Invasive group A streptococcal disease: Management and chemoprophylaxis

Allen, UD; Moore, DL

doi:10.1093/pch/15.5.295

Cited by 17 publications

(8 citation statements)

References 14 publications

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“…46 While penicillin is still considered as the first-choice drug for uncomplicated streptococcal infections, they have been proven ineffective in invasive infections. 47 In fact, based on the recommendations of the Infectious Diseases Society of America, penicillin should be used in combination with a protein synthesis inhibitor (eg, clindamycin) in these clinical cases. 48 The use of clindamycin for lifethreatening invasive infections was shown to reduce mortality rates.…”

Section: Discussionmentioning

confidence: 99%

Beta-Haemolytic Group A, C and G Streptococcal Infections in Southern Hungary: A 10-Year Population-Based Retrospective Survey (2008–2017) and a Review of the Literature

Gajdács¹,

Ábrók²,

Lázár³

et al. 2020

IDR

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Introduction: Pyogenic β-hemolytic streptococci (including Group A, C and G Streptococcus) are some of the most important Gram-positive bacterial pathogens in human medicine. Although effective therapy is available, invasive streptococcal infections are associated with a significant disease burden. Methods: In this retrospective study, the epidemiological characteristics of invasive Group A (iGAS) and Group C and G (iGCGS) streptococci, along with tonsillo-pharyngitis-causing pGAS and pGCGS infections, were assessed in Southern Hungary. A total of 1554 cases of streptococcal tonsillo-pharyngitis infections (26.5-44.1/100,000 persons, pGAS: 95.5%; n=1484) and 1104 cases of invasive streptococcal infections were detected (12.5-31.4/ 100,000 persons, iGAS: 77.9%; n=861). Results: The average age of the affected patients in the various groups were the following: pGAS: 13.2±13.1 years, pGCGS: 21.0±15.0 years (p=0.039), iGAS: 49.1±12.8 years, iGCGS: 58.7±18.5 years (p>0.05). iGAS isolates originated from abscesses (47.1%), blood culture samples (24.1%), surgical samples (16.7%), biopsies (4.6%), pleural fluid (3.5%), pus (2.0%), synovial fluid (1.3%) and cerebrospinal fluid samples (0.7%). In contrast, iGCGS isolates mainly originated from blood culture samples (53.8%), abscesses (22.9%), surgical samples (12.3%), synovial fluid (5.1%), pleural fluid (3.7%), pus (1.8%) and cerebrospinal fluid samples (0.4%). All respective isolates were susceptible to benzyl-penicillin; overall resistance levels for erythromycin (10.5% for GAS, 21.4% for GCGS) and clindamycin (9.2% for GAS, 17.2% for GCGS) were significantly higher in GCGS isolates, while resistance levels for norfloxacin were higher in GAS isolates (13.5% for GAS, 6.9% for GCGS). Conclusion:The rates of resistance to macrolides and clindamycin are a cause for concern (especially among GCGS isolates); however, resistance levels are still relatively low, compared to Southern European countries.

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Section: Discussionmentioning

confidence: 99%

Beta-Haemolytic Group A, C and G Streptococcal Infections in Southern Hungary: A 10-Year Population-Based Retrospective Survey (2008–2017) and a Review of the Literature

Gajdács¹,

Ábrók²,

Lázár³

et al. 2020

IDR

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“…The existence of a therapeutic window of time for treatment of GAS NF is critical ( 8 , 10 , 13 , 15 , 16 ). We showed that treatment of infected mice with ISRIB or GSK2656157 12 hours after infection successfully terminated the infection.…”

Section: Discussionmentioning

confidence: 99%

“…The initial lesion may appear only as mild erythema, but inflammation becomes extensive within a short period, leading to a destructive skin and soft tissue process over large body areas ( 15 ). The mainstay of treatment for invasive GAS diseases is administering antibiotics, surgical debridement of infected tissues, and supportive care ( 16 ). Unfortunately, regardless of prompt therapy, the associated mortality rate from NF remains high, ranging from 23 to 35% in resource-rich settings ( 7 , 8 , 10 , 11 , 13 , 17 ).…”

