5.5 Mycobacteria, Spirochetes, Mycoplasma & Zoonotic Infections
Key Takeaways
Mycobacterium tuberculosis is an acid-fast, slow-growing aerobe; latent infection is detected with an interferon-gamma release assay or tuberculin skin test and must be excluded before TNF-inhibitor therapy.
Isoniazid causes pyridoxine-preventable peripheral neuropathy and pyrazinamide raises serum urate, so both drugs matter when a patient on TB therapy presents with burning feet or podagra.
Hansen disease (Mycobacterium leprae) is a leading infectious cause of insensate feet, plantar ulceration and foot drop; nontuberculous mycobacteria cause fish-tank granulomas and footbath furunculosis.
Treponema pallidum causes a palmoplantar rash in secondary syphilis and tabes dorsalis with Charcot joints in tertiary syphilis; Borrelia burgdorferi causes erythema migrans and large-joint Lyme arthritis.
A zoonosis is an infection transmitted from vertebrate animals to humans by bites, scratches, vectors, ingestion, inhalation or contaminated water; doxycycline treats most tick-borne rickettsial and spirochetal zoonoses.
5.5 Mycobacteria, Spirochetes, Mycoplasma & Zoonotic Infections
The Part I microbiology outline lists acid-fast bacilli, spirochete and Mycoplasma infections as separate bacteriology topics, and it lists zoonotic infections (definitions and modes of transmission) as their own heading. These organisms are less common in the foot than Staphylococcus aureus, but they are high-yield because each one has a distinctive cell wall, stain, transmission route or neurologic consequence.
Acid-Fast Bacilli: Why the Stain Matters
Mycobacteria have a thin peptidoglycan layer covered by arabinogalactan and long-chain mycolic acids (see 5.4). This waxy envelope resists Gram staining, drying and many disinfectants. The Ziehl-Neelsen or Kinyoun carbolfuchsin stain is retained after acid-alcohol decolorization, so the bacilli appear red against a blue background. The envelope also explains slow growth: M. tuberculosis divides about every 15–20 hours, so cultures on Löwenstein-Jensen agar or in liquid broth may take up to 6–8 weeks.
Mycobacterium tuberculosis
- Transmission: inhalation of airborne droplet nuclei from a person with active pulmonary disease.
- Primary infection: a subpleural lower-lobe focus plus hilar node involvement forms the Ghon complex; most people contain the infection as latent TB infection (LTBI) inside caseating granulomas.
- Reactivation: occurs when cell-mediated immunity falls (HIV, diabetes, corticosteroids, transplant drugs, TNF-alpha inhibitors). TNF-alpha maintains granuloma integrity, which is why latent TB screening is required before infliximab, adalimumab or etanercept.
- Testing: the tuberculin skin test (TST) measures a Type IV delayed hypersensitivity response read at 48–72 hours; the interferon-gamma release assay (IGRA) measures T-cell interferon-gamma release to TB-specific antigens and is not affected by prior BCG vaccination.
- Musculoskeletal disease: spinal TB (Pott disease) is the classic skeletal site. Tuberculous osteomyelitis, arthritis or tenosynovitis of the foot and ankle is rare but should be considered when a chronic, culture-negative lesion shows caseating granulomas on biopsy.
| First-line drug | Mechanism | Toxicity a podiatric clinician should recognize |
|---|---|---|
| Isoniazid (INH) | Inhibits mycolic acid synthesis | Hepatitis; peripheral neuropathy from pyridoxine (B6) depletion, prevented with supplemental pyridoxine |
| Rifampin | Inhibits bacterial RNA polymerase | Orange body fluids; potent CYP450 induction (lowers warfarin, oral contraceptive and many other drug levels) |
| Pyrazinamide | Disrupts mycobacterial membrane energetics in acidic phagolysosomes | Hepatotoxicity; hyperuricemia that can precipitate gout |
| Ethambutol | Inhibits arabinosyl transferase (arabinogalactan synthesis) | Optic neuritis with red-green color loss |
Mycobacterium leprae (Hansen Disease)
M. leprae grows best at cooler body temperatures, so it targets skin and peripheral nerves of the face, hands and feet. It cannot be grown on artificial media. In the southern United States, nine-banded armadillos are a recognized reservoir.
