Indian Journal of Medical Microbiology 40 (2022) 46–50

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Indian Journal of Medical Microbiology

journal homepage: www.journals.elsevier.com/indian-journal-of-medical-microbiology

Original Research Article

Stenotrophomonas isolates in a tertiary care centre in South India

Amita Jacob a, *, Ramya Iyadurai a, J.V. Punitha a, Binila Chacko b, Sudha Jasmine a,
Muruga Bharathy a, Divya Mathew a, Balaji Veeraraghavan c
a
Department of Medicine, Christian Medical College, Vellore, Tamil Nadu, India
b
Department of Critical Care, Christian Medical College, Vellore, Critical Care Office, CMC Hospital, Vellore, 632004, Tamil Nadu, India
c
Department of Microbiology, Christian Medical College, Vellore, Microbiology Office, CMC Hospital, Vellore, 632004, Tamil Nadu, India

A R T I C L E I N F O A B S T R A C T

Keywords: Purpose: Stenotrophomonas maltophilia is an emerging multi-drug resistant pathogen increasingly isolated in India.
Stenotrophomonas maltophilia This study aimed to identify patients from whom Stenotrophomonas maltophilia had been isolated and assess
Nosocomial infections predictors of mortality in this population.
Ventilator-associated pneumonia
Methods: This was a retrospective cohort study of hospitalized patients with a positive culture for S. maltophilia
over a 3-year period. Clinical details and laboratory results were assessed from hospital records. Bivariate and
multivariate analysis was used to identify risk factors for mortality.
Results: One hundred and nineteen patients (mean age 48.6 years) were included in the study. Of these, 111
patients were hospitalized for at least 48 hours prior to culture and 98 were admitted in the intensive care unit.
Bivariate analysis revealed multiple associations with mortality, including a background of renal, cardiac, auto-
immune disease, recent carbapenam use and COVID-19 infection and increasing ventilatory requirement, lower
PaO2/FiO2 (P/F) ratio, vasopressor use, thrombocytopenia, and hypoalbuminemia at the time of positive isolate.
Multivariate analysis showed that autoimmune disease [OR 27.38; 95% CI (1.39–540)], a P/F ratio of less than
300 [OR 7.58; 95% CI (1.52–37.9)], vasopressor requirement [OR 39.50; 95% CI (5.49–284)] and thrombocy-
topenia [OR 11.5; 95% CI (2.04–65.0)] were statistically significantly associated with increased mortality, while
recent surgery and receipt of antibiotics [OR 0.16; 95% CI (0.03–0.8)] targeted against S. maltophilia were
associated with decreased mortality.
Conclusion: Stenotrophomonas maltophilia is primarily isolated in patients in the intensive care unit. In our study the
need for vasopressors, autoimmune disease, lower P/F ratios and thrombocytopenia were associated with higher
mortality. The association of targeted antibiotics with reduced mortality suggests that the pathogenic role of
S. maltophilia should not be underestimated. This finding needs to be confirmed with larger, prospective studies.

1. Introduction with bacteriemia [1].

1.1. Background/rationale
Stenotrophomonas maltophilia is an emerging multi-drug resistant
gram-negative bacterium. It can be isolated from the environment and is
seen as a colonizer in patients with chronic lung disease [1]. S. maltophilia
is a pathogen of low virulence but has been increasingly associated with
nosocomial disease. Risk factors for disease include immunocompro-
mised patients or those with pre-existing lung disease [1]. It commonly
causes respiratory infection and bacteremia, but biliary, urinary,
ophthalmic, endocardial, meningeal and skeletal infections have been
documented [1]. These infections are associated with significant mor-
tality of up to 69% in critically-ill and immunocompromised patients
Reports of Stenotrophomonas infections from India have been rising.
These include ventilator-associated infections in infants [2], a cluster of
patients with endophthalmitis after receiving intravitreal bevacizumab
[3] and a series on nosocomial infections in adults [4]. A study examining
changes in antibiotic susceptibility patterns over a 10-year period re-
ported that Stenotrophomonas isolates remained susceptible to cotri-
moxazole and levofloxacin [5].
This study was done to identify the patients from whom Steno-
trophomonas maltophilia was isolated and to assess predictors of mortality
in this population.

