Monday, October 2, 2023
| Characteristic | All cases, N = 34† | Respiratory cases, n = 23‡ | Nonrespiratory cases, n = 11§ | p value |
|---|---|---|---|---|
| Median age, y | 58 (50–71) | 64 (54–72) | 38 (21–61) | 0.03 |
| Sex | ||||
| M | 12 (38.7) | 7 (31.8) | 5 (55.6) | 0.25 |
| F | 19 (61.3) | 15 (68.2) | 4 (44.4) | 0.19 |
| Relationship with animals¶ | 33 (97.1) | 22 (95.7) | 11 (100) | 1.00 |
| Vital signs on admission | ||||
| Heart rate, beats/min | 100 (88–112) | 101 (97–114) | 85 (85–85) | 0.13 |
| Systolic blood pressure, mm Hg | 125 (107–146) | 130 (108–147) | 107 (107–107) | 0.32 |
| Body temperature, °C | 38 (37.4–38.5) | 38 (37.4–38.4) | 38.4 (35.5–38.5) | 0.94 |
| Respiratory rate, breaths/min | 20 (16–26) | 18 (16–28) | 21 (21–21) | 0.61 |
| Laboratory data | ||||
| Leukocytes, cells/mm3 | 13,800 (9,325–18,900) | 14,800 (10,850–21,700) | 10,500 (7,775–12,700) | 0.07 |
| Platelets, × 104/mm3 | 26.3 (22.1–27.2) | 25.1 (19.9–34.1) | 26.6 (26.3–26.8) | 0.51 |
| Creatine, mg/dL | 0.75 (0.66–1.16) | 0.75 (0.67–1.24) | 0.59 (0.38–0.80) | 0.34 |
| C-reactive protein, mg/dL | 6.1 (3.7–16.8) | 10.8 (4.7–21) | 3.9 (2.3–5.7) | 0.07 |
| Treatment antibiotic (no. cases) | ||||
| Penicillins | Penicillin G (2), sulbactam/ampicillin (9), piperacillin (5) |
Penicillin G (1), sulbactam/ampicillin (8), piperacillin (4) |
Penicillin G (1), sulbactam/ampicillin (1), piperacillin (1) |
|
| Macrolides | Erythromycin (9), clarithromycin (6), azithromycin (6), clindamycin (1) |
Erythromycin (6), clarithromycin (5), azithromycin (5), clindamycin (1) |
Erythromycin (3), azithromycin (1), clarithromycin (1) |
|
| Cephalosporins | Cephepime (1), cefazolin (1), ceftriaxone (1) |
Cephepime (1), ceftriaxone (1) |
Cefazolin (1) | |
| Quinolones | Levofloxacin (3) | Levofloxacin (2) | Levofloxacin (1) | |
| Other | Meropenem (3), faropenem (1), minocycline (1) |
Meropenem (3) | Faropenem (1), minocycline (1) |
|
| Diphtheria antitoxin | 4 (11.8) | 4 (17.4) | 0 | 0.28 |
| Classification of respiratory symptoms | ||||
| Mild | 8 | 6 | 2 | |
| Moderate | 16 | 7 | 9 | |
| Severe | 10 | 10 | 0 | |
| Outcome | ||||
| Hospital days | 10 (3–30) | 13 (4–31) | 9 (0–26) | 0.41 |
| Ventilator days | 0 (0–6) | 2 (0–12) | 0 | 0.04 |
| Deaths# | 2 (5.9) | 2 (8.7) | 0 | 1.00 |
Table 1. Characteristics of patients with Corynebacterium ulcerans infection, Japan, 2001–2020*
*Data are medians (interquartile range) for continuous variables and no. (%) for categorical variables.
†Missing data for all cases: age (n = 3), sex (n = 3), heart rate (n = 27), systolic blood pressure (n = 27), body temperature (n = 19), respiratory rate (n = 27), leukocytes (n = 17), platelets (n = 26), creatine (n = 23), C-reactive protein (n = 17), treatment (n = 10), hospital days (n = 8), ventilator days (n = 9).
‡Missing data for respiratory cases: age (n = 1), sex (n = 1), heart rate (n = 17), systolic blood pressure (n = 17), body temperature (n = 11), respiratory rate (n = 17), pseudomembrane (n = 1), leukocyte (n = 10), platelets (n = 17), T-bilirubin (n = 17), creatine (n = 14), C-reactive protein (n = 10), treatment (n = 5), hospital days (n = 3), ventilator days (n = 4). §Missing data for nonrespiratory cases: age (n = 2), sex (n = 2), heart rate (n = 10), systolic blood pressure (n = 10), body temperature (n = 8), respiratory rate (n = 10), leukocytes (n = 7), platelets (n = 10), T-bilirubin (n = 11), creatine (n = 9), C-reactive protein (n = 7), treatment (n = 5), hospital days (n = 5), ventilator days (n = 5).
¶Indicates the presence of animals in the patient’s living environment.
