Actinomycosis and Nocardia — Sulfur Granules, Acid-Fastness and Treatment Compared

Both are filamentous, branching, Gram-positive bacteria that look like fungi under the microscope, which is why Actinomyces were originally classified as fungi. Both cause chronic, granulomatous or suppurative disease that can mimic tuberculosis or cancer. They differ in oxygen requirement, acid-fastness, habitat, host and drug of choice, and that is exactly what exam questions test.

Actinomyces are gram-positive, filamentous, non-acid-fast, anaerobic to microaerophilic bacteria, about 2–30 µm long and 0.3–0.5 µm wide. More than 30 species exist, and *A. israelii* has historically been the commonest in human disease, although A. odontolyticus, A. meyeri and A. naeslundii are increasingly identified.

They are commensals that colonise the mouth, urogenital tract and gut, so they have low virulence and cause disease only after the mucosal barrier is breached. The infection is usually polymicrobial: companion organisms (for example Aggregatibacter actinomycetemcomitans, Prevotella, streptococci) lower local oxygen tension and block host defences, allowing Actinomyces to invade.

Actinomycosis is subacute to chronic, suppurative and granulomatous, and does not respect tissue planes, so it spreads contiguously and forms multiple abscesses and draining sinus tracts. It is about three times commoner in men, with a peak at 40–50 years, and it is often diagnosed late because it imitates malignancy and tuberculosis.

The characteristic finding is the presence of yellow sulfur granules: dense aggregates of mycelial fragments surrounded by a calcium phosphate matrix, the Splendore–Hoeppli phenomenon. This matrix helps the organism evade phagocytosis. Microscopy shows suppurative granulomatous inflammation around the granule, with filamentous Gram-positive bacteria within it.

• Gold standard: tissue biopsy or pus, with anaerobic culture and histology. Avoid swabs.
• Crush the granule between two slides and stain with Gram stain or H&E to show branching, beaded Gram-positive filaments.
• Culture may be negative in about 50% because of previous antibiotics, competing organisms, poor anaerobic transport or short incubation; tell the laboratory so it can incubate longer.
• Serology is not useful. Imaging is non-specific; CT or MRI shows extent and bone destruction.
• Raised white count with neutrophilia, CRP and ESR are non-specific. Molecular methods (MALDI-TOF, 16S rRNA sequencing) help when cultures fail.

For where this fits in the laboratory toolkit, revise stains and culture media; for the TB-versus-actinomycosis differential, see anti-tubercular treatment.

Treatment typically lasts 6–12 months, with a minimum of 8 weeks even in favourable cases; surgery on the infected site may shorten the course. Surgery (drainage of abscesses, excision of sinus tracts) is an adjunct, and adding it to antibiotics is independently linked with better outcomes in extensive disease. Susceptibility testing is not routinely needed because penicillin susceptibility is predictable. The prognosis is excellent with prolonged therapy.

Nocardia are aerobic, gram-positive bacilli with branching, beaded filaments, found in soil, decaying organic matter and fresh or salt water. They are weakly acid-fast, so a modified Ziehl–Neelsen method is used to show them. More than 100 species have been described, and about 30 cause human disease; they are saprophytes, not part of normal human flora.

Nocardiosis is classically an opportunistic infection of people with deficient T-cell-mediated immunity. Risk factors include solid-organ and haematopoietic stem cell transplantation, HIV, long-term corticosteroids, malignancy (especially haematological), alcoholism, chronic lung disease (including pulmonary alveolar proteinosis), lupus, renal failure, inflammatory bowel disease and Whipple disease. Primary cutaneous disease can occur in immunocompetent people after soil-contaminated trauma, for example in agricultural work.

• Diagnosis: culture of sputum, pus, biopsy or aspirate; Nocardia are slow-growing, so alert the laboratory. Take blood cultures if pulmonary or disseminated disease is suspected; CT or MRI brain to look for abscess.
• Treatment: sulfonamides are first-line, especially sulfadiazine (good brain penetration); trimethoprim–sulfamethoxazole is preferred by many clinicians.
• Severe, pulmonary or disseminated disease: 2–3 agents (for example amikacin, imipenem, meropenem, ceftriaxone, linezolid), tailored to sensitivity.
• Duration: at least 6 months and at least 1 month after symptoms resolve; immunocompromised patients continue until symptoms subside. Surgical drainage for abscesses.
• Prophylaxis: TMP-SMX in patients with HIV and a low CD4 count may lower the risk of nocardiosis.

• Both are branching Gram-positive filaments that were once thought to be fungi.
• Actinomyces = commensal, endogenous, mucosal breach; Nocardia = soil, exogenous, immunosuppression.
• Actinomyces spreads by direct extension across planes; Nocardia can spread haematogenously to the brain.
• Treatment duration: actinomycosis 6–12 months (minimum 8 weeks); nocardiosis at least 6 months.
• Surgery is an adjunct in actinomycosis and a necessity for abscess drainage in nocardiosis.