Ocular Mycobacterium haemophilum infection originating in the cornea: a case report.

BACKGROUND: Mycobacterium haemophilum is a slow-growing non-chromogenic nontuberculous Mycobacterium species that can cause skin infection or arthritis in an immunocompromised population or in children. Primary infection of the healthy adult cornea is rare. The special requirements for culture make this pathogen difficult to diagnose. The study aims to report the clinical manifestation and treatment process of corneal infection and notify the awareness of M. Haemophilus keratitis among clinicians. This is the first case report of primary M. haemophilum infection in the cornea of healthy adults reported in the literature. CASE PRESENTATION: A 53-year-old healthy goldminer presented with left eye redness and a history of vision loss for four months. The patient was misdiagnosed with herpes simplex keratitis until M. haemophilum was detected using high-throughput sequencing. Penetrating keratoplasty was performed, and a large number of mycobacteria were detected by Ziehl-Neelsen staining of the infected tissue. Three months later, the patient developed conjunctival and eyelid skin infections that manifested as caseous necrosis of the conjunctiva and skin nodules. After excision and debridement of the conjunctival lesions and systemic antituberculosis drug treatment for 10 months, the patient was cured. CONCLUSION: M. haemophilum could cause primary corneal infection in healthy adults, which is an infrequent or rare infection. Owing to the need for special bacterial culture conditions, conventional culture methods do not provide positive results. High-throughput sequencing can rapidly identify the presence of bacteria, which aids in early diagnosis and timely treatment. Prompt surgical intervention is an effective treatment option for severe keratitis. Long-term systemic antimicrobial therapy is crucial.

[Two severe cases of disseminated cutaneous nontuberculous mycobacteriosis due to Mycobacterium haemophilum]. / Zwei schwere Fälle von disseminiert-kutanen, nichttuberkulösen Mykobakteriosen durch Mycobacterium haemophilum.

Mycobacterium haemophilum is a rare pathogen belonging to the group of slowly growing nontuberculous mycobacteria (NTM) that can cause infections, especially in immunocompromised patients. Detection by culturing is difficult because M. haemophilum only grows under special cultivation conditions. Therefore, it is believed that the pathogen is too rarely identified as a cause of disease overall. In addition to patients with severe immunodeficiency, e.g. due to acquired immunodeficiency syndrome (AIDS), chemotherapy or immunosuppression after transplantation, patients with underlying rheumatic diseases are increasingly described in the literature, who are at risk due to the immunosuppressive treatment regimen. Clinically, ulcerative skin alterations, lymphadenopathy and arthropathy are in the foreground. In immunosuppressed patients with unclear skin lesions, infections due to M. haemophilum should be considered and specific microbiological diagnostics should be initiated.

Mycobacterium haemophilum infection with cutaneous involvement: two case reports and an updated literature review: Mycobacterium haemophilum skin infection.

Mycobacterium haemophilum (MH) is a slow-growing, non-tuberculous Mycobacterium that most commonly causes infections in immunocompromised patients. The skin is the most prevalent site of infection and can be an isolated presentation or part of a disseminated disease. Herein, we reported a case of isolated MH infection of the hand and a case of disseminated MH infection with multiple skin lesions. In addition, other MH cases with cutaneous involvement over the last 10 years, from 2011-2022, were reviewed and analyzed. Among the 79 included cases, the common skin findings in MH infections included nodules, ulcers, abscesses, swelling, and pustules. Middle-aged patients with iatrogenic immunosuppression from glucocorticoids, mycophenolate mofetil, cyclosporine, and cyclophosphamide are the most susceptible to MH infection, with a higher risk of dissemination to internal organs. Disseminated MH infections commonly present as tenosynovitis, arthritis/arthralgia, or osteomyelitis. There is a lack of strong evidence for treatment; however, triple therapy of quinolone, macrolides, and rifampicin is most often used in clinical practice. The overall prognosis is good. The presence of iatrogenic immunocompromised diseases, lesions involving the proximal limbs, and dissemination of MH infections are associated with worse clinical outcomes.

Cryptococcal fungemia and Mycobacterium haemophilum cellulitis in a patient receiving ruxolitinib: a case report and literature review.

BACKGROUND: Ruxolitinib is a novel oral Janus kinase inhibitor that is used for treatment of myeloproliferative diseases. It exhibits potent anti-inflammatory and immunosuppressive effects, and may increase the risk of opportunistic infections. Here, we report a rare case of Cryptococcus neoformans and Mycobacterium haemophilum coinfection in a myelofibrosis patient who was receiving ruxolitinib. CASE PRESENTATION: A 70-year-old Thai man who was diagnosed with JAK2V617F-mutation-positive primary myelofibrosis had been treated with ruxolitinib for 4 years. He presented with cellulitis at his left leg for 1 week. Physical examination revealed fever, dyspnea, desaturation, and sign of inflammation on the left leg and ulcers on the right foot. Blood cultures showed positive for C. neoformans. He was prescribed intravenous amphotericin B deoxycholate with a subsequent switch to liposomal amphotericin B due to the development of acute kidney injury. He developed new onset of fever after 1 month of antifungal treatment, and the lesion on his left leg had worsened. Biopsy of that skin lesion was sent for mycobacterial culture, and the result showed M. haemophilum. He was treated with levofloxacin, ethambutol, and rifampicin; however, the patient eventually developed septic shock and expired. CONCLUSIONS: This is the first case of C. neoformans and M. haemophilum coinfection in a patient receiving ruxolitinib treatment. Although uncommon, clinicians should be aware of the potential for multiple opportunistic infections that may be caused by atypical pathogens in patients receiving ruxolitinib.

