J Med Microbiol International Journal of Systematic and Evolutionary Microbiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gardner, E. M.
Right arrow Articles by Belknap, R. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gardner, E. M.
Right arrow Articles by Belknap, R. W.
Agricola
Right arrow Articles by Gardner, E. M.
Right arrow Articles by Belknap, R. W.
J Med Microbiol 57 (2008), 236-239; DOI: 10.1099/jmm.0.47578-0
© 2008 Society for General Microbiology
ISSN 1473-5644


Case Report

Clostridium butyricum sepsis in an injection drug user with an indwelling central venous catheter

Edward M. Gardner1,2,3, Mary Kestler1,3, Alison Beieler2 and Robert W. Belknap1,2,3

1 Denver Public Health Department, Denver Health and Hospital Authority, 605 Bannock Street, Denver, CO 80204, USA

2 Department of Medicine, Denver Health and Hospital Authority, 605 Bannock Street, Denver, CO 80204, USA

3 Department of Medicine, Division of Infectious Diseases, University of Colorado at Denver and Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA

Correspondence
Edward M. Gardner
edward.gardner{at}dhha.org

Received 17 August 2007
Accepted 9 October 2007


Clostridium novyi has been associated with a large outbreak of severe infections in injection drug users. A case of bacteraemia with Clostridium butyricum in an injection drug user is reported. During treatment for Staphylococcus aureus osteomyelitis, the patient used an indwelling central venous catheter to inject cocaine. He was admitted with C. butyricum sepsis that responded to broad spectrum antibiotics, including vancomycin. Local investigation for other cases was unrevealing; however, growth of an unusual pathogen in clinical specimens should be investigated as it may represent a sentinel event with public health implications.


Abbreviations: CDC, Centers for Disease Control and Prevention; MSSA, meticillin-susceptible Staphylococcus aureus; UCH, University of Colorado Hospital.


    Introduction
 TOP
 Introduction
 Case report
 Discussion
 REFERENCES
 
The incidence of bacterial infections is higher in persons who inject illicit drugs intravenously (Cherubin & Sapira, 1993). Typical organisms include Staphylococcus aureus, various streptococci, aerobic Gram-negative rods and various anaerobic bacteria (Cherubin & Sapira, 1993). In 2000, a large outbreak of severe skin and soft-tissue infections with systemic symptoms in injection drug users was investigated in Scotland, England and Ireland (Jones et al., 2002; McGuigan et al., 2002). The suspected aetiological agent was Clostridium novyi type A and it was believed to have arisen from contaminated street heroin. The extent and severity of this outbreak led to recommendations for vigilance in order to recognize clustered or severe infections in injection drug users that might alert public health officials to potential outbreaks. In July of 2006 we recognized an unusual clostridial pathogen in an injection drug user at our hospital.


    Case report
 TOP
 Introduction
 Case report
 Discussion
 REFERENCES
 
In June of 2006, a 47-year-old man with a history of rheumatoid arthritis and injection drug use was hospitalized 2 weeks after stepping on a piece of glass that penetrated his right foot. Computed tomography revealed a right foot abscess with probable osteomyelitis of the first metatarsal head. The abscess was surgically drained and cultures grew meticillin-susceptible S. aureus (MSSA). He was treated with continuous intravenous infusion of 12 g nafcillin per day during hospitalization and was discharged to complete a 6 week course of this antibiotic at home. One week after discharge he developed a diffuse, confluent, erythematous rash consistent with a drug eruption. His central venous catheter site was without signs of infection. He was switched to 1 g intravenous vancomycin twice daily and sent home.

Three days later the patient injected cocaine through his central venous catheter and reported immediately feeling ‘hot and dizzy’. He proceeded to infuse his regularly scheduled vancomycin dose. Throughout the afternoon he continued to have episodes of dizziness and disorientation. In a moment of confusion he pulled out his central venous catheter. When symptoms worsened that night he called a friend who brought him to the emergency department.

His past medical history was significant for hepatitis C virus infection and rheumatoid arthritis, for which he was treated with 100 mg azathioprine twice daily. In 2004 he had septic arthritis of the left sternoclavicular joint with associated osteomyelitis secondary to MSSA. He denied alcohol use, had a 30 pack per year history of smoking, and admitted to a history of sporadic injection drug use with cocaine. He used a commercially available nutritional supplement containing creatine phosphate but denied probiotic use. A review of systems was positive for the presenting symptoms and, in addition, he complained of bilateral lower back pain that was chronic.

