Molecular epidemiology and risk factors of Stenotrophomonas maltophilia infections in a Chinese teaching hospital

doi:10.21203/rs.3.rs-22304/v4

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Molecular epidemiology and risk factors of Stenotrophomonas maltophilia infections in a Chinese teaching hospital

https://doi.org/10.21203/rs.3.rs-22304/v4

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published 29 Sep, 2020

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Background: Stenotrophomonas maltophilia (S. maltophilia) is an important opportunistic pathogen that can be isolated in hospitals. With the abuse of broad spectrum antibiotics and invasive surgical devices, the rate of S. maltophilia infection is increasing every year. This study is an epidemiological analysis of the clinical and molecular characteristics of S. maltophilia infection in a Chinese teaching hospital. The goal is to obtain a comprehensive understanding of the status of S. maltophilia infection in order to provide strong epidemiological data for the prevention and treatment of S. maltophilia infection.

Results: A total of 93 isolates from Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine were included, in which 62 isolates were from male patients and 81 isolates were isolated from sputum samples. A total of 86 patients had underlying diseases. All of the patients had received antibiotic therapeutics. The multilocus sequence typing (MLST) analysis indicated that 61 different sequence types (STs) were found (including 45 novel STs), and the MLST did not show significantly dominant STs. Pulsed field gel electrophoresis (PFGE) results showed the 93 isolates could be divided into 73 clusters, and they also showed weak genetic linkage between isolates. The resistant rates to Trimethoprim/sulfamethoxazole (TMP/SMX) and levofloxacin were 9.7% and 4.3%, respectively, and all of the isolates were susceptible to minocycline. The positive rates of the four virulence genes Stmpr1, Stmpr2, Smf-1, and Smlt3773 locus were 79.6%, 91.4%, 94.6%, and 52.7%, respectively. The positive rates of the three biofilm genes rmlA, spgM, and rpfF were 82.8%, 92.5%, and 64.5%, respectively. The mean biofilm forming level of OD₄₉₂ was 0.54 ± 0.49, and there was no significant difference between different genders and different age groups. Data from patients in the intensive care unit (ICU) and the control group were analyzed retrospectively, and the independent risk factors of those who were infected in the ICU included immunosuppression and the increased of the antibiotics usage.

Conclusions: Most of the patients had prior medical usage histories and baseline diseases. The positive rate of virulence genes was high, the drug resistance rate of S. maltophilia was low, and the biofilm formation ability was strong. The increased use of antibiotics was an independent risk factor for S. maltophilia infection, which should receive more attention. No obvious clonal transmission was found in the same department.

General Microbiology

Infectious Diseases

Stenotrophomonas maltophilia

MLST

biofilm

epidemiology

S. Maltophilia, called Xanthomonas maltophilia previously, is a non-fermentative, gram-negative aerobic bacilli. It is a cosmopolitan bacteria, which were originally plant pathogens, being ubiquitous in natural environments like water, soils, and plants[1]. S. maltophilia can also be found in medical settings, which has been found in numerous hospital devices, including dialysis devices, blood pressure monitors, faucets, sphygmomanometers, disinfectants, and ventilators, and has the ability to transmit between patients or from patients to healthy persons[2]. Clinical evidence has shown that S. maltophilia can cause nosocomial infections in immunocompromised hosts, such as respiratory system infections, joint infections, and skin infections[3]. Wu et al.[4] also found that the dominant flora in keratitis infection was S. maltophilia. In many China Antimicrobial Surveillance Network (CHINET) reports , among non-fermentative gram-negative bacilli, S. maltophilia was the third largest one every year, just after Pseudomonas aeruginosa and Acinetobacter baumannii, and the number of clinical isolates showed an upward trend[5].

