Abstract
Eggerthella lenta is an emerging pathogen that has been underrecognized due to historical difficulties with phenotypic identification. Until now, its pathogenicity, antimicrobial susceptibility profile, and optimal treatment have been poorly characterized. In this article, we report the largest cohort of patients with E. lenta bacteremia to date and describe in detail their clinical features, microbiologic characteristics, treatment, and outcomes. We identified 33 patients; the median age was 68 years, and there was no gender predominance. Twenty-seven patients (82%) had serious intra-abdominal pathology, often requiring a medical procedure. Of those who received antibiotics (28/33, 85%), the median duration of treatment was 21.5 days. Mortality from all causes was 6% at 7 days, 12% at 30 days, and 33% at 1 year. Of 26 isolates available for further testing, all were identified as E. lenta by both commercially available matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) systems, and none were found to harbor a vanA or vanB gene. Of 23 isolates which underwent susceptibility testing, all were susceptible to amoxicillin-clavulanate, cefoxitin, metronidazole, piperacillin-tazobactam, ertapenem, and meropenem, 91% were susceptible to clindamycin, 74% were susceptible to moxifloxacin, and 39% were susceptible to penicillin.
INTRODUCTION
Eggerthella lenta is an anaerobic, nonsporulating, Gram-positive bacillus in the Coriobacteriaceae family that was first described in 1935 by Arnold Eggerth (1). It has since been characterized in more detail (2) and was called Eubacterium lentum until genetic analysis in 1999 placed it in its own distinct genus (3, 4). Two closely related species, Paraeggerthella hongkongensis and Eggerthella sinensis, have also been described recently (5–7). The complete genomic sequence was first published in 2009 (8, 9).
Due to historical difficulties with laboratory identification, there is a paucity of published data on the spectrum of disease that E. lenta causes and its optimal treatment. E. lenta is part of the normal human intestinal microbiome (10) and has been most commonly associated with infections from a gastrointestinal tract (GIT) source, which are often polymicrobial (11). Severe, disseminated disease has been described (12), and overall mortality is significant, ranging from 36% to 43% (13, 14).
E. lenta is being increasingly recognized in the modern clinical microbiology laboratory due to the widespread uptake of new technologies such as automated phenotypic identification systems and molecular sequencing techniques. More recently, it has been demonstrated that matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is capable of rapidly identifying E. lenta (15–17).
The use of antimicrobial susceptibility testing (AST) for anaerobes remains restricted to specialized reference laboratories, so antimicrobial therapy for patients with infections due to anaerobic bacteria is often empirical. However, given that resistance among anaerobic organisms is increasing, susceptibility data are important to guide therapy (18–20). There are limited published data on the susceptibility profile of E. lenta, and breakpoints are extrapolated from those determined for other species. In 2001, Stinear et al. were developing a rapid PCR-based screening method for detection of fecal carriers of vancomycin-resistant enterococci (VRE) when they identified the vanB locus in Eggerthella lenta, hypothesizing that anaerobic bowel flora may represent the origin of VRE and demonstrating that E. lenta is capable of acquiring vancomycin resistance (21–23).
In this study, we have retrospectively reviewed 33 patients with E. lenta bacteremia, which represents the largest published series to date. We describe their clinical features, laboratory identification by both phenotypic and genotypic methods, and AST results.
MATERIALS AND METHODS
Case ascertainment and clinical data collection.
This study was conducted at Monash Health, a large health care network encompassing 5 campuses and over 2,200 beds in Melbourne, Australia. Cases were identified by searching our Microbiology database for data from January 2000 to September 2013 for all positive blood cultures with Eubacterium lentum or Eggerthella lenta. Clinical data were collected from medical records. Cases were classified community onset if the positive blood culture was collected within 72 h of admission to the hospital and there was no identifiable prior health care contact, health care associated if the positive blood culture was collected within 72 h of admission and contact with the hospital system (e.g., dialysis, admissions, procedures, etc.) had occurred within 1 month after admission, and nosocomial if the positive blood culture was collected beyond 72 h after admission. Measures of illness severity (simplified acute physiology score [SAPS II] [24] and Pitt bacteremia score [25]) as well as comorbidity (Charlson index) (26, 27) were calculated. The study was approved by our Human Research Ethics Committee.
Blood cultures.
E. lenta was isolated from BacT/Alert anaerobic blood culture bottles using a BacT/Alert three-dimensional (3D) automated microbial detection system (bioMérieux, Marcy l'Etoile, France). The number of hours (or days if hour data were not available) to detection of growth was recorded for each case.
Isolate identification.
Available isolates were retrieved from storage and purity plated on Oxoid Anaero plates (Thermo Fisher Scientific, Basingstoke, United Kingdom). After 48 h of incubation, they were identified via multiple methods. Phenotypic identification was performed based on Gram staining, colony morphology, and Vitek-2 ANC card (bioMérieux, Marcy, l'Etoile, France) results. MALDI-TOF identification was performed using both available commercial systems, Bruker MS (Bruker Daltonics, Bremen, Germany) and Vitek MS (bioMérieux, Marcy l'Etoile, France) (formerly known as Axima@SARAMIS; Shimadzu). For isolates that could not be retrieved from storage, original phenotypic identification was performed with a RapID-ANA II system (Innovative Diagnostic Systems, Inc., Atlanta, GA).
Bruker MS analysis was performed as previously described (28, 29). Each isolate was anaerobically grown on a chocolate agar plate for 72 h. The extended direct transfer method was used whereby a single colony was touched and applied as a thin film directly onto a spot on a MALDI target plate, overlaid with 1 μl of 70% formic acid, and allowed to dry at room temperature. A 1-μl volume of HCCA matrix solution (α-cyano-4-hydroxy-cinnamic acid–50% acetonitrile–47.5% water–2.5% trifluoroacetic acid) (Sigma-Aldrich) was added to each spot and allowed to dry. Escherichia coli (strain MB11464_1) was used as a calibration standard. Spectrometric measurements were performed using a Microflex LT mass spectrometer (Bruker Daltonik) and analyzed using MALDI Biotyper software (version 3.1). Per manufacturer instructions, a log score value of ≥2.0 met the criteria for species identification. A score of 1.700 to 1.999 allowed correct identification to the level of the genus, while a score of <1.7 was interpreted as showing no identity.
Vitek MS (bioMérieux) analysis was also performed as previously described (28, 30). Single colonies from a 72-h brain heart infusion agar plate were directly smeared onto wells of the target plate; 0.5 μl of ready-to-use 40% formic acid (bioMérieux, Marcy l'Etoile, France) was added to each sample and allowed to air dry at room temperature. A 1-μl volume of ready-to-use HCCA matrix solution (bioMérieux, Marcy l'Etoile, France) was added to each spot and allowed to dry. E. coli strain ATCC 8739 was used as a calibration standard. To generate protein mass fingerprints, the FlexiMass-DS target was loaded onto an adapter, prior to insertion into a Vitek MS instrument. Raw spectra were generated with Launchpad v. 2.8 software (Shimadzu-Biotech), and protein mass spectrum fingerprints were then directed to SARAMIS (AnagnosTec GmbH) for analysis. Isolates were identified by comparison with spectra in the reference MS database (containing 3,178 SuperSpectrum [SuperS] entries). Identification at the genus or species level was considered reliable when the score was above the 75% confidence level when matched to the SuperS data, a consensus spectrum for that genus or species compiled from reference spectra of that organism in the database. A result was also acceptable if a “comparison” result, indicating a good match to one or more reference spectra but not to the SuperS data, was obtained.
Bacterial DNA was extracted, amplified, and sequenced using a MicroSEQ 16S rRNA bacterial identification kit (PerkinElmer Applied Biosystems Inc., Foster City, CA, USA). The resulting 16S rRNA gene sequences were then analyzed with MicroSeq 500 software (version 2.2.1). If the sequences were ≥99.0% compatible with the database, the identity was acceptable to the level of the species.
AST.