#All deaths were in cases for which respiratory symptoms were classified as severe.
| Characteristic | Mild symptoms, n = 6† | Moderate symptoms, n = 7‡ | Severe symptoms, n = 10§ | p value |
|---|---|---|---|---|
| Age, y | 54 (28–61) | 62 (51–76) | 67 (62–72) | 0.07 |
| Sex | ||||
| M | 3 (60.0) | 3 (42.9) | 1 (10.0) | 0.11 |
| F | 2 (40.0) | 4 (57.1) | 9 (90.0) | 0.29 |
| Vital signs on admission | ||||
| Body temperature, °C | 37 (36.6–37.4) | 38 (37.6–38.8) | 38 (37.5–38.7) | 0.14 |
| Pseudomembrane | 5 (100) | 6 (85.7) | 10 (100) | 0.33 |
| Laboratory data | ||||
| Leukocytes, cells/mm3 | 9,500 (6,700–14,800) | 14,350 (10,363–23,550) | 18,900 (13,400–22,600) | 0.26 |
| C-reactive protein, mg/dL | 4.7 (0.9–6.1) | 7.7 (1.8–12.6) | 21 (11.7–25.4) | 0.02 |
| Treatment antibiotic (no. cases) | ||||
| Penicillins | None | Penicillin G (1), sulbactam/ampicillin (2), piperacillin (2) |
Sulbactam/ampicillin (6), piperacillin (2) |
|
| Macrolides | Erythromycin (1), clarithromycin (2) |
Erythromycin (3), clarithromycin (3), azithromycin (2) |
Erythromycin (2), azithromycin (3), clindamycin (1) |
|
| Cephalosporins | Ceftriaxone (1) | |||
| Quinolones | Levofloxacin (2) | |||
| Other | Meropenem (3) | |||
| Diphtheria antitoxin | 0 | 0 | 4 (40.0) | 0.04 |
| Outcome | ||||
| Hospital days | 0 | 7 (7–10) | 29 (20–56) | <0.01 |
| Ventilator days | 0 | 0 | 12 (5–42) | <0.01 |
| Deaths | 0 | 0 | 2 (20.0) | 0.24 |
Table 2. Comparison of the subgroups of patients with Corynebacterium ulcerans infection with mild, moderate, and severe respiratory symptoms, Japan, 2001–2020*
*Data are medians (interquartile range) for continuous variables and no. (%) for categorical variables.
†Missing data for mild cases: age (n = 1), sex (n = 1), heart rate (n = 6), systolic blood pressure (n = 6), body temperature (n = 4), respiratory rate (n = 6), pseudomembrane (n = 1), leukocytes (n = 3), platelets (n = 6), C-reactive protein (n = 3), treatment (n = 3), hospital days (n = 3), ventilator days (n = 3).
‡Missing data for moderate: heart rate (n = 5), systolic blood pressure (n = 5), body temperature (n = 3), respiratory rate (n = 5), leukocytes (n = 3), platelets (n = 5), T-bilirubin (n = 5), creatine (n = 4), C-reactive protein (n = 3), treatment (n = 1).
§Missing data for severe: heart rate (n = 6), systolic blood pressure (n = 6), body temperature (n = 4), respiratory rate (n = 6), leukocytes (n = 4), platelets (n = 6), T-bilirubin (n = 6), creatine (n = 5), C-reactive protein (n = 4), treatment (n = 1), ventilator days (n = 1).
Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™
ABIM Diplomates - maximum of 1.00 ABIM MOC points
This activity is intended for infectious disease clinicians, intensivists, pulmonologists, dermatologists, and other clinicians who treat and manage patients with Corynebacterium ulcerans infection.
The goal of this activity is for members of the healthcare team to be better able to describe clinical characteristics, treatment-related factors, and outcomes of Corynebacterium ulcerans infection, based on a case series of 34 patients in Japan from 2001 to 2020.
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CME / ABIM MOC Released: 7/21/2023
Valid for credit through: 7/21/2024, 11:59 PM EST
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Corynebacterium ulcerans is a closely related bacterium to the diphtheria bacterium C. diphtheriae, and some C. ulcerans strains produce toxins that are similar to diphtheria toxin. C. ulcerans is widely distributed in the environment and is considered one of the most harmful pathogens to livestock and wildlife. Infection with C. ulcerans can cause respiratory or nonrespiratory symptoms in patients. Recently, the microorganism has been increasingly recognized as an emerging zoonotic agent of diphtheria-like illness in Japan. To clarify the overall clinical characteristics, treatment-related factors, and outcomes of C. ulcerans infection, we analyzed 34 cases of C. ulcerans that occurred in Japan during 2001–2020. During 2010–2020, the incidence rate of C. ulcerans infection increased markedly, and the overall mortality rate was 5.9%. It is recommended that adults be vaccinated with diphtheria toxoid vaccine to prevent the spread of this infection.
Diphtheria is an upper respiratory tract illness caused by toxin-producing Corynebacterium diphtheriae bacteria, and it is characterized by sore throat, fever, and formation of a pseudomembrane on the tonsils, pharynx, or both, along with nasal discharge. C. diphtheriae can also infect the skin, causing open sores or ulcers. However, diphtheria skin infections rarely result in any other severe disease[1]. C. ulcerans is a closely related bacterium to C. diphtheriae, and some strains produce toxins that are very similar to diphtheria toxin[2,3]. C. ulcerans is widely distributed in the environment and is considered one of the most harmful pathogens to livestock and wildlife. This bacterium can cause cutaneous inflammation, including mastitis, in dairy cows[4–6]. C. ulcerans has been increasingly recognized as an emerging zoonotic agent of diphtheria-like illness in the world[7–18].
Infections caused by these 2 bacteria are difficult to distinguish clinically, and the World Health Organization (WHO) treats infections caused by toxin-producing C. ulcerans as part of the diphtheria case definition[19]. C. diphtheriae is thought to be transmitted only among humans, but C. ulcerans can be transmitted to humans by nonhuman mammals and thus should be treated as a zoonosis[7–18]. Dogs and cats as companion animals are considered the major causes of transmission to humans. Although there have been several reports of individual cases of C. ulcerans infection[20–24], information on clinical features, treatment-related factors, and outcomes is limited. In this study we elucidate the clinical features, treatment-related factors, and outcomes of C. ulcerans infection cases in Japan during 2001–2020.
