SYNOPSIS Clostridium diffi cile Bacteremia, Taiwan1 Nan-Yao Lee, Yu-Tsung Huang, Po-Ren Hsueh,2 and Wen-Chien Ko2 MedscapeCME ACTIVITY Medscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians the opportunity to earn CME credit. This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and Emerging Infectious Diseases. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians. Medscape, LLC designates this educational activity for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certifi cate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test and/or complete the evaluation at http://cme.medscape.com/viewpublication/30063; (4) view/print certifi cate. Learning Objectives Upon completion of this activity, participants will be able to: • Identify presenting symptoms of Clostridium diffi cile bacteremia (CDB). • Specify the most common source of bacteremia in cases of CDB and incorporate that knowledge into the development of effective management plans.. • Describe the prognosis of CDB. Editor Nancy Mannikko, MS, PhD, Technical Writer/Editor, Emerging Infectious Diseases. Disclosure: Nancy Mannikko, MS, PhD, has disclosed no relevant fi nancial relationships. CME Author Charles P. Vega, MD, Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine. Disclosure: Charles P. Vega, MD, has disclosed no relevant fi nancial relationships.. Authors Disclosures: Nan-Yao Lee, MD; Yu-Tsung Huang, MD; Po-Ren Hsueh, MD; and Wen-Chien Ko, MD, have disclosed no relevant fi nancial relationships. To determine clinical characteristics and outcome of pa- lostridium diffi cile is well recognized as the etiologic tients with Clostridium diffi cile bacteremia (CDB), we identi- Cagent of pseudomembranous colitis and has been im- fi ed 12 patients with CDB in 2 medical centers in Taiwan; all plicated as the cause of 10%–25% of cases of antimicro- had underlying systemic diseases. Five had gastrointestinal bial drug–associated diarrhea (1). The pathogen has been diseases or conditions, including pseudomembranous coli- responsible for numerous recent hospital-based epidemics tis (2 patients); 4 recalled diarrhea, but only 5 had recent and is also emerging in the community (2). The clinical exposure to antimicrobial drugs. Ten available isolates were susceptible to metronidazole and vancomycin. Five isolates features, disease spectrum and pathogenesis, and optimal had C. diffi cile toxin A or B. Of 5 patients who died, 3 died of treatments of C. diffi cile–associated diarrhea have been CDB. Of 8 patients treated with metronidazole or vancomy- well studied. In contrast, reports of the isolation of C. dif- cin, only 1 died, and all 4 patients treated with other drugs fi cile in body sites other than the intestines, or extraintes- died (12.5% vs. 100%; p = 0.01). C. diffi cile bacteremia, tinal infections, have been anecdotal (3,4). Extracolonic although uncommon, is thus associated with substantial ill- manifestations of C. diffi cile infections reported were vari- ness and death rates. able, including bacteremia, osteomyelitis, visceral abscess, empyema, reactive arthritis, pyelonephritis, prosthetic joint Author affi liations: National Cheng Kung University Hospital and infection, and skin and soft tissue infection (3–10). Most Medical College, Tainan, Taiwan (N.-Y. Lee, W.-C. Ko); and Na- 1This study was presented in part at the Annual Meeting of the tional Taiwan University Hospital and College of Medicine, Taipei, Infectious Disease Society of Taiwan, Taipei, Taiwan, January Taiwan (Y.-T. Huang, P.-R. Hsueh) 9–10, 2010. DOI: 10.3201/eid1608.100064 2These authors contributed equally to this article. 1204 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 16, No. 8, August 2010 Clostridium diffi cile Bacteremia, Taiwan cases of extracolonic C. diffi cile infections have been pre- suggested persistently active infection if the patient had no ceded by gastrointestinal events, either C. diffi cile colitis or other obvious explanation for the death. surgical and anatomic disruption of the colon (4). Bacteremia was defi ned as the presence of an organ- Recently, Libby and Bearman reviewed the literature ism in a blood culture specimen. Clinically signifi cant on bacteremia caused by C. diffi cile (6). Most cases were bacteremia was defi ned as >1 positive blood culture and identifi ed from individual case reports. However, as the clinical features compatible with fever and sepsis syn- incidence of C. diffi cile infection increases, an increase drome; patients with noteworthy