Access to this full-text is provided by Springer Nature.
Content available from BMC Infectious Diseases
This content is subject to copyright. Terms and conditions apply.
R E S E A R C H A R T I C L E Open Access
Group B streptococcal colonization in
elderly women
Rossella Baldan
1
, Sara Droz
1
, Carlo Casanova
1
, Laura Knabben
2
, Dorothy J. Huang
3
, Christine Brülisauer
1
,
André B. Kind
3
, Elke Krause
2
, Stefanie Mauerer
4
, Barbara Spellerberg
4
and Parham Sendi
1,5*
Abstract
Background: In non-pregnant adults, the incidence of invasive Group B Streptococcus (GBS) disease is continuously
increasing. Elderly and immunocompromised persons are at increased risk of infection. GBS commonly colonizes
the vaginal tract, though data on colonization in the elderly are scarce. It is unknown whether the prevalence of
GBS colonization is increasing in parallel to the observed rise of invasive infection. We conducted a three-year
(2017–2019) prospective observational cross-sectional study in two teaching hospitals in Switzerland to determine
the rate of GBS vaginal colonization in women over 60 years and i) to compare the proportions of known risk
factors associated with invasive GBS diseases in colonized versus non-colonized women and ii) to evaluate the
presence of GBS clusters with specific phenotypic and genotypic patterns in this population.
Methods: GBS screening was performed by using vaginal swabs collected during routine examination from
women willing to participate in the study and to complete a questionnaire for risk factors. Isolates were
characterized for antibiotic resistance profile, serotype and sequence type (ST).
Results: The GBS positivity rate in the elderly was 17% (44/255 positive samples), and similar to the one previously
reported in pregnant women (around 20%). We could not find any association between participants’characteristics,
previously published risk factors and GBS colonization. All strains were susceptible to penicillin, 22% (8/36) were not
susceptible to erythromycin, 14% (5/36) were not susceptible to clindamycin and 8% (3/36) showed inducible
clindamycin resistance. Both M and L phenotypes were each detected in one isolate. The most prevalent serotypes
were III (33%, 12/36) and V (31%, 11/36). ST1 and ST19 accounted for 11% of isolates each (4/36); ST175 for 8% (3/
36); and ST23, ST249 and ST297 for 6% each (2/36). Significantly higher rates of resistance to macrolides and
clindamycin were associated with the ST1 genetic background of ST1.
Conclusions: Our findings indicate a similar colonization rate for pregnant and elderly women.
Trial registration: Current Controlled Trial ISRCTN15468519; 06/01/2017
Keywords: Group B Streptococcus, Streptococcus agalactiae, Colonization, Elderly women, Postmenopausal women
© The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,
which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if
changes were made. The images or other third party material in this article are included in the article's Creative Commons
licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons
licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain
permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the
data made available in this article, unless otherwise stated in a credit line to the data.
* Correspondence: parham.sendi@ifik.unibe.ch
1
Institute for Infectious Diseases, University of Bern, Friedbühlstrasse 51, 3010
Bern, Switzerland
5
Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel
and University of Basel, Basel, Switzerland
Full list of author information is available at the end of the article
Baldan et al. BMC Infectious Diseases (2021) 21:408
https://doi.org/10.1186/s12879-021-06102-x
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Background
Group B Streptococcus (GBS, Streptococcus agalactiae)
is a pathobiont frequently found in the normal micro-
biota of the gastrointestinal and vaginal tracts of women
[1,2]. GBS can cause life-threatening infections in neo-
nates, with maternal colonization being the principal
route of transmission. In non-pregnant adults, the inci-
dence of infection is continuously increasing [3,4]. Eld-
erly and immunocompromised persons with underlying
conditions, such as diabetes mellitus and cancer, are at
increased risk of invasive GBS disease [4–6]. A Danish
study showed that from 2005 to 2018, the incidence of
invasive GBS in adults aged 65–74 years increased from
3.23 to 8.34 per 100,000, and in adults over 75 years
from 6.85 to 16.01 per 100,000 [7]. Their finding aligns
with data from Iceland, Finland, Norway, England and
Wales, Canada, and other countries [8–12]. Skin and
soft-tissue infection, primary bacteraemia and urinary
tract infection are the most frequent clinical manifesta-
tions of invasive GBS disease in the elderly [13,14].
Most studies have investigated the prevalence of GBS
colonization in pregnant women, only a few focusing on
non-pregnant adults [13,15]. Vaginal colonization in
pregnant women worldwide ranges between 5 and 30%–
35%, with an average estimate of approximately 20% [14,
16]. In contrast, little is known about the GBS
colonization rate in women older than 60 years of age. It
is unknown whether the prevalence of GBS colonization
is increasing in parallel to the observed rise of invasive
infection. The site of GBS colonization could potentially
be the source of invasive infection, underscoring the im-
portance to investigating the colonization rate in this pa-
tient population.