With the abuse of different types of antibiotics, chemotherapy drugs, and immunosuppressants, and the widespread use of invasive exploration equipment, the isolation and infection rates of S. maltophilia in hospitals are continuing to increase. Brooke[2] reported that particular attention was required for inpatients with immunosuppression. S. maltophilia is intrinsically resistant to several kinds of antibiotics due to various resistance mechanisms. It can produce a penicillinase (L1) and a cephalosporinase (L2), which makes it easily resistant to β-lactam antibiotics, specifically carbapenems[6]. It can produce aminoglycoside modifying enzymes, which make it resistant to aminoglycoside drugs in a certain degree, and the efflux pump system also makes it resistant to a variety of antimicrobial agents[7]. Hence the continuous emergence of multidrug-resistant isolates of S. maltophilia has have brought great challenges for the treatment of serious S. maltophilia infection[5].

There have been few studies that have investigated the comprehensive clinical and molecular characteristics of the S. maltophilia in Shanghai. Therefore, in this study, multilocus sequence typing (MLST) and pulsed field gel electrophoresis (PFGE) are used to analyze the molecular epidemiological characteristics of S. maltophilia isolated from the Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine. The risk factors of S. maltophilia infection from ICU patients are also analyzed. The clinical information of the related patients is collected, and at the same time, the virulence genes and biofilm genes of S. maltophilia are detected. The aim of this study is to develop an intuitive description of the epidemic situation of the strain in clinic. This will provide the necessary groundwork for basic and mechanical studies and provide support for the prevention and treatment of S. maltophilia infection.

Patients and bacteria isolates

Patients’ clinical information was collected, and a total of 93 isolates of non-repetitive S. maltophilia were isolated. Among them, 30 isolates of S. maltophilia were isolated from the ICU, and the rest were from a range of hospital departments (Figure 1). The rest included 13 isolates from neurosurgery, 9 isolates from emergency internal medicine, 8 isolates from cadre health care, 6 isolates from cardiovascular surgery, 5 isolates from hematology, 4 isolates from liver surgery, 3 isolates from oncology, 3 isolates from nephrology, 2 isolates from emergency medicine, 2 isolates from neurology, 2 isolates from cholangio-pancreatic surgery, 1 from thoracic surgery, 1 from gastrointestinal surgery, 1 from respiratory medicine, 1 from digestive medicine, 1 from general surgery, and 1 from urology.

Among the patients with S. maltophilia infection, 62 males (66.7%) and 31 females (33.3%) were included. A total of 73 patients were aged 60 years or above (78.5%). Before bacterial isolation, 35 patients (37.6%) were subjected to invasive examinations or treatments. Among all the S. maltophilia isolates, there were 81 isolates (87.1%) isolated from sputum, 7 isolates (7.5%) from drains, 2 isolates from pleural effusion, 1 strain from ascites, 1 strain from urine, and 1 strain from blood.

Of the 93 patients, 7 (7.5%) had no basic diseases but primarily fractures and malnutrition, and 86 (92.5%) had one to five underlying diseases. Of these, 25 had malignant tumors, 24 had hypertension, 12 had coronary heart disease, 10 had renal insufficiency, 5 had leukemia, 14 had head trauma, 20 had chronic bronchitis or pneumonia, and 12 had liver injury. All of the patients had a history of antibiotic use (1-6 types), with an average of three antibiotics per person prior to isolation of S. maltophilia, of which 69 had used three or more antibiotics. The antibiotics primarily included cephalosporins (65/93), carbapenem (53/93), β-lactamase inhibitors (51/93), quinolones (35/93), glycopeptide (22/93), aminoglycosides (13/93), and tetracyclines (9/93) (Table 1).

