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We report a case of pyomyositis due to Mycobacterium haemophilum in a renal transplant recipient. M. haemophilum was identified by PCR-mediated sequence analysis of the heat shock protein gene in the DNA of the specimen. The patient was successfully treated with repeated surgical debridement and prolonged antimycobacterial therapy.

Nontuberculous mycobacterial (NTM) infections are becoming an increasingly important complication in ophthalmology, particularly among immunocompromised patients. We report a case of NTM in a 66-year-old male immunosuppressed after cardiac transplantation. Chronic granulomatous iridocyclitis progressed to purulent endophthalmitis despite intraocular and systemic antimicrobial therapy. Direct immunoflourescent staining of the vitrectomy specimen revealed acid-fast bacilli. Biopsies of nodular skin lesions revealed non-caseating granulomas with acid-fast bacilli. Cultures of skin and eye biopsies yielded Mycobacterium haemophilum. Despite aggressive combination antimicrobial therapy, the eye was eventually enucleated. Resolution of systemic infection occurred with the addition of granulocyte macrophage-colony stimulating factor. This is the first reported case of M. haemophilum endophthalmitis.

Purpose: To report a case of Mycobacterium hemophilum of the eye., Methods: Case report with pathologic correlation. A 55-year-old Malaysian man with a 3-year history of graft-versus-host disease presented with dry eye and keratopathy., Results: The diagnosis was not initially evident, despite biopsy specimens of the conjunctiva. Definitive diagnosis was made after dermatology consultation suggested a histoid variant of lepromatous leprosy, prompting Ziehl-Neelsen staining of the initial and subsequent conjunctival biopsies with subsequent polymerase chain reaction testing. Anti-M. hemophilum treatment resulted in prompt resolution of ocular signs., Conclusions: Mycobacterium hemophilum is a rare condition, affecting mainly immunocompromised patients. Although filamentary keratopathy has been described as common manifestations of leprosy, to date, no ocular manifestations of M. hemophilum have been described. Conjoint management with infectious disease and clinical microbiology is imperative to ensure accurate diagnosis and appropriate early intervention. The effect of systemic immunosuppression is relevant in such patients.

Atypical mycobacterial skin infections are difficult to diagnose owing to their aspecific histopathologic presentations and to the presence of few bacteria. Therefore, these infections are often not recognized. Molecular detection of mycobacterial DNA has proven to be useful in clinical samples. The aim of this study was to investigate the incidence of mycobacterial involvement in skin biopsies showing granulomatous inflammation, using real-time polymerase chain reaction (PCR). Real-time PCR specific for the genus Mycobacterium and the species Mycobacterium avium and Mycobacterium haemophilum was performed on formalin-fixed/paraffin-embedded biopsies from patients with granulomatous inflammation of the skin, from the period 1984 to 2004. A control group was assembled from patients with proven basal cell carcinoma. Amplicons of all positive reactions were sequenced to confirm or identify the mycobacterial species. Of 30 patients, 13 (43%) were found to be positive for mycobacterial infection, of whom only 5 patients had been previously diagnosed with a mycobacterial disease. M. haemophilum was identified as the most common species (n=7). The other identified species were Mycobacterium malmoense, Mycobacterium gordonae, and Mycobacterium marinum. The results show that real-time PCR is useful in detecting mycobacterial infections in undiagnosed formalin-fixed/paraffin-embedded skin samples and that the application of molecular approaches would improve the diagnoses of mycobacterial skin infections.

We report a case of primary cutaneous infection by Mycobacterium haemophilum after the bite of an aquarium fish in a severely immunodepressed AIDS patient. Clinical features consisted in nodular and ulcerative lesions that followed a sporotrichoid pattern. Histological study of nodular lesions showed a granulomatous dermatitis with numerous acid-fast bacilli. The mycobacterium was identified 3 months later by genetic hybridization from a cultive in solid medium. Combined therapy with isoniazid, rifampin, clarithromycin, ethambutol, amikacin and ciprofloxacin resulted in complete resolution of the lesions. Infection by Mycobacterium haemophilum is a rare mycobacteriosis that usually affects immunodepressed patients. The most common clinical manifestations are cutaneous lesions but the development of sporotrichoid nodular lymphangitis is exceptional.