We present here the results of a prospective observa-
tional cross-sectional study in which we aimed to deter-
mine the vaginal colonization rate in women over the
age of 60 in two teaching hospitals in Switzerland. Sec-
ondary objectives of the study were to compare the pro-
portions of known risk factors associated with invasive
GBS diseases in colonized versus non-colonized women
and to evaluate the presence of clusters with specific
phenotypic and genotypic patterns in GBS strains iso-
lated in our population.
Methods
Study design and participants’data
Women presenting at the outpatient clinic of two cen-
tres (Bern and Basel University hospitals) for a routine
vaginal examination between January 2017 and Decem-
ber 2019 were screened for eligibility. Participants to be
included in the study had to be ≥60 years old and cap-
able of reading and understanding the patient informa-
tion sheet and giving voluntary written consent to
participate in the study, in which a vaginal swab would
be collected during their routine gynaecological examin-
ation and cultured for the presence of GBS. In addition,
participants were asked to complete a short question-
naire to obtain data regarding ethnicity, current or prior
medical conditions, menstrual history and sexual history
(Supplementary Material). Patient consent, study infor-
mation and questionnaires were available in four lan-
guages (German, French, Italian and English). The swab
and the questionnaire were coded to protect partici-
pants’identifiable data and privacy, according to the ap-
proved study protocol (trial registration no. ISRC
TN15468519). The study was approved by the local eth-
ical committee (Kantonale Ethikkommission-Bern:
2016–01669).
GBS culture and characterization
GBS screening was carried out with the same method-
ology throughout the whole study period. Isolation of
the strain from vaginal samples was performed by
growth in an enrichment medium (Todd–Hewitt broth)
followed by subculture on a selective GBS chromagar
plate (StrepB, CHROMagarTM, Paris, France). Identified
colonies were subjected to MALDI-TOF mass
spectrometry.
GBS isolates were further characterized at the pheno-
typic and genotypic level to determine the antibiotic re-
sistance profile, the capsular serotype and the clone
sequence type (ST). The minimal inhibitory concentra-
tions (MICs) for penicillin, clindamycin and erythro-
mycin were determined by E-test (bioMérieux, Marcy
l’Etoile, France) and interpreted according to CLSI
guidelines [17]. Detection of the macrolide-lincosamide-
streptogramin B (MLS
B
) resistance phenotype was
assessed by double disk diffusion test [18,19]. Capsular
serotyping was performed by use of a rapid latex agglu-
tination test and polymerase chain reaction analysis, as
previously described [20,21] Sequence type was deter-
mined by multilocus sequence typing as described else-
where (https://pubmlst.org/sagalactiae/). One sample per
patient was included in the analysis. In the case of mul-
tiple sampling from the same participant, only the swab
obtained at the first visit was analysed.
Data analysis
Questionnaire and microbiology data were recorded in
an electronic database designed with REDCap software
(Research Electronic Data CAPture). Significant associa-
tions between participants’characteristics/risk factors,
GBS carrier status, GBS antibiotic resistance profiles, se-
rotypes and sequence types were investigated. In the
case of missing answers per single question, the denom-
inator for each analysis was adapted accordingly. Graph-
Pad Prism 8.0 was used for statistical analysis. The
association between age variables and a positive GBS
Baldan et al. BMC Infectious Diseases (2021) 21:408 Page 2 of 8
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
result was investigated by using the Mann-Whitney test.
Differences in the prevalence of risk factors between
GBS-positive and GBS-negative groups were assessed by
contingency tables and the chi-square test, or by Fisher’s
exact probability test if the frequency was less than 5.
For direct comparisons, distribution analyses were also
performed by using the chi-square test, Fisher’s exact
test or Cochran-Armitage trend analysis. A two-tailed p-
value of ≤0.05 was considered significant.
Results
During the study period, 263 samples were collected
from a total of 259 patients from the two centres, as
shown in Fig. 1. Four samples were excluded from ana-
lysis, as they were obtained from the same patients dur-
ing a second clinic visit. Another four were excluded
because the samples could not be cultured. Thus, a total
of 255 unique samples were included in the study.
Overall, the GBS positivity rate was 17% (44/255 posi-
tive samples), which was similar in both study sites (Bern
centre: 18%, 35/199; Basel centre: 16%, 9/56). The results
of the questionnaire data, including participants’demo-
graphic characteristics and risk factors for GBS
colonization, were analysed overall and divided by GBS
carrier status, a summary of which is shown in Table 1.
No significant associations were found between the par-
ticipants’demographic characteristics, medical history,
menstrual history, sexual activity and GBS status.
Of the 44 swabs that tested positive, 36 GBS isolates
were available for phenotypic and genotypic
characterization (Fig. 1). The results are presented in
Table 2. All 36 GBS isolates were susceptible to penicil-
lin, with an MIC ranging between 0.032 and 0.094 mg/L.
Eight GBS isolates (22%) were not susceptible to
erythromycin, and three of them (3/8, 37.5%) had a MIC
of ≥256 mg/L. Five isolates (14%) were not susceptible to
clindamycin, four of them (4/5, 80%) with a MIC of
≥256 mg/L and one with a MIC of 1.5 mg/L. In addition,
three GBS isolates (8%) that were considered clindamy-
cin susceptible by E-test (MIC 0.19 mg/L) showed the
MLS
B
phenotype when tested by the double disk diffu-
sion test, indicating inducible clindamycin resistance.
