Abstract
We describe 16 patients with bacteremia caused by Eggerthella lenta (n = 7), Paraeggerthella hongkongensis (n = 3), Eubacterium limosum (n = 4), Eubacterium callanderi (n = 1), and concomitant Eubacterium limosum/Eggerthella lenta (n = 1). Nine (56%) patients had polymicrobial bacteremia. The overall 60-day mortality rate was 19%, and all deaths occurred in patients with E. lenta bacteremia.
TEXT
Eubacterium and Eggerthella species are Gram-positive, non-spore-forming, obligately anaerobic rods that previously belonged to the Eubacterium genus. Eggerthella species were reclassified as belonging to a novel genus because of their distinct 16S rRNA sequence (4). Eggerthella hongkongensis was reclassified as Paraeggerthella hongkongensis gen. nov., comb. nov. based on 16S rRNA sequencing (19). Eubacterium and Eggerthella species are common gastrointestinal commensals and have been implicated as the cause of intra-abdominal infections and bacteremia (8). They have been isolated from various human sites, including the gastrointestinal tract, the female genital tract, the oral cavity, the thoracic cavity, and the prostate (8).
Correct identification of Eggerthella, Paraeggerthella, and Eubacterium to the species level is difficult with conventional phenotypic methods (12). The patterns of acid produced in peptone-yeast extract glucose broth can be used to differentiate Eggerthella and Eubacterium from other closely related genera, such as Propionibacterium, Bifidobacterium, Lactobacillus, and Actinomyces (4). Furthermore, other newer genera closely related to Eubacterium and Eggerthella species, such as Atopobium, Slackia, and Solobacterium, were also associated with bacteremia (5, 6, 7, 15, 18). Even with biochemical and fermentation reactions, the subspecies of Eubacterium cannot be reliably differentiated (4, 8). Furthermore, newer subspecies of Eggerthella, Paraeggerthella, and Eubacterium are not included in the databases of commercial rapid identification systems.
Patients with laboratory-documented Eubacterium bacteremia during the period from January 2001 to December 2010 at the National Taiwan University Hospital, a 2,500-bed tertiary medical center in northern Taiwan, were included in the analysis. Disease severity was evaluated by the Pittsburgh bacteremia score (14). Healthcare-associated bacteremia was defined as infections that were acquired during the course of receiving treatment for other conditions within a health care setting. Community-associated bacteremia was defined as infections that were acquired outside the hospital setting (9, 10).
All Eubacterium isolates were initially identified by conventional methods and were reidentified using partial sequencing of the 16S rRNA gene as previously described (11, 17). The results were compared with published sequences in the GenBank database using the BLASTN algorithm. Based on the results of partial sequencing of 16S rRNA genes, Eggerthella lenta bacteremia was diagnosed in seven patients, Eubacterium limosum bacteremia in four, Paraeggerthella hongkongensis bacteremia in three, Eubacterium callanderi bacteremia in one, and concomitant Eubacterium limosum and Eggerthella lenta bacteremia in one patient (Table 1).
Table 1.