Antimicrobial susceptibility testing (AST) was performed for E. lenta clinical isolates and E. lenta strain ATCC 43055 (31) using the reference agar dilution procedure (Wadsworth method) and Brucella agar supplemented with 5 μg/ml hemin plus 1 μg/ml vitamin K plus 5% (vol/vol) laked sheep blood, with a final volume of 20 ml/plate (18 ml agar plus 2 ml antibiotic). The “direct colony suspension” method (32, 33) was used. Plates were incubated in an anaerobic chamber for 48 h in an atmosphere of 4% to 7% CO2. An inoculum of 105 CFU/spot was used. Antibiotic powders were supplied by Sigma-Aldrich (penicillin, cefoxitin, ceftriaxone, vancomycin, piperacillin-tazobactam, metronidazole, clindamycin), GlaxoSmithKline (amoxicillin-clavulanate), Merck (ertapenem), Pfizer (tazobactam, tigecycline), Bayer (moxifloxacin), and AstraZeneca (meropenem).
Testing for teicoplanin was performed using the Etest method (bioMérieux) (lot number 1002276240) according to the manufacturer's recommended guidelines (34).
Interpretative criteria.
MICs were compared to standard Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (available only for Gram-positive anaerobes) and are reported as susceptible, intermediate, or resistant.
van gene PCR.
After incubation for 48 h, the Anaero (Oxoid) plates were swabbed with a dry sterile cotton swab and the organisms were placed into sterile saline solution. Bacteria were pelleted at 10,000 × g for 10 min, and the supernatant was discarded. DNA was extracted from pellets of bacteria using a PureLink DNA miniprep kit with the Gram-positive modification protocol (Invitrogen). DNA was eluted using 200 μl of 10 mM Tris (pH 8.5). DNA concentrations were determined by Qubit assay. Real-time PCR for vanA and vanB was performed using a Roche LightCycler FastStart DNA Master HybProbe kit as described by Palladino et al. (35). Control isolates were strain MLG043 (E. lenta containing vanB [23]) and clinical isolates of Enterococcus faecium containing vanA and E. faecium containing vanB (22).
Statistical analysis.
Categorical data are presented as total numbers and percentages. Continuous data are expressed as means and standard deviations with medians and ranges as required.
RESULTS
Clinical data.
The clinical characteristics of 33 patients with E. lenta bacteremia are summarized in Tables 1 and 2. The median age was 68 years (mean, 62.4 ± 23.9; range, 11 to 95), and 17/33 (52%) were male. The median length of stay was 11 days (24 ± 26; 1 to 94), and 10/33 (30%) patients were admitted to the intensive care unit (ICU). The majority (64%) of patients had community onset disease, and 39% had polymicrobial bacteremia, with a variety of enteric organisms isolated. Blood cultures flagged positive after a median of 3 days of incubation (2.85 ± 1.09; 1 to 5). Time to positivity could be determined for 30 patients; the median time was 65.5 h (72.5 ± 25.2; 40.1 to 122.6). The most common presenting symptoms were fever (82%) and abdominal pain (64%). A total of 82% of patients had the GIT identified as the likely source. The median SAPS II score was 25 (27 ± 12.2; 6 to 64), the median Charlson comorbidity score was 2 (2.45 ± 2.25; 0 to 7), and the Pitt bacteremia score was 2 (2.15 ± 1.9; 0 to 8). A total of 67% of patients had an abnormal white cell count (WCC; <4 × 109/liter or >11 × 109/liter) at the time of bacteremia, and the C-reactive protein (CRP) level was elevated in all 31 patients in whom it was measured.
TABLE 1.
E. lenta bacteremia patient characteristics and clinical featuresa
| Patient clinical characteristic | Values |
|---|---|
| Demographics | |
| Mean age ± SD (median, range) | 62.4 ± 23.9 (68, 11–95) |
| Male sex | 17 (52%) |
| Mean no. of days of stay ± SD (median, range) | 23.6 ± 26.3 (11, 1–94) |
| Admission to intensive care, no. (%) | 10 (30.3) |
| Admitting unit | |
| Medical, no. (%) | 16 (48.5) |
| Surgical, no. (%) | 13 (39.4) |
| Other, no. (%) | 4 (12.1) |
| Onset | |
| Community, no. (%) | 21 (63.6) |
| Health care associated, no. (%) | 2 (6.1) |
| Nosocomial, no. (%) | 10 (30.3) |
| Microbiological characteristics | |
| Anaerobic bottle only, no. (%) | 33 (100) |
| Mean day blood culture flagged positive± SD (median, range) | 2.85 ± 1.09 (3, 1–5) |
| Mean time to positivity (h) ± SD (median, range) | 72.5 ± 25.2 (65.6, 40.1–122.6) |
| Polymicrobial bacteremia, no. (%) | 13 (39.4) |
| Symptoms | |
| Fever, no. (%) | 27 (81.8) |
| Abdominal pain, no. (%) | 21 (63.6) |
| Vomiting, no. (%) | 12 (36.4) |
| Diarrhea, no. (%) | 8 (24.2) |
| Severity scores | |
| Mean simplified acute physiology score (SAPS II) ± SD (median, range) | 27 ± 12.2 (25, 6–64) |
| Mean Pitt bacteremia score ± SD (median, range) | 2.15 ± 1.9 (2, 0–8) |
| Medical comorbidities | |
| Diverticular disease, no. (%) | 8 (24.2) |
| Colonic polyps, no. (%) | 5 (15.2) |
| Gastrointestinal malignancy, no. (%) | 4 (12.1) |
| Inflammatory bowel disease, no. (%) | 1 (3) |
| Chronic liver disease, no. (%) | 1 (3) |
| Gastrointestinal instrumentation or surgery within 30 days, no. (%) | 5 (15.2) |
| Any chronic gastrointestinal pathology, no. (%) | 19 (57.6) |
| Immunosuppression, no. (%) | 5 (15.2) |
| Diabetes, no. (%) | 9 (27.3) |
| Renal failure, no. (%) | 12 (36.4), including 3 (9.1) dialysis |
| Nongastrointestinal malignancy, no. (%) | 4 (12.1) |
| No significant comorbidities, no. (%) | 5 (15.1) |
| Mean Charlson comorbidity score ± SD (median, range) | 2.45 ± 2.25 (2, 0–7) |
| Likely source | |
| Hepatobiliary (liver, pancreas, gallbladder, biliary), no. (%) | 3 (9.1) |
| Upper gastrointestinal tract, no. (%) | 5 (15.2) |
| Colon, no. (%) | 10 (30.3) |
| Bowel (unable to localize), no. (%) | 5 (15.2) |
| Appendix, no. (%) | 4 (12.1) |
| Skin or soft tissue, no. (%) | 3 (9.1) |
| Other, no. (%) | 3 (9.1) |
| Investigations | |
| Mean hemoglobin level (g/liter) ± SD (median, range) (RR, 119–160 g/liter) | 112 ± 24 (112, 77–167) |
| Mean white cell count (× 109/liter) ± SD (median, range) (RR, 4.0–11.0 × 109/liter) | 14.9 ± 8.7 (3.2–39) |
| Mean albumin level (g/liter) ± SD (median, range) (RR, 35–45 g/liter) | 27 ± 6.8 (26, 14–39) |
| C-reactive protein level (mg/liter) ± SD (median, range) (RR, 0–5 mg/liter) | 138.5 ± 107.1 (26, 14–39) |
| Abdominal CT, no. (%) (tested/abnormal) | 17 (51.5)/13 (39.4) |
| Abdominal ultrasound, no. (%) (tested/abnormal) | 9 (27.3)/6 (18.2) |
| Treatment | |
| No directed treatment, no. (%) | 5 (15.2%) |
| Antibiotic therapy, no. (%) | 28 (84.8%) |
| Mean duration of antibiotics if treated (days) ± SD (median, range) | 36.7 ± 56.2 (21.5, 2–301) |
| Surgical procedure, no. (%) | 12 (36.4) |
| Radiological procedure, no. (%) | 3 (9.1) |
| Endoscopy performed (diagnostic and/or therapeutic), no. (%) | 11 (33.3) |
| Outcome | |
| 7-day mortality, no. (%) | 2 (6.1) |
| 30-day mortality, no. (%) | 4 (12.1) |
| 1-yr mortality, no. (%) | 11 (33.3) |
| Readmission | |
| Within 3 mos, no. (%) | 11 (33.3) |
| Within 12 mos, no. (%) | 16 (48.5) |
n = 33 patients. CT, computed tomography; RR, reference range; SD, standard deviation.
