Invasive Group B Streptococcal Disease in Neonates and Infants, Italy, Years 2015–2019

Invasive infections by group B streptococci (iGBS) are the leading cause of sepsis and meningitis in the first three months of life worldwide. The clinical and microbiological characteristics of neonatal and infant iGBS in Italy during the years 2015–2019 were investigated. Voluntary-based surveillance reported 191 cases (67 early-onset (EOD) and 124 late-onset disease (LOD)) and 89 bacterial isolates were received. The main clinical manifestations were sepsis (59.2%) followed by meningitis (21.5%), bacteremia (12.0%) and septic shock (6.3%). Hospitalized preterm babies accounted for one third of iGBS and constituted the most fragile population in terms of mortality (8.2%) and brain damage (16.4%). GBS serotype III was predominant in EOD (56%) and caused almost all LOD (95%). The rate of resistance to clindamycin reached 28.8%. Most of clindamycin-resistant GBS strains (76%) were serotype III-ST17 and possessed the genetic markers of the emerging multidrug resistant (MDR) CC-17 sub-clone. Our data revealed that iGBS is changing since it is increasingly reported as a healthcare-associated infection (22.6%), mainly caused by MDR-CC17. Continuous monitoring of the clinical and microbiological characteristics of iGBS remains of primary importance and it represents, at present, the most effective tool to support prevention strategies and the research on the developing GBS vaccine

Invasive Group B Streptococcal Disease in Neonates and Infants, Italy, Years 2015–2019

Invasive infections by group B streptococci (iGBS) are the leading cause of sepsis and meningitis in the first three months of life worldwide. The clinical and microbiological characteristics of neonatal and infant iGBS in Italy during the years 2015–2019 were investigated. Voluntary-based surveillance reported 191 cases (67 early-onset (EOD) and 124 late-onset disease (LOD)) and 89 bacterial isolates were received. The main clinical manifestations were sepsis (59.2%) followed by meningitis (21.5%), bacteremia (12.0%) and septic shock (6.3%). Hospitalized preterm babies accounted for one third of iGBS and constituted the most fragile population in terms of mortality (8.2%) and brain damage (16.4%). GBS serotype III was predominant in EOD (56%) and caused almost all LOD (95%). The rate of resistance to clindamycin reached 28.8%. Most of clindamycin-resistant GBS strains (76%) were serotype III-ST17 and possessed the genetic markers of the emerging multidrug resistant (MDR) CC-17 sub-clone. Our data revealed that iGBS is changing since it is increasingly reported as a healthcare-associated infection (22.6%), mainly caused by MDR-CC17. Continuous monitoring of the clinical and microbiological characteristics of iGBS remains of primary importance and it represents, at present, the most effective tool to support prevention strategies and the research on the developing GBS vaccine

Mice repeatedly exposed to Group-A \u3b2-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon

Repeated exposure to Group-A \u3b2-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. Here, we exposed developing SJL male mice to four injections with a GAS homogenate and evaluated the following domains: motor coordination; general locomotion; repetitive behaviors; perseverative responses; and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that behavioral changes were associated with immune-mediated brain alterations, we analyzed, in selected brain areas, the presence of infiltrates and microglial activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased repetitive and perseverative behaviors, impaired PPI, and reduced concentrations of serotonin in prefrontal cortex, a brain area linked to the behavioral domains investigated, wherein they also showed remarkable elevations in lactate. Active inflammatory processes were substantiated by the observation of infiltrates and microglial activation in the white matter of the anterior diencephalon. These data support the hypothesis that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and perseverative behavior, and result in phenotypic abnormalities

Detection of Genes Encoding Internalization-Associated Proteins in Streptococcus pyogenes Isolates from Patients with Invasive Diseases and Asymptomatic Carriers

