Gram-Positive Cocci Overview

Gram-Positive Cocci

• Gram-positive cocci are medically important bacteria
• Two medically important genera are Staphylococcus and Streptococcus
• Staphylococci and streptococci are nonmotile and do not form spores
• Distinguishing criteria:
  • Microscopically: staphylococci form grape-like clusters, streptococci form chains
  • Biochemically: staphylococci produce catalase (degrades hydrogen peroxide), streptococci do not

Staphylococci

• Spherical gram-positive cocci arranged in irregular grape-like clusters
• All staphylococci produce catalase (degrades H₂O₂ to O₂ and H₂O)
• Catalase is an important virulence factor.
• Important human pathogens: S. aureus, S. epidermidis, and S. saprophyticus

Staphylococcus aureus

• Causes abscesses, various pyogenic infections (e.g., endocarditis, septic arthritis, osteomyelitis), food poisoning, scalded skin syndrome, and toxic shock syndrome
• A common cause of hospital-acquired pneumonia, septicemia, and surgical wound infections
• A significant cause of skin and soft tissue infections (folliculitis, cellulitis, impetigo)
• The most common cause of bacterial conjunctivitis
• Most strains resistant to penicillin G
• Produce β-lactamase
• Treatable with β-lactamase-resistant penicillins (e.g, nafcillin or cloxacillin), some cephalosporins, or vancomycin
• Combination therapy with β-lactamase-sensitive penicillin (e.g., amoxicillin) and a β-lactamase inhibitor (e.g., clavulanic acid) is also useful
• Approximately 20% of strains are methicillin-resistant (MRSA or NRSA), vancomycin the drug of choice
• Other treatments include Daptomycin (Cubicin) and Quinupristin-dalfopristin (Synercid) for resistant strains

Staphylococcus epidermidis

• Causes prosthetic valve endocarditis and prosthetic joint infections
• Most common cause of central nervous system shunt infections and sepsis in newborns

Staphylococcus saprophyticus

• Causes urinary tract infections, especially cystitis

Staphylococci: Transmission

• Human bodies are the reservoir
• The nose is the main site of colonization of S. aureus (approximately 30% of people are colonized)
• Skin, especially of hospital personnel and patients, is a common colonization site
• Hand contact is an important mode of transmission, handwashing reduces transmission

Staphylococci: Pathogenesis

• Toxigenic (superantigen): toxic shock syndrome, food poisoning
• Pyogenic (abscess): Local: skin infections, disseminated: sepsis, endocarditis, osteomyelitis, arthritis, intravenous catheter infections, prosthetic device infections

Staphylococci: Clinical Findings

• Divided into two groups: pyogenic (pus-producing) and toxin-mediated
• Toxin-mediated: abscess, impetigo, furuncles, cellulitis, folliculitis, conjunctivitis, eyelid infections
• Septicemia can originate from localized lesions, especially wound infections
• Endocarditis may occur on normal or prosthetic heart valves, especially on the right side
• Osteomyelitis and septic arthritis
• Pneumonia can occur in postoperative patients or following viral respiratory infection (influenza)
• Food poisoning (gastroenteritis) caused by ingestion of enterotoxin, short incubation period (1-8 hours). Vomiting is typically more prominent than diarrhea.
• Toxic shock syndrome characterized by fever, hypotension, diffuse macular, sunburn-like rash involving liver, kidney, gastrointestinal tract, CNS, muscle, or blood
• Scalded-skin syndrome characterized by fever, large bullae, and an erythematous macular rash

Streptococcus

• Family of Gram-positive, nonmotile, non-spore-forming, catalase-negative cocci
• Streptococcus genus are the most common facultative anaerobic cocci
• Divided into three groups based on hemolysis on blood agar:
  • α-hemolytic: incomplete lysis of red blood cells (green zone around colonies), also known as Streptococcus viridans
  • β-hemolytic: complete lysis of red blood cells (clear zone around colonies)
  • γ-hemolytic: no hemolysis (no zone around colonies), also known as non-hemolytic streptococci

Streptococcus pyogenes (Group A)

• Leading bacterial cause of pharyngitis, cellulitis, impetigo, necrotizing fasciitis, and streptococcal toxic shock syndrome
• Inciting factor of rheumatic fever and acute glomerulonephritis (AGN)

Streptococcus agalactiae (Group B)

• Leading cause of neonatal sepsis and meningitis

Viridans group streptococci

• Most common cause of endocarditis in patients undergoing surgical procedures in the oral cavity

Transmission: Streptococci

• Part of the normal flora of the throat, skin, and intestines
• Produce disease when gaining access to tissues or blood
• Streptococcus pneumoniae and Viridans streptococci are found chiefly in the oropharynx
• S. pyogenes found on the skin and oropharynx; S. agalactiae occurs in the vagina and colon; Enterococci and anaerobic streptococci are in the colon

Pathogenesis: Streptococci

• Pyogenic: impetigo, cellulitis, pharyngitis, sepsis
• Toxigenic: Scarlet fever, toxic shock
• Immune-mediated (post-streptococcal, nonsuppurative): acute glomerulonephritis, rheumatic fever