* Corresponding author.

https://doi.org/10.1016/j.ijmmb.2021.11.004
Received 19 August 2021; Received in revised form 14 October 2021; Accepted 7 November 2021
Available online 19 November 2021
0255-0857/© 2021 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.
A. Jacob et al. Indian Journal of Medical Microbiology 40 (2022) 46–50

2. Materials and methods
2.1. Study design
This retrospective cohort included all hospitalized patients in the
general medicine department between 2018 and 2020 with culture
reports growing Stenotrophomonas maltophilia. The study was approved
by the institutional review board of the hospital where it was
conducted.
2.2. Setting
The study was conducted among in-patients in the medical wards and
medical intensive care units.
2.3. Participants
Consecutive adult patients admitted in the medical wards or medical
intensive care units with a blood or respiratory culture that had grown
Stenotrophomonas maltophilia were included in the study.
variables with a p-value of less than 0.1 were included in the multivariate
model. Analysis was done on SPSS v16.0.
3. Results
One hundred and nineteen patients were identified and included in
the study. The clinical and microbiological characteristics of the sample
are described in Tables 1 and 2 respectively. 61% of patients were male
with a mean age of 48.6 years. 93% of cultures were isolated more than
48 h after admission to hospital, with 82% being admitted in the inten-
sive care unit and 83% receiving invasive ventilation at the time of cul-
ture. 89.9% of patients had Stenotrophomonas isolated from respiratory
cultures, 7.6% had growth in blood cultures and 2.5% had both blood
and respiratory cultures positive. The majority (66%) had received car-
bapenem antibiotics within the preceding month. Most patients had
empiric antibiotic therapy initiated before culture reports became
available and most (78.1%) received Meropenem, an antibiotic to which
Stenotrophomonas is inherently resistant. A majority of patients had
polymicrobial respiratory cultures while a 22% had a simultaneous blood

Table 1
2.4. Variables
Clinical details of included patients.

Demographic details (age, sex, residence), clinical characteristics Characteristic N (%)

