Necrotizing Pancreatitis Infected with Stenotrophomonas maltophilia: An Emerging Rare Multidrug-Resistant Organism

Stenotrophomonas maltophilia (SM) is a multidrug-resistant, Gram-negative (GN) bacillus that is an increasingly recognized nosocomial and environment pathogen. It is intrinsically resistant to carbapenems, a drug commonly utilized in the management of necrotizing pancreatitis (NP). We report a 21-year-old immunocompetent female with NP complicated by pancreatic fluid collection (PFC) infected with SM. One-third of patients with NP will develop infections by GN bacteria, while broad-spectrum antibiotics, including carbapenems, cover most infections, trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line treatment antibiotic for SM. This case is critical because it highlights a rare pathogen that should be considered a causal pathogen in patients who do not respond to their care plan.


Introduction
SM is an aerobic, multidrug-resistant, GN, and ubiquitous bacillus. It is an environmental pathogen that has become an increasingly important cause of nosocomial infections [1][2][3][4]. Its pathogenicity has led to an escalating number of cases in immunocompromised patients, patients on mechanical ventilation, and patients subject to invasive procedures [1][2][3][4]. SM can lead to several medical conditions including soft tissue infections, endocarditis, pneumonia, meningitis, and peritonitis, but not limited to bacteremia [1][2][3][4]. SM is consistently resistant to multiple antibiotics, including carbapenems, the latter being a drug commonly used in the management of NP [3]. Traditionally, the drug of choice (DOC) of SM infections has been with the bacteriostatic compound TMP-SMX [3].
We report a patient with NP complicated by a PFC infected with SM. Te patient was successfully treated with endoscopic interventions and antibiogram-based antibiotic therapy. To our knowledge, there are only a few documented cases of PFC infected by SM, but none in an otherwise immunocompetent patient whose likely source was the community. Physicians treating patients with severe NP, especially in those with extended hospital stay in the intensive care unit (ICU), multiple comorbidities, exposure to prosthetic devices or other equipment, and prolonged exposure to broad-spectrum antibiotics such as carbapenems should be aware of SM as a potential pathogen in their patients.

