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Streptococcus species represent a significant global cause of meningitis, leading to brain damage through bacterial virulence factors and the host inflammatory response. Upon entering the central nervous system (CNS), excessive inflammation leads to various neurological and psychological complications. This review explores the pathophysiological mechanisms and associated outcomes of streptococcal meningitis, particularly its short- and long-term neurological sequelae. Neurological symptoms, such as cognitive impairment, motor deficits, and sensory loss, are shown to vary in severity, with children being particularly susceptible to lasting complications. Among survivors, hearing loss, cognitive decline, and cranial nerve palsies emerge as the most frequently reported complications. The findings highlight the need for timely intervention, including neurorehabilitation strategies that focus on optimizing recovery and mitigating long-term disabilities. Future recommendations emphasize improving early diagnosis, expanding vaccine access, and personalizing rehabilitation protocols to enhance patient outcomes. As a novel contribution, this review proposes the term "post-meningitic syndrome" to showcase the broad spectrum of CNS complications that persist following streptococcal meningitis, providing a framework for a future clinical and research focus.

Excessive production of reactive oxygen species (ROS) leads to oxidative stress in host cells and affects the progress of disease. Mitochondria are an important source of ROS and their dysfunction is closely related to ROS production. S. uberis is a common causative agent of mastitis. The expression of key enzymes of the mitochondrial apoptotic pathway is increased in mammary epithelial cells after S. uberis stimulation, while expression of proteins related to mitochondrial function is decreased. Drp1, a key protein associated with mitochondrial function, is activated upon infection. Accompanied by mitochondria-cytosol translocation of Drp1, Fis1 expression is significantly upregulated while Mfn1 expression is downregulated implying that the balance of mitochondrial dynamics is disrupted. This leads to mitochondrial fragmentation, decreased mitochondrial membrane potential, higher levels of mROS and oxidative injury. The AMPK activator AICAR inhibits the increased phosphorylation of Drp1 and the translocation of Drp1 to mitochondria by salvaging mitochondrial function in an AMPK/Drp1 dependent manner, which has a similar effect to Drp1 inhibitor Mdivi-1. These data show that AMPK, as an upstream negative regulator of Drp1, ameliorates mitochondrial dysfunction induced by S. uberis infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Pore-forming toxins (PFTs) are commonly produced by pathogenic bacteria, and understanding them is key to the development of virulence-targeted therapies. Streptococcus agalactiae, or group B Streptococcus (GBS), produces several factors that enhance its pathogenicity, including the PFT β-hemolysin/cytolysin (βhc). Little is understood about the cellular factors involved in βhc pore formation. We conducted a whole-genome CRISPR-Cas9 forward genetic screen to identify host genes that might contribute to βhc pore formation and cell death. While the screen identified the established receptor, CD59, in control experiments using the toxin intermedilysin (ILY), no clear candidate genes were identified that were required for βhc-mediated lethality. Of the top targets from the screen, two genes involved in membrane remodeling and repair represented candidates that might modulate the kinetics of βhc-induced cell death. Upon attempted validation of the results using monoclonal cell lines with targeted disruption of these genes, no effect on βhc-mediated cell lysis was observed. The CRISPR-Cas9 screen results are consistent with the hypothesis that βhc does not require a single nonessential host factor to mediate target cell death. IMPORTANCE CRISPR-Cas9 forward genetic screens have been used to identify host cell targets required by bacterial toxins. They have been used successfully to both verify known targets and elucidate novel host factors required by toxins. Here, we show that this approach fails to identify host factors required for cell death due to βhc, a toxin required for GBS virulence. These data suggest that βhc may not require a host cell receptor for toxin function or may require a host receptor that is an essential gene and would not be identified using this screening strategy.

Purpose: To describe the presentation, microbiology, management, and prognosis of eyes with endophthalmitis after Boston keratoprosthesis implantation., Methods: Retrospective case series with history, diagnostics, management, and outcomes data in endophthalmitis after keratoprosthesis implantation presenting to a tertiary center between 2009 and 2020., Results: Of 137 keratoprosthesis-implanted eyes, 7 eyes of 7 patients (5%) developed endophthalmitis. On presentation, 6 (86%) reported decreased visual acuity, and only 1 (14%) reported pain. Peripheral corneal ulcers were present in 2 eyes (29%). Seidel testing was negative in all cases. Six eyes (86%) had retroprosthetic membranes. One (14%) underwent initial pars plana vitrectomy with mechanical vitreous biopsy, whereas 6 (86%) received a needle vitreous tap-half of which were dry. Organisms were isolated after vitreous tap in two eyes: Streptococcus intermedius and Mycobacterium abscessus. The mean visual acuity preendophthalmitis, at presentation, and at 6 months were 20/267, 20/5,944, and 20/734, respectively. The visual acuity improved 9.08 ± 11.78 Early Treatment Diabetic Retinopathy Study lines from presentation to 6 months. Six-month visual acuity was correlated with preendophthalmitis visual acuity (r = 0.92, P = 0.003) but not presenting visual acuity (P = 0.838)., Conclusion: Visual acuity at 6 months is correlated with preendophthalmitis visual acuity, not presenting visual acuity. Endophthalmitis should be considered in the differential diagnosis of painless intraocular inflammation any time after keratoprosthesis implantation, even if Seidel negative.

Background: Purpura and glomerulonephritis are typical presentations in IgA vasculitis. Infective endocarditis mimicking IgA vasculitis by presenting with glomerulonephritis and purpura is rarely reported., Methods: We searched for cases with infective endocarditis-associated purpura and glomerulonephritis in a tertiary hospital in China and retrospectively reviewed their clinicopathological features. Differential diagnosis and treatment in patients with infective endocarditis-associated purpura and glomerulonephritis were discussed., Results: A total of 20 cases with infective endocarditis-associated purpura and glomerulonephritis were identified among 548 cases with infective endocarditis in our center during an 8-year period: 7 of the 20 cases (35%) were initially misdiagnosed as IgA vasculitis and 10 cases (50%) presented with left-sided endocarditis caused by Streptococcus viridans. Fever (100%, 20 out of 20), prior valvular deformities (80%, 16 out of 20), cardiac murmur (95%, 19 out of 20), splenomegaly (84%, 16 out of 19), embolism (55%, 11 out of 20), and hypocomplementemia (76%, 13 out of 17) were present in most patients. Crescents and mesangial hypercellularity with or without endothelial hypercellularity were the primary findings on light microscopy, with C3-dominant deposition on immunofluorescence. But IgA-dominant staining was also observed (40%, 2 out of 5). In patients with rapidly progressive glomerulonephritis, patients with complete recovery of renal function had shorter disease duration and higher ratio (67% vs 20%) of immunosuppressive therapy compared with patients with partial recovery., Conclusions: Infective endocarditis-associated glomerulonephritis and purpura can closely mimic IgA vasculitis. Differential diagnosis is challenging, particularly when typical presentations of infective endocarditis are absent. In adults with presentations like IgA vasculitis, infective endocarditis should be evaluated through comprehensive clinical and pathological investigations. Immunosuppressive therapy can be considered in patients with severe glomerulonephritis who do not improve after proper anti-infective therapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

