Mycobacterium haemophilum Infection

Updated: Jun 11, 2020
Author: Shirin A Mazumder, MD, FIDSA; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD 

Overview

Background

Mycobacterium haemophilum is an acid-fast bacillus that has a wide geographic distribution, having been described in many parts of the world, including France, the United Kingdom, Israel, parts of Africa, Australia, Canada, the United States, and Brazil. In addition to infecting humans, M haemophilum has been isolated from the environment and has been found in several animal species.[1]

Distinct from most other nontuberculous mycobacteria, M haemophilum in vitro growth requires a lower incubation temperature and iron supplementation. M haemophilum is unable to synthesize iron-binding siderophores, so it requires iron supplementation to grow in culture. Its preference for lower temperatures, similar to that of Mycobacterium leprae and Mycobacterium marinum, has been associated with a predilection for clinical infections to be located over the extremities.[1]

M haemophilum can cause localized or disseminated infection, usually in individuals with an underlying immunomodulatory condition such as HIV/AIDS, organ transplant recipients, and patients with autoimmune disorders undergoing immunomodulation. The source of M haemophilum is often environmental habitats such as water reservoirs. While most reported cases do not have a clearly identified source, infection in adults has been associated with tattoo parlors and acupuncture needles.[1]

Pathophysiology

The pathophysiology, natural habitat, and mechanism for acquisition of M haemophilum infection are not known. Water reservoirs may be the source of M haemophilum infections. Immunocompromised adults with M haemophilum infection most commonly present with skin lesions. Septic arthritis and osteomyelitis may also occur. Pulmonary infection is much less common and may follow skin disease. M haemophilum infection occasionally causes pulmonary infection initially. Mycobacteremia may occur.

Epidemiology

Frequency

United States

More than 40 cases of M haemophilum infection have been reported, including 10 cases in Arizona from 1984-1994. Most cases occurred in immunosuppressed patients. The incidence of disease is unknown.

International

Cases of M haemophilum infection have been reported sporadically from Australia, France, Germany,[2] Canada, Israel, United Kingdom, and South Africa.

Mortality/Morbidity

In healthy children, localized cervical lymphadenopathy is a benign disease that responds well to excision of the involved lymph nodes.

In immunocompromised patients, the outcome of disease is determined by the degree of underlying immunosuppression. Some patients with AIDS respond to therapy, while others respond initially but relapse later. Fatalities have occurred in bone marrow transplant recipients.

Sex

M haemophilum infection is more common in males than in females. This may be related to the higher incidence of HIV infection in males.

Age

Lymphadenitis occurs in young children.

Most cases in immunocompromised patients occur in adults.

Prognosis

Prognosis for children with localized lymphadenitis is good.

In adults, the outcome is determined by their immune function.

In severely immunosuppressed patients, disease may require long-term therapy. Despite maintenance therapy, infection may persist or recur.

Patient Education

Adherence to medication is of utmost importance to prevent resistance.

Instruct patients to list all medications to avoid drug interactions.

Rifampin and rifabutin may interfere with contraceptives and numerous other medications, especially HIV-related therapy.

 

Presentation

History

Lymphadenitis in children

The most common symptom is swelling of the neck, which slowly enlarges over several weeks to months. The enlarged nodes may be painful. A course of antimicrobial therapy (eg, 2 wk of oral amoxicillin/clavulanic acid) does not cure the swelling.

Inguinal lymphadenitis has also been reported.[3]

Systemic symptoms are absent except for low-grade fever.

Lymphadenitis in adults

Six cases have occurred in immunocompetent adults.[4]

Cervicofacial lymphadenitis has been reported in immunocompromised adults.[5]

Skin lesions

Skin lesions are the most common presenting symptom in immunosuppressed patients.

Lesions usually develop on the upper and lower extremities over joints. They may begin as papules, subcutaneous nodules, scales, or cysts and are initially painless but often become tender and pruritic. Painful ulcerations may occur. Erythema may surround the lesion.

Nodular lesions involving the peripheral extremities is among the most common presentation.

Lesions may resemble sporotrichosis.[6]

Oculofacial lesions have been reported in an immunocompetent child.[7]

Erythematous plaques and subcutaneous nodules of the face mimicking leprosy have been reported.[8, 9]

Nodular skin lesions have occurred after permanent tattooing of eyebrows in 2 women.[10]

Tattoo-associated skin lesions have occurred in immunocompetent adults.[11]

Skin lesions have been reported prior to onset of B cell lymphoma in a liver transplant recipient.[12]

Septic arthritis

Patients present with pain and swelling over a joint, usually the knee or elbow. Often, the patient has a history of cutaneous lesions overlying the joint.[13]

Pyomyositis

This has been reported in a renal transplant recipient.[14]

Osteomyelitis

This is reported in patients with AIDS.

