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

Metcalf, Ben J.; Chochua, Sopio; Gertz, Robert E.; Hawkins, Paulina A.; Ricaldi, Jessica N.; Li, Z.; Walker, Hollis; Tran, Theresa; Rivers, Joy; Mathis, Saundra; Jackson, Delois; Glennen, Anita; Lynfield, Ruth; McGee, Lesley; Beall, Bernard; Reingold, Arthur; Brooks, Shelise; Randel, H.; Miller, L. L.; White, Brad J.; Aragon, Deborah; Barnes, Meghan; Sadlowski, J.; Petit, Susan; Cartter, Matthew L.; Márquez, Carolina; Wilson, Michael; Farley, Monica M.; Thomas, Sabu; Tunali, Amy; Baughman, Wendy; Harrison, Lee H.; Benton, Jonathan L.; Carter, T.; Hollick, Rosemary; Holmes, King K.; Riner, Andrea N.; Holtzman, Corinne; Danila, Richard; MacInnes, K.; Scherzinger, Karen; Angeles, K.; Bareta, Joseph; Butler, L. O.; Khanlian, S.; Mansmann, Richard A.; Nichols, Megin; Bennett, Nancy M.; Zansky, Shelley; Currenti, Salvatore; McGuire, Suzanne; Thomas, Ann; Schmidt, Malthe; Thompson, Jessica; Poissant, Tasha; Schaffner, William; Barnes, Brenda; Leib, Katja; Dyer, Kelly A.; McKnight, Laura E.; Almendares, Olivia; Hudson, James B.; McGlone, Londell; Whitney, Cynthia G.; Schrag, Stephanie J.; Langley, Gayle

doi:10.1016/j.cmi.2017.02.021

Cited by 117 publications

(166 citation statements)

References 28 publications

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“…Four instances of chloramphenicol resistance, corresponding to the presence of a cat gene, were found (Table 2). We found no resistance to rifampin, gentamicin, or vancomycin, consistent with finding no previously described rpoB substitutions associated with rifampin resistance (17,21,22) and no genes for gentamicin or vancomycin resistance (23,24). All isolates were also susceptible to daptomycin and linezolid.…”

Section: Resultssupporting

confidence: 68%

“…The most frequently occurring macrolide resistance determinant was ermT, because of its association with emm92 as previously described (19) and possibly more recent associations with the emm4/ST39 and emm77/ST399 lineages ( Table 1). As previously noted in GBS, the ermT determinant was detected at an approximately 10-fold greater read depth than other markers, consistent with its presence on a multicopy plasmid (17). Analysis of highquality assemblies from two randomly selected ermT-positive strains (one type emm4 [isolate 20155033) and one type emm92 [isolate 20154014]) revealed that the single ermT-positive contig in each strain compared to previously described (17) plasmid pRW35 (4,968 bp) had 100% coverage, Ͼ99% identity, and a length of~4,970 bp.…”

Section: Resultssupporting

confidence: 55%

“…In GBS, we found that this combination confers decreased susceptibility to quinupristindalfopristin, presumably because of streptogramin A resistance conferred by lsaC and streptogramin B resistance conferred by ermB (17). In this iGAS isolate, the MIC of quinupristin-dalfopristin was somewhat higher (1 g/ml) than the average (~0.3 g/ml) but still below the MIC (2 g/ml) indicative of intermediate resistance (20).…”

Section: Resultsmentioning

confidence: 93%

“…We found in invasive GBS that PBP2x typing was actually more reliable and sensitive for detecting first-step mutations leading to ␤-lactam nonsusceptibility (17), and having this system in place for iGAS allows us greater vigilance for this potential threat. We now see that ermT, discovered in GAS only in the last decade (19), actually accounts for the major percentage of emerging GAS resistance to macrolides and lincosamides.…”