Hence, eight (22%) GBS isolates were considered non-
susceptible to clindamycin. Twenty-seven GBS isolates
(75%) were susceptible to both clindamycin and
erythromycin.
One GBS isolate belonging to capsular serotype Ia and
ST624 (3%) showed an M phenotype, with erythromycin
resistance only (MIC 4 mg/L). One GBS isolate assigned
to capsular serotype III and ST19 (3%) displayed the L
phenotype, being resistant to clindamycin only (MIC 1.5
mg/L).
Capsular serotyping showed that the most prevalent
serotypes were III (33%, 12/36), V (31%, 11/36) and Ia
(17%, 6/36). Multilocus sequence typing analysis showed
that the most common sequence types were ST1 and
Fig. 1 GBS Cite study flowchart
Baldan et al. BMC Infectious Diseases (2021) 21:408 Page 3 of 8
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
ST19, accounting for four isolates each (11%); ST175
with three isolates (8%); and ST23, ST249 and ST297
with two isolates each (6%). Five strains could not be
assigned to a sequence type (no exact match, 14%), while
the remaining 14 isolates belonged to unique sequence
types, including one to ST17 and capsular serotype III.
Compared with non-ST1 isolates, ST1 (serotype V)
isolates were significantly associated with resistance to
Table 1 Participants’demographic characteristics and risk factors for GBS acquisition overall and by GBS carrier status
Participants’characteristics/risk factors Overall (n=
255)
GBS positive (n=
44)
GBS negative (n=
211)
P-Value
Demographic characteristics
Mean age at enrolment (years, SD) 68 (6) 68 (5) 69 (6) 0.59
Minimum-maximum age (years) 69–98 60–84 60–98 Na
Participants’origin 0.46*
Swiss (%) 205/239 (86%) 38/42 (90%) 167/197 (85%)
Other (%) 34/239 (14%) 4/42 (10%) 30/197 (15%)
Not answered (%) 16/255 (6%) 2/44 (5%) 14/255 (7%) Na
Medical history
No. of participants with diabetes (%) 20/254 (8%) 3/44 (7%) 17/210 (8%) > 0.99*
No. of participants with liver disease (%) 7/253 (3%) 0/44 (0%) 7/209 (3%) 0.60*
No. of participants with history of stroke (%) 6/253 (2%) 1/44 (2%) 5/209 (2%) > 0.99*
No. of participants with bladder weakness (%) 84/246 (34%) 10/43 (23%) 74/203 (36%) 0.09
No. of participants with history of cancer (%) 43/251 (17%) 9/44 (20%) 34/207 (16%) 0.51
No. of participants still receiving cancer treatment (%) 17/39 (44%) 4/9 (44%) 13/30 (43%) > 0.99*
Menstruation
Mean age of first menstruation (years, SD) 14 (2) 14 (2) 14 (2) 0.97
Not answered 14/255 1/44 13/211 Na
Mean age of menopause (years, SD) 49 (7) 48 (8) 49 (7) 0.69
Not answered 25/255 2/44 23/211 Na
Sexual activity
No. of sexual partners during life 0.73
§
/
0.80°
1 or less (%) 77/247 (31%) 13/42 (31%) 64/205 (31%) 0.97
2 or 3 (%) 80/247 (32%) 14/42 (33%) 66/205 (32%) 0.88
3 or 4 (%) 42/247 (17%) 5/42 (12%) 37/205 (18%) 0.33
5 or more (%) 48/247 (20%) 10/42 (24%) 38/205 (19%) 0.43
Not answered (%) 8/255 (3%) 2/44 (4%) 6/211 (3%) Na
No. of participants with a new sexual partner in the last few months
before enrolment
11/255 (4%) 1/44 (2%) 10/211 (5%) 0.69*
No. of participants’sexual encounters in the 6 months before enrolment 0.98
§
*/
0.65°
1 or less (%) 141/235 (60%) 24/41 (59%) 117/194 (60%) 0.83
2 or 3 (%) 15/235 (6%) 2/41 (4%) 13/194 (7%) > 0.99*
3 or 4 (%) 18/235 (8%) 3/41 (7%) 15/194 (8%) > 0.99*
At least once per month (%) 31/235 (13%) 6/41 (15%) 25/194 (13%) 0.76
At least once per week (%) 30/235 (13%) 6/41 (15%) 24/194 (12%) 0.69
Not answered (%) 20/255 (8%) 3/44 (7%) 17/211 (8%) Na
Association between age variables and GBS status was investigated by using the Mann-Whitney test; association between other risk factors and GBS status was
assessed by using the chi-square test or Fisher’s exact test (indicated by *); distribution analysis was also performed by using the chi-square test (indicated by §),
Fisher’s exact test (*) or Cochran-Armitage trend analysis (°). In each analysis, the denominator includes only participants who provided the information;
participants who did not answer the question were excluded. SD Standard deviation, Na Not applicable
Baldan et al. BMC Infectious Diseases (2021) 21:408 Page 4 of 8
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
both clindamycin and erythromycin (p= 0.0129, when
considering constitutive resistance only; p= 0.0008,
when also including inducible clindamycin resistance)
and to the MLS
B
phenotype (p= 0.0060, Table 2).
