Stenotrophomonas Maltophilia Infection in Cancer Patients Undergoing Major Surgery in A Tertiary Cancer Centre

Background: We aim to study the impact of postoperative Stenotrophomonas maltophilia infections among cancer patients undergoing major surgery. Methods: Ambispective, observational study. Study period from 1st November 2019 to 31st March 2024. The study population included patients with a definite diagnosis of cancer who underwent a major surgical procedure in a single, dedicated surgical unit and developed postoperative infection which showed a documented growth of Stenotrophomonas maltophilia. Clinical and laboratory parameters were collected and data represented as median values, percentages and range. Results: Nine patients were identified to have Stenotrophomonas maltophilia infection in the postoperative period among a total of 2506 patients. Co-morbid illnesses were noted in 33.3% patients; all were nosocomial infections. Fever was a manifestation in 77.8% patients, 44.4% had leukocytosis. Of all samples, 33.3% were respiratory ones. Co-infection was noted in 44.4% patients. Sensitivity to trimethoprim-sulphamethoxazole was seen in 44.4% and to levofloxacin in 66.7% isolates. Mortality rate was 11.1%. Conclusion: Stenotrophomonas maltophilia causes uncommon but clinically significant infections among cancer patients in the postoperative period.

 Introduction

Stenotrophomonas maltophilia is a multi-drug resistant gram-negative bacillus and it acts as an opportunistic pathogen. Such infections are usually encountered in hospitalized patients and often result in high incidence of morbidity and mortality. The bacillus has inherent resistance to several antibiotics like carbapenems and the indiscriminate use of antibiotics may potentially make it a prominent nosocomial infection. The predisposing factors for S. maltophilia infection include in-dwelling central venous catheters, urinary catheters, mechanical ventilation, a post-surgical period, cancer, an intensive care unit (ICU) setting, use of immunosuppressive drugs and neutropenia. It can cause a wide array of manifestations ranging from pneumonia, bacteremia and sepsis, urinary tract infections, peritonitis, wound infections, cholangitis, arthritis, meningitis and endocarditis. The existing literature about this uncommon pathogen and its implication in patients undergoing major cancer surgery is limited world-wide and non-existent from our region. Our results will be a useful guide with respect to the clinical significance of this pathogen in the context described.

The aim of the study was to describe the impact of Stenotrophomonas maltophilia infection in the postoperative period of patients undergoing major cancer surgery. The primary objective was to estimate the clinical outcomes in terms of in-hospital morbidity and mortality associated with Stenotrophomonas maltophilia infection and the secondary objective was to report about the antibiotic sensitivity profile of these infections besides describing the clinical profile of the patients who had those infections.

Materials and Methods

An ambispective, observational study was done in the surgical oncology unit of a tertiary care cancer centre in North-East India during the study period from 1st November 2019 to 31st March 2024. The study population included patients with a definite diagnosis of cancer who underwent a major surgical procedure in a single, dedicated surgical unit and developed postoperative infection which showed a documented growth of Stenotrophomonas maltophilia. All the microbiological samples were processed by standard procedures including inoculation in blood agar and MacConkey agar plates incubated overnight at 37 degrees centigrade and all the plates were examined for visible growth (Figure 1 and 2).

The colonies were identified as per standard microbiological procedures (Figure 3).

The samples of blood culture were processed in BACT/ALERT 3D (bioMérieux). The final identification of the organisms was identified using a fully automated system, VITEK 2 (bioMérieux).The antibiotic sensitivity profile was done using the same system. For data collection, microbiological and clinical data variables obtained from review of EMR and physical case records. Variables to be studied include: age, sex, co-morbidity, primary malignancy, surgery performed, presence of fever, number of days of ICU and hospital stay, outcomes including whether recovered or succumbed, specimen types, presence of co-infection, blood parameters including total leucocytic count (TLC) and differential leucocytic count (DLC) and antibiotic sensitivity profile. The results were presented with the use of median values, percentages and range. The study was approved by the Institutional Ethical Committee (IEC).

 Results

Atotal of 9 patients were found to have Stenotrophomonas maltophilia infection in the postoperative period among the 2506 patients undergoing major oncologic surgeries in the surgical unit concerned. The median age of the patients was 54 years (range 23 to 77 years). There were five male patients and four females. Three patients had co-morbid illnesses (33.3%), other than cancer. Seven patients (77.8%) were those who had major surgery for gastrointestinal and pancreatic cancers. All nine patients had the infection while they were hospitalized. Fever was a manifestation in 77.8% patients (Table 1).