TABLE 2.
Individual patient diagnoses and treatment informationa
| Case | Age (yrs)/sex | Diagnosis | Treatment details |
Outcome | ||
|---|---|---|---|---|---|---|
| Procedure | Antibioticb | Duration (days) | ||||
| 1 | 57/F | Viral gastroenteritis | None | Metronidazole | 10 | Alive at 12 mos |
| 2 | 75/F | Metastatic gastric cancer | Distal gastrectomy and Roux-en-y reconstruction | Trimethoprim | 16 | Death at 9 mos |
| 3 | 44/F | Chronic cholelithiasis | Cholecystectomy | None | 0 | Alive at 12 mos |
| 4 | 68/F | Urinary tract sepsis | Sigmoidoscopy | Amoxicillin and metronidazole | 12 | Alive at 12 mos |
| 5 | 85/F | Sepsis of unknown source | None | Ceftriaxone | 8 | Alive at 12 mos |
| 6 | 87/M | Diabetic foot infection | None | Ticarcillin-clavulanate | 12 | Death on day 6 |
| 7 | 17/F | Fecal peritonitis secondary to anastomotic leak | Laparotomy, washout, end-ileostomy | Meropenem | 71 | Alive at 12 mos |
| 8 | 68/M | Perforated gangrenous appendicitis | Open appendectomy | Ceftriaxone and metronidazole | 8 | Alive at 12 mos |
| 9 | 57/F | Perforated sigmoid diverticulum | Pelvic washout + Hartmann's | Amoxicillin-clavulanate | 48 | Alive at 12 mos |
| 10 | 81/M | Diverticulitis | Colonoscopy | Ciprofloxacin and metronidazole | 19 | Death at 8 mos |
| 11 | 81/M | Prosthetic hip joint infection | None | Ticarcillin-clavulanate | 2 | Death on day 17 |
| 12 | 12/M | Gastroenteritis | None | None | 0 | Alive at 12 mos |
| 13 | 45/F | Diverticulitis | Colonoscopy | Cephalexin and metronidazole | 21 | Alive at 12 mos |
| 14 | 94/M | Ischial osteomyelitis | Debridement | Cotrimoxazole and ciprofloxacin | 301 | Alive at 12 mos |
| 15 | 81/M | Acute appendicitis | Laparoscopic appendectomy | Metronidazole | 3 | Alive at 12 mos |
| 16 | 37/M | Diverticular abscess with colovesical fistula | Gastroscopy | Meropenem | 32 | Death on day 24 |
| 17 | 11/M | Portal vein thrombophlebitis | None | Clindamycin and ciprofloxacin | 43 | Alive at 12 mos |
| 18 | 95/F | Myocardial infarction | Gastroscopy | Ceftriaxone and azithromycin | 4 | Death on day 4 |
| 19 | 29/F | Labor | None | None | 0 | Alive at 12 mos |
| 20 | 77/M | Colitis | Colonoscopy | Amoxicillin-clavulanate | 42 | Alive at 12 mos |
| 21 | 70/M | L1–L2 discitis, osteomyelitis, paravertebral abscess, psoas abscess, and meningitisc | CT-guided drainage | Meropenem and linezolid | 90 | Alive at 12 mos |
| 22 | 47/M | Perforated appendix | Laparoscopic appendectomy | Amoxicillin-clavulanate | 18 | Alive at 12 mos |
| 23 | 78/F | Viral gastroenteritis | None | None | 0 | Alive at 12 mos |
| 24 | 66/M | Stroke | Colonoscopy | Ceftriaxone and metronidazole | 44 | Alive at 12 mos |
| 25 | 87/F | Exacerbation of COPD | None | Amoxicillin and doxycycline | 6 | Death at 11 mos |
| 26 | 88/F | Colonic arteriovenous malformations, diverticular disease | Colonoscopy | Amoxicillin-clavulanate | 7 | Death at 7 mos |
| 27 | 66/M | Infected femoral artery puncture site, ischemic gut | Debridement and femoral arterial repair; gastroscopy, colonoscopy, and push enteroscopy | Meropenem | 43 | Death at 3 mos |
| 28 | 72/M | Biliary sepsis, pancreatic cancer | Percutaneous transhepatic cholangiogram | Amoxicillin-clavulanate and metronidazole | 46 | Death at 4 mos |
| 29 | 30/M | Gastroenteritis | None | None | 0 | Alive at 12 mos |
| 30 | 87/M | Sigmoid diverticulitis; Clostridium difficile colitis | None | Metronidazole | 23 | Death at 3 mos |
| 31 | 45/F | Left thigh abscess | Debridement and washout of abscess | Amoxicillin-clavulanate | 23 | Alive at 12 mos |
| 32 | 65/F | Non-small-cell lung cancer | Right upper/middle lobectomy; sigmoidoscopy | Piperacillin-tazobactam | 54 | Alive at 12 mos |
| 33 | 57/F | Enterocutaneous fistula | Laparotomy, mesh removal, fistula repair, cholecystectomy | Piperacillin-tazobactam | 22 | Alive at 12 mos |
F, female; M, male; COPD, chronic obstructive pulmonary disease; CT, computed tomography.
As most patients received multiple antibiotics, those displayed are the ones used for the longest time.
Previously described case report (12).
Abdominal imaging was performed in more than half of the total number of patients, and in three-fourths, an abnormality was found. Treatment was dependent on the underlying pathology, with 21/33 patients undergoing at least one procedure. Twelve patients underwent surgery, 3 had radiologically guided procedures (e.g., drainage of abscess), and 11 proceeded to diagnostic and/or therapeutic endoscopy. Antibiotic treatment was variable. Five patients received no antibiotic therapy, and all were alive at 1 year. These were generally patients with self-limiting illnesses who had clinically improved by the time their blood cultures had flagged positive, so their treating clinicians had decided that antibiotic therapy was not indicated. Of those treated with antibiotics, the median duration of treatment was 21.5 days (36.7 ± 56.2; 2 to 301). A wide range of antibiotics were used, most often metronidazole-containing regimens (8 patients) or amoxicillin-clavulanate (6 patients). A 1-year follow-up was available for all patients. Mortality from all causes was 6% at 7 days, 12% at 30 days, and 33% at 1 year.
Isolate identification.
A total of 28 isolates were available for comprehensive testing. All were confirmed as E. lenta using a Vitek-2 ANC card and 16S rRNA gene sequencing. Five older isolates originally identified by Rapid-ANA were not viable. Twenty-six isolates were available for testing in the Bruker MS system, which accurately identified all 26 to the genus level (log score, >1.7), including 19/26 as E. lenta (>2.0). Twenty-three isolates were tested in the bioMérieux MALDI system; all were identified as E. lenta with a 99.9% confidence value.
Antimicrobial susceptibility testing (AST).
Table 3 shows the AST results for 23 E. lenta isolates. Applying CLSI interpretative criteria (32), all isolates were susceptible to amoxicillin-clavulanate, cefoxitin, metronidazole, ertapenem, piperacillin-tazobactam, and meropenem. Susceptibility to clindamycin was 91%, to moxifloxacin was 74%, and to penicillin was 39%; all isolates were resistant to ceftriaxone. No CLSI breakpoints are available for tigecycline, vancomycin, or teicoplanin; however, all isolates had an MIC of ≤1 mg/liter. Using EUCAST breakpoints, interpretations were similar, except for penicillin and piperacillin-tazobactam, to which no isolates were susceptible (36).
TABLE 3.