Table 1. The clinical characteristics of adult and pediatric patients

	Adult(n=93)
Demographics
Age(year, average, range)	66.3 (16-99)
Gender: male	62 (66.7%)

Baseline diseases, n(%)
Hypertension	24 (25.8)
Heart Disease	12 (12.9)
Malignancy	25 (26.9)
Pulmonary Disease	20 (21.5)
Liver Disease	12 (12.9)
Leukemia	5 (5.4)
Head trauma	14 (15.1)

Strain isolation n(%)
ICU	30 (32.3)
Sputum	81 (87.1)

Invasive operation n(%)	35 (37.6)

Previous antibiotics usage n(%)
The number of antibiotics ≥3	69 (74.2)
Cephalosporins	65 (69.9)
Carbapenems	53 (57.0)
β-lactamase Inhibitors	51 (54.8)
Quinolones	35 (37.6)
Glycopeptides	22 (23.7)
Aminoglycosides	13 (14.0)

MLST analysis

The distribution of the clonal typing of S. maltophilia was relatively scattered. According to the different alleles, the isolates were assigned to 61 sequence types. Among them, 45 types of the 60 isolates were different from those published on the PubMLST database (recorded as STnew1-STnew45). The other 33 isolates consisted of existing types in the database, of which a relatively larger number was ST23 (n=8). There were also some isolates of ST5 (n=3), ST15 (n=3), ST24 (n=3), ST3 (n=2), ST84 (n=2), ST89 (n=2), and ST99 (n=2), while some isolates were assigned to ST4, ST8, ST13, ST36, ST77, ST98, ST102, and ST112. The eight S. maltophilia isolates of ST23 were distributed in five different departments, and the 30 isolates isolated from the ICU were classified into 24 sequence types. S. maltophilia isolates of the exact same sequence types were not collected in other departments, indicating that there was no obvious clonal transmission of S. maltophilia infections in this study [1]. The detailed results are shown in Figure 2.

PFGE typing results

According to the fragment diagnostic criteria of PFGE, the PFGE types can be classified into a group or cluster if there are no more than 3 bands[8, 9], and the 93 SMA strains was scattered and could be divided into 73 clusters in this study. Among them, 13 strains could be divided into the same cluster (from 8 departments, not from the same department). Another five and two strains were divided into the same cluster, and the others were quite different. These results suggest that these isolates do not have an outbreak in the department, and the detailed results are shown in Supplementary Figure 1.

Virulence gene detection

The results of the virulence gene detection showed that the positive rates of the four virulence genes were 79.6% (74/93) for Stmpr1, 91.4% (85/93) for Stmpr2, 94.6% (88/93) for Smf-1, and 52.7% (49/93) for Smlt3773. There were 31 isolates of S. maltophilia that carried all four of the genes.

Analysis of drug resistance

The resistance rates of S. maltophilia to levofloxacin and TMP/SMX were 4.3% and 9.7%, respectively. All of S. maltophilia isolates were susceptible to minocycline. Among these isolates, one isolate, numbered ji82, was resistant to both TMP/SMX and levofloxacin.

Biofilm forming ability

The average biofilm forming ability of S. maltophilia was OD₄₉₂=0.54 ± 0.49 (0.044–2.34). The OD values of S. maltophilia isolated from the male and female patients were OD₄₉₂of 0.52 ± 0.51 and OD₄₉₂of 0.57 ± 0.47, respectively, and there was no significant difference between the two groups. There was no significant difference in the biofilm formation ability between people aged 60 or above and those under 60 years old, as shown in Figure 3. In addition, the drug resistance and biofilm forming ability of the isolates were analyzed, and there was no obvious correlation between the drug-resistant phenotype and the biofilm forming ability, as shown in Table 2. The positive rates of the three biofilm genes rmlA, spgM, and rpfF were 82.8% (77/93), 92.5% (86/93), and 64.5% (60/93), respectively. The point mutations of the spgM gene in the isolates with strong biofilm forming abilities were relatively consistent and significantly different from those with weak biofilm forming abilities. The detailed sequencing results of some isolates are shown in Figure 4 (the base-pairs of the two isolates with different biofilm forming abilities were selected as the representatives). However, the other two biofilm genes did not have obvious point mutations in the isolates with different biofilm forming abilities.