This association was based on small absolute numbers
(n<5).
Discussion
The number of invasive GBS infections in the elderly
population is continuously increasing [5], but the reason
for this phenomenon is unclear. In Denmark, between
2005 and 2018 the incidence of invasive GBS in adults
above the age of 65 years old increased more than two-
fold (from 3.23 to 8.34 per 100,000). Similar trends have
been reported in other countries [8–12]. The prevalence
of comorbidities that increase in parallel with age or an
increase in GBS colonization have been discussed as po-
tential contributing factors. Although the prevalence of
GBS colonization in pregnant women has been investi-
gated in numerous studies, with an average estimate
around 20%, the prevalence in the elderly population –
notably a group with increasing invasive GBS infections
–is unknown. The GBS colonization rate is associated
with sexual experience and activity [22,23]. Considering
that sexual activity in older people can change over time
[24] and may have increased in recent decades, we
aimed to determine the vaginal GBS colonization rate in
elderly women. Our study showed a prevalence of GBS
colonization of 17% in postmenopausal women (mean
age, 68 years), similar to that reported by Moltó-Garcia
et al. (17.8%) in Spain [25]. Edwards et al. reported a
colonization rate of 21.7% in 254 healthy elderly partici-
pants (mean age, 73 years) in 2005 [15]. Kaplan et al.
found a prevalence of GBS colonization of 12% among
167 elderly home residents (median age, 84 years) in
1983 [26]. These data indicate that the GBS colonization
rate in pregnant women and healthy elderly adults is
similar [16].
All GBS isolates preserved susceptibility to penicillin.
However, compared with our previous study conducted
on GBS isolates from pregnant women tested between
2009 and 2010 in the same geographical area, we ob-
served a higher proportion of isolates that were non-
susceptible to erythromycin (22% vs 14.6%), to clindamy-
cin (14% vs 8.2%), and to both clindamycin and erythro-
mycin (11% vs 7.7%) and that displayed inducible
clindamycin resistance (8% vs 5.8%) [20]. However, a sci-
entific comparison is not possible, because no longitu-
dinal data were obtained. Moltó-Garcia et al. reported a
similar resistance rate to erythromycin (23.4%) among
their GBS samples collected between 2011 and 2012. Al-
though they detected a higher prevalence of constitutive
clindamycin resistance (20.6%), they observed the MLS
B
phenotype in only 0.9% of their strains. Increasing trends
Table 2 Phenotypic and genotypic characterization results of
GBS isolates
No. of isolates
(%)
Drug susceptibility testing
Penicillin susceptible 36/36 (100%)
Clindamycin susceptible
a
28/36 (78%)
Clindamycin non-susceptible
b
8/36 (22%)
Erythromycin susceptible 28/36 (78%)
Erythromycin non-susceptible 8/36 (22%)
MLS
B
phenotype (inducible clindamycin resistance) 3/36 (8%)
L phenotype (clindamycin resistant, erythromycin
susceptible)
1/36 (3%)
M phenotype (clindamycin susceptible, erythromycin
resistant)
1/36 (3%)
Clindamycin + Erythromycin non-susceptible
a
4/36 (11%)
Clindamycin + Erythromycin non-susceptible
b
7/36 (19%)
Serotyping
Serotype III 12/36 (33%)
Serotype V 11/36 (31%)
Serotype Ia 6/36 (17%)
Serotype Ib 2/36 (5%)
Serotype II 2/36 (5%)
Serotype IV 2/36 (5%)
Serotype VI 1/36 (3%)
Multilocus sequence typing
ST - no exact match 5/36 (14%)
ST1 4/36 (11%)
ST19 4/36 (11%)
ST175 3/36 (8%)
ST23 2/36 (6%)
ST249 2/36 (6%)
ST297 2/36 (6%)
Other STs 14/36 (38%)
Phenotype association with genotype
Clindamycin + Erythromycin susceptible/non-
susceptible
a
p= 0.0129
ST1 0/2
Non-ST1 27/2
Clindamycin + Erythromycin susceptible/non-
susceptible
b
p= 0.0008
ST1 0/4
Non-ST1 27/3
MLS
B
phenotype negative/positive p= 0.0060
ST1 0/2
Non-ST1 29/1
MLS
B
Macrolide-lincosamide-streptogramin A, ST Sequence type as
determined by multilocus sequence typing
a
Excluding isolates showing inducible clindamycin resistance by double
disk diffusion test
b
Including isolates showing inducible clindamycin resistance
Baldan et al. BMC Infectious Diseases (2021) 21:408 Page 5 of 8
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
of resistance were also reported elsewhere [7–11,25,
27]. It is possible that elderly individuals were exposed
to antibiotics more frequently than were pregnant
women, and hence, GBS isolates display a higher resist-
ance rate. However, we did not make such a comparison
in our study.
