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

Louise K Francois Watkins; Lesley McGee; Stephanie J Schrag; Bernard Beall; Jennifer Hudson Jain; Tracy Pondo; Monica M Farley; Lee H Harrison; Shelley M Zansky; Joan Baumbach; Ruth Lynfield; Paula Snippes Vagnone; Lisa A Miller; William Schaffner; Ann R Thomas; James P Watt; Susan Petit; Gayle E Langley

doi:10.1001/jamainternmed.2018.7269

. 2019 Feb 18;179(4):479–488. doi: 10.1001/jamainternmed.2018.7269

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

Louise K Francois Watkins ^1,^2,^3,^✉, Lesley McGee ², Stephanie J Schrag ², Bernard Beall ², Jennifer Hudson Jain ², Tracy Pondo ², Monica M Farley ⁴, Lee H Harrison ⁵, Shelley M Zansky ⁶, Joan Baumbach ⁷, Ruth Lynfield ⁸, Paula Snippes Vagnone ⁸, Lisa A Miller ^9,¹⁰, William Schaffner ¹¹, Ann R Thomas ¹², James P Watt ¹³, Susan Petit ¹⁴, Gayle E Langley ^2,¹⁵

¹Epidemic Intelligence Service Program, Centers for Disease Control and Prevention, Atlanta, Georgia

²Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia

³Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia

⁴Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia

⁵Johns Hopkins Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland

⁶New York State Department of Health, Albany

⁷New Mexico Department of Health, Santa Fe

⁸Minnesota Department of Health, St Paul

⁹Colorado School of Public Health, University of Colorado Denver, Aurora

¹⁰Colorado Department of Public Health and Environment, Denver

¹¹Vanderbilt University Medical Center, Nashville, Tennessee

¹²Oregon Public Health Division, Portland

¹³California Department of Public Health, Richmond

¹⁴Connecticut Department of Public Health, Hartford

¹⁵Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia

Accepted for Publication: October 26, 2018.

^✉

Corresponding Author: Louise K. Francois Watkins, MD, MPH, Epidemic Intelligence Service Program, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mail Stop H24-9, Atlanta, GA 30329 (hvu9@cdc.gov).

Published Online: February 18, 2019. doi:10.1001/jamainternmed.2018.7269

Author Contributions: Dr Francois Watkins had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Francois Watkins, Schrag, Beall, Lynfield, Watt, Langley.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Francois Watkins, McGee, Harrison, Zansky, Langley.

Critical revision of the manuscript for important intellectual content: Francois Watkins, McGee, Schrag, Beall, Jain, Pondo, Farley, Zansky, Baumbach, Lynfield, Snippes Vagnone, Miller, Schaffner, Thomas, Watt, Petit, Langley.

Statistical analysis: Francois Watkins, Pondo, Zansky.

Obtained funding: Farley, Zansky, Schaffner.

Administrative, technical, or material support: Francois Watkins, McGee, Schrag, Beall, Jain, Farley, Baumbach, Lynfield, Snippes Vagnone, Miller, Schaffner, Thomas, Watt, Langley.

Supervision: Francois Watkins, Schrag, Beall, Farley, Schaffner, Thomas, Watt, Langley.

Conflict of Interest Disclosures: Dr Harrison reported receiving travel support from Sanofi Pasteur to attend a meeting on meningococcal disease and vaccines, reported receiving consulting fees from Merck to make a presentation on pneumococcal epidemiology and vaccines, and reported serving on a GlaxoSmithKline scientific advisory board on meningococcal vaccines. Dr Schaffner reported being a member of data safety monitoring boards for Merck and Pfizer and reported consulting with Dynavax, Seqirus, SutroVax, and Shionogi Inc. No other disclosures were reported.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Additional Contributions: We acknowledge all of the Active Bacterial Core surveillance (ABCs) team members who contributed to this project. Specifically, we thank Carmen Marquez from the Connecticut Department of Public Health; Steve Burnite, Deborah Aragon, MSPH, Benjamin White, MPH, Claire Reisenauer, DVM, MPH, Shelli Marks, Nisha Alden, MPH, and Jennifer Sadlowski, MSPH, from the Colorado Department of Public Health and Environment; Terresa R. Carter and Rosemary A. Hollick, MS, from the Johns Hopkins Bloomberg School of Public Health; Joanne Bartkus, PhD, Kathy Como-Sabetti, MPH, Richard Danila, PhD, MPH, Anita Glennen, Corinne Holtzman, MPH, Brenda Jewell, Billie Juni, MS, MT, Catherine Lexau, PhD, Craig Morin, MPH, Jean Rainbow, RN, MPH, Megan Sukalski, Lori Triden, and Sara Vetter, PhD, from the Minnesota Department of Health; Kathleen A. Shutt, MS, from the University of Pittsburgh; Brenda Barnes, RN, Tiffanie Markus, PhD, and Terri McMinn from the Vanderbilt University Medical Center; and Huong Pham, MPH, Karrie-Ann Toews, MPH, and Emily Weston, MPH, from the Centers for Disease Control and Prevention. No compensation was received.

^✉

Corresponding author.

PMCID: PMC6450309 PMID: 30776079

Key Points

Question

What are the key epidemiologic findings and trends in invasive group B Streptococcus infections among nonpregnant adults?