On presentation, he appeared moderately ill but was afebrile (35.7 °C). The remainder of his vital signs were as follows: heart rate 111 beats min–1, blood pressure 85/43 mmHg (his discharge blood pressure 1 week prior to this was 123/81 mmHg), respiratory rate 17 breaths min–1 and room air oxygen saturation by pulse oximetry 95 %. His lungs were clear, heart tachycardic but regular and without murmurs, and his abdominal exam benign. His back exam was normal without lumbar redness, warmth, swelling or tenderness. His right foot had a clean-appearing open post-surgical wound with minimal surrounding erythema. Skin was without rashes or lesions and there were no signs of infection at his recent central venous catheter insertion site. His initial white blood cell count was 15 300 cells µl–1 (up from 5700 cells µl–1 2 days prior to this) with 14 g haemoglobin dl–1 and 301 000 platelets µl–1. His blood urea nitrogen and creatinine were newly elevated at 24 mg dl–1 and 1.6 mg dl–1, respectively, and he had a mild non-anion gap metabolic acidosis with 19 mmol HCO3 l–1 and an anion gap of 12. Venous lactate was 3.9 mmol l–1. An EKG showed sinus tachycardia and a chest roentgenogram was normal.

He was treated aggressively with intravenous hydration and admitted to the medical intensive care unit. He required blood pressure support with intravenous noradrenaline and vasopressin, and was started empirically on 2 g cefepime every 12 hours, 1 g vancomycin every 12 hours and 500 mg levofloxacin once daily. He responded favourably to these measures and was weaned off vasopressors within 24 h. He remained afebrile and was transferred to a medical floor continuing the same antibiotics. His white blood cell count increased to 29 300 cells µl–1 during the first 72 h of hospitalization. Two blood cultures drawn on admission grew anaerobic Gram-positive rods, later identified as Clostridium butyricum using Electronic RapID Compendium software, RapID ANA II positive rods (Remel), with a probability of greater than 99.9 %. Two follow-up blood cultures obtained on the third hospital day grew C. butyricum. On the sixth hospital day blood cultures were sterile.

The patient remained clinically stable, and cefepime and levofloxacin were discontinued on the fifth hospital day. A test for antibodies against the human immunodeficiency virus was negative. Evaluation of the right foot by surgical consultants and using radiographs suggested improvement in the right foot infection without residual abscess. Transoesophageal echocardiography revealed no signs of infective endocarditis. Computed tomography of the abdomen and pelvis after the administration of oral and intravenous contrast showed no evidence of a gastrointestinal source of infection or lymphadenopathy but was suspicious for a prostatic abscess. Further evaluation, including prostate biopsy and culture, revealed no evidence of infection, and suggested that the reported abnormality represented a bladder diverticulum. Computed tomography of the lumbar spine showed no evidence of infection.

The patient continued to do well and was discharged to complete a 6 week course of vancomycin for his MSSA osteomyelitis. He was switched to oral levofloxacin for the last 2 weeks of therapy when his central venous catheter was removed secondary to continued injection drug use. This switch occurred 12 days after his last positive blood culture for C. butyricum. Outpatient colonoscopy was scheduled to rule out colonic malignancy as a source of his clostridial bacteraemia but the patient did not keep his appointment with gastroenterology. One year after the initial admission he is without evidence of recurrent infection.

In order to investigate the possibility of a local outbreak of clostridial infections in injection drug users secondary to contaminated drug we took the following steps. First we reviewed blood and abscess culture results at our institution from the prior 2 months. Second, we contacted the microbiology lab at the major teaching hospital in Denver, Colorado, the University of Colorado Hospital (UCH), to review recent culture results. Our institution, Denver Health and UCH provide the majority of care for the underserved population in the city of Denver. Third, we contacted our state health department, the Colorado Department of Public Health and Environment, to report our case and ask whether or not they had received other reports of severe infections in injection drug users in the state of Colorado. No other cases were identified in this manner. One month after our initial inquiry we reviewed culture results at our institution and spoke again with UCH and Colorado Department of Public Health and Environment. No other cases were identified.


