Resistance Trends of Bacteroides fragilis Group Over an 8-Year Period, 1997-2004, in Korea
2009; 29(4): 293-298
Ann Lab Med 2022; 42(2): 188-195
Published online March 1, 2022 https://doi.org/10.3343/alm.2022.42.2.188
Copyright © Korean Society for Laboratory Medicine.
Myungsook Kim , Ph.D.1, Shin Young Yun , M.D.1, Yunhee Lee , B.D.1, Hyukmin Lee , M.D.1, Dongeun Yong , M.D.1, Kyungwon Lee , M.D.1,2
1Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Korea; 2Seoul Clinical Laboratories Academy, Yongin, Korea
Correspondence to: Hyukmin Lee, M.D.
Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea
Tel: +82-2-2228-3777
Fax: +82-2-313-0956
E-mail: HMLEE71@yuhs.ac
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background: Fusobacterium species are obligately anaerobic, gram-negative bacilli. Especially, F. nucleatum and F. necrophorum are highly relevant human pathogens. We investigated clinical differences in patients infected with Fusobacterium spp. and determined the antimicrobial susceptibility of Fusobacterium isolates.
Methods: We collected clinical data of 86 patients from whom Fusobacterium spp. were isolated from clinical specimens at a tertiary-care hospital in Korea between 2003 and 2020. In total, 76 non-duplicated Fusobacterium isolates were selected for antimicrobial susceptibility testing by the agar dilution method, according to the Clinical and Laboratory Standards Institute guidelines (M11-A9).
Results: F. nucleatum was most frequently isolated from blood cultures and was associated with hematologic malignancy, whereas F. necrophorum was mostly prevalent in head and neck infections. Anti-anaerobic agents were more commonly used to treat F. nucleatum and F. varium infections than to treat F. necrophorum infections. We observed no significant difference in mortality between patients infected with these species. All F. nucleatum and F. necrophorum isolates were susceptible to the antimicrobial agents tested. F. varium was resistant to clindamycin (48%) and moxifloxacin (24%), and F. mortiferum was resistant to penicillin G (22%) and ceftriaxone (67%). β-Lactamase activity was not detected.
Conclusions: Despite the clinical differences among patients with clinically important Fusobacterium infections, there was no significant difference in the mortality rates. Some Fusobacterium spp. were resistant to penicillin G, ceftriaxone, clindamycin, or moxifloxacin. This study may provide clinically relevant data for implementing empirical treatment against Fusobacterium infections.
Keywords: Fusobacterium nucleatum, Fusobacterium necrophorum, Fusobacterium species, Clinical difference, Antimicrobial susceptibility, Korea
Fusobacteria are obligately anaerobic, non-spore forming, gram-negative bacilli that inhabit the oral, gastrointestinal, and vaginal mucosa as part of the normal microbiota [1]. The genus
The Clinical and Laboratory Standards Institute (CLSI) suggests that antimicrobial susceptibility testing (AST) of
We investigated the clinical differences, including mortality and associated malignancies, among patients with clinically important
Clinical specimens were routinely cultured under anaerobic conditions at 35°C on phenylethyl-blood agar (Becton Dickinson, Sparks, MD, USA) or Brucella agar (Asan, Hwaseong, Korea).
In total, 76
Differences among patients infected with
The baseline characteristics of the patients with
Clinical characteristics of patients with
Sex | 0.376 | |||