Antimicrobial susceptibility testing results for 23 isolates plus control straina
| Patient isolate | MIC, mg/liter (interpretive criteria) or [no. (%) susceptible] |
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PEN | FOXb | CRO | AMC | TZP | CLI | MOXb | MET | ERT | MEM | TGC | VANc | TEC | |
| ATCC 43055 | 0.5 (S/I) | 8 (S) | >128 (R) | 1 (S) | 16 (S/I) | 0.25 (S) | 0.25 (S) | 2 (S) | 1 (S) | 0.5 (S) | 0.5 | 1 (S) | 0.12 |
| 3 | 1 (I/R) | 8 (S) | >128 (R) | 1 (S) | 16 (S/I) | 1 (S) | 0.5 (S) | 2 (S) | 1 (S) | 0.5 (S) | 0.5 | 1 (S) | 0.12 |
| 6 | 1 (I/R) | 8 (S) | >128 (R) | 1 (S) | 16 (S/I) | 0.25 (S) | 4 (I) | 2 (S) | 1 (S) | 0.5 (S) | 0.5 | 1 (S) | 0.12 |
| 8 | 0.5 (S/I) | 4 (S) | 128 (R) | 1 (S) | 16 (S/I) | 0.25 (S) | 4 (I) | 2 (S) | 1 (S) | 0.25 (S) | 0.5 | 1 (S) | 0.12 |
| 9 | 1 (I/R) | 8 (S) | 128 (R) | 1 (S) | 16 (S/I) | 0.5 (S) | 8 (R) | 2 (S) | 1 (S) | 0.5 (S) | 0.5 | 1 (S) | 0.12 |
| 10 | 0.5 (S/I) | 8 (S) | 128 (R) | 1 (S) | 16 (S/I) | 0.25 (S) | 4 (I) | 2 (S) | 1 (S) | 0.25 (S) | 1 | 1 (S) | 0.12 |
| 11 | 1 (I/R) | 16 (S) | >128 (R) | 1 (S) | 32 (S/R) | 0.5 (S) | 0.25 (S) | 2 (S) | 1 (S) | 0.5 (S) | 0.5 | 1 (S) | 0.12 |
| 12 | 0.5 (S/I) | 8 (S) | >128 (R) | 1 (S) | 16 (S/I) | 0.25 (S) | 0.5 (S) | 2 (S) | 1 (S) | 0.5 (S) | 0.5 | 1 (S) | 0.12 |
| 13 | 1 (I/R) | 8 (S) | >128 (R) | 1 (S) | 16 (S/I) | 0.25 (S) | 0.25 (S) | 2 (S) | 1 (S) | 0.5 (S) | 0.5 | 1 (S) | 0.12 |
| 14 | 1 (I/R) | 8 (S) | >128 (R) | 1 (S) | 16 (S/I) | 0.12 (S) | 0.25 (S) | 2 (S) | 1 (S) | 0.5 (S) | 1 | 1 (S) | 0.25 |
| 16 | 0.5 (S/I) | 8 (S) | >128 (R) | 1 (S) | 16 (S/I) | 2 (S) | 0.25 (S) | 2 (S) | 1 (S) | 0.5 (S) | 0.5 | 0.5 (S) | 0.12 |
| 17 | 1 (I/R) | 16 (S) | >128 (R) | 1 (S) | 32 (S/R) | 0.5 (S) | 0.25 (S) | 2 (S) | 1 (S) | 0.5 (S) | 0.5 | 1 (S) | 0.12 |
| 18 | 0.5 (S/I) | 8 (S) | >128 (R) | 1 (S) | 16 (S/I) | 0.25 (S) | 1 (S) | 2 (S) | 1 (S) | 0.5 (S) | 1 | 1 (S) | 0.12 |
| 19 | 0.5 (S/I) | 8 (S) | >128 (R) | 1 (S) | 16 (S/I) | 32 (R) | 0.25 (S) | 2 (S) | 1 (S) | 0.25 (S) | 0.5 | 1 (S) | 0.12 |
| 21 | 1 (I/R) | 8 (S) | >128 (R) | 1 (S) | 16 (S/I) | 8 (R) | 64 (R) | 2 (S) | 1 (S) | 0.5 (S) | 0.5 | 1 (S) | 0.12 |
| 22 | 0.5 (S/I) | 8 (S) | >128 (R) | 1 (S) | 16 (S/I) | 0.25 (S) | 0.25 (S) | 2 (S) | 1 (S) | 0.5 (S) | 1 | 1 (S) | 0.25 |
| 23 | 0.5 (S/I) | 8 (S) | >128 (R) | 1 (S) | 16 (S/I) | 0.25 (S) | 0.25 (S) | 2 (S) | 1 (S) | 0.5 (S) | 0.5 | 1 (S) | 0.25 |
| 24 | 1 (I/R) | 8 (S) | >128 (R) | 1 (S) | 16 (S/I) | 0.25 (S) | 4 (I) | 2 (S) | 1 (S) | 0.5 (S) | 1 | 1 (S) | 0.25 |
| 25 | 1 (I/R) | 16 (S) | >128 (R) | 1 (S) | 16 (S/I) | 0.25 (S) | 0.25 (S) | 2 (S) | 1 (S) | 0.5 (S) | 0.5 | 1 (S) | 0.12 |
| 26 | 1 (I/R) | 8 (S) | >128 (R) | 1 (S) | 16 (S/I) | 0.12 (S) | 2 (S) | 2 (S) | 1 (S) | 0.25 (S) | 0.5 | 1 (S) | 0.25 |
| 27 | 1 (I/R) | 8 (S) | >128 (R) | 1 (S) | 16 (S/I) | 1 (S) | 0.25 (S) | 2 (S) | 1 (S) | 0.5 (S) | 0.5 | 1 (S) | 0.25 |
| 28 | 1 (I/R) | 8 (S) | >128 (R) | 1 (S) | 32 (S/R) | 0.5 (S) | 0.25 (S) | 2 (S) | 1 (S) | 0.5 (S) | 0.5 | 1 (S) | 0.12 |
| 29 | 1 (I/R) | 8 (S) | >128 (R) | 1 (S) | 32 (S/R) | 0.5 (S) | 0.25 (S) | 2 (S) | 1 (S) | 0.5 (S) | 0.5 | 1 (S) | 0.12 |
| 30 | 0.5 (S/I) | 8 (S) | >128 (R) | 1 (S) | 16 (S/I) | 0.25 (S) | 0.25 (S) | 2 (S) | 1 (S) | 0.5 (S) | 0.5 | 1 (S) | 0.12 |
| Total [no. (%) susceptible] | 9 (39) | 23 (100) | 0 | 23 (100) | 23 (100) | 21 (91) | 17 (74) | 23 (100) | 23 (100) | 23 (100) | NB | 23 (100) | NB |
PEN, penicillin; FOX, cefoxitin; CRO, ceftriaxone; AMC, amoxicillin-clavulanate; TZP, piperacillin-tazobactam; CLI, clindamycin; MOX, moxifloxacin; MET, metronidazole; ERT, ertapenem; MEM, meropenem; TGC, tigecycline; VAN, vancomycin; TEC, teicoplanin; S, susceptible; I, intermediate; R, resistant; CLSI/EUCAST results (where interpretations are discordant); NB: no breakpoints available.
CLSI breakpoint only.
EUCAST breakpoint only.
van gene PCR.
A total of 23 E. lenta isolates were tested; all were negative for vanA and vanB genes. All positive controls tested positive.
DISCUSSION
Our report represents the largest, most comprehensive study of patients with E. lenta bacteremia described in the literature to date. Our findings suggest that E. lenta bacteremia is associated with a spectrum of disease, ranging from asymptomatic bacteremia (generally seen in the setting of a transient gastrointestinal illness) to part-polymicrobial bacteremia from an intra-abdominal source (e.g., perforated viscus) to severe monomicrobial disseminated disease. A significant proportion of our cohort had serious GIT pathology, often requiring surgical or radiological intervention and ICU admission to achieve cure. This suggests that when identified in blood cultures, E. lenta should not necessarily be dismissed as a contaminant but rather should represent a trigger for more-detailed evaluation of the patient and appropriate abdominal diagnostic imaging.