Section: Introductionmentioning

confidence: 99%

Unfolded protein response inhibitors cure group A streptococcal necrotizing fasciitis by modulating host asparagine

et al. 2021

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Group A streptococcus (GAS) is among the top 10 causes of mortality from an infectious disease, producing mild to invasive life-threatening manifestations. Necrotizing fasciitis (NF) is characterized by a rapid GAS spread into fascial planes followed by extensive tissue destruction. Despite prompt treatments of antibiotic administration and tissue debridement, mortality from NF is still high. Moreover, there is no effective vaccine against GAS, and early diagnosis of NF is problematic because its clinical presentations are not specific. Thus, there is a genuine need for effective treatments against GAS NF. Previously, we reported that GAS induces endoplasmic reticulum (ER) stress to gain asparagine from the host. Here, we demonstrate that GAS-mediated asparagine induction and release occur through the PERK-eIF2α-ATF4 branch of the unfolded protein response. Inhibitors of PERK or integrated stress response (ISR) blocked the formation and release of asparagine by infected mammalian cells, and exogenously added asparagine overcame this inhibition. Moreover, in a murine model of NF, we show that the inhibitors minimized mortality when mice were challenged with a lethal dose of GAS and reduced bacterial counts and lesion size when mice were challenged with a sublethal dose. Immunohistopathology studies demonstrated that PERK/ISR inhibitors protected mice by enabling neutrophil infiltration into GAS-infected fascia and reducing the pro-inflammatory response that causes tissue damage. Inhibitor treatment was also effective in mice when started at 12 hours after infection. We conclude that host metabolic alteration induced by PERK or ISR inhibitors is a promising therapeutic strategy to treat highly invasive GAS infections.

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“…In Australia, a lincosamide antibiotic (usually clindamycin) and IVIG are generally recommended for the management of severe iGAS disease, albeit with limited evidence in children. [28][29][30] Previous studies suggest that adding clindamycin may reduce mortality. 31 An adult study demonstrated increased survival when IVIG was used for patients with STSS (34% vs. 87% survival rate at 30 days).…”

Section: Discussionmentioning

confidence: 99%

Clinical Description and Outcomes of Australian Children With Invasive Group A Streptococcal Disease

Thielemans

Oliver

McMinn

et al. 2020

Pediatric Infectious Disease Journal

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Background: Invasive group A streptococcal disease is a severe infection with a high case fatality rate, estimated to cause more than 150,000 deaths per year worldwide. The clinical presentation of this infection is variable, and early diagnosis can be challenging. There are few data on its short-and longer-term outcomes, especially in children. The aim of this study was to assess the clinical presentation, management and short-and longer-term outcomes of invasive group A streptococcal disease in children in Australia. Methods: We undertook a prospective surveillance study of children with laboratory-confirmed invasive group A streptococcus disease admitted to 7 sentinel tertiary and quaternary pediatric hospitals in Australia between July 2016 and June 2018. We collected demographic and clinical data and contacted patients 6 months after discharge to assess longer-term outcomes. Results: We enrolled 181 children, 7 days to 16 years of age. The principal site of invasive infection was blood (126 children, 69.6%), and the most frequent clinical presentation was pneumonia in 46 children (25.4%). Twentysix children developed streptococcal toxic shock syndrome (14.4%), and 74 had severe disease (40.9%), including 71 admitted to the intensive care unit. Five children died (2.8%). At discharge and 6 months, 29.3% and 15.2% of the children had persisting health problems, respectively. Conclusions: Invasive group A streptococcal infection in Australian children is frequently severe and has a high long-term morbidity burden, highlighting the need for strengthened clinical care pathways, epidemiological surveillance and prevention strategies.

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Invasive group A streptococcal disease: Management and chemoprophylaxis

Cited by 17 publications

References 14 publications

Beta-Haemolytic Group A, C and G Streptococcal Infections in Southern Hungary: A 10-Year Population-Based Retrospective Survey (2008–2017) and a Review of the Literature

Beta-Haemolytic Group A, C and G Streptococcal Infections in Southern Hungary: A 10-Year Population-Based Retrospective Survey (2008–2017) and a Review of the Literature

Unfolded protein response inhibitors cure group A streptococcal necrotizing fasciitis by modulating host asparagine

Clinical Description and Outcomes of Australian Children With Invasive Group A Streptococcal Disease

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