A total of 161 Streptococcus pyogenes isolates from patients with invasive infections or from asymptomatic carriers were examined for genes (prtF1, prtF2, and fba) coding for fibronectin-binding proteins to evaluate their involvement in the pathogenesis of different streptococcal manifestations. We found no significant differences in the presence of these three genes between the two groups. Overall, the prtF2 gene was present in similar percentages among strains from both sources (61% versus 63%). Strains carrying the gene fba were slightly more common among those isolated from asymptomatic carriers (72.6% versus 65%). Also, the prtF1 gene was present in a higher, but not significant, percentage among strains from throat swabs than among isolates from invasive infections (75% versus 64.9%). However, this more detailed characterization of the genes encoding fibronectin-binding proteins allowed us to identify a strong association of genes of the erm class, coding for macrolide resistance, with prtF1 and prtF2 rather than with prtF1 alone. Since macrolide resistance was significantly associated with throat swab isolates, it may be hypothesized that proteins coded by prtF1 and prtF2 genes may be synergic in providing support for cell invasion and/or colonizing or persistence efficiency

Neonatal group B streptococcus infections: Prevention strategies, clinical and microbiologic characteristics in 7 years of surveillance

Background: The characteristics of group B streptococcus (GBS) neonatal disease in a period of 7 years are reported. Methods: The estimation of the neonatal GBS disease risk and prevention strategies adopted at delivery in absence of national guidelines was evaluated by the analysis of 3501 questionnaires. Notification of 194 neonatal GBS infections was recorded. In addition, 115 strains from neonatal earlyonset disease (EOD) and late-onset disease, respectively, plus 320 strains from pregnant women were analyzed by molecular typing methods and for antibiotic resistance. Results: Preterm deliveries, precipitous labor and GBS negatively screened mothers were the prominent causes for an inadequate or lack of intrapartum antibiotic prophylaxis and EOD occurrence. The superimposable serotype distribution of GBS strains from EOD and from antenatal screening confirmed the vertical transmission from mother to neonate as the cause of disease. On the contrary, late-onset disease was almost exclusively caused by the internationally diffused clonal complex 17. Erythromycin resistance was detected in 17% of strains. Resistance to clindamycin was 15.3 %. Conclusions: The administration of intrapartum antibiotic prophylaxis to negatively GBS screened women in presence of risk factors was a deviation from the recommendations issued by the Centers for Disease Control and Prevention, and it should deserve further consideration. Routine surveillance and molecular typing of circulating clones are essential for the effective management of the neonatal GBS disease

Invasive beta-haemolytic group A, C, and G streptococcal infections in Italy: a 2015-2016 survey

Background: In Europe, with few exceptions, there is a lack of systematic reporting for invasive infections by Streptococcus pyogenes (Group A Streptococcus, GAS), making the assessment of national and global disease burden very scattered. In Italy, except for scarlet fever, invasive GAS infection is not a notifiable disease. Material/methods: A nationwide enhanced laboratory-based surveillance on invasive infections by GAS and other beta-haemolytic streptococci (group G and C streptococci) was launched from January 2015 to June 2016. Cases were notified according to a common questionnaire. Invasive infection was defined as the isolation of the bacterium from a usually sterile site, from deep-body-site exudates, or from a nonsterile site in association with one of the following conditions: necrotizing fasciitis, clinically diagnosed pneumonia, or STSS. Species identification was confirmed by the Lancefield group and the API 20 Strep system. Susceptibility to penicillin, norfloxacin, rifampicin, vancomycin, tetracycline, erythromycin, clindamycin was assessed by the disc diffusion method. emm sequence typing was performed on all strains. The presence of the superantigen speA and speC genes in GAS, and tet, erm and mef resistance genes in all isolates was determined by PCR. Results: 104 notifications and 95 bacterial strains were received; 66 strains were identified as GAS, 26 as S. dysgalatiae subsp. equisimilis (SDSE) and three strains as S. equi subsp. zooepidemicus (SESZ). Most infections affected elderly (> 65 years old, 55.5% and 92% for GAS and SDSE, respectively). The majority of strains were isolated from blood (70.8% and 72% for GAS and SDSE, respectively) and skin and soft tissue infections were the prevalent clinical manifestations (57.1% for GAS; 54.2% for SDSE). The case fatality rate was 24.3% for GAS and 0% for SDSE. One out of two patients infected with SESZ died. Among GAS isolates, emm types 1, 28, and 5 were predominant. The spe genes strongly correlated to emm type. Low resistance rate to norfloxacin (4.5%), and erythromycin (6%) was recorded. Tetracycline resistance rate was of 22.7%. Among SDSE, the most abundant emm types were stG2078, stG480, and stG6. The resistance rate to tetracycline (26.9%) was comparable to that of GAS, while resistance rates to norfloxacin (19.2%) and erythromycin (15.4%) were higher. All three S. equi subsp. zooepidemicus strains were erythromycin susceptible and clindamycin resistant. Conclusions: By providing new data on the epidemiology of invasive infections caused by GAS and other beta-haemolytic streptococci, this work is a priming effort to fill the gap represented by the non-inclusion of invasive infections by beta-haemolytic streptococci among the currently networks of surveillance in Italy. Enhanced surveillances are the only means to assess the real time burden of such infections, their outcomes as well as to monitor the antibiotic resistance and virulence traits of circulating bacterial clones

