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Group B streptococcal colonization in elderly women

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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
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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
(20172019) 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 participantscharacteristics,
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
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* 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 [46]. A Danish
study showed that from 2005 to 2018, the incidence of
invasive GBS in adults aged 6574 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 [812]. 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 participantsdata
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-
pantsidentifiable 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:
201601669).
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 (ToddHewitt 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
lEtoile, 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 participantscharacteristics/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 Fishers
exact probability test if the frequency was less than 5.
For direct comparisons, distribution analyses were also
performed by using the chi-square test, Fishers 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 participantsdemo-
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-
ticipantsdemographic 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 Participantsdemographic characteristics and risk factors for GBS acquisition overall and by GBS carrier status
Participantscharacteristics/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) 6998 6084 6098 Na
Participantsorigin 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 participantssexual 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 Fishers exact test (indicated by *); distribution analysis was also performed by using the chi-square test (indicated by §),
Fishers 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 [812]. 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 [711,25,
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 [3134]. 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.
Authorscontributions
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 participantssamples 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
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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: 201601669).
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 Womens 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
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... It typically occurs in children aged 2-16 years and is extremely rare in elderly people [1][2][3]. Streptococcus agalactiae (Group B Streptococcus) is a bacterium that commonly colonizes the gastrointestinal and vaginal tracts in women, and causes invasive infections in neonates, the elderly and immunocompromised subjects [4]. To date, only two cases of BDD caused by S. agalactiae have been reported, occurring in an infant [5] and a diabetic adult [6]. ...
... S. agalactiae infection in adults has increasingly become a public health problem with an increasing prevalence of risk factors, including old age and diabetes [10]. Although the vaginal S. agalactiae colonization rate in women aged ≥ 60 is 17% [4], the overall prevalence of S. agalactiae in skin and soft tissue infections is 1.89% at all ages [10]. In the present case, the minor finger trauma from garbage cans could have promoted S. agalactiae autoinoculation from the gastrointestinal or vaginal tracts. ...
... Typically causing neonatal sepsis and meningitis, GBS results in irreversible neurological damage such as cerebral palsy, hearing loss, and vision impairment affecting approximately 37,000 infants annually, with a case fatality rate of approximately 5% [1,2,4,5]. Furthermore, there has been a more than twofold increase in aggressive GBS cases among older adults (≥65 years) over the past two decades, especially those with comorbidities like diabetes and obesity, with a case fatality rate ranging from 10 to 15% [2,[6][7][8][9]. ...
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... [35][36][37][38][39][40][41]. As an illustration, the presence and changes of group B Streptococcus, which is a member of Streptococcus, in the vagina can cause shedding of vaginal epithelial cells to induce rising infection and inflammation [42], stimulate host immune response [43], and is detected at a higher rate in older women [44]. Group B Streptococcus colonization is impacted by dysbiosis of the vaginal flora, altered vaginal pH, decreased abundance of Lactobacillus, and increased non-commensal bacteria. ...
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Background: The clindamycin-resistant erythromycin-susceptible (CRES) phenotype is rare in Streptococcus agalactiae (group B streptococci). We aimed to determine the molecular characteristics of CRES S. agalactiae using whole genome sequencing (WGS). Methods: Sixty-six S. agalactiae isolates obtained from blood (N=26), cerebrospinal fluid (N=10), urine (N=17), and vaginal discharge (N=13) between 2010 and 2017 in Korea were subjected to WGS. Based on the WGS data, we analyzed antimicrobial resistance (AMR) determinants, sequence types (STs), capsular polysaccharide (CPS) genotypes, and virulence gene profiles, and constructed a phylogenetic tree. We included the clindamycin-susceptible erythromycin-resistant (CSER) phenotype for comparison. Results: We identified seven CRES S. agalactiae isolates from urine (N=5) and vaginal discharge (N=2) collected between 2010 and 2011. All CRES isolates harbored AMR determinants of lnu(B), lsa(E), and aac(6')-aph(2″), revealed ST19 and CPS genotype III, and had a virulence gene profile of rib-lmb-cylE. Phylogenetic tree analysis revealed that all CRES isolates belonged to the same cluster, suggesting a clonal distribution. In contrast, seven CSER isolates showed a diverse distribution and clustered separately from the CRES isolates. Conclusions: CRES isolates collected between 2010 and 2011 showed a unique cluster with ST19 and CPS genotype III in Korea. This is the first report on WGS-based characteristics of S. agalactiae in Korea.
