Streptococcus, Enterococcus, and Pneumococcus
Streptococcus Pyogenes (Group A)
Virulence Factors
Table of Contents
Read And Learn More: Micro Biology And Immunology Notes
Manifestations
Streptococcus pyogenes causes both suppurative and nonsuppurative manifestations.
Nonsuppurative Complications
Streptococcal antigens show molecular mimicry with human antigens. Due to antigenic cross reactivity, antibodies produced against previous streptococcal infections cross-react with human tissues to produce lesions. This accounts for a number of nonsuppurative complications such as:
Antigenic cross-reactivity between streptococcal antigens and the corresponding human antigens
Differences between acute rheumatic fever and post-streptococcal glomerulonephritis
Laboratory Diagnosis of Streptococcus pyogenes
- Transport medium: Pike’s medium
- Direct smear microscopy: Pus cells with gram-positive cocci in short chains
- Culture:
- Blood agar: Pinpoint colony with a wide zone of β-hemolysis
- Selective media: Crystal violet blood agar and PNF (polymyxin B, neomycin, fusidic acid) media
- Liquid media: Granular turbidity with powdery deposit
- Biochemical identification: Catalase negative, Bacitracin sensitive and Pyrrolidonyl
- Arylamidase (PYR) test is positive
- Typing:
- Lancefield grouping: Shows group A Streptococcus
- Typing of group A Streptococcus: Griffith typing and emm typing
- Serology: ASO antibodies and Anti-DNase B antibodies
- ASO antibodies titer is elevated > 200 Todd unit/ml in most streptococcal infections except in pyoderma and PSGN.
- Anti-DNase-B Ab – Titer > 300–350 units/ml is diagnostic of PSGN and pyoderma.
- Other antibodies elevated are Antihyaluronidase and anti streptokinase antibodies.
Treatment of Streptococcal Infection
Penicillin is the drug of choice for all type of streptococcal infections
Prophylaxis
Long-term maintenance therapy with penicillin (alternative-sulfadiazine or erythromycin in penicillin allergy) is required for children who develop early signs of rheumatic fever. This prevents streptococcal reinfection and further damage to heart.
Group B Streptococcus (S. Agalactiae)
Pathogenesis: Approximately 30% of women are vaginal or rectal carriers of group B Streptococcus. Hence, the infection is common in neonates and in pregnancy. It is a major cause of:
- Neonatal sepsis and meningitis: Neonatal sepsis can be of two types-early onset and late onset type
- Puerperal sepsis and peripartum fever
- Infections in elderly people with underlying illness, such as diabetes mellitus or malignancy:
Cellulitis and soft tissue infections, UTI, pneumonia, and endocarditis.
Laboratory Diagnosis: It can be differentiated from Group A Streptococcus by following biochemical tests (see table)
- CAMP positive, Hippurate hydrolysis test positive, Bacitracin resistant and PYR test is negative
- Orange pigment production enhanced in Islam’s medium.
β hemolytic colonies, which are mucoid and slightly larger (2 mm). - It has a capsular polysaccharide, which can be typed into nine serotypes.
- Early and late onset Group B Streptococcus disease in neonates
Enterococcus
The enterococci were initially grouped under group-D Streptococcus, but later, it has been reclassified as a separate genus Enterococcus under family Enterococcaceae.
- Enterococci are the part of normal flora of human GIT. At the same time, they are also increasingly important agents of human disease especially in hospitals mainly because of their resistance to antibiotics.
- E. faecalis is the most common species found in clinical specimens; whereas E. faecium is more drug resistant than E. faecalis.
- Various Clinical Manifestations
- Urinary tract infections (cystitis, urethritis, pyelonephritis and prostatitis)
- Bacteremia and mitral valve endocarditis (in IV drug abusers)
- Intra-abdominal, pelvic, and soft tissue infection
- Late-onset neonatal sepsis and meningitis
- Infection on burn surface.