Infections caused by Mycobacterium haemophilum in immunocompetent patients are unusual. M. haemophilum have been associated with cervicofacial lymphadenitis in children, but inguinal infections have not yet been described. We present a case of an inguinal lymphadenitis caused by M. haemophilum in an immunocompetent girl.

Mycobacterium haemophilum, a nontuberculous mycobacterium, is a pathogen in immunocompromised human patients. We report a case of M haemophilum-induced granuloma in the spinal cord of an American Bison (Bison bison). M haemophilum infection was diagnosed by sequencing a portion of the 16 S ribosomal DNA and comparing the amplicon sequence with sequences in GenBank.

Background: Mycobacterium haemophilum is a slow-growing, fastidious, iron-requiring microorganism that, relative to other non-tuberculous mycobacterial species, has rarely been documented as a cause of human infection. This microorganism appears to be acquired via environmental exposure although its natural habitat and mode of acquisition are unknown. It has primarily been implicated as a cause of ulcerating cutaneous or subcutaneous nodular skin lesions, particularly in immunocompromised patients, although infections at extracutaneous sites have also been described. Osteomyelitis, while rarely documented, appears to be an important complication of infection with M. haemophilum in these patients., Case Presentation: We describe a unique case of culture-confirmed M. haemophilum osteomyelitis in an adult woman with polycythemia vera and review the world literature on bone infections due to this organism., Conclusion: Mycobacterium haemophilum is an important but infrequently encountered cause of osteomyelitis in immunocompromised patients, often requiring months to years of medical therapy, with or without surgery, to effect a clinical cure.

Background: Nontuberculous mycobacterial (NTM) lymphadenitis in children is most often caused by Mycobacterium avium. In a prospective, multicenter trial of the optimal treatment, 23.7% of the NTM cervicofacial lymphadenitis cases in children were caused by Mycobacterium haemophilum. In this article, we describe the epidemiological and clinical features of M. haemophilum cervicofacial lymphadenitis., Methods: The diagnosis of Mycobacterium avium or M. haemophilum infection was established by culture or polymerase chain reaction. Demographic characteristics and data regarding clinical presentation and possible environmental exposure were compared for patients infected with M. avium and those infected with M. haemophilum., Results: Ninety-four (69.9%) of 135 infections were caused by M. avium, 32 (23.7%) by M. haemophilum, and 9 (6.4%) by other NTM species. The median age of the M. haemophilum-infected children was 72 months, compared with 41 months for the M. avium-infected children (P < .001), with an equal distribution for both sexes. Involvement of multiple lymph nodes was frequently observed among the M. haemophilum-infected patients (56% of patients). Extranodal localizations were only observed in M. haemophilum-infected patients. Children with M. haemophilum infection were more likely to have a non-Dutch background (P = .001), and in most cases, they had a history of contact with swimming water (P = .03), whereas M. avium-infected patients were more likely to have a history of playing in sandpits (P = .01). In a multivariate analysis, only older age and a non-Dutch background were predisposing risk factors for M. haemophilum infection, compared with M. avium infection., Conclusion: Higher age, non-Dutch background, and involvement of multiple cervicofacial lymph nodes with extranodal localizations distinguished M. haemophilum infection from M. avium infection.

Introduction: According to foreign literature Mycobacterium haemophilum causes diseases of the skin, subcutis and lymph nodes in immunocompetent individuals, while in AIDS patients and in subjects after kidney transplantations it is responsible for osteomyelitis and disseminated infections., Material and Methods: The authors tested the possibility of using a BioFM medium with the X-factor for the detection of Mycobacterium haemophilum in clinical samples and Middlebrook's 7H9 medium with ADC and the X-factor to establish the sensitivity of strains to antimicrobials using the MIC method., Conclusions: Given the favourable results of preliminary tests the use of the BioFM medium was included among the routine methods applied at the department. In one year Mycobacterium haemophilum was detected with this method in 3 patients presenting extrapulmonary mycobacteriosis.

