Friday, March 31, 2023
| Characteristic | Value |
|---|---|
| Median age, y (IQR) | 81.0 (72.0–88.0) |
| Age group, y | |
| <30 | 1 (0.8) |
| 30–39 | 4 (3.0) |
| 40–49 | 5 (3.6) |
| 50–59 | 6 (4.5) |
| 60–69 | 12 (9.0) |
| 70–79 | 29 (21.8) |
| 80–89 | 50 (37.6) |
| ≥90 | 26 (19.5) |
| Sex | |
| M | 72 (54.1) |
| F | 61 (45.9) |
| Medical history | |
| No underlying conditions | 15 (11.3) |
| Solid organ tumor† | 36 (27.1) |
| History of surgery, n = 36 | 15 (41.7) |
| Active malignancy, n = 36‡ | 22 (61.1) |
| Metastasis, n = 36 | 10 (27.8) |
| Hematologic malignancy | 6 (4.5) |
| Hematopoietic stem cell transplant, n = 6 | |
| Cardiovascular disease | 21 (15.8) |
| Cerebral artery diseases | 38 (28.6) |
| Chronic kidney diseases | 27 (20.3) |
| Diabetes mellitus | 22 (16.5) |
| Dementia | 31 (23.3) |
| Collagen diseases | 8 (6.0) |
| Chronic lung diseases | 7 (5.3) |
| HIV | 0 |
| Chemotherapy | 12 (9.0) |
| Immune suppressive therapy | 6 (4.5) |
| Neutropenia, neutrophil count <500 cells/µL | 5 (3.8) |
Table 1. Characteristics of 133 patients with Streptococcus dysgalactiae subspecies equisimilis bacteremia, Japan, 2005–2021*
*Values are no. (%) except as indicated. For patients with multiple episodes, variables for the first episode are described. †Ten patients with prostate cancer; 8 with cervical cancer; 7 with colon, rectal, or anal cancer; 3 with lung cancer; 2 with stomach cancer; 2 with endometrial cancer; 2 with bladder cancer; 2 with breast cancer; and 1 with cancer categorized as other (esophageal cancer, ovarian cancer, pharyngeal cancer, salivary gland cancer, vaginal cancer, and extramammary Paget’s disease), including duplicates. ‡Treated within 5 years.
| Characteristics | No. (%) |
|---|---|
| Type of infection | |
| Community-acquired | 136 (93.2) |
| Nosocomial | 10 (6.8) |
| Clinical source of bacteremia† | |
| Cellulitis | 74 (50.7) |
| Primary bacteremia without focus | 27 (18.5) |
| Necrotizing fasciitis | 10 (6.8) |
| Vertebral osteomyelitis and discitis | 10 (6.8) |
| Psoas abscess | 6 (4.1) |
| Septic arthritis | 11 (7.5) |
| Infectious endocarditis | 4 (2.7) |
| Urinary tract infection | 7 (4.8) |
| Pneumonia | 1 (0.7) |
| Others‡ | 14 (9.6) |
| Clinical characteristics | |
| Body temperature ≥38°C, n = 143 | 100 (69.9) |
| Mean arterial pressure <80 mm Hg, n = 140 | 42 (30.0) |
| Heart rate >90 beats/min, n = 138 | 83 (60.1) |
| Disturbance of consciousness, n = 141 | 54 (38.3) |
| Severe disease, n = 142 | |
| Streptococcus toxic shock syndrome | 7 (4.9) |
| Vasopressor support required | 11 (7.7) |
| Ventilator support required | 6 (4.2) |
| Admission to intensive care unit required | 9 (6.3) |
| Death | |
| In-hospital death, n = 143 | 10 (7.0) |
| 30-d mortality, n = 138 | 5 (3.6) |
Table 2. Clinical manifestations and severity markers for 146 episodes of multidrug-resistant Streptococcus dysgalactiae subspecies equisimilis bacteremia, Japan, 2005–2021*
*Data include 13 relapse or reinfection episodes among 9 patients (details are available in Appendix 2 Table 1). †Data include ≥1 instance per patient, including 3 case-patients with cellulitis and septic arthritis; 2 with vertebral osteomyelitis and psoas abscess; and 1 with each of the following co-infections: cellulitis and vertebral osteomyelitis; cellulitis and psoas abscess; cellulitis and urinary tract infection; necrotizing fasciitis and septic arthritis; vertebral osteomyelitis and septic arthritis; psoas abscess and septic arthritis; infective endocarditis and vertebral osteomyelitis; cellulitis and mycotic aneurysm; vertebral osteomyelitis, psoas abscess, and pyogenic lymphadenitis; vertebral osteomyelitis, psoas abscess, and urinary tract infection; vertebral osteomyelitis, septic arthritis, and empyema. ‡Other infections were 3 cases of catheter-related bloodstream infection; 3 cases of decubitus infection; 2 cases of secondary peritonitis; and 1 case each of empyema; surgical site infection; retroperitoneal abscess; pyogenic lymphadenitis; and mycotic aneurysm.