emm Types, Virulence Factors, and Antibiotic Resistance of Invasive Streptococcus pyogenes Isolates from Italy: What Has Changed in 11 Years?▿

To investigate the epidemiology and characteristics of invasive group A streptococcal (GAS) disease over 11 years in Italy, this study compared the emm types and the superantigen toxin genes speA and speC as well as the erythromycin, clindamycin, and tetracycline susceptibilities of 207 invasive GAS strains collected during two national enhanced surveillance periods (1994 to 1996 and 2003 to 2005) and the time between each set of surveillance periods. The present study demonstrated that emm1 strains were consistently responsible for about 20% of invasive GAS infections, while variations in the frequencies of the other types were noted, although the causes of most cases of invasive infections were restricted to emm1, emm3, emm4, emm6, emm12, and emm18. During the 1994 to 1996 surveillance period, an emm89 epidemic clone spread across the northern part of Italy. A restricted macrolide resistance phenotype-type distribution of the bacteriophage-encoded speA toxin as well as of macrolide resistance genes was noted over time. Indeed, the recent acquisition of macrolide resistance in previously susceptible emm types was observed

Therapeutic Failures of Antibiotics Used To Treat Macrolide-Susceptible Streptococcus pyogenes Infections May Be Due to Biofilm Formation

Streptococcus pyogenes infections often fail to respond to antibiotic therapy, leading to persistent throat carriage and recurrent infections. Such failures cannot always be explained by the occurrence of antibiotic resistance determinants, and it has been suggested that S. pyogenes may enter epithelial cells to escape antibiotic treatment. We investigated 289 S. pyogenes strains isolated from different clinical sources to evaluate their ability to form biofilm as an alternative method to escape antibiotic treatment and host defenses. Up to 90% of S. pyogenes isolates, from both invasive and noninvasive infections, were able to form biofilm. Specific emm types, such as emm6, appeared to be more likely to produce biofilm, although variations within strains belonging to the same type might suggest biofilm formation to be a trait of individual strains rather than a general attribute of a serotype. Interestingly, erythromycin-susceptible isolates formed a significantly thicker biofilm than resistant isolates (P < 0.05). Among resistant strains, those carrying the erm class determinants formed a less organized biofilm than the mef(A)-positive strains. Also, prtF1 appeared to be negatively associated with the ability to form biofilm (P < 0.01). Preliminary data on a selection of strains indicated that biofilm-forming isolates entered epithelial cells with significantly lower efficiency than biofilm-negative strains. We suggest that prtF1-negative macrolide-susceptible or mef(A)-carrying isolates, which are poorly equipped to enter cells, may use biofilm to escape antimicrobial treatments and survive within the host. In this view, biofilm formation by S. pyogenes could be responsible for unexplained treatment failures and recurrences due to susceptible microorganisms

A new genotyping scheme based on MLVA for inter-laboratory surveillance of Streptococcus pyogenes.

International audienceA newly developed MLVA seven-loci scheme for Streptococcus pyogenes is described. The method can be successfully applied by using both agarose gel with visual inspections of bands and Lab on Chip technology. The potential of the present MLVA has been tested on a collection of 100 clinical GAS strains representing the most common emm types found in high-income countries plus 18 published gap-free genomes, in comparison to PFGE and MLST. The MLVA analysis defined 30 MLVA types with ten out of the considered 15 emm types exhibiting multiple and specific MLVA types. In only one occasion the same MLVA profile was shared between isolates belonging to two different emm types. A robust congruency between the methods was observed, with MLVA discriminating within clonal complexes as defined by PFGE or MLST. This new MLVA scheme can be adopted as a quick, low-cost and reliable typing method to track the short-term diffusion of GAS clones in inter-laboratory-based surveillance