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EDITORIAL

Viridans group streptococci: a reservoir of resistant bacteria


in oral cavities
A. Bryskier

AVENTIS Pharma, Romainville, France


The worldwide spread of erythromycin A-resistant streptococci, including Streptococcus
pneumoniae, is of concern. Many studies have demonstrated that the viridans group
streptococci can be a reservoir of erythromycin A resistance. Within oral streptoccoci, an
important difference in the susceptibility pattern has been noted. The purpose of this
short editorial is to highlight the importance of this group of bacteria as a reservoir of
resistance to erythromycin A and the possible transfer of resistance to S. pneumoniae and
S. pyogenes.
Keywords Viridans group streptococci, penicillan resistance, S. pneumoniae, S. pyogenes,
erythromycin
Clin Microbiol Infect 2002; 8: 65–69

The nasooropharynx is the first line of defense evidence to show that there is extensive exchange
against infections. The microflora is part of the of genetic information between these species [2].
host defense system which is established during The oral streptococci are normal commensals of
the first week of life. In the nasal cavities, the the human mouth and play a role in resistance to
bacterial flora is mainly composed of coryneforms colonization by other bacterial species such as
and coagulase-negative staphylococci, but in the staphylococci. Colonization is inhibited by hydro-
oropharynx the dominant bacterial inhabitants are gen peroxide production by some oral streptococ-
the oral streptococci. The different species of oral cal species. However, it offers a pool of genetic
streptococci are not distributed uniformly in these material which can undergo gene shuffling with
cavities. other bacteria, including pathogenic species, and
Currently, at least 18 species are recognized, lead to the emergence of resistant strains [3]. Inter-
since the taxonomy of viridans group streptococci est has been renewed in these species due to the
has undergone considerable revision in recent emergence and spread of bacterial resistance
years. The mitis group contains the largest number within respiratory microorganisms to penicillin
of named species of oral streptococci. The species G and erythromycin A and also the possibility
or group species comprising these streptococci are of transferring genetic material from oral strepto-
S. salivarius, S. mutans, the Anginosus group (S. cocci to S. pneumoniae or S. pyogenes. Antibiotic
anginosus, S. constellatus and S. intermedius), S. resistance within these oral streptococcal species
sanguis and the S. mitis group [1]. Data from rRNA may act as a reservoir of resistance. As viridans
show that S. pneumoniae belongs to the mitis group group streptococci form part of the normal flora, it
of oral streptococci. Though the main S. pneumo- is hypothesized that the presence of a resident
niae habitat is considered to be the nasopharynx microflora in the throat is important to protect
rather than the oral cavity, S. pneumoniae is closely against the invasive capacity of S. pyogenes [4,5].
related to S. oralis and S. mitis, and there is enough In vitro and in vivo studies have demonstrated
that the viridans group streptococci inhabiting the
oropharynx suppress the growth of Gram-positive
cocci and bacilli but are not responsible for growth
Corresponding author and reprint requests: A. Bryskier, control of Gram-negative bacteria in vivo.
AVENTIS Pharma, 102, route de Noisy, 93235 Romainville, It has also been shown that there is heterogene-
France
Tel: þ33 1 49 91 51 21
ity in antibiotic susceptibility among species in the
Fax: þ33 1 49 91 50 20 group, especially for penicillin G and erythromy-
E-mail: andre.bryskier@aventis.com cin A and derivatives [6].

ß 2002 Copyright by the European Society of Clinical Microbiology and Infectious Diseases
66 Clinical Microbiology and Infection, Volume 8 Number 2, February 2002