During infection and inflammation, a reduced oxygen level clearly affects cellular functions. Oxygen levels during CNS infections are unknown. Here we established and evaluated an in vivo measurement system to characterize the oxygen level in parallel with bacterial numbers (CFU/mL), the cell number and pH level inside the CSF of healthy compared to Streptococcus suis-infected pigs. The animals were anesthetized over a seven-hour period with isoflurane in air/oxygen at physiologic arterial partial pressure of oxygen. Oxygen levels in CSF of anesthetized pigs were compared to euthanized pigs. The detected partial pressure of oxygen in the CSF remained constant in a range of 47-63 mmHg, independent of the infection status (bacterial or cell number). In contrast, the pH value showed a slight drop during infection, which correlated with cell and bacterial number in CSF. We present physiologic oxygen and pH values in CSF during the onset of bacterial meningitis.

Background: The present study focuses on the associations of streptococcal infection with the clinical phenotypes, relapse/recurrence and renal involvement in Henoch-Schönlein purpura (HSP) children., Methods: Two thousand seventy-four Chinese children with HSP were recruited from January 2015 to December 2019. Patients' histories associated with HSP onset were obtained by interviews and questionnaires. Laboratory data of urine tests, blood sample and infectious agents were collected. Renal biopsy was performed by the percutaneous technique., Results: (1) Streptococcal infection was identified in 393 (18.9%) HSP patients, and served as the most frequent infectious trigger. (2) Among the 393 cases with streptococcal infection, 43.0% of them had arthritis/arthralgia, 32.1% had abdominal pain and 29.3% had renal involvement. (3) 26.1% of HSP patients relapsed or recurred more than 1 time within a 5-year observational period, and the relapse/recurrence rate in streptococcal infectious group was subjected to a 0.4-fold decrease as compared with the non-infectious group. (4) No significant differences in renal pathological damage were identified among the streptococcal infectious group, the other infectious group and the non-infectious group., Conclusions: Streptococcal infection is the most frequent trigger for childhood HSP and does not aggravate renal pathological damage; the possible elimination of streptococcal infection helps relieve the relapse/recurrence of HSP.

Case Presentation: A 70-year-old man presented to the ED with sudden onset of left thigh pain followed by transient chest discomfort. His history included cerebrovascular disease, hypertension, and cocaine and methamphetamine use. Physical examination revealed an uncomfortable male subject with a temperature of 37 °C, heart rate of 129 beats/min, BP of 130/65 mm Hg, and 98% oxygen saturation on room air. There was point tenderness in the left lateral thigh without erythema, swelling, or overlying skin changes. His cardiac examination revealed an irregular tachycardia at 129 beats/min and normal first and second heart sounds without murmurs, gallops, or rubs. The remainder of the examination was unremarkable., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: Polymerase chain reaction (PCR)-based testing of cerebrospinal fluid (CSF) samples has greatly facilitated the diagnosis of central nervous system (CNS) infections. However, the clinical significance of Epstein-Barr virus (EBV) DNA in CSF of individuals with suspected CNS infection remains unclear. We wanted to gain a better understanding of EBV as an infectious agent in immunocompetent patients with CNS disorders., Methods: We identified cases of EBV-associated CNS infections and reviewed their clinical and laboratory characteristics. The study population was drawn from patients with EBV PCR positivity in CSF who visited Pusan National University Hospital between 2010 and 2019., Results: Of the 780 CSF samples examined during the 10-year study period, 42 (5.4 %) were positive for EBV DNA; 9 of the patients (21.4 %) were diagnosed with non-CNS infectious diseases, such as optic neuritis, Guillain-Barré syndrome, and idiopathic intracranial hypotension, and the other 33 cases were classified as CNS infections (22 as encephalitis and 11 as meningitis). Intensive care unit admission (13/33 patients, 39.3 %) and presence of severe neurological sequelae at discharge (8/33 patients, 24.2 %) were relatively frequent. In 10 patients (30.3 %), the following pathogens were detected in CSF in addition to EBV: varicella-zoster virus (n = 3), cytomegalovirus (n = 2), herpes simplex virus 1 (n = 1), herpes simplex virus 2 (n = 1), Streptococcus pneumomiae (n = 2), and Enterococcus faecalis (n = 1). The EBV-only group (n = 23) and the co-infection group (n = 10) did not differ in age, gender, laboratory data, results of brain imaging studies, clinical manifestations, or prognosis; however, the co-infected patients had higher CSF protein levels., Conclusion: EBV DNA in CSF is occasionally found in the immunocompetent population; the virus was commonly associated with encephalitis and poor prognosis, and frequently found together with other microbes in CSF., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study aimed to evaluate the effects of chronic subclinical mastitis (CSM) on milk production and component yields in dairy cows. A total of six herds located in the Midwest area of São Paulo State, Brazil were selected. Herds were visited once every 2 weeks to measure milk yield and to collect milk samples from lactating Holstein cows. Milk samples were collected at two stages (1 and 2), and each stage comprised three milk samplings. In stage 1, a total of 117 of 647 cows were diagnosed with CSM based on at least two of three repeated somatic cell counts (SCC) > 2000,000 cells/mL and positive bacterial milk culture results (BC). Cows with CSM were selected for the second stage. In stage 2, selected cows had quarter sampling aseptically collected for BC analyses prior to milking, and quarter milk yield was measured. Milk components (total protein, fat, lactose, and total solids) were measured using mid-infrared spectroscopy. Mammary quarters were considered healthy if all three repeated SCC results were ≤ 200,000 cells/mL and no bacterial growth was detected on BC. All quarters with positive bacterial growth were classified as having (non-chronic) subclinical mastitis when only one of three SCC results were > 200,000 cells/mL, and CSM when at least two of three SCC results were > 200,000 cells/mL. The effects of CSM by type of pathogen on milk and components yield were assessed using a linear mixed model. Mammary quarters with CSM caused by major pathogens had milk loss of 1.1 kg/quarter milking in comparison to healthy quarters. Milk losses were 0.8 and 1.3 kg/quarter milking when CSM was caused by Staphylococcus aureus or environmental streptococci, respectively. In addition, healthy quarters produced more milk components than quarters with CSM caused by major pathogens. Minor pathogens causing CSM (non-aureus staphylococci and Corynebacterium spp.) had no effect on milk yield. Quarters with CSM had lower milk and component yields when compared with healthy quarters. Milk losses varied according to the type of pathogen and were higher when associated with major pathogens such as S. aureus and environmental streptococci compared with healthy quarters., (Copyright © 2020. Published by Elsevier Ltd.)

