Electronic supplementary material

Enterococcus avium Bacteremia: A 12-year Clinical Experience with 53 Patients

European Journal of Clinical Microbiology & Infectious Diseases

Shin Naa,c, Hyun Jung Parka,c, Ki-Ho Parka,c, Oh-Hyun Choa,c, Yong Pil Chonga,c, Sung-Han Kima,c, Sang-Oh Leea,c, Heungsup Sungb,Mi-Na Kimb, Jin-Yong Jeonga,c, Yang Soo Kima,c, Jun Hee Wooa,c, Sang-Ho Choia,c

aDepartment of Infectious Diseases, bDepartmentof Laboratory Medicine, and cCenter for Antimicrobial Resistance and Microbial Genetics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

Corresponding author and reprints:

Sang-Ho Choi, MD

Department of Infectious Diseases

Asan Medical Center

86, Asanbyeongwon-gil,

Songpa-gu, Seoul 138-736

Republic of Korea

Tel: +82-2-3010-3304

Fax: +82-2-3010-6970

E-mail:

Supplementary material

Between February 1997 and February 2009 at the Asan Medical Center, Seoul, Korea, 24 Enterococcus hirae, 18 Enterococcus durans, and 13 Enterococcus raffinosus strains were isolated from blood cultures. Of all patients with Enterococcus infections, five with E. hirae and three with E. durans did not satisfy the criteria for clinically significant bacteremia. Thus, we compared the epidemiological, clinical, and microbiological characteristics of 19 patients with E. hirae bacteremia, 15 with E. durans, and 13 with E. raffinosus.

Microorganisms

Of the 47 patients (19 with E. hirae, 15 with E. durans, and 13 with E. raffinosus), 22 (46.8%) had polymicrobial bacteremia (8of the E. hirae patients, 8of those with E. durans, and 6 of those with E. raffinosus). Organisms observed concomitantly with such enterococci were, in decreasing order of frequency: Escherichia coli (2 E. hirae, 2 E. durans, and5 E. raffinosus), Pseudomonas aeruginosa (2 E. hirae and 4 E. durans), Enterococcus faecium (4 E. hirae and1 E. raffinosus), Enterobacter cloacae (1 E. hirae and2 E. durans), Klebsiella pneumoniae (1 E. hirae and1 E. durans), Klebsiella oxytoca (2 E. raffinosus), Aeromonas hydrophila (2 E. raffinosus), Provotella orallis(1 E. hirae), Bacteroides fragilis (1 E. raffinosus), methicillin-resistant Staphylococcus epidermidis (1 E. durans), Clostridium perfringens (1 E. hirae), and Bacillus (1 E. durans). Nine cases (4 E. hirae, 3 E. durans, and 2 E. raffinosus) were associated with the presence of ≥2 other organisms.

Epidemiological data and underlying diseases/conditions

The epidemiological characteristics of and underlying diseases/conditions in the 47 patients with E. hirae, E. durans, and E. raffinosus bacteremia are shown in Supplementary Table 1.

Portal of entry

As is the case with Enterococcus avium bacteremia (EAB), the biliary tract was the most common portal of entry in each patient group (31.6% E. hirae, 53.3% E. durans, and 76.9% E. raffinosus). Endocarditis was the portal of entry in some patients with E. hirae (3/19, 15.8%), E. durans (1/15, 6.7%), and E. raffinosus (1/13, 7.7%) infections, unlike the situation with EAB (Supplementary Table 2).

Clinical and microbiological features

The clinical and microbiological features of the patients are shown in Supplementary Table 2. The extent of resistance to penicillin and ampicillin of E. durans (33.3% each) and E. raffinosus (57.1% and 53.8%, respectively) strains were noticeably higher than the extent of resistance to penicillin and ampicillin of E. avium (20.8% and 21.3%, respectively) strains. In addition, unlike what was noted with E. avium, 1 of 18 E. hirae strains and 1 of 12 E. durans strains showed resistance to vancomycin.

Antimicrobial therapy

The treatment regimens are shown in Supplementary Table 3. Twenty-six patients (11 E. hirae, 8 E. durans, and 7 E. raffinosus) were treated with appropriate antimicrobial agents, including 8 E. hirae, 7 E. durans, and 7 E. raffinosus patients who received monotherapy. Vancomycin and ciprofloxacin were the most commonly used antimicrobial agents (8 patients each).