(diagnosis at admission, comorbid illnesses, risk factors for infection), Demographic details
microbiology (source of culture, drug susceptibility), laboratory results Agea 48.6 (19.1)
Sex-Male 73 (61.3)
(blood counts, arterial blood gases, electrolytes, renal and liver func-
Diagnosis at admission
tions) and clinical outcomes (mortality, time to discharge) were retrieved Respiratory disease 95 (79.8)
for all patients. Treatment with Co-trimoxazole, Levofloxacin or Mino- Infectionb 82 (68.9)
cycline was considered appropriate antibiotic therapy for Renal disease 55 (46.2)
Stenotrophomonas. Neurological disease 36 (30.3)
Cardiac disease 35 (29.4)
Toxin/poisoning 20 (16.8)
2.5. Data sources and measurement Liver/GI disease 20 (16.8)
Malignancy 7 (5.9)
Data was collected from electronic medical records, which contained Autoimmune disease 11 (9.2)
Endocrine/metabolic disease 7 (5.9)
details of admission, treatment received, clinical course of illness and
COVID 19 pneumoniac 23 (19.3)
outcomes. All microbiological cultures and the results of all laboratory Risk factors for infection
tests during admission were also available from these records. Bacterial Hospital admission 111 (93.3)
isolates were identified by using either the conventional biochemical test ICU admission 98 (82.4)
or Matrix-assisted laser desorption/ionization-time of flight (MALDI- Invasive Ventilation 99 (83.2)
Any Non-invasive ventilation 41 (34.7)
TOF) mass spectrometry (MS). Laboratory results including arterial blood Only non-invasive ventilation 3 (2.5)
gas results, electrolytes and blood counts and clinical details such as Recent antibiotic use 105 (88.2)
hypoxia and vasopressor use were taken from a period within 24 h of the Recent Carbapenem use 79 (66.4)
positive culture result. Recent surgery done 14 (11.8)
Diabetes mellitus present 40 (33.6)
Dialysis 18 (15.1)
2.6. Bias Recent Steroid use 42 (35.3)
Day of hospital staya 11.89 (9.74)
All patients within the specified time period were included in the Day of ICU staya 9.77 (7.89)
study. Objective measures of outcomes such as mortality and time to Days after intubationa 9.05 (7.02)
Outcome at discharge
discharge were specified prior to data collection. Records of exposure Alive and well 57 (47.9)
including prior antibiotics and steroid use were taken from pharmacy and Discharge against advice 7 (5.9)
medical records. Clinical details and treatment
Fever 84 (70.6)
Hypothermia 6 (5.0)
2.7. Study size
Hypoxia 111 (93.3)
New infiltrates on Chest X-ray 62 (58.5)
The required study sample was calculated using the Single Propor- Vasopressor use 68 (57.1)
tion- Absolute Precision method. Assuming an expected proportion of Increased oxygen or ventilatory requirement 80 (69.0)
0.57 for mortality [6] with 10% precision, a desired confidence level of Empirical Antibiotics initiated 114 (96.6)
Appropriate antibiotics used 37 (31.1)
95%, the calculated sample size was 94. Out-patient follow up 41 (66.1)
Time to discharge in days (from culture)a 19.1 (14.5)
2.8. Statistical methods Days in ICU(from culture)a 7.7 (10.6)
a
Values given are Mean (Standard deviation).
Mean and standard deviation for continuous variables and fre- b
Infection included 46.2% pneumonia including COVID 19, 4.6% pyelone-
quencies for categorical variable were calculated. Associations of various phritis, 9.2% CNS infections, 6.2% skin and soft tissue infection, 9.2% tubercu-
factors with mortality were analyzed using chi-square test. Multi-variate losis, 12.3% scrub typhus and 12.3% other infections.
c
analysis was done using forward conditional logistic regression. All COVID 19 pneumonia was included as both infection and respiratory disease.

