Invasive Streptococcal Infections Research Articles

Host Defense Susceptibility and Invasive Streptococcal Infections.

Host Defense Susceptibility and Invasive Streptococcal Infections.

Fulminant invasive group A streptococcal infection in children

Group A streptococcal infections dominate among invasive streptococcal infections, with the major causative agent, Streptococcus pyogenes, being quite stable in the environment and bearing a large number of chromosome encoded pathogenicity factors or transmitted by horizontal transfer through bacteriophages. Different genetic variants of S. pyogenes can have a different set of pathogenicity factors able to change during pathogen evolution and determine virulence level for specific isolate. With a short incubation period, the disease can proceed with developing invasive infection and toxic shock syndrome with unfavorable outcome within 7 days from disease onset. The purpose of this article is to increase the doctors’ alertness to early recognition and diagnosis, which directly affects adequate treatment in a timely manner and disease outcome. The data on streptococcal morbidity in Russia and worldwide, review of laboratory diagnostic methods and pathogen genetic typing are presented. The maximum number of cases of streptococcal septicemia in Russia was registered in 2022, which accounted for 69% of all cases during the 2014–2022 observation period. The article also describes two clinical cases of fulminant invasive group A streptococcal infection in children with symptoms of acute respiratory viral infections at the onset of the disease. The results of various laboratory diagnostics methods verifying the diagnosis are presented. The genetic characterization of microbial isolates was performed by deep DNA sequencing. In the biological material from patients (including autopsy in one case), S. pyogenes sequence type ST-28, serotypes emm-1.25 and emm-1.0 were identified. The increasing importance of invasive streptococcal infection for health care in Russia and other countries may be associated with a possible change in dominating S. pyogenes genetic variants. In this regard, the study on circulating S. pyogenes genotypes on an ongoing basis as part of surveillance of streptococcal infection and development of vaccine for specific prevention are required.

Case Series With Streptococcus pyogenes -related Toxic Shock Syndrome in the Post-COVID Period [RETRACTED

After the COVID-19 pandemic restrictions are nullified, increasing bacterial infections are reported such as invasive pneumococcal diseases and Streptococcus pyogenes infections. Streptococcal infections are common in children and usually have a mild clinical course. It can also cause life-threatening invasive infections such as streptococcal toxic shock syndrome. Group A Streptococcus surveillance data was last reported by the Centers for Disease Control and Prevention in 2020. Although surveillance data are insufficient in our country, invasive streptococcal infections are seen with increasing frequency in our clinic in the postpandemic period, especially in the last weeks. In this case series, 3 patients with streptococcal toxic shock syndrome followed in the last 2 weeks are presented.

Invasive beta-haemolytic streptococcal infections, Finland, 2006 to 2020: increase in Lancefield group C/G infections.

BackgroundInvasive infections with beta-haemolytic streptococci of Lancefield groups A (iGAS), B (iGBS) and C/G (iGCGS) are a major cause of morbidity and mortality worldwide.AimWe studied incidence trends of invasive beta-haemolytic streptococcal infections in Finland, focusing on iGCGS.MethodsWe conducted a retrospective register-based study. Cases were defined as isolations from blood and/or cerebrospinal fluid and retrieved from the National Infectious Disease Register where all invasive cases are mandatorily notified.ResultsBetween 2006 and 2020, the mean annual incidence was 4.1 per 100,000 for iGAS (range: 2.1-6.7), 5.2 for iGBS (4.0-6.3) and 10.1 for iGCGS (5.4-17.6). The incidence displayed an increasing trend for all groups, albeit for iGBS only for individuals 45 years and older. The increase was particularly sharp for iGCGS (8% annual relative increase). The incidence rate was higher in males for iGCGS (adjusted incidence rate ratio (IRR) = 1.6; 95% confidence interval (CI): 1.5-1.8) and iGAS (adjusted IRR = 1.3; 95% CI: 1.1-1.4); for iGBS, the association with sex was age-dependent. In adults, iGCGS incidence increased significantly with age. Recurrency was seen for iGCGS and secondarily iGBS, but not for iGAS. Infections with iGCGS and iGBS peaked in July and August.ConclusionsThe incidence of invasive beta-haemolytic streptococcal infections in Finland has been rising since 2006, especially for iGCGS and among the elderly population. However, national surveillance still focuses on iGAS and iGBS, and European Union-wide surveillance is lacking. We recommend that surveillance of iGCGS be enhanced, including systematic collection and typing of isolates, to guide infection prevention strategies.

