| Literature DB >> 35421136 |
Se Ju Lee1, Yae Jee Baek1, Jin Nam Kim1, Ki Hyun Lee1, Eun Hwa Lee1, Joon Sup Yeom1, Jun Yong Choi1, Nam Su Ku1, Jin Young Ahn1, Jung Ho Kim1, Su Jin Jeong1.
Abstract
Infections caused by Fusobacterium species are rare; however serious infections with complications or mortality may occur occasionally. We conducted a retrospective study to investigate the clinical features of patients with Fusobacterium infections and the differences between infections caused by the species F. necrophorum, F. nucleatum, and F. varium. Additionally, we attempted to identify risk factors for Fusobacterium-associated mortality. This study included all patients at a large tertiary care teaching hospital in South Korea with Fusobacterium infections from January 2006 to April 2021. Demographic, clinical, laboratory, and outcome data were analyzed. Multiple logistic regression analysis was performed to assess the risk factors for in-hospital mortality associated with F. nucleatum and F. varium infections. We identified 272 patients with Fusobacterium infections during the study period. The number of Fusobacterium cases has increased recently, with F. varium infections markedly increasing since 2016 and causing a significant proportion of infections. Patients with F. varium infections were older and had a higher proportion of nosocomial infections than the other groups. The F. nucleatum and F. varium groups showed higher in-hospital mortality than the F. necrophorum group. Through logistic regression analysis, APACHE II score and serum albumin level were considered risk factors for in-hospital mortality. APACHE II score was positively correlated with age, red cell distribution width, and serum blood urea nitrogen, and negatively correlated with serum albumin level. Infections caused by Fusobacterium species are increasing. F. varium causes a significant proportion of severe infections.Entities:
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Year: 2022 PMID: 35421136 PMCID: PMC9009667 DOI: 10.1371/journal.pone.0266610
Source DB: PubMed Journal: PLoS One ISSN: 1932-6203 Impact factor: 3.752
Comparison of clinical characteristics of each species.
| p-value | p’ | p" | ||||
|---|---|---|---|---|---|---|
| Age, years, median (IQR) | 55.5 (39.5–67.5) | 27 (22.5–39.0) | 62.5 (50.75–69.0) | <0.001 | 0.115 | <0.001 |
| Male sex, n (%) | 48 (55.8%) | 51 (71.8%) | 44 (78.6%) | 0.011 | 0.009 | 0.507 |
| Community acquired, n (%) | 59 (68.6%) | 63 (88.7%) | 19 (33.9%) | <0.001 | <0.001 | <0.001 |
| Comorbidities, n (%) | ||||||
| •Hypertension | 26 (30.2%) | 6 (8.5%) | 30 (53.6%) | <0.001 | 0.009 | <0.001 |
| •Diabetes mellitus | 12 (14.0%) | 0 | 14 (25.0%) | <0.001 | 0.149 | <0.001 |