bacteremia were included in cases of C. diffi cile bacteremia (CDB) is likely (10). in this study. An episode of bacteremia was considered to Knowledge of the clinical signs and symptoms of these ex- be hospital acquired if a bacteremic episode was noted at tracolonic manifestations of bloodstream infections will be >48 hours after hospitalization; healthcare associated if useful in patient care and could improve clinical outcomes it occurred within 48 hours of hospitalization in patients (4). To outline the spectrum and clinical signifi cance of with extensive contact with the healthcare system (such as CDB, we report 12 cases of CDB over a recent 10-year nursing home residence, organ transplantation, hemodialy- period at 2 medical centers in Taiwan and review the litera- sis dependence, presence of an indwelling intravascular ture published in English. catheter, or surgery within the previous 30 days), or the patients had been transferred from another hospital or long- Patients term care facility; or community acquired if it occurred <48 Patients with blood cultures positive for C. diffi cile at 2 hours of admission in patients without extensive healthcare teaching hospitals (National Cheng Kung University Hos- contact. In the case of secondary bacteremia, a primary fo- pital, a 1,100-bed tertiary care hospital in southern Taiwan cus of infection was defi ned according to the criteria of the and National Taiwan University Hospital, a 2,800-bed ter- Centers for Disease Control and Prevention (17). tiary care hospital in northern Taiwan) during January 1989 Antimicrobial drug therapy in the preceding 30 days through February 2009, were retrospectively identifi ed was documented through a review of medical records. Pre- from laboratory records, and their medical records were re- vious antimicrobial drug therapy was defi ned as the receipt viewed. If a patient experienced >1 episode of CDB, only of an oral or parenteral antimicrobial agent for >72 hours information about the fi rst episode was included. Informa- within the preceding 2 months. tion about age, sex, underlying diseases, clinical course, antimicrobial drug therapy, and clinical outcome was re- Identifi cation of Isolates and Clonality corded in a case-record form. Bacteria colonies suspected of being C. diffi cile on the We conducted a literature review to fi nd relevant ar- basis of characteristic odor, typical morphologic features, ticles published between January 1, 1962, and August 31, and Gram staining results were phenotypically identifi ed 2009, by querying the PubMed database using the keywords by using standard methods (18) and the API 32A system “Clostridium diffi cile,” “bacteremia,” “sepsis,” and “blood- (bioMérieux, Las Halles, France). These organisms were stream infection.” The references of available articles were further confi rmed to the species level by using partial 16S surveyed for additional cases. rRNA gene sequence analysis. Two primers were used: PS13 5′-GGAGGCAGCAGTGGGGAATA-3′ and PS14 Defi nitions 5′-TGACGGGCGGTGTGTACAAG-3′, as described (19). Underlying conditions were stratifi ed on the basis of The partial sequences obtained (529 bp) were compared the McCabe and Jackson score (11) and the comorbidity with published sequences in the GenBank database by us- score of Charlson et al. (12). Severity of illness was evalu- ing the BLASTN algorithm (www.ncbi.nlm.nih.gov/blast). ated on the fi rst day of bacteremia onset by means of the Molecular typing of these isolates by pulsed-fi eld gel elec- Acute Physiology and Chronic Health Evaluation II Score trophoresis (PFGE) using SmaI (New England Biolabs, (13), Simplifi ed Acute Physiology Score II (14), and the Beverly, MA, USA)–digested DNA and repetitive-element Pittsburgh bacteremia score (15). The physiologic response PCR typing (DiversiLab Kits for C. diffi cile; bioMérieux) to bacteremia was categorized as severe sepsis if the patient were performed to identify the clonality of the isolates met the criteria for severe sepsis specifi ed by the American (20,21). For PFGE, gels were run for 22 h at 13°C by using College of Chest Physicians/Society for Critical Care Med- a CHEF DR-III system (Bio-Rad Laboratories, Hercules, icine Consensus Conference Committee (16). Immunosup- CA, USA) at 5.5 V/cm with initial and fi nal pulse times of pressive therapy was defi ned as the receipt of corticosteroid 5 s and 60 s, respectively (20). The production of C. dif- treatment (10 mg/day or an equivalent dosage) for >2 weeks