Phenotypic Characterization of Acoustically Enriched Extracellular Vesicles from Pathogen-Activated Platelets

Extracellular vesicles (EVs) are derived from the membrane of platelets and released into the circulation upon activation or injury. Analogous to the parent cell, platelet-derived EVs play an important role in hemostasis and immune responses by transfer of bioactive cargo from the parent cells. Platelet activation and release of EVs increase in several pathological inflammatory diseases, such as sepsis. We have previously reported that the M1 protein released from the bacterial pathogen Streptococcus pyogenes directly mediates platelet activation. In this study, EVs were isolated from these pathogen-activated platelets using acoustic trapping, and their inflammation phenotype was characterized using quantitative mass spectrometry-based proteomics and cell-based models of inflammation. We determined that M1 protein mediated release of platelet-derived EVs that contained the M1 protein. The isolated EVs derived from pathogen-activated platelets contained a similar protein cargo to those from physiologically activated platelets (thrombin) and included platelet membrane proteins, granule proteins, cytoskeletal proteins, coagulation factors, and immune mediators. Immunomodulatory cargo, complement proteins, and IgG3 were significantly enriched in EVs isolated from M1 protein-stimulated platelets. Acoustically enriched EVs were functionally intact and exhibited pro-inflammatory effects on addition to blood, including platelet-neutrophil complex formation, neutrophil activation, and cytokine release. Collectively, our findings reveal novel aspects of pathogen-mediated platelet activation during invasive streptococcal infection.

The increasing incidence of invasive infections caused by Streptococcus pyogenes in Europe

At the end of the year 2022, it was reported in some Euro­pean countries an increase in the incidence of invasive in­fec­tion/disease caused by Streptococcus pyogenes (group A beta-hemolytic Streptococcus; GAS), especially in case of children younger than 10 years old, in which fatalities oc­curred. It is worth mentioning that the GAS strains isolated in these cases didn’t have special particularities, such as the emergence of a new strain, and an increase of GAS re­sis­tance to antibiotics wasn’t revealed, either. Through this article, we intend to issue a warning regarding the risks of invasive streptococcal infection, reviewing some im­por­tant aspects on the etiology, diagnosis, treatment and pre­ven­tion of these infections.

Invasive Streptococcal Infection Can Lead to the Generation of Cross-Strain Opsonic Antibodies.

The human pathogen Streptococcus pyogenes causes substantial morbidity and mortality. It is unclear if antibodies developed after infections with this pathogen are opsonic and if they are strain specific or more broadly protective. Here, we quantified the opsonic-antibody response following invasive S. pyogenes infection. Four patients with S. pyogenes bacteremia between 2018 and 2020 at Skåne University Hospital in Lund, Sweden, were prospectively enrolled. Acute- and convalescent-phase sera were obtained, and the S. pyogenes isolates were genome sequenced (emm118, emm85, and two emm1 isolates). Quantitative antibody binding and phagocytosis assays were used to evaluate isolate-dependent opsonic antibody function in response to infection. Antibody binding increased modestly against the infecting isolate and across emm types in convalescent- compared to acute-phase sera for all patients. For two patients, phagocytosis increased in convalescent-phase serum both for the infecting isolate and across types. The increase was only across types for one patient, and one had no improvement. No correlation to the clinical outcomes was observed. Invasive S. pyogenes infections result in a modestly increased antibody binding with differential opsonic capacity, both nonfunctional binding and broadly opsonic binding across types. These findings question the dogma that an invasive infection should lead to a strong type-specific antibody increase rather than a more modest but broadly reactive response, as seen in these patients. Furthermore, our results indicate that an increase in antibody titers might not be indicative of an opsonic response and highlight the importance of evaluating antibody function in S. pyogenes infections. IMPORTANCE The bacterium Streptococcus pyogenes is a common cause of both mild and severe human diseases resulting in substantial morbidity and mortality each year. No vaccines are available, and our understanding of the antibody response to this human pathogen is still incomplete. Here, we carefully analyzed the opsonic antibody response following invasive infection in four patients. Unexpectedly, the patients did not always generate opsonic antibodies against the specific infecting strain. Instead, we found that some patients could generate cross-opsonic antibodies, leading to phagocytosis of bacteria across strains. The emergence of cross-opsonic antibodies is likely important for long-term immunity against S. pyogenes. Our findings question the dogma that mostly strain-specific immunity is developed after infection and add to our overall understanding of how immunity to S. pyogenes can evolve.