We found one GBS isolate with L phenotype (clinda-
mycin resistant but erythromycin susceptible). This
phenotype is rare and may occur via the inactivation of
lincosamide-specific nucleotidyl-transferases encoded by
lnu genes [28]. Alternatively, this unusual mechanism of
resistance may also be mediated by the ABC transporter,
encoded by lsaC genes, and be responsible for cross-
resistance to streptogramin A (LSA phenotype) and
pleuromutilins (LSAP phenotype) [29,30]. Recently,
there have been increasing reports of such a phenotype
in the United States, Europe, China, Korea and other
countries, with a prevalence ranging from 0.26% in Italy
to 15.9% in Korea [31–34]. This phenotype was detected
in one of the most common clones circulating world-
wide, ST19. This observation is worrisome because clin-
damycin is a frequently used alternative in patients with
documented allergy to penicillin.
The most prevalent capsular serotypes in our popula-
tion were III, V and Ia [20]. ST1, ST19 and ST23 were
the predominant clones, accounting for 28% of our iso-
lates. All three STs have been consistently reported to
be significantly associated with asymptomatic
colonization because of their limited invasive ability [14].
However, when it belongs to capsular serotype V, ST1
has been related to invasive disease, and a possible origin
from a bovine ancestor has been hypothesized, similar to
the case for hypervirulent clone ST17 [35]. Likewise,
ST23 was found in carriage and invasive isolates [36].
Clone ST17 was identified in only one strain.
We confirmed significantly higher rates of resistance
to macrolides and clindamycin associated with the gen-
etic background of ST1, belonging to clonal complex 1,
as previously described [27]. However, in contrast to
Lopes et al., who reported the association of ST1 and
capsular serotype Ib, we observed a relation to capsular
serotype V [27]. The association of ST1 and capsular
serotype V has also been described elsewhere [37].
Our study has limitations. Because of slow recruit-
ment, the study was terminated prior to reaching the
calculated target sample size, ending in a relatively small
study population. However, the number of participants
was comparable to (or even larger) than those in previ-
ous studies, and the GBS prevalence was similar to that
of a study that included 600 individuals [15,25,26]. We
only obtained vaginal and not recto-vaginal swabs, and
may have missed an unknown proportion of GBS colo-
nized individuals. However, we are convinced that the
potential difference between the two sampling methods
did not influence significantly the overall GBS
colonization rate in our study population. Eight GBS iso-
lates were lost for phenotypic and genotypic analysis
(Fig. 1). Given the lack of association between risk fac-
tors, resistance testing and serotype, it is unlikely that
the results of these eight lost GBS isolates would have
changed the overall findings.
Conclusions
The GBS vaginal colonization rate in women aged 60 or
more was 17%. The observed increase in invasive GBS
infections in elderly women may be for reasons other
than the colonization rate. We found no associations
with patient characteristics, comorbidities, menstrual
history, menopause or sexual activity. Twenty-two per-
cent of the isolates were not susceptible to clindamycin,
and this pattern was associated with ST1. The most fre-
quently found capsular serotypes were III and V. Our re-
sults indicate that the prevalence of colonization, the
antibiotic susceptibility and the molecular patterns are
similar in pregnant and elderly women.
Abbreviations
GBS: Group B Streptococcus; ST: Sequence type; MIC: Minimum inhibitory
concentration; MLS
B
: Macrolide-lincosamide-streptogramin B
Supplementary Information
The online version contains supplementary material available at https://doi.
org/10.1186/s12879-021-06102-x.
Additional file 1.
Acknowledgements
We thank Annina Tramèr, RN, and the nursing team of the Department of
Gynaecology and Gynaecological Oncology of the University Hospital Basel;
Eveline Hediger; and Lilo Schweizer of the University Hospital Bern
(Inselspital) for valuable work in the operating procedure issues during the
study. We are grateful to the laboratory technicians of the Institute for
Infectious Diseases for performing the phenotypic tests of GBS isolates.
Barbara Every, ELS, of BioMedical Editor, St Albert, Alberta, Canada, provided
English language editing.
Authors’contributions
PS was the principal investigator and initiated and conducted the study and
co-wrote the manuscript. LK, DH, AK and EK recruited the study participants,
obtained swabs and completed questionnaires, and had the clinical responsi-
bility for patients. SD and CC processed study participants’samples and per-
formed phenotypic characterization of GBS isolates. SM and BS performed
genotypic characterization of GBS isolates. RB designed the study database,
analysed the data and co-wrote the manuscript. CB recorded participants’
questionnaire data in the study database. All authors revised and approved
the manuscript.
Funding
This project was funded by Freie Akademische Gesellschaft Basel and
Stiftung für Infektiologie beider Basel. The funding bodies had no role in the
design of the study and no role in the collection, analysis, and interpretation
of data and in writing the manuscript.
Availability of data and materials
The data sets used and/or analysed during the current study may be made
available upon reasonable written request to the corresponding author.
