Gram-Positive Cocci — Staphylococci and Streptococci

• **Catalase-positive → *Staphylococcus***. Clusters on Gram stain.
• **Coagulase-positive → *S. aureus*: golden colonies, protein A (binds IgG Fc), and toxins driving toxic shock syndrome (TSST-1 superantigen), scalded skin syndrome (exfoliative toxin) and rapid-onset food poisoning (preformed enterotoxin). Causes skin and soft tissue infection, acute endocarditis, osteomyelitis, septic arthritis and post-influenza pneumonia. MRSA resistance is mediated by mecA**, altering penicillin-binding protein 2a.
• Coagulase-negative: S. epidermidis forms biofilm on prosthetic material and catheters; S. saprophyticus causes urinary tract infection in young women.
• **Catalase-negative → *Streptococcus***. Chains or pairs.
• Alpha-haemolytic: S. pneumoniae (optochin-sensitive, bile-soluble, encapsulated — lobar pneumonia, meningitis, otitis media, and a particular threat in asplenia) and the viridans group (optochin-resistant; dental caries, subacute endocarditis on damaged valves).
• Beta-haemolytic: **group A *S. pyogenes* (bacitracin-sensitive — pharyngitis, impetigo, erysipelas, necrotising fasciitis, and the sequelae rheumatic fever and post-streptococcal glomerulonephritis) and group B *S. agalactiae*** (neonatal sepsis and meningitis; screened at 35–37 weeks).
• Gamma / non-haemolytic: Enterococcus (bile-esculin positive, grows in 6.5% NaCl; VRE).

Staphylococci — catalase-positive clusters

• Catalase: degrades H₂O₂, blunting the neutrophil oxidative burst; the bubbling reaction is also the first branch point of the identification algorithm.
• S. aureus: coagulase-positive (converts fibrinogen to fibrin, walling off abscesses), ferments mannitol (yellow on mannitol salt agar), beta-haemolytic, and produces the carotenoid staphyloxanthin — the golden pigment, itself an antioxidant.
• Surface: protein A binds the Fc portion of IgG, inverting the antibody and preventing opsonophagocytosis; fibronectin-binding proteins mediate adhesion to valve endothelium and prosthetic material.
• Toxins: TSST-1 and enterotoxins A–E (superantigens), exfoliative toxins A/B (serine proteases that cleave desmoglein-1), and Panton–Valentine leukocidin, characteristic of the USA300 community-acquired MRSA clone.
• Coagulase-negative staphylococci: separated by novobiocin — S. epidermidis sensitive, S. saprophyticus resistant. Epidermidis secretes a polysaccharide biofilm on plastic.

Streptococci — catalase-negative chains and pairs

• Alpha-haemolysis is green partial haemolysis from bacterial H₂O₂ oxidising haemoglobin. S. pneumoniae is a lancet-shaped diplococcus, optochin-sensitive and bile-soluble (endogenous autolysin), with a positive quellung reaction; virulence rests on the polysaccharide capsule, IgA1 protease and pneumolysin. Viridans streptococci are optochin-resistant, bile-insoluble, and synthesise dextrans/glucans from sucrose that glue them to enamel and to fibrin-platelet vegetations.
• Beta-haemolysis is complete clearing from streptolysins. Group A S. pyogenes: bacitracin-sensitive, PYR-positive; M protein is antiphagocytic and the antigen implicated in molecular mimicry; streptolysin O is oxygen-labile and immunogenic (basis of the ASO titre) whereas streptolysin S causes the surface haemolysis; also DNase B, streptokinase, hyaluronidase, C5a peptidase, and SpeA/SpeC superantigens.
• Group B S. agalactiae: bacitracin-resistant, CAMP test-positive, hydrolyses hippurate.
• Enterococcus: PYR-positive, grows on bile-esculin and in 6.5% NaCl; vanA VRE substitutes D-Ala-D-Lac for the D-Ala-D-Ala vancomycin target.

Toxin-mediated disease (no bacteraemia required)

• Superantigens (TSST-1, staphylococcal enterotoxins, streptococcal SpeA/C): bridge MHC class II to the T-cell receptor Vβ region outside the antigen groove, polyclonally activating up to a fifth of T cells. The resulting IL-2/IFN-γ/TNF storm produces capillary leak, vasodilation, diffuse macular erythroderma and later desquamation — explaining shock with sterile blood cultures in menstrual/nasal-packing TSS.
• Preformed enterotoxin: heat-stable, so reheating food does not help; it stimulates vagal afferents in the gut, giving vomiting within 1–6 hours without fever or invasion.
• Exfoliative toxin: cleaves desmoglein-1 in the granular layer, splitting the superficial epidermis → flaccid bullae and a positive Nikolsky sign with sparing of mucous membranes (contrast the full-thickness dermo-epidermal split of SJS/TEN).