Serial brain magnetic resonance imaging in a patient with invasive streptococcal infection with ventriculitis and choroid plexitis

Serial brain magnetic resonance imaging in a patient with invasive streptococcal infection with ventriculitis and choroid plexitis

Effectiveness of adjunctive clindamycin in β-lactam antibiotic-treated patients with invasive β-haemolytic streptococcal infections in US hospitals: a retrospective multicentre cohort study

Clindamycin is strongly recommended as an adjunctive treatment to β-lactam antibiotics in patients with severe invasive group A β-haemolytic streptococcal (iGAS) infections. However, there is little evidence of a benefit in the use of clindamycin in humans, and its role, if any, in treating patients with invasive non-group A/B β-haemolytic streptococcal (iNABS) infections is unclear. For this retrospective multicentre cohort study, we used a dataset from patients in the Cerner Health Facts database, which contains electronic health-based data from 233 US hospitals. We queried the Cerner Health Facts database for inpatients (no age restriction) admitted to hospital in 2000-15, with any clinical cultures positive for β-haemolytic streptococcal taxa of interest, and who had received β-lactam antibiotics within 3 days either side of culture sampling. This group of patients was then queried for those who had also received intravenous or oral clindamycin within 3 days either side of culture sampling. Patients were excluded if they had polymicrobial growth or clindamycin non-susceptible isolates, received linezolid, or had missing variable data needed for analysis. Patients were categorised by Lancefield group (iGAS or iNABS); β-lactam antibiotic-treated patients who had received clindamycin were propensity-matched (1:2) to those who did not receive clindamycin separately for iGAS and iNABS cohorts, and logistic regression was then used to account for residual confounding factors. The primary outcome was the adjusted odds ratio (aOR) of in-hospital mortality in propensity-matched patients treated with adjunctive clindamycin versus those not treated with clindamycin in the iGAS and iNABS infection cohorts. We identified 1956 inpatients with invasive β-haemolytic streptococcal infection who had been treated with β-lactam antibiotics across 118 hospitals (1079 with iGAS infections and 877 with iNABS infections). 459 (23·4%) of these patients had received adjunctive clindamycin treatment (343 [31·7%] patients with iGAS infections and 116 [13·2%] patients with iNABS infections). The effect of adjunctive clindamycin therapy on in-hospital mortality differed significantly and showed the opposite trend in iGAS and iNABS infection cohorts (p=0·013 for an interaction). In the iGAS cohort, in-hospital mortality in propensity-matched patients who received adjunctive clindamycin (18 [6·5%] of 277 patients) was significantly lower than in those who did not (55 [11·0%] of 500 patients; aOR 0·44 [95% CI 0·23-0·81]). This survival benefit was maintained even in patients without shock or necrotising fasciitis (six [2·6%] of 239 patients treated with adjunctive clindamycin vs 27 [6·1%] of 422 patients not treated with adjunctive clindamycin; aOR 0·40 [0·15-0·91]). By contrast, in the iNABS infection cohort, in-hospital mortality in propensity-matched patients who received adjunctive clindamycin (ten [9·8%] of 102) was higher than in those who did not (nine [4·6%] of 193), but this difference was not significant (aOR 2·60 [0·94-7·52]). Several subset analyses found qualitatively similar results. Real-world data suggest that increased use of adjunctive clindamycin for invasive iGAS infections, but not iNABS infections, could improve outcomes, even in patients without shock or necrotising fasciitis. Intramural Research Program of the National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Disease.