Characteristic category Characteristics No of patients/ Value
Median age   54 years(range 23 to 77 years)
Sex Male 5
  Female 4
Co-morbidity Diabetes mellitus 1
  Hypertension 1
  Idiopathic thrombocytopenic purpura 1
  Others 0
Primary malignancy Esophageal cancer 3
  Pancreatic cancer 2
  Colon cancer 1
  Rectal cancer 1
  Breast cancer 2
Surgery performed Esophagectomy 3
  Whipple’s surgery 1
  Extended right hemicolectomy 1
  Low anterior resection 1
  Modified radical mastectomy 2
  Distal pancreaticosplenectomy and en bloc left nephrectomy andduodenojejunal flexure resection 1
Hospitalized patient Yes 9
  No 0
Fever Yes 7
  No 2
Median ICU stay   4 days(range 0 to 31 days)
Median hospital stay   15 days(range 0 to 42 days)
Outcome Recovered 8
  Succumbed 1
Risk factors In-dwelling central venous catheter 5
  Urinary catheter 8
  Mechanical ventilation 5
  ICU stay > 1 day 5

We noted that 44.4% patients had leukocytosis and one patient (11.1%) had leucopenia. The specimens that yielded Stenotrophomonas maltophilia included wound swabs, blood samples, abdominal fluid (from drainage tube), pleural fluid (from pleural effusion) and tracheal swab and secretions. We found that 33.3% of positive samples were pertaining to the respiratory system (Table 2).

Test Test categories Value/ number of patients/ Percentage
Total leucocytic count (TLC) Median total count 10,630 cells/mm3 (range 1,850 to 33,710 cells/ mm3)
Leukocytosis 4
Leukopenia 1
Differential leucocytic count (DLC) Neutrophilia 8
Eosinophilia 1
Specimen type
Wound swab Wound swab 2
Blood Blood 2
Abdominal fluid Abdominal (drain) fluid 2
Pleural fluid Pleural fluid 1
Tracheal swab/ secretion Tracheal swab/ secretion 2
Antibiotic sensitivity
Levofloxacin 66.70%
Trimethoprim-sulphamethoxazole 44.40%

It was found that the bacillus was sensitive to the antibiotic levofloxacin in 66.7% samples and it was sensitive to the antibiotic trimethoprim and sulphamethoxazole in 44.4% samples. Co-infection was noted in 44.4% of patients and these included Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Enterococcus faecalis VRE (Vancomycin Resistant Enterococcus) (Table 3).

Surgery Surgical complication Specimen that yielded S. maltophilia Co-infection Sample yielding co-infection
Minimally invasive McKeown’s esophagectomy Pneumonia Tracheal swab Pseudomonas aeruginosa Pus from neck wound
Minimally invasive McKeown’s esophagectomy Pleural effusion Pleural fluid Enterococcus faecalis VRE, Pseudomonas aeruginosa Abdominal drain fluid
Whipple’s pancreaticoduodenectomy Pancreatojejunostomy anastomosis leak Blood None None
Distal pancreaticosplenectomy with en bloc resection of duodenojejunal flexure and left nephrectomy Peripancreatic collection Abdominal fluid None None
Extended right hemicolectomy Surgical site infection (SSI) Blood None None
Low anterior resection Anastomotic leak Abdominal fluid Acinetobacter baumannii, Klebsiella oneumoniae Pus from abdominaldrain fluid
Modified radical mastectomy + thoraco-abdominal flap Surgical site infection (SSI) Wound swab None None
Modified radical mastectomy Surgical site infection (SSI) Wound swab None None
Minimally invasive McKeown’s esophagectomy Anastomotic leak in the neck Tracheal secretion Acinetobacter baumannii Chest drain fluid

Out of the nine patients in the study, 88.9% of them recovered with appropriate antibiotics. The patients had a median period of intensive care unit (ICU) stay of 4 days (range 0 to 31 days) and a median period of hospital stay of 15 days (range 0 to 42 days). Every patient did have surgical morbidity and one patient succumbed to sepsis (11.1% mortality).