Infections associated with Mycobacterium haemophilum are underdiagnosed because specific culture methods required for its recovery are not applied routinely. Using polymerase chain reaction (PCR) technology on fine needle aspirates and biopsied specimens from 89 children with cervicofacial lymphadenitis, we assessed the importance of M. haemophilum. Application of a Mycobacterium genus-specific real-time PCR in combination with amplicon sequencing and a M. haemophilum-specific PCR resulted in the recognition of M. haemophilum as the causative agent in 16 (18%) children with cervicofacial lymphadenitis. M. avium was the most frequently found species (56%), and M. haemophilum was the second most commonly recognized pathogen. Real-time PCR results were superior to culture because only 9 (56%) of the 16 diagnosed M. haemophilum infections were positive by culture.

PCR-restriction endonuclease analysis (PRA) was used for direct identification of Mycobacterium haemophilum in clinical specimens from immunocompromised patients. PRA correctly identified M. haemophilum in four smear-positive specimens. Direct identification by PRA takes 2 to 3 working days compared to the 3 to 5 weeks required for culture isolation and identification by conventional methods.

A 53-year-old, male patient presented with pain in the middle area of the back of his left foot. The painful area was associated with a reddish dome-shaped swelling of 24 by 18 mm which had ulcerated in the center part. Histopathologically, the cutaneous lesion consisted of an ulcer surrounded by abscess and granuloma and numerous acid-fast organisms were observed. Subsequently, the area just below the left inguinal area developed redness and swelling approaching the size of a quail egg. The patient responded favorably with rifampicin, levofloxacin, and minocycline therapy. The patient was immunodeficient, but negative for HIV-1 and HIV-2 antibodies and the etiology of his immunodeficient state is unclear. Skin tissues or pus were cultured at 37 degrees C on 2% Ogawa and BBL MGIT. Acid-fast organisms were recovered on MGIT within 4 to 12 days, while 2% Ogawa medium failed to recover acid-fast bacteria. Using growth from the positive MGIT tube as inoculum, MycoBroth, 7H9 broth, 7H11.2% Ogawa supplemented with or without iron complexes, and blood agar were inoculated and cultured at 30 and 37 degrees C. Growth at 30 and 37 degrees C was seen with MycoBroth, 7H9, hemin (60 microM) or ferric ammonium citrate (15 mg/ml) supplemented 7H11 and blood agar as well as 7H11 supplemented with factor X. Growth at 30 degrees C only was observed for ferric ammonium citrate supplemented 7H9 and 2% Ogawa. Generally, growth at 30 degrees C was better than that at 37 degrees C in all media. No growth at either temperature was observed with hemin or factor X supplemented 2% Ogawa. With respect to the biochemical characterization, the isolate was negative for niacin, nitrate reduction, urease, arylsulfatase, Tween 80 hydrolysis, catalase, 68 degrees C catalase, acid phosphatase, and tellurite reduction, while strongly positive for neutral red test. Sequencing of the 16S rRNA gene showed the isolate to be consistent with Mycobacterium haemophilum. Based on the composite characterization, the isolate was identified as M. haemophilum. This is the second case report of M. haemophilum infection in Japan in the literature.

Mycobacterium haemophilum has rarely been implicated in human disease. The organisms have been isolated mainly in patients with human immunodeficiency virus (HIV) disease or transplant recipients. We describe the first case of a disseminated M. haemophilum infection as initial manifestation of AIDS in Europe.

Mycobacterium haemophilum, a strongly acid- and alcohol-fast bacillus belonging to the group of non-tuberculous mycobacteria was first described in 1978 as the cause of cutaneous ulcerating lesions in a woman with Hodgkin's disease. Infection due to M. haemophilum is rare but increasing in prevalence in immnunosuppressed subjects, particularly in patients with acquired immunodeficiency syndrome (AIDS) patients. The skin is the most common site of infection with erythematous or violaceous papules and/or nodules that are usually painless at first, but some elements develop into abscesses or ulcers that can become very painful. The incidence of M. haemophilum is unknown, but cases of infection have been reported in Australia, Canada, the United States, France, Israel, the United Kingdom and Taiwan; to date no cases have been reported in Italy, thus the case reported here is apparently the first one observed in our country.