- Tuberculoid leprosy: strong Th1 response, few bacilli, a small number of hypopigmented anesthetic plaques and thickened nerves.
- Lepromatous leprosy: weak cell-mediated (Th2-skewed) response, abundant bacilli, diffuse nodular skin lesions and symmetric nerve involvement.
- Lower extremity consequences: posterior tibial nerve damage produces an insensate sole and recurrent plantar ulcers; common fibular nerve damage produces foot drop. Neuropathic bone resorption and Charcot-type joint destruction follow.
- Therapy: multidrug therapy with dapsone, rifampin and clofazimine.
Nontuberculous Mycobacteria (NTM)
- Mycobacterium marinum: enters minor abrasions from aquariums, fish handling or salt water and causes a nodular "fish-tank granuloma" that may spread along lymphatics in a sporotrichoid pattern. It grows best near 30–32°C, so the laboratory must be told to incubate at a lower temperature.
- Rapid growers (M. fortuitum, M. abscessus, M. chelonae): cause furunculosis on the legs after pedicure whirlpool footbaths, leg shaving and contaminated injections, and they cause postoperative wound infections that fail routine antibiotics.
Spirochetes
Spirochetes are thin, helical, motile organisms with axial filaments (endoflagella) inside the periplasm. They stain poorly with Gram stain and are seen with darkfield microscopy, silver stains or immunofluorescence.
Treponema pallidum (Syphilis)
| Stage | Typical timing | Key findings |
|---|---|---|
| Primary | About 3 weeks after exposure (range about 10–90 days) | Painless indurated chancre with regional nodes |
| Secondary | Weeks to months later | Diffuse maculopapular rash including palms and soles, condylomata lata, fever, lymphadenopathy |
| Latent | Years | Seropositive without symptoms |
| Tertiary | Years to decades | Gummas, aortitis, tabes dorsalis (dorsal column degeneration) |
Tabes dorsalis destroys dorsal columns and dorsal roots, producing lancinating leg pains, a positive Romberg sign, loss of proprioception and Charcot neuroarthropathy, historically of the knee and also of the foot and ankle. Testing combines a nontreponemal test (RPR or VDRL, which tracks disease activity) with a treponemal test (FTA-ABS, TP-PA or immunoassay, which usually remains positive for life). Benzathine penicillin G is the treatment of choice; the Jarisch-Herxheimer reaction (fever and rigors within hours of the first dose) reflects release of spirochete lipoproteins.
Borrelia burgdorferi (Lyme Disease)
Transmitted by Ixodes ticks, usually after about 36–48 hours or more of attachment. Early localized disease produces erythema migrans, an expanding annular erythema at least 5 cm across. Early disseminated disease causes multiple lesions, facial nerve palsy, carditis with heart block and meningitis. Late disease causes a monoarticular or oligoarticular arthritis, most often of the knee. Doxycycline is first-line for most adults; amoxicillin or cefuroxime are alternatives, and ceftriaxone is used for some neurologic or cardiac disease.
Leptospira interrogans
Leptospirosis is a zoonosis acquired when abraded skin or mucosa contacts water or soil contaminated by rodent or livestock urine, a risk for barefoot workers, flood exposure and freshwater sports. Severe disease (Weil disease) combines jaundice, renal failure and hemorrhage; calf myalgia and conjunctival suffusion are classic early clues.
Mycoplasma Infections
Mycoplasma pneumoniae lacks a cell wall and incorporates sterols into its membrane. It is therefore intrinsically resistant to beta-lactams and vancomycin and invisible on Gram stain. It causes "walking" atypical pneumonia, cold-agglutinin (IgM) hemolysis, and mucocutaneous eruptions such as erythema multiforme and Mycoplasma-induced rash and mucositis. Macrolides, doxycycline or respiratory fluoroquinolones are used.