Discussion

Stenotrophomonas maltophilia is recognized as an emerging gram-negative multi-drug resistant organism (MDRO) and an opportunistic pathogen. It is mostly described in a hospital-acquired scenario, when the patient is immunocompromised. Even though it mostly causes respiratory infections, it has the ability to present with a wide spectrum of manifestations including pneumonia and acute exacerbations of chronic obstructive pulmonary disease (COPD), bacteremia and sepsis, urinary tract infections, peritonitis, wound infections, cholangitis, cellulitis and myositis, osteomyelitis and arthritis, eye infections, meningitis and endocarditis. The predisposing factors for S. maltophilia infection include in-dwelling central venous catheters, urinary catheters, mechanical ventilation, a post-surgical period, cancer, an intensive care unit (ICU) setting, use of immunosuppressive drugs and neutropenia [1-6]. We studied a population of patients who underwent major surgery for cancer and had several of such risk factors. Cancer itself has been described as a predisposing condition and the implications of infection by this organism has been described recently in the available literature. Cancer patients may be immunocompromised due to the debilitating disease per se or the use of chemotherapeutic agents. A major surgery also has its effect on the immune system, especially during the well-recognized phase of perioperative catabolism [7]. In our study, the median duration of ICU stay was 4 (range 0 to 31 days). Five patients had in-dwelling central venous catheters and a same number had mechanical ventilator support (55.6%).

Stenotrophomonas maltophilia was first isolated in 1943 as Bacterium bookeri and was subsequently named Pseudomonas maltophilia, then Xanthomonas maltophilia and eventually, the present nomenclature [8, 9]. The organism is often isolated from aqueous-associated sources like water-treatment and distribution sources, sinkholes, tap water, contaminated chlorhexidine-cetrimide antiseptic solutions, irrigating solutions, hand-washing soaps etc. It has a special ability to adhere to plastic and produce biofilms, such as in intravenous cannulae and catheters, nebulizers and prosthesis [5] [10-14].

Stenotrophomonas maltophilia has intrinsic resistance to carbapenems and prior history of use of these agents is implicated in selection pressure for this pathogen [15-20]. Trimethoprim-sulfamethoxazole has been often viewed as the antimicrobial agent of choice, but resistance has increasingly been reported [21-24]. In our study, only 44.4% of the isolates were sensitive to this antibiotic. The susceptibility to alternative antimicrobial agents is often explored [25-28]. Sensitivity to levofloxacin was seen in 66.7% of isolates in our study. In certain situations, combination therapy or alternative routes of drug administration such as in aerosol form for pulmonary infections may be considered [29].

The crude mortality rate for patients with infection with this pathogen has been reported within the range of 14 to 69%. In our series, one patient succumbed to the infection (11.1%). A systematic review has highlighted that a significantly higher mortality occurs in patients treated with an initially inappropriate antibiotic, 61% as opposed to 30%. And, up to 37.5% of mortality was found to be attributable to Stenotrophomonas maltophilia infections. [30] From our series, we can note that outcomes of S. maltophilia infections have been varied, with two patients who had skin wound infections having a clinically non-significant course even with multi-drug resistance to the pathogen, whereas those with abdominal and thoracic cavity infections or bloodstream infections, especially in the presence of an adverse risk factor or an underlying serious surgical complication, having a significant clinical course. This re-iterates the fact that clinicians should not underestimate the clinical significance of these infections. In conclusion, Stenotrophomonas maltophilia infections, even though unusual, causes serious clinical manifestations with high morbidity and mortality rates and requires pinpoint antimicrobial therapy in view of several resistance patterns. These are opportunistic hospital-acquired infections which occur in patients with one or more adverse risk factors. Such risk factors become very prominent for patients being treated for cancer. The judicious use of currently available antimicrobial agents known as Antimicrobial Stewardship with pro-active hospital infection control policies will go a long way in curbing this menace.

Acknowledgments <italic id="italic-532b6e07fea4bc0f91944ff987709fa4">Funding<italic id="italic-7483b4e00466b3fbdeef350ad94cf188"/></italic>

None

<italic id="italic-50ff496cad891eec6603df6712541205">Competing interests<italic id="italic-495dc86772eac88b953d13b2e1eaef72"/></italic>

None

<italic id="italic-5">Author contributions<italic id="italic-6"/></italic>

Author contributions: Both authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Amrita Talukdar and Gaurav Das. The first draft of the manuscript was written by Amrita Talukdar and Gaurav Das. Both authors read and approved the final manuscript.

