Date Published: March 7, 2019
Publisher: Public Library of Science
Author(s): Yoshihiro Fujiya, Kayoko Hayakawa, Yoshiaki Gu, Kei Yamamoto, Momoko Mawatari, Satoshi Kutsuna, Nozomi Takeshita, Yasuyuki Kato, Shuzo Kanagawa, Norio Ohmagari, Ray Borrow.
Invasive Group G streptococcal infection (iGGS) has increasingly been recognized as a cause of severe disease, mainly among elderly people with chronic illnesses. This study aimed to examine age-related differences in clinical characteristics of iGGS and describe its characteristics among very elderly individuals (≥80 years).
Fifty-four iGGS patients for whom detailed clinical information was available were identified from 2002 to 2014 in a tertiary care hospital in Japan. iGGS (n = 54) was compared with invasive Group A (iGAS; n = 17) and B streptococcal infection patients (iGBS; n = 52) based on patient age.
The incidence of iGGS in our catchment area significantly increased during the study period. The prevalence of iGGS in the very elderly population was higher than that of iGAS or iGBS (p<0.001). Among iGGS patients, cardiovascular disease, chronic kidney disease, oxygen demand, and bacteremia with unknown focus of infection were more frequent in the very elderly population (p = 0.009, p = 0.02, p = 0.04, and p = 0.04, respectively). Altered mental status was present in half of iGGS patients aged ≥60 years (p = 0.03). In contrast, alcohol drinking and liver cirrhosis were significantly more frequent in patients with iGGS aged <60 years than in other age groups (p<0.001, p = 0.001, respectively). Levofloxacin resistance in GBS isolates was significantly more frequent among very elderly patients than among other age groups (p<0.001). The burden of iGGS has been increasing in our catchment area. Different iGGS-associated clinical characteristics were found in each age group. Unclear and atypical clinical manifestations and syndromes were likely to be observed in very elderly patients. Alcohol drinking and liver cirrhosis may contribute to iGGS even in patients aged <60 years. Understanding these age-related differences could be helpful for optimal diagnosis and treatment.
The beta-hemolytic streptococci (BHS) belonging to the Lancefield group A, B, and G (GAS, GBS, and GGS, respectively) are common pathogens for a wide spectrum of infectious diseases in humans. Invasive GAS and GBS infections (iGAS and iGBS, respectively), including bacteremia, pneumonia, arthritis, meningitis, necrotizing fasciitis, and streptococcal toxic shock syndrome (STSS), have been reported worldwide and are diseases with high fatality rates (typically 10–60% fatal) [1–6]. Recently, an increased number of cases of bacteremia due to GGS have been reported [7, 8]. GGS has been increasingly recognized as an important pathogen causing invasive infections. Invasive GGS infections (iGGS) occur most commonly in elderly patients and those with underlying diseases [9, 10]. Bacteremic cellulitis, bacteremia without focus, and bone and joint infections are the most common clinical manifestations among patients with iGGS [9–11]. Life-threatening diseases caused by GGS, such as necrotizing fasciitis, STSS, pneumonia, endocarditis, and others resembling those by GAS, have been reported recently, even though GGS is considered a less virulent pathogen than GAS [9, 11, 12]. Some studies indicate that the case fatality ratio of iGGS is as high as that of iGAS, and optimal clinical management is therefore essential [9, 11, 13].
During the study period, 189 patients with invasive streptococcal infection were detected in the laboratory database; of these, there were 36 (19%), 83 (44%), and 70 (37%) patients with iGAS, iGBS, and iGGS, respectively. All patients had no recurrence and had only one episode of invasive infection. All GAS, GBS, and GGS were identified as Streptococcus pyogenes, S. agalactiae, and S. dysgalactiae subspecies equisimilis, respectively. All BHS were isolated from sterile site specimens; of these, 170 (90%) were from blood, 3 (2%) from CSF, 3 (2%) from pleural effusion, 6 (3%) from ascites, and 7 (4%) from synovial fluid. The overall age-adjusted incidences for iGAS, iGBS, and iGGS from 2003 to 2013 (95% confidence interval) were 0.9 (0.4–1.4), 2.5 (1.8–3.1), and 2.1 (1.5–2.7) per 100,000 inhabitants, respectively. Their annual trends are presented in Fig 1. There was a significant increase in iGGS incidence from the first to the last 5-year period (IRR 1.89, p = 0.02), with annual incidence peaking at 3.3/100,000 inhabitants in 2013. The iGAS incidence showed marked fluctuations over time, ranging from 0.0/100,000 (2006 and 2009) to 1.9/100,000 (2007). However, no statistically significant trend was observed (IRR 0.61, p = 0.40). The iGBS incidence remained steady from about 2.0/100,000 to 3.0/100,000, with no statistically significant trend (IRR 1.13, p = 0.92). During the most recent year (2013), iGGS was the dominant iBHS.
The purpose of this study was to show age-related differences in clinical characteristics of invasive streptococcal infection, particularly iGGS. Over 12 years, iGGS was dominant in very elderly patients aged ≥80 years, and the incidence of iGGS had been increasing. CVD and CKD as comorbidities, unknown focus of infection, and atypical clinical manifestations, such as altered mental status, were frequent among very elderly patients with iGGS.