Baldan et al. BMC Infectious Diseases (2021) 21:408 Page 6 of 8
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Declarations
Ethics approval and consent to participate
This study was registered in the ISRCTN registry with trial registration no.
ISRCTN15468519. Written informed consent was obtained from all
participants. The study was approved by the local ethical committee
(Kantonale Ethikkommission-Bern: 2016–01669).
Consent for publication
Not applicable (included in patient consent and ethics approval).
Competing interests
The authors declare that they have no competing interests.
Author details
1
Institute for Infectious Diseases, University of Bern, Friedbühlstrasse 51, 3010
Bern, Switzerland.
2
Department of Gynecology and Obstetrics, Inselspital,
Bern University Hospital and University of Bern, Bern, Switzerland.
3
Outpatient Department & Colposcopy Unit, University Women’s Hospital
Basel, Basel, Switzerland.
4
Institute of Medical Microbiology and Hygiene,
University Hospital Ulm, Ulm, Germany.
5
Division of Infectious Diseases &
Hospital Hygiene, University Hospital Basel and University of Basel, Basel,
Switzerland.
Received: 10 October 2020 Accepted: 22 April 2021
References
1. Verani JR, McGee L, Schrag SJ, Division of Bacterial Diseases NCfI, Respiratory
Diseases CfDC, Prevention. Prevention of perinatal group B streptococcal
disease--revised guidelines from CDC, 2010. MMWR Recomm Rep. 2010;
59(RR-10):1–36.
2. Meyn LA, Krohn MA, Hillier SL. Rectal colonization by group B Streptococcus
as a predictor of vaginal colonization. Am J Obstet Gynecol. 2009;201(1):76.
e71–7.
3. Dermer P, Lee C, Eggert J, Few B. A history of neonatal group B
streptococcus with its related morbidity and mortality rates in the United
States. J Pediatr Nurs. 2004;19(5):357–63. https://doi.org/10.1016/j.pedn.2004.
05.012.
4. Farley MM. Group B streptococcal disease in nonpregnant adults. Clin Infect
Dis. 2001;33(4):556–61. https://doi.org/10.1086/322696.
5. Skoff TH, Farley MM, Petit S, Craig AS, Schaffner W, Gershman K, et al.
Increasing burden of invasive group B streptococcal disease in nonpregnant
adults, 1990-2007. Clin Infect Dis. 2009;49(1):85–92. https://doi.org/10.1086/
599369.
6. Kothari NJ, Morin CA, Glennen A, Jackson D, Harper J, Schrag SJ, et al.
Invasive group B streptococcal disease in the elderly, Minnesota, USA, 2003-
2007. Emerg Infect Dis. 2009;15(8):1279–81. https://doi.org/10.3201/eid1508.
081381.
7. Slotved HC, Hoffmann S. The epidemiology of invasive group B
Streptococcus in Denmark from 2005 to 2018. Front Public Health. 2020;8:
40. https://doi.org/10.3389/fpubh.2020.00040.
8. Lamagni TL, Keshishian C, Efstratiou A, Guy R, Henderson KL, Broughton K,
et al. Emerging trends in the epidemiology of invasive group B
streptococcal disease in England and Wales, 1991-2010. Clin Infect Dis. 2013;
57(5):682–8. https://doi.org/10.1093/cid/cit337.
9. Bergseng H, Rygg M, Bevanger L, Bergh K. Invasive group B streptococcus
(GBS) disease in Norway 1996-2006. Eur J Clin Microbiol Infect Dis. 2008;
27(12):1193–9. https://doi.org/10.1007/s10096-008-0565-8.
10. Alhhazmi A, Hurteau D, Tyrrell GJ. Epidemiology of invasive group B
streptococcal disease in Alberta, Canada, from 2003 to 2013. J Clin
Microbiol. 2016;54(7):1774–81. https://doi.org/10.1128/JCM.00355-16.
11. Bjornsdottir ES, Martins ER, Erlendsdottir H, Haraldsson G, Melo-Cristino J,
Kristinsson KG, et al. Changing epidemiology of group B streptococcal
infections among adults in Iceland: 1975–2014. Clin Microbiol Infect. 2016;
22(4):379.e379–16.
12. Balla rd MS, Schonheyder HC, Knudsen JD, Lyytikainen O, Dryden M,
Kennedy KJ, et al. The changing epidemiology of group B
streptococcus bloodstream infection: a multi-national population-based
assessment. Infect Dis (Lond). 2016;48(5):386–91. https://doi.org/10.31
09/23744235.2015.1131330.
13. Edwards MS, Baker CJ. Group B streptococcal infections in elderly adults.
Clin Infect Dis. 2005;41(6):839–47. https://doi.org/10.1086/432804.
14. Shabayek S, Spellerberg B. Group B streptococcal colonization, molecular
characteristics, and epidemiology. Front Microbiol. 2018;9:437. https://doi.
org/10.3389/fmicb.2018.00437.
15. Edwards MS, Rench MA, Palazzi DL, Baker CJ. Group B streptococcal
colonization and serotype-specific immunity in healthy elderly persons. Clin
Infect Dis. 2005;40(3):352–7. https://doi.org/10.1086/426820.
