Anaerobe 28 (2014) 1e3

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Ventriculoperitoneal shunt infection caused by Bifidobacterium breve Nuntra Suwantarat a, *, Mark Romagnoli b, Teresa Wakefield b, Karen C. Carroll a, b a b

Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Microbiology Laboratory, Johns Hopkins Hospital, Baltimore, MD, USA

a r t i c l e i n f o

a b s t r a c t

Article history: Received 18 February 2014 Received in revised form 2 April 2014 Accepted 5 April 2014 Available online 19 April 2014

Bifidobacterium breve is a rare cause of human infections. Previously, bacteremia and meningitis caused by this organism linked to probiotic use have been reported in a neonate. We report the first case of a ventriculoperitoneal shunt infection caused by B. breve in an adult without a history of probiotic use. Ó 2014 Elsevier Ltd. All rights reserved.

Keywords: Bifidobacterium breve Ventriculoperitoneal shunt infection Anaerobe Gram-positive rods

1. Introduction Bifidobacterium spp. are anaerobic non-sporeforming Grampositive rods that are commensals in the human oral cavity, intestinal tract, and genitourinary tract [1e5]. B. breve is one of several bacteria that is often used as probiotic therapy [3]. Infections caused by these organisms are rare. We report the first case of a ventriculoperitoneal (VP) shunt infection caused by B. breve. 2. Case report The patient is a 45-year-old Caucasian female, with a history of cerebral palsy, congenital hydrocephalus and VP shunt placement since the age of 2 months without a history of infection and with the last revision being 2 years ago. The patient recently had a 7 day-hospitalization with a diagnosis of Klebsiella pneumoniae urinary tract infection (UTI). She was transferred from a long-term care facility and hospitalized for decreased level of consciousness. Intravenous vancomycin and aztreonam were started as empirical treatment for suspected recurrent UTI. The patient had a percutaneous endoscopic gastrostomy (PEG) tube, which was recently noted to be occluded. Physical examination was unremarkable except for poor oral hygiene and dentition. Specifically, the area around the VP shunt reservoir showed no signs of * Corresponding author. Division of Medical Microbiology, Meyer B1-193, 600 N. Wolfe St., Baltimore, MD 21287, USA. Tel.: þ1 410 955 5077; fax: þ1 410 614 8087. E-mail addresses: [email protected], [email protected] (N. Suwantarat). http://dx.doi.org/10.1016/j.anaerobe.2014.04.003 1075-9964/Ó 2014 Elsevier Ltd. All rights reserved.

erythema, swelling or drainage. There were no signs or peripheral stigmata of endocarditis. Fluid was able to be delivered via the PEG tube after repeatedly flushing it with water. Laboratory data were significant for leukocytosis (white blood cell count (WBC) of 17,800 cells/mL), with neutrophilia of 80%; hemoglobin (13.9 g/dL), and a normal platelet count (345,000 per mL). In addition, the patient had a significantly increased C-reactive protein level of 8.8 mg/L and the urinalysis demonstrated increased WBCs at 30 cells/mL. Renal and liver function tests were all within normal limits. Urine and blood cultures were obtained and were negative. CT scan of the abdomen and pelvis showed no significant signs of bowel obstruction or fluid collection. CT scan of the brain demonstrated an interval increase in the size of ventricles since the last image 2 years ago. VP shunt function study demonstrated slow flow but persistent patency of the VP shunt catheter. Aspiration of cerebrospinal fluid (CSF) from the VP shunt reservoir was performed. CSF analysis was significant for an elevated protein level of 1360 mg/mL, WBC count of 1985 cells/mm3 (96% neutrophils), red blood cell count of 1073 cells/mm3, and glucose of 75 mg/mL (serum glucose of 120 mg/dL). Gram stain of the CSF revealed heavy polymorphonuclear leukocytes and moderate Gram-positive coccobacilli. CSF aerobic culture grew Grampositive rods (small whitish colonies) whose growth was enhanced when incubated in CO2 and also under anaerobic conditions. The catalase reaction was negative. Cell wall fatty acid analysis using gaseliquid chromatography (GLC) (MIDI, Inc., Newark, DE), was able to identify the organism as a Bifidobacterium spp. Finally, sequencing of the first 500 bp of the 16S-rRNA