47
A. Jacob et al. Indian Journal of Medical Microbiology 40 (2022) 46–50

Table 2 Table 3
Laboratory results and microbiology of patients with Stenotrophomonas isolates. Predictors of mortality: Bivariate and multivariate analysis.
Characteristic N (%) Characteristic Alive Dead (n Bi-variate Multivariate
(n ¼ ¼ 55) analysis OR analysisa OR
Culture and sensitivity reports
64) N (%) (95%CI); p value (95%CI); p value
Blood culture positive 9 (7.6)
N (%)
Respiratory culture positive 107 (89.9)
Both Blood and respiratory cultures positive 3 (2.5) Toxin/poisoning 19 1 (1.8) 0.04 NS
Other organism in blood culturea 26 (21.8) present (29.7) (0.01–0.34);
Other organism in respiratory cultureb 88 (73.9) 0.001
Respiratory culture-Endotracheal aspirate 93 (78.2) Cardiac disease 14 21 2.2 (1.0–4.9); NS
Drug susceptibility present (21.9) (38.2) 0.05
Cotrimoxazole (n ¼ 100) 93 (93) Renal disease 22 33 2.9 (1.4–6.0); NS
Levofloxacin (n ¼ 111) 107 (96.4) present (34.4) (60.0) 0.01
Minocycline (n ¼ 71) 69 (97.2) Autoimmune 3 (4.7) 8 (14.5) 3.5 (0.9–13.8); 27.4
disease present 0.06 (1.4–539.7);
Laboratory results
0.05
Mean(SD)
COVID 19 5 (7.8) 18 5.7 (2.0–16.8); 15.5
Haemoglobin (Gm%) 9.4 (2.2) pneumonia (32.7) 0.001 (0.9–268.7);
Total WBC count (per mm3) 12786 (7450) present 0.06
Platelets (per mm3)c 161000 (61000–271000) Non-Invasive 12 29 4.7 (2.1–10.8); NS
Creatinine (mg%)c 0.99 (0.65–2.39) Ventilation use (19.0) (52.7) 0.001
Urea (mg%)c 92 (62.5–123.25) Recent 36 43 2.9 (1.3–6.7); NS
pH 7.4 (0.1) carbapenem use (57.1) (79.6) 0.01
pO2(mmHg) 106.6 (41.8) Recent surgery 11 3 (5.5) 0.3 (0.1–1.1); 0.5 (0.0–0.6);
pCO2(mmHg) 38.2 (16.9) (17.2) 0.05 0.05
Fio2 (%) 44.1 (22.8) Steroid use 14 28 3.6 (1.64–8.0); NS
P/F ratio 291.5 (148.9) (22.2) (50.9) 0.001
Lactate(mmol/L)c 1.5 (1.1–2.55) Respiratory 54 54 10.0 NS
Albumin 2.6 (0.9) culture positive (84.4) (98.2) (1.24–80.9);
a
0.01
Other organisms in blood cultures included Klebsiella pneumonia (n ¼ 5), Hypoxia present 56 55 2.0 (1.7–2.8); NS
Candida species (n ¼ 6), E. Coli (n ¼ 4), Pseudomonas (n ¼ 4), Acinetobacter (87.5) (100.0) 0.01
baumanii (n ¼ 3), Other (n ¼ 7). Vasopressor use 25 43 5.6 (2.5–12.6); 39.5
b
Other organisms in respiratory cultures included Acinetobacter baumanii (39.1) (78.2) 0.001 (5.5–284.1);
(32.8%), Klebsiella pneumoniae (26.9%), Pseudomonas (19.3%); 43% had mul- 0.001
tiple other organisms grown. Increase in 38 42 2.5 (1.1–5.8); NS
c oxygen or (60.3) (79.2) 0.05
Values given are Median (Inter-quartile range).
ventilatory
requirement
Use of antibiotics 24 13 0.5 (0.2–1.1); 0.16 (0.03–0.8);
culture with growth of another pathogen. More than 90% of Steno- directed against (38.7) (23.6) 0.08 0.05
trophomonas isolates were susceptible to levofloxacin and minocycline S.maltophilia
and to a lesser extent to co-trimoxazole. Only about one-third of patients Platelet count  29 36 2.4 (1.1–5.2); 11.53
with Stenotrophomonas infection received antibiotics directed against 150000/mcL (48.3) (69.2) 0.05 (2.0–65.2);
0.01
S. maltophilia during their hospital stay. Most patients were critically ill Urea > 40 mg/dL 26 36 2.8 (1.1–6.9); NS
with worsening of respiratory function or the need for vasopressors. (56.5) (78.3) 0.05
Mortality at hospital discharge was 46%. Survivors also required long pH < 7.4 10 26 4.5 (1.9–10.8); NS
hospital (mean 19.1 days) and ICU stays (mean 7.7 days). (17.5) (49.1) 0.001
PaO2/FiO2 < ¼ 21 37 4.0 (1.8–9.8); 7.6 (1.5–37.9);
Bivariate analysis was used to identify risk factors for mortality as
300 (36.8) (69.8) 0.001 0.01
described in Table 3. Several risk factors for in-hospital mortality were Lactate > 2 mg/dL 12 24 3.0 (1.3–7.0); NS
identified including co-existing renal or cardiac disease, an admission (21.4) (45.3) 0.001
diagnosis of COVID 19 pneumonia, requirement of non-invasive venti- Albumin < 3.0 mg 43 46 3.9 (1.3–11.3); NS
lation, recent use of carbapenem antibiotics, steroid use, increased oxy- (70.5) (90.2) 0.01

