Streptococcus Anginosus Group Infections: Management and Outcome

Journal of Infection and Public Health 13 (2020) 1749–1754

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Original Article

Streptococcus anginosus group infections: Management and outcome

at a tertiary care hospital

a,∗ a a b c a

F. Al Majid , A. Aldrees , M. Barry , K. Binkhamis , A. Allam , A. Almohaya

Infectious Diseases Division, Department of Medicine, King Saud University, King Khalid University Hospital, Riyadh, Saudi Arabia

Microbiology Unit, Department of Pathology, King Saud University, King Khalid University Hospital, Riyadh, Saudi Arabia

Department of Internal Medicine & Critical Care, King Abdullah bin Abdulaziz University Hospital, Princess Nourah Bint Abdulrahman University, Riyadh,

Saudi Arabia

a r t i c l e i n f o a b s t r a c t

Article history: Background: Data on patients with invasive Streptococcus anginosus group (SAG) infections is limited, as

Received 27 April 2020

it’s been considered commensal bacteria in the human microbiota. We conducted an analysis of SAG

Received in revised form 7 July 2020

infections to assist clinicians in understanding their burden and clinical outcomes.

Accepted 28 July 2020

Methods: A retrospective study of medical records, identifying invasive SAG bacteria of sterile-site isolates

that were managed from May 2015 to April 2017, at a tertiary care hospital in Riyadh, Saudi Arabia.

Keywords:

Demographic data, clinical presentation, site of infection, antibiotic use, and outcome were recorded and

Streptococcus anginosus group

analyzed to identify factors associated with poor outcome and/or polymicrobial growth.

Burden

Abscess Results: We identiﬁed 105 cases of SAG infections in adults, with 52% of the patients being male and the

Polymicrobial mean age of 52.4 years with comorbidities occurring in more than half of the cases such as diabetes (38%)

Mortality and malignancy (15%). Overall mortality was 6%, and it was statistically associated with age older than

65 years, polymicrobial growth and a history of malignancy. The infection frequencies were skin and soft

tissue infections (SSTI; 55%), intra-abdominal infections (24%), bacteremia (14%), genitourinary infec-

tions (8.5%), and pleuropulmonary infections (5%). Abscesses accounted for 68% of cases. Polymicrobial

infection (46%) with Enterobacteriaceae and Gram-negative anaerobes coincided with SAG infection.

Polymicrobial growth was signiﬁcantly associated with abscess formation, intra-abdominal source of

infections, and poor outcome. In addition, death in patients with SAG was statistically associated with

patients older than 65 years of age and those with history of cancer or transplant.

Conclusion: SSTIs and intra-abdominal infections are the most common clinical presentations in our

cohort. Bacteremia was uncommon; however, the prognosis is less favorable. Overall susceptibility to

penicillin was 91%, therefore ␤-lactam antibiotics are the drug of choice and additional coverage for

anaerobic and gram-negative bacteria should be considered for intra-abdominal collection and solid or

organ abscesses.

Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.

org/licenses/by-nc-nd/4.0/).

Introduction cus intermedius, and Streptococcus constellatus [1,2]. SAG bacteria

are considered commensals of mucosal membranes, i.e., of the

The Streptococcus anginosus group (SAG), commonly referred oropharyngeal [2], gastrointestinal, and genitourinary tract [3],

to as the Streptococcus milleri group, is among ﬁve subgroups with vaginal colonization resulting from spread from the digestive

within the viridans-group streptococci that includes three distinct system [4]. There have been several studies demonstrating that SAG

species streptococcal species: Streptococcus anginosus, Streptococ- members are increasingly recognized as an etiology of invasive pyo-

genic infections at almost every sites in the body in both adults and

children [3,5–9]. SAG bacteria were initially recovered from dental

abscesses causing oral infections and are frequently isolated from

∗

Corresponding author. dental caries and periodontal diseases [9].