Section: Discussionmentioning

confidence: 99%

“…Determination of PBP2x transpeptidase sequence types (STs) of group B streptococci (GBS) and pneumococci is a very sensitive mechanism for detecting potential first-step mutations conferring decreased susceptibility or intermediate resistance to penicillin and other ␤-lactam antibiotics (16)(17)(18). We used this same approach with the corresponding PBP2x region from S. pyogenes.…”

Section: Resultsmentioning

confidence: 99%

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Population and Whole Genome Sequence Based Characterization of Invasive Group A Streptococci Recovered in the United States during 2015

Chochua

Metcalf

et al. 2017

mBio

107

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Group A streptococci (GAS) are genetically diverse. Determination of strain features can reveal associations with disease and resistance and assist in vaccine formulation. We employed whole-genome sequence (WGS)-based characterization of 1,454 invasive GAS isolates recovered in 2015 by Active Bacterial Core Surveillance and performed conventional antimicrobial susceptibility testing. Predictions were made for genotype, GAS carbohydrate, antimicrobial resistance, surface proteins (M family, fibronectin binding, T, R28), secreted virulence proteins (Sda1, Sic, exotoxins), hyaluronate capsule, and an upregulated nga operon (encodes NADase and streptolysin O) promoter (Pnga3). Sixty-four M protein gene (emm) types were identified among 69 clonal complexes (CCs), including one CC of Streptococcus dysgalactiae subsp. equisimilis. emm types predicted the presence or absence of active sof determinants and were segregated into sof-positive or sof-negative genetic complexes. Only one "emm type switch" between strains was apparent. sof-negative strains showed a propensity to cause infections in the first quarter of the year, while sof ϩ strain infections were more likely in summer. Of 1,454 isolates, 808 (55.6%) were Pnga3 positive and 637 (78.9%) were accounted for by types emm1, emm89, and emm12. Theoretical coverage of a 30-valent M vaccine combined with an M-related protein (Mrp) vaccine encompassed 98% of the isolates. WGS data predicted that 15.3, 13.8, 12.7, and 0.6% of the isolates were nonsusceptible to tetracycline, erythromycin plus clindamycin, erythromycin, and fluoroquinolones, respectively, with only 19 discordant phenotypic results. Close phylogenetic clustering of emm59 isolates was consistent with recent regional emergence. This study revealed strain traits informative for GAS disease incidence tracking, outbreak detection, vaccine strategy, and antimicrobial therapy.IMPORTANCE The current population-based WGS data from GAS strains causing invasive disease in the United States provide insights important for prevention and control strategies. Strain distribution data support recently proposed multivalent M type-specific and conserved M-like protein vaccine formulations that could potentially protect against nearly all invasive U.S. strains. The three most prevalent clonal complexes share key polymorphisms in the nga operon encoding two secreted virulence factors (NADase and streptolysin O) that have been previously associated with high strain virulence and transmissibility. We find that Streptococcus pyogenes is phylogenetically subdivided into loosely defined multilocus sequence type-based clusters consisting of solely sof-negative or sof-positive strains; with sof-negative strains demonstrating differential seasonal preference for infection, consistent with the recently demonstrated differential seasonal preference based on phylogenetic clustering of full-length M proteins. This might relate to the differences in GAS strain com-

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Section: Resultssupporting

confidence: 68%

Section: Resultssupporting

confidence: 55%

Section: Resultsmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Population and Whole Genome Sequence Based Characterization of Invasive Group A Streptococci Recovered in the United States during 2015