<italic id="italic-7">Data availability<italic id="italic-8"/></italic>

The datasets generated during and analysed during the current study are available with the corresponding author on reasonable request and are not available publicly as per the permissions obtained from Institutional Ethics Committee (IEC).

<italic id="italic-9">Ethics Approval<italic id="italic-10"/></italic>

This study was performed in line with the principles of the Declaration of Helsinki and the Indian Good Clinical Practice. Approval was granted by the Institutional Ethics Committee.

<italic id="italic-11">Consent to participate<italic id="italic-12"/></italic>

Waiver of consent was obtained from the Institutional Ethics Committee by virtue of this being a retrospective and observational study using de-identified patient information and variables already present in the hospital information system.

References 1 01 2-41 25 2012 10.1128/CMR.00019-11 Brooke JS Clinical Microbiology Reviews Stenotrophomonas maltophilia: an emerging global opportunistic pathogen 15 12 12 1602-1609 45 2007 10.1086/522998 Safdar A Rolston KV Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America Stenotrophomonas maltophilia: changing spectrum of a serious bacterial pathogen in patients with cancer 1 01 57-80 11 1998 10.1128/CMR.11.1.57 Denton M. Kerr K. G. Clinical Microbiology Reviews Microbiological and clinical aspects of infection associated with Stenotrophomonas maltophilia 2 10 101-108 70 2008 10.1016/j.jhin.2008.05.020 Paez JJG Costa S. F. The Journal of Hospital Infection Risk factors associated with mortality of infections caused by Stenotrophomonas maltophilia: a systematic review 10 10 986-991 12 2006 10.1111/j.1469-0691.2006.01511.x Lai C.-H. Wong W.-W. Chin C. Huang C.-K. Lin H.-H. Chen W.-F. Yu K.-W. Liu C.-Y. Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases Central venous catheter-related Stenotrophomonas maltophilia bacteraemia and associated relapsing bacteraemia in haematology and oncology patients 5 05 605-608 29 2010 10.1007/s10096-010-0882-6 Araoka H. Baba M. Yoneyama A. European Journal of Clinical Microbiology & Infectious Diseases: Official Publication of the European Society of Clinical Microbiology Risk factors for mortality among patients with Stenotrophomonas maltophilia bacteremia in Tokyo, Japan, 1996-2009 4 04 269-274 24 2003 10.1086/502197 Apisarnthanarak A Mayfield JL Garison T McLendon PM DiPersio JF Fraser VJ Polish LB Infection Control and Hospital Epidemiology Risk factors for Stenotrophomonas maltophilia bacteremia in oncology patients: a case-control study 133 138 13 1963 Hugh R Leifson E Nomencl Taxon A description of the type strain of Pseudomonas maltophilia. Int. Bull. Bacteriol 3 07 606-609 43 1993 10.1099/00207713-43-3-606 Palleroni N. J. Bradbury J. F. International Journal of Systematic Bacteriology Stenotrophomonas, a new bacterial genus for Xanthomonas maltophilia (Hugh 1980) Swings et al. 1983 2 03 124-127 63 2010 Yorioka K Oie S Kamiya A Japanese Journal of Infectious Diseases Microbial contamination of suction tubes attached to suction instruments and preventive methods 4 12 289-292 49 2001 10.1053/jhin.2001.1099 Rogues A. M. Maugein J. Allery A. Fleureau C. Boulestreau H. Surcin S. Bebear C. Janvier G. Gachie J. P. The Journal of Hospital Infection Electronic ventilator temperature sensors as a potential source of respiratory tract colonization with Stenotrophomonas maltophilia 3 11 180-183 55 2003 10.1016/s0195-6701(03)00299-8 Denton M. Rajgopal A. Mooney L. Qureshi A. Kerr K. G. Keer V. Pollard K. Peckham D. G. Conway S. P. The Journal of Hospital Infection Stenotrophomonas maltophilia contamination of nebulizers used to deliver aerosolized therapy to inpatients with cystic fibrosis 11 11 756-758 20 1999 10.1086/501578 Klausner J. D. Zukerman C. Limaye A. P. Corey L. Infection Control and Hospital Epidemiology Outbreak of Stenotrophomonas