Characterisation of clinical manifestations and treatment strategies for invasive beta-haemolytic streptococcal infections in a Swiss tertiary hospital.

Invasive streptococcal infections affect more than half a million patients worldwide every year and have a high lethality. Little is known about the epidemiology and microbiological characteristics of streptococcal infections in Switzerland. This case series study aims to describe the demographics, known risk factors for streptococcal skin and soft tissue infections, clinical presentations, treatment and outcomes of patients admitted to the University Hospital Zurich between 2000 and 2014 with invasive streptococcal infections caused by Streptococcus pyogenes (group A Streptococcus), Streptococcus dysgalactiae ssp. equisimilis or the Streptococcus anginosus group, as well as the microbiological characteristics of the clinical isolates. Data collected retrospectively from patients hospitalised between 2000 and 2014 with invasive streptococcal infections were analysed. M protein gene (emm) typing of the bacterial clinical isolates was carried out according to the Centers for Disease Control and Prevention guidelines. A total of 86 patients with invasive beta-haemolytic streptococcal infections were included in this study, of which 49% presented with necrotising fasciitis (NF). The median age was 44 years and half were female. The most common risk factor was acute skin lesions. C-reactive protein levels were significantly higher in patients with NF, as were acute renal failure and distributive shock. Beta-lactam antibiotics were given to most patients, and intravenous immunoglobulins were given to 18% of patients within the first 24 hours. All patients suffering from NF underwent surgery. The overall case fatality rate was 8.1% at 30 days post admission. All Group A Streptococcus strains were susceptible to penicillin and clindamycin, and we found resistance to tetracycline in 11.9% of strains. The most common emm-type isolated was emm1 (44.4%). Invasive beta-haemolytic streptococcal infections, the most severe presentation of which is NF, remain a serious clinical issue and require rapid diagnosis and treatment. This is the first representative analysis monitoring clinical and microbiological characteristics of patients with a severe invasive beta-haemolytic streptococcal infection and treated in Zurich, Switzerland. In addition to the detailed reporting of various clinical and microbiological characteristics, we show that C-reactive protein levels, acute renal failure and distributive shock were higher in the patients with NF. We also found a low case fatality rate compared to other reports. The detailed clinical data and microbiological characteristics depicted in this study will lead to a better understanding of regional differences in severe invasive streptococcal infections.

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.

IntroductionPyogenic 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.MethodsIn 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).ResultsThe 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).ConclusionThe 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.

Streptococcus agalactiae and Chlamydia trachomatis detection in women without symptoms of infection.