Findings

In this population-based study of 21 250 patients with invasive group B Streptococcus detected by the Active Bacterial Core surveillance network from 2008 through 2016, invasive group B Streptococcus incidence among nonpregnant adults increased significantly from 8.1 cases per 100 000 population in 2008 to 10.9 in 2016; incidence was highest among those with male sex, age 65 years or older, and black race. Cases had high rates of obesity (53.9%) and diabetes (53.4%).

Meaning

The incidence of invasive group B Streptococcus continues to rise among nonpregnant adults; chronic diseases, such as obesity and diabetes, may contribute.

Using population-based surveillance data, this case study reports epidemiology trends in invasive group B Streptococcus disease among US nonpregnant adults according to demographic characteristics, underlying clinical conditions, and isolate characteristics.

Abstract

Importance

Group B 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.

Introduction

Group B Streptococcus (GBS) emerged as a leading cause of neonatal sepsis in the 1970s¹ and has been identified as a cause of infection in pregnant and postpartum adults.² Since the late 1980s, GBS disease has gained recognition as a significant and increasing cause of severe infections among nonpregnant adults, especially the elderly and those with underlying conditions.^{3,4,5,6,7,8,9,10,11,12,13,14,15,16,17} In particular, obesity and diabetes have been associated with an increased risk of disease.^8,10,16,18

A previous analysis showed that rates of invasive GBS disease among nonpregnant adults more than doubled between 1990 and 2007 and approached those of invasive pneumococcal disease in adults 65 years or older; approximately 8% of cases resulted in death.³ There are no current strategies to prevent invasive GBS disease in adults. Vaccines to prevent infant disease are under development and may also hold promise for direct protection of adults at risk for invasive GBS disease.^19,20,21,22 We used active, population-based surveillance for invasive GBS disease via the Active Bacterial Core surveillance (ABCs) network to determine the incidence of disease among nonpregnant adults from 2008 to 2016 and to characterize antimicrobial susceptibility and serotype trends.

Methods

Population-Based Surveillance

Active, population-based and laboratory-based surveillance for invasive GBS disease in adults was conducted at 10 sites in the United States as part of the Centers for Disease Control and Prevention (CDC) Emerging Infections Program’s ABCs as previously described.²³ Briefly, ABCs staff contacted all microbiology laboratories serving patients in the ABCs catchment area. Between January 1, 2008, and December 31, 2016, surveillance was conducted in California (3-county San Francisco Bay area), Colorado (5-county Denver area, 2011-2016 only), Connecticut (entire state, 2016 only), Georgia (20-county Atlanta area), Maryland (entire state), Minnesota (entire state), New Mexico (entire state), New York (15 counties surrounding the Rochester and Albany areas), Oregon (3 counties in the Portland area), and Tennessee (11 counties surrounding Nashville in 2008-2010 and 20 counties surrounding Nashville and Memphis in 2011-2016). The adult population under surveillance ranged from 21.4 million in 2008 to 28.8 million in 2016 (approximately 9.3% and 11.5% of the US adult population, respectively). Demographic and clinical information was abstracted from medical records. The outcome of death was considered GBS associated if it occurred during the hospitalization for invasive GBS; cause of death was not assessed. If the outcome status was unknown during initial medical record review, vital records were used to determine if the patient died during his or her hospitalization for invasive GBS. Laboratory audits were conducted at least yearly to ensure complete case ascertainment.

Activities of the ABCs network are considered part of public health surveillance and have been determined to be nonresearch by CDC’s Institutional Review Board. Where required, institutional review board approval for surveillance activities was obtained at ABCs site health departments and academic institutions. Informed consent was not required for this surveillance activity.

Definitions

A case of invasive GBS disease in a nonpregnant adult was defined as GBS isolated from a normally sterile site in a surveillance area resident who was 18 years or older and neither pregnant nor less than 30 days postpartum on the day of culture. Women for whom pregnancy status was missing or unknown were excluded. The GBS disease was considered recurrent if the patient had a positive GBS culture at least 30 days after a prior positive culture and was considered health care associated if GBS was isolated more than 2 days into hospital admission. Patients were classified as residents of long-term care facilities if that was their designated place of residence at the time of initial culture.

Specimen Collection and Testing

Surveillance isolates were forwarded to the Streptococcus laboratory at CDC from 6 ABCs sites (Colorado, Georgia, Maryland, Minnesota, New Mexico, and Oregon) throughout the study period and from California (2014-2016 only). From 2008 to 2015, serotyping was performed by latex agglutination using rabbit antisera to 9 GBS capsular polysaccharides (Ia, Ib, and II-VIII); for isolates that could not be typed by latex agglutination, an attempt was made to type by polymerase chain reaction (PCR).²⁴ If PCR was unsuccessful, the isolate was considered nontypeable. Antimicrobial susceptibility testing to ampicillin, cefazolin, cefotaxime, cefoxitin, ceftizoxime, clindamycin, daptomycin, erythromycin, levofloxacin, penicillin, tetracycline, and vancomycin was performed at CDC by reference broth microdilution, and isolates were classified according to standards established by the Clinical and Laboratory Standards Institute.^25,26 For this report, the term resistant was applied to isolates with intermediate or resistant interpretation; for antimicrobials without defined Clinical and Laboratory Standards Institute break points, the term nonsusceptible was used. From 2011 to 2015, isolates were also tested for inducible clindamycin resistance by the single-well broth test.^25,26,27,28 Broth microdilution testing was performed by the Minnesota Public Health Laboratory for isolates from Minnesota. The CDC Streptococcus laboratory conducted whole-genome sequencing (WGS) for all isolates in 2015 and 2016 and for select isolates from 2008 to 2014. For this analysis, serotypes were assigned using latex agglutination for 2008 to 2014 and predicted from WGS using the CDC bioinformatics pipeline for 2015 and 2016 (https://github.com/BenJamesMetcalf).²⁹ Antimicrobial susceptibility profiles were also predicted from WGS data for all year 2016 isolates.²⁹