Published reports of E. lenta bacteremia are outlined in Table 4. Our cohort has some differences from previous case series. Venugopal et al. (14) provided detailed clinical information on 25 cases but no microbiological data. They reported a higher proportion of health care onset bacteremias (50%). Only 44% of their patients had an abdominal disease source, and 40% had a skin or soft-tissue disease source, most often infected decubitus ulcers, associated with high (44%) rates of hospitalized, bedridden patients. They identified ICU admission and absence of fever on the day of admission as risk factors for increased 30-day mortality, which was much higher than in our series (36% versus 12%). Interestingly, of our 10 patients admitted to ICU, all were alive at 30 days, and of the 4 patients dead at 30 days, 2 were febrile on admission. Lee et al. (13) described 7 patients with E. lenta bacteremia. They had a comparatively lower median age of 56, 71% were in the community onset category, and 43% had an underlying malignancy. The report did not identify the source of infections, although 30% had “abdominal symptoms.” Lau et al. (5, 6) described 5 cases of E. lenta bacteremia, 3 of which were polymicrobial and 2 of which occurred in patients with infected decubitus ulcers.
TABLE 4.
Previously reported case series and case reports of E. lenta bacteremia
| Category and reference (no. of patients) | Age(s) (range)/no. of patients of indicated sex | Diagnosis | Treatment detail(s) |
Outcome | ||
|---|---|---|---|---|---|---|
| Procedure | Antibiotic | Duration | ||||
| Case series | ||||||
| 14 (25) | 36–90/5 M | Decubitus ulcer (8 patients) | NSa | 4 received piperacillin-tazobactam, 1 metronidazole and ciprofloxacin, 1 ampicillin-sulbactam—amoxicillin-clavulanate, 1 vancomycin, ceftazidime and metronidazole, 1 ceftriaxone and metronidazole | NS | 50% survival |
| 36–83/4 M | Intra-abdominal sepsis (10 patients) | NS | Different regimens, including piperacillin-tazobactam, amoxicillin-clavulanate, ciprofloxacin or ceftriaxone and metronidazole, imipenem/cilastatin | NS | 80% survival | |
| 72, 78/F | Urinary source (2 patients) | NS | Ceftriaxone-ciprofloxacin; vancomycin and metronidazole | NS | 50% survival | |
| 51/M | Gluteal abscess and left hip osteomyelitis | NS | Piperacillin-tazobactam | NS | Survived | |
| 81/M, 72/F | Not stated (2 patients) | NS | Metronidazole and ciprofloxacin; none | NS | 50% survival | |
| 71/F | Gastrointestinal bleed | NS | None | NS | Death | |
| 79/F | Percutaneous endoscopy gastrostomy site infection | NS | Clindamycin | NS | Survival | |
| 13 (7) | Median, 56 (51–93) | Two patients had “abdominal symptoms” | NS | 2 received penicillins, 4 cephalosporins, 1 metronidazole | NS | 3 deaths within 60 days |
| 5, 6b (5) | 69/F | Lung cancer, intestinal obstruction | NS | Metronidazole | NS | Cured |
| 74/M | Alcoholic cirrhosis, gastrointestinal bleeding | NS | Ticarcillin/clavulanate | NS | Died | |
| 75/F | Pelvic inflammatory disease | NS | Cefuroxime + metronidazole | NS | Cured | |
| 87/F | Infected decubitus ulcer | NS | Cefuroxime + cloxacillin | NS | Died | |
| 84/F | Infected decubitus ulcer | NS | Cefuroxime + metronidazole + netilmicin | NS | Cured | |
| 37 (2) | 82/M | Intestinal perforation | Colostomy | Piperacillin-tazobactam and ciprofloxacin, imipenem | 1 mo | Favorable |
| 33/M | Acute appendicitis and parietal abscess | Appendicectomy | Amoxicillin-clavulanate | Unclear | Favorablec | |
| Case reports | ||||||
| 12 | 70/M | Spondylodiscitis, osteomyelitis, meningitis, and multiple abscesses | Drainage of subdiaphragmatic and right psoas collections | Meropenem and linezolid | 3 mos | Favorable |
| 38 | 19/M | Multifocal abscesses—brain, liver, spleen, lung | Laparoscopic cholecystectomy | i.v.d penicillin G and oral metronidazole | 5 mos | Favorable |
| 39 | 53/M | Metastatic rectal cancer | None | i.v. cefotaxime and amikacin—oral antibiotics | >4 days | Favorablec |
| 40 | 21/F | Crohn's disease; small bowel obstruction | Ileocecal resection and repair of anastomotic leak | Vancomycin and piperacillin-tazobactam—vancomycin, meropenem and metronidazole—meropenem | 3 weeks | Favorablec |
| 41 | 86/F | Infected decubitus ulcer | None | Cefuroxime—amoxicillin | >2 days | Favorablec |
| 42 | 68/F | Tubo-ovarian abscess; postoperative bowel leak | Hysterectomy, salpingo-oophrectomy; sigmoid resection and Hartmann's, drainage of perisplenic collection | Ampicillin, gentamicin, metronidazole—vancomycin, ticarcillin/clavulanate, metronidazole | >1 mo | Favorablec |
NS, not stated.
Two publications describing the same patient cohort.
Alive and well at hospital discharge; long-term follow-up not reported.
i.v., intravenous.
In addition to these series, there are 6 published case reports of patients with E. lenta bacteremia. Two describe severe, disseminated disease with multifocal abscesses requiring extended courses of intravenous antibiotics and/or surgical drainage to cure (12, 38). There are other published cases of severe E. lenta infection without definite bacteremia, including reports of frontal sinusitis (43), pyomyositis (44), cutaneous abscesses (45), spondylodiscitis (46), and liver abscess (47). E. lenta has also been implicated in the pathogenesis of bacterial vaginosis (48–50) and linked to appendicitis in children (51).
Identification of E. lenta by MALDI-TOF was initially not reliable due to the limited number of anaerobic bacterial species included in earlier versions of the databases (28, 52). In 2011, Justesen et al. (30) reported that one E. lenta isolate was identified by the Bruker MS method using an updated database but not by the Shimadzu MALDI-TOF MS method. In more recent studies, E. lenta has been correctly identified using the Bruker MS method: 2/2 isolates to the species level (15), 8/8 isolates to the genus level and 6/8 isolates to the species level (16), and 8/10 isolates to the genus level and 2/10 isolates to the species level (17). Our study showed that E. lenta can be reliably identified using both available commercial MALDI-TOF MS platforms.
Access to anaerobic AST is problematic, however, and a lack of available data has led to breakpoint extrapolation from other anaerobic species to E. lenta. Our antimicrobial susceptibility results are consistent with those of previous studies (Table 5), which have shown that isolates are frequently resistant to penicillin and have variable susceptibility to clindamycin and moxifloxacin but remain susceptible to amoxicillin-clavulanate, cefoxitin, metronidazole, and carbapenems. The differences between the EUCAST (susceptible [S], ≤8/4 mg/liter; resistant [R], >16/4 mg/liter) and CLSI (S, ≤32/4 mg/liter; intermediate [I], 64/4 mg/liter; R, ≥128/4 mg/liter) breakpoints for piperacillin-tazobactam are significant and, given the high piperacillin-tazobactam MICs of our isolates, have resulted in significant differences in the interpretations of our susceptibility results. Neither criterion is supported by clinical outcome studies, and it may well be that piperacillin-tazobactam has activity against E. lenta. Although vanB has been detected previously in E. lenta in our laboratory (21–23) and high vancomycin MICs have been reported in the literature (53), we did not detect vancomycin resistance gene vanA or vanB or phenotypic resistance in any of the isolates that were tested.
TABLE 5.
