Case ReportClostridium subterminale Septicemia in a PatientwithMetastaticGastrointestinal Adenocarcinoma

Kevin M. Trapani ,1 Leigh J. Boghossian ,2 and Elizabeth Caskey3

1Nazareth Hospital, Philadelphia, PA, USA2Lankenau Medical Center, Wynnewood, PA, USA3Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA

Correspondence should be addressed to Kevin M. Trapani; kevintrapani44@gmail.com

Received 5 November 2017; Accepted 26 April 2018; Published 22 May 2018

Academic Editor: Gernot Walder

Copyright © 2018 KevinM. Trapani et al.,is is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Clostridium subterminale is a rare member of the Clostridiaceae family that is rarely cultured. ,is report examines a case ofClostridium subterminale cultured from the blood of a 72-year-old man who was ultimately diagnosed with metastatic gastroin-testinal (GI) adenocarcinoma.,e patient was receiving treatment for nosocomial pneumonia prior to culture of theC. subterminale,which led to suspicion for malignancy. Extensive GI and oncologic workup demonstrated multiple comorbidities and a primary GIcancer, which likely caused a breach in the GImucosa andC. subterminale entrance into the bloodstream. After a prolonged intensivecare unit (ICU) stay, the patient died on hospital day 23. ,ough rarely reported, C. subterminale septicemia has been demonstratedin patients with malignancy, specifically of the GI tract. ,erefore, this case represents a typical C. subterminale septicemia patient.Given the prevalence of Clostridia and the contemporary emergence of multidrug resistant (MDR)microorganisms, both typical andatypical cases regarding rare members of the species have a significant role in the clinical management and public health planning.

1. Introduction

,e Clostridium genus is comprised of mostly Gram-positive,variably spore-forming anaerobic to aerotolerant rods in pairsor short chains.,ey most commonly colonize the human GIand female genitourinary tracts, but more rarely, the skin’ssurface or the oral cavity. ,ey are widely found in the en-vironment, as they are components of the digestive flora inmammals [1]. Given the ubiquity ofClostridia, their reservoirsinclude humans, animals, and the environment. Only a few ofthe nearly 200 Clostridia species are pathogenic to humans,but while they are some of the most extensively studiedpathogenic anaerobes, there is limited literature regardingClostridium subterminale [1]. Further, while there are manygeneralizations regarding Clostridia–frequently opportunisticpathogens that produce spores and protein exotoxins–members of the genus exhibit such heterogeneity thatthere are many exceptions or only specific conditions underwhich generalizations will apply [1]. ,erefore, novel cases,especially of the lesser-studied organisms, are of particularimportance among Clostridium literature.

2. Case Report

A 72-year-old male with a past medical history of quadri-plegia, hypertension, hyperlipidemia, neurogenic bladder,type 2 diabetes mellitus, chronic obstructive pulmonarydisease, and chronic hepatitis presented to the emergencydepartment with an acute change in mental status. He wasa full-time resident at an assisted living nursing home, andhis baseline mental status was awake, alert, and oriented toperson, place, and time (AAOx3). Upon arrival in theemergency department, he was oriented only to self. Prior tothis admission, the patient was being treated for a urinarytract infection and was on day seven of nitrofurantoin andcefepime. On examination, he was hypotensive at a bloodpressure of 81/59mmHg, pulse rate of 115 beats per minute,respiratory rate of 21 breaths per minute, and oxygen sat-uration of 78%while breathing ambient air. He was in visiblerespiratory distress and was lethargic, but arousable. Hereceived a nebulizer treatment and was placed on a non-rebreather mask at 6 liters, after which his oxygen saturationrose to 99%. A chest X-ray was taken and revealed left lower

HindawiCase Reports in Infectious DiseasesVolume 2018, Article ID 6031510, 3 pageshttps://doi.org/10.1155/2018/6031510

lobe pneumonia. His urinalysis was positive for an infectiondespite current antibiotic compliance. He began vancomycinand piperacillin/tazobactam for health care-associatedpneumonia and was admitted to the ICU. Respiratory sta-tus worsened, and he required intubation.

Despite these interventions, on his second day of ad-mission, he continued to have copious clear secretions.Pulmonology diagnosed him with aspiration pneumoniaand sputum cultures were obtained, which demonstratedmoderate white blood cells, rare epithelial cells, few Gram-positive cocci in clusters, and rare yeast. His antibiotics wereadjusted for sensitivities to vancomycin and meropenem. Tofurther evaluate his ongoing pulmonary issues, a chest CTscan was obtained, revealing increasing bilateral pleuraleffusions and patchy sclerotic foci concerning for possiblebone metastases, enlarged mediastinal lymph nodes, andnodular infiltrate in the right mid- and upper lung fields.Gastroenterology was consulted for colonoscopy to identifya primary tumor, but the patient was deemed too unstablefor a nonemergent procedure. ,oracocentesis revealedexudative pleural effusions negative for malignancy. Ab-dominal and pelvic CT demonstrated hydronephrosis anda right-sided staghorn renal calculus but no masses.