Statistical Analysis

Disease incidence was calculated using case counts from ABCs as numerators and population estimates from the bridged-race vintage postcensal file from the US Census Bureau as denominators. Missing data were multiply imputed by fully conditional specification using Markov chain Monte Carlo methods.^30,31 To obtain national estimates of cases in 2016, age group and race–specific rates of disease were applied from the aggregate surveillance area to the age and racial distribution of the US population for that year. Trends were assessed using the Cochran-Armittage test (2-sided P < .05 was considered statistically significant); when data were not linear, we reported the percentage change in incidence or proportion over time or used the nonparametric Mann-Kendall test for trend. Sensitivity analysis showed that incidence trends did not differ markedly when analysis was restricted to cases from regions that were included all years of the study period (91.8% of cases came from these regions); therefore, trends were calculated using all available data for each year. We used body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) to determine obesity (BMI≥30). For patients whose height and weight were in the medical record, BMI was calculated; if height or weight was missing or the calculated BMI was thought implausible (≤12 or >100), BMI was imputed 30 times³² using a regression model that included sex, age, race, insurance status, year, location, clinical syndrome, presence of underlying conditions, and height (if available) and weight (if available). We used Pearson χ² test and 2-tailed Fisher exact test to compare proportions; P < .05 was considered statistically significant. Poisson regression models were used to estimate variance for comparisons of incidence rates involving multiply-imputed data. Log binomial models were used to estimate variance for comparisons of proportions involving multiply-imputed data. Standard methods were used to combine estimates from multiply-imputed data sets.³³

Results

Trends Over Time

A total of 21 250 invasive GBS cases among nonpregnant adults were identified in the ABCs catchment area from 2008 through 2016. The incidence of invasive GBS in nonpregnant adults increased from 8.1 to 10.9 cases per 100 000 population between 2008 and 2016 (P = .002 for trend). Incidence increased significantly with age, with the highest incidence observed in persons 80 years or older, who accounted for 17.7% of total cases (Figure 1). The overall case fatality rate from 2008 to 2016 was 6.5%, which declined from 7.5% in 2008 to 5.6% in 2016 (P < .001 for trend).

Figure 1. — Data are shown for Active Bacterial Core surveillance sites, 2008-2016.

The incidence of invasive GBS disease differed by race and sex across all age groups. Blacks had a significantly higher incidence than whites overall, although the absolute rate difference declined over time, and the difference was no longer significant in 2016 (Figure 2A). Men had a significantly higher incidence than women for all years, and this difference grew more pronounced over time (Figure 2B). Overall, the increase was more pronounced among whites, particularly among white men aged 18 to 64 years and 80 years or older and among white women aged 40 to 79 years. Incidence also increased among black men aged 40 to 64 years but decreased among black men 80 years or older. Case fatality rates were higher among blacks than whites (7.4% vs 6.3%; P = .008) but were comparable between women and men (6.8% vs 6.3%; P = .20).

Figure 2. — A and B, Data are shown for Active Bacterial Core surveillance sites, 2008-2016.

The percentage of patients with invasive GBS who had at least 1 underlying condition increased from 90.7% in 2008 to 94.6% in 2016 (P = .005 for trend). A significant increase between 2008 and 2016 was observed in the percentage of patients with obesity (47.6% to 53.8%; P = .02 for trend), diabetes (43.5% to 53.4%; P < .001 for trend), heart failure (13.5% to 18.1%; P < .001 for trend), and chronic skin disease (9.1% to 17.3%; P < .001 for trend); however, the percentage of patients with cancer remained stable (range, 13.5%-16.8%), and the percentage of patients with atherosclerotic cardiovascular disease declined from 23.4% to 20.7%. Among leading clinical syndromes, the percentage of patients with skin and soft-tissue infections (SSTIs) increased from 27.2% in 2008 to 34.0% in 2016 (P < .001 for trend).

Descriptive Epidemiology, 2016

There were 3146 GBS cases reported in 2016, corresponding to an estimated 27 729 cases of invasive GBS disease and 1541 deaths in 2016 nationwide. Among ABCs cases, 59% were male, 75% were white, and the median age was 64 years (age range, 18-103 years) (Table). Ninety-five percent of patients were admitted to the hospital; 27.3% of those required intensive care, and 5.7% died. Group B Streptococcus was isolated predominantly from blood (83.5%), joint (7.7%), and bone (6.3%) specimens. Invasive disease manifested most commonly as SSTIs (34.0%), bacteremia without a focus (32.3%), osteomyelitis (13.3%), pneumonia (10.2%), and septic arthritis (10.2%) (Table). Patients 65 years or older were more likely to have pneumonia and less likely to have osteomyelitis or septic arthritis than younger patients, and they were more likely to have bacteremia without a focus than patients aged 40 to 64 years. Recurrent disease was observed in 7.3% of cases; these cases were significantly more likely to manifest as SSTIs (43.9% vs 33.2%) and to be associated with diabetes (63.0% vs 52.7%), obesity (62.3% vs 51.7%), renal disease (28.7% vs 22.0%), and chronic skin disease (28.7% vs 16.4%) (P < .05 for all comparisons).