Laboratory Diagnosis
Enterococci show the following characteristics that help in the identification:
- They are gram-positive oval cocci arranged in pairs (spectacle eyed appearance)
- Nonmotile cocci (except E. gallinarum and E. casseliflavus)
- Blood agar: It produces nonhemolytic, translucent colonies (rarely produces α or β hemolysis)
- MacConkey agar: It produces minute magenta-pink colonies.
- Bile aesculin hydrolysis test is positive
- PYR test is positive
- Growth occurs in presence of:
- 6.5% NaCl, 40% bile and pH 9.6
- Heat tolerance test: They are relatively heat resistant, can survive 60°C for 30 minutes.
Treatment
Most strains of enterococci are resistant to penicillins, aminoglycosides and sulfonamides. They show intrinsic resistance to cephalosporins and cotrimoxazole.
- Resistance is overcome by combination therapy with penicillin and aminoglycoside (due to synergistic effect) and is the standard therapy for life-threatening enterococcal infections;however in UTI, monotherapy with ampicillin or nitrofurantoin is sufficient. Resistance to this combination therapy may also develop.
- Vancomycin is usually indicated in resistant cases but resistance to vancomycin has also been reported.
Vancomycin-Resistant Enterococci (VRE)
Vancomycin resistance in enterococci has been increasingly reported nowadays.
- The prevalence of VRE varies with time and place. A report in 2016 revealed that among hospitalized patients the VRE frequency is high in America (35%) and low in Europe (4%) and moderate (10–15%) in Asian countries.
- In India, the VRE rate varies from 5–10%.
- VRE is mediated by van gene, which alters the target site for vancomycin present in the cell wall; i.e. D-alanyl-D-alanine side chain of peptidoglycan layer (which is the usual target site for vancomycin), is altered to D-alanyl-D-serine or D-alanyl-D-lactate. This altered side chains have less affinity for binding to vancomycin
- Van gene has 11 genotypes: (van A, B, C1-C3, D, E, G, L, M and N). The van A and van B genotypes predominate worldwide; expressed by E. faecalis and more commonly by E.Faecium
- All van genes are located on transposons and are inducible; except type C and N (chromosomal and constitutive).
- Strains with van A gene show high level resistance to both vancomycin and teicoplanin
- Strains with van B gene show low level resistance to vancomycin, but sensitive to teicoplanin
- E. gallinarum and E. casseliflavus possess van C genes and they show intrinsic resistance to both the glycopeptides.
- VRE Carriers:
- VRE often colonizes the intestine and poses a risk of transmitting to other patients.
- Screening for VRE: It is recommended for high risk patients from ICUs and transplantation units
- Detection: Rectal swab is collected and subjected to (i) Sodium azide agar added with 6 μg/mL of vancomycin or (ii) chromogenic media or (iii) PCR for detection of van gene
- Management: Ensure infection control measures such as hand hygiene and isolation precautions. Treatment (i.e. decolonization) is not recommended for VRE carriers.
Viridans Streptococci
Viridans streptococci are α hemolytic, commensal of mouth:
Treatment: Usually sensitive to penicillin (except neutropenic patients with bacteremia; where vancomycin is given).
Streptococcus pneumoniae Or Pneumococcus
Virulence Factors and Pathogenesis
S. pneumoniae possesses a number of virulence factors such as:
- Capsular polysaccharide: It protects the cocci from phagocytosis:
- It is type specific (about 95 capsular serotypes are recognized), serotypes are detected by Quellung reaction.
- Quellung reaction: Capsular swelling occurs when colonies are added with typespecific antiserum and methylene blue dye.
- It diffuses (soluble) into culture media, tissue and exudates, hence also called soluble specific substance.
- C-carbohydrate antigen (C-polysaccharide or C-substance): It is species-specific.
CRP (C-reactive protein) present in sera of patients with acute inflammation. It is so named because; it precipitates with pneumococcal C-antigen.