E-mail addresses: [email protected] (F. Al Majid), a m al [email protected] However, these bacteria are now increasingly being found to

(A. Aldrees), [email protected] (M. Barry), [email protected]

cause infection at any anatomical site in the body, including the

(K. Binkhamis), [email protected] (A. Allam), [email protected]

lungs, liver, brain, intra-abdominal areas, as well as the skin and

(A. Almohaya).

https://doi.org/10.1016/j.jiph.2020.07.017

BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1750 F. Al Majid et al. / Journal of Infection and Public Health 13 (2020) 1749–1754

Table 1

soft tissues [10–13]. Clinically, this group is associated with variable

Characteristics and laboratory ﬁndings of 105 patients.

clinical presentation, with a proclivity for causing pyogenic and sys-

temic infections with abscess formation [6,14–16]. The incidence of Variable n (%)

pyogenic invasive infections caused by SAG exceeds the combined

Age, median (years)

incidence of group A (Streptococcus pyogenes) and B (Streptococ- Above 65 years 15 (14.3%)

cus agalactiae) and different tertiary hospitals have reported an Below 65 years 90 (85.7%)

Sex

estimated incidence of 8.6–8.8/10,000 hospitalized patients [6].

Male 55 (52.4%)

The organisms in this group are microaerophilic, catalase-

Female 50 (47.6%)

␣

negative, gram-positive cocci that are often -hemolytic, although Comorbidities

␤

they may occasionally be -hemolytic or nonhemolytic. SAG bac- None 38 (36%)

Diabetes mellitus 36 (38%)

teria grow aerobically and anaerobically, forming minute colonies

Malignancies 16 (15%)

(less than 0.5 mm) and producing a sweetish caramel-like odor

Chronic renal failure 13 (12%)

related to the production of diacetyl [17,18]. They are generally

Pregnancy and postpartum 9 (8%)

␤

susceptible to -lactam antibiotics. Site of infection

Failure to properly identify the species in streptococcal iso- SSTI 58 (55%)

Intra-abdomen 25 (24%)

lates in routine diagnosis is a probable explanation for why the

Bacteremia 15 (14%)

pathogenicity of these species may have previously been over-

Genitourinary 9 (8.5%)

looked. Another reason may be that they are considered part of

Pleuropulmonary 6 (5%)

human commensals and are therefore commonly considered a Liver abscess 1(0.9%)

Brain abscess 1(0.9%)

contaminant, especially in diagnostic samples of polymicrobial

infections. Penicillin susceptibility

Resistant 6 (5%)

The three species in this group tend to be associated with a

Intermediate 4 (3%)

different clinical presentation [7]. S. anginosus, for example, is pre- Susceptible 95 (91%)

dominantly isolated from blood cultures and often presents as part Organisms isolated

Monomicrobial 57 (54%)

of a polymicrobial infection in patients with oral, head and neck,

Polymicrobial 48 (46%)

and abdominal abscesses [3,19,20]. S. intermedius is often present

Mortality

in brain abscesses, while S. constellatus is frequently isolated

No 99 (95%)

from soft tissue infections, respiratory tract and intra-abdominally Yes 6 (5%)

located abscesses [20–22]. However, these species’ associations

SSTI: Skin and soft tissue infection.

have recently been challenged, and discrepancies between per-

ceived species’ associations and clinical presentations may be due

with characteristics caramel odor) as well as negative catalase test

to different identiﬁcation methods [6,16]. An increasing number of

results [1]. Deﬁnite identiﬁcation was obtained using the VITEK 2

recent ﬁndings have shown that SAG members have a pathogenic

(BioMerieux,´ Marcy-l’Etoile,´ France) and isolates had been reported

effect in cystic ﬁbrosis [6,16,23,24]. Fortunately, the treatment of

as SAG and species was not identiﬁed. Testing for antimicrobial sus-

SAG infection is feasible, as most isolates are susceptible to ␤-

ceptibility had been performed using the VITEK 2 Streptococci AST

lactam antibiotics [25].

card and the E test (BioMerieux,´ Marcy-l’Etoile,´ France) gradient

Since the discovery of SAG in 1956, a number of case series

diffusion method for penicillin and ceftriaxone. Clinical & Labora-

have been published in the international literature. However, there

tory Standards Institute interpretive breakpoints were used [27].

has only been one study conducted in Saudi Arabia, in 1987 [26].