Table. Characteristics of Nonpregnant Adults With Invasive Group B Streptococcal Infections, 2016.

Variable	All (n = 3146)	18-39 y (n = 239)	40-64 y (n = 1391)	≥65 y (n = 1516)	P Value^a
Male sex, No. (%)	1857 (59.0)	135 (56.5)	872 (62.7)	850 (56.1)	<.001
Age, median, y	64	33	55	75	NA
Race, No. (%)^b
White	2365 (75.2)	132 (55.2)	979 (70.4)	1254 (82.7)	<.001
Black	576 (18.3)	85 (35.6)	318 (22.9)	173 (11.4)	<.001
Other	205 (6.5)	22 (9.2)	94 (6.8)	89 (5.9)	.14
Case fatality, No./total No. (%)^c	176/3127 (5.6)	7/236 (3.0)	70/1383 (5.1)	99/1508 (6.6)	.04
Hospitalized, No./total No. (%)^c	2957/3127 (94.6)	221/238 (92.8)	1303/1381 (94.3)	1433/1508 (95.0)	.35
Intensive care unit admission	808 (27.3)	57 (25.7)	357 (27.4)	394 (27.4)	.87
Health care associated, No. (%)	241 (7.7)	31 (13.0)	129 (9.3)	81 (5.3)	<.001
Long-term care resident, No. (%)^c	226 (7.2)	5 (2.0)	51 (3.7)	170 (11.2)	<.001
Recurrent disease, No. (%)	230 (7.3)	17 (7.1)	103 (7.4)	110 (7.3)	.98
Clinical syndrome, No. (%)^d
Skin/soft-tissue infection^e	1071 (34.0)	72 (30.1)	502 (36.1)	497 (32.8)	.07
Bacteremia without focus	1016 (32.3)	82 (34.3)	418 (30.1)	516 (34.0)	.06
Osteomyelitis	418 (13.3)	36 (15.1)	262 (18.8)	120 (7.9)	<.001
Pneumonia^f	322 (10.2)	9 (3.8)	87 (6.3)	226 (14.9)	<.001
Septic arthritis	321 (10.2)	13 (5.4)	173 (12.4)	135 (8.9)	<.001
Septic shock	296 (9.4)	20 (8.4)	122 (8.8)	154 (10.2)	.37
Abscess	202 (6.4)	26 (10.9)	102 (7.3)	74 (4.9)	<.001
Intra-abdominal infection^g	97 (3.1)	15 (6.3)	58 (4.2)	24 (1.6)	<.001
Endocarditis	65 (2.1)	9 (3.8)	18 (1.3)	38 (2.5)	.01
Meningitis	34 (1.1)	4 (1.7)	19 (1.4)	11 (0.7)	.12
Necrotizing fasciitis	15 (0.5)	1 (0.4)	13 (0.9)	1 (0.1)	.002
Other^h	169 (5.4)	15 (6.3)	59 (4.2)	95 (6.3)	.04
Unknown	63 (2.0)	13 (5.4)	30 (2.2)	20 (1.3)	<.001
Underlying condition, No. (%)
≥1 Condition	2977 (94.6)	216 (90.4)	1323 (95.1)	1438 (94.9)	.01
Obesityⁱ	1695 (53.9)	116 (48.5)	843 (60.6)	736 (48.5)	<.001
Diabetes	1681 (53.4)	100 (41.8)	805 (57.9)	776 (51.2)	<.001
Neurologic disease^j	829 (26.4)	41 (17.2)	311 (22.4)	477 (31.5)	<.001
Renal disease^k	708 (22.5)	31 (13.0)	252 (18.1)	425 (28.0)	<.001
Atherosclerotic cardiovascular disease	650 (20.7)	8 (3.3)	176 (12.7)	466 (30.7)	<.001
Heart failure	570 (18.1)	5 (2.1)	167 (12.0)	398 (26.3)	<.001
Chronic skin disease	545 (17.3)	47 (19.7)	241 (17.3)	257 (17.0)	.59
Cancer^l	514 (16.3)	13 (5.4)	167 (12.0)	334 (22.0)	<.001
Chronic obstructive pulmonary disease	405 (12.9)	2 (0.8)	133 (9.6)	270 (17.8)	<.001
Current smoker	362 (11.5)	43 (18.0)	236 (17.0)	83 (5.5)	<.001
Immunosuppression^m	252 (8.0)	19 (7.9)	119 (8.6)	114 (7.5)	.59
Asthma	233 (7.4)	22 (9.2)	123 (8.8)	88 (5.8)	.004
Liver disease	229 (7.3)	17 (7.1)	148 (10.6)	64 (4.2)	<.001
Alcoholism	219 (7.0)	16 (6.7)	145 (10.4)	58 (3.8)	<.001
Substance abuseⁿ	217 (6.9)	44 (18.4)	152 (10.9)	21 (1.4)	<.001
Dialysis	125 (4.0)	14 (5.9)	74 (5.3)	37 (2.4)	<.001

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Abbreviation: NA, not applicable.

^{^a}

For the comparison of results among the groups of cases in patients aged 18 to 39 y, 40 to 64 y, and 65 y or older.

^{^b}

Unknown race distributed based on knowns.

^{^c}

The denominators used to calculate percentages were numbers of case patients with known outcome, hospitalization status, or residence.