Chlamydia trachomatis (C. trachomatis) and Streptococcus agalactiae (GBS) may be present in the female cervical canal without any symptoms of infection. Chronic chlamydial infections lead to many serious complications and perinatal infections, while the presence of GBS is a reservoir for infections of newborns or invasive streptococcal infection in adults. To examine healthy women for C. trachomatis without symptoms from the reproductive system, assess the frequency of asymptomatic infections, detect GBS in the cervical canal, demonstrate differences in drug susceptibility, and determine the serotype of S. agalactiae strains and correlations among the ones present in the cervical canal. A total of 315 cervical swabs were collected for genetic and microbiological analysis for the presence of C. trachomatis and S. agalactiae. Latex and diffusion-disk methods were used to determine the serotype and susceptibility of streptococci. Ten out of 315 women (3.2%) were C. trachomatis-positive. Using traditional methods of microscopy, culture and serology, 42 strains (13.3% of the subjects) obtained from patients were identified as S. agalactiae and further analyzed. The most common serotypes identified were II (18/42, 42.9%), V (11/42, 26.2%) and III (10/42, 23.8%). The less common serotypes found were VII (2/10, 4.8%), and Ib (1/10, 2.4%); no Ia, IV or VII serotypes were found. All the strains were susceptible to penicillin, while 71.4% of them were susceptible to erythromycin and 81.0% were susceptible to clindamycin. Seven isolates (16.7%) were concomitantly resistant to erythromycin and clindamycin. Chlamydia trachomatis was confirmed in 3.2% of the respondents, and GBS was found in 13.3%, despite a lack of symptoms of infection. The incidence of C. trachomatis infections and GBS colonization in Poland is similar to those in other European countries.

Prevalence and genomic characterization of Group A Streptococcus dysgalactiae subsp. equisimilis isolated from patients with invasive infections in Toyama prefecture, Japan

Streptococcus dysgalactiae subsp. equisimilis (SDSE) causes severe invasive streptococcal infections, especially in elderly people. Between 2013 and 2018, 88 streptococci were isolated from clinical blood culture in a hospital in Toyama prefecture, Japan. The collection included six Group A SDSE (ASD) strains, which are rarely isolated. Multilocus sequence typing categorized five of the six strains into ST128 and the remaining strain into a new type. Maximum-likelihood phylogenetic analysis revealed that the six ASD strains had highly similar genome sequences. Bayesian analysis indicated that the most recent common ancestor of the strains appeared 39 years ago. The ASD strains possessed carbohydrate synthase genes that are conserved in Streptococcus pyogenes strains, whereas one strain featured a different arrangement of the gene cluster. The carbohydrate synthase genes varied by Lancefield type (A, C, and G).

„Tempus fugit, venit mors” – a streptococcalis toxikus sokk szindrómáról egy eset kapcsán

Streptococcal toxic shock syndrome (STSS) is a hyperacute, life-threatening illness, a complication of invasive streptococcal (mostly group A, rarely groups B, G or C) infection. There is no portal of entry (skin, vagina, pharynx) in nearly half of the STSS cases. The initial signs and symptoms (fever, flu-like complaints, hypotension) are scarce and aspecific, but because of its rapid progression and poor prognosis, early high level of suspicion is necessary. Management has 3 crucial points: initiation of anti-streptococcal regimen (and intravenous immunoglobulin in some cases), aggressive intensive care support of multi-organ failure, and surgical control of the infective source. In this article, we present a case of a patient succumbing to streptococcal toxic shock syndrome which was preceded by primary S. pyogenes bacteremia, and review the key points of this potentially fatal disease for practising clinicians. Orv Hetil. 2019; 160(48): 1887-1893.

473. Impact of Adjunctive Clindamycin in Invasive β-Hemolytic Streptococcal Infections: A Propensity Score-matched Analysis of 1956 β-lactam Treated Patients from 118 US Hospitals