Zoonotic Infections: Definitions & Modes of Transmission
A zoonosis is an infection naturally transmitted between vertebrate animals and humans. Humans are frequently dead-end hosts that do not continue the transmission cycle. Transmission routes include:
- Direct contact, bites and scratches
- Arthropod vectors (ticks, fleas, mosquitoes, sandflies)
- Ingestion of contaminated meat, unpasteurized dairy or water
- Inhalation of aerosols from animal products or excreta
- Indirect environmental contact with soil or water contaminated by animal urine or feces
| Organism / disease | Reservoir and route | Lower extremity or systemic clue | Usual therapy |
|---|---|---|---|
| Pasteurella multocida | Cat and dog bites | Cellulitis within 24 hours (see 5.2) | Amoxicillin-clavulanate |
| Capnocytophaga canimorsus | Dog bites or licks | Fulminant sepsis in asplenic or alcohol-dependent patients | Amoxicillin-clavulanate or a beta-lactam/beta-lactamase inhibitor |
| Bartonella henselae | Cat scratch, cat fleas | Regional lymphadenitis; bacillary angiomatosis in AIDS | Azithromycin for lymphadenitis |
| Erysipelothrix rhusiopathiae | Fish, shellfish, swine (handlers) | Violaceous erysipeloid plaque at the inoculation site | Penicillin |
| Rickettsia rickettsii (Rocky Mountain spotted fever) | Dermacentor ticks | Rash beginning on wrists and ankles, spreading centrally and onto palms and soles | Doxycycline at any age |
| Brucella species | Unpasteurized dairy, livestock | Undulant fever; sacroiliitis and spondylitis | Doxycycline plus rifampin |
| Francisella tularensis | Rabbits, ticks, deer flies | Ulceroglandular lesion with painful nodes | Gentamicin or streptomycin |
| Rabies virus | Bats, raccoons, skunks, foxes, unvaccinated dogs | Ascending encephalitis | Wound cleansing plus post-exposure vaccine and rabies immune globulin when indicated |
| Toxoplasma gondii | Cat feces, undercooked meat | Congenital infection; encephalitis in AIDS | Pyrimethamine-based therapy |
| Microsporum canis, Sporothrix | Cats and dogs | Zoophilic tinea; cat-transmitted sporotrichosis | Antifungals (see 6.1) |
Tip
When a foot or leg infection does not respond to standard antistaphylococcal therapy, ask about animal bites, aquariums, livestock, travel, freshwater exposure, pedicures and tick bites. Those exposures change both the culture request and the empiric antibiotic.
A 44-year-old aquarium hobbyist has a slowly enlarging nodule on the dorsum of the hallux with two similar nodules ascending along the dorsal foot. Routine bacterial cultures are negative. Which organism and laboratory request are most appropriate?
Pasteurella multocida, with routine aerobic culture at 37°C and an indole test
Treponema pallidum, with darkfield microscopy of the nodule
Mycobacterium marinum, with mycobacterial culture incubated near 30–32°C
Mycobacterium leprae, with culture on Löwenstein-Jensen agar at 37°C
Three months into four-drug therapy for pulmonary tuberculosis, a patient develops burning paresthesias of both forefeet and, separately, an acutely swollen first metatarsophalangeal joint. Which drug pair best explains these two problems?
Isoniazid causing neuropathy and pyrazinamide causing hyperuricemia
Rifampin causing neuropathy and ethambutol causing hyperuricemia
Pyrazinamide causing neuropathy and isoniazid causing hyperuricemia
Ethambutol causing neuropathy and rifampin causing hyperuricemia
Which statement correctly describes a zoonotic infection and its route?
Leptospirosis is acquired chiefly by eating undercooked pork containing encysted larvae
Erysipelothrix rhusiopathiae is acquired mainly by inhaling aerosols from dried bird droppings in barns
Rocky Mountain spotted fever is tick-borne, and its rash typically starts at the wrists and ankles
Brucellosis is transmitted mainly by mosquito bites and is treated with vancomycin
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