With these interventions, our patient began to improve,yet daily sedation interruptions and spontaneous breathingtrials failed. Initial blood culture results showed Gram-positive bacilli, and further speciation of the organismwas requested. On day 13, blood cultures were finalized andgrew Clostridium subterminale. Sputum and stool testingshowed Pseudomonas aeruginosa and Clostridium difficile,so metronidazole was started. Gastroenterology again statedthat the patient was too unstable for colonoscopy andsuggested a bone biopsy, which he underwent the followingday. ,e preliminary pathology report stated that the bonebiopsy was likely malignant adenocarcinoma, which wasconfirmed on hospital day 21. Biopsy indicated that thetumor was positive for markers CK7 and CA19-9; primarysites with this immunophenotypic profile include the upper GItract and pancreaticobiliary system. Carcinoembryonic antigen(CEA) was elevated at 73.8 (normal CEA nonsmokers< 5.1;smokers< 6.6) and CA19-9 was 3,146 (normal< 45). Per on-cology, he was not a candidate for any interventions due to hiscomorbidities.

On day 23, he had increasing secretions and was agitateddespite completion of his antibiotic course. ,e patient’sthree daughters decided on terminal extubation, and comfortmeasures were initiated. At 21 :12 on hospital day 23, thepatient was pronounced dead.

3. Discussion

In general, the pathogenic species of Clostridium arenot invasive. As such, available literature has shownthat pathogenic Clostridia transmission occurs throughbreaches in the GI tract and wound contamination al-though spontaneous cases have occurred. Most Clostridiumspecies have shown susceptibility to common antibiotics,including penicillin, clindamycin, chloramphenicol, piper-acillin, metronidazole, imipenem, and combinations of

β-lactams with β-lactamase inhibitors; others show variableresistance [1]. Clostridia also exhibit the ability to formabundant, largely heat-resistant endospores, requiring specificmethods for extermination. Clostridium toxins can causea variety of infections, including abscesses, tissue necrosis,and empyema. Symptoms of Clostridial septicemia can bevague, often fever, chills, and leukocytosis. ,e morbidityfrom Clostridial bacteremia is estimated to be 25–50% [1].Among the Clostridia species, Clostridium difficile, Clostrid-ium perfringens, and Clostridium botulinum largely pre-dominate the available literature and reported clinical cases.,ere are a number of other species notable for infectionamong the immunocompromised, about which there islittle available information. One such species is Clostridiumsubterminale.

In Minelli et al.’s study of normal fecal flora in healthyfemales, Clostridia were found in the intestinal flora of everysubject. Of the Clostridium species, C. subterminale wasnoted to be one of the most frequently encountered or-ganisms [2]. While this study specifically examined healthysubjects, the authors state, “human flora does not varygreatly from individual to individual,” noting that intestinalflora appears stable in the absence of antimicrobial therapyor disease [2]. In fact, intestinal flora remains as it wasestablished in infancy [3]. Furthermore, C. subterminaledoes not induce gut-associated lymphoid tissue (GALT), oneof the GI tract’s inherent mechanisms for protection [4]. Inlight of this, we hypothesize that our patient’s comorbiditiesof GI malignancy and C. difficile led to breaches in thecolonic mucosa and ultimately C. subterminale septicemia.Additionally, his colonoscopy record from 2014 indicatedcolonic polyps and diverticuli, which are consistent withimpaired GI tract integrity. ,erefore, C. subterminale likelyinfiltrated his intestinal mucosa, accessing his bloodstreamand causing bacteremia.

,ere is significant variability in disease processes causedby pathogenic Clostridia. Furthermore, reliable and efficientidentification of Clostridial isolates is imperative to establishbest management practices. Because of the scarcity of casereports involving C. subterminale septicemia, it is worthnoting the sources of C. subterminale infection. Conse-quently, many of these sources are from compromised tissueand patients with malignancies, both of which were presentin our patient. Sources of C. subterminale include but are notlimited to abscesses, blood, and wounds. One case report ofC. subterminale septicemia in a patient with esophagealcancer stated that the likely source of the C. subterminaleinfection was mucosal manipulation during stent placement orrepeat endoscopy [5]. Another report describedC. subterminalesepticemia potentially from ulceration near the distaledge of the anal canal in a 51-year-old patient with acutelymphoblastic leukemia [6]. In another case report on C.subterminale septicemia in a 41-year-old chronic mye-logenous leukemia patient with prior cord blood trans-plantation, the authors describe the plausibility of previousGI tract colonization by C. subterminale, which sub-sequently accessed the blood though damaged mucosa [7].In summary, many of the cases of C. subterminale septi-cemia are from patients who were immunosuppressed

2 Case Reports in Infectious Diseases

secondary to malignancy. Additionally, there was evidenceof damage to the gastric mucosa in many of these cases,supporting the theory that disruption of the mucosal tissueallowed C. subterminale’s entrance into the blood. Dueto the frequent association between GI malignancy andC. subterminale, we recommend looking for a GI cancer inpatients with C. subterminale septicemia.