BackgroundClindamycin suppresses invasive β-hemolytic streptococcal (iBHS) toxin production and its cidality, unlike β-lactams, is independent of bacterial inoculum. Evidence favoring the use of adjunctive clindamycin in iBHS is predominantly from in vitro and animal studies. Clinical studies, limited to single-center series or active surveillance, have yielded mixed results. Furthermore, its role in infections caused by non–group A or B β-hemolytic streptococci (NABS) remains poorly defined. Previously we were unable to demonstrate a clindamycin survival benefit in patients with group A streptococci (GAS) bacteremia. Here we examined the impact of adjunctive clindamycin on survival among patients with either invasive GAS or NABS infections from all sites.MethodsClinical characteristics, in vitro susceptibility and antibiotic therapy were examined for unique inpatient encounters with iBHS (GAS + NABS) infections in the Cerner HealthfactsTM Database. β-Lactam treated cases receiving clindamycin were matched 1:1 to non-clindamycin cases by propensity of receiving clindamycin using nearest neighbor propensity score matching with downstream adjustment using logistic regression. In-hospital mortality, length of stay (LOS) and Sequential Organ Failure (SOFA) score trajectory was compared based on the matched sample.ResultsOf 1,956 inpatients with iBHS infection treated with β-lactams at 118 hospitals between 2000 and 2015, 459 (23.5%) received adjunctive clindamycin. Propensity score matching generated 389 case-pairs with good covariate balance (Table 1, Figure 1). In-hospital mortality did not differ between matched clindamycin and non-clindamycin cases (7.2% vs. 8.0%, P = 0.66, aOR 0.88, [95% CI .49–1.57]) (Figure 2). Receipt of clindamycin early (within 24h vs. no clindamycin) also did not display a survival advantage (aOR 1.04 [0.51–2.14]). On day 4 of therapy Median SOFA score (P = 0.586) and SOFA delta (day 0–day 4) were similar between the two groups (P = 0.13; Figure 3). Amongst survivors, median [IQR] LOS was greater in the clindamycin group (8[5,12] vs. 6[4,9]; P = 0.001)ConclusionAdjunctive clindamycin was not associated with decreased mortality or degree of organ dysfunction among patients with iBHS infection already treated with β-lactams. Figure 2: Odds Ratio of In-Hospital Mortality Abbreviations: GAS: Group A Streptococcus , ICU: intensive care unit, iβHS: invasive β-Hemolytic streptococcus, NABS: Non group A β-Hemolytic streptococci , OR: odds ratioFigure 2 Legend: The figure reports the odds ratios (ORs) of in-hospital mortality and 95% confidence intervals in the unmatched and unadjusted analysis, matched and unadjusted analysis, and primary analysis of all propensity-matched pairs with downstream adjustment with logistic regression for proven ißHS, vasopressor use and ICU (within 24h of culture sampling), as well as sensitivity analyses on propensity matched pairs of 2:1 match and subgroup analysis on propensity matched pairs of (1) proven ißHS alone (2) probable ißHS alone (3) ICU admission (within 24h of culture sampling) (4) patients receiving vasopressor therapy (within 24h of culture sampling) (5) Group A ißHS alone (6) Non Group A ißHS alone. There was no statistically significant difference in the ORs for in-hospital mortality between clindamycin and propensity-matched non-clindamycin cases in the primary analysis (*) as well as all sensitivity and subgroup (†) analyses.Figure 3: SOFA Score Trajectory by Survival Status Abbreviations: B: Non-Clindamycin cases, BC: Clindamycin CasesFigure 3 Legend: SOFA score by day of therapy of clindamycin and non-clindamycin matched cases based on survival status from day zero (day prior to antibiotic therapy) to day four of therapy. The linear mixed models were used to assess the time trends and the clindamycin effect on the longitudinal SOFA scores. SOFA trajectory was examined for the post matching sample. Square root transformation was applied to the SOFA score to meet the normality assumption Mean Baseline SOFA scores prior to therapy were similar amongst clindamycin and non-clindamycin subjects (mean [standard deviation(SD)] SOFA score: 1.88[2.48] vs. 1.96[2.60]; p= 0.634). On day 4 of therapy SOFA scores were similar between remaining 310 clindamycin and 286 non-clindamycin hospitalized patients (mean[SD] SOFA score: 1.79[2.88] vs. 1.67 [2.49]; p=0.586). The SOFA delta (day 0 SOFA score - day 4 SOFA score) was similar between the two groups (p=0.1331). When examined amongst survivors only, SOFA scores on day 4 of therapy were similar between and 272 non-clindamycin and 310 clindamycin hospitalized patients (mean[SD] SOFA score: 1.45 [2.20] vs. 1.52 [2.44])This work was funded in part by the Intramural Research Program of the National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Diseases.The opinions expressed in this abstract are those of the authors and do not represent any position or policy of the National Institutes of Health, the United States Department of Health and Human Services, or the United States government.Disclosures All authors: No reported disclosures.