Table 2. Drug-resistant rates and relationship between the drug resistance and biofilm formation

Antibiotics	Resistant rate	Pearson's correlation
levofloxacin	4.3%	0.02
TMP/SMX	9.7%	0.04
minocycline	0%	NA

The carriage of the virulence genes

The carriage of the four virulence genes Stmpr1, Stmpr2, smf-1,and Smlt3773locus were 79.6%, 91.4%, 94.6%, and 52.7%, respectively.

Analysis of the risk factors in ICU patients infected with the S. maltophilia

By using a univariate analysis, it was concluded that the changes in lymphocytes, albumin, and the use of antibiotics were infection risk factors in the ICU patients (Table 3). After the multivariate analysis, the type of antibiotic use and lymphocyte count were found to be independent risk factors of infection with S. maltophilia (Table 4). These findings may be used as a new reference index for clinical sensitivity and control of S. maltophilia.

Table 3. Univariate analysis of risk factors of S. maltophilia infections in the ICU

Items	Patients (n=30)	Control (n=60)	P value	OR(95%CI)
male (sex)	23 (76.7%)	38 (63.3%)	0.263	0.565 (0.208-1.534)
Age (years)	64.8 ± 19.1	65.5 ± 16.9	0.873
leukocyte	11.5 ± 5.4	10.9 ± 4.1	0.777
neutrophil	9.4 ± 4.9	9.4 ± 3.9	0.767
lymphocyte	1.3 ± 0.9	0.9 ± 0.4	0.012
monocyte	0.7 ± 0.5	0.5 ± 0.4	0.536
albumin	30.6 ± 4.2	28.3 ± 5.7	0.033
globulin	29.0 ± 6.4	28.2 ± 7.0	0.286
prealbumin	129.0 ± 52.3	124.8 ± 49.9	1.000
surgeries	14 (46.7%)	27 (45.0%)	0.496	0.724 (0.286-1.835)
organ transplantation	5 (16.7%)	9 (15.0%)	0.987	0.990 (0.296-3.310)
malignant tumor	8 (26.7%)	15 (25.0%)	0.894	0.933 (0.337-2.585)
hypertension	7 (23.3%)	15 (25.0%)	0.923	0.949 (0.328-2.748)
diabetes	3 (10.0%)	9 (15.0%)	0.397	0.547 (0.135-2.213)
pulmonary infection	9 (30.0%)	16 (26.7%)	0.990	1.007 (0.374-2.712)
cardiopathy	4 (13.3%)	9 (15.0%)	0.841	0.875 (0.238-3.213)
liver injury	4 (13.3%)	7 (11.7%)	0.972	1.024 (0.272-3.856)
trachea intubation	12 (40.0%)	21 (35.0%)	0.941	1.036 (0.406-2.640)
chemotherapy	2 (6.7%)	3 (5.0%)	0.843	1.205 (0.189-7.681)
immunosuppressor	9 (30.0%)	17 (28.3%)	0.867	0.920 (0.343-2.464)
number of antibiotics	3.6 ± 1.2	3.0 ± 1.1	0.029
carbapenems	21 (70.0%)	40 (66.7%)	0.731	1.187 (0.445-3.167)
cephalosporins	20 (66.7%)	45 (75.0%)	0.604	0.771 (0.289-2.059)
quinolones	16 (53.3%)	30 (50.0%)	1.000	1.000 (0.396-2.523)

Table 4. Multivariate logistic regression analysis associated with S. maltophilia infections in the ICU

Risk factors	B value	Wals	P value	OR value	95% CI
					lower limit		upper limit
lymphocyte	1.077	4.208	0.04	2.937	1.049	8.222
albumin	0.099	3.05	0.081	1.104	0.988	1.234
antibiotics	0.596	5.956	0.015	1.814	1.124	2.927

