We sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A Streptococcus to unravel the nature and timing of molecular events contributing to the emergence, dissemination, and genetic diversification of an unusually virulent clone that now causes epidemic human infections worldwide. We discovered that the contemporary epidemic clone emerged in stepwise fashion from a precursor cell that first contained the phage encoding an extracellular DNase virulence factor (streptococcal DNase D2, SdaD2) and subsequently acquired the phage encoding the SpeA1 variant of the streptococcal pyrogenic exotoxin A superantigen. The SpeA2 toxin variant evolved from SpeA1 by a single-nucleotide change in the M1 progenitor strain before acquisition by horizontal gene transfer of a large chromosomal region encoding secreted toxins NAD + -glycohydrolase and streptolysin O. Acquisition of this 36-kb region in the early 1980s into just one cell containing the phage-encoded sdaD2 and speA2 genes was the final major molecular event preceding the emergence and rapid intercontinental spread of the contemporary epidemic clone. Thus, we resolve a decades-old controversy about the type and sequence of genomic alterations that produced this explosive epidemic. Analysis of comprehensive, population-based contemporary invasive strains from seven countries identified strong patterns of temporal population structure. Compared with a preepidemic reference strain, the contemporary clone is significantly more virulent in nonhuman primate models of pharyngitis and necrotizing fasciitis. A key finding is that the molecular evolutionary events transpiring in just one bacterial cell ultimately have produced millions of human infections worldwide.pathogenesis | phylogeography | mobile genetic element | flesh-eating disease | molecular clock

Summary Objectives To understand relationships between microbes in pathogenesis of acute otitis media during respiratory tract infections, we compared nasopharyngeal bacteria and respiratory viruses in symptomatic children with and without AOM. Methods We enrolled children (6–35 months) with acute symptoms suggestive of AOM and analyzed their nasopharyngeal samples for bacteria by culture and for 15 respiratory viruses by PCR. Non-AOM group had no abnormal otoscopic signs or only middle ear effusion, while AOM group showed middle ear effusion and acute inflammatory signs in pneumatic otoscopy along with acute symptoms. Results Of 505 children, the non-AOM group included 187 and the AOM group 318. One or more bacterial AOM pathogen (Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis) was detected in 78% and 96% of the non-AOM and AOM group, respectively (P < .001). Colonization with S. pneumoniae and H. influenzae, each alone, increased risk of AOM (odds ratio (OR) 2.92; 95% confidence interval (CI), .91–9.38, and 5.13; 1.36–19.50, respectively) and co-colonization with M. catarrhalis further increased risk (OR 4.36; 1.46–12.97, and 9.00; 2.05–39.49, respectively). Respiratory viruses were detected in 90% and 87% of the non-AOM and AOM group, respectively. RSV was significantly associated with risk of AOM without colonization by bacterial AOM pathogens (OR 6.50; 1.21–34.85). Conclusions Co-colonization by M. catarrhalis seems to increase risk of AOM and RSV may contribute to AOM pathogenesis even without nasopharyngeal bacterial colonization.

In December 2018, a ceftazidime-avibactam (CAZ-AVI)-resistant KPC-2-producing Klebsiella pneumoniae strain was isolated in Finland. CAZ-AVI resistance was observed 34 days after CAZ-AVI treatment in a trauma patient transferred from a hospital in Greece who had been colonised with bla KPC-2 -producing K. pneumoniae ST39, and later developed a bloodstream infection. The CAZ-AVI-resistant strain contained a novel 15 amino acid insertion in the KPC-2 protein causing structural changes proximal to the KPC-2 active site.

Analysis of sequencing data for 143 bla NDM-1- and bla OXA-48-positive Klebsiella pneumoniae isolates from 13 European national collections and the public domain resulted in the identification of 15 previously undetected multi-country transmission clusters. For 10 clusters, cases had prior travel/hospitalisation history in countries outside of the European Union including Egypt, Iran, Morocco, Russia, Serbia, Tunisia and Turkey. These findings highlight the benefit of European whole genome sequencing-based surveillance and data sharing for control of antimicrobial resistance.

Background: Rhinovirus is the most common virus causing respiratory tract illnesses in children. Rhinoviruses are classified into species A, B and C. We examined the associations between different rhinovirus species and respiratory illness severity. Methods: This is a retrospective observational cohort study on confirmed rhinovirus infections in 134 children 3–23 months of age, who were enrolled in 2 prospective studies on bronchiolitis and acute otitis media, respectively, conducted simultaneously in Turku University Hospital, Turku, Finland, between September 2007 and December 2008. Results: Rhinovirus C is the most prevalent species in our study, and it was associated with severe wheezing and febrile illness. We also noted that history of atopic eczema was associated with wheezing. Conclusions: Our understanding of rhinovirus C as the most pathogenic rhinovirus species was fortified. Existing research supports the idea that atopic characteristics are associated with the severity of the rhinovirus C-induced illness.