16. Russell NJ, Seale AC, O'Driscoll M, O'Sullivan C, Bianchi-Jassir F, Gonzalez-
Guarin J, et al. Maternal colonization with group B streptococcus and
serotype distribution worldwide: systematic review and meta-analyses. Clin
Infect Dis. 2017;65(suppl_2):S100–11.
17. Institute CaLS. M100 performance standards for antimicrobial susceptibility
testing. 30th ed; 2020.
18. Woods CR. Macrolide-inducible resistance to clindamycin and the D-test. Pediatr
Infect Dis J. 2009;28(12):1115–8. https://doi.org/10.1097/INF.0b013e3181c35cc5.
19. EUCAST. Expert rules. European Commitee on Antimicrobial Susceptibility
Testing. https://www.eucast.org/expert_rules_and_intrinsic_resistance/.
Accessed 9 Oct 2020.
20. Frohlicher S, Reichen-Fahrni G, Muller M, Surbek D, Droz S, Spellerberg B,
et al. Serotype distribution and antimicrobial susceptibility of group B
streptococci in pregnant women: results from a Swiss tertiary centre. Swiss
Med Wkly. 2014;144:w13935.
21. Poyart C, Tazi A, Reglier-Poupet H, Billoet A, Tavares N, Raymond J, et al.
Multiplex PCR assay for rapid and accurate capsular typing of group B
streptococci. J Clin Microbiol. 2007;45(6):1985–8. https://doi.org/10.1128/
JCM.00159-07.
22. Manning SD, Neighbors K, Tallman PA, Gillespie B, Marrs CF,
Borchardt SM, et al. Prevalence of group B streptococcus colonization
and potential for transmission by casual contact in healthy young
men and women. Clin Infect Dis. 2004;39(3):380–8. https://doi.org/10.1
086/422321.
23. Foxman B, Gillespie BW, Manning SD, Marrs CF. Risk factors for group B
streptococcal colonization: potential for different transmission systems by
capsular type. Ann Epidemiol. 2007;17(11):854–62. https://doi.org/10.1016/j.a
nnepidem.2007.05.014.
24. Beckman N, Waern M, Ostling S, Sundh V, Skoog I. Determinants of sexual
activity in four birth cohorts of Swedish 70-year-olds examined 1971-2001. J
Sex Med. 2014;11(2):401–10. https://doi.org/10.1111/jsm.12381.
25. Molto-Garcia B, Liebana-Martos Mdel C, Cuadros-Moronta E, Rodriguez-
Granger J, Sampedro-Martinez A, Rosa-Fraile M, et al. Molecular
characterization and antimicrobial susceptibility of hemolytic Streptococcus
agalactiae from post-menopausal women. Maturitas. 2016;85:5–10. https://
doi.org/10.1016/j.maturitas.2015.11.007.
26. Kaplan EL, Johnson DR, Kuritsky JN. Rectal colonization by group B beta-
hemolytic streptococci in a geriatric population. J Infect Dis. 1983;148(6):
1120. https://doi.org/10.1093/infdis/148.6.1120.
27. Lopes E, Fernandes T, Machado MP, Carrico JA, Melo-Cristino J, Ramirez M,
et al. Increasing macrolide resistance among Streptococcus agalactiae
causing invasive disease in non-pregnant adults was driven by a single
capsular-transformed lineage, Portugal, 2009 to 2015. Euro Surveill. 2018;
23(21):1700473.
28. Achard A, Villers C, Pichereau V, Leclercq R. New lnu(C) gene conferring
resistance to lincomycin by nucleotidylation in Streptococcus agalactiae
UCN36. Antimicrob Agents Chemother. 2005;49(7):2716–9. https://doi.org/1
0.1128/AAC.49.7.2716-2719.2005.
29. Malbruny B, Werno AM, Anderson TP, Murdoch DR, Leclercq R. A new
phenotype of resistance to lincosamide and streptogramin A-type
antibiotics in Streptococcus agalactiae in New Zealand. J Antimicrob
Chemother. 2004;54(6):1040–4. https://doi.org/10.1093/jac/dkh493.
30. Malbruny B, Werno AM, Murdoch DR, Leclercq R, Cattoir V. Cross-resistance
to lincosamides, streptogramins A, and pleuromutilins due to the lsa(C)
gene in Streptococcus agalactiae UCN70. Antimicrob Agents Chemother.
2011;55(4):1470–4. https://doi.org/10.1128/AAC.01068-10.
31. Hawkins PA, Law CS, Metcalf BJ, Chochua S, Jackson DM, Westblade LF,
et al. Cross-resistance to lincosamides, streptogramins A and pleuromutilins
in Streptococcus agalactiae isolates from the USA. J Antimicrob Chemother.
2017;72(7):1886–92. https://doi.org/10.1093/jac/dkx077.
32. Arana DM, Rojo-Bezares B, Torres C, Alos JI. First clinical isolate in Europe of
clindamycin-resistant group B Streptococcus mediated by the lnu(B) gene.
Rev Esp Quimioter. 2014;27(2):106–9.