^{^d}

Case patients may have had more than 1 syndrome (overall, 785 [25.0%] had >1 clinical syndrome), except in the case of Bacteremia without focus, which was only considered to have occurred when no other syndrome was present.

^{^e}

Skin infections included cellulitis, wound, gangrene, skin ulcer, and skin abscess.

^{^f}

Pneumonia includes empyema and/or positive pleural fluid culture.

^{^g}

Intra-abdominal infection includes peritonitis/positive peritoneal fluid culture, intra-abdominal abscess, or specified infection of the pancreas, liver, intestine, or gallbladder.

^{^h}

Other clinical syndromes included upper or lower urinary tract infection (n = 129), pelvic infection (n = 14), scrotal infection (n = 7), endometritis (n = 5), central nervous system infection (n = 4), infection of an indwelling or implanted medical device (n = 3), infected hematoma (n = 3), phlebitis or other vascular infection (n = 3), sinusitis (n = 2), and pericarditis (n = 2).

^ⁱ

Obesity status was estimated using multiple imputations (9.3% imputed data).

^{^j}

Neurologic disease includes multiple sclerosis, neuromuscular disease, Parkinson disease, history of stroke, peripheral neuropathy, paraplegia, dementia, seizure disorder, or cerebrospinal fluid leak.

^{^k}

Renal disease includes chronic kidney disease, chronic renal insufficiency, chronic renal failure, and chronic dialysis.

^{^l}

Cancer includes Hodgkin and non-Hodgkin lymphoma, leukemia, multiple myeloma, and solid organ tumor.

^{^m}

Immune suppression includes HIV/AIDS, complement deficiency, immunoglobulin deficiency, immunosuppressive therapy, organ transplant, and splenectomy and/or asplenia.

^ⁿ

Substance abuse included prior injection drug use (1.2% of total patients), current injection drug use (1.0%), prior noninjection drug use (1.3%), or current noninjection drug use (4.8%).

Ninety-five percent of case patients had at least 1 underlying condition; proportions were similar by sex or race. Obesity and diabetes were the most common underlying conditions, and both conditions were more common among patients aged 40 to 64 years than among older or younger groups. Patients with diabetes were more likely to have SSTIs or osteomyelitis than to have bacteremia without a focus or joint infection compared with nondiabetic patients. Obese patients were more likely to have SSTIs and less likely to have bacteremia without a focus or osteomyelitis than nonobese patients.

Isolate Characteristics

From 2008 to 2016, a total of 13 563 isolates were analyzed for serotype, representing 87.0% of cases from sites collecting isolates. Through 2014, most isolates were serotyped by latex agglutination, with 9.4% tested by PCR. The overall distribution of serotypes changed over the study period (eFigure 1 and eTable 1 in the Supplement), with serotypes Ib, II, and IV becoming more prevalent and serotypes Ia, III, and V becoming less prevalent. 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). Between 2008 and 2016, the incidence of serotype Ib disease doubled from 0.8 to 1.6 cases per 100 000, the incidence of serotype II disease increased by more than 70% from 1.1 to 1.9 cases per 100 000, and the incidence of serotype IV quadrupled from 0.3 to 1.2 cases per 100 000 (Figure 3). Together, these 3 serotypes accounted for 75% of the overall increase in incidence among patients for whom serotype information was available. Serotype distribution did not vary consistently between sites (eFigure 2 and eTable 2 in the Supplement).

Figure 3. — Data are shown for Active Bacterial Core surveillance (ABCs) sites, 2008-2016. Other serotypes include Ic, VI, VII, VIII, IX, and nontypeable isolates.

Among 1953 isolates sequenced in 2016, a total of 83.9% showed resistance to tetracycline (range, 66.5% for serotype IV to 93.0% for Ib), 54.8% showed resistance to erythromycin (range, 39.3% for serotype III to 78.7% for IV) (eFigure 3A and eTable 3A in the Supplement), 43.2% showed resistance to clindamycin (range, 6.6% for serotype Ia to 79.2% for IV) (eFigure 3B and eTable 3B in the Supplement), and 2.3% showed resistance to levofloxacin (most common in serotype Ib at 6.0%). Resistance to erythromycin and clindamycin has been stable since 2013 at approximately 55% and 43%, respectively (Figure 4). Resistance to clindamycin increased from 37.0% of isolates in 2011 to 43.2% in 2016 (P = .02).

Figure 4. — Data are shown for Active Bacterial Core surveillance sites, 2008-2016. In 2008 to 2010, conventional antimicrobial susceptibility testing without clindamycin inducible-resistance testing was performed. In 2011 to 2015, both conventional antimicrobial susceptibility testing and clindamycin inducible-resistance testing were performed; inducible clindamycin resistance accounted for 6.8% to 7.2% of the total. In 2016, resistance was determined based on the presence of resistance genes in sequenced isolates (the presence of a resistance gene predicts total clindamycin resistance).

During the study period, 68 of 13 563 isolates (0.5%) had laboratory findings suggestive of nonsusceptibility to 1 or more β-lactam antibiotics, including 48 isolates (0.4%) collected during 2008 to 2015 with elevated minimum inhibitory concentration values and 20 isolates (1.0%) collected during 2016 with a pbp2x (GenBank AE009948) gene variant associated with an elevated minimum inhibitory concentration (eTable 4 in the Supplement). In addition, 1 isolate was nonsusceptible to linezolid (from 2014), 3 were nonsusceptible to vancomycin (1 from 2011 described in a 2014 study³⁴ and 2 from 2016), and none were nonsusceptible to daptomycin.