E. lenta MIC ranges and susceptibility rates reported in the literaturea
| Reference (yr) | No. of isolates | MIC range (mg/liter), % susceptibleb |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PEN | FOX | CRO | AMC | TZP | CLI | MOX | MET | ERT | MEM | TGC | VAN | ||
| 53 (2013) | 20 | 0.125 to 0.5 | 1 to 8 | ||||||||||
| 54 (2013) | 10 | 8 to 16, 100 | 16 to 64, 90 | 0.25 to 0.5, 100 | 0.5 to 1, 100 | 1 to 2, 100 | 0.5 | ||||||
| 13 (2012) | 8 | 1 to 4, 0 | 32 to 64, 87.5 | 0.5 to >32, 37.5 | 0.25 to >32, 75 | 1 to 2, 100 | 0.5, 100 | 0.12 to 0.25 | 0.5 to 2 | ||||
| 55 (2009) | 17 | 0.5 to 1 | 8 to 16 | 0 to >32 | 0.25 to 0.5 | ||||||||
| 33 (2006) | 10 | ≤0.06 to 4, 10 | 0.5 to 8, 100 | ≤0.12 to 256, 30 | ≤0.06 to 1, 100 | ≤0.12 to 32, 100 | ≤0.06 to 1, 100 | 0.12 to 1, 100 | ≤0.06 to 0.5, 100 | ||||
| 6 (2005) | 9 | 0.12 to 0.5* | 0.12 to 0.5 | 0.5 to 1 | |||||||||
| 56 (2005) | 14 | ≤0.12 to 32 | ≤0.06 to 1 | 0.25 to 2 | |||||||||
| 57 (2004) | 10 | ≤0.03 to 0.5* | ≤0.03 to 32 | 0.5 to 1 | |||||||||
| 58 (2004) | 20 | 0.25 to 32, 95 | 0.12 to 8, 90 | 0.03 to 1, 100 | 0.06 to 4, 100 | ||||||||
| 59 (2003) | 8 | 1* | 1 | 0.06 to 0.25 | 0.25 to 0.5 | ≤0.125 to 0.5 | 1 to 2 | ||||||
| 60 (2003) | 12 | ≤0.06 to 1* | ≤0.06 to 2 | ≤0.06 to 0.5 | ≤0.06 to 1 | ≤0.06 to >64 | |||||||
| 61 (2003) | 17 | 0.25 to 2* | 1 to 16 | ≤0.03 to 1 | 0.125 to 1 | 0.5 to 2 | |||||||
| 62 (2002) | 16 | 0.25 to >64 | ≤0.125 to 32 | 0.03 to >32 | 0.25 to >16 | 0.06 to 2 | 0.06 to 4 | ||||||
| 64 (1998) | Group A, 25 | 2,* 0 | 32 to 128, 0 | 0.5 to 4, 88 | 1 to 2, 100 | ||||||||
| Group B, 6 | 0.5,* 100 | 1, 100 | ≤0.06, 100 | 1 to 2, 100 | |||||||||
All studies utilized CLSI agar dilution methodology and CLSI breakpoints.
PEN, penicillin (*, ampicillin); FOX, cefoxitin; CRO, ceftriaxone; AMC, amoxicillin-clavulanate; TZP, piperacillin-tazobactam; CLI, clindamycin; MOX, moxifloxacin; MET, metronidazole; ERT, ertapenem; MEM, meropenem; TGC, tigecycline; VAN, vancomycin.
In summary, Eggerthella lenta appears to be a significant human pathogen that is often associated with serious GIT pathology. If the diagnosis is not apparent at the time of isolation of this organism in blood cultures, detailed investigation of the abdomen should be undertaken. E. lenta is likely to be increasingly identified given the ease and rapidity of MALDI-TOF MS and the uptake of this technology into many clinical microbiology laboratories worldwide. The most reliable antibiotic treatment options appear to be cefoxitin, metronidazole, amoxicillin-clavulanate, and the carbapenems, with the role of piperacillin-tazobactam currently unclear. However, with rising rates of resistance in anaerobes increasingly reported, AST should be considered to guide therapy, particularly in serious infections.
ACKNOWLEDGMENTS
We thank the Microbiology Departments at Monash Health (particularly Richard Streitberg and Megan Wieringa) and Auckland Hospital (Patricia Dove, Audrey Tiong, and Nadia Al Anbuky).
We declare that we have no conflicts of interest.
The work represented by this article received no financial support.
REFERENCES
- 1.Eggerth AH. 1935. The Gram-positive non-spore-bearing anaerobic bacilli of human feces. J Bacteriol 30:277–299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Moore WEC, Cato EP, Holdeman LV. 1971. Eubacterium lentum (Eggerth) Prevot 1938: emendation of description and designation of the Neotype strain. Int J Syst Bacteriol 21:299–303. [Google Scholar]
- 3.Kageyama A, Benno Y, Nakase T. 1999. Phylogenetic evidence for the transfer of Eubacterium lentum to the genus Eggerthella as Eggerthella lenta gen. nov., comb. nov. Int J Syst Bacteriol 49(Pt 4):1725–1732. [DOI] [PubMed] [Google Scholar]
- 4.Wade WG, Downes J, Dymock D, Hiom SJ, Weightman AJ, Dewhirst FE, Paster BJ, Tzellas N, Coleman B. 1999. The family Coriobacteriaceae: reclassification of Eubacterium exiguum (Poco et al. 1996) and Peptostreptococcus heliotrinreducens (Lanigan 1976) as Slackia exigua gen. nov., comb. nov. and Slackia heliotrinireducens gen. nov., comb. nov., and Eubacterium lentum (Prevot 1938) as Eggerthella lenta gen. nov., comb. nov. Int J Syst Bacteriol 49(Pt 2):595–600. [DOI] [PubMed] [Google Scholar]
- 5.Lau SK, Woo PC, Woo GK, Fung AM, Wong MK, Chan KM, Tam DM, Yuen KY. 2004. Eggerthella hongkongensis sp. nov. and eggerthella sinensis sp. nov., two novel Eggerthella species, account for half the cases of Eggerthella bacteremia. Diagn Microbiol Infect Dis 49:255–263. doi: 10.1016/j.diagmicrobio.2004.04.012. [DOI] [PubMed] [Google Scholar]
- 6.Lau SK, Woo PC, Fung AM, Chan KM, Woo GK, Yuen KY. 2004. Anaerobic, non-sporulating, Gram-positive bacilli bacteremia characterized by 16S rRNA sequencing. J Med Microbiol 53:1247–1253. doi: 10.1099/jmm.0.45803-0. [DOI] [PubMed] [Google Scholar]
- 7.Wurdemann D, Tindall BJ, Pukall R, Lunsdorf H, Strompl C, Namuth T, Nahrstedt H, Wos-Oxley M, Ott S, Schreiber S, Timmis KN, Oxley AP. 2009. Gordonibacter pamelaeae gen. nov., sp. nov., a new member of the Coriobacteriaceae isolated from a patient with Crohn's disease, and reclassification of Eggerthella hongkongensis Lau et al. 2006 as Paraeggerthella hongkongensis gen. nov., comb. nov. Int J Syst Evol Microbiol 59:1405–1415. doi: 10.1099/ijs.0.005900-0. [DOI] [PubMed] [Google Scholar]
- 8.Saunders E, Pukall R, Abt B, Lapidus A, Glavina Del Rio T, Copeland A, Tice H, Cheng JF, Lucas S, Chen F, Nolan M, Bruce D, Goodwin L, Pitluck S, Ivanova N, Mavromatis K, Ovchinnikova G, Pati A, Chen A, Palaniappan K, Land M, Hauser L, Chang YJ, Jeffries CD, Chain P, Meincke L, Sims D, Brettin T, Detter JC, Göker M, Bristow J, Eisen JA, Markowitz V, Hugenholtz P, Kyrpides NC, Klenk HP, Han C. 2009. Complete genome sequence of Eggerthella lenta type strain (VPI 0255T). Stand Genomic Sci 1:174–182. doi: 10.4056/sigs.33592. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Yokoyama SI, Oshima K, Nomura I, Hattori M, Suzuki T. 2011. Complete genomic sequence of the equol-producing bacterium Eggerthella sp. strain YY7918, isolated from adult human intestine. J Bacteriol 193:5570–5571. doi: 10.1128/JB.05626-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Li F, Hullar MAJ, Schwarz Y, Lampe JW. 2009. Human gut bacterial communities are altered by addition of cruciferous vegetables to a controlled fruit- and vegetable-free diet. J Nutr 139:1685–1691. doi: 10.3945/jn.109.108191. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Brook I, Frazier EH. 1993. Significant recovery of nonsporulating anaerobic rods from clinical specimens. Clin Infect Dis 16:476–480. doi: 10.1093/clind/16.4.476. [DOI] [PubMed] [Google Scholar]
- 12.Gardiner BJ, Korman TM, Junckerstorff RK. 2014. Eggerthella lenta bacteremia complicated by spondylodiscitis, psoas abscess and meningitis. J Clin Microbiol 52:1278–1280. doi: 10.1128/JCM.03158-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Lee MR, Huang YT, Liao CH, Chuang TY, Wang WJ, Lee SW, Lee LN, Hsueh PR. 2012. Clinical and microbiological characteristics of bacteremia caused by Eggerthella, Paraeggerthella, and Eubacterium species at a university hospital in Taiwan from 2001 to 2010. J Clin Microbiol 50:2053–2055. doi: 10.1128/JCM.00548-12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Venugopal AA, Szpunar S, Johnson LB. 2012. Risk and prognostic factors among patients with bacteremia due to Eggerthella lenta. Anaerobe 18:475–478. doi: 10.1016/j.anaerobe.2012.05.005. [DOI] [PubMed] [Google Scholar]