Baldan et al. BMC Infectious Diseases (2021) 21:408 Page 7 of 8
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
33. Zhou K, Zhu D, Tao Y, Xie L, Han L, Zhang Y, et al. New genetic context of
lnu(B) composed of two multi-resistance gene clusters in clinical
Streptococcus agalactiae ST-19 strains. Antimicrob Resist Infect Control. 2019;
8(1):117. https://doi.org/10.1186/s13756-019-0563-x.
34. Takahashi T, Maeda T, Lee S, Lee DH, Kim S. Clonal distribution of
clindamycin-resistant erythromycin-susceptible (CRES) Streptococcus
agalactiae in Korea based on whole genome sequences. Ann Lab Med.
2020;40(5):370–81. https://doi.org/10.3343/alm.2020.40.5.370.
35. Salloum M, van der Mee-Marquet N, Valentin-Domelier AS, Quentin R.
Diversity of prophage DNA regions of Streptococcus agalactiae clonal
lineages from adults and neonates with invasive infectious disease. PLoS
One. 2011;6(5):e20256. https://doi.org/10.1371/journal.pone.0020256.
36. Jones N, Bohnsack JF, Takahashi S, Oliver KA, Chan MS, Kunst F, et al.
Multilocus sequence typing system for group B streptococcus. J Clin
Microbiol. 2003;41(6):2530–6. https://doi.org/10.1128/JCM.41.6.2530-2536.2
003.
37. Luan SL, Granlund M, Sellin M, Lagergård T, Spratt BG, Norgren M.
Multilocus sequence typing of Swedish invasive group B streptococcus
isolates indicates a neonatally associated genetic lineage and capsule
switching. J Clin Microbiol. 2005;43(8):3727–33. https://doi.org/10.1128/
JCM.43.8.3727-3733.2005.
Publisher’sNote
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
Baldan et al. BMC Infectious Diseases (2021) 21:408 Page 8 of 8
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
1.
2.
3.
4.
5.
6.
Terms and Conditions
Springer Nature journal content, brought to you courtesy of Springer Nature Customer Service Center GmbH (“Springer Nature”).
Springer Nature supports a reasonable amount of sharing of research papers by authors, subscribers and authorised users (“Users”), for small-
scale personal, non-commercial use provided that all copyright, trade and service marks and other proprietary notices are maintained. By
accessing, sharing, receiving or otherwise using the Springer Nature journal content you agree to these terms of use (“Terms”). For these
purposes, Springer Nature considers academic use (by researchers and students) to be non-commercial.
These Terms are supplementary and will apply in addition to any applicable website terms and conditions, a relevant site licence or a personal
subscription. These Terms will prevail over any conflict or ambiguity with regards to the relevant terms, a site licence or a personal subscription
(to the extent of the conflict or ambiguity only). For Creative Commons-licensed articles, the terms of the Creative Commons license used will
apply.
We collect and use personal data to provide access to the Springer Nature journal content. We may also use these personal data internally within
ResearchGate and Springer Nature and as agreed share it, in an anonymised way, for purposes of tracking, analysis and reporting. We will not
otherwise disclose your personal data outside the ResearchGate or the Springer Nature group of companies unless we have your permission as
detailed in the Privacy Policy.
While Users may use the Springer Nature journal content for small scale, personal non-commercial use, it is important to note that Users may
not:
use such content for the purpose of providing other users with access on a regular or large scale basis or as a means to circumvent access
control;
use such content where to do so would be considered a criminal or statutory offence in any jurisdiction, or gives rise to civil liability, or is
otherwise unlawful;
falsely or misleadingly imply or suggest endorsement, approval , sponsorship, or association unless explicitly agreed to by Springer Nature in
writing;
use bots or other automated methods to access the content or redirect messages
override any security feature or exclusionary protocol; or
share the content in order to create substitute for Springer Nature products or services or a systematic database of Springer Nature journal
content.
In line with the restriction against commercial use, Springer Nature does not permit the creation of a product or service that creates revenue,
royalties, rent or income from our content or its inclusion as part of a paid for service or for other commercial gain. Springer Nature journal
content cannot be used for inter-library loans and librarians may not upload Springer Nature journal content on a large scale into their, or any
other, institutional repository.
These terms of use are reviewed regularly and may be amended at any time. Springer Nature is not obligated to publish any information or
content on this website and may remove it or features or functionality at our sole discretion, at any time with or without notice. Springer Nature
may revoke this licence to you at any time and remove access to any copies of the Springer Nature journal content which have been saved.
To the fullest extent permitted by law, Springer Nature makes no warranties, representations or guarantees to Users, either express or implied
with respect to the Springer nature journal content and all parties disclaim and waive any implied warranties or warranties imposed by law,
including merchantability or fitness for any particular purpose.
Please note that these rights do not automatically extend to content, data or other material published by Springer Nature that may be licensed
from third parties.
If you would like to use or distribute our Springer Nature journal content to a wider audience or on a regular basis or in any other manner not
expressly permitted by these Terms, please contact Springer Nature at
onlineservice@springernature.com