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N. Suwantarat et al. / Anaerobe 28 (2014) 1e3

gene (Applied Biosystems, Foster City, CA) identified the organism as Bifidobacterium breve (agreement score of 100%, Genbank accession number CP000303). Repeated CSF examination on the following day revealed the same morphology of Gram-positive rod-shaped organisms on Gram stain but the culture failed to grow when incubated aerobically and anaerobically on enriched media. However, on the third hospital day, repeat tap of the shunt showed Gram-positive rods again and this time the organism was isolated from an enrichment broth. This second isolate was also identified by sequencing as B. breve (agreement score of 99.8%, Genbank accession number CP000303). MALDI-TOF MS analysis was performed using the Bruker Microflex instrument, Biotyper software V. 3.0, and database v. 3.1.66 (Bruker Daltonics, Billerica, MA), according to the manufacturer’s instructions. It was able to identify B. breve from both specimens with a score of 2.150 and 2.128. The patient underwent VP shunt removal and placement of an external ventricular device. She was treated with intravenous ampicillin and completed 7 days of antibiotic treatment after the new VP shunt was placed. Susceptibility testing of B. breve was performed anaerobically using the E-test (AB bioMerieux, Durham, NC) [6]. The minimum inhibitory concentration (MIC) of B. breve isolates were interpreted as susceptible to penicillin (MIC  0.5 mg/ mL), ertapenem (MIC ¼ 2 mg/mL), piperacillin/tazobactam (MIC  4 mg/mL) but resistant to metronidazole (MIC ¼ 32 mg/mL) using the Clinical and Laboratory Standards Institute Interpretive Guidelines for anaerobes [6]. 3. Discussion Bifidobacterium spp. are rare causes of infections in humans and are estimated to cause 0.05e0.4% of cases of endocarditis and bacteremia [1]. Bourne et al. [2] reported 10 isolates of Bifidobacterium spp. from 91,493 blood cultures during the period 1972e 1977. Four patients had peripartum infections. The sources of bacteremia were related to gynecological and abdominal infections. Two patients had mixed infections with other organisms as well. In children, Brook et al. [7] recovered 57 clinical isolates of Bifidobacterium spp. (3%) from 2033 specimens during 1974e1994. The majority of the isolates were obtained from patients with otitis media (40%), abscesses (12%), and peritonitis (12%). In adults, similar findings have been reported and Bifidobacterium spp. are often recovered along with other anaerobic bacterial species such as Bifidobacterium fragilis, Peptostreptococus spp., and Fusobacterium spp. In addition to the reported series above, a small number of case reports and associated reviews have noted a variety of infections caused by Bifidobacterium spp. such as recurrent UTI (Bifidobacterium scardovii), peritonsillar abscess (Bifidobacterium dentitium), wound abscess, myositis, and bacteremia related to acupuncture (Bifidobacterium longnum) and meningitis, wound infection, UTI, and bacteremia attributed to B. breve [3e5,8e10]. We report the first case of VP shunt infection caused by B. breve. Previously, bacteremia caused by B. breve has been reported in a neonate who received probiotics (Bifidobacterium breve BBG-01, Yakult Honsya Co Ltd, Tokyo, Japan) [4]. Mahlen et al. [3] reported 5 isolates of B. breve from 4 patients during 2000e2007. In that study, B. breve organisms were isolated from the blood cultures of two patients, a urine culture (1 isolate), a wound culture (1 isolate) and an unknown site (1 isolate). There has been only one reported case of B. breve causing meningitis. In that report the patient was a neonate and the presumed source of infection was maternal vaginal flora [5]. In our patient, Gram positive rods were seen on three separate CSF specimens and B. breve was successfully isolated from two of these specimens. Initially, B. breve grew from the aerobic

culture under enhanced CO2 conditions. The organism was successfully identified to species level by 16S-rRNA gene sequencing and by MALDI-TOF MS. Predisposing factors for acquisition of B. breve infection in our patient could be her poor oral hygiene and dentition which resulted in transient bacteremia and hematogenous seeding of the VP shunt. Another possibility could be transient bacteremia from forceful manipulation of the occluded PEG tube. However, there was no sign of bowel obstruction or peritonitis on exam and abdominal imaging. The incidence of VP shunt infection caused by anaerobic bacteria is unknown. Only a few cases of anaerobic VP shunt infections have been reported. Propionibacterium acnes is the most common anaerobic bacterium associated with VP shunt infections because of its presence on the skin [11]. Polymicrobial infections involving Bacteroides spp., Clostridium spp., Gramnegative bacteria, and Candida spp. have been reported in association with peritonitis and bowel perforation by the distal end of a VP shunt [11,12]. Previous studies reported susceptibility of B. breve to vancomycin using a variable range (0.05e1 mg/mL) for susceptible MIC breakpoints. Compared to beta-lactam antibiotics, vancomycin may have less antimicrobial activity against B. breve especially for the treatment of central nervous system infections. Currently there are no CLSI interpretive guidelines for testing vancomycin against anaerobes. B. breve is intrinsically resistant to metronidazole which should not be used to empirically treat infections caused by anaerobic Gram-positive rods [13]. Bifidobacterium spp. may be difficult to recover because of their fastidious growth requirements and may be misidentified because of difficulties in distinguishing them from other catalase-negative, Gram-positive rods, such as Actinomyces spp., Lactobacillus spp., Alloscardovia omnicolens, and Actinobaculum spp [3,8]. 16S-rRNA gene sequencing is the identification method of choice for B. breve. Although, there were only a few B. breve clinical isolates identified by MALDI-TOF MS, the literature suggests that this method may be accurate for identification of Bifidobacterium isolates to the species level [14,15]. In summary, B. breve is a rare but possible cause of VP shunt infections and should be considered in patients on probiotics and those patients who have risk factors that predispose them to anaerobic infections. These organisms will likely be covered by empiric beta-lactam treatment frequently prescribed for patients with meningitis.