Invasive disease

• Abscess formation: coagulase generates a fibrin shell around S. aureus, limiting antibiotic and leukocyte penetration — the mechanistic reason drainage, not antibiotics alone, cures an abscess.
• Endocarditis: S. aureus adheres to intact valve endothelium via fibronectin-binding proteins and destroys it rapidly (acute, large vegetations, embolic phenomena); viridans streptococci require pre-existing turbulent flow and non-bacterial thrombotic vegetations and use dextran to bind, giving indolent subacute disease.
• Encapsulated pneumococcus: the capsule resists complement deposition, so clearance depends on opsonising anticapsular antibody and splenic macrophages — hence fulminant disease in asplenia, sickle cell disease, HIV and myeloma.

Post-streptococcal sequelae

• Rheumatic fever: antibodies to M protein cross-react with cardiac myosin and valve glycoproteins (type II hypersensitivity) → pancarditis with Aschoff bodies and Anitschkow cells, mitral valve predominance.
• PSGN: immune complexes deposit subepithelially (subepithelial humps, "starry sky" granular IgG/C3) → nephritic syndrome. It follows pharyngitis or impetigo, and unlike rheumatic fever is not prevented by treating the pharyngitis.

Staphylococcus aureus

• Skin and soft tissue: folliculitis, furuncle, abscess, cellulitis; risk with IV drug use, diabetes, atopic dermatitis and nasal colonisation.
• Acute endocarditis: high fever, rapid valve destruction, tricuspid involvement in people who inject drugs with septic pulmonary emboli; also prosthetic valves and haemodialysis catheters.
• Osteomyelitis and septic arthritis: the most common cause overall; haematogenous metaphyseal osteomyelitis in children, a hot swollen monoarticular knee in adults.
• Post-influenza or post-viral pneumonia: rapid cavitation, empyema; PVL-positive CA-MRSA causes necrotising pneumonia in previously healthy young patients.
• Toxic shock syndrome: fever, hypotension, diffuse sunburn-like rash with desquamation of palms and soles, plus multiorgan involvement; tampons, nasal packing, surgical wounds.
• Scalded skin syndrome: neonates and young children, periorificial crusting, sloughing sheets of skin, mucosa spared.
• Food poisoning: vomiting 1–6 hours after mayonnaise, custard or ham at a picnic; afebrile, self-limited.

Coagulase-negative staphylococci

• S. epidermidis: indolent prosthetic joint/valve infection, CSF shunt and central line infection; a single positive blood culture is often a contaminant.
• S. saprophyticus: acute cystitis in a sexually active young woman — second most common cause after E. coli.

Streptococci

• S. pneumoniae: rusty sputum lobar pneumonia, otitis media and sinusitis in children, and the leading cause of adult community-acquired bacterial meningitis.
• Viridans group: dental caries (S. mutans) and subacute endocarditis after dental work on an abnormal valve.
• S. pyogenes: exudative pharyngitis with tender anterior cervical nodes and no cough; scarlet fever with sandpaper rash and strawberry tongue; impetigo with honey-crusted lesions; erysipelas with a sharply demarcated raised border; necrotising fasciitis with pain out of proportion and crepitus.
• S. agalactiae: early-onset neonatal sepsis, pneumonia and meningitis; also skin and bone infection in diabetic and elderly adults.
• Enterococcus: nosocomial UTI, biliary sepsis, and endocarditis after GU/GI instrumentation.

Initial approach

• Gram stain and culture of the involved site come first: clusters versus chains immediately narrows the differential, and blood agar plus catalase/coagulase or haemolysis/optochin/bacitracin testing completes the algorithm.
• ***S. aureus* bacteraemia is never dismissed as a contaminant. IDSA guidance is to obtain repeat blood cultures to document clearance**, remove intravascular catheters, and image for metastatic foci; echocardiography is expected in essentially all cases.

Endocarditis

• Three sets of blood cultures from separate sites before antibiotics, then transthoracic echocardiography, escalating to transoesophageal echocardiography (far more sensitive for vegetations, abscess and prosthetic valves).
• Diagnosis is formalised by the modified Duke criteria — typical organism in persistently positive cultures and echocardiographic evidence of endocardial involvement as major criteria; fever, predisposing lesion or IV drug use, vascular and immunologic phenomena (Janeway lesions, Osler nodes, Roth spots) as minor.

Pharyngitis and its sequelae

• The Centor/McIsaac score (fever, tonsillar exudate, tender anterior cervical adenopathy, absence of cough, age) guides testing. Per the IDSA group A streptococcal pharyngitis guideline, a rapid antigen detection test is the initial study; a negative RADT in a child or adolescent must be backed up by throat culture, the gold standard, because of lower sensitivity.
• ASO and anti-DNase B titres are serologic, not acute, tests — used for rheumatic fever (AHA 2015 revised Jones criteria: evidence of preceding GAS infection plus major/minor criteria) and PSGN, where low C3 with haematuria is the classic pairing.

