Importance Invasive disease owing to group BStreptococcus(GBS) remains an important cause of illness and death among infants younger than 90 days in the United States, despite declines in early-onset disease (EOD; with onset at 0-6 days of life) that are attributed to intrapartum antibiotic prophylaxis (IAP). Maternal vaccines to prevent infant GBS disease are currently under development. Objective To describe incidence rates, case characteristics, antimicrobial resistance, and serotype distribution of EOD and late-onset disease (LOD; with onset at 7-89 days of life) in the United States from 2006 to 2015 to inform IAP guidelines and vaccine development. Design, Setting, and Participants This study used active population-based and laboratory-based surveillance for invasive GBS disease conducted through Active Bacterial Core surveillance in selected counties of 10 states across the United States. Residents of Active Bacterial Core surveillance areas who were younger than 90 days and had invasive GBS disease in 2006 to 2015 were included. Data were analyzed from December 2017 to April 2018. Exposures Group BStreptococcusisolated from a normally sterile site. Main Outcomes and Measures Early-onset disease and LOD incidence rates and associated GBS serotypes and antimicrobial resistance. Results The Active Bacterial Core surveillance program identified 1277 cases of EOD and 1387 cases of LOD. From 2006 to 2015, EOD incidence declined significantly from 0.37 to 0.23 per 1000 live births (P  Conclusions and Relevance The rates of LOD among US infants are now higher than EOD rates. Combined with addressing IAP implementation gaps, an effective vaccine covering the most common serotypes might further reduce EOD rates and help prevent LOD, for which there is no current public health intervention.

/pdf/epidemiology-of-invasive-early-onset-and-late-onset-group-b-nj58n9rnt2.pdf

Epidemiology of Invasive Early-Onset and Late-Onset Group B Streptococcal Disease in the United States, 2006 to 2015: Multistate Laboratory and Population-Based Surveillance.

Nontyphoidal Salmonella species are the leading bacterial cause of foodborne disease in the United States. Whole-genome sequences and paired antimicrobial susceptibility data are available for Salmonella strains because of surveillance efforts from public health agencies. In this study, a collection of 5,278 nontyphoidal Salmonella genomes, collected over 15 years in the United States, was used to generate extreme gradient boosting (XGBoost)-based machine learning models for predicting MICs for 15 antibiotics. The MIC prediction models had an overall average accuracy of 95% within ±1 2-fold dilution step (confidence interval, 95% to 95%), an average very major error rate of 2.7% (confidence interval, 2.4% to 3.0%), and an average major error rate of 0.1% (confidence interval, 0.1% to 0.2%). The model predicted MICs with no a priori information about the underlying gene content or resistance phenotypes of the strains. By selecting diverse genomes for the training sets, we show that highly accurate MIC prediction models can be generated with less than 500 genomes. We also show that our approach for predicting MICs is stable over time, despite annual fluctuations in antimicrobial resistance gene content in the sampled genomes. Finally, using feature selection, we explore the important genomic regions identified by the models for predicting MICs. To date, this is one of the largest MIC modeling studies to be published. Our strategy for developing whole-genome sequence-based models for surveillance and clinical diagnostics can be readily applied to other important human pathogens.

Using machine learning to predict antimicrobial MICs and associated genomic features for nontyphoidal Salmonella

Background: Tracking the spread of antimicrobial-resistant Neisseria gonorrhoeae is a major priority for national surveillance programmes. / Objectives: We investigate whether WGS and simultaneous analysis of multiple resistance determinants can be used to predict antimicrobial susceptibilities to the level of MICs in N. gonorrhoeae. / Methods: WGS was used to identify previously reported potential resistance determinants in 681 N. gonorrhoeae isolates, from England, the USA and Canada, with phenotypes for cefixime, penicillin, azithromycin, ciprofloxacin and tetracycline determined as part of national surveillance programmes. Multivariate linear regression models were used to identify genetic predictors of MIC. Model performance was assessed using leave-one-out cross-validation. / Results: Overall 1785/3380 (53%) MIC values were predicted to the nearest doubling dilution and 3147 (93%) within ±1 doubling dilution and 3314 (98%) within ±2 doubling dilutions. MIC prediction performance was similar across the five antimicrobials tested. Prediction models included the majority of previously reported resistance determinants. Applying EUCAST breakpoints to MIC predictions, the overall very major error (VME; phenotypically resistant, WGS-prediction susceptible) rate was 21/1577 (1.3%, 95% CI 0.8%–2.0%) and the major error (ME; phenotypically susceptible, WGS-prediction resistant) rate was 20/1186 (1.7%, 1.0%–2.6%). VME rates met regulatory thresholds for all antimicrobials except cefixime and ME rates for all antimicrobials except tetracycline. Country of testing was a strongly significant predictor of MIC for all five antimicrobials. / Conclusions: We demonstrate a WGS-based MIC prediction approach that allows reliable MIC prediction for five gonorrhoea antimicrobials. Our approach should allow reasonably precise prediction of MICs for a range of bacterial species.

WGS to predict antibiotic MICs for Neisseria gonorrhoeae.

Group B streptococcal (GBS) infection remains the most common cause of neonatal early-onset sepsis and a significant cause of late-onset sepsis among young infants. Administration of intrapartum antibiotic prophylaxis is the only currently available effective strategy for the prevention of perinatal GBS early-onset disease, and there is no effective approach for the prevention of late-onset disease. The American Academy of Pediatrics joins with the American College of Obstetricians and Gynecologists to reaffirm the use of universal antenatal microbiologic-based testing for the detection of maternal GBS colonization to facilitate appropriate administration of intrapartum antibiotic prophylaxis. The purpose of this clinical report is to provide neonatal clinicians with updated information regarding the epidemiology of GBS disease as well current recommendations for the evaluation of newborn infants at risk for GBS disease and for treatment of those with confirmed GBS infection. This clinical report is endorsed by the American College of Obstetricians and Gynecologists (ACOG), July 2019, and should be construed as ACOG clinical guidance.

/pdf/management-of-infants-at-risk-for-group-b-streptococcal-uj4lier7x1.pdf

Management of Infants at Risk for Group B Streptococcal Disease

Rapid advances in DNA sequencing technology ("next-generation sequencing") have inspired optimism about the potential of human genomics for "precision medicine." Meanwhile, pathogen genomics is already delivering "precision public health" through more effective investigations of outbreaks of foodborne illnesses, better-targeted tuberculosis control, and more timely and granular influenza surveillance to inform the selection of vaccine strains. In this article, we describe how public health agencies have been adopting pathogen genomics to improve their effectiveness in almost all domains of infectious disease. This momentum is likely to continue, given the ongoing development in sequencing and sequencing-related technologies.

https://www.nejm.org/doi/pdf/10.1056/NEJMsr1813907?listPDF=true

Pathogen Genomics in Public Health

Using whole genome sequencing to identify resistance determinants and predict antimicrobial resistance phenotypes for year 2015 invasive pneumococcal disease isolates recovered in the United States

Short-read whole genome sequencing for determination of antimicrobial resistance mechanisms and capsular serotypes of current invasive Streptococcus agalactiae recovered in the USA

R. Mansmann

Papers

Using whole genome sequencing to identify resistance determinants and predict antimicrobial resistance phenotypes for year 2015 invasive pneumococcal disease isolates recovered in the United States

Short-read whole genome sequencing for determination of antimicrobial resistance mechanisms and capsular serotypes of current invasive Streptococcus agalactiae recovered in the USA