Among 1957 sequenced isolates from 2016, 170 multilocus sequence typing sequence types (STs) were represented. The most common were ST1 (20.5%; predominantly serotypes V, Ib, and II), ST23 (17.4%; predominantly serotype Ia), ST22 (8.4%; predominantly serotype II), ST19 (7.9%; predominantly serotypes III and V), ST459 (7.6%; predominantly serotype IV), and ST8 (6.5%; predominantly serotype Ib). Among sequenced isolates containing resistance determinants, resistance to tetracyclines was largely due to the presence of the tetM (GenBank HG799494) gene (95.3% of isolates). Resistance to macrolides and lincosamides was due to an ermB (GenBank HG799494) gene in 34.9% of isolates, an ermTR (GenBank CP002121) gene in 33.1%, and a mef (GenBank CP000921) gene in 22.9%. Resistance to fluoroquinolones was typically due to mutations in the quinolone resistance–determining regions of gyrA (GenBank CP007571) (49%) or parC (GenBank CP007571) (51%). The virulence gene hvgA (GenBank CP022537) was present in 77 (3.9%) of isolates, 73 of which were serotype III and a part of the ST17 clonal complex; of the remainder, 1 was serotype III but a part of the ST23 clonal complex, and 3 were serotype IV (2 ST17 clonal complex and 1 ST23 clonal complex).

Discussion

The incidence of invasive GBS disease among nonpregnant US adults continues to rise, roughly tripling between 1990 and 2016 (from 3.6 to 10.9 cases per 100 000).³ Given the severity of invasive GBS (94.6% of cases were hospitalized, 27.3% of cases required intensive care unit admission, and 5.6% of cases were fatal in 2016), this rise represents a clinical and public health concern. Incidence is rising disproportionately among certain demographic groups, particularly whites, men, and adults aged 40 to 64 years. The difference in incidence between black and white participants has declined markedly, while the difference between men and women continues to grow; this factor may be related to higher rates of important underlying conditions among men, such as diabetes or smoking. Incidence remains highest among blacks, men, and those 80 years or older. In 2016, the incidence rate of invasive GBS was 60% higher than the rate of invasive group A streptococcal infections and 20% higher than the rate of invasive pneumococcal infections among all adults, and the differences in rates were more pronounced in older age groups.^35,36 The latter may be due to improvements in 13-valent pneumococcal conjugate vaccine coverage among adults 65 years or older or herd immunity from infant vaccination. The incidence of invasive GBS appears to be higher than the incidence of community-acquired methicillin-resistant Staphylococcus aureus but lower than the incidence of hospital-acquired methicillin-resistant Staphylococcus aureus among adults 65 years or older.³⁷

Surveillance data do not allow us to determine the direct cause of the rising incidence. However, the data suggest that the increase may be associated with certain serotypes because serotypes Ib, II, and IV accounted for three-quarters of the increase in incidence between 2008 and 2016. Increasing prevalence of underlying health conditions associated with invasive GBS likely also contributes. A 2014 study³⁸ linked obesity and diabetes to an increased risk of invasive GBS infections. Our analysis found an increasing prevalence of obesity and diabetes among patients with invasive GBS over the study period. Both obesity and diabetes have been linked to increased risk for SSTIs,^39,40 a syndrome that showed significant gains during the study period. An aging US population may also have contributed to the rise, but the greatest relative increase in incidence rates occurred among those aged 40 to 64 years.

Group B Streptococcus remains highly susceptible to β-lactams and vancomycin; however, rare examples of resistance to both have been documented from multiple geographic areas, and their emergence should be monitored.^29,34 Resistance to erythromycin and clindamycin was higher than previously reported³ and increased over the study period; most of this increase was due to resistance in emerging serotypes Ib and IV. Clinician awareness of trends in antimicrobial resistance of GBS is important when susceptibility results are not available and empirical therapy is necessary. Rising clindamycin resistance is of particular clinical significance in the setting of SSTIs, where clindamycin is often considered a first-line antimicrobial agent.⁴¹

Multivalent vaccines to prevent infant disease through maternal immunization are under development, and several have entered clinical trials.^{19,20,21,22,42} Such vaccines may also hold potential for reducing GBS disease in the adult population. There are some data suggesting that adults can mount an immune response to vaccines targeting GBS capsular polysaccharides,⁴³ but whether they would be effective at preventing invasive GBS in adults, particularly those 80 years or older and those with significant underlying conditions, needs to be determined. Although a pentavalent vaccine containing the most common serotypes (Ia, Ib, II, III, and V) would currently cover 86.4% of nonpregnant adult cases, the recent rise in serotype IV has prompted consideration for including this serotype in vaccine development. The emergence of serotype IV could demonstrate a rise and sustained increase similar to that observed with serotype V disease in nonpregnant adults.¹⁴

Limitations

This study has several limitations. We did not have denominators to calculate incidence rates by underlying conditions, so we could not directly assess risk posed by common conditions, such as obesity and diabetes, but prevalences of these conditions among GBS cases were much higher than the US adult population (diabetes is estimated to be 12% to 14%⁴⁴ and obesity 36%⁴⁵ among adults). We excluded female cases missing pregnancy status (89 of 21 250 [0.5% of all cases]), which likely had only a small influence on the overall incidence and case characteristics. We included all cases in trend analyses, which may have differed slightly from analyses than if we had included only cases from catchment areas common to all years of the study. The focus of this study was limited to invasive GBS disease. Group B Streptococcus also causes a substantial burden of noninvasive disease, including urinary tract infections, noninvasive SSTIs, and pneumonia, so the overall burden in adults is likely much higher.^10,46,47,48