A 61-year-old previously healthy man developed chronic dermal granulomata in his right arm after receiving a coral injury in Thailand. After 7 biopsies, infection caused by Mycobacterium haemophilum was diagnosed. This case highlights the difficulty of isolating this fastidious organism in the laboratory and suggests that seawater or coral was the source of the infection.

In an 8.5-year-old boy with severe recurring unilateral swelling of the neck, infection with Mycobacterium haemophilum was established. In addition to the more usual causative agents, cervical lymphadenopathy in children can, in rare cases, be caused by M. haemophilum. The skin tests did not differentiate between Mycobacterium avium and Mycobacterium tuberculosis infection. There was no evidence of specific immune deficiencies. The swelling did not respond to treatment with four tuberculostatic drugs (rifampicin, isoniazid, pyrazinamide and ethambutole), nor to repeated surgical excision. Finally, M. haemophilum grew on the culture despite sub-optimal culture conditions. Thereupon the patient was treated with co-trimoxazole and recovered in two weeks. This is the first patient with cervical lymphadenopathy caused by M. haemophilum to be described in the Netherlands. M. haemophilum grows on an iron-rich medium at a relatively low temperature (30-32 degrees C). In cases of cervical lymphadenopathy, it is advisable to consider M. haemophilum as a cause and to adjust the culture conditions accordingly.

This study attempted to isolate mycobacteria from hospital and household cockroaches from 90 hospitals and 40 households in Kaohsiung City and Kaohsiung County, South Taiwan. Among 203 cockroaches (139 Periplaneta americana and 64 Blattella germanica) collected from the hospitals, six Mycobacterium spp. were isolated and identified by polymerase chain reaction-restriction fragment length polymorphism analysis. In 12 cockroaches (P. americana): four Mycobacterium kansaii, three Mycobacterium xenopi, two Mycobacterium gordonae, one Mycobacterium hemophilium, one Mycobacterium fortuitum, and one Mycobacterium avium. However, no mycobacteria were obtained form the hospital B. germanica or 226 household cockroaches (123 P. americana and 103 B. germanica). As cockroach infestation occurs commonly in the hospital environment, they may potentially be implicated as a cause of hospital-acquired infections due to non-tuberculous mycobacteria.

History and Admission Findings: A 53-year-old man with known HIV infection and AIDS was admitted because of painful swelling at the right knee for 6 weeks. The cause was thought to be osteomyelitis and surgical treatment was planned., Investigations: No causative pathogen was found at curettage and lavage of an abscess at the right medical head of the tibia, but at a subsequent operative revision acid-fast rods were seen and identified as Mycobacterium haemophilum., Treatment and Course: A systemic antibiotic, 1 g levofloxacin daily, had been started at the initial abscess operation. 2 weeks later, because swelling of the right knee had recurred with marked local and systemic signs of infection, a second surgical intervention was performed. Afterwards, in view of the histological finding of acid-fast bacteria suggesting tubercular osteomyelitis, the patient was put on combined treatment with 300 mg/d of isoniazid, 1600 mg/d of ethambutol, 2 g/d of pyrazinamide, and 1 g of streptomycin i.m. every other day. After molecular microbiological identification of M. haemophilum the antibiotic treatment was changed to 1600 mg/d of ethambutol, 300 mg/d of rifabutin and 1 g/d of clarithromycin. The operation wound healed well., Conclusion: M. haemophilum infection can be lethal in immunodeficient patients if untreated. Although there is no standard treatment, this rare infectious disease responds relatively well to a modified combined tuberculostatic regimen. Special laboratory techniques to identify the specific causative pathogen are therefore of great importance.

An adult female royal python was referred with an 18-month history of chronic respiratory tract disease. Anemia and moderate leukocytosis with heterophilia and monocytosis were detected and interpreted as evidence of a chronic inflammatory condition. Evaluation of lateral and dorsoventral radiographic views revealed multiple soft-tissue opacities within the cranial lung fields. Endoscopic evaluation revealed that the normal reticulated pattern on the surface of the lung had been largely replaced by diffuse, granulomatous tissue. Histologic examination of biopsy specimens revealed classic pyogranulomas. Ziehl-Neelsen stains revealed numerous acid-fast bacilli consistent with Mycobacterium spp. Molecular methods including polymerase chain reaction restriction assays and DNA sequencing confirmed the identification of M. haemophilum and M. marinum. The snake was euthanatized. Mycobacteriosis is an uncommon and sporadic pyogranulomatous disease of reptiles. In most cases of reptile mycobacteriosis, treatment is not advised because of the chronic nature and often advanced stage of the disease, long-term and expensive nature of potential treatment regimens, and the risk of spread to other animals, including humans.