S. maltophilia is an environmental global emerging gram-negative multiple-drug-resistant organism that is most commonly associated with respiratory infections in human beings[2, 10]. It is also responsible for many other infectious diseases including bacteremia, endocarditis, and urethral infection, especially among the immunocompromised, as well as those undergoing aggressive treatments[1]. In patients with pneumonia infections, the mortality rate can be as high as 14% to 69%[11]. In recent years, S. maltophilia has been ranked third among non-fermentative gram-negative bacteria according to the CHINET monitoring service and has been relatively stable, just following Pseudomonas aeruginosa and Acinetobacter baumannii, and its isolation rate has displayed an increasing trend[5]. According to the results of this study, patients aged 60 or elder were more susceptible to S. maltophilia infection, which may be related to their immunosuppression. Most of the patients had underlying diseases, and 37.6% of the patients had previously invasive examinations or treatments. In addition, there were relatively more male patients. These findings remind clinicians to pay more attention in the prevention of S. maltophilia infections for certain population groups.

The sequence types of the 93 isolates were quite scattered, which indicated that these isolates had loose associations, and thus outbreaks of S. maltophilia infection have typically not occurred. Through the MLST results, we can make a comparison with ourselves and other reporters' results easily, while the PFGE is more about detecting outbreaks in the same hospital. The primary sequence types in this study were not consistent with that reported in other countries, indicating the isolates from our hospital were quite different from other countries. In addition, the consistency between the MLST and PFGE results was poor, and the same ST genotype had no similarity with the PFGE typing. These indicated that the S. maltophilia isolates had genetic diversity, which was consistent with the results of foreign studies regarding the differences between the two detection methods[12-14].

All of the patients had antibiotic usage (1 to 6 types) prior to the isolation, of which, 69 patients had used antibiotics three or more times. The majority of antibiotics included cephalosporins, carbapenem, and β-lactamase inhibitors. However, the use of cephalosporins and carbapenem can easily cause S. maltophilia to be selected as the dominant flora. According to the epidemic characteristics of S. maltophilia, it is believed that S. maltophilia infection is an endogenous infection under the interaction between drug selection and its own environment, rather than an interpersonal infection in a ward[2].

S. maltophilia exhibits complicated resistance to a broad array of antibiotics, limiting available therapeutic options. Because maltophilia is intrinsically resistant to a variety of antibiotics, a drug resistance analysis to other drugs was not performed in this study. However, three commonly used antimicrobial agents against S. maltophilia infection in clinic were analyzed. The results of the antibiotic susceptibility test showed that the S. maltophilia isolates in this study were susceptible to three targeted antimicrobial agents in clinic, and the drug resistance rate was low. However, one isolate was still resistant to two of the tested antibiotics. Due to the existence of complicated multidrug-resistant mechanisms in S. maltophilia and the worsened co-infection phenomenon, it is suggested that diligence to this infection be still needed, especially in monitoring of the multidrug-resistant S. maltophilia. In the analysis of risk factors, in addition to the analysis of common factors, indicators related to immunosuppression, such as leukocytes, neutrophils, and immunoglobulins, were specifically examined. However, leukocytes and neutrophils are greatly affected by the outside influences, the number of which will rise once there is a bacterial infection. It was speculated that lymphocytes (which are less affected by stress and microbial factors), immunoglobulin, albumin, and prealbumin affected by nutritional factors, may be used as observable indicators. The results also showed that lymphocytes and albumin were independent risk factors of S. maltophilia infection, and lymphocytes could be used as independent factors to provide an important method and basis for guiding clinically S. maltophilia monitoring, prevention, and control. In the S. maltophilia infection group, the concentration of albumin was higher than that in the control group. However, whether this was caused by compensation or other factors needs to be deeply studied. In this study, the times of carbapenem usage and endotracheal intubation, which are likely to be risk factors, were not accurately recorded. This was a major defect of this study, and a supplement study to investigate these two indicators will be performed in the future. There are also some other inadequacies in this study. It was found that mutations in the spgM gene in the isolates with strong biofilm forming abilities were significantly different from those with weak biofilm forming abilities. However, further exploration was not performed to investigate the exact mechanisms. This aspect requires further attention in a future study.

