The answer is anaerobic bacteremia due to Enterocloster clostridioformis. E. clostridioformis was recently reclassified from Clostridium clostridioforme based on 16S rRNA phylogeny (1).
Direct microscopic examination revealed cigar-shaped Gram-variable bacilli. Clostridium strains belonging to the so-called RIC group (Clostridium ramosum, Clostridium innocuum, and E. clostridioformis) usually appear Gram negative or Gram variable (2). E. clostridioformis organisms are cigar shaped, whereas C. innocuum and C. ramosum form slender rods.
Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) identification was performed directly from the blood culture using the MBT Sepsityper (Bruker Daltonics, Wissembourg, France). E. clostridioformis was identified with a score of 2.01. Results of the nitrocefin test (Cefinase disks; Thermo Fisher Scientific, Waltham, MA, USA) were positive for subcultures, revealing β-lactamase production. Antimicrobial susceptibility testing using gradient diffusion showed resistance to benzylpenicillin and moxifloxacin but susceptibility to amoxicillin-clavulanate, piperacillin-tazobactam, meropenem, vancomycin, and metronidazole, according to the EUCAST guidelines for Gram-positive anaerobes (3). The patient recovered after 2 weeks of treatment with cefotaxime, metronidazole, and fluconazole.
The clinical relevance of Clostridium bacteremia has been challenged in the literature. Proposed criteria for clinical relevance include the presence of at least one of the following characteristics: (i) more than one positive blood culture, (ii) appropriate focus or source of infection (e.g., intraabdominal), or (iii) sepsis without another evident source of infection (4). Using these criteria, the clinical relevance of Clostridium bacteremia ranged from 68% to 83% (4, 5). For clinically relevant bacteremia, mortality rates at 30 days were higher in cases of hypothermia or inadequate empirical antimicrobial therapy (5).
Accurate identification of Clostridium strains from the RIC group is important because these Clostridium species are usually more resistant to antimicrobial agents. Indeed, E. clostridioformis strains are often resistant to benzylpenicillin (2). Moreover, resistance to β-lactam-β-lactamase inhibitor combinations (amoxicillin-clavulanate and piperacillin-tazobactam) has also been described (6). E. clostridioformis might act as a reservoir of antibiotic resistance genes in the gut microbiota (7). Despite its Gram-negative appearance, E. clostridioformis is usually susceptible to vancomycin, whereas C. ramosum and C. innocuum present low-level intrinsic resistance (2, 8). MALDI-TOF MS identification directly from positive blood cultures seems particularly interesting for anaerobic bacteria because of their slow growth.
ACKNOWLEDGMENTS
No funding was received for this work.
All authors report no conflicts of interest relevant to this article.
Footnotes
See https://doi.org/10.1128/JCM.00328-21 in this issue for photo quiz case presentation.
Contributor Information
Rémi Le Guern, Email: remi.leguern@chru-lille.fr.
Erik Munson, Marquette University.
REFERENCES
- 1.Haas KN, Blanchard JL. 2020. Reclassification of the Clostridium clostridioforme and Clostridium sphenoides clades as Enterocloster gen. nov. and Lacrimispora gen. nov., including reclassification of 15 taxa. Int J Syst Evol Microbiol 70:23–34. doi: 10.1099/ijsem.0.003698. [DOI] [PubMed] [Google Scholar]
- 2.Alexander CJ, Citron DM, Brazier JS, Goldstein EJ. 1995. Identification and antimicrobial resistance patterns of clinical isolates of Clostridium clostridioforme, Clostridium innocuum, and Clostridium ramosum compared with those of clinical isolates of Clostridium perfringens. J Clin Microbiol 33:3209–3215. doi: 10.1128/jcm.33.12.3209-3215.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.European Committee on Antimicrobial Susceptibility Testing. 2021. Breakpoint tables for interpretation of MICs and zone diameters, version 11.0. https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_11.0_Breakpoint_Tables.pdf.
- 4.Benjamin B, Kan M, Schwartz D, Siegman-Igra Y. 2006. The possible significance of Clostridium spp. in blood cultures. Clin Microbiol Infect 12:1006–1012. doi: 10.1111/j.1469-0691.2006.01464.x. [DOI] [PubMed] [Google Scholar]
- 5.Stabler S, Titecat M, Duployez C, Wallet F, Loiez C, Bortolotti P, Faure E, Faure K, Kipnis E, Dessein R, Le Guern R. 2020. Clinical relevance of Clostridium bacteremia: an 8-year retrospective study. Anaerobe 63:102202. doi: 10.1016/j.anaerobe.2020.102202. [DOI] [PubMed] [Google Scholar]
- 6.Brook I, Wexler HM, Goldstein EJ. 2013. Antianaerobic antimicrobials: spectrum and susceptibility testing. Clin Microbiol Rev 26:526–546. doi: 10.1128/CMR.00086-12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Dehoux P, Marvaud JC, Abouelleil A, Earl AM, Lambert T, Dauga C. 2016. Comparative genomics of Clostridium bolteae and Clostridium clostridioforme reveals species-specific genomic properties and numerous putative antibiotic resistance determinants. BMC Genomics 17:819. doi: 10.1186/s12864-016-3152-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Chia JH, Feng Y, Su LH, Wu TL, Chen CL, Liang YH, Chiu CH. 2017. Clostridium innocuum is a significant vancomycin-resistant pathogen for extraintestinal clostridial infection. Clin Microbiol Infect 23:560–566. doi: 10.1016/j.cmi.2017.02.025. [DOI] [PubMed] [Google Scholar]