- 15.Fedorko DP, Drake SK, Stock F, Murray PR. 2012. Identification of clinical isolates of anaerobic bacteria using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Eur J Clin Microbiol Infect Dis 31:2257–2262. doi: 10.1007/s10096-012-1563-4. [DOI] [PubMed] [Google Scholar]
- 16.Schmitt BH, Cunningham SA, Dailey AL, Gustafson DR, Patel R. 2013. Identification of anaerobic bacteria by Bruker Biotyper matrix-assisted desorption ionization-time of flight mass spectrometry with on-plate formic acid preparation. J Clin Microbiol 51:782–786. doi: 10.1128/JCM.02420-12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Barreau M, Pagnier I, La Scola B. 2013. Improving the identification of anaerobes in the clinical microbiology laboratory through MALDI-TOF mass spectrometry. Anaerobe 22:123–125. doi: 10.1016/j.anaerobe.2013.04.011. [DOI] [PubMed] [Google Scholar]
- 18.Wybo I, Van den Bossche D, Soetens O, Vekens E, Vandoorslae K, Claeys G, Glupczynski Y, Leven M, Melin P, Nonhoff C, Rodriguez-Villalobos H, Verhaegen J, Piéard D. 2014. Fourth Belgian multicenter survey of antibiotic susceptibility of anaerobic bacteria. J Antimicrob Chemother 69:155–161. doi: 10.1093/jac/dkt344. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Snydman DR, Jacobus NV, McDermott LA, Golan Y, Goldstein EJ, Harrell L, Jenkins S, Newton D, Pierson C, Rosenblatt J, Venezia R, Gorbach SL, Queenan AM, Hecht DW. 2011. Update on resistance of Bacteroides fragilis group and related species with special attention to carbapenems 2006–2009. Anaerobe 17:147–151. doi: 10.1016/j.anaerobe.2011.05.014. [DOI] [PubMed] [Google Scholar]
- 20.Schuetz AN. 2014. Antimicrobial resistance and susceptibility testing of anaerobic bacteria. Clin Infect Dis 59:698–705. doi: 10.1093/cid/ciu395. [DOI] [PubMed] [Google Scholar]
- 21.Stinear TP, Olden DC, Johnson PDR, Davies JK, Grayson ML. 2001. Enterococcal vanB resistance locus in anaerobic bacteria in human faeces. Lancet 357:855–856. doi: 10.1016/S0140-6736(00)04206-9. [DOI] [PubMed] [Google Scholar]
- 22.Ballard SA, Grabsch EA, Johnson PD, Grayson ML. 2005. Comparison of three PCR primer sets for identification of vanB gene carriage in feces and correlation with carriage of vancomycin-resistant enterococci: interference by vanB-containing anaerobic bacilli. Antimicrob Agents Chemother 49:77–81. doi: 10.1128/AAC.49.1.77-81.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Ballard SA, Pertile KK, Lim M, Johnson PD, Grayson ML. 2005. Molecular characterization of vanB elements in naturally occurring gut anaerobes. Antimicrob Agents Chemother 49:1688–1694. doi: 10.1128/AAC.49.5.1688-1694.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Le Gall JR, Lemeshow S, Saulnier F. 1993. A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963. [DOI] [PubMed] [Google Scholar]
- 25.Paterson DL, Ko WC, Von Gottberg A, Mohapatra S, Casellas JM, Goossens H, Mulazimoglu L, Trenholme G, Klugman KP, Bonomo RA, Rice LB, Wagener MM, McCormack JG, Yu VL. 2004. Antibiotic therapy for Klebsiella pneumonia bacteremia: implications of production of extended-spectrum beta-lactamases. Clin Infect Dis 39:31–37. doi: 10.1086/420816. [DOI] [PubMed] [Google Scholar]
- 26.Charlson ME, Pompei P, Ales KL, MacKenzie CR. 1987. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383. doi: 10.1016/0021-9681(87)90171-8. [DOI] [PubMed] [Google Scholar]
- 27.Hall WH, Ramachandran R, Narayan S, Jani AB, Vijayakumar S. 2004. A new electronic application for rapidly calculating Charlson comorbidity score. BMC Cancer 4:94. doi: 10.1186/1471-2407-4-94. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Veloo AC, Knoester M, Degener JE, Kuijper EJ. 2011. Comparison of two matrix-assisted laser desorption ionisation-time of flight mass spectrometry methods for the identification of clinically relevant anaerobic bacteria. Clin Microbiol Infect 17:1501–1506. doi: 10.1111/j.1469-0691.2011.03467.x. [DOI] [PubMed] [Google Scholar]
- 29.Haigh J, Degun A, Eydmann M, Millar M, Wilks M. 2011. Improved performance of bacterium and yeast identification by a commercial matrix-assisted laser desorption ionization-time of flight mass spectrometry system in the clinical microbiology laboratory. J Clin Microbiol 49:3441. doi: 10.1128/JCM.00576-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Justesen US, Holm A, Knudsen E, Anderson LB, Jensen TG, Kemp M, Skov MN, Gahrn-Hansen B, Møller JK. 2011. Species identification of clinical isolates of anaerobic bacteria: a comparison of two matrix-assisted laser desorption ionization-time of flight mass spectrometry systems. J Clin Microbiol 49:4314–4318. doi: 10.1128/JCM.05788-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Barry AL, Zabransky RJ. 1990. Eubacterium lentum ATCC 43055, a new reference strain for quality control of anaerobic susceptibility tests. J Clin Microbiol 28:2375–2376. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Clinical and Laboratory Standards Institute (CLSI). 2012. Methods for antimicrobial susceptibility testing of anaerobic bacteria; approved standard—eighth edition. CLSI document M11-A8. CLSI, Wayne, PA. [Google Scholar]
- 33.Roberts SA, Shore KP, Paviour SD, Holland D, Morris AJ. 2006. Antimicrobial susceptibility of anaerobic bacteria in New Zealand: 1999–2003. J Antimicrob Chemother 57:992–998. doi: 10.1093/jac/dkl052. [DOI] [PubMed] [Google Scholar]
- 34.Biodisk AB. 1996. Etest technical guide 1B: susceptibility testing of anaerobes. AB Biodisk, Solna, Sweden. [Google Scholar]
- 35.Palladino S, Kay ID, Costa AM, Lambert EJ, Flexman JP. 2003. Real-time PCR for the rapid detection of vanA and vanB genes. Diagn Microbiol Infect Dis 45:81–84. doi: 10.1016/S0732-8893(02)00505-9. [DOI] [PubMed] [Google Scholar]
- 36.The European Committee on Antimicrobial Susceptibility Testing. 2014. Breakpoint tables for interpretation of MICs and zone diameters. Version 4.0. http://www.eucast.org. [Google Scholar]
- 37.Landais C, Doudier B, Imbert G, Fenollar F, Brouqui P. 2007. Application of rrs gene sequencing to elucidate the clinical significance of Eggerthella lenta infection. J Clin Microbiol 45:1063–1065. doi: 10.1128/JCM.01805-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Salameh A, Klotz SA, Zangeneh TT. 2012. Disseminated infection caused by Eggerthella lenta in a previously healthy young man: a case report. Case Rep Infect Dis 2012:517637. doi: 10.1155/2012/517637. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Lee HJ, Hong SK, Choi WS, Kim EC. 2014. The first case of Eggerthella lenta bacteremia in Korea. Ann Lab Med 34:177–179. doi: 10.3343/alm.2014.34.2.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Thota VR, Dacha S, Natarajan A, Nerad J. 2011. Eggerthella lenta bacteremia in a Crohn's disease patient after ileocecal resection. Future Microbiol 6:595–597. doi: 10.2217/fmb.11.31. [DOI] [PubMed] [Google Scholar]