The genotyping of the isolates showed high diversity, indicating the distant correlation of these isolates and the low-occurring clonal transmission of S. maltophilia in the same department. This suggested that clinical S. maltophilia infections are perhaps endogenous infections under antibiotic selection. This conclusion is a reminder that antibiotics should be reasonably used so as to reduce the incidence of infection. The types of antibiotic use and lymphocyte counts were found to be independent risk factors of S. maltophilia infection. The mutations in the spgM gene are associated with biofilm forming abilities, which is worthy of future research. Due to the strong biofilm forming ability and high virulence gene carrying rate, high risk patient groups should receive more attention to avoid potential risk of S. maltophilia infection.

Materials and reagents

A total of 93 non-repetitive isolates of S. maltophilia from outpatients and inpatients from Renji hospital in 2014 were collected, in addition to the patients’ clinical information. These isolates were identified using the VITEK-2 Compact System (bioMérieux, France) and confirmed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS, Bruker Daltonics, Bremen, Germany). The samples were then stored at minus 80°C.

The bacteria were then grown in tryptic soy broth (TSB; Oxoid) at 37°C overnight. The antibiotics used for disk diffusion testing were levofloxacin, TMP/SMX, and minocycline (Oxoid, UK). The quality control isolates included Escherichia coli ATCC25922 and Pseudomonas aeruginosa ATCC27853.

Disk diffusion testing

Disk diffusion was performed according to the Clinical and Laboratory Standards Institute (CLSI) 2019 recommendations for levofloxacin, TMP/SMX, and minocycline.

Multi-locus sequence typing (MLST) analysis

Primer sequences targeting the conserved regions of seven housekeeping genes of S. maltophilia were used, as shown on the MLST site (http://pubmlst.org/smaltophilia/). The MLST was performed as described by Kaiser et al.[15].

Seven pairs of primers for the housekeeping genes (atpD, gapA, guaA, mutM, nuoD, ppsA, and recA) were synthesized (Supplementary Table 1).

The PCR mixture (2ÍPCR mix, primers, DNA template, and double distilled water) was incubated at 94°C for 5 min; 35 cycles at 94°C for 10 s, 55°C for 30 s, and 72°C for 30s; with a final extension step at 72°C for 1 min. The sequence was analyzed using DNAstar software, and the obtained sequence was submitted to the MLST database to acquire sequence type. Seven housekeeper genes were assembled using MEGA.4 software, and a phylogenetic analysis was conducted.

Pulsed-field gel electrophoresis (PFGE) analysis

The PFGE was performed using the Bio-Rad system, and protocol was slightly modified according to the Tanimoto’s and Shueh CS’s reports[14, 16] and our preliminary experiments: Restriction enzyme Xbal (Roche Diagnostics) was digested at 37 °C for 3 hours; PGFE electrophoresis conditions followed the manufacturer’s protocol: 2000 mL 0.5 *TBE, voltage 6.0 V max, temperature 14 °C, pulse angle 120, start pulse time 5 s, end pulse time 20 s, electrophoresis time 19 hours. The results were analyzed using BioNumerics software (version 4.0, Applied Maths, Belgium). Salmonella serotype Braenderup strain (H9812) was molecular weight Marker.

Biofilm formation assay

The overnight cultured S. maltophilia was diluted in TSB to D₆₀₀ of 0.01. A total of 200 µl of the solution in each well was cultured at 37°C for 24 hours in a 96-well plate (Corning, USA). The biofilm formation ability was determined using dye crystal violet staining. After incubation, the plate was fixed at 60°C for 1 hour. The non-adherent bacteria was removed and washed with sterile phosphate buffer solution (PBS) four times, then 50 µL of crystal violet dye was added to each well and kept at room temperature for 5 min. This was followed by rinsing under running tap water. The plate was dried at room temperature and 250 µL of 33% glacial acetic acid was added to each well to dissolve the staining for 15 min. To measure the absorbance, the optical density was read at 492 nm. A low cut-off (ODc) was defined as 3× standard deviation (SD) above the mean OD of the control wells, and the ability of biofilm formation was classified as follows: no biofilm producer (OD≤ODc), weak biofilm producing (ODc<OD≤2×ODc), moderate biofilm producing (2×ODc<OD≤4×ODc), and strong biofilm producing (4×ODc<OD).