If undiagnosed and untreated, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) can suddenly and drastically disrupt the lives of previously healthy children and their families. The key to prompt diagnosis of PANDAS and its appropriate treatment is provider awareness that streptococcal infection may present with neuropsychiatric symptoms. The authors discuss the signs and symptoms that characterize PANDAS, as well as its presumed pathogenesis, and illustrate, through a composite case history, a symptom presentation, diagnostic journey, treatment course, and recovery that is representative of many PANDAS cases.

Background : Streptococcal Toxic Shock Syndrome (STSS) is a serious condition that can arise from streptococcal postpartum endometritis. It is associated with a substantial increase in mortality rate and can rarely result in multiorgan infarction. Early recognition plays a vital role in patients' outcome. Objective : To report a case of complicated STSS and review the literature for previous case reports of streptococcal postpartum endometritis to determine if STSS diagnostic criteria (published by the Centers for Disease Control and Prevention) were fulfilled. Case presentation : This is a 41-year-old woman who presented 5 days after an uncomplicated vaginal delivery with endometritis complicated by invasive group A β-hemolytic streptococcus (GAS) infection and confirmed toxic shock syndrome. The patient was initially admitted to the critical care unit due to hemodynamic compromise requiring intravenous (IV) fluids, IV antibiotic therapy with penicillin and clindamycin, and IV immunoglobulin therapy. The patient subsequently developed multi-organ infarctions, acute respiratory distress syndrome requiring noninvasive respiratory support, and severe reactive arthritis. Literature review revealed 15 case reports of GAS postpartum endometritis, five met criteria for confirmed STSS. One patient died from severe septic shock leading to cardiopulmonary arrest. Thirteen out of 15 cases of postpartum endometritis occurred after uncomplicated vaginal delivery. Conclusion : STSS is a serious and possibly fatal medical condition that requires early diagnosis and treatment to prevent poor patient outcomes and death. Careful consideration to the patient's postpartum clinical presentation with the implementation of an intradisciplinary approach should be utilized.

Group A Streptococcus (GAS), one of the most common extracellular pathogens, has been reported to invade epithelial and endothelial cells. Our results reveal that M1 GAS strain SF370 can be effectively eliminated by respiratory epithelial cells. Emerging evidence indicates that autophagy is an important strategy for nonphagocytes to eliminate intracellular bacteria. Upon pathogen recognition, cell surface receptors can directly trigger autophagy, which is a critical step in controlling infection. However, the mechanisms of how cells sense invading bacteria and use this information specifically to trigger autophagy remain unclear. In this study, we stimulated cells and infected mice with M and FbaA mutants of M1 GAS strain SF370 or with purified M and FbaA proteins (two critical surface structural proteins of GAS), and found that only FbaA protein was involved in autophagy induction. Furthermore, the FbaA protein induced autophagy independent of common pattern recognition receptors (such as Toll-like receptors); rather, it relies on binding to integrin α5β1 expressed on the cell surface, which is mediated by extracellular matrix protein fibronectin (Fn). The FbaA-Fn-integrin α5β1 complex activates Beclin-1 through the mTOR-ULK1-Beclin-1 pathway, which enables the Beclin-1/Vps34 complex to recruit Rab7 and, ultimately, to promote the formation of autophagosomes. By knocking down integrin α5β1, Fn, Atg5, Beclin-1, and ULK1 in Hep2 cells and deleting Atg5 or integrin α5β1 in mice, we reveal a novel role for integrin α5β1 in inducing autophagy. Our study demonstrates that integrin α5β1, through interacting with pathogen components, initiates effective host innate immunity against invading intracellular pathogens. IMPORTANCE Autophagy is generally considered a strategy used by the innate immune system to eliminate invasive pathogens through capturing and transferring them to lysosomes. Currently, researchers pay more attention to how virulence factors secreted by GAS regulate the autophagic process. Here, we provide the first evidence that the structural protein FbaA of M1 GAS strain SF370 is a potent inducer of autophagy in epithelial cells. Furthermore, we demonstrate that integrin α5β1 in epithelial cells in vitro and in vivo acts as a receptor to initiate the signaling for inducing autophagy by binding to FbaA of M1 GAS strain SF370 via Fn. Our study reveals the underlying mechanisms by which pathogens induce Fn-integrin α5β1 to trigger autophagy in a conserved pattern in epithelial cells., (Copyright © 2020 Wang et al.)

We describe a rare case of bloodstream infection and disseminated septic arthritis in a relatively fit and well 73-year-old retired farmer and gamekeeper, due to the zoonotic organism Streptococcus equi The presence of the organism in multiple joints led to slow clinical response to treatment and was complicated by relapse of infection and lengthy disability. Source control was achieved with multiple joint washouts and spinal cord decompression. Following this, a 6-week course of intravenous antibiotics was required for complete clearance of infection. After a long period of rehabilitation, the patient made a good recovery. This case demonstrates that S. equi can cause life threatening and difficult to treat sepsis in humans and requires a high index of suspicion in people who have regular contact with equine species, cattle and unpasteurised milk., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Necrotizing fasciitis is a major health problem throughout the world. The purpose of this review is to assist providers with the care of these patients through a better understanding of the pathophysiology and management options. Methods: This is a collaborative review of the literature between members of the Surgical Infection Society of North America and World Society of Emergency Surgery. Results: Necrotizing fasciitis continues to be difficult to manage with the mainstay being early diagnosis and surgical intervention. Recognition of at-risk populations assists with the initiation of treatment, thereby impacting outcomes. Conclusions: Although there are some additional treatment strategies available, surgical debridement and antimicrobial therapy are central to the successful eradication of the disease process.

Streptococcus dysgalactiae (SD) is a common pathogen among elderly population. However, to our knowledge, there is no periprosthetic joint infection case reported that is infected with Streptococcus dysgalactiae subspecies equisimilis (SDSE) in the English literature. In this article, we report a 77-year-old male patient who had undergone total knee arthroplasty three years ago and had the diagnosis of cellulitis at his leg followed by swelling, pain and hyperemia localized at his knee. Three knee aspirations were performed and the SDSE was identified. There was no direct contact of patient to animals.