Despite lack of clinical improvement with treatment inour patient, some cases of C. subterminale bacteremiarecovered. Timely treatment after septicemia identificationleads to decreased morbidity and mortality, as well as lowerhealthcare costs. Given the emergence of MDR organismsand the high frequency of comorbidities and immuno-suppression, infection represents a significant cause ofmorbidity and mortality. Additionally, the cost in dis-ability adjusted life-years from bacteremia and the risk ofhealthcare-associated infections (HAI’s) are significant. Inthe US, the annual direct costs of HAI’s are estimated to be$28.4 to $33.8 billion [8]. In Pennsylvania alone, an in-dependent state agency reported that one year’s worth ofhospital admissions associated with infections incurred1,510 additional deaths, 205,000 additional hospital days,and $2 billion in extra hospital charges compared tohospital admissions wherein infections had not occurred[9]. ,e same agency presented information in their2012 report that procedures associated with the GI tracthad the highest percentage of surgical site infections [9].C. subterminale colonizes the GI tract, and therefore propermanagement is essential in reducing cost, length ofstay, and most importantly, morbidity and mortality. Itis clear that efforts to track, prevent, and manage patho-genic bacteria, particularly those that significantly affectimmunocompromised and/or hospitalized patients, willrepresent large improvements to public health in life-yearsand cost savings.

,e significance of the current case report is four-fold:(1) Clostridium subterminale is exceedingly rare, and theavailable literature on the organism is extremely limited;this paper contributes to that important gap in the liter-ature; (2) it demonstrates what we believe is the typicalC. subterminale septicemia patient; (3) it addresses thetraits of C. subterminale and the commonalities betweenC. subterminale and a number of other individual Clostridialstrains; and (4) it provides a compiled source of much of theinformation available regarding C. subterminale. Limitationsto this report include the common issue of Clostridial mis-identification; potential for contamination; and lack of accessto this patient’s complete medical, social, and family history.Our recommendations for future studies are to documentcases ofC. subterminale using provided and available literatureand to further explore its presentation. We hope this willperpetuate the search for avenues to prevent and treat bac-teremia, particularly in the immunocompromised with raremicrobial infections.

Conflicts of Interest

,e authors declare that there are no conflicts of interestregarding the publication of this paper.

References

[1] C. L. Wells and T. D. Wilkins, “Clostridia: Spore-forminganaerobic bacilli,” in Medical Microbiology, S. Baron, Ed.,University of Texas Medical Branch at Galveston, Galveston,TX, USA, 4th edition, 1996.

[2] E. B. Minelli, A. Benini, A. M. Beghini, R. Cerutti, andG. Nardo, “Bacterial faecal flora in healthy women of differentages,” Microbial Ecology in Health and Disease, vol. 6, no. 2,pp. 43–51, 1993.

[3] J. G. Bartlett, “Anaerobic bacteria: history and role in normalhuman flora,” inAnaerobic Bacterial Infections, S. B. Calderwoodand A. R. ,orner, Eds., UpToDate, Waltham, MA, USA, 2015.

[4] K. Rhee, P. Sethupathi, A. Driks, D. K. Lanning, andK. L. Knight, “Role of commensal bacteria in development ofgut-associated lymphoid tissues and preimmune antibodyrepertoire,” Journal of Immunology, vol. 172, no. 2, pp. 1118–1124, 2004.

[5] S. K. ,ind and J. I. Preis, “Case report: Clostridium sub-terminale septicemia in a patient with esophageal cancer,”ID Cases, vol. 1, no. 3, pp. 47–49, 2014.

[6] D. C. Haussen, F. Y. B. Macedo, C. V. Caperton, andD. C. Zuckerman, “Clostridium subterminale sepsis in adultacute lymphoblastic leukemia,” Leukemia and Lymphoma,vol. 52, no. 6, pp. 1137-1138, 2011.

[7] K. Miyazaki, T. Mori, N. Takayam, Y. Tsukasa, Y. Ikeda, andS. Okamoto, “Clostridium subterminale septicemia in a re-cipient of allogeneic cord blood transplantation,” InternalMedicine, vol. 42, no. 4, pp. 374-375, 2003.

[8] Division of Healthcare Quality Promotion National Center forPreparedness, Detection, and Control of Infectious DiseasesCoordinating Center for Infectious Diseases Centers for DiseaseControl and Prevention. R. Douglas Scott II, Economist. 3eDirect Medical Costs of Healthcare-Associated Infections in U.S.Hospitals and the Benefits of Prevention, 2009, http://www.cdc.gov/HAI/pdfs/hai/Scott_CostPaper.pdf.

[9] Pennsylvania Health Care Cost Containment Council, 3eImpact of Healthcare-associated Infections in Pennsylvania 2010,2012, http://www.phc4.org/reports/hai/10/docs/hai2010report.pdf.

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