Mantoux results were examined for 29 children with culture-proven nontuberculous mycobacterial lymphadenitis, and 4 species were isolated: Mycobacterium avium-intracellulare complex (from 14 patients [48%]), Mycobacterium haemophilum (from 12 [41%]), Mycobacterium simiae (from 2 [7%]), and Mycobacterium scrofulaceum (from 1 [3%]); the median indurations for each species were 15.5 mm, 14.5 mm, 20 mm, and 23 mm, respectively, and in 17 cases (59%), they were > or =15 mm. In regions with a low incidence of tuberculosis, lymphadenitis thought to be due to nontuberculous mycobacteria should be managed as such, regardless of Mantoux results, thereby avoiding antituberculosis treatment.

Mycobacterium haemophilum has been described as a pathogen that causes cutaneous lesions in immunocompromised patients. A specimen from a skin ulcer on the leg of a Japanese patient with acquired immunodeficiency syndrome yielded acid-fast bacilli on blood agar plates after 4 weeks of incubation at 30 degrees C, but the organism was not found on Ogawa egg slants. The organism was identified as M. haemophilum, on the basis of 16S rRNA gene sequence analysis. Prolonged culture in an optimal environment that includes an iron supplement, and growth temperatures at 28 degrees to 33 degrees C are necessary to grow M. haemophilum. Genotypic characterization of 16S rRNA is useful for a rapid diagnosis of this slowly growing mycobacterium.

Mycobacterium haemophilum, a recently described pathogen, can cause an array of symptoms in immunocompromised patients. To date, 90 patients with this infection have been described worldwide. We report our institution's experience with 23 patients who were treated from 1990 through 2000. Fourteen patients had undergone bone marrow transplantation, 5 were infected with human immunodeficiency virus, 3 had hematologic malignancies, and 1 had no known underlying immunosuppression. Clinical syndromes on presentation included skin lesions alone in 13 patients, arthritis or osteomyelitis in 4 patients, and lung disease in 6 patients. Although patients with skin or joint involvement had favorable outcomes, 5 of 7 patients with lung infection died. Prolonged courses of multidrug therapy are required for treatment. A diagnosis of M. haemophilum infection must be considered for any immunocompromised patient for whom acid-fast bacilli are identified in a cutaneous, synovial fluid or respiratory sample or for whom granulomas are identified in any pathological specimen.

Acid-fast bacilli from pediatric patients with lymphadenopathy were detected in the BACTEC radiometric system and in MB Redox broth, but not on Löwenstein Jensen medium. PCR amplification identified the isolates as Mycobacterium haemophilum, which has special nutrition requirements (iron supplements) for growth. Suitable culture medium ensures optimal recovery of this microorganism, avoiding underdiagnosis.

We describe a case of osteomyelitis due to Mycobacterium haemophilum in a cardiac transplant recipient and review the two other reported cases of M. haemophilum infection in cardiac transplant patients. Our patient had an excellent response to a prolonged course of therapy with clarithromycin and rifampin. We examine in detail the interactions between these two antibiotics and cyclosporine, including the apparently offsetting effects of clarithromycin/rifampin combination therapy on blood levels of cyclosporine.