Case Presentation
A 21-year-old female presented to the emergency department (ED) with one day of vomiting and progressive and severe abdominal pain (AP) localized to the right upper quadrant and epigastric pain radiating to the back. She had nausea for the prior few weeks, which she had attributed to her pregnancy. She also had darker-colored urine and claycolored stools. Her past medical history was signifcant for a spontaneous vaginal delivery two weeks prior and primary hypothyroidism appropriately managed with medical therapy (TSH-3.210 μIU/mL/T4-0.97 μg/dL on 100 mcg Synthroid). On physical examination, the patient is obese (BMI 32.12 kg/m 2 ), temperature of 98.3 F, heart rate of 63 beats per minute, and blood pressure of 128/66 mm·Hg. She appeared mildly jaundiced without any stigmata of chronic liver disease. Abdominal examination revealed a soft and nondistended abdomen positive for epigastric tenderness. Te patient denied any history of alcohol abuse. Admission laboratory values were hemoglobin of 14.2 gm/dL, leucocyte count 15.6/mcl, platelet count 371/mcl, serum glucose 139 mg/dL, serum aspartate transaminase (AST) 331 IU/L, serum alanine transaminase (ALT) 522 IU/L, total bilirubin 6.2 mg/dL, blood sugar ranging 93-117 mg/dL, triglycerides 80 mmol/L, amylase 1847 U/L, and lipase >8000 U/L.
Te patient subsequently had magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) revealing severe NP involving the body and predominantly the tail of the pancreas, cholelithiasis without biliary ductal dilation or visible stones, and ascites with small bilateral pleural efusions. Te patient was initially treated with intravenous fuids (IV), IV piperacillin-tazobactam (PT), and kept NPO (nothing by mouth). Te patient became febrile a few days into admission leading to a computerized tomography (CT) scan done on day (D) 4, which showed extensive NP and peripancreatic fuid in the retro gastric region. Despite antipyretic medications, she continued to be febrile. On D8, a repeat CT scan showed NP with a large developing PFC collection measuring 13.2 × 5.5 cm in cross-section and 12.8 cm in craniocaudal length ( Figure 1). Te patient was then started on a seven-day IV meropenem and vancomycin course. A CT-guided fne-needle aspiration done on D10 withdrew fve cc of serosanguinous fuid, which was found to be sterile. Te patient's hospital course continued to be complicated by fevers and AP. On D16, the PFC had reached a 13 cm anteroposterior diameter, replacing the pancreatic body and tail seen. On D17, the patient started to feel better and demanded to go home. She was informed that the pseudocyst was quite large and would not resolve without intervention.
On day 27, she returned as her symptoms returned and had an esophago-gastroduodenoscopy performed frst, before stent placement, using a gastroscope (GIF-H190; Olympus, Tokyo, Japan). Te esophagus and stomach were cleared of any retained particulate matter with water lavage and suction. Te routine forward-view examination allowed the endoscopist to evaluate for other possible pathologies and identify any areas with extrinsic compression.
Ten, a linear echoendoscope (GF-UCT180; Olympus, Tokyo, Japan) was used for the echo-endoscopic portion of the procedure. Under sonographic guidance, the PFC was carefully evaluated for an internal vessel, solid debris, and location in relation to the gastric wall. An efacement between the gastric and cystic walls with <1 cm distance and absence of vascular structures in the needle trajectory was confrmed under sonographic guidance before stent placement.
An ELAMS (Boston Scientifc, USA) was placed by puncturing into the fuid collection either directly under a "pure-cut" generator setting or over the guidewire after a fne-needle aspiration needle pierced the cyst. Te inner fange was deployed frst under endosonographic guidance. Te opened fange was then pulled into the cyst wall, pressing against its opposing stomach wall. Ten, the outer fange was deployed inside the gastric lumen, confrmed by both endoscopy and fuoroscopy. Carbon dioxide was used for insufation (UCR, Olympus, Japan) during the entire length of the procedure.
Puncturing the gastric wall, stent deployment, and fnal stent position was guided and confrmed under EUS with additional fuoroscopic guidance. Fluoroscopy was used primarily to monitor the stent deployment process and evaluate the stent position, while other utilities such as assessing the needle trajectory while puncturing the fuid collection, aiding in guidewire placement before stent placement, and documenting the stent position for subsequent evaluation when stent migration was suspected were also applied. Cystic fuid was aggressively suctioned to minimize aspiration risk. 600 mL of necrotic debris was noted to drain ( Figure 2). Te patient was discharged home.
On D31, the patient returned to the ED complaining of fever (101.1 F), AP radiating to her back, and vomiting. A CT scan was performed and showed an interval decrease in size of the sizeable peripancreatic pseudocyst, now measuring 8.7 mm maximally anteroposterior diameter and interval air related to communication with the tip of the stomach. She was then readmitted for an endoscopic pancreatic necrosectomy (PN) and started on ceftriaxone 2 g ever 12 hours. On D35, extensive PN was performed, and the walled-of necrotic cavity was irrigated with 1.5% hydrogen peroxide. Te cystogastrostomy was stented concentrically with the AXIOS stent (10°F). Antibiotics were also switched to IV meropenem and IV vancomycin empirically for another seven-day course.
Gram stain of the PFC revealed the presence of Grampositive cocci in pairs and chains and GN bacilli. Te fuid cultures grew methicillin-resistantStaphylococcus aureus (MRSA) and 2.5 × 10 7 cfu/mL SM. Te antibiotic susceptibility report (antibiogram) revealed that MRSA was sensitive to clindamycin, TMP-SMX, and vancomycin. SM was susceptible to TMP-SMX. Antibiotic therapy was then narrowed to TMP-SMX (800 − 160 mg 4 times a day) and vancomycin (1 g every 12 hours) on D37. Te patient improved on these antibiotics and was no longer febrile and no longer had signifcant AP. On D48, the patient was discharged on Linezolid 600 mg every 12 hours for a complete antibiotic course of 21 days.

Case Reports in Gastrointestinal Medicine
She underwent three more endoscopic necrosectomies with hydrogen peroxide irrigation. Te AXIOS stent was removed on the patient's third endoscopic necrosectomy at D60. One month after the last endoscopic pancreatic drainage, the patient underwent laparoscopic cholecystectomy for acute gallstone pancreatitis. Imaging at this time revealed the gallbladder to be thickened and contracted with cholelithiasis and resolution of the pancreatic pseudocyst.