gen or ventilatory requirement or vasopressor use. Patients with
thrombocytopenia, elevated urea or lactate and those with lower pH, P/F
ratios or albumin had worse outcomes. A diagnosis of a poisoning at
admission and those who had a recent surgery appeared to have lower
mortality. Patients who had received antibiotics directed against
S. maltophilia had lower mortality, although this association just missed
statistical significance and hence was included in the multivariate
analysis.
In view of multiple associations on bivariate analysis, multivariate
analysis was done using forward conditional logistic regression. This
showed that a diagnosis of autoimmune disease (OR ¼ 27.4, 95%CI ¼
1.4–539.6), a P/F ratio of less than 300 (7.6, 95%CI ¼ 1.5–37.9), hy-
potension requiring vasopressors (OR ¼ 39.5, 95%CI ¼ 5.5–284.1) and
thrombocytopenia (OR ¼ 11.5, 95%CI ¼ 2.0–65.2) remained statistically
significantly associated with increased mortality, after adjusting for other
variables significant on bivariate analysis, while recent surgery (OR ¼
Variables for which no significant association was found: Age, sex, residence,
prior ICU or hospital admission, diabetes, dialysis, invasive ventilation, duration
of antibiotic use, days in ICU or in hospital prior to culture report, neurological
disease, liver or GI disease, malignancy, blood culture positive, presence of other
organism is blood or urine, hemoglobin, total WBC count, neutrophil or
lymphocyte percentage, creatinine, sodium, potassium, bicarbonate, calcium,
phosphate, FiO2, total and direct bilirubin, SGOT, SGPT; NS -not statistically
significant.
a
Multi-variate analysis done using forward conditional logistic regression
including variables with a p value of <0.1.
0.53, 95%CI ¼ 0.004–0.63) and receipt of appropriate antibiotics (OR ¼
0.16, 95%CI ¼ 0.03–0.77) were associated with decreased mortality.
4. Discussion
This study is one of the few describing Stenotrophomonas isolates