    Discussion
 TOP
 Introduction
 Case report
 Discussion
 REFERENCES
 
C. butyricum is a strictly anaerobic endospore-forming Gram-positive rod that is uncommonly reported as a human pathogen. It is a soil inhabitant in various parts of the world, has been cultured from the stool of healthy children and adults, and is common in soured milk and cheeses (Meng et al., 1999; Schechter & Arnon, 1999). At least two prior cases of bacteraemia with C. butyricum have been reported in case series of clostridial bacteraemia (Haddy et al., 2000; Rechner et al., 2001). Two cases of polymicrobial peritonitis, including C. butyricum in paediatric patients, have been reported, and it is has been cultured from blood in the setting of neonatal necrotizing enterocolitis (Howard et al., 1977; Gothefors & Blenkharn, 1978; Sturm et al., 1980; Brook, 1995). Finally, C. butyricum appears to be one of the aetiological agents of type E infantile botulism and has been implicated in outbreaks of foodborne botulism (Aureli et al., 1986; McCroskey et al., 1986; Meng et al., 1997; Chaudhry et al., 1998; Fenicia et al., 1999, 2002).

To the best of our knowledge C. butyricum has not been described as a pathogen in injection drug users. However, as a genus, Clostridia are known to cause infectious complications in injection drug users and have been cultured frequently from both street heroin and injection paraphernalia (Tuazon et al., 1974). In the case presented here, the acute onset of symptoms and the persistence of the bacteraemia suggest the possibility of injection of contaminated drug or contaminated injection paraphernalia. An alternative source of C. butyricum bacteraemia seems unlikely in this case for at least two reasons. First, extensive evaluation for another source of infection was not revealing. Second, the patient was receiving intravenous infusions of vancomycin at home, an effective antibiotic for treatment of this infection. It is possible that the organism was misidentified by our anaerobic identification system, but this appears very unlikely based on the identification report (Table 1Go).


View this table:
[in this window]
[in a new window]

 
Table 1. Results of the RapID II positive rods identification report for the organism cultured from blood identified as C. butyricum

 
Chemical and infectious contamination of street drugs is known to occur (Hamilton et al., 2000; Jones et al., 2002; McGuigan et al., 2002; CDC, 2005). It is interesting that C. butyricum spores are commercially available in Japan where they are used as a probiotic (Seki et al., 2003; Shimbo et al., 2005). We considered this a possible source in our case but felt it was very unlikely as the patient denied probiotic use. We believe it is more likely that our patient's syringe was heavily contaminated by spores of this bacterium from an environmental source, but we also considered the possibility of cocaine contaminated by C. butyricum spores. Unfortunately, the cocaine and injection paraphernalia were not available for evaluation.

In summary, we have presented a case of C. butyricum bacteraemia and sepsis in an injection drug user. To the best of our knowledge, this is the first such report. We suspect contamination of injection paraphernalia as the source, although this was unproven. Growth of unusual human pathogens in clinical specimens should be investigated thoroughly as it can represent a sentinel event with public health implications. Suspected illicit substance contamination, both infectious and non-infectious, should be considered a public health threat and surveillance for this possibility is warranted in the appropriate setting.


    REFERENCES
 TOP
 Introduction
 Case report
 Discussion
 REFERENCES
 
Aureli, P., Fenicia, L., Pasolini, B., Gianfranceschi, M., McCroskey, L. M. & Hatheway, C. L. (1986). Two cases of type E infant botulism caused by neurotoxigenic Clostridium butyricum in Italy. J Infect Dis 154, 207–211.[Medline]

Brook, I. (1995). Clostridial infection in children. J Med Microbiol 42, 78–82.[Abstract/Free Full Text]

CDC (2005). Atypical reactions associated with heroin use – five states, January–April 2005. MMWR Morb Mortal Wkly Rep 54, 793–796.[Medline]

Chaudhry, R., Dhawan, B., Kumar, D., Bhatia, R., Gandhi, J. C., Patel, R. K. & Purohit, B. C. (1998). Outbreak of suspected Clostridium butyricum botulism in India. Emerg Infect Dis 4, 506–507.[Medline]

Cherubin, C. E. & Sapira, J. D. (1993). The medical complications of drug addiction and the medical assessment of the intravenous drug user: 25 years later. Ann Intern Med 119, 1017–1028.[Abstract/Free Full Text]

Fenicia, L., Franciosa, G., Pourshaban, M. & Aureli, P. (1999). Intestinal toxemia botulism in two young people, caused by Clostridium butyricum type E. Clin Infect Dis 29, 1381–1387.[CrossRef][Medline]

Fenicia, L., Da Dalt, L., Anniballi, F., Franciosa, G., Zanconato, S. & Aureli, P. (2002). A case of infant botulism due to neurotoxigenic Clostridium butyricum type E associated with Clostridium difficile colitis. Eur J Clin Microbiol Infect Dis 21, 736–738.[CrossRef][Medline]

Gothefors, L. & Blenkharn, I. (1978). Clostridium butyricum and necrotising enterocolitis. Lancet 1, 52–53.[Medline]