1625. Risk of Invasive Group A Streptococcus, Group B Streptococcus, and Streptococcus pneumoniae Infection Among Adults Experiencing Homelessness—Anchorage, Alaska, 2002–2015

BackgroundPeople experiencing homelessness (PEH) have an increased risk of infectious disease. However, for many infections, this increased risk has not been clearly quantified. For example, the risk of invasive streptococcal infection has not been established among PEH in the United States.MethodsWe compared the incidence of detected cases of invasive group A Streptococcus (GAS) infection, group B Streptococcus (GBS) infection, and Streptococcus pneumoniae (pneumococcal) infection among adult PEH to that in the general adult population in Anchorage, Alaska from 2005 through 2015 using data from the CDC Arctic Investigations Program surveillance system, the US census, and the Anchorage Point in Time count (PIT [a yearly census of PEH]).ResultsDuring 2005–2015, the PIT counted a mean number of 970 adults (minimum 795, maximum 1486) in Anchorage who were homeless, which accounted for 0.4% of the total population. Compared with the general population, PEH were 53 times as likely to have invasive GAS infection (95% CI 47–61), 7 times as likely to have invasive GBS infection (95% CI 6, 8), and 36 times as likely to have invasive pneumococcal infection (95% CI 33, 40). Of all invasive GAS cases in Anchorage over the time period, 19% occurred within the homeless population, while 3% of invasive GBS cases and 14% of invasive pneumococcal cases were within the homeless population. Additionally, the predominant subtypes of GAS and pneumococcus differed among PEH compared with the general population.ConclusionA disproportionate burden of invasive streptococcal disease in Anchorage was detected among PEH, indicating a need for further focus on this high-risk group.Disclosures All authors: No reported disclosures.

Risk for Invasive Streptococcal Infections among Adults Experiencing Homelessness, Anchorage, Alaska, USA, 2002-2015.

The risk for invasive streptococcal infection has not been clearly quantified among persons experiencing homelessness (PEH). We compared the incidence of detected cases of invasive group A Streptococcus infection, group B Streptococcus infection, and Streptococcus pneumoniae (pneumococcal) infection among PEH with that among the general population in Anchorage, Alaska, USA, during 2002–2015. We used data from the Centers for Disease Control and Prevention’s Arctic Investigations Program surveillance system, the US Census, and the Anchorage Point-in-Time count (a yearly census of PEH). We detected a disproportionately high incidence of invasive streptococcal disease in Anchorage among PEH. Compared with the general population, PEH were 53.3 times as likely to have invasive group A Streptococcus infection, 6.9 times as likely to have invasive group B Streptococcus infection, and 36.3 times as likely to have invasive pneumococcal infection. Infection control in shelters, pneumococcal vaccination, and infection monitoring could help protect the health of this vulnerable group.