Outcomes

The crude mortalities from E. hirae, E. durans, and E. raffinosus infections were 2/19 (10.5%), 4/15 (26.7%), and 3/13 (23.1%), respectively; one death (1/19, 5.3%), two deaths (2/15, 13.3%), and no death were considered to be bacteremia-related, respectively. We found that EAB-associated crude mortality (13/53, 24.5%) and EAB-related mortality rates (6/53, 11.3%) were higher than were the crude mortality and bacteremia-related mortality rates for patients in our hospital who had E. hirae and E. raffinosus bacteremia, but lower than the crude mortality and bacteremia-related mortality rates of patients in our hospital who had E. durans bacteremia.
Supplementary Table1. Epidemiological characteristics of patients with E. hirae, E. durans, and E. raffinosus bacteremia.

Characteristic / No. of patients
Enterococcus hirae (N=19) / Enterococcus durans (N=15) / Enterococcus raffinosus (N=13)
Male sex / 9 (47.4) / 6 (40) / 3 (23.1)
Age (years), median age (range) / 62 (16-77) / 61 (19-81) / 65 (43-85)
Underlying diseasea
Any disease / 15 (78.9) / 15 (100) / 13 (100)
Biliary disease (benign) / 6 (31.6) / 5 (33.3) / 7 (53.8)
Solid cancer / 3 (15.8) / 6 (40.0) / 3 (23.1)
Hepatobiliary pancreatic / 3 (15.8) / 3 (20.0) / 3 (23.1)
Gastrointestinal / 0 / 3 (20.0) / 0
Diabetes mellitus / 2 (10.5) / 2(13.3) / 3 (23.1)
Liver cirrhosis / 2 (10.5) / 3 (20.0) / 2 (15.4)
Chronic renal failure / 1 (5.3) / 0 / 0
Congestive heart failure / 3 (15.8) / 0 / 0
Alcoholism / 2 (10.5) / 0 / 0
End-stage renal disease on dialysis / 1 (5.3) / 0 / 0
Hematologic disease / 1 (5.3) / 1 (6.7) / 1 (7.7)
McCabe and Jackson criteria
Nonfatal disease / 14 (73.7) / 10 (66.7) / 10 (76.9)
Ultimately fatal disease / 5 (26.3) / 5 (33.3) / 3(23.1)
Rapidly fatal disease / 0 / 0 / 0
Underlying conditiona
Prior hospital admission within 6 months / 6 (31.6) / 7 (46.7) / 4 (30.8)
Prior use of any antibioticb / 6 (31.6) / 11 (73.3) / 5 (38.5)
Indwelling urinary catheterc / 1 (5.3) / 3 (20.0) / 0
Biliary drainage catheterc / 2 (10.5) / 6 (40.0) / 5 (38.5)
Central venous catheter in situc / 1 (5.3) / 1 (6.7) / 0
Total parenteral nutritionc / 1 (5.3) / 3 (20.0) / 0
Recent bleedingd (within 2 weeks) / 1 (5.3) / 0 / 0
Recent surgeryb / 1 (5.3) / 3 (20.0) / 0
Prior ICU carec / 2 (10.5) / 1 (6.7) / 0
Cancer chemotherapyb / 2 (10.5) / 2 (13.3) / 0
Leukopeniae / 1 (5.3) / 1 (6.7) / 1 (7.7)
Mechanical ventilationc / 1 (5.3) / 1 (6.7) / 0
Immunosuppressive therapyf / 1 (5.3) / 1 (6.7) / 1 (7.7)
Transarterial chemoembolization for
hepatocellular carcinomab / 2 (10.5) / 0 / 0
Acquisition of bacteremia
Hospital / 8 (42.1) / 8 (53.3) / 7 (53.8)
Healthcare-associated / 4 (21.1) / 3 (20.0) / 2 (15.4)
Community-acquired / 7 (36.8) / 4 (26.7) / 4 (30.8)
Ward at the time of bacteremia
Medical ward / 6 (31.6) / 9 (60.0) / 7 (53.8)
Surgical ward / 1 (5.3) / 3 (20.0) / 2 (15.4)
Medical ICU / 2 (10.5) / 0 / 0
Surgical ICU / 0 / 1 (6.7) / 0
Emergency room / 10 (52.6) / 2 (13.3) / 4 (30.8)
Length of hospital stay before bacteremia,
median days (range)g / 0 (0-28) / 5 (0-36) / 2 (0-97)

NOTE. Data are nos., no. (%) of patients, or n/N (%) of patients, unless otherwise indicated.