- Pneumolysin: It is a membrane-damaging toxin, inhibits neutrophil chemotaxis.
- Autolysin: It is an amidase enzyme that cleaves peptidoglycan leading to autolysis of cells.
This property is responsible for bile solubility and draughtsman appearance of pneumococcal colonies. - Clinical Manifestation
S. pneumoniae is the most common cause of: - Lobar pneumonia, empyema and parapneumonic effusion
- Pyogenic meningitis in all ages (except in neonates)
- Noninvasive manifestations such as otitis media and sinusitis.
- Invasive pneumococcal disease (IPD): Defined as an infection confirmed by isolation of pneumococci from a normally sterile site. Various examples include:
- Bloodstream infection
- Pyogenic meningitis: S. pneumoniae is the leading cause of meningitis in all ages (except in neonates)
- Other invasive manifestations: S. pneumoniae can cause osteomyelitis, septic arthritis, endocarditis, pericarditis, primary peritonitis, rarely, brain abscess and hemolyticuremic syndrome
Epidemiology
- Source of infection in humans is upper respiratory tract of carriers (less often patients).
- Carrier rate > 90% of children of 6 months to 5 years of age harbor S. pneumoniae in the nasopharynx.
- Mode of transmission is by inhalation of contaminated droplet nuclei.
Risk factors:
Children (< 2 years)
- Splenectomy, sickle cell disease and other hemoglobinopathies: As spleen is the site of destruction of capsulated bacteria, the conditions where the opsonization and clearance of circulating bacteria by the spleen is hampered, there is increase risk of pneumococcal infection.
- Underlying comorbid diseases, such as chronic lung, heart, kidney and liver disease, cochlear implants, diabetes mellitus and immunosuppression (e.g. HIV).
- Underlying viral upper respiratory tract infections (e.g. Influenza).
- Nature of infecting serotypes: Serotypes vary in their virulence, geographical distribution and age affected.
- Most common: 6 and 19 F are reported universally as major serotypes. In India serotype 1, 6, 19A and 19F are commonly reported.
- Age: In children, seven serotypes (1, 5, 6A, 6B, 14, 19F and 23F) account for nearly 60% of IPD cases.
Laboratory Diagnosis
S. pneumoniae can be differentiated from Viridans streptococci by various features:
Treatment
- Penicillin G remains the drug of choice, for meningitis.
- If resistant to penicillin, then alternative options are:
- Cephalosporins (e.g. ceftriaxone) or vancomycin for meningitis isolates
- Quinolones such as IV levofloxacin for non-meningeal infections
- Oral amoxicillin is recommended for children with acute otitis media.
Drug Resistance in Pneumococcus
- About 30% of IPD, Pneumococcus shows resistance to at least one antibiotic or more.
- Penicillin resistance in pneumococci has been reported increasingly nowadays.
- This is due to alteration of penicillin-binding protein (PBP) to PBP2b; has low affinity for β lactam drugs.
- This gene is acquired by transformation and horizontal transfer of DNA from related streptococcal species.
- Macrolides are given as alternative for penicillin-resistant pneumococci or for patients allergic to penicillin.
- Multidrug-resistant (MDR) S. pneumoniae is defined as nonsusceptible to ≥3 antibiotic classes is increasingly reported.
- Resistant to penicillin, tetracycline, erythromycin, sulfonamides and clindamycin have shown to coexist.
- Serotype 19A is the most common serotype to exhibit multidrug resistant. As it was not a part of 7-valent conjugate vaccine, it has caused major outbreak. Now, it has been included in 13-valent conjugated vaccine
- Some serotypes can undergo capsule switching (change from one serotype to another), which may contribute to the development of antibiotic resistance.
Prevention (Capsular Polysaccharide Vaccines)
There are two vaccines available for Pneumococcus:
- 23-valent pneumococcal polysaccharide vaccine (PPSV23) and
- pneumococcal conjugate vaccine (PCV13)
Leave a Reply