It has been demonstrated that uptake of DNA S. anginosus. In Japan, isolates containing erm(B)
from related bacterial species present in the same and mef(E) were equally represented in a 1999
ecologic niche, such as S. mitis, S. oralis and S. study [19].
gordonii, followed by recombination into the chro- The variation in antibacterial resistance within
mosome, can provide S. pneumoniae with ‘new the different viridans group streptococcal species
genes’. Mosaic pbp genes found in clinical isolates has been demonstrated in a study from the UK [11]
of S. pneumoniae resistant to penicillin G are an and in another from Taiwan [20].
example of replacement of parts of susceptible In the Taiwan study, a bimodal distribution of
genes by sequences from related species. S. oralis erythromycin A susceptibility has been shown in
and S. mitis are likely donors of some of the the anginosus group of streptococci, in S. mitis
sequences [7,8]. Another example, the transforma- and in S. salivarius, with erythromycin A MIC50
tion of S. pneumoniae isolates from optochin sus- and MIC90 values of 0.06 mg/L and >64 mg/L,
ceptible to optochin resistant, has been observed respectively. S. mitis was the most resistant species,
using S. oralis chromosomal DNA as donor [9]. with only 50% of the isolates being susceptible
In vitro transfer of fluoroquinolone determinants to erythromycin A (MIC50 0.25 mg/L, MIC90 
from viridans group streptococci to S. pneumoniae 512 mg/L); S. oralis isolates were poorly susceptible
has also been demonstrated [10]. to erythromycin A (only 45% were susceptible),
Viridans group streptococci are mainly in- with erythromycin A MIC50 and MIC90 values of 4.0
volved in endocarditis or infection in neutropenic and 512 mg/L, respectively, followed by S. san-
patients. As was shown in a recent survey in the guis (47% susceptible), with erythromycin A MIC50
the UK [11], 86% of the 607 clinical isolates from and MIC90 values of 2.0 and 512 mg/L, respec-
endocarditis patients were viridans group strep- tively. The species most susceptible to erythromy-
tococci, and four main species accounted for over cin A was S. mutans (100%), with erythromycin A
two-thirds of the isolates. Some 15% of S. oralis, MIC50 and MIC90 values of <0.03 and 0.25 mg/L,
14.5% of S. sanguis and 5.5% of S. gordonii isolates respectively. In this study, there was a high inci-
had reduced susceptibility to penicillin G, whereas dence of penicillin G and tetracycline resistance
all S. bovis type 1 and S. mutans isolates were combined with resistance to erythromycin A.
susceptible to penicillin G and erythromycin A. This fact was also demonstrated by other studies
There have been few epidemiologic surveys in [21].
patients. In 1996, 56% of viridans streptococci isolates
In the Netherlands, in a recent study carried out were resistant to penicillin G in the USA. This
from September 1995 to June 1999, 342 isolates antibacterial agent had exhibited good antistrep-
were recovered and only 11 (3.2%) were consid- tococcal activity 20 years ago [22,23]. In Canada,
ered to be resistant to erythromycin A, which was of 418 viridans streptococcal strains isolated from
regarded as a moderate increase in comparison blood culture between May 1995 and March 1997,
with a previous period in the same hospital, when 28%, 12%, 40%, 4%, 24% and 34% were interme-
2.6% of the isolates were resistant to erythromycin diately susceptible or resistant to penicillin G,
A [12,13]. Comparable data were reported from amoxicillin, ceftriaxone, erythromycin A, clinda-
Argentina in 1996 [14]. A higher resistance rate mycin, tetracycline, and co-trimoxazole, respec-
had been reported from Spain, with 14.3% and tively. Two hundred and thirty-six isolates were
17.7% of erythromycin A resistance in 1994 and resistant to at least one or more antibacterials.
1999, respectively [15,16]. In France, the incidence Within the 236 strains, 125, 56, 17 and 13 were
rate of erythromycin A within the viridans group S. mitis, S. sanguis, S. salivarius, and non-typable,
streptococci was about 40% between 1988 and 1995 respectively. For an erythromycin A MIC ¼
[17]. 0.5 mg/L, 53%, 32%, 41% and 62% of these isolates
In the study from the Netherlands, the presence were resistant to erythromycin A, respectively [24].
of erm(B), erm(TR) and mef(A) genes was demon- During 1999, 198 pharyngeal exudates obtained
strated. The erm(B)-containing isolates were domi- from outpatients in Madrid were studied. A con-
nant, accounting for 68.2% of the isolates; this trol group of 50 healthy persons (adults and chil-
was also found in another study [18]. The erm(TR) dren) who had not received antibiotic treatment
gene-containing isolates are uncommon, and are in the previous 3 months were collected. Of the
only reported in one study [13] from two isolates of viridans group streptococci, 60.8% were resistant

ß 2002 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 8, 65–69
Editorial 67

to erythromycin A or azithromycin, due to an A-resistant streptococci were found to persist for


mef(A) gene (MICs ranged from 2 to 4 mg/L), up to 43 weeks in some subjects [32]. The ecological
and 15.6% were resistant to erythromycin A, effect on the oral commensal flora during admin-
due to an MLSB mechanism of resistance. In istration of telithromycin and clarithromycin has
healthy persons, 50.7% of the viridans group strep- also been investigated in healthy volunteers. In the
tococci isolates were resistant to erythromycin A, oropharyngeal microflora, the viridans strepto-
harboring an mef(A) gene, and 12.7% harbored an cocci population decreased significantly with both
erm gene. No detail at the species level has been compounds, but telithromycin MICs remained
reported [25]. low (MICs ranged from 0.016 to 1.0 mg/L) [33].
Since the first report of decreased erythromycin The resistance profiles of some species of vir-
susceptibility, in 1959, in S. pyogenes [26], erythro- idans group streptococci can represent a good
mycin A resistance has spread worldwide. The marker for the risk of emergence of resistance to
same pattern occurred with S. pneumoniae, with erythromycin A in a given bacterial population of
an increased incidence rate of resistance to ery- S. pyogenes or S. pneumoniae. The transfer by con-
thromycin A and with full cross-resistance jugation of erythromycin A resistance from viri-
between erythromycin A, clarithromycin and azi- dans group streptococci to S. pneumoniae, and vice
thromycin. versa, have been demonstrated [34], as well as
Many studies have investigated the relationship from strains of S. pyogenes to S. pyogenes BMI37
between antibacterial treatment of a patient and and Enterococcus faecalis [35].
that patient’s risk of carrying or being colonized or
infected by a penicillin G- and/or erythromycin A-
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ß 2002 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 8, 65–69

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