| •Congestive heart failure | 3 (3.5%) | 0 | 0 | 0.106 | 0.278 | - |
| •Coronary artery disease | 2 (2.3%) | 0 | 8 (14.3%) | 0.000 | 0.014 | 0.001 |
| •Peripheral arterial occlusive disease | 0 | 0 | 3 (5.4%) | 0.014 | 0.059 | 0.083 |
| •Chronic obstruction pulmonary disease | 1 (1.2%) | 1 (1.4%) | 5 (8.9%) | 0.022 | 0.035 | 0.086 |
| •Chronic kidney disease | 2 (2.3%) | 0 | 14 (25.0%) | <0.001 | <0.001 | <0.001 |
| •Chronic liver disease | 9 (10.5%) | 3 (4.2%) | 5 (8.9%) | 0.341 | 0.99 | 0.474 |
| •Cerebrovascular accident | 3 (3.5%) | 1 (1.4%) | 2 (3.6%) | 0.680 | 1 | 0.835 |
| •Connective tissue disease | 1 (1.2%) | 0 | 0 | 0.476 | 1 | - |
| •Inflammatory bowel disease | 0 | 0 | 1 (1.8%) | 0.278 | 0.828 | 0.441 |
| •Solid organ transplantation | 2 (2.3%) | 0 | 0 | 0.225 | 0.674 | - |
| •Immunosuppressive therapy | 3 (3.5%) | 0 | 2 (3.6%) | 1 | 1 | 0.193 |
| •Solid cancer | 24 (27.9%) | 8 (11.3%) | 28 (50.0%) | <0.001 | 0.013 | <0.001 |
| •Hematologic malignancy | 3 (3.5%) | 0 | 3 (5.4%) | 0.172 | 0.68 | 0.083 |
| Charlson Comorbidity Index, median (IQR) | 2.0 (0.0–5.0) | 0.0 (0.0–0.0) | 4.0 (2.0–6.0) | <0.001 | 0.034 | <0.001 |
| Recent surgery history, n (%) | 9 (10.5%) | 7 (9.9%) | 30 (53.6%) | <0.001 | <0.001 | <0.001 |
| Laboratory data (culture day), median (IQR) | ||||||
| •White blood cell count, 103/μL | 10.8 (6.4–16.1) | 15.7 (13.1–18.7) | 9.4 (6.5–12.6) | <0.001 | 0.246 | <0.001 |
| •Segmented neutrophil, % | 83.0 (71.1–89.2) | 82.8 (78.2–85.3) | 80.7 (71.4–89.5) | 0.583 | 0.465 | 0.254 |
| •Lymphocyte count, 103/μL | 0.9 (0.6–1.6) | 1.6 (1.3–2.0) | 0.9 (0.6–1.4) | <0.001 | 0.851 | <0.001 |
| •Red cell distribution width, % | 12.9 (12.4–14.9) | 12.4 (12.0–13.0) | 13.8 (12.8–15.1) | <0.001 | 0.159 | <0.001 |
| •Platelet count, 103/μL | 275.5 (179.0–343.0) | 285.0 (242.5–324.5) | 230.5 (178.5–353.5) | 0.229 | 0.456 | 0.042 |
| •Blood urea nitrogen mg/dL | 13.4 (9.1–23.0) | 12.8 (10.1–15.6) | 15.6 (11.3–21.4) | 0.044 | 0.335 | 0.007 |
| •Creatinine, mg/dL | 0.7 (0.6–1.0) | 0.8 (0.7–0.9) | 0.8 (0.6–1.1) | 0.733 | 0.530 | 0.969 |
| •Albumin, mg/dL | 3.5 (2.9–4.0) | 4.3 (3.9–4.5) | 3.2 (2.8–3.5) | <0.001 | 0.002 | <0.001 |
| •Total bilirubin, mg/dL | 0.8 (0.5–1.3) | 0.8 (0.6–1.2) | 0.7 (0.4–1.2) | 0.129 | 0.060 | 0.121 |
| •Aspartate aminotransferase, IU/L | 28.5 (18.0–45.0) | 20.0 (16.0–30.5) | 24.5 (17.0–36.5) | 0.009 | 0.259 | 0.076 |
| •Alanine aminotransferase, IU/L | 18.5 (13.0–38.0) | 16.0 (11.5–27.0) | 21.0 (11.0–40.5) | 0.433 | 0.890 | 0.369 |
| •International normalized ratio | 1.1 (1.0–1.2) | 1.1 (1.0–1.2) | 1.1 (1.1–1.2) | 0.067 | 0.071 | 0.021 |
| •C-reactive protein, mg/L | 72.7 (31.9–122.8) | 72.8 (29.0–137.7) | 96.3 (50.8–151.4) | 0.547 | 0.356 | 0.301 |