Data on surgical intervention, including drainage of abscesses and

Therefore, we aimed to describe the largest series of SAG infections

debridement of wounds, were recorded. The outcome was deter-

reported in Saudi Arabia to assist clinicians in better understanding

mined based on the inpatient survival of the SAG infectious episode.

the clinical presentations, potential risk factors, and management

Statistical analysis was performed by the SPSS software (version-

outcomes of SAG infection.

23, IBM Corp., Armonk, N.Y., USA) to explore the p-value using

Pearson chi-square test, and to subject study variables to calculate

Methodology the odds ratio and 95% conﬁdence interval. In addition, a dedicated

analysis was performed to identify the most signiﬁcant variables

associated with survival and/or polymicrobial growth using the

This was a retrospective study identifying all invasive SAG infec-

Pearson chi-square test, p-value and odds ratio.

tion cases from the database of all sterile-site isolates managed

over a two-year period from May 2015 to April 2017 at King Khalid

University Hospital in Riyadh. Demographic data were obtained Results

from the patient’s medical records, which included clinical features,

vital signs, site of infection, comorbidities, and details of recent We identiﬁed 105 deﬁnitive cases of SAG infections in adults

surgery. Other data collected were the presence of other organisms, over a period of 2 years (2015–2017), with 52% of cases being

antimicrobial susceptibility, and management including antibiotic males and the mean age being 48 years. The age of the largest

therapy, surgical intervention, and outcome. number of patients was in the range of 35–55 years (43%). More

We obtained approval from the Institutional Review Board of than half of the cases had one or more underlying comorbidi-

King Khalid University Hospital in Riyadh (IRB# E-19-4092) and ties, diabetes being the most common (n = 36, 38%), followed by

collected information on all patients with invasive SAG infections malignancies (n = 16, 15%), and chronic kidney disease (n = 13, 12%)

and their isolates. SAG bacteria were identiﬁed when cultured from (Table 1). Abscesses accounted for 72 cases (68%). Skin and soft

normally sterile sites and from other specimens with signiﬁcant tissue infections (SSTIs) were the most common (n = 58/105, 55%)

and predominant growth. Any culture with more than one organ- and included decubitus ulcers, pilonidal sinuses, abscesses of the

ism type was considered polymicrobial. peripheral extremities, and surgical site infections. Nine patients

We used the Standard laboratory method and SAG bacteria is had a genitourinary infections. Two pregnant woman, had abscess

recognized by its microaerophilic or anaerobic growth, the for- of bartholin gland, presented with pain and swelling of the left labia

mation of minute colonies (alpha, beta or non-hemolytic colonies and was treated by the incision of the gland and drainage of pus

F. Al Majid et al. / Journal of Infection and Public Health 13 (2020) 1749–1754 1751

with a pure growth of S. anginosus, and seven postpartum women from the gastrointestinal tract, where SAG bacteria are known to

with infected episiotomy wound (three patients with a pure growth be commensal inhabitants [31,32]. Most organisms found in cul-

of SAG and four patients with a polymicrobial of Escherichia coli and tures isolated from intra-abdominal collections of pus have been

S. anginosus). The prevalence of diabetes in SSTI patients was high, identiﬁed as SAG bacteria [33]. The tendency of SAG bacteria to

as expected, at 34%. Most cases of SSTI were managed and sent form abscesses has long been recognized. However, the reasons

home after surgical drainage and treatment with antibiotics in the for this are not yet completely understood, and it may be that

Emergency Department. mixed infection with other microbes, such as Eikenella corrodens,

The second most common type of infection was the abdomi- Enterobacteriaceae and gram-negative anaerobes encourages rapid

nal infections, which included appendicular abscesses, post-sleeve replication of SAG bacteria [31–33]. Another potential virulence

leaks, cholangitis, colon cancer with leakage, perforated appen- factor is the frequent presence of polysaccharide capsules, which

dices, post-abdominal surgeries, and abdominal wound infections. hinder phagocytosis, in SAG species [34].