A hallmark feature of severe Group A Streptococcus pyogenes (GAS) infection is dysregulated hemostasis. Hemostasis is the primary pathway for regulating blood flow through events that contribute towards clot formation and its dissolution. However, a number of studies have identified components of hemostasis in regulating survival and dissemination of GAS. Several proteins have been identified on the surface of GAS and they serve to either facilitate invasion to host distal sites or regulate inflammatory responses to the pathogen. GAS M-protein, a surface-exposed virulence factor, appears to be a major target for interactions with host hemostasis proteins. These interactions mediate biochemical events both on the surface of GAS and in the solution when M-protein is released into the surrounding environment through shedding or regulated proteolytic processes that dictate the fate of this pathogen. A thorough understanding of the mechanisms associated with these interactions could lead to novel approaches for altering the course of GAS pathogenicity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Atherosclerosis is exacerbated by periodontal pathogens, which induce vascular inflammation after entering the bloodstream. Among oral indigenous bacteria, Streptococcus sanguinis and S. anginosus are related to systemic disorders, such as infective endocarditis and abscess, and are sometimes detected in human atherosclerotic plaques or blood. Thus, these oral streptococci may contribute to the progression of atherosclerosis. To test this hypothesis, apolipoprotein E-deficient spontaneously hyperlipidemic mice were intraorally challenged with S. sanguinis or S. anginosus. Atherosclerotic plaque formation increased significantly in the S. sanguinis-challenged group compared with the carboxymethylcellulose-treated control group. Expression levels of mRNAs of proinflammatory cytokines in the aorta and levels of atherosclerosis-related mediators in blood increased upon S. sanguinis challenge. Adaptor molecule TNF receptor-associated factor 6 was also enhanced in the aorta when mice were challenged with S. sanguinis. Furthermore, challenge with S. anginosus induced systemic inflammation, but inflammation-related mRNA expression levels in the aorta only increased slightly and were accompanied by minimal expansion of the lesion area. By contrast, with the exception of IL-1α, the expression levels of inflammation-related genes did not change in gingival tissues of both bacteria- and sham-challenged groups. These results reveal that S. sanguinis causes aortic inflammation that leads to accelerated progression of atherosclerosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background:  A patient presenting with fever and purpura after a stay in the tropics tempts a physician to make a differential diagnosis mainly focusing on imported diseases. Although the importance of considering a tropical disease is obvious, the fact that cosmopolitan infections account for one third of the cases in a febrile returning traveler must not be overseen. Toxic Shock Syndrome is amongst the most notorious diseases due to the high mortality when inappropriately managed and the association with necrotizing fasciitis. Methods  : We present a 60-year old female with fever, shock syndrome and progressive appearance of painful purpura on the lower legs after a 2-week holiday in Zanzibar. Results  : The patient was diagnosed with Streptococcal Toxic Shock Syndrome. Treatment focusing on aggressive fluid resuscitation, prompt administration of antibiotics (ceftriaxon, doxycycline and one dose of amikacin) and adjunctive treatment by clindamycin and immunoglobulin was initiated. She was also immediately taken into surgery for a bilateral fasciotomy and surgical exploration of the lower legs. Histology appeared compatible with purpura fulminans, thereby excluding necrotizing fasciitis. No source of infection could be identified.  Conclusion : Toxic Shock Syndrome remains a challenging diagnosis and even more in a returning traveler with an extensive differential diagnosis containing both tropical and cosmopolitan diseases. Cornerstones for the treatment of Streptococcal Toxic Shock Syndrome are abrupt administration of antimicrobial therapy comprising beta-lactam antibiotics and clindamycin and surgical exploration to apply source control when indicated.

In 2 epidemiological studies, we evaluated the effect of mastitis induced by gram-positive Streptococcus and gram-negative Escherichia coli on impaired reproductive performance in lactating Holstein cows. In the first study, 52,202 cows from 178 dairy farms throughout Israel were divided into groups based on infection before first artificial insemination (AI) with Streptococcus or E. coli, 3 groups with elevated somatic cell count (SCC) without infection by those pathogens [low SCC (200-400) × 10 3 cell/mL; medium SCC (401-1,000) × 10 3 cell/mL; high SCC, >1,000 × 10 3 cell/mL], and uninfected controls. Pregnancy per first AI (P/1stAI) and pregnancy rate at 300 d in milk (PREG 300) were analyzed by the GLIMMIX procedure (SAS); number of AI per pregnancy (AI/P), days open, and rest days (calving to first AI) were analyzed by the MIXED procedure (SAS Institute Inc., Cary, NC). Values of P/1stAI were similarly low for Streptococcus and E. coli (27-28%) versus 42% in controls; PREG 300 was lower for Streptococcus (76%) than for E. coli (79%) versus 88% for uninfected controls and a mean 83% for the elevated SCC groups. Days open and number of AI/P were higher than in controls and similar in Streptococcus and E. coli groups. The second study included 778 cows on 6 dairy farms; the cows were infected before first AI by Streptococcus or E. coli or uninfected. Resumption of cyclicity was determined by an automated activity-monitoring system, and data were sorted by time of infection before or after cyclicity resumed. The Streptococcus group had lower P/1stAI before and after cyclicity (26 and 27%, respectively) than the E. coli group (31 and 34%, respectively) and uninfected controls (42%). Notably, PREG 300 in the Streptococcus group before (73%) and after (67%) cyclicity was much lower than for the E. coli group (85 and 93%, respectively) and the controls (95%). A marked rise in day of cyclicity resumption (∼80 d) was observed in cows that were infected early on. Number of AI/P was higher in the mastitic groups than in uninfected controls. Uterine disease postpartum, although more prevalent among Streptococcus cows, did not substantially alter the larger reduction in P/1stAI and PREG 300 in Streptococcus versus E. coli cows. Thus, long-term Streptococcus-induced mastitis disrupted fertility more than short-term acute E. coli-induced mastitis, resulting in a much higher percentage of Streptococcus cows in late lactation that did not conceive due to reproduction failure., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

We present a rare case of a rapidly fulminant and destructive breast abscess with gas production by the synergistic infection of Veillonella and Streptococcus species. To our knowledge, this is the first reported case of Veillonella infection in the breast. Early recognition, empiric antibiotic cover, aggressive surgical debridement, and drainage are necessary to avoid systemic septicemia. Staged reconstructive breast surgery allows for correction any resultant breast deformity., (© 2019 Wiley Periodicals, Inc.)