Skin lesions are usually present.

Septic arthritis is usually present.

Pneumonia

Symptoms include fever, cough, pleuritic chest pain, and dyspnea.

Patients may have a history of treated cutaneous lesions.

This is reported in bone marrow transplant recipients and patients with AIDS.[15, 16, 17]

Central venous catheter tunnel infection

Two cases in immunosuppressed patients have been reported. The first patient presented with a supraclavicular mass with overlying cellulitis that progressed to ulceration. The second patient had an ulceration and purulent discharge at the former site of a Hickman catheter.[18]

Chronic cutaneous granulomata

One case was described in a previously healthy man following a coral injury in Thailand.[19]

Endophthalmitis

This has been reported in a cardiac transplant patient.[20]

Epididymal abscess

This has been reported in a renal transplant patient.[21]

Central nervous system infection

This has been reported in patients with AIDS.[22, 23]

Physical

Lymphadenitis

The submandibular and cervical nodes are most frequently involved. Perihilar nodes are involved less frequently. Enlarged nodes are usually unilateral and may be tender and fluctuant. Overlying skin may be erythematous.

Low-grade fever may be present.

Skin lesions

Lesions include the following:

  • Papules

  • Subcutaneous abscesses

  • Nodules

  • Cysts

  • Scaly plaques

  • Ulcers

Initially, they are painless but may become painful or pruritic.

They may be localized on extremities over joints, or they may be diffuse.

Septic arthritis

The major finding is a swollen fluctuant knee.

Osteomyelitis

Septic arthritis is also present.

Pneumonia

Fever is present.

Central venous catheter tunnel infection

Ulcerations develop at the exit site and along the catheter track.

Lymphadenopathy

Lymphadenopathy may occur.

Bacteremia

While uncommon, M haemophilum bloodstream infections have been described in individuals with immunologically advanced HIV infection and in persons with significant non-HIV immunosuppressive conditions.[1]

Causes

Risk factors for M haemophilum infection include the following:

  • HIV/AIDS

  • Immunosuppression[24, 25, 26, 27, 28]

  • Patients receiving biological agents such as anti-TNF-α agents[29]

  • Steroid use[30] - In 30 steroid-treated mice injected with M haemophilum, 12 developed ear lesions similar to the skin lesions observed in humans; no legions developed in mice that were not treated with steroids.[31]

  • Tattooing and eyebrow permanent makeup

 

DDx

Differential Diagnoses

Workup
 

Workup

Laboratory Studies

Evaluate the CBC count, liver enzymes, and serum electrolyte levels, including creatinine.

Acid-fast bacillus smear and culture

M haemophilum is a slow-growing, acid-fast–positive, nontuberculous mycobacterium that requires media supplemented with ferric iron–containing compounds and grows best at 30-32°C. Growth on solid media usually takes 2-3 weeks. The organism typically does not stain with Gram stain.

Aspirate of lesions may reveal acid-fast bacilli.

Perform an acid-fast bacillus (AFB) smear on excised lymph nodes. Culture a specimen at 30-32°C in media supplemented with iron or heme.

In patients with septic arthritis and osteomyelitis, submit synovial fluid specimens and bone biopsy samples for AFB smear and culture. Synovial fluid is usually purulent, and M haemophilum may be isolated from the fluid.

Submit sputum from immunosuppressed patients with pneumonia for AFB smear and culture. M haemophilum can be cultured from the blood of some patients with AIDS using special isolator tubes.

In appropriate clinical settings (eg, skin lesions, lymphadenopathy), informing the mycobacteriology laboratory to culture for M haemophilum may be useful. Iron must be added to grow this organism.

M haemophilum is unlikely to be a saprophyte (an innocent bystander) or a laboratory contaminant in the appropriate clinical setting.

Polymerase chain reaction (PCR)–restriction endonuclease analysis has been used for direct identification of M haemophilum in clinical specimens from immunocompromised patients.[32, 33, 34, 35]

M haemophilum –specific PCR has been used to diagnosis M haemophilum cervicofacial lymphadenitis in children and was superior to culture in one series of patients from the Netherlands.[36]

Imaging Studies

Radiography of involved joints or bone may demonstrate soft tissue swelling and lytic lesions. Chest radiograph findings are abnormal in patients with pneumonia. Unilateral or bilateral infiltrates may appear.