The most common risk factors for this local infection were bariatric In contrast to the abovementioned ﬁndings, other studies

surgery (10 patients), appendicular abscess (nine patients), and have reported different clinical presentations [26,35,36]. Intra-

appendectomy (six patients). There were 15 patients with bac- abdominal infections were nearly always polymicrobial (OR: 2.99,

teremia (14%), and transthoracic echocardiograms were performed 95%CI = 1.25−7.15), with Enterobacteriaceae and gram-negative

in nine of them; ventricular septal defects and infective endo- anaerobes present, and were generally seen as complications of an

carditis were conﬁrmed in only one case. The site of origin of the intestinal surgery or procedure, particularly after appendectomy or

bacteremia was determined clinically in ﬁve (31%) of bacteremic bariatric surgery. All patients with abdominal collection of pus were

patients; one patient had a liver abscess and four had an infec- treated with both antibiotics and surgical drainage using a percu-

tion of the lower extremities (diabetic foot). Infections of solid taneous approach. Surprisingly, no single case of intra-abdominal

organs were documented in only eight (8%) patients (pleuropul- infection yielded a positive blood culture, thus differing from pre-

monary infections, six; liver abscess, one; and brain abscess, one). vious studies that reported a frequency of 20–70% [30].

Empyema (ﬁve patients) was more common than lung abscess (one Only 5% of patients in our study suffered from pleuropulmonary

patient). Polymicrobial infections were seen in 48 (45%) patients, infection (empyema and lung abscess) due to SAG, in contrast

with members of the Enterobacteriaceae (mainly E. coli) being to other studies which reported an incidence of 20% [12,21,37].

the most common (n = 10/48, 21%), followed by Gram-negative Incidence of empyema is higher than that of lung abscess, which

anaerobes (n = 6/48, 12%). Penicillin susceptibility of SAG bacteria agrees with other reports [34–36]. All patients with pleuropul-

showed that 95 (91%) isolates were sensitive, four isolates (3%) had monary infections in this study had negative blood cultures, thus

intermediate resistance, and six (6%) were resistant. Three of the contrasting a study that reported a percentage of 58% of patients

penicillin-resistant isolates were also resistant to cephalosporin, with concomitant bacteremia [29].

and all (100%) isolates were sensitive to vancomycin. Manage- SAG causing Bartholin gland abscess in these two patients is

ment included antibiotics alone in 11 (10%) patients, while 94 rarely reported as E. coli and Bacteroides species are the common-

(90%) patients were treated with a combination of antibiotics and est organisms [37]. Drainage of the abscess was done through a

surgical intervention. The majority (n = 63, 60%) received combina- small surgical cut under local anesthesia in the out- patient clinic

tion therapy with clindamycin, metronidazole, or cephalosporin, as considered the primary treatment [38].

36 (34%) were treated with ␤-lactam antibiotics, and six (6%) with Monomicrobial SAG infection was the only etiology of lung

vancomycin. The outcome was poor in six (5.5%) patients. Statis- abscess and empyema in all patients with pulmonary infec-

tically signiﬁcant risk factors for death in these SAG cases were tions, and treatment with antibiotics and surgical drainage proved

the age older than 65 years or history of cancer or transplant enough [39]. Despite there being 21 patients with bacteremia, only

(Tables 2 and 3). one patient presented with endocarditis, and this patient was suc-

Given the large proportion of polymicrobial growth in cessfully treated with antibiotics. Over half (57%) of the bacteremia

this series, we investigated the associated factors with the patients were either diabetic or immunosuppressed, and only 24%

microbiological growth type and found signiﬁcant statistical had polymicrobial infections (p-value = 0.247). Several studies have

associations between polymicrobial growth and abscess forma- found varying rates of bacteremia; however, the occurrence of

tion (OR: 2.36, 95%CI = 1.06−5.22), intra-abdominal infections infective endocarditis was rare in comparison to that of other strep-

(OR: 2.99, 95%CI = 1.25−7.15), and death outcome (OR: 9.56, tococcal infections [11,12,40,41].