Streptococcosis in tilapia Oreochromis sp. is possibly the most important bacterial disease for fish production worldwide. In Colombia, streptococcosis is caused by Streptococcus agalactiae (GBS), but in other countries, Streptococcus iniae is also involved. Prevention of streptococcosis is required and must be addressed for economic, social, international trade and public health reasons. This research used an in vitro culture of tilapia intestine to detail the intestinal mucosal response once the pathogen contacts the epithelium. We show that S. agalactiae sheds off its capsule to adhere to the epithelium. The bacterium adheres as a single individuum, in groups or in chains and is able to divide on the apical border of enterocytes. GBS adheres at and invades exclusively through the apical portion of the intestinal folds, using the transepithelial route. Once within the cytoplasm of enterocytes, the bacteria continue to divide. On the basolateral side of the epithelium, the microorganisms leave the cells to reach the propria and travel through the microcirculation. No evidence of an immuno-inflammatory reaction or goblet cell response in the epithelium or the lamina propria was seen during the process of adherence and invasion of the pathogen., (© 2019 John Wiley & Sons Ltd.)

Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) describes a disorder that develops in children who abruptly develop neurologic abnormalities following a streptococcal infection. The authors discuss what is known about this poorly understood disorder and how nurses can educate and support patients and their families.

This case report is about a boy born extremely preterm at gestational age of 24 weeks, with extremely low birth weight, developing severe bronchopulmonary dysplasia and in need of mechanical ventilation for 155 days. He also had five recurrent infections with group B streptococcus (GBS) within 4 months from birth, and his respiratory condition clearly deteriorated with every GBS infection. It was difficult to wean him from mechanical ventilation. Finally he was extubated when he was 7 months old and kept out of mechanical ventilation after receiving high-dose methylprednisolone, given according to international recommendations. After GBS was cultured for the fifth time, he received oral rifampicin along with intravenous penicillin and after this treatment, GBS did not occur again. At the age of 22 months, the boy no longer needed any respiratory support and he was about 6 months late in his neurological development., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

A 10-year-old girl, suspected 2 days prior to have streptococcal pharyngitis, presented with diffuse erythema, tense bullae, Nikolsky-positive desquamation, as well as ulcerations of her oral and genital mucosa. She denied recent travel, sick contacts, or preceding and concurrent use of medications, including over-the-counter and herbal supplements. A comprehensive viral polymerase chain reaction (PCR) panel, Mycoplasma pneumoniae PCR and IgM, streptococcal molecular antigen test, urine culture, blood culture, and rheumatologic serologies were negative. Based on the patient's clinical presentation and biopsy results, she was diagnosed with idiopathic toxic epidermal necrolysis., (© 2019 Wiley Periodicals, Inc.)

Background: Sydenham's chorea is the most common acquired movement disorder of adolescence. This clinical manifestation of acute rheumatic fever has a clear and documented relationship with Group A streptococcal infections. The symptoms are involuntary choreiform movements that can affect the face and all extremities. The pathophysiology remains unclear., Case Report: A 12-year-old female was brought to the emergency department with a 2-week history of involuntary muscle spasms of her right arm and leg. Her parents reported intermittent slurred speech and difficulty grasping utensils. Physical examination revealed an awake, alert, age-appropriate female with normal cranial nerves. Patient was found to have choreoathetoid movements on the right extremities with dystonia of right leg with ambulation. Neurology consultation, computed tomography of the head, and magnetic resonance imaging of the brain did not show any acute pathology. Echocardiogram did show mild tricuspid regurgitation, suggestive of rheumatic fever. Anti-streptolysin O titer was markedly elevated, along with DNAse-B antibodies. The patient had marked improvement of movement disorder at just over 1 week later. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Sydenham's chorea is a rare but important movement disorder often related to Group A streptococcus and rheumatic fever. The incidence of rheumatic fever has been decreasing in North America but continues to be much more prevalent in developing countries as well as immigrant populations. This diagnosis is rare and can occasionally be misdiagnosed as a "fidgety" child or as a psychiatric manifestation. Sydenham's chorea is important to diagnose because acute treatment and prophylactic antibiotics can help improve symptoms and minimize cardiac damage., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Objectives: Empirical treatment of sore throat with antibiotics has historically been aimed at preventing complications of group A β-haemolytic streptococcus infection. Threats posed by multi-resistant organisms mean that antimicrobial stewardship is important. The aim of this study was to investigate antibiotic prescribing for tonsillopharyngitis in relation to components of the Modified Centor Criteria (MCC) documented in consultation records., Method: Analysis of two rural Australian general practices was performed using clinic management software. A keyword search for 'tonsillopharyngitis/tonsillitis/pharyngitis' identified consultations., Results: Antibiotic prescribing was frequent and congruent with existing studies; however, documented evidence of history and examination covering MCC components was associated with lower antibiotic prescribing (77.7% versus 85.5%, P <0.001; odds ratio: 2.4; 95% confidence interval: 1.8, 3.3, P <0.0001)., Discussion: We believe this is the first study that assesses the correlation between documentation and prescribing. Adopting and documenting MCC may improve appropriate prescription and patient safety and significantly reduce antibiotic prescription rates.

Objectives: Whether PANS (pediatric acute-onset neuropsychiatric syndrome) and PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) represent true clinical entities is debated and data for a characteristic phenotype are still controversial. In this study, we aim to characterize clinical, neuropsychological, and biochemical aspects in a sample of PANS and PANDAS patients. Methods: Patients fulfilling a clinical diagnosis of PANS or PANDAS from 2014 to 2017 were enrolled. Neurological and psychiatric examination and biochemical and instrumental assessment results were collected. A neuropsychological battery was administered. For comparison purposes, a control group of patients with Sydenham's chorea (SC) was evaluated. Descriptive and comparative statistical analyses were performed. Results: Seven subjects received a diagnosis of PANS, 12 of PANDAS, and 11 of SC. Clinical presentation of PANS children showed statistically significant differences compared with both PANDAS and SC, in particular, with the presence of obsessive symptoms, behavioral regression, and somatic symptoms in the first group. Moreover, all PANS patients showed some neuropsychological deficits in visual-motor abilities, short- and long-term memory, and processing speed. Conclusions: Our experience confirms that patients with PANS had a complex clinical presentation and a compromised neuropsychological profile with respect to patients with PANDAS or SC. However, the absence of biological markers or instrumental alterations made the diagnosis of the two entities, PANS and PANDAS, a matter of exclusion. For these reasons, we propose a pilot diagnostic protocol that (when applied in a prospective manner) will allow comparison with similar childhood-onset neuropsychiatric disorders, such as obsessive-compulsive or tic disorders, and efficacy evaluation of different therapeutic approaches.