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Previous epidemiology reports on invasive Streptococcus agalactiae (GBS) infections in Denmark did not include all patient age groups. The aim of this study was therefore to analyze the GBS incidence in all age groups during the period 2005–2018 and to present the serotype distribution and the antibiotic susceptibility. Data were retrieved from the Danish laboratory surveillance system, and these included data on typing and susceptibility testing for erythromycin and clindamycin. Early-onset disease (EOD) (mean incidence 0.17 per 1,000 live births) and late-onset disease (LOD) (mean incidence 0.14 per 1,000 live births) showed a low level during the period. The incidence was stable in the age groups 91 days to 4 years, 5–19 years, and 20–64 years. From 2005 to 2018, the incidence in the elderly showed a significantly increasing trend (P < 0.05), that in the 65–74 years increased from 3.23 to 8.34 per 100,000, and that in the 75+ years increased from 6.85 to 16.01 per 100,000. Erythromycin and clindamycin resistance fluctuated over the period; however, the overall trend was increasing. Data showed that EOD and LOD incidence continued to be low, whereas an increasing trend in GBS infections in the elderly was observed. The prevalence of erythromycin and clindamycin resistance increased from 2005 to 2018.
Article
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Background: Clindamycin is a lincosamide antibiotic used to treat staphylococcal and streptococcal infections. Reports of clinical Streptococcus agalactiae isolates with the rare lincosamide resistance/macrolide susceptibility (LR/MS) phenotype are increasing worldwide. In this study, we characterised three clinical S. agalactiae strains with the unusual L phenotype from China. Methods: Three clinical S. agalactiae strains, Sag3, Sag27 and Sag4104, with the L phenotype were identified from 186 isolates collected from 2016 to 2018 in Shanghai, China. The MICs of clindamycin, erythromycin, tetracycline, levofloxacin, and penicillin were determined using Etest. PCR for the lnu(B) gene was conducted. Whole genome sequencing and sequence analysis were carried out to investigate the genetic context of lnu(B). Efforts to transfer lincomycin resistance by conjugation and to identify the circular form by inverse PCR were made. Results: Sag3, Sag27, and Sag4104 were susceptible to erythromycin (MIC ≤0.25 mg/L) but resistant to clindamycin (MIC ≥1 mg/L). lnu(B) was found to be responsible for the L phenotype. lnu(B) in Sag3 and Sag27 were chromosomally located in an aadE-spw-lsa(E)-lnu(B) resistance gene cluster adjacent to an upstream 7-kb tet(L)-cat resistance gene cluster. Two resistance gene clusters were flanked by the IS6-like element, IS1216. Sag4104 only contained partial genes of aadE-spw-lsa(E)-lnu(B) resistance gene cluster and was also flanked by IS1216. Conclusion: These results established the presence of the L phenotype associated with lnu(B) in clinical S. agalactiae isolates in China. The lnu(B)-containing multi-resistance gene cluster possibly acts as a composite transposon flanked by IS1216 and as a vehicle for the dissemination of multidrug resistance among S. agalactiae.
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Background: Maternal rectovaginal colonization with group B Streptococcus (GBS) is the most common pathway for GBS disease in mother, fetus, and newborn. This article, the second in a series estimating the burden of GBS, aims to determine the prevalence and serotype distribution of GBS colonizing pregnant women worldwide. Methods: We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus), organized Chinese language searches, and sought unpublished data from investigator groups. We applied broad inclusion criteria to maximize data inputs, particularly from low- and middle-income contexts, and then applied new meta-analyses to adjust for studies with less-sensitive sampling and laboratory techniques. We undertook meta-analyses to derive pooled estimates of maternal GBS colonization prevalence at national and regional levels. Results: The dataset regarding colonization included 390 articles, 85 countries, and a total of 299924 pregnant women. Our adjusted estimate for maternal GBS colonization worldwide was 18% (95% confidence interval [CI], 17%-19%), with regional variation (11%-35%), and lower prevalence in Southern Asia (12.5% [95% CI, 10%-15%]) and Eastern Asia (11% [95% CI, 10%-12%]). Bacterial serotypes I-V account for 98% of identified colonizing GBS isolates worldwide. Serotype III, associated with invasive disease, accounts for 25% (95% CI, 23%-28%), but is less frequent in some South American and Asian countries. Serotypes VI-IX are more common in Asia. Conclusions: GBS colonizes pregnant women worldwide, but prevalence and serotype distribution vary, even after adjusting for laboratory methods. Lower GBS maternal colonization prevalence, with less serotype III, may help to explain lower GBS disease incidence in regions such as Asia. High prevalence worldwide, and more serotype data, are relevant to prevention efforts.
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