| Characteristics | No. (%) isolates | p value | |
|---|---|---|---|
| 2005–2017, n = 58 | 2018–2021, n = 88 | ||
| CC or ST | |||
| CC17 | 23 (39.7) | 27 (30.7) | 0.288 |
| CC25 | 13 (22.4) | 28 (31.8) | 0.261 |
| CC29 | 5 (8.6) | 8 (9.1) | 1.000 |
| ST525 | 1 (1.7) | 15 (17.1) | 0.001 |
| Others | 16 (27.6) | 10 (11.4) | 0.015 |
| Antimicrobial nonsusceptibility | |||
| Erythromycin | 16 (27.6) | 30 (34.1) | 0.469 |
| Minocycline | 17 (29.3) | 28 (31.8) | 0.855 |
| Clindamycin | 11 (19.0) | 26 (29.5) | 0.176 |
| MDR† | 5 (8.6) | 19 (21.6) | 0.042 |
Table 3. Temporal changes in clonal complexes and sequence types and antimicrobial nonsusceptibility rates of Streptococcus dysgalactiae subspecies equisimilis bacteremia, Japan, 2005–2021*
*CC, clonal complex; MDR, multidrug resistance; ST, sequence type. †Resistant to erythromycin, minocycline, and clindamycin.
| CC or ST | Penicillin G | Cefotaxime | Meropenem | Erythromycin | Minocycline | Clindamycin |
|---|---|---|---|---|---|---|
| CC17, n = 50 | 0 | 0 | 0 | 9 (18.0) | 2 (4.0) | 8 (16.0) |
| CC25, n = 41 | 0 | 0 | 0 | 12 (29.3) | 16 (39.0) | 12 (29.3) |
| ST525, n = 16 | 0 | 0 | 0 | 16 (100) | 16 (100) | 16 (100) |
| CC29, n = 13 | 0 | 0 | 0 | 1 (7.7) | 1 (7.7) | 1 (7.7) |
| Others, n = 26 | 0 | 0 | 0 | 8 (30.8) | 10 (38.5) | 0 |
| Total, n = 146 | 0 | 0 | 0 | 46 (31.5) | 45 (30.8) | 37 (25.5) |
Table 4. Antimicrobial nonsusceptibility rates among Streptococcus dysgalactiae subspecies equisimilis clonal complexes and sequence types, Japan, 2005–2021*
*Values are no. (%) isolates. CC, clonal complex; ST, sequence type.
| CC or ST | ermB | ermA | mef(A/E) | tetM | tetL | Tn916-like ICE |
|---|---|---|---|---|---|---|
| CC17, n = 50 | 2 (4.0) | 7 (14.0) | 0 | 2 (4.0) | 0 | 2 (4.0) |
| CC25, n = 41 | 12 (29.3) | 0 | 0 | 18 (43.9) | 0 | 17 (41.5) |
| ST525, n = 16 | 16 (100) | 0 | 0 | 16 (100) | 0 | 16 (100) |
| CC29, n = 13 | 0 | 1 (7.7) | 0 | 0 | 0 | 0 |
| Others, n = 26 | 0 | 5 (19.2) | 5 (19.2) | 10 (38.5) | 2 (7.7) | 3 (11.5) |
| Total, n = 146 | 30 (20.5) | 13 (8.9) | 5 (3.4) | 46 (31.5) | 2 (1.4) | 38 (26.0) |
Table 5. Prevalence of antimicrobial resistance determinant genes and Tn916-like integrative and conjugative elements among Streptococcus dysgalactiae subspecies equisimilis clonal complexes and sequence types, Japan, 2005–2021*
*Values are no. (%) isolates. CC, clonal complex; ICE, integrative and conjugative element; ST, sequence type.