| •Erythrocyte sedimentation rate, mm/hr | 56.0 (40.0–77.0) | 44.0 (32.5–62.0) | 56.0 (40.5–72.0) | 0.021 | 0.727 | 0.014 |
| Severity scale, median (IQR) | ||||||
| •SOFA | 0.0 (0.0–3.0) | 0.0 (0.0–0.0) | 1.0 (0.0–3.0) | <0.001 | 0.405 | <0.001 |
| •APACHE II | 7.0 (3.0–11.0) | 2.0 (1.0–4.5) | 6.5 (4.0–11.0) | <0.001 | 0.816 | <0.001 |
| Polymicrobial infection, n (%) | 44 (51.2%) | 44 (62.0%) | 51 (91.1%) | <0.001 | <0.001 | <0.001 |
| •Common co-pathogens, n (%) | ||||||
| •α- | 23 (52.3%) | 40 (90.9%) | 8 (15.7%) | |||
| • | 5 (11.4%) | 1 (2.3%) | 32 (62.7%) | |||
| • | 4 (9.1%) | 2 (4.5%) | 17 (33.3%) | |||
| Infection site, n (%) | <0.001 | <0.001 | <0.001 | |||
| •Upper respiratory tract infection | 25 (29.1%) | 60 (84.5%) | 0 | |||
| •Intra-abdominal infection | 21 (24.4%) | 8 (11.3%) | 43 (76.8%) | |||
| •Pleuropulmonary infection | 4 (4.7%) | 0 | 1 (1.8%) | |||
| •Urinary tract infection | 1 (1.2%) | 0 | 0 | |||
| •Cardiovascular infection | 1 (0.4%) | 0 | 0 | |||
| •Central nervous system infection | 5 (5.8%) | 1 (1.4%) | 0 | |||
| •Skin and soft tissue infection | 7 (8.1%) | 0 | 7 (12.5%) | |||
| •Bond and joint infection | 1 (1.2%) | 0 | 1 (1.8%) | |||
| •Reproductive organ infection | 0 | 1 (1.4%) | 2 (3.6%) | |||
| •Unspecified bacteremia | 21 (24.4%) | 1 (1.4%) | 2 (3.6%) | |||
p’, F. varium and F. nucleatum; p", F. varium and F. necrophorum;
*, Mann Whitney U test;
#, Fisher test,
IQR, Interquartile range; SOFA, Sequential Organ Failure Assessment; APACHE, Acute Physiology and Chronic Health Evaluation.
Fig 1Year-wise distribution of cases and proportion of each species.
Outcome analysis of Fusobacterial infections.
| p-value | p’ | p" | ||||
|---|---|---|---|---|---|---|
| In-hospital mortality, n (%) | 11 (12.8%) | 1 (1.4%) | 7 (12.5%) | 0.025 | 1 | 0.021 |
| ICU admission, n (%) | 11 (12.8%) | 3 (4.2%) | 15 (26.8%) | 0.001 | 0.059 | 0.001 |
| Re-admission in 30days, n (%) | 6 (7.0%) | 5 (7.0%) | 3 (5.4%) | 0.913 | 1 | 1 |
| Hospital stay, days, median (IQR) | 11.0 (2.0–19.0) | 4.0 (3.0–6.5) | 23.5 (11.0–38.5) | <0.001 | <0.001 | <0.001 |
| Hemodynamic instability, n (%) | 18 (20.9%) | 3 (4.2%) | 12 (21.4%) | 0.006 | 1 | 0.007 |
| Respiratory failure, n (%) | 8 (9.3%) | 2 (2.8%) | 9 (16.1%) | 0.033 | 0.342 | 0.011 |
| AKI requiring RRT, n (%) | 2 (2.3%) | 0 | 8 (14.3%) | <0.001 | 0.014 | 0.001 |
| Duration of antibiotic therapy, days, median (IQR) | 14.5 (9.0–23.0) | 13.0 (10.0–17.5) | 24.0 (14.0–38.5) | 0.007 | 0.001 | <0.001 |
| Requiring intervention or surgery for treatment, n (%) | 54 (62.8%) | 65 (91.5%) | 49 (87.5%) | <0.001 | 0.002 | 0.651 |
| Thrombophlebitis (including Lemierre`s syndrome), n (%) | 4 (4.7%) | 3 (4.2%) | 2 (3.6%) | 0.952 | 1 | 1 |
p’, F. varium and F. nucleatum; p", F. varium and F. necrophorum.