Conclusions

In summary, the incidence of invasive GBS in nonpregnant adults continues to rise, with rates now exceeding those for invasive pneumococcal disease. The rise parallels an increasing prevalence of underlying conditions, such as obesity and diabetes, and was associated with serotypes Ib, II, and IV. Increasing resistance to clindamycin is also a concern given its clinical use in the management of SSTIs, a common manifestation of GBS disease. A multivalent vaccine could target a substantial portion of adult disease but would be most influential if it included serotype IV, as well as the other major serotypes. Ongoing surveillance to monitor future trends in serotype distribution and antibiotic resistance is warranted. Improved physician awareness and efforts aimed at reducing risk factors, such as obesity and diabetes, along with efforts to maintain skin integrity and provide optimal wound care, may help prevent invasive GBS infections.

Supplement.

eFigure 1. Serotype Distribution of Invasive Group B Streptococcal Infections Among Nonpregnant Adults by Serotype—ABCs Surveillance Sites, 2008–2016

eFigure 2. Serotype Distribution of Invasive Group B Streptococcal Isolates by Site—ABCs Surveillance Sites, 2016

eFigure 3A and B. Resistance of Invasive Group B Streptococcal Isolates to (A) Erythromycin and (B) Clindamycin by Serotype, Over Time—ABCs Surveillance Sites, 2008–2016

eTable 1. Serotype Distribution of Invasive Group B Streptococcal Infections Among Nonpregnant Adults by Serotype—ABCs Surveillance Sites, 2008–2016

eTable 2. Serotype Distribution of Invasive Group B Streptococcal Isolates by Site—ABCs Surveillance Sites, 2016

eTable 3A. Invasive Group B Streptococcal Isolates From Nonpregnant Adults Resistant to Erythromycin by Serotype, Over Time—ABCs Surveillance Sites, 2008–2016

eTable 3B. Invasive Group B Streptococcal Isolates From Nonpregnant Adults Resistant to Clindamycin by Serotype, Over Time—ABCs Surveillance Sites, 2008–2016

eTable 4. Invasive Group B Streptococcus Isolates Cultured From Nonpregnant Adults With Elevated Minimum Inhibitory Concentrations or pbp2x Variant Suggestive of Beta Lactam Nonsusceptibility—ABCs Surveillance Sites, 2008–2016

Click here for additional data file.^{(465.2KB, pdf)}

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplement.

eFigure 1. Serotype Distribution of Invasive Group B Streptococcal Infections Among Nonpregnant Adults by Serotype—ABCs Surveillance Sites, 2008–2016

eFigure 2. Serotype Distribution of Invasive Group B Streptococcal Isolates by Site—ABCs Surveillance Sites, 2016

eFigure 3A and B. Resistance of Invasive Group B Streptococcal Isolates to (A) Erythromycin and (B) Clindamycin by Serotype, Over Time—ABCs Surveillance Sites, 2008–2016

eTable 1. Serotype Distribution of Invasive Group B Streptococcal Infections Among Nonpregnant Adults by Serotype—ABCs Surveillance Sites, 2008–2016

eTable 2. Serotype Distribution of Invasive Group B Streptococcal Isolates by Site—ABCs Surveillance Sites, 2016

eTable 3A. Invasive Group B Streptococcal Isolates From Nonpregnant Adults Resistant to Erythromycin by Serotype, Over Time—ABCs Surveillance Sites, 2008–2016

eTable 3B. Invasive Group B Streptococcal Isolates From Nonpregnant Adults Resistant to Clindamycin by Serotype, Over Time—ABCs Surveillance Sites, 2008–2016

Click here for additional data file.^{(465.2KB, pdf)}

[ioi180117r1] 1.McCracken GH., Jr Group B streptococci: the new challenge in neonatal infections. J Pediatr. 1973;82(4):703-706. doi: 10.1016/S0022-3476(73)80603-1 [DOI] [PubMed] [Google Scholar]

[ioi180117r2] 2.Deutscher M, Lewis M, Zell ER, Taylor TH Jr, Van Beneden C, Schrag S; Active Bacterial Core Surveillance Team . Incidence and severity of invasive Streptococcus pneumoniae, group A Streptococcus, and group B Streptococcus infections among pregnant and postpartum women. Clin Infect Dis. 2011;53(2):114-123. doi: 10.1093/cid/cir325 [DOI] [PubMed] [Google Scholar]

[ioi180117r3] 3.Skoff TH, Farley MM, Petit S, et al. Increasing burden of invasive group B streptococcal disease in nonpregnant adults, 1990-2007. Clin Infect Dis. 2009;49(1):85-92. doi: 10.1086/599369 [DOI] [PubMed] [Google Scholar]

[ioi180117r4] 4.Batalis NI, Caplan MJ, Schandl CA. Acute deaths in nonpregnant adults due to invasive streptococcal infections. Am J Forensic Med Pathol. 2007;28(1):63-68. doi: 10.1097/01.paf.0000248775.34108.da [DOI] [PubMed] [Google Scholar]