48
A. Jacob et al.
from India. These isolates were primarily seen among patients admitted
to the intensive care unit (82.4%). Over all these patients had poor
outcomes with a high mortality rate (46.2%).
The results of the study showed that a diagnosis of autoimmune
disease, a P/F ratio of less than 300, vasopressor use and thrombocyto-
penia remained statistically significantly associated with increased
mortality after multivariate analysis, while recent surgery and receipt of
appropriate antibiotics were associated with decreased mortality. Most
(71.4%) of those patients who had recent surgeries had emergency
procedures (E.g., decompressive craniectomy, emergency laparotomy for
peritonitis, below-knee amputation for necrotizing fasciitis). The better
outcomes seen in this group are likely due to the acute nature of the
illnesses in patients who had been pre-morbidly healthy.
Autoimmune disease was one of the factors which contributed to poor
prognosis. The association between sepsis and autoimmune disease is
well documented and multifactorial with the effect of immunosuppres-
sive treatment playing an important role [7]. Immunocompromised pa-
tients are also at increased risk from infection by Stenotrophomonas
infection.
Hypotension requiring vasopressors, a low PaO2/FiO2 ratio and
thrombocytopenia suggest multi-organ dysfunction, which accompanies
severe sepsis. These are also components of the SOFA (sequential organ
failure assessment) score which is used to quantify organ dysfunction and
predict mortality in sepsis. As this was a retrospective study, data on the
SOFA score itself was not available for the patients included at the time of
culture.
Among the patients who were admitted in the year 2020, many had a
diagnosis of COVID 19. The mortality among COVID 19 patients in the
ICU and requiring invasive ventilation is known to be high [8] and this
was reflected in our study. However, the association with mortality fell
short of statistical significance on multivariate analysis.
Risk factors for mortality among patients with S. maltophilia infections
that have been documented in other studies are include mechanical
ventilation, ICU stay, central venous catheter use [9], failure to remove a
central line, malignancy, lack of effective antibiotic treatment [10],
thrombocytopenia, hypotension [11], neutropenia and mixed infection
with enterococci [12].
Differentiating Stenotrophomonas colonization from infection among
isolates from respiratory cultures is a challenge. The majority of these
cultures were from ventilated patients and the diagnosis of ventilator-
associated pneumonia is notoriously complex with both clinical and
bacteriological approaches having limited sensitivity and specificity
[13]. However, there is some evidence that the majority of our sample
constituted true infections by Stenotrophomonas. Firstly, most patients
had evidence of new organ dysfunction (hypotension, worsening respi-
ratory function) as well as fever. Secondly, the majority of the samples
were treated with empirical antibiotics by the treating physicians sug-
gesting a clinical diagnosis of sepsis. Thirdly, the association of appro-
priate antibiotics directed against Stenotrophomonas with reduced
mortality even after adjustment for other predictors of mortality suggests
a pathogenic role for these bacteria. Similar findings to this have been
noted in other studies [10,14]. Pneumonia has been documented to be
the most common infection caused by S. maltophilia, followed by
bacteremia [15].
The polymicrobial nature of cultures in which Stenotrophomonas
species were identified also meant that the other pathogens identified
including Acinetobacter, Pseudomonas and Klebsiella species were
preferentially treated as the cause of the nosocomial infections. Steno-
trophomonas bacteremia has been documented to polymicrobial in other
studies [16,17].
It should also be noted that the common antibiotics administered
empirically in these patients were ineffective against Stenotrophomonas.
The Stenotrophomonas isolates identified were largely susceptible to
easily available and inexpensive antibiotics such as cotrimoxazole and
levofloxacin.
Although co-trimoxazole is the drug of choice for Stenotrophomonas
49
Indian Journal of Medical Microbiology 40 (2022) 46–50
infections, in this sample sensitivity was higher to Levofloxacin and
Minocycline. A similar observation has been made in other studies [10].
As Stenotrophomonas was primarily isolated from patients in the
intensive care unit, infection control strategies, periodic surveillance and
source tracing play an important role in the prevention of infection.
4.1. Limitations
Stenotrophomonas maltophilia is known to be a colonizer of the res-
piratory tract in those with chronic respiratory disease [1]. Differenti-
ating true infection from colonization is a complex clinical decision. The
evidence supporting the pathogenic role of Stenotrophomonas in our
sample has been described above. However, it is possible that some of
these cultures were due to colonization and not infection. Some associ-
ations had wide confidence intervals and require larger, prospective
studies for confirmation of these findings. We found that 7% of cultures
were positive within 48 h of hospital admission without documented
prior hospital admission. This may be due to missing data which is a
limitation in this retrospective study.
5. Conclusion
Stenotrophomonas maltophilia insolates are primarily seen in patients
requiring intensive care and ventilation. In our study autoimmune dis-
ease, lower P/F ratios and thrombocytopenia were associated with
higher mortality. A recent history of surgery and use of antibiotics
directed against S. maltophilia were associated with a lower risk of
mortality. The findings need to be replicated using prospective cohort
design and larger samples.
Funding
Nil.
CRediT authorship contribution statement
Amita Jacob: Methodology, Data curation, Data collection, Formal
analysis, Writing – original draft. Ramya Iyadurai: Conceptualization,
Methodology, Writing – review & editing, Supervision. J.V. Punitha:
Methodology, Data curation, Data collection, Writing – review & editing,
Supervision. Binila Chacko: Methodology, Writing – review & editing,
Supervision. Sudha Jasmine: Methodology, Writing – review & editing,
Supervision. Muruga Bharathy: Data curation, Data collection, Meth-
odology, Writing – review & editing. Divya Mathew: Data curation, Data
collection, Methodology, Writing – review & editing. Balaji Veerar-
aghavan: Methodology, Writing – review & editing, Supervision.
Declaration of competing interest
The author declare no conflicts of interest.
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