95%CI = 1.13–80.8). There was no statistical associations between Penicillin susceptibility tests showed extremely low (5%) peni-

polymicrobial growth with age category, gender, past medical his- cillin resistance, with intermediate susceptibility observed in only

tory, bacteremia, genitourinary, SSTI, or pleuropulmonary (Table 4). 3% of patients, a ﬁnding like that of other studies reporting peni-

cillin sensitivity in 87–94% isolates [29,30]. Nineteen percent of our

bacteremia patients had intermediate susceptibility, indicating a

Discussion higher proportion in this group.

The prognosis of SAG infection was generally good, and only 5%

This study showed almost equal sex distribution (52% males of patients succumbed. In these cases, uncontrolled sepsis due to

and 48% females) for SAG infections among adults; this is not in Gram-negative rods was the likely cause of deterioration and shock

agreement with other studies, which have generally reported a given the signiﬁcant association between death and polymicrobial

male-to-female ratio of 3:2 [14,27,28], apart from a recent study by growth observed in our analysis. Similar rates of mortality, rang-

Shaukat et al., which reported a higher incidence amongst females ing from 2 to 4% in the nonbacteremic group to 11% in bacteremia

(55%) [29]. Comorbidities, including diabetes mellitus, neoplasm patients, have been reported in other studies [10,11]. The mortality

and chronic renal failure were present in 64% of our patients. The rate of 10% in our bacteremia population indicates that prognosis is

skin and soft tissues were the most dominant sites of infection, a less favorable with bacteremia [29]. Unfortunately, species infor-

ﬁnding consistent with those of other reports [10,21]. Most of the mation for SAG isolates was not available to better delineate the

SSTIs were abscesses. Intra-abdominal infections with abscesses clinical presentation and outcome.

accounted for about 24% of all cases, a frequency like that reported Our study provides valuable information regarding the com-

in several previous studies [3,10,11,30]. SAG infections within mon risk factors and presentations of SAG infections, in addition

the abdominal cavity are not surprising, owing to local invasion to the relationships between severe infection and the presence

1752 F. Al Majid et al. / Journal of Infection and Public Health 13 (2020) 1749–1754

Table 2

Characteristics of patients who died from Streptococcus anginosus group infections.

Age, sex Underlying condition Site of infection Isolates grown Antibiotics used

60, F Cholangiocarcinoma Blood Klebsiella pneuomoniae ␤-lactam

63, M Diabetes mellitus Abdomen Escherichia coli Vancomycin and ceftazidime

63, M Oropharyngeal cancer Neck ulcer Pseudomonas aeruginosa Vancomycin and tazocin

77, F None Breast abscess Morganella morganii Vancomycin and tazocin

81, M Diabetes mellitus Blood Bacteroides fragilis Vancomycin and tazocin

56, M Diabetes mellitus and cancer Thoracic empyema Klebsiella pneuomoniae Vancomycin and tazocin

82, M Rectal cancer with metastasis Fournier’s gangrene Escherichia coli Vancomycin + beta-lactam + metronidazole + Ciproﬂoxacin

M: male, F: female.

Table 3

The study variables stratiﬁed by the outcome among patients with Streptococcus anginosus infections.

