Scandinavian Journal of Infectious Diseases, 2014; 46: 73–75

CASE REPORT

Cellulomonas, an emerging pathogen: A case report and review of the literature

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NATALIE MARIAM SALAS1, MERIDETH PREVOST2, DIEDRE HOFINGER2 & HOLLY FLEMING2 From the 1Department of Internal Medicine, University of New Mexico Health Science Center, and 2Department of Infectious Disease, Raymond G Murphy VA Medical Center, Albuquerque, New Mexico, USA

Abstract Cellulomonas is a rare but emerging human pathogen, causing infection in only 4 reported cases in the literature. We present the first case of ascending cholangitis with Cellulomonas bacteremia and sepsis, as well as a brief review of the literature. We summarize every case of Cellulomonas reported in the medical literature, including treatments and outcomes.

Keywords: Bacteremia, bacteria, Cellulomonas, ascending cholangitis, Corynebacterium

Introduction Cellulomonas spp are mostly motile, aerobic to facultative anaerobic, Gram-positive pleomorphic bacilli of the coryneform bacteria family. These are environmental pathogens, typically growing in decaying plant-rich soil. They share genetic similarities to other coryneform bacteria such as Oerskovia and Microbacterium, yet remain a distinct microbiological and clinical entity [1]. Infections with these rare bacteria are on the rise as our ability to detect these pathogens improves. The 2 subspecies Cellulomonas hominis and Cellulomonas denverensis are the most clinically relevant, as they have been the only Cellulomonas species cultured in active human infections [2]. We present the first case of ascending cholangitis in the setting of Cellulomonas bacteremia and review the literature.

Case report An 81-y-old male with a history of peptic ulcer disease, cholecystectomy, Billroth I procedure, interstitial lung disease, and peripheral vascular disease was admitted to the hospital with ascending cholangitis

and pancreatitis secondary to choledocholithiasis. The patient presented with acute onset of fevers, leukocytosis, elevated liver enzymes, and abdominal pain. On physical examination he appeared ill and in mild distress. Vital signs showed a maximum temperature of 38.2°C, pulse of 90/min, blood pressure of 121/64 mmHg, respirations of 18/min, and pulse oximetry of 94% on room air. An abdominal examination was remarkable for exquisite tenderness to palpation in the right upper quadrant. Laboratory data were significant for a white blood cell count of 13,000 cells/mm3 with 92% neutrophils. Liver function tests were remarkable for total bilirubin of 3.5 mg/dl, alkaline phosphatase of 380 U/l, aspartate aminotransferase of 75 U/l, and alanine aminotransferase of 76 U/l. A computed tomography (CT) scan of the abdomen revealed severe dilatation of the intrahepatic and extrahepatic biliary ducts containing multiple non-calcified biliary stones, with subtle stranding localized to the common bile duct, suggesting the possibility of cholangitis. There was also mild dilatation of the pancreatic duct within the pancreatic head and neck. The patient was started on piperacillin–tazobactam and ciprofloxacin with resolution of fever and

Correspondence: N. M. Salas, University of New Mexico Health Science Centre, 2211 Lomas Blvd SE, Albuquerque, New Mexico, 87106, USA. Tel: ⫹ 1 505 720 9252. Fax: ⫹ 505 256 2803. E-mail: [email protected] (Received 11 September 2013 ; accepted 17 September 2013) ISSN 0036-5548 print/ISSN 1651-1980 online © 2014 Informa Healthcare DOI: 10.3109/00365548.2013.847531

82 Present case, 2013

F, female; M, male; CSF, cerebrospinal fluid; IV, intravenous; PO, oral; TMP–SMX, trimethoprim–sulfamethoxazole. aThe first 3 entries are isolates from humans, later identified as Cellulomonas spp, but with no record of their clinical courses; treatment and outcomes are unknown. Four other human isolates containing Cellulomonas exist, but there are no clinical data to suggest that they represent true Cellulomonas infection.