References [1] Borriello SP, Hammes WP, Holzapfel W, Marteau P, Schrezenmeir J, Vaara M, et al. Safety of probiotics that contain Lactobacilli or Bifidobacteria. Clin Infect Dis 2003;36:775e80. [2] Bourne KA, Beebe JL, Lue YA, Ellner PD. Bacteremia due to Bifidobacterium, Eubacterium or Lactobacillus; twenty-one cases and review of the literature. Yale J Biol Med 1978;51:505e12. [3] Mahlen SD, Clarridge III JE. Site and clinical significance of Alloscardovia omnicolens and Bifidobacterium species isolated in the clinical laboratory. J Clin Microbiol 2009;47:3289e93. [4] Ohishi A, Takahashi S, Ito Y, Ohishi Y, Tsukamoto K, Nanba Y, et al. Bifidobacterium septicemia associated with postoperative probiotic therapy in a neonate with omphalocele. J Pediatr 2010;156:679e81. [5] Nakazawa T, Kaneko K, Takahashi H, Inoue S. Neonatal meningitis caused by Bifidobacterium breve. Brain Dev 1996;18:160e2. [6] Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: 23th informational supplement. CLSI M100S23. Wayne, PA: Clinical and Laboratory Standards Institute; 2013. [7] Brook I. Isolation of non-sporing anaerobic rods from infections in children. J Med Microbiol 1996;45:21e6. [8] Barberis CM, Cittadini RM, Almuzara MN, Feinsilberg A, Famiglietti AM, Ramirez MS, et al. Recurrent urinary infection with Bifidobacterium scardovii. J Clin Microbiol 2012;50:1086e8.

N. Suwantarat et al. / Anaerobe 28 (2014) 1e3 [9] Civen R, Vaisanen M-L, Finegold SM. Peritonsillar abscess, retropharyngeal abscess, mediastinitis, and nonclostridial anaerobic myonecrosis: a case report. Clin Infect Dis 1993;16(Suppl. 4):S299e303. [10] Ha GY, Yang CH, Kim H, Chong Y. Case of sepsis caused by Bifidobacterium longum. J Clin Microbiol 1999;37:1227e8. [11] Garbarini-Maywood C, Mulligan ME. Ventriculoperitoneal shunt infection due to anaerobic and facultative bacteria: case report. Clin Infect Dis 1995;20(Suppl. 2):S240e1. [12] Brook I, Johnson N, Overturf GD, Wilkins J. Mixed bacterial meningitis; a complication of ventriculoperitoneal and lumboperitoneal shunts: report of two cases. J Neurosurg 1977;47:961e4.

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[13] Moubareck C, Gavini F, Vaugien L, Butel MJ, Doucet-Populaire F. Antimicrobial susceptibility of bifidobacteria. J Antimicrob Chemother 2005;55: 38e44. [14] Lau SK, Tang BS, Teng JL, Chan TM, Curreem SO, Fan RY, et al. Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry for identification of clinically significant bacteria that are difficult to identify in clinical laboratories. J Clin Pathol 2014;64(4):361e6. [15] Barreau M, Pagnier I, La Scola B. Improving the identification of anaerobes in the clinical microbiology laboratory through MALDI-TOF mass spectrometry. Anaerobe 2013;22:123e5.

Ventriculoperitoneal shunt infection caused by Bifidobacterium breve.

Bifidobacterium breve is a rare cause of human infections. Previously, bacteremia and meningitis caused by this organism linked to probiotic use have ...
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