maltophilia bacteremia among patients undergoing bone marrow transplantation: association with faulty replacement of handwashing soap 6 997-1003 12 1990 10.1093/clinids/12.6.997 Khardori N. Elting L. Wong E. Schable B. Bodey G. P. Reviews of Infectious Diseases Nosocomial infections due to Xanthomonas maltophilia (Pseudomonas maltophilia) in patients with cancer 4 246-250 37 1991 10.1159/000238862 Cullmann W. Chemotherapy Antibiotic susceptibility and outer membrane proteins of clinical Xanthomonas maltophilia isolates 4 10 208-213 35 1991 10.1099/00222615-35-4-208 Akova M. Bonfiglio G. Livermore D. M. Journal of Medical Microbiology Susceptibility to beta-lactam antibiotics of mutant strains of Xanthomonas maltophilia with high- and low-level constitutive expression of L1 and L2 beta-lactamases 6 06 1131-1134 24 1997 10.1086/513652 Carmeli Y. Samore M. H. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America Comparison of treatment with imipenem vs. ceftazidime as a predisposing factor for nosocomial acquisition of Stenotrophomonas maltophilia: a historical cohort study 4 04 229-237 26 2007 10.1007/s10096-007-0279-3 Nicodemo A. C. Paez JJG European Journal of Clinical Microbiology & Infectious Diseases: Official Publication of the European Society of Clinical Microbiology Antimicrobial therapy for Stenotrophomonas maltophilia infections 7 07 495-501 101 2002 Liaw S Teng L Hsueh P Ho S Luh K Journal of the Formosan Medical Association = Taiwan Yi Zhi In vitro activities of antimicrobial combinations against clinical isolates of Stenotrophomonas maltophilia 6 08 655-660 4 2009 10.2217/fmb.09.45 Sanchez MB Hernandez A Martinez JL Future Microbiology Stenotrophomonas maltophilia drug resistance 5 11 889-894 62 2008 10.1093/jac/dkn301 Falagas ME Valkimadi P Huang Y Matthaiou DK Hsueh P The Journal of Antimicrobial Chemotherapy Therapeutic options for Stenotrophomonas maltophilia infections beyond co-trimoxazole: a systematic review 5 05 1140-1142 41 1997 10.1128/AAC.41.5.1140 Alonso A. Martínez J. L. Antimicrobial Agents and Chemotherapy Multiple antibiotic resistance in Stenotrophomonas maltophilia 18 09 23 5 2006 10.1186/1476-0711-5-23 Al-Jasser AM Annals of Clinical Microbiology and Antimicrobials Stenotrophomonas maltophilia resistant to trimethoprim-sulfamethoxazole: an increasing problem 4 04 559-565 13 2007 10.3201/eid1304.061378 Toleman MA Bennett PM Bennett DMC Jones RN Walsh TR Emerging Infectious Diseases Global emergence of trimethoprim/sulfamethoxazole resistance in Stenotrophomonas maltophilia mediated by acquisition of sul genes 3 03 946-953 48 2004 10.1128/AAC.48.3.946-953.2004 Ba BB Feghali H Arpin C Saux M Quentin C Antimicrobial Agents and Chemotherapy Activities of ciprofloxacin and moxifloxacin against Stenotrophomonas maltophilia and emergence of resistant mutants in an in vitro pharmacokinetic-pharmacodynamic model 4 10 664-689 22 2009 10.1128/CMR.00016-09 Strahilevitz J Jacoby GA Hooper DC Robicsek A Clinical Microbiology Reviews Plasmid-mediated quinolone resistance: a multifaceted threat 09 10 10 1226 10 2021 10.3390/antibiotics10101226 Gibb J Wong DW Antibiotics (Basel, Switzerland) Antimicrobial Treatment Strategies for Stenotrophomonas maltophilia: A Focus on Novel Therapies 1 01 39-43 51 2005 10.1016/j.diagmicrobio.2004.09.002 Zelenitsky SA Iacovides H Ariano RE Harding GKM Diagnostic Microbiology and Infectious Disease Antibiotic combinations significantly more active than monotherapy in an in vitro infection model of Stenotrophomonas maltophilia 3 09 107-114 27 2009 10.1002/hon.898 Rolston KVI Hematological Oncology New antimicrobial agents for the treatment of bacterial infections in cancer patients 9 11 1103-1109 4 2009 10.2217/fmb.09.84 Falagas ME Kastoris AC Vouloumanou EK Rafailidis PI Kapaskelis AM Dimopoulos G Future Microbiology Attributable mortality of Stenotrophomonas maltophilia infections: a systematic review of the literature