Detection of biofilm and virulence genes

Three biofilm genes, rmlA, spgM, and rpfF, and four virulence genes, Stmpr1, Stmpr2, smf-1, and Smlt3773, were amplified using PCR. PCR was performed as previously described in the MLST section, and these genes’ primers are shown in Supplementary Table 1.

Risk factor analysis

Clinical information of 30 patients with S. maltophilia infections from the ICU was collected. Each S. maltophilia-infected patient was matched with two patients without S. maltophilia infection from the same department during the same period and with age differences of less than three years. In addition, the blood infection routines and the results of their biochemical tests were analyzed. Additionally, clinical diseases, operations, treatments, and other items for each patient were combined to analyze the risk factors of S. maltophilia infection in patients from the ICU.

Statistical analysis

SPSS 22 (IBM SPSS Statistics for Windows 22.0, IBM Corp. Armonk, NY, USA) and GraphPad Prism 8 (GraphPad software Inc.; San Diego, CA, USA) were used for the data processing. The normality was analyzed using the Shapiro-Wilk test. The median and range (or mean ± SD) and a one-way ANOVA were used for the continuous variables, and a chi-square test was used for the categorical data. Percentages (%) were used for the positive rates, such as the drugs resistant rate, biofilm genes positive rate, and virulence genes positive rate. Values of p < 0.05 were considered to be statistically significant. The correlation between the clonal typing and drug resistance rate, and the correlation between the biofilm and drug resistance rate were compared using the Pearson correlation coefficients.

S. maltophilia: Stenotrophomonas maltophilia; PCR: Polymerase chain reaction; ATCC: American Type Culture Collection; MIC: Minimum inhibitory concentration; MLST: Multilocus sequence typing; PFGE: Pulsed field gel electrophoresis; ST: Sequence type; TMP/SMX: Trimethoprim/sulfamethoxazole; TSB: tryptic soy broth; OD: Optical density; CLSI: Clinical and Laboratory Standards Institute; PBS: Phosphate buffer solution

Ethics approval and consent to participate

This study was approved by Institutional Review Board of the Renji Hospital. As a retrospective study, informed consent was granted exemption.

Consent for publication

Not applicable.

Availability of data and material

The data used and analysed during the current study are available from the first author on reasonable request.

Competing interests

The authors declare that there is no conflict of interest.

Funding

This study was supported by the National Natural Science Foundation of China (No. 81873970) and Scientific Research Project of Shanghai Municipal Health Bureau (20164Y0105). The first author of this paper was in charge of the latter project, and the corresponding author was in charge of the former project.

Authors’ contributions

ZLD and JXQ operated all the experiments and this manuscript. YL assisted in writing manuscript. CL assisted in data analysis. CMY conceived and supervised this study. All authors approve this manuscript.

Acknowledgments

We thank professor Min Li of Renji Hospital for technology assistance. We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

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supplementaryfig1.tif
Supplementary Figure 1 Dendrogram of obtained PFGE XbaI profiles of S. maltophilia clinical isolates. Distance showed above the dendrogram represents genetic relatedness between the analyzed isolates.
supplementarytable1.doc
Supplementary Table 1 Primers for MLST, biofilm, and virulence genes of S. maltophilia

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Molecular epidemiology and risk factors of Stenotrophomonas maltophilia infections in a Chinese teaching hospital

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Abstract

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Background

Results

Discussion

Conclusions

Methods

Abbreviations

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References

Supplementary Files

Status:

Journal Publication

Version 4