Aim: The association between cranial ultrasound (CUS) or magnetic resonance imaging (MRI) lesions and neonatal Group B streptococcal (GBS) meningitis outcome has not been studied in detail., Methods: This retrospective study assessed CUS, cranial MRI and neurodevelopmental outcome in 50 neonates with GBS meningitis admitted to three neonatal intensive care units in the Netherlands between 1992 and 2014. Death, cognitive outcome and motor outcome below -1 SD were considered as adverse outcomes., Results: CUS was available in all and MRIs in 31 infants (62%) with 28 CUS (56%) and 27 MRIs (87%) being abnormal. MRI lesions were multifocal (n = 10, 37%), bilateral (n = 22; 82%) and extensive (n = 11; 41%). A total of 10 died in the neonatal period. Median age at assessment was 24 months. Among survivors, abnormal cognitive outcome and motor outcome were seen in 23 and 20 patients, respectively. Abnormal CUS [odds ratio (OR) 5.3, p = 0.017], extensive bilateral deep grey lesions (OR 6.7, p = 0.035) and white matter lesions (OR 14.0, p = 0.039) correlated with abnormal motor outcome. Extensive bilateral deep grey matter lesions correlated with abnormal cognitive outcome (OR 8.1, p = 0.029)., Conclusion: Abnormal CUS and the most severely affected MRIs were associated with poor neurodevelopmental outcome in neonatal GBS meningitis., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Streptococcus suis is an important porcine bacterial pathogen and a zoonotic agent causing a variety of pathologies including sudden death, septic shock, and meningitis. Though serotype 2 is the most studied serotype due to its presence worldwide, serotype 9 is responsible for the greatest number of porcine cases in Spain, the Netherlands, and Germany. Regardless of its increasing importance, very few studies have investigated S. suis serotype 9 virulence factors and pathogenesis. Antigens I/II (AgI/II) are multimodal adhesion proteins implicated in host respiratory tract and oral cavity persistence of various pathogenic human streptococci. It was recently demonstrated that AgI/II is involved in various bacterial functions for serotype 9, participating in the initial steps of the pathogenesis of the infection. However, its contribution to the systemic infection remains unknown. As such, we evaluated herein the role of the S. suis serotype 9 AgI/II in the interactions with phagocytes and the development of systemic disease in a mouse model of infection. Results demonstrated that the presence of AgI/II is important for the development of clinical systemic disease by promoting bacterial survival in blood possibly due to its effect on S. suis phagocytosis, as shown with macrophages and dendritic cells. Furthermore, AgI/II directly participates in dendritic cell activation and pro-inflammatory mediator production following recognition by the Toll-like receptor pathway, which may contribute to the exacerbated systemic inflammation responsible for host death. Taken together, this study demonstrates that the S. suis serotype 9 AgI/II is important for virulence during systemic infection and development of disease. In fact, this is the first study to describe a role of an AgI/II family member in systemic bacterial disease.

Simultaneous left and right-sided native valve infective endocarditis (IE) is rare. Staphylococcus aureus was the predominant organism for bilateral IE. Shunt diseases are common risk factors of both-sided IE. Streptococcus anginosus (S. anginosus) is usually associated with pyogenic infections, but rarely a cause of IE. Here we present an extremely rare case of simultaneous left and right-sided native valve IE affecting the mitral and tricuspid valves caused by S. anginosus in an adult patient that has not been reported in the literature previously, particularly without the most frequent predisposing factors of IE. A 66-year-old man was admitted due to generalized fatigue, chills, malaise, and intermittent fevers for 1 year. A grade III-IV/VI systolic murmur at the mitral area and a III/VI systolic murmur at the tricuspid area were noted on physical examination. Laboratory evaluation revealed an elevated erythrocyte sedimentation rate and C-reactive protein level, and high fasting blood glucose. Blood culture was positive for S. anginosus. Echocardiography revealed vegetations in both sides of the heart: a large mitral valve vegetation with severe mitral regurgitation, as well as another vegetation on the tricuspid valve with moderate regurgitation. The case highlights a rare pathogen of both-sided IE, a rare presentation of S. anginosus infection, and several points worthy of note in echocardiography of IE.

Objective: In the clinical syndrome Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), obsessive compulsive disorder (OCD) and/or food refusal symptoms have an abrupt-onset (over 48 h) coupled with at least two other specified neuropsychiatric symptoms. We aimed to characterize in detail for the first time, psychotic symptoms experienced by children with PANS as well as the impact of psychotic symptoms on disease severity and course of illness. We inform about the diagnosis of the clinical description: PANS and hope to improve evaluation, treatment, diagnostic validity and future investigation., Methods: Retrospective review of 143 consecutive PANS clinic patient charts meeting inclusion criteria. The Caregiver Burden Inventory, Global Impairment Score, and Children's Global Assessment Scale were used to assess impairment., Results: Visual and auditory hallucinations were each experienced by 36%, of which most (83%) were transient and complex (non-threatening voices or figures). 6.3% and 5.5% of patients experienced delusions and thought disorganization respectively. Those with psychotic symptoms showed statistically significant differences in disease impairment and caregiver burden. There were no differences in time to treatment access or length of illness., Conclusions: Over 1/3 of children with PANS experienced transient hallucinations. They were more impaired than those without psychotic symptoms, but showed no differences in disease progression. This difference may point toward heterogeneity in PANS. When evaluating children with acute psychotic symptoms, clinicians should screen for abrupt-onset of a symptom cluster including OCD and/or food refusal, with neuropsychiatric symptoms (enuresis, handwriting changes, tics, hyperactivity, sleep disorder) before initiating treatment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Severe infections due to Streptococcus dysgalactiae subsp. equisimilis (SDSE) have been identified in adults and may cause toxic shock syndrome, although with a low frequency., Case Report: A preschool-age female patient, who started with an upper respiratory tract infection developing a gradual deterioration in the following three days, is described. She was admitted to the hospital in severe conditions, with tachypnea, tachycardia (200/min), hypotension (blood pressure 68/40 mmHg), capillary refill of 7 s, and erythematous maculopapular rash in thorax, abdomen and lower extremities. She received intensive management with an inadequate response. Furthermore, she developed multiple organ failure and died 8 h after admission. The blood culture was positive for S. dysgalactiae subsp. equisimilis., Conclusions: SDSE is a rare pathogen in children. In Mexico, cases of SDSE have not been reported probably due to an inaccurate identification. Mexican pediatricians should be alert to this situation.., (Copyright: © 2019 Permanyer.)