Clinical Findings: Streptococci

• Streptococcus pyogenes causes three types of diseases: pharyngitis and cellulitis
  • Pharyngitis: (sore throat), characterized by throat pain and fever. An inflamed throat and tonsils with yellowish exudate, accompanied by tender cervical lymph nodes. Untreated pharyngitis may extend to the middle ear (otitis media), sinuses (sinusitis), mastoids (mastoiditis), or meninges (meningitis)
• Toxigenic diseases example: scarlet fever and toxic shock syndrome
• Immunological diseases example: acute glomerulonephritis and rheumatic fever
• Viridans streptococci (e.g., S. mutans, S. sanguinis, S. salivarius, and S. mitis) are the most common cause of infective endocarditis
  • Enter the bloodstream from the oropharynx, typically after dental surgery
  • Signs of endocarditis: fever, heart murmur, anemia, and embolic events (e.g., splinter hemorrhages, subconjunctival petechial hemorrhages, and Janeway lesions)

Treatment: Streptococci

• Group A streptococcal infections: Penicillin G or Amoxicillin; mild infections: oral Penicillin V
• Penicillin-allergic patients: Erythromycin or azithromycin or clindamycin
• Endocarditis caused by viridans streptococci: prolonged penicillin treatment; enterococcal endocarditis requires penicillin or vancomycin combined with an aminoglycoside

Prevention: Streptococci

• Prompt treatment of group A streptococcal pharyngitis with penicillin G or oral penicillin V prevents rheumatic fever
• Prophylactic benzathine penicillin once a month for several years (in people with rheumatic fever) prevents recurrence
• Patients with acute glomerulonephritis do not require similar penicillin prophylaxis
• To avoid unnecessary antibiotic use, use amoxicillin prophylaxis only for high-risk patients (prosthetic heart valves, previous infective endocarditis, high-risk dental procedures)
• No vaccines for streptococci, except for Streptococcus pneumoniae

Pneumococci

• Streptococcus pneumoniae (Pneumococci)
• Causes pneumonia, bacteremia, meningitis, upper respiratory tract infections (otitis media, mastoiditis, sinusitis), and sepsis (especially in splenectomized individuals)
• Common cause of community-acquired pneumonia, sinusitis, otitis media
• A common cause of bacterial conjunctivitis, especially in children
• Gram-positive, lancet-shaped cocci arranged in pairs (diplococci) or short chains
• On blood agar, they produce α-hemolysis
• Possess polysaccharide capsules of >85 antigenically distinct types
  • Capsules are virulence factors; type-specific antiserum can be used to identify types through Quellung reaction.
• C-substance/C-polysaccharide, a teichoic acid in the cell wall, reacts with a normal serum protein (C-reactive protein (CRP))
• Humans are the only known hosts - not considered highly communicable as substantial proportion of population has virulent organisms in oropharynx
• Resistance high in healthy young people, disease results when predisposing factors are present

Pneumococci: Pathogenesis

• Capsular polysaccharide is the major virulence factor; anti-capsular antibodies are protective
• Lipoteichoic acid: activates complement, induces inflammatory cytokine production; contributes to inflammatory response
• Pneumolysin: hemolysin that causes α-hemolysis; may contribute to pathogenesis
• IgA protease: enhances colonization of the upper respiratory tract by cleaving IgA
• Pneumococci multiply in tissues and cause inflammation; when they reach alveoli, fluid, and red/white blood cells result in lung consolidation
• Trauma to the head that causes spinal fluid leakage through the nose predisposes to pneumococcal meningitis

Pneumococci: Clinical Findings

• Pneumonia often begins with a sudden chill, fever, cough, and pleuritic pain
• Sputum is often a rusty red or brown color
• Bacteremia occurs in 15-25% of cases
• Spontaneous recovery may begin in 5-10 days
• Common cause of otitis media, sinusitis, mastoiditis, conjunctivitis, purulent bronchitis, pericarditis, bacterial meningitis; the leading cause of sepsis in patients without a functional spleen.

Pneumococci: Treatment

• Most pneumococci are susceptible to penicillins and erythromycin
• Penicillin-allergic patients: erythromycin or azithromycin
• Severe pneumococcal infections: penicillin G; mild infections: oral penicillin V
• Penicillin-resistant pneumococci: vancomycin
• Less severely ill patients: ceftriaxone or levofloxacin

Pneumococci: Prevention

• Immunization with 13-valent pneumococcal conjugate vaccine (pneumococcal polysaccaride of 13 most prevalent serotypes conjugated to a carrier protein (diphtheria toxoid)) vital for immunocompromised patients (especially splenectomized patients), children younger than 5
• Unconjugated 23-valent pneumococcal vaccine (Pneumovax 23) for healthy individuals aged 50 and older
• Booster doses recommended for those older than 65 who received the vaccine more than 5 years ago when younger than 65, also for asplenic patients, those with HIV, cancer chemotherapy, or immunosuppressives for transplant rejection