[ioi180117r5] 5.Jackson LA, Hilsdon R, Farley MM, et al. Risk factors for group B streptococcal disease in adults. Ann Intern Med. 1995;123(6):415-420. doi: 10.7326/0003-4819-123-6-199509150-00003 [DOI] [PubMed] [Google Scholar]

[ioi180117r6] 6.Farley MM, Harvey RC, Stull T, et al. A population-based assessment of invasive disease due to group B Streptococcus in nonpregnant adults. N Engl J Med. 1993;328(25):1807-1811. doi: 10.1056/NEJM199306243282503 [DOI] [PubMed] [Google Scholar]

[ioi180117r7] 7.Smith EM, Khan MA, Reingold A, Watt JP. Group B Streptococcus infections of soft tissue and bone in California adults, 1995-2012. Epidemiol Infect. 2015;143(15):3343-3350. doi: 10.1017/S0950268815000606 [DOI] [PMC free article] [PubMed] [Google Scholar]

[ioi180117r8] 8.Park SY, Park Y, Chung JW, et al. Group B streptococcal bacteremia in non-pregnant adults: results from two Korean centers. Eur J Clin Microbiol Infect Dis. 2014;33(10):1785-1790. doi: 10.1007/s10096-014-2140-9 [DOI] [PubMed] [Google Scholar]

[ioi180117r9] 9.Lambertsen L, Ekelund K, Skovsted IC, Liboriussen A, Slotved HC. Characterisation of invasive group B streptococci from adults in Denmark 1999 to 2004. Eur J Clin Microbiol Infect Dis. 2010;29(9):1071-1077. doi: 10.1007/s10096-010-0941-z [DOI] [PubMed] [Google Scholar]

[ioi180117r10] 10.Blancas D, Santin M, Olmo M, Alcaide F, Carratala J, Gudiol F. Group B streptococcal disease in nonpregnant adults: incidence, clinical characteristics, and outcome. Eur J Clin Microbiol Infect Dis. 2004;23(3):168-173. doi: 10.1007/s10096-003-1098-9 [DOI] [PubMed] [Google Scholar]

[ioi180117r11] 11.Tyrrell GJ, Senzilet LD, Spika JS, et al. ; Sentinel Health Unit Surveillance System Site Coordinators . Invasive disease due to group B streptococcal infection in adults: results from a Canadian, population-based, active laboratory surveillance study: 1996. J Infect Dis. 2000;182(1):168-173. doi: 10.1086/315699 [DOI] [PubMed] [Google Scholar]

[ioi180117r12] 12.Muñoz P, Llancaqueo A, Rodríguez-Créixems M, Peláez T, Martin L, Bouza E. Group B Streptococcus bacteremia in nonpregnant adults. Arch Intern Med. 1997;157(2):213-216. doi: 10.1001/archinte.1997.00440230087011 [DOI] [PubMed] [Google Scholar]

[ioi180117r13] 13.Huang PY, Lee MH, Yang CC, Leu HS. Group B streptococcal bacteremia in non-pregnant adults. J Microbiol Immunol Infect. 2006;39(3):237-241. [PubMed] [Google Scholar]

[ioi180117r14] 14.Blumberg HM, Stephens DS, Modansky M, et al. Invasive group B streptococcal disease: the emergence of serotype V. J Infect Dis. 1996;173(2):365-373. doi: 10.1093/infdis/173.2.365 [DOI] [PubMed] [Google Scholar]

[ioi180117r15] 15.Schwartz B, Schuchat A, Oxtoby MJ, Cochi SL, Hightower A, Broome CV. Invasive group B streptococcal disease in adults: a population-based study in metropolitan Atlanta. JAMA. 1991;266(8):1112-1114. doi: 10.1001/jama.1991.03470080082034 [DOI] [PubMed] [Google Scholar]

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PERMALINK

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

Louise K Francois Watkins, MD, MPH

Lesley McGee, PhD

Stephanie J Schrag, DPhil

Bernard Beall, PhD

Jennifer Hudson Jain, MPH

Tracy Pondo, MSPH

Monica M Farley, MD

Lee H Harrison, MD

Shelley M Zansky, PhD

Joan Baumbach, MD, MPH, MS

Ruth Lynfield, MD

Paula Snippes Vagnone, MT(ASCP)

Lisa A Miller, MD, MSPH

William Schaffner, MD

Ann R Thomas, MD

James P Watt, MD, MPH

Susan Petit, MPH

Gayle E Langley, MD, MPH

Key Points

Question

Findings

Meaning

Abstract

Importance

Objective

Design, Setting, and Participants

Main Outcomes and Measures

Results

Conclusions and Relevance

Introduction

Methods

Population-Based Surveillance

Definitions

Specimen Collection and Testing

Statistical Analysis

Results

Trends Over Time

Figure 1. Incidence of Invasive Group B Streptococcal Infections Among Nonpregnant Adults.

Figure 2. Incidence of Invasive Group B Streptococcal Infections Among Nonpregnant Adults by Race and Sex.

Descriptive Epidemiology, 2016

Table. Characteristics of Nonpregnant Adults With Invasive Group B Streptococcal Infections, 2016.

Isolate Characteristics

Figure 3. Incidence of Invasive Group B Streptococcal Infections Among Nonpregnant Adults by Serotype.

Figure 4. Resistance of Invasive Group B Streptococcal Isolates to Erythromycin and Clindamycin Over Time.

Discussion

Limitations

Conclusions

References

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

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