Clinical features of 16 patients with Eggerthella, Paraeggerthella, or Eubacterium bacteremia
| Characteristic | Patients [no. (%) or as indicated] with: |
Total [16 (100)] | ||||
|---|---|---|---|---|---|---|
| E. lenta [7 (44)] | P. hongkongensis [3 (19)] | E. limosum [4 (25)] | E. callanderi [1 (6)] | E. lenta and E. limosum [1 (6)] | ||
| Age [yr; median (range)] | 56 (51–93) | 49 (32–73) | 76 (26–81) | 44 | 66 | 58.5 (26–93) |
| Gender | ||||||
| No. male/no. female | 4:3 | 2:1 | 2:2 | 0:1 | 0:1 | 8:8 |
| Abdominal symptoms | 2 (29) | 1 (33) | 3 (75) | 0 | 1 | 7 (44) |
| Healthcare associated/community acquired | 2 (29)/5 (71) | 1 (33)/2 (67) | 0/4 (100) | 1 (100)/0 | 1 (100)/0 | 5 (31)/11 (69) |
| Underlying health status | ||||||
| Steroid usage | 2 (29) | 0 | 0 | 1 (100) | 0 | 3 (19) |
| Diabetes mellitus | 1 (14) | 0 | 1 (25) | 0 | 0 | 2 (13) |
| End-stage renal disease | 2 (29) | 0 | 0 | 0 | 0 | 2 (13) |
| Recent chemotherapy | 1 (14) | 0 | 0 | 1 (100) | 0 | 2 (13) |
| Malignancies | 3 (43) | 0 | 1 (25) | 1 (100) | 1 (100) | 6 (38) |
| Gynecologic malignancy | 1 (14) | 0 | 0 | 0 | 1 (100) | 2 (13) |
| Gastrointestinal disease | 1 (14) | 1 (33) | 3 (75) | 0 | 1 (100) | 6 (38) |
| Abdominal operation within 4 weeks | 0 (0) | 1 (33) | 1 (25) | 0 | 0 | 2 (13) |
| Polymicrobial bacteremia | 3 (43) | 1 (33) | 4 (100) | 0 | 1 (100) | 9 (56) |
| Pitt bacteremia score (mean ± SD)a | 2.85 ± 3.67 | 2 ± 3.46 | 1 ± 1.1 | 3 | 0 | 2.06 ± 2.86 |
| Initial antibiotic treatment | ||||||
| Penicillins | 2 (29) | 0 | 2 (50) | 1 (100) | 1 (100) | 6 (38) |
| Carbapenems | 0 (0) | 2 (67) | 0 | 0 | 0 | 2 (13) |
| Cephalosporins | 4 (57) | 0 | 1 (25) | 0 | 1 (100) | 6 (38) |
| Vancomycin | 0 | 1 (33) | 0 | 0 | 0 | 1 (6) |
| Metronidazole | 1 (14) | 0 | 0 | 0 | 0 | 1 (6) |
| All-cause mortality at: | ||||||
| 14 days | 1 (14) | 0 | 0 | 0 | 0 | 1 (6) |
| 30 days | 1 (14) | 0 | 0 | 0 | 0 | 1 (6) |
| 60 days | 3 (43) | 0 | 0 | 0 | 0 | 3 (19) |
Disease severity at bacteremia onset.
The MICs of 16 antimicrobial agents (except daptomycin) were determined using the agar dilution method according to Clinical and Laboratory Standards Institute (CLSI) guidelines with Brucella agar supplemented with 5 μg/ml hemin, 1 μg/ml vitamin K1, and 5% laked sheep blood (2). For daptomycin susceptibility assay, the broth microdilution method was performed. Brucella broth (BBL Microbiology Systems) supplemented with hemin (5 μg/ml), vitamin K1 (1 μg/ml), lysed horse blood (5%), and calcium (50 μg/ml) was used (2). Clostridium difficile ATCC 700057 and Bacteroides fragilis ATCC 25285 were used as quality control strains. The MIC data of the 17 agents against the 17 isolates are shown in Table 2. According to 2010 CLSI breakpoints (1), all 17 isolates were susceptible to ampicillin-sulbactam, metronidazole, imipenem, and meropenem, while 82%, 88%, and 88% of the isolates were susceptible to moxifloxacin, cefmetazole, and piperacillin-tazobactam, respectively. In contrast, 71% of the isolates were resistant to penicillin. Eggerthella species showed the highest rate of resistance to clindamycin (63%).
Table 2.