Invasive Eyelid Infections by β-Hemolytic Streptococci of Serogroup A

Invasive soft tissue infections by Streptococcus pyogenes are rapidly progressive and potentially life-threatening infectious diseases. These can also affect the eyelid. Aggressive virulence factors and the synthesis of exotoxins can lead to complications, such as periorbital necrotizing fasciitis (PONF) and streptococcal toxic shock syndrome (STSS). The clinical picture is characterized by four patients with invasive eyelid infections. Photographic documentation, radiological imaging, laboratory and smear diagnostics and intravenous antibiotic therapy were performed on all patients according to the recommendations of the German Robert Koch Institute and the local infectiology board. In all patients, Streptococcus pyogenes was culturally detected in a direct swab. The antibiogram showed sensitivity to the common intravenous antibiotics. The time interval between symptom onset and presentation at the clinic was between two days and one week. All patients had high systemic inflammatory parameters on admission: Pat. 1: CRP 259 mg/l, leukocytes 20.1 giga/l; Pat. 2: CRP 375 mg/l, leukocytes 15.6 giga/l; Pat. 3: CRP 378 mg/l, leukocytes 38.7 giga/l; Pat. 4: CRP 483 mg/l, leukocytes 1.7 giga/l; normal values: CRP < 5 mg/l, leucocytes 4.4 - 11.3 giga/l. In Pat. 2 and 3, a periorbital necrotizing fasciitis was diagnosed due to rapidly progressing necrosis in the area of cutis and subcutis and systemic toxicity. Pat. 3 and 4 met the diagnostic criteria of STSS. Pat.2, 3 and 4 had to be relocated to an intermediate or intensive care unit with sepsis, despite immediate intravenous antibiotic therapy. Patient 3 underwent surgical debridement during the stay in the intensive care unit. Thanks to interdisciplinary management (ophthalmology, infectiology, ear, nose and throat medicine, internal medicine and intensive care medicine), all patients were finally discharged from our inpatient treatment in a significantly improved general condition. Invasive streptococcal infections represent a challenge in the daily routine of an ophthalmologist. Interdisciplinary management and immediate onset of high-dose intravenous antibiotic therapy are crucial for successful treatment.

The Emergence of Hypervirulent M1T1 Clone of Group A Streptococcus via Genetic Recombination and Host Selection.

Streptococcus pyogenes (Group A Streptococcus, GAS) is a strictly human bacterial pathogen. Since the mid-1980s, GAS M1T1 clone has been the most prevalent and globally disseminated serotype and is the culprit causing invasive and severe streptococcal infections, urging a better understanding of the emergence of hypervirulent M1T1 clone from an evolutionary perspective. This review highlights the molecular and evolutionary events leading to pandemic M1T1 strains, and discusses the pressure driving the genetic acquisition of novel virulence genes and the selection of hypervirulent isolates in host. By understanding the evolutionary selection and pressures that select and shape the pandemic M1T1 clone, we could potentially develop new therapeutic strategies to tackle challenges when dealing with the globally disseminated M1T1 GAS clone.

Secular trends in incidence of invasive beta-hemolytic streptococci and efficacy of adjunctive therapy in Quebec, Canada, 1996-2016.

ObjectivesTo examine secular changes in the incidence of invasive beta-hemolytic streptococcal infections, and to assess the efficacy of immunoglobulins and clindamycin as adjunctive therapies in the management of Streptococcus pyogenes infections.MethodsRetrospective cohort study of all cases of invasive group A (GAS), B (GBS), C or G (GCGS) streptococcal infections managed in a Canadian tertiary center from 1996–2016. Population incidence was measured for diabetics and non-diabetics. Adjusted odds ratios (AOR) and their 95% confidence intervals (CI) were calculated by logistic regression.Results741 cases were identified (GAS: 249; GBS: 304; GCGS: 188). While the incidence of invasive GAS infections fluctuated with no clear trend, incidence of invasive GBS and GCGS increased over time and were 8.4 and 6.3 times higher in diabetics. Mortality of invasive GAS infections decreased from 16% (6/37) in 1996–2001 to 4% (4/97) in 2011–15. Among patients with GAS infections, clindamycin administered concomitantly with a beta-lactam within 24 hours of admission decreased mortality (AOR: 0.04, 95%CI: 0.003–0.55, P = 0.02. Immunoglobulins had no such effect (AOR: 1.66, 95%CI: 0.16–17.36, P = 0.67). The protective effect of clindamycin was similar in patients with pneumonia/empyema compared to all others.ConclusionIncidence of GBS and GCGS infections increased due to an expansion of the high-risk population (elderly diabetics), but also rose in non-diabetics. No such secular change was seen for invasive GAS infections. The decrease in mortality in patients with invasive GAS infections presumably reflects better case-management. Adjunctive clindamycin reduced mortality in invasive GAS infections; immunoglobulins did not, but power was limited. The highest mortality was seen in patients with GAS pneumonia/empyema, for whom clindamycin was protective but underused.