Male | 13 (68) | 18 (75) | 36 (84) | |
Female | 6 (32) | 6 (25) | 7 (16) | |
Age in years | 59 (35–76) | 27 (19–66) | 59 (40–73) | <0.001 |
WBC count, ×109/L | 7.53 (0.48–13.15) | 14.66 (7.60–19.39) | 9.93 (5.27–16.14) | <0.001 |
Clinical specimen type | <0.001 | |||
Blood | 11 (58) | 3 (13) | 1 (2) | |
Aspirate from head and neck | 4 (21) | 18 (75) | 0 (0) | |
Peritoneal fluid | 2 (11) | 2 (8) | 38 (88) | |
Others* | 2 (11) | 1 (4) | 4 (9) | |
Comorbidity | ||||
DM | 4 (21) | 1 (4) | 6 (14) | 0.004 |
Renal failure | 2 (11) | 0 (0) | 9 (21) | 0.077 |
Heart failure | 1 (5) | 0 (0) | 1 (2) | 0.257 |
Coronary artery disease (myocardial infarction) | 0 (0) | 0 (0) | 5 (12) | 0.002 |
Cerebrovascular disease | 0 (0) | 0 (0) | 1 (2) | 0.564 |
Chronic pulmonary disease | 0 (0) | 0 (0) | 2 (5) | 0.102 |
Malignancy | 10 (53) | 3 (13) | 29 (67) | <0.001 |
Metastasis | 2 (11) | 1 (4) | 6 (14) | 0.066 |
CCI 0/1/≥2 | 4/2/13 (21/11/68) | 19/2/3 (79/8/13) | 4/1/38 (9/2/88) | <0.001 |
CRP, mg/L | 69.45 (10.21–252.88) | 51.59 (3.97–145.87) | 94.9 (20.5–204.62) | 0.096 |
Current cancer diagnosis | 10 (53) | 3 (13) | 29 (67) | <0.001 |
Hematologic malignancy | 3 (16) | 0 (0) | 0 (0) | |
Stomach cancer | 1 (5) | 2 (9) | 3 (7) | |
Colorectal cancer | 1 (5) | 1 (4) | 22 (51) | |
Hepatobiliary cancer | 3 (16) | 0 (0) | 3 (7) | |
Other cancer type† | 2 (11) | 0 (0) | 1 (2) | |
Surgery | 7 (37) | 5 (21) | 38 (88) | <0.001 |
GI tract surgery | 3 (16) | 2 (8) | 32 (74) | |
Head and neck surgery | 2 (11) | 3 (13) | 0 (0) | |
Other type of surgery | 2 (11) | 0 (0) | 6 (14) | |
Antimicrobials prescribed | 15 (79) | 22 (92) | 42 (98) | 0.045 |
Anti-anaerobic agents used | 12 (63) | 7 (29) | 41 (95) | <0.001 |
Days in hospital | 16.5 (7–46) | 4 (2–14) | 28 (9–74) | <0.001 |
Mortality | ||||
Seven days | 1 (5) | 1 (4) | 0 (0) | 0.739 |
30 days | 2 (11) | 1 (4) | 3 (7) | 0.186 |
12 months | 3 (16) | 2 (8) | 6 (14) | 0.255 |
Data are presented as number (%) or median (10–90%-tile).
*
Abbreviations: CCI, Charlson comorbidity index; CRP, C-reactive protein; DM, diabetes mellitus; GI, gastrointestinal; WBC, white blood cell.
The MICs of the antimicrobial agents and the antimicrobial susceptibility of the
Antimicrobial susceptibility of the 76
Organism and antimicrobial agent | MIC (μg/mL) | Susceptibility (%) | ||||
---|---|---|---|---|---|---|
Range | 50% | 90% | S | I | R | |
Penicillin G | ≤0.12–0.25 | ≤0.12 | 0.25 | 100 | 0 | 0 |
Piperacillin-tazobactam | ≤0.12 | ≤0.12 | ≤0.12 | 100 | 0 | 0 |
Cefoxitin | ≤0.12–1 | 0.25 | 1 | 100 | 0 | 0 |
Cefotetan | ≤0.12–0.25 | ≤0.12 | 0.25 | 100 | 0 | 0 |
Ceftriaxone | ≤0.12–0.5 | ≤0.12 | 0.5 | 100 | 0 | 0 |
Imipenem | ≤0.12 | ≤0.12 | ≤0.12 | 100 | 0 | 0 |
Clindamycin | ≤0.12 | ≤0.12 | ≤0.12 | 100 | 0 | 0 |
Moxifloxacin | ≤0.12–0.25 | ≤0.12 | 0.25 | 100 | 0 | 0 |
Chloramphenicol | 0.5–1 | 1 | 1 | 100 | 0 | 0 |
Metronidazole | ≤0.12–0.5 | ≤0.12 | 0.5 | 100 | 0 | 0 |
Penicillin G | ≤0.12 | ≤0.12 | ≤0.12 | 100 | 0 | 0 |
Piperacillin-tazobactam | ≤0.12–0.25 | ≤0.12 | ≤0.12 | 100 | 0 | 0 |
Cefoxitin | ≤0.12–1 | ≤0.12 | 1 | 100 | 0 | 0 |
Cefotetan | ≤0.12–2 | ≤0.12 | 2 | 100 | 0 | 0 |
Ceftriaxone | ≤0.12–0.5 | ≤0.12 | 0.25 | 100 | 0 | 0 |
Imipenem | ≤0.12–1 | ≤0.12 | ≤0.12 | 100 | 0 | 0 |
Clindamycin | ≤0.12 | ≤0.12 | ≤0.12 | 100 | 0 | 0 |
Moxifloxacin | 0.5–2 | 1 | 2 | 100 | 0 | 0 |
Chloramphenicol | 0.25–2 | 1 | 2 | 100 | 0 | 0 |
Metronidazole | ≤0.12–1 | ≤0.12 | 0.5 | 100 | 0 | 0 |