Other syndromes

• Pneumococcal pneumonia: sputum Gram stain with lancet-shaped diplococci; urinary pneumococcal antigen is useful and remains positive after antibiotics.
• Meningitis: CSF shows neutrophil predominance, markedly elevated protein and low glucose; culture and Gram stain are definitive.
• Septic arthritis: arthrocentesis with a markedly elevated, neutrophil-predominant synovial WBC count.
• Osteomyelitis: MRI is the most sensitive imaging test; bone biopsy culture is the gold standard for organism-directed therapy.

Staphylococcal infection

• Incision and drainage is the primary therapy for a cutaneous abscess per the IDSA skin and soft tissue infection guideline; antibiotics are added for systemic signs, large or multiple lesions, or immunocompromise.
• MSSA: an antistaphylococcal penicillin (nafcillin, oxacillin) or cefazolin — both outperform vancomycin for MSSA bacteraemia. Penicillin-allergic patients can usually receive cefazolin; true cephalosporin cross-reactivity is only about 1–3% and is driven by shared R1 side chains, not the beta-lactam ring.
• MRSA: resistance is from mecA-encoded PBP2a, which no beta-lactam except ceftaroline binds. Use vancomycin, dosed to a 24-hour AUC with a target AUC/MIC of 400–600 (2020 IDSA/ASHP/PIDS/SIDP consensus); older trough targets of 15–20 mcg/mL have been retired. Alternatives: daptomycin (never for pneumonia — inactivated by pulmonary surfactant), linezolid (watch serotonin syndrome and myelosuppression), ceftaroline.
• Outpatient CA-MRSA: trimethoprim-sulfamethoxazole, doxycycline or clindamycin.
• Toxin-mediated syndromes: source control (remove tampon/packing) plus an antitoxin protein-synthesis inhibitor, clindamycin, added to the cell-wall agent.

Streptococcal infection

• GAS pharyngitis: penicillin V or amoxicillin for 10 days (IDSA) — GAS has never developed penicillin resistance. Treatment prevents rheumatic fever and suppurative complications but does not prevent PSGN.
• Necrotising fasciitis: emergent surgical debridement plus penicillin combined with clindamycin; clindamycin shuts off exotoxin synthesis and is effective at high inoculum (Eagle effect).
• Pneumococcal pneumonia/meningitis: ATS/IDSA community-acquired pneumonia therapy; for suspected meningitis, vancomycin plus ceftriaxone with dexamethasone given before or with the first antibiotic dose to reduce hearing loss.
• Enterococcus: ampicillin (plus an aminoglycoside or ceftriaxone for endocarditis); VRE requires linezolid or daptomycin.

Prevention

• ACIP recommends pneumococcal conjugate vaccination for all young children and for older adults and at-risk groups, including asplenia.
• ACOG advises universal rectovaginal GBS screening in the late third trimester with intrapartum IV penicillin G for carriers.
• AHA limits dental endocarditis prophylaxis (amoxicillin 2 g orally one hour before) to the highest-risk cardiac lesions.

• Catalase then coagulase: the two-step algorithm is the most repeated vignette skeleton. Clusters + catalase-positive + coagulase-positive = S. aureus; clusters + coagulase-negative + novobiocin-resistant = S. saprophyticus (young woman with dysuria).
• Vomiting within hours of picnic food, no fever: preformed, heat-stable staphylococcal enterotoxin. The distractor is Bacillus cereus (reheated fried rice) — same rapid vomiting, different food.
• **Positive blood cultures with S. aureus → the single best next step is echocardiography plus repeat blood cultures and source control**, not simply starting antibiotics and observing.
• Nikolsky sign with mucosal sparing in an infant is staphylococcal scalded skin syndrome (desmoglein-1 cleavage). If mucosa is involved, think SJS/TEN instead.
• Optochin and bile solubility separate the alpha-haemolytics: optochin-Sensitive and bile-soluble = pneumococcus; optochin-Resistant = viridans. Pair viridans with dental procedures and a previously damaged valve; pair *S. bovis*/*gallolyticus* bacteraemia with colonoscopy for colon cancer.
• Penicillin prevents rheumatic fever but not post-streptococcal glomerulonephritis — a favourite trap. Rheumatic fever follows pharyngitis only; PSGN follows pharyngitis or impetigo.
• MRSA is mecA/PBP2a, so every standard beta-lactam fails; daptomycin must never be chosen for pneumonia because surfactant inactivates it. Vancomycin is monitored by AUC/MIC 400–600, not by a 15–20 mcg/mL trough.
• Clindamycin is added for toxin-mediated disease (TSS, necrotising fasciitis) because it inhibits ribosomal exotoxin synthesis — the mechanism, not the spectrum, is why it is on the list.
• Asplenia, sickle cell disease and complement/humoral defects point to encapsulated organisms, with S. pneumoniae first; vaccination status is usually the hidden stem detail.