The aim of the study was to investigate the concentrations of acute-phase inter-α-trypsin inhibitor heavy chain 4 (ITIH4) in serum and milk of cows with subclinical mastitis caused by Streptococcus spp. (STR) and coagulase-negative Staphylococcus spp. (CNS) and healthy cows. The blood and milk samples were obtained from 60 mid-lactation, multiparous Holstein-Friesian cows from 7 herds in the Lublin region of Poland. In the milk samples from 40 cows with subclinical mastitis, Streptococcus spp. and CNS were isolated. The ITIH4 was significantly higher in serum of cows with subclinical mastitis caused both by STR and CNS compared with healthy cows. One hundred percent of animals infected with Streptococcus spp. and 89% of animals infected with Staphylococcus spp. showed ITIH4 concentration in sera higher than 0.5 mg/mL. The concentration of ITIH4 in milk also was significantly higher in cows with subclinical mastitis caused by Streptococcus spp. and Staphylococcus spp. compared with the control group. Seventy percent of cows infected by STR and CNS showed ITIH4 concentration in milk higher than 2.5 μg/mL. Milk ITIH4 concentration higher than 5 µg/mL was found in 55% of animals infected with Streptococcus spp. and in 40% of animals infected with Staphylococcus spp. No statistically significant differences were observed in ITIH4 concentrations both in serum and in milk between the studied unhealthy animal groups. These results suggest that ITIH4 may be used in the future as a novel diagnostic marker in serum and in milk of subclinical mastitis in cows., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Group A β-haemolytic Streptococcus or Streptococcus pyogenes is a gram-positive coccus that tends to grow in chains. Streptococcus pyogenes is the cause of many important human diseases, ranging from pharyngitis and mild superficial skin infections to life-threatening systemic diseases. Infections typically begin in the throat or skin. Mild Streptococcus pyogenes infections include pharyngitis (strep throat) and localised skin infections (impetigo). Erysipelas and cellulitis are characterised by multiplication and lateral spread of Streptococcus pyogenes in deep layers of the skin. Streptococcus pyogenes invasion and fascial involvement can lead to necrotising fasciitis, a life-threatening condition. Scarlet fever is characterised by a sandpaper-like rash in children with fever and is caused by a streptococcal toxin. Severe infections that lead to septicaemia or toxic shock syndrome are associated with high mortality. Autoimmune reactions cause characteristic syndromes such as rheumatic fever and nephritis. Epidemiology, disease presentation, diagnosis, and treatment of paediatric patients in Hong Kong with group A β-haemolytic Streptococcus are reviewed in this article. Streptococcus pyogenes disease is readily treatable, as the organism is invariably sensitive to penicillin. Delayed treatment of this common childhood pathogen is associated with significant mortality and morbidity.

Background: We describe a patient with Strongyloides stercoralis hyperinfection associated with Streptococcus pyogenes and with streptococcal toxic shock syndrome. To the best of our knowledge this association has not been previously described., Case Presentation: A 78 year-old Israeli man, who was born in Iraq but lived in Israel for 66 years, presented with multi-organ failure including acute kidney and hepatic injury, coagulopathy, and lactic acidosis. He had a medical history including aortic valve replacement, diabetes mellitus, spinal stenosis, and low back pain treated with repeated local steroid injections. Blood cultures were positive for Streptococcus pyogenes and antibiotic treatment was switched to penicillin G, clindamycin, and intravenous immunoglobulins. Repeated physical examinations failed to identify the source of the bacteremia. On day 12 of hospitalization the serology results for Strongyloides stercoralis sent on admission, because of chronic eosinophilia, came back positive. A microscopic stool examination and stool polymerase chain reaction were positive for Strongyloides stercoralis. Ivermectin therapy was commenced and continued for a total of 4 weeks. He was discharged for rehabilitation after 25 days. He had no exposure to endemic countries or to immigrants. During many years he had multiple gastrointestinal symptoms, respiratory symptoms, cutaneous symptoms, chronic eosinophilia, and high immunoglobulin E levels. He underwent several operative procedures and numerous hospitalizations and medical encounters with different experts but a parasitic infection was not considered. His asymptomatic daughter was also found to be serologically positive., Conclusions: Strongyloides stercoralis hyperinfection associated with Streptococcus pyogenes bacteremia and toxic shock is described for the first time. The case also highlights the importance of history taking and reviewing past laboratory results, the utility of serological tests for Strongyloides stercoralis, and the importance of screening asymptomatic family members of an infected patient. Strongyloides stercoralis hyperinfection must be considered in the differential diagnosis of any patient with Streptococcus pyogenes bacteremia or toxic shock of no clear source as well as in symptomatic patients with chronic or intermittent eosinophilia, even without any epidemiological risk factors.

Purpose: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to support conventional unsuccessful resuscitation and it is mandatory to rapidly initiate invasive hemodynamic monitoring, as soon as ECPR therapy is commenced. Commonly, this is achieved by establishing an additional arterial line via the right radial artery for invasive blood pressure measurement, but this can be challenging and risky on the one hand and might lead to erroneous measurements on the other hand. Therefore, a faster, easier, safer and more valid method for hemodynamic monitoring is pressingly needed., Methods and Results: We exemplarily describe one in four clinical cases, where hemodynamic monitoring was rapidly established in an ECPR supported patient by modification of the usual VA-ECMO setup: as previously described, a Y connector was implemented in the arterial cannula and equipped with a hemostatic valve at its blind end. Then, a 5 F pigtail catheter was introduced, pushed forward, and connected with a pressure transducer. This approach allows for a rapid and safe measurement of central blood pressure without need for a potentially hazardous additional arterial line., Conclusion: Invasive hemodynamic monitoring in critically ill patients with VA-ECMO support is easily and rapidly achievable by introducing a pigtail catheter through a modified arterial ECMO cannula. Validation of this method in larger clinical trials is warranted., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Most children with severe respiratory failure require extracorporeal membrane oxygenation (ECMO) for 7-10 days. However, some may need prolonged duration ECMO (> 14 days). To date, no consensus exists on how long to wait for native lung recovery. Here we report the case of a 3-year-old boy who developed severe necrotizing pneumonia requiring venovenous (VV) ECMO after 19 days of mechanical ventilation. In the first 4 weeks of his ECMO run, he showed no lung aeration, requiring total extracorporeal support. However, after we started strategies for promoting lung recovery such as daily prone positioning and regular use of toilet bronchoscopy and inhalative DNAse to clear secretions, by week five his tidal volumes gradually increased and he was successfully decannulated after 43 days. Moreover, we decided not to proceed to a surgical removal of the necrotic lung area. At present, he is 1-year post discharge and has fully recovered. This report shows that unexpected native lung recovery is possible even after prolonged loss of lung function and that a previous healthy lung can recover from apparent irreversible lung injury.

Group B streptococcal (GBS) meningitis remains a devastating disease. The absence of an animal model reproducing the natural infectious process has limited our understanding of the disease and, consequently, delayed the development of effective treatments. We describe here a mouse model in which bacteria are transmitted to the offspring from vaginally colonised pregnant females, the natural route of infection. We show that GBS strain BM110, belonging to the CC17 clonal complex, is more virulent in this vertical transmission model than the isogenic mutant BM110∆cylE, which is deprived of hemolysin/cytolysin. Pups exposed to the more virulent strain exhibit higher mortality rates and lung inflammation than those exposed to the attenuated strain. Moreover, pups that survive to BM110 infection present neurological developmental disability, revealed by impaired learning performance and memory in adulthood. The use of this new mouse model, that reproduces key steps of GBS infection in newborns, will promote a better understanding of the physiopathology of GBS-induced meningitis.