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 physicians, internists, intensivists, and other physicians caring for patients with or at risk for Streptococcus dysgalactiae subspecies equisimilis (SDSE).
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Incidence of Streptococcus dysgalactiae subspecies equisimilis (SDSE) bacteremia is increasing in the Kyoto-Shiga region of Japan. We retrospectively analyzed clinical features of SDSE bacteremia and conducted comparative genomic analyses of isolates collected from 146 bacteremia episodes among 133 patients during 2005–2021. Of those patients, 7.7% required vasopressor support, and 7.0% died while in the hospital. The prevalence of isolates resistant to erythromycin, minocycline, and clindamycin increased from 8.6% during 2005–2017 to 21.6% during 2018–2021. Our genomic analysis demonstrated that sequence type 525 and clonal complex 25 were predominant in SDSE isolates collected during 2018–2021. In addition, those isolates had acquired 2 antimicrobial-resistance genes, ermB and tetM, via Tn916-like integrative and conjugative elements (ICEs). Phylogenetic analysis revealed clonal distribution of Tn916-like ICEs in SDSE isolates. Our findings suggest that Tn916-like ICEs contributed to the emergence and recent increase of multidrug-resistant SDSE bacteremia in this region of Japan.
Streptococcus dysgalactiae subspecies equisimilis (SDSE) is a member of the pyogenic group of streptococci that typically is agglutinated by serum against Lancefield group G or C antigens (rarely A or L antigens)[1]. Although SDSE has been considered a part of the commensal flora and is much less virulent than S. pyogenes, SDSE increasingly has been recognized as a clinically relevant pathogenic bacterium[2–4]. SDSE can cause a broad range of diseases, from milder illnesses such as pharyngitis and skin and soft-tissue infections to severe conditions such as streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis that can resemble infections caused by S. pyogenes [2,4–6].
Invasive SDSE infections mainly affect elderly persons with underlying illnesses[2,4,6]; fatality rates of 2%–20% have been reported[4,7]. Moreover, multiple countries, including Israel, Denmark, Norway, and Canada, have reported increasing incidence of invasive diseases caused by SDSE or group C or G Streptococcus (GCGS)[8–11]. In Japan, a single-center study in Tokyo reported a substantial increase in the age-adjusted incidence of invasive group G Streptococcus from 2003–2007 to 2008–2013[12]. An aging population with multiple underlying conditions only partially explains those reports[8,12] and other reasons for the growing prevalence of invasive SDSE infections remain unclear.
SDSE is essentially susceptible to penicillin and other β-lactam antibiotics, but resistance to other antimicrobial agents has emerged. Multiple countries, including the United States, Japan, and Norway, have reported increased prevalence of erythromycin- and clindamycin-resistant isolates[2,5,13]. Moreover, recent studies in countries in eastern Asia showed much higher prevalence of resistance to multiple antimicrobial agents, including macrolides, tetracyclines, and lincosamide[14,15]. A multicenter study in China showed resistance rates of 71.4% to erythromycin, 71.4% to clindamycin, and 60.7% to tetracycline[15]. The prevalent genes responsible for macrolide resistance in those studies were mefA/E, ermA, and ermB[5,13–15]; ermA and ermB are also responsible for clindamycin resistance and typically confer inducible and constitutive resistance.
We conducted a retrospective, multicenter, surveillance study of SDSE bacteremia cases in the Kyoto-Shiga region of Japan. We also performed a comparative genomic analysis of clinical SDSE isolates preserved in 3 hospitals in the region to explore the phylogenetic relationships and emergence of antimicrobial resistance (AMR).