Antimicrobial susceptibilities of 17 blood isolates of Eggerthella, Paraeggerthella, and Eubacterium species
| Isolate no. (bacterial species) | MIC (susceptibility)a |
||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PEN | SAM | CMZ | FLO | TZP | MEM | DOR | MOX | NEM | CLI | VAN | LIN | MET | FID | IMI | TIG | DAP | |
| 1 (E. lenta) | 2 (R) | 4 (S) | 16 (S) | 16 | 32 (S) | 0.5 (S) | 0.25 | 0.25 (S) | 0.12 | >32 (R) | 1 | 0.5 | 1 (S) | 0.015 | 1 (S) | 0.12 | 0.25 |
| 2 (E. lenta) | 2 (R) | 4 (S) | 16 (S) | 8 | 32 (S) | 0.5 (S) | 0.25 | 0.25 (S) | 0.25 | >32 (R) | 1 | 1 | 1 (S) | 0.06 | 1 (S) | 0.12 | 0.25 |
| 3 (E. lenta) | 2 (R) | 4 (S) | 16 (S) | 16 | 32 (S) | 0.5 (S) | 0.25 | 0.25 (S) | 0.5 | >32 (R) | 1 | 1 | 2 (S) | 0.03 | 1 (S) | 0.12 | 0.5 |
| 4 (E. lenta) | 2 (R) | 4 (S) | 16 (S) | 16 | 32 (S) | 0.5 (S) | 0.25 | 4 (I) | 2 | 2 (S) | 2 | 1 | 2 (S) | 0.06 | 1 (S) | 0.25 | 0.25 |
| 5 (E. lenta) | 4 (R) | 4 (S) | 32 (I) | 16 | 32 (S) | 0.5 (S) | 0.25 | 0.25 (S) | 0.5 | >32 (R) | 2 | 1 | 2 (S) | 0.25 | 1 (S) | 0.25 | 0.25 |
| 6 (E. lenta) | 4 (R) | 4 (S) | 32 (I) | 16 | 64 (I) | 0.5 (S) | 0.25 | 0.5 (S) | 0.5 | 1 (S) | 2 | 1 | 2 (S) | 0.12 | 1 (S) | 0.25 | 0.25 |
| 7 (E. lenta) | 1 (I) | 4 (S) | 16 (S) | 8 | 32 (S) | 0.5 (S) | 0.25 | >32 (I) | >32 | >32 (R) | 2 | 1 | 2 (S) | 0.06 | 0.5 (S) | 0.12 | 0.25 |
| 8 (E. lenta) | 1 (I) | 4 (S) | 16 (S) | 8 | 32 (S) | 0.5 (S) | 0.25 | 0.25 (S) | 0.25 | 0.5 (S) | 0.5 | 1 | 2 (S) | 0.015 | 1 (S) | 0.12 | 0.25 |
| 9 (P. hongkongensis) | 0.5 (S) | 4 (S) | 8 (S) | 8 | 32 (S) | 0.5 (S) | 0.25 | 0.25 (S) | 0.5 | 4 (I) | 1 | 1 | 2 (S) | 0.12 | 0.5 (S) | 0.06 | 0.25 |
| 10 (P. hongkongensis) | 2 (R) | 4 (S) | 16 (S) | 16 | 64 (I) | 0.5 (S) | 0.25 | 4 (I) | 1 | 4 (I) | 2 | 1 | 4 (S) | 0.12 | 1 (S) | 0.25 | 0.25 |
| 11 (P. hongkongensis) | 0.5 (S) | 2 (S) | 8 (S) | 8 | 16 (S) | 0.5 (S) | 0.25 | 0.25 (S) | 2 | 4 (I) | 2 | 1 | 4 (S) | 0.25 | 0.5 (S) | 0.12 | 0.25 |
| 12 (E. limosum) | 2 (R) | 0.12 (S) | 0.5 (S) | 0.25 | 0.03 (S) | 0.03 (S) | 0.03 | 2 (S) | 1 | 2 (S) | 1 | 2 | 0.12 (S) | 32 | 0.06 (S) | 0.06 | 0.06 |
| 13 (E. limosum) | 2 (R) | 0.25 (S) | 2 (S) | 1 | 0.12 (S) | 0.06 (S) | 0.06 | 2 (S) | 1 | 2 (S) | 2 | 2 | 0.25 (S) | 32 | 0.12 (S) | 0.06 | 0.12 |
| 14 (E. limosum) | 2 (R) | 0.5 (S) | 1 (S) | 1 | 0.25 (S) | 0.03 (S) | 0.06 | 2 (S) | 1 | 2 (S) | 2 | 4 | 0.25 (S) | 32 | 0.12 (S) | 0.12 | 0.25 |
| 15 (E. limosum) | 2 (R) | 0.12 (S) | 1 (S) | 0.5 | 0.06 (S) | 0.03 (S) | 0.03 | 2 (S) | 2 | 2 (S) | 2 | 2 | 0.12 (S) | 32 | 0.12 (S) | 0.12 | 0.12 |
| 16 (E. limosum) | 1 (I) | 0.25 (S) | 2 (S) | 1 | 0.12 (S) | 0.03 (S) | 0.12 | 2 (S) | 1 | >32 (R) | 2 | 4 | 0.12 (S) | 16 | 0.12 (S) | 0.06 | 0.12 |
| 17 (E. callanderi) | 4 (R) | 0.5 (S) | 2 (S) | 1 | 0.25 (S) | 0.03 (S) | 0.12 | 2 (S) | 2 | 4 (I) | 2 | 4 | 0.25 (S) | 32 | 0.12 (S) | 0.12 | 0.25 |
MICs are in μg/ml. PEN, penicillin; SAM, ampicillin-sulbactam; CMZ, cefmetazole; FLO, flomoxef; TZP, piperacillin-tazobactam; MEM, meropenem; DOR, doripenem; MOX, moxifloxacin; NEM, nemofloxacin; CLI, clindamycin; VAN, vancomycin; LIN, linezolid; MET, metronidazole; FID, fidaxomicin; IMI, imipenem; TIG, tigecycline; DAP, daptomycin; S, susceptible; I, intermediate; R, resistant (according to CLSI MIC interpretive breakpoints) (1).