- 41.Liderot K, Larsson M, Boräng S, Ozenci V. 2010. Polymicrobial bloodstream infection with Eggerthella lenta and Desulfovibrio desulfuricans. J Clin Microbiol 48:3810–3812. doi: 10.1128/JCM.02481-09. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42.Chan RC, Mercer J. 2008. First Australian description of Eggerthella lenta bacteremia identified by 16S rRNA gene sequencing. Pathology 40:409–439. doi: 10.1080/00313020802036772. [DOI] [PubMed] [Google Scholar]
- 43.Moon T, Lin RY, Jahn AF. 1986. Fatal frontal sinusitis due to Neisseria sicca and Eubacterium lentum. J Otolaryngol 15:193–195. [PubMed] [Google Scholar]
- 44.Palomino-Nicás J, González E, Arroyo A, Cañas E, Hernanz W, Pachón J. 1996. Pyomyositis due to Eubacterium lentum and Streptococcus constellatus from a periodontal source. Clin Infect Dis 22:176–178. doi: 10.1093/clinids/22.1.176. [DOI] [PubMed] [Google Scholar]
- 45.Lattuada E, Zorzi A, Lanzafame M, Antolini D, Fontana R, Vento S, Concia E. 2005. Cutaneous abscess due to Eubacterium lentum in injection drug user: a case report and review of the literature. J Infect 51:E71–E72. doi: 10.1016/j.jinf.2004.08.026. [DOI] [PubMed] [Google Scholar]
- 46.Bok CW, Ng YS. 2009. Eggerthella lenta as a cause of anaerobic spondylodiscitis. Singapore Med J 50:e393–e396. [PubMed] [Google Scholar]
- 47.Elias RM, Khoo SY, Pupaibool J, Nienaber JS, Cummins NW. 2012. Multiple pyogenic liver abscesses caused by Eggerthella lenta treated with ertapenem: a case report. Case Rep Med 2012:718130. doi: 10.1155/2012/718130. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48.Srinivasan S, Hoffman NG, Morgan MT, Matsen FA, Fiedler TL, Hall RW, Ross FJ, McCoy CO, Bumgarner R, Marrazzo JM, Fredricks DN. 2012. Bacterial communities in women with bacterial vaginosis: high resolution phylogenetic analyses reveal relationships of microbiota to clinical criteria. PLoS One 7:e37818. doi: 10.1371/journal.pone.0037818. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49.Ling ZX, Kong JM, Liu F, Zhu HB, Chen XY, Wang YZ, Li LJ, Nelson KE, Xia YX, Xiang C. 2010. Molecular analysis of the diversity of vaginal microbiota associated with bacterial vaginosis. BMC Genomics 11:488. doi: 10.1186/1471-2164-11-488. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 50.Shipitsyna E, Annika R, Datcu R, Hallén A, Fredlung H, Jensen JS, Engstrand L, Unemo M. 2013. Composition of the vaginal microbiota in women of reproductive age – sensitive and specific molecular diagnosis of bacterial vaginosis is possible? PLoS One 8:e60670. doi: 10.1371/journal.pone.0060670. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51.Rautio M, Saxen H, Siitonen A, Nikku R, Jousimies-Somer H. 2000. Bacteriology of histopathologically defined appendicitis in children. Pediatr Infect Dis J 19:1078–1083. [DOI] [PubMed] [Google Scholar]
- 52.La Scola B, Fournier PE, Raoult D. 2011. Burden of emerging anaerobes in the MALDI-TOF and 16S rRNA gene sequencing era. Anaerobe 17:106–112. doi: 10.1016/j.anaerobe.2011.05.010. [DOI] [PubMed] [Google Scholar]
- 53.Goldstein EJ, Citron DM, Tyrrell KL, Merriam CV. 2013. Comparative in vitro activities of SMT19969, a new antimicrobial agent, against Clostridium difficile and 350 gram-positive and gram-negative aerobic and anaerobic intestinal flora isolates. Antimicrob Agents Chemother 57:4872–4876. doi: 10.1128/AAC.01136-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 54.Goldstein EJ, Citron DM, Tyrrell KL, Merriam CV. 2013. In vitro activity of Biapenem plus RPX7009, a carbapenem combined with a serine β-lactamase inhibitor, against anaerobic bacteria. Antimicrob Agents Chemother 57:2620–2630. doi: 10.1128/AAC.02418-12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55.Ednie LM, Appelbaum PC. 2009. Antianaerobic activity of sulopenem compared to six other agents. Antimicrob Agents Chemother 53:2163–2170. doi: 10.1128/AAC.01557-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 56.Bradford PA, Weaver-Sands DT, Petersen PJ. 2005. In vitro activity of tigecycline against isolates from patients enrolled in phase 3 clinical trials of treatment for complicated skin and skin-structure infections and complicated intra-abdominal infections. Clin Infect Dis 41(Suppl 5):S315–32. doi: 10.1086/431673. [DOI] [PubMed] [Google Scholar]
- 57.Goldstein EJ, Citron DM, Merriam CV, Warren YA, Tyrrell KL, Fernandez HT. 2004. In vitro activities of the new semisynthetic glycopeptide telavancin (TD-6424), vancomycin, daptomycin, linezolid, and four comparator agents against anaerobic gram-positive species and Corynebacterium spp. Antimicrob Agents Chemother 48:2149–2152. doi: 10.1128/AAC.48.6.2149-2152.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 58.Edmiston CE, Krepel CJ, Seabrook GR, Somberg LR, Nakeeb A, Cambria RA, Towne JB. 2004. In vitro activities of moxifloxacin against 900 aerobic and anaerobic surgical isolates from patients with intra-abdominal and diabetic foot infections. Antimicrob Agents Chemother 48:1012–1016. doi: 10.1128/AAC.48.3.1012-1016.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 59.Ednie LM, Rattan A, Jacobs MR, Appelbaum PC. 2003. Antianaerobe activity of RBX 7644 (ranbezolid), a new oxazolidinone, compared with those of eight other agents. Antimicrob Agents Chemother 47:1143–1147. doi: 10.1128/AAC.47.3.1143-1147.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 60.Liebetrau A, Rodloff AC, Behra-Miellet J, Dubreuil L. 2003. In vitro activities of a new des-fluoro(6) quinolone, garenoxacin, against clinical anaerobic bacteria. Antimicrob Agents Chemother 47:3667–3671. doi: 10.1128/AAC.47.11.3667-3671.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 61.Citron DM, Merriam CV, Tyrrell KL, Warren YA, Fernandez H, Goldstein EJ. 2003. In vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, bacitracin, and four other antimicrobials against intestinal anaerobic bacteria. Antimicrob Agents Chemother 47:2334–2338. doi: 10.1128/AAC.47.7.2334-2338.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 62.Hoellman DB, Kelly LM, Credito K, Anthony L, Ednie LM, Jacobs MR, Appelbaum PC. 2002. In vitro antianaerobic activity of ertapenem (MK-0826) compared to seven other compounds. Antimicrob Agents Chemother 46:220–224. doi: 10.1128/AAC.46.1.220-224.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 63.Goldstein EJ, Citron DM, Merriam CV, Warren YA, Tyrrell KL, Fernandez HT, Bryskier A. 2005. Comparative in vitro activities of XRP 2868, pristinamycin, quinupristin-dalfopristin, vancomycin, daptomycin, linezolid, clarithromycin, telithromycin, clindamycin, and ampicillin against anaerobic gram-positive species, actinomycetes, and lactobacilli. Antimicrob Agents Chemother 49:408–413. doi: 10.1128/AAC.49.1.408-413.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 64.Mosca A, Summanen P, Finegold SM, De Michele G, Miragliotta G. 1998. Cellular fatty acid composition, soluble-protein profile, and antimicrobial resistance pattern of Eubacterium lentum. J Clin Microbiol 36:725–755. [DOI] [PMC free article] [PubMed] [Google Scholar]