Not speciated Ascending cholangitis, bacteremia

82 30 Ohtaki et al., 2009 [9] Logar and Lejko-Zupanc 2013 [10]

M

C. denverensis Not speciated Cholecystitis, bacteremia Bacterial endocarditis

78 Lai et al., 2009 [8]

F M

Endocarditis, osteomyelitis Not speciated

70 Sharma et al., 2007 [2]

F

Vancomycin IV, piperacillin–tazobactam

Not specified

Vancomycin, ceftazidime (intravitreal/IV) Penicillin, gentamicin (IV), TMP–SMX (PO) Ampicillin–sulbactam (IV) Cefotaxime (IV), gentamicin (IV) Not speciated

Unknown Unknown Unknown Unknown Unknown Unknown C. hominis C. hominis C. denverensis

F Isolated from CSF M Isolated from CSF Unknown Isolated from blood and homograft heart valve M Endophthalmitis Unknown Unknown Unknown

Sex Age, y Reference

Cellulomonas spp is a rare human pathogen. Despite a number of isolates from human sources of unknown clinical significance, there are only 5 case reports where Cellulomonas spp have been cultured in an active human infection (Table I). We report the first case in the medical literature of ascending cholangitis with Cellulomonas bacteremia. The genus Cellulomonas is of the coryneform bacteria family. Cellulomonas spp are aerobic to facultative anaerobic, Gram-positive bacilli that produce smooth convex white to yellow colonies [1,3]. Microscopically, they appear as mostly motile pleomorphic bacilli lacking both spores and capsules [4]. A distinct feature of all Cellulomonas species is their ability to hydrolyze cellulose, with the exception of C. hominis [3]. Definitive speciation of Cellulomonas after culture growth requires 16S rRNA gene sequencing. This technique has led to the identification of 20 Cellulomonas species, as well as distinguishing this genus from other related genera like Oerskovia and Microbacterium. Cellulomonas is an environmental pathogen first identified in soil, dust, and compost [3]. In 1981,

Infection type

Discussion

Funke et al., 1995 [7]a Funke et al., 1995 [7]a Brown et al., 2005 [4]a

Cellulomonas species

Antibiotic therapy

Duration of therapy

Unknown Unknown Unknown

Outcomes

leukocytosis and normalization of liver enzymes. Thirty-nine hours after hospitalization, 4 of 4 blood culture bottles that were drawn prior to antibiotics grew Cellulomonas spp, as identified using the bioMérieux API bacterial identification system. The infectious disease consultants recommended discontinuing ciprofloxacin and initiating vancomycin to treat Cellulomonas bacteremia, with continuation of piperacillin–tazobactam until completion of endoscopic retrograde cholangiopancreatography (ERCP). Repeat blood cultures on hospital day 4 were negative. ERCP was performed 4 days after initiation of antibiotic therapy with stone removal and biliary stent placement. Biliary cultures were negative for Cellulomonas spp but positive for Enterococcus faecalis and Stenotrophomonas maltophilia, which are known gut colonizers and were not treated as active infections. The patient was treated for ascending cholangitis and Cellulomonas bacteremia for which he received antibiotic therapy consisting of piperacillin–tazobactam 3.375 g every 8 h (extended infusion) with the addition of vancomycin 1 g every 12 h for a total of 14 days. Subsequent to his initial hospitalization, the patient underwent 4 ERCP procedures with multiple stent placements. The final biliary stent was removed 5 months after initial hospitalization. The patient was placed on ursodiol therapy without recurrence of stone-related biliary disease.

Infection resolved, stable after 1 y IV for 4 weeks, Infection resolved, PO for 12 weeks stable at 3 months 6 days Infection resolved at discharge 6 weeks, gentamicin was Infection resolved; course discontinued after complicated by valve perforation 2 weeks and valve replacement 14 days Infection resolved, stable after 1.5 y

N. M. Salas et al.

Table I. Reported cases of Cellulomonas infections.

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Cellulomonas as a cause of bacteremia and sepsis Hollis and Weaver described several coryneform clinical isolates as Centers for Disease Control and Prevention (CDC) coryneform group A-3 and A-4 [5]. Later, genetic sequencing confirmed that many species in these groups in fact belonged to the Cellulomonas genus [4]. The most clinically significant species are C. hominis and C. denverensis, as they are the only isolates to be cultured in documented human infections (Table I). Gene sequencing was not performed in our patient. However, it was noted that the Cellulomonas species cultured did not hydrolyze cellulose, leading us to suspect that our patient was infected with C. hominis. For the purpose of this review, we have made a distinction between human isolates and clinical infections. Eight isolates from human sources have been found to contain Cellulomonas spp (Table I). Of these, 4 isolates (2 from the same patient) are known to have caused an infection, though no data on the clinical course or treatment of these infections are available. The first documented clinical infection with Cellulomonas was in 2007 [2]. However, it should be noted that as early as 1989 infections caused by CDC coryneform group A-3 and A-4 had been identified [6]. Cellulomonas was originally thought to be an opportunistic infection [4]. However, the 5 clinical cases reported were in immunocompetent adults. With the exception of 1 case, all patients were over the age of 65 y. It is noteworthy that all of the infections caused by these bacteria have been severe, but patients responded well to appropriate antibiotic therapy. Table I presents all of the Cellulomonas cases reported in the literature [7–10]. The cases of CDC coryneform group A-3 and A-4 infections that were not further speciated, as well as human isolates with no clinical data to support infection, are not included. There are no guidelines for the treatment of Cellulomonas infections. Because there are no recommendations from the Clinical and Laboratory Standards Institute (CLSI) regarding antimicrobial susceptibility to this species, it is recommended to compare the minimum inhibitory concentration (MIC) measurements of susceptibility to those established for streptococci [2]. Cellulomonas spp are generally susceptible to beta-lactams, vancomycin, tetracycline, and rifampin [3]. Our patient was started on piperacillin–tazobactam followed by vancomycin once blood cultures grew Cellulomonas spp. Biliary cultures obtained during ERCP did not grow Cellulomonas but grew other organisms resistant to piperacillin–tazobactam and vancomycin. This leads us to believe that Cellulomonas was the cause of his ascending cholangitis but was eradicated by the time biliary cultures were obtained. Our