Reports of the association of Mycobacterium haemophilum with disease in humans have greatly increased. At least 64 cases have now been reported, with symptoms ranging from focal lesions to widespread, systemic disease. The organism is now known to cause primarily cutaneous and subcutaneous infection, septic arthritis, osteomyelitis, and pneumonitis in patients who are immunologically compromised and lymphadenitis in apparently immunocompetent children. Underlying conditions in the compromised patients have included AIDS; renal, bone marrow, and cardiac transplantation; lymphoma; rheumatoid arthritis; marrow hypoplasia; and Crohn's disease. Reports have originated from diverse geographic areas worldwide. The epidemiology of M. haemophilum remains poorly defined; there appears to be a genetic diversity between strains isolated from different regions. The organism is probably present in the environment, but recovery by sampling has not been successful. M. haemophilum has several unique traits, including predilection for lower temperatures (30 to 32 degrees C) and requirement for iron supplementation (ferric ammonium citrate or hemin). These may in the past have compromised recovery in the laboratory. Therapy has not been well elucidated, and the outcome appears to be influenced by the patient's underlying immunosuppression. The organisms are most susceptible to ciprofloxacin, clarithromycin, rifabutin, and rifampin. Timely diagnosis and therapy require communication between clinician and the laboratory.

History and Findings: A 35-year-old HIV-infected man with a CD4 cell count of 100/microliter who had returned from a holiday in Spain presented with fever, chronic diarrhoea, cough, oral ulcers, subcutaneous nodules of about 1 cm in diameter and crusted skin ulcers of about 2 cm in diameter at his right arm, both wrists and buttocks., Investigations: Microscopic examination and culture of smears of a skin ulcer revealed acid-fast bacteria. Mycobacterial cultures of blood, sputum, urine and stool remained sterile., Treatment and Course: Before the microorganisms were identified culturally, atypical mycobacteriosis was assumed and treatment with rifampicin, ethambutol, isoniazid and clarithromycin was started. Mycobacterium haemophilum was identified by using molecular biological techniques. Within 3 weeks the patient became afebrile and the skin ulcers healed completely. After a 7-week course, the treatment had to be stopped, and one month later painful subcutaneous nodules developed again at his arms and legs. A relapse of Mycobacterium haemophilum infection was confirmed by culture of a fine needle aspirate of a nodule. The same treatment was restarted and the nodules disappeared., Conclusions: Mycobacterium haemophilum, first identified in 1978, is an emerging pathogen in immunocompromised patients. Clinical manifestations usually are skin ulcers, subcutaneous nodules and subcutaneous abscesses, and less frequently, systemic infection. Treatment options of this life threatening disease have yet to be defined but therapeutic response to tuberculostatic combination therapy has been observed. Since Mycobacterium haemophilum is a fastidious organism, special laboratory methods are required for cultivation as well as for identification.

Biopsy samples from a heart transplant patient with cellulitis and bursitis yielded an isolate of Mycobacterium haemophilum. The isolate was identified on the basis of a growth requirement for haemin or ferric ammonium citrate, growth at 30 degrees C but not at 37 degrees C, negative catalase test, intracellular growth in McCoy fibroblasts and sequence identify with a portion of the 16S rRNA sequence of the type strain. In comparisons with known 16S rRNA sequences, M. haemophilum grouped with other pathogenic, slow-growing mycobacteria, showing close sequence similarity to M. marinum (98.8%) and lower similarity to M. ulcerans and M. tuberculosis complex organisms. M. haemophilum and M. marium share other features including optimal growth at 30 degrees C and the ability to cause superficial skin lesions in man.

A patient with indolent, non-Hodgkin's lymphoma developed a pretibial soft tissue abscess caused by a fastidious mycobacterium. Because the organism could not be definitively identified by standard microbiologic testing, whole cell fatty acid analysis and 16S rDNA sequencing were performed. These procedures identified the organism as Mycobacterium haemophilum. We review the diagnostic considerations with regard to this pathogen.

Mycobacterium haemophilum is emerging as a pathogen of immunocompromised patients particularly those with AIDS and organ transplants. Infection has also occurred in healthy children. Adults usually present with cutaneous manifestations, septic arthritis or occasionally pneumonia. Children have perihilar, cervical or submandibular adenitis. The organism grows on mycobacterial media supplemented with ferric ammonium citrate or hemin, incubated at 30 degrees C to 32 degrees C, two to three weeks after inoculation. The most active antimicrobial agents in vitro are amikacin, ciprofloxacin, clarithromycin, rifabutin and rifampin. Development of resistance to the rifamycins has been demonstrated after patients were treated for several months with several antimycobacterial agents, including the rifamycins. Treatment for several months with at least two agents demonstrated to have low MICs for the organism has been shown to be effective.