STREPTOCOCCUS ANGINOSUS Streptococcus anginosus Group Bacteria: No longer a Case of Mistaken Identity Ralph K. Funckerstorff et al. Article Review by Andrea Prinzi
INTRODUCTION In 1906, two scientists (Andrew and Horder) from the Lancet attempted to classify the genus Streptococcus The name S. anginosus was proposed and it was described as resembling S. pyogenes in its haemolytic powers. They suggested the organism was associated with: pharyngitis, endocarditis, appendicitis, mastoiditis and empyema.
TAXONOMY S. anginosus has been the subject of much taxonomic confusion! Previously called S. milleri Recent comparative whole genome analysis concluded there are 3 distinct species in the SAG group (S. anginosus, S. constellatus, S. intermedius) Whiley and colleagues used Multilocus sequence analysis (MLSA) to further sub-speciate this group and further definte it
TAXONOMY 1999: Whiley and colleagues looked at the beta-hemolytic group C strep members of the SAG group and further speciated them. These were further broken down into two groups: DNA Group 1 represented a subspecies of S. constellatus DNA Group II represented a subspecies of S. anginosus
TAXONOMY 2013: Jensen and colleagues performed MLSA (in combination with 16S and phenotypic analyses) on 123 SAG isolates Isolates were from seven countries: UK, US, France, Denmark, Sweden, Netherlands and Japan Isolates were from mixed sources (sore throats, bacteremia, oral and non-oral clinical isolates, reference lab isolates) Using MLSA, they discovered 2 main things: 1. The SAG bacteria are a phylogenetically different branch within the genus Streptococcus II. SAG can be further sub-divided into 7 clusters
S. ANGINOSUS CLUSTERS 1 S. intermedius 2 S. constellatus subspecies constellatus 3 S. constellatus subspecies pharyngis 4 S. constellatus subspecies viborgensis Isolated from patients with a sore throat 5 Believed to be a separate taxon S. anginosus genomsubspecies AJ1 6 Primarily Lancefield Group F isolates S. anginosus subspecies anginosus 7 S. anginosus subspecies whileyi Primarily beta-hemolytic Lancefield Group C isolates Predominantly from patients with sore throats
VIRULENCE FACTORS In the oral cavity: SAG adheres to fibronectin, fibrinogen and laminin. This has been thought to be a factor in the organism s ability to cause endocarditis
VIRULENCE FACTORS A novel cholesterol-dependent cytotoxin called intermedilysin Targets human cells and causes direct cell membrane damage in human erythrocytes and in cell lines from major organs Expression of this is controlled by autoinducer-2 (AI-2) AI-2 is used by bacterial to talk to each other and regulate things like toxin production, protease activity and biofilm formation (quorum sensing) Decreasing the AI-2 activity decreases the hemolytic activity of S. intermedius
VIRULENCE FACTORS The genes responsible for beta hemolysis produced by S. anginosus is very similar to the gene that encodes for beta-hemolysis in Group A Strep. Hydrolytic enzyme production: This includes RNase and DNase. Hyaluronidase is also produced, and in S. intermedius it allows for bacterial detachment from the biofilm, which enables further spread throughout the body.
CLINICAL SYNDROMES SAG bacteria are considered to be normal flora of the oropharynx, GI tract, female urogenital tract and upper respiratory tract. Have the capacity to cause severe invasive infections No virulence factor has been found that differentiates between commensal and invasive isolates In vitro studies have shown that invasive isolates invoke a more pronounced inflammatory response than commensal isolates
CLINICAL SYNDROMES Due to difficulty in laboratory identification, prospective clinical data is hard to come by Pooled data from 7 studies and 215 patients concluded the following: Patients of all ages can be affected Male predominance Two-thirds had underyling co-morbidities Polymicrobial infection occurs in 25% of cases Intra-abdominal infection is the most commonly identified focus Sepsis without a discrete focus occurred in 20% of cases All-cause in-hospital mortality was estimated to be approximately 16%
CLINICAL SYNDROMES SAG infections of the respiratory tract are often associated with pleural effusion or empyema. This can be hard to interpret! Recently, SAG has been identified as a cause of CF exacerbations Data is conflicting: Which strain of SAG causes the worst type of infection? One small retrospective study found that patients with S. intermedius had a higher 30-day mortality rate, but data is lacking overall.
LABORATORY IDENTIFICATION Growth characteristics on plate: small, can be any hemolysis, butterscotch odor MLSA: Should be used as the gold standard (?) All isolates were identified and sub-speciated MALDI-TOF correctly identified 92% of the isolates to the species level, but did not perform well at the subspecies level. All of the studies they looked at found that S. intermedius was poorly identified by MALDI
ANTIMICROBIAL SUSCEPTIBILITY SAG bacteria are still reliably susceptible to most antibiotics yay! Macrolide resistance varies: from 3% to 18.5% Clindamycin: from 5% to 14% SAG is known to have the ERM gene mechanism. This study recommends the use of a D-test on SAG isolates SAG also has the M phenotype. This is caused by the mefa (macrolide efflux gene) which induces the active efflux of erythromycin and other macrolides. A recent study reported tetracycline resistance at a rate of 21.7% A German study of 141 SAG isolates reported 1.4 % resistant to Cipro and 4.3 % intermediate
TREATMENT A study by Casariego et al highlights how variable SAG infections can be: 32 patients total: 18 had bacteremia with localized infection, 8 had bacteremia without localized infection, 6 had endocarditis. The majority had intraabdominal abscesses as well Duration of ABX therapy ranged from 0-110 days Of the bacteremia patients: majority were treated with a beta-lactam for a mean duration of 11 days. One patient died. One patient was considered cured without any ABX treatment. 6 patients with endocarditis were treated with penicillin or ceftriaxone for a median duration of 14 days. Three of them were also treated with synergistic gentamicin. Five of the 6 were considered cured.
TREATMENT As a general rule, severe SAG infections should be treated with IV ABX You should try to find the source! You may need to drain or remove that source
REFERENCES Funckerstorff, Ralph K et al. Streptococcus anginosus Group Bacteria: No longer a Case of Mistaken Identity. ASM Clinical Microbiology Newsletter. Vol 38, No. 5. March 1 2016.