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patient received a total of 14 days of antibiotic therapy. The duration of therapy was directed by the site of infection; in this case bacteremia. Site-specific duration of therapy led to complete resolution of infection in all documented cases (Table I). In conclusion, infections caused by Cellulomonas spp are increasing, likely due to a combination of our aging population and our improved ability to detect these organisms. Speciation of these bacteria is made through 16S rRNA gene sequencing. There is a trend toward infections targeting elderly immunocompetent patients. These infections are severe and debilitating, so it is important to not disregard Gram-positive bacilli as contaminants if cultured from a septic patient. Fortunately, these infections respond well to appropriate antibiotic therapy. Declaration of interest: There is no conflict of interest for any of the authors and this paper received no funding. References [1] Whitman WB, Goodfellow M, Kampfer P. Family V. Cellulomonadaceae. In: Whitman WB, Goodfellow M, Kampfer P, editors. Bergey’s manual of systematic bacteriology. Vol. 5. Springer; 2009 pp 701–5. [2] Sharma S, Saffra NA, Chinyadza T, Ghitan M, Chapnick EK. Endocapsular Cellulomonas as a cause of persistent postoperative endophthalmitis. Ophthalmic Surg Lasers Imaging 2008;39:328–30. [3] Funke G, von Graevenitz A, Clarridge JE 3rd, Bernard KA. Clinical microbiology of coryneform bacteria. Clin Microbiol Rev 1997;10:125–59. [4] Brown JM, Frazier RP, Morey RE, Steigerwalt AG, Pellegrini GJ, Daneshvar MI, et al. Phenotypic and genetic characterization of clinical isolates of CDC coryneform group A-3: proposal of a new species of Cellulomonas, Cellulomonas denverensis sp. nov. J Clin Microbiol 2005; 43:1732–7. [5] Hollis DG, Weaver RE. Gram-positive organisms: a guide to identification. Atlanta, GA: Special Bacteriology Section, Centers for Disease Control and Prevention; 1981. [6] Barker C, Leitch J, Brenwald NP, Farrington M. Mixed haematogenous endophthalmitis caused by Candida albicans and CDC fermentative Corynebacterium group A-4. Br J Ophthalmol 1990;74:247–8. [7] Funke G, Ramos CP, Collins MD. Identification of some clinical strains of CDC coryneform group A-3 and A-4 bacteria as Cellulomonas species and proposal of Cellulomonas hominis sp. nov. for some group A-3 strains. J Clin Microbiol 1995;33:2091–7. [8] Lai PC, Chen YS, Lee SS. Infective endocarditis and osteomyelitis caused by Cellulomonas: a case report and review of the literature. Diagn Microbiol Infect Dis 2009;65: 184–7. [9] Ohtaki H, Ohkusu K, Sawamura H, Ohta H, Inoue R, Iwasa J, et al. First report of acute cholecystitis with sepsis caused by Cellulomonas denverensis. J Clin Microbiol 2009;47:3391–3. [10] Logar M, Lejko-Zupanc T. Infective endocarditis caused by Cellulomonas spp. in an intravenous drug user: case report. Wien Klin Wochenschr 2013;125:334–6.

Cellulomonas, an emerging pathogen: a case report and review of the literature.

Cellulomonas is a rare but emerging human pathogen, causing infection in only 4 reported cases in the literature. We present the first case of ascendi...
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