CT scans of the chest may reveal abnormalities that are not revealed with chest radiography. Regular cuts of 5-7 mm should be sufficient; high-resolution CT scan is rarely necessary.

MRI demonstrates medullary lesions and cortical disruption.

Diagnosis has been made using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scanning.[37]

Other Tests

In children with lymphadenitis a tuberculin skin test result with purified protein derivative (PPD) of tuberculosis may be positive; however, it is rarely larger than 9 mm.[38]

Procedures

Aspirate of lesions may reveal AFB.

Histologic Findings

Biopsy specimens of skin lesions show granulomatous panniculitis and caseating or noncaseating granulomas. Patients with AIDS have poorly formed granulomas. A neutrophilic infiltrate with multinucleated giant cells may be observed. AFB smear results are usually positive, revealing large, pleomorphic, or curved AFB.

Lymph node biopsy may reveal granulomas, necrosis, granulating tissue, or multinucleated giant cells, and the specimen may be smear-positive for AFB.

 

Treatment

Medical Care

Treatment is determined by the degree of immunosuppression. In healthy children with lymphadenitis, surgical excision is the preferred treatment. In immunosuppressed patients, reversal of immunosuppression is the most effective treatment. Immunosuppressed patients require combination therapy to prevent the development of resistance. Susceptibility testing is not standardized, but M haemophilum is usually susceptible to amikacin, ciprofloxacin, and other quinolones (eg, levofloxacin, moxifloxacin), clarithromycin, rifabutin, rifampin. M haemophilum is usually resistant to ethambutol, ethionamide, isoniazid, and streptomycin. Although the optimal regimen is not known, combinations have had some clinical success.

Effective drug combinations include the following:

  • Rifampin and ciprofloxacin

  • Ciprofloxacin, clarithromycin, and rifampin

  • Rifampin and minocycline

  • Clarithromycin, minocycline, and rifampin

  • The treatment duration can vary from 12-24 months depending on numerous factors, including disease severity, anatomic location, and immunologic status of the host.[1]

  • Patients with M haemophilum infection may also experience immune reconstitution events analogous to paradoxical immune reactions seen after initiating antimycobacterial therapy in patients with M tuberculosis infection.[29]

Surgical Care

Lymphadenitis in children: Total excision of the involved lymph node or nodes is the treatment of choice.[39]

Consultations

See the list below:

  • Infectious disease expert

  • Pulmonologist

  • Mycobacterium expert

  • Health department

Further Outpatient Care

Patients require close outpatient follow-up care to document response to therapy (eg, every 2-4 wk). Length of therapy is prolonged in immunosuppressed patients, and patients with irreversible immunosuppression may require life-long suppressive therapy. Relapses have occurred in patients with AIDS who were on suppressive therapy. Whether patients on highly active antiretroviral therapy (HAART) can stop therapy if they have a good HAART response is unknown.

Discuss adherence to medications extensively with the patient to avoid development of resistance.

Further Inpatient Care

M haemophilum infection is diagnosed in many immunosuppressed patients who are hospitalized.

Treatment can be started or continued on an outpatient basis in most patients.

 

Medication

Medication Summary

Although no standardized treatment exists, a regimen that includes a combination of at least 2 drugs with low minimum inhibitory concentrations (MICs) against M haemophilum is preferred.

A 3-drug combination of ciprofloxacin, clarithromycin, and rifampin or rifabutin has been used for cutaneous disease in bone marrow transplant recipients. No standard treatment exists; optimal treatment time is unknown.

Antimicrobial agents

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Clarithromycin (Biaxin XL)

Macrolide with activity against various nontuberculous mycobacteria. Binds to bacterial 50S ribosomal subunit and inhibits RNA-dependent protein synthesis.

Rifampin (Rifadin, Rimactane)

Important drug used in the treatment of infection with M tuberculosis and nontuberculous mycobacterial infections. Inhibits DNA-dependent RNA polymerase activity.

Ciprofloxacin (Cipro)

Fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth. Other quinolones such as levofloxacin, sparfloxacin, and ofloxacin may also be effective.

Amikacin (Amikin)

Expected to be a powerful drug for mycobacteremia. Starting amikacin may be beneficial at least as long as the patient is septic.