The details of the 16 patients are depicted in Table 1. The majority of infections were community acquired. Almost half of the patients (44%) presented with abdominal symptoms. The most common immunocompromised status was malignancy (n = 6, 38%). Gynecologic malignancy was noted in two patients. None of the patients had gastrointestinal tract malignancy. Nine (56%) patients had polymicrobial bacteremia. The most common concomitant polymicrobial pathogens were Bacteroides species, including four cases of bacteremia due to Bacteroides caccae and two due to B. fragilis, and three cases were due to Escherichia coli. Other pathogens associated with polymicrobial bacteremia included coagulase-negative staphylococci, Clostridium clostridioforme, Staphylococcus aureus, and Klebsiella pneumoniae. The overall 60-day mortality rate was 19% (n = 3), and all deaths occurred in patients with E. lenta bacteremia. The cause of mortality was directly attributed to profound shock due to monomicrobial E. lenta bacteremia in one patient. The Pitt bacteremia score was 6 in this patient. The other two patients, with concomitant multiple comorbidity conditions (one patient had gastrointestinal bleeding, biliary tract infection, and venous thrombosis, and one had nasopharyngeal and tongue cancer), subsequently developed clinical deterioration during the episode of E. lenta bacteremia and died of repeated nosocomial infections and multiorgan failure. The Pitt bacteremia scores of these two patients with fatal outcomes were 0 and 8.
Bacterial species in the Eubacterium and Eggerthella genera are common gastrointestinal commensals (3, 8). Previous reports, therefore, focused on associated gastrointestinal diseases as the disease mechanism (8, 16). In our series, about half of the patients presented with abdominal symptoms. Two patients had gynecological malignancies. This may highlight the importance of the female reproductive tract as another potential portal of entry, since the vaginal tract has also been reported to be a natural human habitat of Eubacterium and Eggerthella species (8).
In our series, E. lenta was isolated primarily from patients with significant comorbidities, and it is likely that the preexisting disease state of the patient allowed the organism to gain access to the bloodstream. P. hongkongensis is a novel species first discovered in blood from four bacteremic patients in Hong Kong (8, 19). Our study also supports the idea that P. hongkongensis may be the second-most-common Eggerthella species causing bacteremia (8).
In one case series including 29 clinical isolates of E. lenta, all were susceptible to clindamycin, piperacillin, and imipenem (13). In the study by Lau et al., all 10 Eggerthella and Paraeggerthella isolates were susceptible to penicillins and metronidazole (8). In our study, there was a high rate of resistance to penicillin, as defined by CLSI breakpoints (1). In the present study, novel antibiotics, including doripenem, tigecycline, and daptomycin, all showed low MICs against Eggerthella, Paraeggerthella, and Eubacterium species.
In summary, Eggerthella, Paraeggerthella, and Eubacterium species can cause invasive human infections in immunocompromised hosts. More than 50% of the infections were polymicrobial, so that these organisms participated in bacteremias in patients with leaky guts or diseased female reproductive tract. Eggerthella lenta bacteremia is associated with significant mortality and morbidity. Ampicillin-sulbactam, metronidazole, carbapenems, tigecycline, and daptomycin all possess low MICs against species of these three genera.
Footnotes
Published ahead of print 11 April 2012
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