+, Kruskal-Wallis test;
*, Mann Whitney U test;
#, Fisher test.
IQR, Interquartile range; ICU, Intensive care unit; AKI, Acute kidney injury; RRT, Renal replacement therapy.
Univariate analysis of risk factors for mortality in the F. nucleatum and F. varium groups.
| Survival (n = 124) | Mortality (n = 18) | p-value | |
|---|---|---|---|
| Age, years, median (IQR) | 55.5 (40.5–67.0) | 69.5 (62.0–80.0) | <0.001 |
| Male sex, n (%) | 82 (66.1%) | 10 (55.6%) | 0.539 |
| Community acquired, n (%) | 72 (58.1%) | 6 (33.3%) | 0.086 |
| Charlson Comorbidity Index, median (IQR) | 3.0 (0.0–5.0) | 7.0 (6.0–8.0) | <0.001 |
| Recent surgery history, n (%) | 34 (27.4%) | 5 (27.8%) | 1 |
| Laboratory data (culture day), median (IQR) | |||
| •Lymphocyte count, 103/μL | 1.0 (0.6–1.6) | 0.6 (0.4–0.8) | 0.002 |
| •Platelet count, 103/μL | 269.5 (190.5–348.5) | 138.5 (69.0–301.0) | 0.002 |
| •Red cell distribution width, % | 13.1 (12.4–14.2) | 15.8 (14.8–17.6) | <0.001 |
| •Blood urea nitrogen mg/dL | 13.5 (9.3–19.9) | 32.2 (17.0–47.3) | <0.001 |
| •Albumin, mg/dL | 3.5 (3.0–3.9) | 2.6 (2.4–2.9) | 0.000 |
| •Total bilirubin, mg/dL | 0.7 (0.5–1.2) | 1.1 (0.7–1.4) | 0.017 |
| Severity scale, median (IQR) | |||
| •SOFA | 0.0 (0.0–2.0) | 5.5 (3.0–9.0) | <0.001 |
| •APACHE II | 6.0 (3.0–10.0) | 18.0 (11.0–23.0) | <0.001 |
| Infection site, n (%) | 0.095 | ||
| •Upper respiratory tract infection | 25 (20.2%) | 0 | |
| •Intra-abdominal infection | 54 (43.5%) | 10 (55.6%) | |
| •Skin and soft tissue infection | 14 (11.3%) | 0 | |
| •Pleuropulmonary infection | 3 (2.4%) | 2 (11.1%) | |
| •Central nervous system infection | 5 (4.0%) | 0 | |
| •Reproductive organ infection | 2 (1.6%) | 0 | |
| •Urinary tract infection | 1 (0.8%) | 0 | |
| •Cardiovascular infection | 1 (0.8%) | 0 | |
| •Bone and joint infection | 2 (1.6%) | 0 | |
| •Unspecified bacteremia | 17 (13.7%) | 6 (33.3%) | |
| 1 | |||
| • | 75 (60.5%) | 11 (61.1%) | |
| • | 49 (39.5%) | 7 (38.9%) | |
IQR, Interquartile range; SOFA, Sequential Organ Failure Assessment; APACHE, Acute Physiology and Chronic Health Evaluation.
Multivariate analysis of risk factors for mortality, F. nucleatum and F. varium groups.
| Covariate | OR (95% CI) | p-value |
|---|---|---|
| APACHE II | 1.12 (1.02–1.25) | 0.021 |
| Serum albumin | 0.30 (0.09–0.92) | 0.045 |
| Blood urea nitrogen | 1.01 (0.99–1.05) | 0.358 |
| Lymphocyte count | 0.66 (0.20–1.32) | 0.367 |
| Platelet count | 1.00 (0.99–1.00) | 0.401 |
| Serum Total bilirubin | 0.99 (0.83–1.16) | 0.866 |
OR, Odds ratio; CI, Confidence interval, APACHE, Acute Physiology and Chronic Health Evaluation.
Fig 2Correlations between APACHE II score and Age, RDW, BUN, and albumin.