Study variables Death n (%) Survived n (%) p-Value* OR (95% CI)

Above 65 3 (42.9) 12 (12.2) 5.38 (1.07−27.01)

Age (years) 0.025

Below 65 4 (57.1) 86 (87.8) Ref. [1]

Female 2 (28.6) 48 (49) NS

Gender 0.296

Male 5 (71.4) 50 (51) NS

Yes 0 (0) 18 (18.4) NS

Medically free 0.213

No 7 (100) 80 (81.6) NS

Yes 3 (42.9) 30 (30.6) NS

DM 0.5

No 4 (57.1) 68 (69.4) NS

Yes 4 (57.1) 12 (12.2) 9.56 (1.9–48.01)

Cancer or transplant 0.001

No 3 (42.9) 86 (87.8) Ref. [1]

History of obstetric Yes 0 (0) 9 (9.2) NS

0.403

procedure No 7 (100) 89 (90.8) NS

Yes 2 (28.6) 41 (41.8) NS

Abscess 0.49

No 5 (71.4) 57 (58.2) NS

Infection site: NS

Yes 2 (28.6) 16 (16.3) NS

Bacteremia 0.406

No 5 (71.4) 82 (83.7) NS

Yes 0 (0) 11 (11.2) NS

Genito-urinary 0.349

No 7 (100) 87 (88.8) NS

Yes 1 (14.3) 30 (30.6) NS

Intra-abdomen 0.36

No 6 (85.7) 68 (69.4) NS

Yes 3 (42.9) 34 (34.7) NS

Skin/soft tissue 0.662

No 4 (57.1) 64 (65.3) NS

Yes 1 (14.3) 7 (7.1) NS

Pleuro-pulmonary 0.491

No 6 (85.7) 91 (92.9) NS

NS: not signiﬁcant. OR: odds ratio. CI: conﬁdence interval.

p-Value is signiﬁcant at <0.05.

Table 4

Study variables stratiﬁed by whether the growth of Streptococcus anginosus is poly- or mono-microbial among patients in this series.

Study variables Poly-microbial n (%) Mono-microbial n (%) p-Value* OR (95% CI)

≥65 10 (20.8) 5 (8.8) NS

Age (years) 0.078

<65 38 (79.2) 52 (91.2) NS

Female 21 (43.8) 29 (50.9) NS

Gender 0.466

Male 27 (56.3) 28 (49.1) NS

Yes 7 (14.6) 11 (19.3) NS

Medically free 0.523

No 41 (85.4) 46 (80.7) NS

Yes 17 (35.4) 16 (28.1) NS

DM 0.419

No 31 (64.6) 41 (71.9) NS

Yes 10 (20.8) 6 (10.5) NS

Cancer or transplant 0.143

No 38 (79.2) 51 (89.5) NS

Yes 25 (52.1) 18 (31.6) 2.36 (1.06–5.22)

Complication, abscess 0.033

No 23 (47.9) 39 (68.4) Ref. [1]

Infection site

Yes 6 (12.5) 12 (21.1) NS

Bacteremia 0.247

No 42 (87.5) 45 (78.9) NS

Yes 5 (10.4) 6 (10.5) NS

Genito-urinary 0.985

No 43 (89.6) 51 (89.5) NS

Yes 20 (41.7) 11 (19.3) 2.99 (1.25−7.15)

Intra-abdomen 0.012

No 28 (58.3) 46 (80.7) Ref. [1]

Yes 15 (31.3) 22 (38.6) NS

Skin/soft tissue 0.432

No 33 (68.8) 35 (61.4) NS

Yes 2 (4.2) 6 (10.5) NS

Pleuro-pulmonary 0.221

No 46 (95.8) 51 (89.5) NS

Death 7 (14.6) 0 (0) 9.56 (1.13–80.8)

Outcome 0.014

Survived 41 (85.4) 57 (100) Ref. [1]

NS: not signiﬁcant. OR: odds ratio. CI: conﬁdence interval.

p-Value is signiﬁcant at <0.05.

F. Al Majid et al. / Journal of Infection and Public Health 13 (2020) 1749–1754 1753

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This research was funded by the deanship of Scientiﬁc Research

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at Princess Nourah Bint Abdulrahman University through the Fast-

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