We report a previously well paediatric patient with two distinct presentations of invasive group A streptococcus (GAS) infection resulting in significant morbidity. The first episode, following GAS pharyngitis, involved multiorgan dysfunction syndrome. This included cardiorespiratory and acute hepatorenal failure and purpura fulminans that eventually necessitated four-limb amputation. The second episode occurred 12 months later, from undetermined aetiology, and resulted in septic shock. Molecular analysis of the emm gene and PCR for Serum Opacity Factor revealed that the initial isolate was M Type 4 and sof gene positive while the second isolate was M Type 1 and sof gene negative. Immunological investigations, including CH50, quantitative IgA, IgM and IgG, and flow cytometry measuring lymphocyte subsets, and vaccine response to measles, mumps, rubella and pneumococcus were normal. This is the first report of recurrent bacteraemia from different strains of Streptococcus pyogenes infection in an apparently immunocompetent child., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To identify clinical variables associated with increased risk of composite adverse outcome in a cohort of women with puerperal group A streptococci infection., Methods: Our prospective case registry enrolled patients between 1991 and 2017. Chart abstraction was conducted for admission demographic and clinical data in patients with culture-proven puerperal group A streptococci infection. We created a composite variable of signs of capillary leakage including pulmonary edema, pleural effusion, ascites, and abdominal distention. The composite adverse outcome included death, hysterectomy, intensive care unit admission, mechanical ventilation, and blood transfusion. Clinical characteristics were compared between those with a composite adverse outcome and those without. We fit unadjusted log-linear models with robust error variance to measure the relative risk of a composite adverse outcome associated with clinical and demographic variables among patients with group A streptococci., Results: Thirty-five of 71 (49%) patients had an adverse outcome. Women who had adverse outcomes had higher admission heart rates (126±19 vs 112±22 beats per minute, P=.008) and respiratory rates (26±10 vs 20±5 breaths per minute, P=.01), lower systolic blood pressure (98±24 vs 114±19 mm Hg, P=.004), and were more likely to have signs of capillary leakage (77% vs 20%, P<.001) and symptoms of capillary leakage (dyspnea, cough, shoulder pain, abdominal bloating, and chest pain) (40% vs 17%, P=.03) compared with those without adverse outcomes. Log-linear models indicated that these clinical variables were individually associated with increased risk of a composite adverse outcome. The relative risk of an adverse outcome was 3.5 times higher among women with signs of capillary leakage (relative risk 3.67, 95% CI 1.94-6.94, P<.001)., Conclusion: Vital sign parameters consistent with severe infection correlate with adverse outcomes in women with puerperal group A streptococci infection. Signs of capillary leakage are most strongly associated with a composite adverse outcome. These clinical characteristics, particularly signs of capillary leakage, are potentially useful to guide clinical care.

Streptococcus agalactiae (group B Streptococcus [GBS]) is often a commensal bacterium that colonizes healthy adults asymptomatically and is a frequent inhabitant of the vaginal tract in women. However, in immunocompromised individuals, particularly the newborn, GBS may transition to an invasive pathogen and cause serious disease. Despite the use of the currently recommended intrapartum antibiotic prophylaxis for GBS-positive mothers, GBS remains a leading cause of neonatal septicemia and meningitis. To adapt to the various host environments encountered during its disease cycle, GBS possesses multiple two-component regulatory systems (TCSs). Here we investigated the contribution of a transcriptional regulator containing a LytTR domain, LtdR, to GBS pathogenesis. Disruption of the ltdR gene in the GBS chromosome resulted in a significant increase in bacterial invasion into human cerebral microvascular endothelial cells (hCMEC) in vitro as well as the greater penetration of the blood-brain barrier (BBB) and the development of meningitis in vivo Correspondingly, infection of hCMEC with the Δ ltdR mutant resulted in increased secretion of the proinflammatory cytokines interleukin-8 (IL-8), CXCL-1, and IL-6. Further, using a mouse model of GBS vaginal colonization, we observed that the Δ ltdR mutant was cleared more readily from the vaginal tract and also that infection with the Δ ltdR mutant resulted in increased cytokine production from human vaginal epithelial cells. RNA sequencing revealed global transcriptional differences between the Δ ltdR mutant and the parental wild-type GBS strain. These results suggest that LtdR regulates many bacterial processes that can influence GBS-host interactions to promote both bacterial persistence and disease progression., (Copyright © 2018 American Society for Microbiology.)

Lipschütz ulcers (LU) are non-sexually related genital ulcers, rarely reported. We describe a healthy 11-year-old girl, who presented with fever and a painful vulvar ulcer associated with erythematous tonsillitis. Throat swab test for Group A Streptococcus (GAS) was positive. She was treated with amoxicillin. Further investigation was negative, including Herpes Simplex virus DNA from ulcer swab and serology for Epstein-Barr virus, cytomegalovirus and Mycoplasma pneumoniae Antistreptolysin O titre was high. The ulcer healed in 2 weeks, with no recurrence in a 1 year follow-up period. The association of LU with GAS tonsillitis is very rare., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Necrotizing soft-tissue infections (NSTI) are the most severe form of bacterial-induced tissue pathology. Their unpredictable onset and rapid development into life-threatening conditions considerably complicate patient treatment. Understanding the risk factors for NSTI in individual patients is necessary for selecting the appropriate therapeutic option., Methods: We investigated the role of pathogen-specific antibodies in the manifestation of NSTI by performing a comparative serologic approach, using plasma samples and bacterial isolates from patients with clinical NSTIs or nonnecrotizing STIs caused by Streptococcus pyogenes. We also evaluated the potential beneficial effect of intravenous immunoglobulin (IVIG) treatment., Results: We identified a hitherto overlooked state of serologic susceptibility in patients with NSTIs during the earliest stages of the infection that is potentially linked to disease progression. Thus, all patients with NSTIs included in this study exhibited a deficiency in specific antibodies directed against the causative S. pyogenes strains and the majority of their exotoxins during the initial stage of the infection. We also showed that the clinical use of IVIG during the course of infection compensates the observed antibody deficiency but is unable to halt the disease progression, once tissue necrosis has developed., Conclusion: These observations emphasize the requirement of preexisting pathogen-specific antibodies to prevent the irreversible progression of tissue infections into severely spreading NSTIs and urge further investigations on the beneficial effect of IVIG-based early phase intervention strategies to prevent the severe effects of this devastating bacterial infection.