Chochua

Metcalf

et al. 2017

mBio

107

175

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Epidemiology of Invasive Group B Streptococcal Infections Among Nonpregnant Adults in the United States, 2008-2016

et al. 2019

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Streptococcus (GBS) is an important cause of invasive bacterial disease. Previous studies have shown a substantial and increasing burden of GBS infections among nonpregnant adults, particularly older adults and those with underlying medical conditions. OBJECTIVE To update trends of invasive GBS disease among US adults using population-based surveillance data. DESIGN, SETTING, AND PARTICIPANTS In this population-based surveillance study, a case was defined as isolation of GBS from a sterile site between January 1, 2008, and December 31, 2016. Demographic and clinical data were abstracted from medical records. Rates were calculated using US Census data. Antimicrobial susceptibility testing and serotyping were performed on a subset of isolates. Case patients were residents of 1 of 10 catchment areas of the Active Bacterial Core surveillance (ABCs) network, representing approximately 11.5% of the US adult population. Patients were included in the study if they were nonpregnant, were 18 years or older, were residents of an ABCs catchment site, and had a positive GBS culture from a normally sterile body site. MAIN OUTCOMES AND MEASURES Trends in GBS cases overall and by demographic characteristics (sex, age, and race), underlying clinical conditions of patients, and isolate characteristics are described. RESULTS The ABCs network detected 21 250 patients with invasive GBS among nonpregnant adults from 2008 through 2016. The GBS incidence in this population increased from 8.1 cases per 100 000 population in 2008 to 10.9 in 2016 (P = .002 for trend). There were 3146 cases reported in 2016 (59% male; median age, 64 years; age range, 18-103 years). The GBS incidence was higher among men than women and among blacks than whites and increased with age. Projected to the US population, an estimated 27 729 cases of invasive disease and 1541 deaths occurred in the United States in 2016. Ninety-five percent of cases in 2016 occurred in someone with at least 1 underlying condition, most commonly obesity (53.9%) and diabetes (53.4%). Resistance to clindamycin increased from 37.0% of isolates in 2011 to 43.2% in 2016 (P = .02). Serotypes Ia, Ib, II, III, and V accounted for 86.4% of isolates in 2016; serotype IV increased from 4.7% in 2008 to 11.3% in 2016 (P < .001 for trend). CONCLUSIONS AND RELEVANCE The public health burden of invasive GBS disease among nonpregnant adults is substantial and continues to increase. Chronic diseases, such as obesity and diabetes, may contribute.

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Epidemiology of Invasive Early-Onset and Late-Onset Group B Streptococcal Disease in the United States, 2006 to 2015

et al. 2019

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IMPORTANCE Invasive disease owing to group B Streptococcus (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 B Streptococcus isolated 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 < .001), and LOD rates remained stable (mean, 0.31 per 1000 live births). Among the mothers of 1277 infants with EOD, 617 (48.3%) had no indications for IAP and did not receive it, and 278 (21.8%) failed to receive IAP despite having indications. Serotype data were available for 1743 of 1897 patients (91.3%) from 7 sites that collect GBS isolates. Among patients with EOD, serotypes Ia (242 [27.3%]) and III (242 [27.3%]) were most common. Among patients with LOD, serotype III was most common (481 [56.2%]), and this increased from 2006 to 2015 from 0.12 to 0.20 cases per 1000 live births (P < .001). Serotype IV caused 53 cases (6.2%) of EOD and LOD combined. The 6 most common serotypes (Ia, Ib, II, III, IV, and V) caused 881 EOD cases (99.3%) and 853 LOD cases (99.7%). No β-lactam resistance was identified; 359 isolates (20.8%) tested showed constitutive clindamycin resistance. In 2015, an estimated 840 EOD cases and 1265 LOD cases occurred nationally. 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.

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

Abstract: The WGS-based assignment of iGBS resistance features and serotypes is an accurate substitute for phenotypic testing.

Cited by 117 publications

References 28 publications

Population and Whole Genome Sequence Based Characterization of Invasive Group A Streptococci Recovered in the United States during 2015

Population and Whole Genome Sequence Based Characterization of Invasive Group A Streptococci Recovered in the United States during 2015

Epidemiology of Invasive Group B Streptococcal Infections Among Nonpregnant Adults in the United States, 2008-2016

Epidemiology of Invasive Early-Onset and Late-Onset Group B Streptococcal Disease in the United States, 2006 to 2015

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