Haddy, R. I., Nadkarni, D. D., Mann, B. L., Little, D. R., Domers, T. D., Clover, R. D. & Silvers, M. J. (2000). Clostridial bacteremia in the community hospital. Scand J Infect Dis 32, 27–30.[CrossRef][Medline]

Hamilton, R. J., Perrone, J., Hoffman, R., Henretig, F. M., Karkevandian, E. H., Marcus, S., Shih, R. D., Blok, B. & Nordenholz, K. (2000). A descriptive study of an epidemic of poisoning caused by heroin adulterated with scopolamine. J Toxicol Clin Toxicol 38, 597–608.[CrossRef][Medline]

Howard, F. M., Flynn, D. M., Bradley, J. M., Noone, P. & Szawatkowski, M. (1977). Outbreak of necrotising enterocolitis caused by Clostridium butyricum. Lancet 2, 1099–1102.[Medline]

Jones, J. A., Salmon, J. E., Djuretic, T., Nichols, G., George, R. C., Gill, O. N., Brazier, J. S., Brett, M. M., Duerden, B. I. & other authors (2002). An outbreak of serious illness and death among injecting drug users in England during 2000. J Med Microbiol 51, 978–984.[Abstract/Free Full Text]

McCroskey, L. M., Hatheway, C. L., Fenicia, L., Pasolini, B. & Aureli, P. (1986). Characterization of an organism that produces type E botulinal toxin but which resembles Clostridium butyricum from the feces of an infant with type E botulism. J Clin Microbiol 23, 201–202.[Abstract/Free Full Text]

McGuigan, C. C., Penrice, G. M., Gruer, L., Ahmed, S., Goldberg, D., Black, M., Salmon, J. E. & Hood, J. (2002). Lethal outbreak of infection with Clostridium novyi type A and other spore-forming organisms in Scottish injecting drug users. J Med Microbiol 51, 971–977.[Abstract/Free Full Text]

Meng, X., Karasawa, T., Zou, K., Kuang, X., Wang, X., Lu, C., Wang, C., Yamakawa, K. & Nakamura, S. (1997). Characterization of a neurotoxigenic Clostridium butyricum strain isolated from the food implicated in an outbreak of food-borne type E botulism. J Clin Microbiol 35, 2160–2162.[Abstract]

Meng, X., Yamakawa, K., Zou, K., Wang, X., Kuang, X., Lu, C., Wang, C., Karasawa, T. & Nakamura, S. (1999). Isolation and characterisation of neurotoxigenic Clostridium butyricum from soil in China. J Med Microbiol 48, 133–137.[Abstract/Free Full Text]

Rechner, P. M., Agger, W. A., Mruz, K. & Cogbill, T. H. (2001). Clinical features of clostridial bacteremia: a review from a rural area. Clin Infect Dis 33, 349–353.[CrossRef][Medline]

Schechter, R. & Arnon, S. S. (1999). Commentary: where Marco Polo meets Meckel: type E botulism from Clostridium butyricum. Clin Infect Dis 29, 1388–1393.[CrossRef][Medline]

Seki, H., Shiohara, M., Matsumura, T., Miyagawa, N., Tanaka, M., Komiyama, A. & Kurata, S. (2003). Prevention of antibiotic-associated diarrhea in children by Clostridium butyricum MIYAIRI. Pediatr Int 45, 86–90.[CrossRef][Medline]

Shimbo, I., Yamaguchi, T., Odaka, T., Nakajima, K., Koide, A., Koyama, H. & Saisho, H. (2005). Effect of Clostridium butyricum on fecal flora in Helicobacter pylori eradication therapy. World J Gastroenterol 11, 7520–7524.[Medline]

Sturm, R., Staneck, J. L., Stauffer, L. R. & Neblett, W. W., III (1980). Neonatal necrotizing enterocolitis associated with penicillin-resistant, toxigenic Clostridium butyricum. Pediatrics 66, 928–931.[Abstract/Free Full Text]

Tuazon, C. U., Hill, R. & Sheagren, J. N. (1974). Microbiologic study of street heroin and injection paraphernalia. J Infect Dis 129, 327–329.[Medline]





This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gardner, E. M.
Right arrow Articles by Belknap, R. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gardner, E. M.
Right arrow Articles by Belknap, R. W.
Agricola
Right arrow Articles by Gardner, E. M.
Right arrow Articles by Belknap, R. W.


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
INT J SYST EVOL MICROBIOL J MED MICROBIOL MICROBIOLOGY J GEN VIROL ALL SGM JOURNALS