ICU, intensive care unit.

a Some patients had more than one underlying disease or condition

b Within the past month

c Within the previous 3days

d Gastrointestinal or intra-abdominal bleeding

e Leukocytes <4,000/mm 3

f Receipt of steroid therapy for >10 days or use of other immunosuppressant for >1 week

within the previous 1 month.

g The analysis includes data on only those patients who became infected in the Asan Medical Center.

Supplementary Table 2. Clinical and microbiological features of patients with E. hirae, E. durans, and E. raffinosus bacteremia.

Characteristic / No. of patients
Enterococcus hirae (N=19) / Enterococcus durans (N=15) / Enterococcus raffinosus (N=13)
Polymicrobial bacteremia / 8 (42.1) / 8 (53.3) / 6 (46.2)
Portal of entry
Biliary / 6 (31.6) / 8 (53.3) / 10 (76.9)
Urinary / 6 (31.6) / 1 (6.7) / 0
Abdomen / 1 (5.3) / 3 (20.0) / 2 (15.4)
Endocarditis / 3 (15.8) / 1 (6.7) / 1 (7.7)
Unknown / 3 (15.8) / 2 (13.3) / 0
Initial manifestation within 24 h
Bacteremia without SIRS / 1 (5.3) / 0 / 2 (15.4)
Sepsis / 14 (73.7) / 10 (66.7) / 5 (38.5)
Severe sepsis / 3 (15.8) / 3 (20.0) / 5 (38.5)
Septic shock / 1 (5.3) / 2 (13.3) / 1 (7.7)
Drug resistancea
Penicillin / 2/18 (11.1) / 4/12 (33.3) / 4/7 (57.1)
Ampicillin / 2/18 (11.1) / 4/12 (33.3) / 7/13 (53.8)
Vancomycin / 1/18 (5.6) / 1/12 (8.3) / 0/13
Quinupristin-dalfopristin / 7/17 (41.2) / 1/3 (33.3) / 9/12 (75.0)
Tetracycline / 2/18 (11.1) / 4/12 (33.3) / 7/13 (53.8)
Erythromycin / 4/19 (22.2) / 4/12 (33.3) / 8/13 (61.5)
Ciprofloxacin / 3/18 (16.7) / 4/12 (33.3) / 1/13 (7.7)
Rifampin / 2/18 (11.1) / 4/12 (33.3) / 2/13 (15.4)
Imipenem / 0/1 / 11/1 (9.1) / 1/1 (100)
Linezolid / 0/1 / 0/0 / 0/0
High-level resistance to gentamicin / 1/18 (5.6) / 2/12 (16.7) / 2/13 (15.4)
High-level resistance to streptomycin / 0/18 / 0/12 / 3/13 (23.1)

a Not all strains underwent susceptibility testing.

Supplementary Table 3. Treatment and outcomes of patients with E. hirae, E. durans, and E. raffinosus bacteremia.

Characteristic / No. of patients
Enterococcus hirae (N=19) / Enterococcus durans (N=15) / Enterococcus raffinosus (N=13)
Received appropriate therapy
All / 11 (57.9) / 8 (53.3) / 7 (53.8)
Monotherapy / 8 / 7 / 7
Ampicillin / 2 / 1 / 1
Vancomycin / 3 / 1 / 5
Ciprofloxacin / 3 / 5 / 1
Combination therapy / 3 / 1 / 0
Ampicillin plus gentamicin / 2 / 1 / 0
Penicillin plus gentamicin / 1 / 0 / 0
Duration of appropriate therapy,
median days (range) / 14 (6-56) / 14 (11-42) / 9 (4-23)
Mortality
Crude mortality / 2/19 (10.5) / 4/15 (26.7) / 3/13 (23.1)
Bacteremia-related mortality / 1/19 (5.3) / 2/15 (13.3) / 0

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