Extensive/Multidrug-Resistant Pneumococci Detected in Clinical Respiratory Tract Samples in Southern Sweden Are Closely Related to International Multidrug-Resistant Lineages

BACKGROUND/OBJECTIVE: The frequencies of non-susceptibility against common antibiotics among pneumococci vary greatly across the globe. When compared to other European countries antibiotic resistance against penicillin and macrolides has been uncommon in Sweden in recent years. Multidrug resistance (MDR) is, however, of high importance since relevant treatment options are scarce. The purpose of this study was to characterize the molecular epidemiology, presence of resistance genes and selected virulence genes of extensively drug-resistant (XDR) (n=15) and MDR (n=10) Streptococcus pneumoniae detected in clinical respiratory tract samples isolated from patients in a southern Swedish county 2016-2018. With the aim of relating them to global MDR pneumococci. METHODS: Whole genome sequencing (WGS) was performed to determine molecular epidemiology, resistance genes and presence of selected virulence factors. Antimicrobial susceptibility profiles were determined using broth microdilution testing. Further analyses were performed on isolates from the study and from the European nucleotide archive belonging to global pneumococcal sequence cluster (GPSC) 1 (n=86), GPSC9 (n=55) and GPSC10 (n=57). Bacteria were analyzed regarding selected virulence determinants (pilus islet 1, pilus islet 2 and Zinc metalloproteinase C) and resistance genes. RESULTS: Nineteen of 25 isolates were related to dominant global MDR lineages. Seventeen belonged to GPSC1, GPSC9 or GPSC10 with MDR non-PCV serotypes in GPSC9 (serotype 15A and 15C) as well as GPSC10 (serotype 7B, 15B and serogroup 24). Pilus islet-1 and pilus islet-2 were present in most sequence types belonging to GPSC1 and in two isolates within GPSC9 but were not detected in isolates belonging to GPSC10. Zinc metalloproteinase C was well conserved within all analyzed isolates belonging to GPSC9 but were not found in isolates from GPSC1 or GPSC10. CONCLUSIONS: Although MDR S. pneumoniae is relatively uncommon in Sweden compared to other countries, virulent non-PCV serotypes that are MDR may become an increasing problem, particularly from clusters GPSC9 and GPSC10. Since the incidence of certain serotypes (3, 15A, and 19A) found among our MDR Swedish study isolates are persistent or increasing in invasive pneumococcal disease further surveillance is warranted.