Summary
Group B Streptococcus (GBS) is a leading cause of neonatal disease. Mothers are the main source for newborn colonization since this microorganism can be found in the anovaginal tract of 40% of pregnant women. The only currently available tool to prevent GBS neonatal infections is the intrapartum antibiotic prophylaxis. However, this approach may contribute to the emergence of antimicrobial-resistant GBS isolates and/or multidrug-resistant bacteria (MDR) such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and carbapenem-resistant enterobacteria (CRE), which can also colonise the anovaginal tract of pregnant women.
Although GBS and MDR can share this habitat, it is still unknown if they can present mutual interference. GBS vaccines based on capsular polysaccharides are currently in advanced development, but their impact in the anovaginal microbiota, especially in MDR, and potential coverage in many LMIC, including Brazil, are still unknown. There are 10 different GBS capsular types, but vaccines are being developed against 5 or 6; thus, estimating vaccine coverage in different countries is important.
Considering the imminence of a GBS capsular-based vaccine, the lack of information on GBS-related characteristics in Brazil, and the potential interrelationship between GBS and MDR in the anovaginal microbiota, this proposal aims to evaluate coverage and impact of a future GBS vaccine by collecting data on capsular types and antimicrobial resistance of GBS isolates circulating in Brazil, estimating correlate of protection (with opsonophagocytic killing assay) of current vaccine proposals, and predicting the potential impact in the interrelationships between GBS and major MDR in the anovaginal tract of pregnant women.
Project Outcome
We have determined anovaginal colonization rates of group B Streptococcus (GBS) and three groups of multidrug resistant (MDR) bacteria (namely methicillin-resistant Staphylococcus or MRS, vancomycin-resistant Enterococcus or VRE, and carbapenem-resistant gram-negative bacilli or CRGNB) among pregnant women attended at a maternity in Rio de Janeiro, Brazil between 2019 and 2021. We have also evaluated correlates of protection of a maternal GBS vaccine by opsonophagocytic killing assays (OPKA), and assessed the impact of the pandemic by comparing characteristics before (Jan 2019 to Feb 2020) and after (Mar 2020 to Mar 2021) the onset of COVID-19. GBS was detected in 10.8% of clinical samples, while MDR bacteria were detected in 25.9%. GBS colonization rate significantly decreased after the onset of the pandemic while MDR anovaginal colonization rate increased. No difference in the population profile of pregnant women attended at the maternity was detected between before and after the onset of COVID-19; likewise, there was no correlation between GBS and MDR, suggesting that changes in GBS and MDR incidence could not be attributed to changes in population profile and that increase of MDR was probably not due to reduction in GBS or vice versa. However, the use of different antibiotics during pregnancy was associated with presence or absence of certain MDR.
Distribution of GBS serotypes and antimicrobial susceptibility profiles was also different between before and after the onset of COVID-19, highlighting serotype Ib that increased in occurrence and is mostly associated with antibiotic resistance. Nevertheless, all recent GBS isolates from pregnant women in Brazil belong to serotypes comprised by frontrunner GBS vaccine proposals. Additionally, all isolates were susceptible to killing using standard human homologous vaccine reference sera in an opsonophagocytosis assay, implying efficacy of polysaccharide vaccines against all isolates.
Among MDR detected, MRS was the most frequent followed by CRGNB. VRE was not detected. More than half of MRS strains were also resistant to other three or more antibiotics, and harbored SCCmec V, a type that is usually associated with community-acquired staphylococcal strains, corroborating the hypothesis that our findings were not due to hospital (maternity) cross-contamination. Five different extended-spectrum beta-lactamase (ESBL) and carbapenemase genes were detected among CRGNB strains, highlighting blaTEM (68%), and their distribution varied between pre- and post-COVID onset.
Our results show a remarkable reduction in GBS anovaginal colonization with a concomitant increase in MDR colonizing pregnant women in Brazil after the onset of COVID-19. Our data suggest an expected positive impact in our setting of GBS vaccines currently in development, but also highlight the possible rise of new threats in maternal and child health, with a special attention to antibiotic-resistant variants. Novel personal habits and changes in clinical practices due to the onset of COVID-19 may have an impact in the broad scenario of infectious diseases. Continued and sustained surveillance in our setting is required to evaluate if these changes are only temporary and to keep tracking these potential post-pandemic bacterial threats in the perinatal population.