and review of literature. Heart Lung 29(5),
351–355 (2000).
Aydemir C, Aktas E, Eldes N, Kutsal E,
Demirel F, Ege A. Community-acquired
infection due to Stenotrophomonas
maltophilia: a rare cause of septic arthritis.
Turk. J. Pediatr. 50(1), 89–90 (2008).
178
167
Grindler D, Thomas C, Hall GS, Batra PS.
The role of Stenotrophomonas maltophilia in
refractory chronic rhinosinusitis. Am. J.
Rhinol. Allergy 24(3), 200–204 (2010).
Belzunegui J, De Dios JR, Intxausti JJ,
Iribarren JA. Septic arthritis caused by
Stenotrophomonas maltophilia in a patient
with acquired immunodeficiency syndrome.
Clin. Exp. Rheumatol. 18(2), 265 (2000).
168
Gunnarsson G, Steinsson K. Sinusitis due
to Stenotrophomonas maltophilia. Scand. J.
Infect. Dis. 34(2), 136–137 (2002).
179
169
Miyairi I, Franklin JA, Andreansky M,
Knapp KM, Hayden RT. Acute
necrotizing ulcerative gingivitis and
bacteremia caused by Stenotrophomonas
maltophilia in an immunocompromised
host. Pediatr. Infect. Dis. J. 24(2), 181–183
(2005).
Papadakis KA, Vartivarian SE, Vassilaki
ME, Anaissie EJ. Septic prepatellar bursitis
caused by Stenotrophomonas
(Xanthomonas) maltophilia. Clin. Infect.
Dis. 22(2), 388–389 (1996).
180
Landrum ML, Conger NG, Forgione MA.
Trimethoprim–sulfamethoxazole in the
treatment of Stenotrophomonas maltophilia
osteomyelitis. Clin. Infect. Dis. 40(10),
1551–1552 (2005).
181
German V, Tsimpoukas F, Goritsas C,
Ferti A. Spondylodiscitis due to
Stenotrophomonas maltophilia. Eur. J.
Intern. Med. 18(6), 501–503 (2007).
182
Yemisen M, Mete B, Tunali Y, Yentur E,
Ozturk R. A meningitis case due to
Stenotrophomonas maltophilia and review of
the literature. Int. J. Infect. Dis. 12(6),
e125–e127 (2008).
183
Lo WT, Wang CC, Lee CM, Chu ML.
Successful treatment of multi-resistant
Stenotrophomonas maltophilia meningitis
with ciprofloxacin in a pre-term infant.
Eur. J. Pediatr. 161(12), 680–682 (2002).
184
Takeuchi H, Fujita T, Ebisu T, Mineura K.
Primary intracerebral hemorrhage due to
probable cerebral amyloid angiopathy
complicated by brain abscess: case report.
No Shinkei Geka 35(5), 489–493 (2007).
185
Hellmig S, Ott S, Musfeldt M et al.
Life-threatening chronic enteritis due to
colonization of the small bowel with
Stenotrophomonas maltophilia.
Gastroenterology 129(2), 706–712 (2005).
186
Papadakis KA, Vartivarian SE, Vassilaki
ME, Anaissie EJ. Stenotrophomonas
maltophilia: an unusual cause of biliary
sepsis. Clin. Infect. Dis. 21(4), 1032–1034
(1995).
170
Sengor A, Willke A, Aydin O, Gundes S,
Almac A. Isolated necrotizing epiglottitis:
report of a case in a neutropenic patient
and review of the literature. Ann. Otol.
Rhinol. Laryngol 113(3 Pt 1), 225–228
(2004).
171
Borner D, Marsch WC, Fischer M.
Necrotizing otitis externa caused by
Stenotrophomonas maltophilia. Hautarzt
54(11), 1080–1082 (2003).
172
Bin Abdulhak AA, Zimmerman V, Al
Beirouti BT, Baddour LM, Tleyjeh IM.
Stenotrophomonas maltophilia infections of
intact skin: a systematic review of the
literature. Diagn. Microbiol. Infect. Dis.
63(3), 330–333 (2009).
173
174
175
Thomas J, Prabhu VN, Varaprasad IR,
Agrawal S, Narsimulu G. Stenotrophomonas
maltophilia: a very rare cause of tropical
pyomyositis. Int. J. Rheum. Dis. 13(1),
89–90 (2010).
Belvisi V, Fabietti P, Del Borgo C et al.
Successful treatment of Stenotrophomonas
maltophilia soft tissue infection with
tigecycline: a case report. J. Chemother.
21(3), 367–368 (2009).
Bello G, Alberto Pennisi M, Fragasso T,
Mignani V, Antonelli M. Acute upper
airway obstruction caused by
487
Review
Abbott, Slavin, Turnidge, Thursky & Worth
187
Monkemuller KE, Morgan DE, Baron TH.
Stenotrophomonas (Xanthomonas)
maltophilia infection in necrotizing
pancreatitis. Int. J. Pancreatol. 25(1),
59–63 (1999).
196
Kim JH, Shin HH, Song JS, Kim HM.