Discussion
SM is a more commonly known as a nosocomial pathogen but is also a rising cause of community-acquired infections. SM is commonly associated with respiratory tract infections, bacteremia, biliary sepsis, endocarditis, meningitis, and urinary tract infections but is also associated with other multisystem infections [1][2][3][4]. Te literature review showed cases infected with SM as one of the polymicrobial infections of the respiratory tract of cystic fbrosis [5]. Cases of community-acquired SM infections have been reported, but the incidence of hospital-acquired SM infections has been increasing, particularly in the immunocompromised population [2][3][4]. In both nosocomial and environmental settings, the organism has been known to be isolated from aqueous associated sources [3]. Tese include sources such as animals, lakes, hemodialysis water, and even dialysate samples [3]. One key virulence factor is its ability to use its polar fagella to form a bioflm [3]. Te bioflm allows it to adhere to plastics and fnd itself on the surfaces of intravenous (IV) cannulae, prosthetic devices, and even nebulizers [3]. Tere are reports of SM infecting the biliary tree, but it is an unusual cause of necrotizing pancreatitis with infected pancreatic fuid collections [6]. However, one study compared nonzymogenic with zymogenic bacteria as a cause of pancreatitis and pancreatic necrosis and revealed an increased infection rate of nonzymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia) compared to zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae) (P < 0.01) [7]. Te molecular and cellular mechanisms essential for its survival, persistence, and pathogenesis are likely the reason for its ability to persist in nutrient-poor regions such as fuid collections [3]. Tere are some reports in the literature of similar pathogens that have been pathogenic likely by their ability to form a bioflm; however, in this case, we do not believe the patient encountered any surgical instrumentation exposing her to any such pathogens.
Te source of the patient's infection remains unclear. She could have acquired the pathogen from her environment, and it is still possible that it somehow colonized her biliary tree. However, she likely developed the infection [11] due to selective pressure from multiple antibiotic courses, which led to SM being the predominant infection. We believe that it was unlikely to be colonization as she had not had any surgical procedures that would have predisposed her to colonization prior to the diagnosis. She also had a signifcant amount of the bacteria in the pancreatic fuid and responded extremely well after the antibiotic treatment was changed to target the SM. During her hospitalization, she received one entire seven-day course of meropenem and vancomycin and numerous short courses of ceftriaxone and piperacillintazobactam. Had a more common pathogen been the cause for her pancreatitis, her disease course should have resolved after receiving multiple lines of frst-line antibiotics. We believe the multiple courses of the antibiotics actually worsened the disease through selective pressure.
Te patient noted that her symptoms of nausea started at the end of her pregnancy, although she attributed the symptoms to the pregnancy itself. She had a healthy delivery and was immunocompetent for the remainder of her illness. She had no prior history of serious medical diseases and had no family history of immune-compromising medical conditions. Her blood cell lines also remained within normal limits for the duration of her treatment. A few reported cases of biliary sepsis have been seen in the past postinstrumentation with biliary drainage catheters [6]. Tis may show that the organism has the potential to colonize the biliary tree. Tis patient, however, had no prior instrumentation that may have led to colonization. Her PFC may have become infected with SM and in her instance, become a true pathogen; conceivably, this patient may have Case Reports in Gastrointestinal Medicine developed an invasive infection due to SM as a result of selective pressure caused by the multiple courses of antibiotics that she received. Indeed, during her hospital stay, she received various courses of antibiotics, including two days of ceftriaxone, four days of PT, nine days of meropenem, and nine days of vancomycin before her culture returned positive for SM. Her antibiotics were narrowed to TMP-SMX and vancomycin. Tis case is critical because it is the only welldocumented case of documented SM infection of a PFC in an immunocompetent patient whose likely source was the environment. Trough selective pressure from multiple antibiotics, it became a true pathogen. We expect that there have been numerous cases prior that have passed with this organism unidentifed. It is essential to consider SM as a possible cause of infection of PFC in patients that initial broad-spectrum antibiotics do not show improvement. A human study investigating the levels of penetration of diferent broad-spectrum antibiotics found that ciprofoxacin, ofoxacin, imipenem, and pefoxacin provided sufcient tissue concentrations to reduce mortality and rates of infection [8]. Tese antibiotics cover the most common microbes identifed in infected PN, which are Escherichia coli (20.0%) and Enterococcus faecalis and faecium (22.5% and 20.0%) [9]. Many cases, however, are shown to be polymicrobial [9]. SM is known for its resistance to multiple broad-spectrum antibiotics, including imipenem that current guidelines recommend using as the frst line. As previously mentioned, SM is more sensitive to TMP-SMX alone or in synergistic combinations. Few previous studies showed that although trimethoprimsulfamethoxazole is the drug of choice when studied in vitro, few other medicines, including ticarcillinclavulanic acid, minocycline, some of the new fuoroquinolones, and tigecycline, are useful as well [10]. Considering there are only a few documented case reports, it is unnecessary to cover empirically for SM initially in these patients, but suspected infected PFC should be cultured and regularly reviewed in patients with progressively worsening clinical pictures. Tese patients may not have appropriate antibiotic coverage despite the broad-spectrum antibiotics, as in the case of our patient. A physician should have a low index of suspicion in patients whose clinical condition is deteriorating and whose patients have had a prolonged course of carbapenems.

Data Availability
Te data used to support the fndings of this publication are included in this article and references.

Additional Points
Key Highlights. (i) Tis patient is an unusual case of Stenotrophomonas maltophilia and emphasizes the need to explore rare infectious agents when the patient is not responsive to treatment. (ii) Tere is also an emphasis on treating with the most efective antibiotic for the infectious agent, which in this was trimethoprim-sulfamethoxazole.
(iii) Interventional methods (such as, in this case, endoscopic necrosectomy) are essential for both source control and acquiring samples for culture and sensitivity.