Penicillin G | ≤0.12–1 | 0.25 | 0.5 | 96 | 4 | 0 |
Piperacillin-tazobactam | 1–16 | 4 | 8 | 100 | 0 | 0 |
Cefoxitin | 2–16 | 4 | 16 | 100 | 0 | 0 |
Cefotetan | ≤0.12–64 | 2 | 16 | 92 | 0 | 8 |
Ceftriaxone | 1−>128 | 4 | 8 | 96 | 0 | 4 |
Imipenem | 0.5–2 | 1 | 2 | 100 | 0 | 0 |
Clindamycin | 1−>128 | 4 | 32 | 36 | 16 | 48 |
Moxifloxacin | 2–32 | 4 | 16 | 24 | 52 | 24 |
Chloramphenicol | 2–4 | 4 | 4 | 100 | 0 | 0 |
Metronidazole | ≤0.12–1 | 0.5 | 0.5 | 100 | 0 | 0 |
Penicillin G | ≤0.12–2 | 1 | 2 | 44 | 33 | 22 |
Piperacillin-tazobactam | 0.25–8 | 2 | 8 | 100 | 0 | 0 |
Cefoxitin | 2–8 | 4 | 4 | 100 | 0 | 0 |
Cefotetan | 1–4 | 2 | 4 | 100 | 0 | 0 |
Ceftriaxone | 8−>128 | 64 | 128 | 11 | 22 | 67 |
Imipenem | 0.5–1 | 1 | 1 | 100 | 0 | 0 |
Clindamycin | ≤0.12–0.5 | ≤0.12 | 0.5 | 100 | 0 | 0 |
Moxifloxacin | 0.5–2 | 0.5 | 0.5 | 89 | 0 | 11 |
Chloramphenicol | 0.5–1 | 0.5 | 1 | 100 | 0 | 0 |
Metronidazole | 0.25–1 | 0.25 | 0.5 | 100 | 0 | 0 |
Penicillin G | ≤0.12 | ≤0.12 | ≤0.12 | 100 | 0 | 0 |
Piperacillin-tazobactam | ≤0.12–1 | ≤0.12 | 1 | 100 | 0 | 0 |
Cefoxitin | ≤0.12–0.5 | ≤0.12 | 0.5 | 100 | 0 | 0 |
Cefotetan | ≤0.12–0.25 | ≤0.12 | 0.25 | 100 | 0 | 0 |
Ceftriaxone | ≤0.12 | ≤0.12 | ≤0.12 | 100 | 0 | 0 |
Imipenem | ≤0.12 | ≤0.12 | ≤0.12 | 100 | 0 | 0 |
Clindamycin | ≤0.12–1 | ≤0.12 | 1 | 100 | 0 | 0 |
Moxifloxacin | ≤0.12–16 | 2 | 16 | 75 | 0 | 25 |
Chloramphenicol | 0.5–2 | 0.5 | 2 | 100 | 0 | 0 |
Metronidazole | ≤0.12–0.5 | ≤0.12 | 0.5 | 100 | 0 | 0 |
*
Abbreviations: MIC, minimum inhibitory concentration; S, susceptible; I, intermediate; R, resistant.
The patient age distribution differed significantly according to the
The presence of diabetes mellitus, coronary artery disease, malignancy, and metastasis in patients with comorbidities differed significantly among the
The treatment of anaerobic infections is complicated by the slow growth of the organisms, their polymicrobial nature, and their growing resistance to antimicrobial agents [14]. Penicillin and amoxicillin are generally appropriate for the treatment of non-β-lactamase-producing fusobacterial infections. Clindamycin or a combination of a penicillin and a β-lactamase inhibitor can be used to treat dental, oropharyngeal, or pulmonary infection. Metronidazole plus a third-generation cephalosporin can be used for central nervous system infection and bacteremia. Antimicrobial treatment is usually prolonged depending on the site of infection, adequacy of surgical intervention, and host factors [29, 30].
Antimicrobial treatment was given to most patients, albeit more frequently to those with
Despite the clinical differences among patients with
All
Resistance to β-lactams in
The major limitations of our study were that the data were collected from a small number of patients in a single medical center and that we could not analyze any antimicrobial usage data, which may be correlated with antimicrobial susceptibility, for the isolates tested.
In summary,
We thank Ms. Young-Hee Seo for assistance with the experiments.
Lee H and Lee K designed the study; Kim M conducted the experiments and Yun SY investigated the clinical data of patients; Kim M and Lee Y performed the experiments and analyzed the results; Yong D commented on the manuscript. All authors reviewed and approved the manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.
This study was supported by a faculty research grant from the Yonsei University College of Medicine awarded to KL (No. 6-2016-0071).