Infectious keratitis caused by
Stenotrophomonas maltophilia and yeast
simultaneously. Cornea 25(10), 1234–1236
(2006).
188
Calza L, Manfredi R, Marinacci G,
Fortunato L, Chiodo F. Liver abscess
caused by Stenotrophomonas (Xanthomonas)
maltophilia in a patient with AIDS. AIDS
15(18), 2465–2467 (2001).
197
204
189
Petri A, Tiszlavicz L, Nagy E et al. Liver
abscess caused by Stenotrophomonas
maltophilia: report of a case. Surg. Today
33(3), 224–228 (2003).
Horster S, Bader L, Seybold U, Eschler I,
Riedel KG, Bogner JR. Stenotrophomonas
maltophilia induced post-cataract-surgery
endophthalmitis: outbreak investigation
and clinical courses of 26 patients. Infection
37(2), 117–122 (2009).
198
Das T, Deshmukh HS, Mathai A, Reddy
AK. Stenotrophomonas maltophilia
endogenous endophthalmitis: clinical
presentation, sensitivity spectrum and
management. J. Med. Microbiol. 58(Pt 6),
837–838 (2009).
Websites
190
Vaidyanathan S, Bowley JA, Soni BM et al.
Superinfection of perinephric abscess by
Stenotrophomonas maltophilia in a
tetraplegic patient. Spinal Cord 43(6),
394–395 (2005).
191
Lee YK, Kim JK, Oh SE, Lee J, Noh JW.
Successful antibiotic lock therapy in
patients with refractory peritonitis. Clin.
Nephrol. 72(6), 488–491 (2009).
192
Taneja N, Meharwal SK, Sharma SK,
Sharma M. Significance and
characterisation of pseudomonads from
urinary tract specimens. J. Commun. Dis.
36(1), 27–34 (2004).
193
Vartivarian SE, Papadakis KA, Anaissie EJ.
Stenotrophomonas (Xanthomonas)
maltophilia urinary tract infection. A
disease that is usually severe and
complicated. Arch. Intern. Med. 156(4),
433–435 (1996).
194
Khassawneh M, Hayajneh W. Treatment of
Stenotrophomonas neonatal urinary tract
infection with instillation of ciprofloxacin.
Pediatr. Nephrol. 25(7), 1377 (2010).
195
Penland RL, Wilhelmus KR.
Stenotrophomonas maltophilia ocular
infections. Arch. Ophthalmol. 114(4),
433–436 (1996).
488
199
200
201
Lai TY, Kwok AK, Fung KS, Chan WM,
Fan DS, Lam DS. Stenotrophomonas
maltophilia endophthalmitis after
penetrating injury by a wooden splinter.
Eye (Lond.) 15(Pt 3), 353–354 (2001).
Liu DT, Lee VY, Chi-Lai L, Lam DS.
Stenotrophomonas maltophilia and
Mycobacterium chelonae coinfection of the
extraocular scleral buckle explant. Ocul.
Immunol. Inflamm. 15(6), 441–442
(2007).
Betriu C, Rodriguez-Avial I, Sanchez BA,
Gomez M, Picazo JJ. Comparative in vitro
activities of tigecycline (GAR-936) and
other antimicrobial agents against
Stenotrophomonas maltophilia. J.
Antimicrob. Chemother. 50(5), 758–759
(2002).
202
Valdezate S, Vindel A, Loza E, Baquero F,
Canton R. Antimicrobial susceptibilities of
unique Stenotrophomonas maltophilia
clinical strains. Antimicrob. Agents
Chemother. 45(5), 1581–1584 (2001).
203
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. 52(3),
203–208 (2005).
Hu ZQ, Yang YM, Ke XM et al.
Antimicrobial resistance of clinical isolates
of Stenotrophomonas maltophilia. Nan Fang
Yi Ke Da Xue Xue Bao 29(5), 852–855
(2009).
301
Pseudomonas spp. and Stenotrophomonas
maltophilia bacteraemia in England, Wales,
and Northern Ireland, 2005 to 2009
www.hpa.org.uk/web/HPAwebFile/
HPAweb_C/1281952800376
(Accessed 19 December 2010)
302
European Committee on Antimicrobial
Susceptibility Testing
www.eucast.org/fileadmin/src/media/
PDFs/EUCAST_files/Disk_test_
documents/EUCAST_breakpoints_
v1.1.pdf
(Accessed 19 December 2010)
303
Methods for Antimicrobial Susceptibility
Testing. Version 9.1. March 2010. British
Society For Antimicrobial Therapy
www.bsac.org.uk/Resources/BSAC/
Version_9.1_March_2010_final.pdf
(Accessed 19 December 2010)
304
Expert Rules in Antimicrobial
Susceptibility Testing
www.escmid.org/fileadmin/src/media/
PDFs/4ESCMID_Library/3Publications/
EUCAST_Documents/Other_
Documents/EUCAST_Expert_rules_
final_April_20080407.pdf
(Accessed 19 December 2010)
Expert Rev. Anti Infect. Ther. 9(4), (2011)
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.