Nontuberculous mycobacterial endophthalmitis: case series and review of literature.

BACKGROUND: To report three cases of nontuberculous mycobacterial (NTM) endophthalmitis following multiple ocular surgeries and to review previous literature in order to study the clinical profile, treatment modalities, and visual outcomes among patients with NTM endophthalmitis. METHODS: Clinical manifestation and management of patients with NTM endophthalmitis in the Department of Ophthalmology, Faculty of Medicine, Siriraj hospital, Mahidol University, Bangkok, Thailand were described. In addition, a review of previously reported cases and case series from MEDLINE, EMBASE, and CENTRAL was performed. The clinical information and type of NTM from the previous studies and our cases were summarized. RESULTS: We reported three cases of NTM endophthalmitis caused by M. haemophilum, M. fortuitum and M. abscessus and a summarized review of 112 additional cases previously published. Of 115 patients, there were 101 exogenous endophthalmitis (87.8%) and 14 endogenous endophthalmitis (12.2%). The patients' age ranged from 13 to 89 years with mean of 60.5 ± 17.7 years with no gender predominance. Exogenous endophthalmitis occurred in both healthy and immunocompromised hosts, mainly caused by cataract surgery (67.3%). In contrast, almost all endogenous endophthalmitis patients were immunocompromised. Among all patients, previous history of tuberculosis infection was identified in 4 cases (3.5%). Rapid growing NTMs were responsible for exogenous endophthalmitis, while endogenous endophthalmitis were commonly caused by slow growers. Treatment regimens consisted of macrolides, fluoroquinolones or aminoglycosides, which were continued for up to 12 months. Initial and final vision were generally worse than 6/60. CONCLUSIONS: NTM endophthalmitis is a serious intraocular infection that leads to irreversible loss of vision. The presentation can mimic a chronic recurrent or persistent intraocular inflammation. History of multiple intraocular surgeries or immune-deficiency in patient with chronic panuveitis should raise the practioner's suspicion of NTM endophthalmitis. Appropriate diagnosis and treatment are important to optimize visual outcome.

Mycobacterium haemophilum scleritis: two case reports and review of literature.

BACKGROUND: Mycobacterium haemophilum is a rare and emerging nontuberculous mycobacteria (NTM). It normally causes localized or disseminated systemic diseases, particularly skin infections and arthritis in severely immunocompromised patients. There have been 5 cases of M. haemophilum ocular infections reported in the literature. Only 1 case presented with scleritis with keratitis. Here, we reported 2 cases of M. haemophilum scleritis. One of them was immunocompetent host and had keratitis with radial keratoneuritis as a presenting sign. CASE PRESENTATION: Case 1: A 52-year-old Thai female with rheumatoid arthritis presented with scleritis. Conjunctival scraping was carried out and the culture result was positive for M. haemophilum. Despite receiving systemic and topical antibiotics, her clinical symptoms and signs worsened. Surgical debridement was performed. After surgery, the lesion was significantly improved and finally turned to conjunctival scarring. Case 2: A 32-year old healthy Thai male without underlying disease presented with nodular scleritis and keratouveitis with multiple radial keratoneuritis. Surgical debridement of the scleral nodule was performed. Initial microbiological investigations were negative. Herpes ocular infections was suspected. Topical antibiotics, oral acyclovir, low-dose topical steroids and systemic steroids were started. The scleral inflammation subsided but later the keratitis relapsed, requiring corneal biopsy. Histopathology of the specimen revealed acid-fast bacteria and M. haemophilum was identified by polymerase chain reaction (PCR) and sequencing. The diagnosis of Mycobacterial keratitis was made. Although using the combination of systemic and topical antibiotics, his clinical status progressively deteriorated. Multiple therapeutic penetrating keratoplasties were required to eradicate the infection. No recurrence was found during the 1-year follow-up in both cases. CONCLUSIONS: M. haemophilum can cause scleritis and keratitis, even in immunocompenent host. Radial keraoneuritis is first described in M. haemophilum keratitis. NTM keratitis should be considered in the differential diagnosis of patients with radial keratoneuritis. Increased awareness and early diagnosis using appropriate culture conditions and molecular techniques are important for the proper treatment of this infection. Prompt surgical intervention appears to be vital for successful management of M. haemophilum scleritis and keratitis.

Clinical Characteristics and Treatment Outcomes for Patients Infected with Mycobacterium haemophilum.

Mycobacterium haemophilum is a nontuberculous mycobacterium that can infect immunocompromised patients. Because of special conditions required for its culture, this bacterium is rarely reported and there are scarce data for long-term outcomes. We conducted a retrospective study at Siriraj Hospital, Bangkok, Thailand, during January 2012-September 2017. We studied 21 patients for which HIV infection was the most common concurrent condition. The most common organ involvement was skin and soft tissue (60%). Combination therapy with macrolides and fluoroquinolones resulted in a 60% cure rate for cutaneous infection; adding rifampin as a third drug for more severe cases resulted in modest (66%) cure rate. Efficacy of medical therapy in cutaneous, musculoskeletal, and ocular diseases was 80%, 50%, and 50%, respectively. All patients with central nervous system involvement showed treatment failures. Infections with M. haemophilum in HIV-infected patients were more likely to have central nervous system involvement and tended to have disseminated infections and less favorable outcomes.

Cluster of Lymphadenitis due to Nontuberculous Mycobacterium in Children and Adolescents 8-15 Years of Age.

BACKGROUND: Nontuberculous mycobacteria (NTM) lymphadenitis is an under-recognized entity, and data of the true burden in children are limited. Without a high index of suspicion, diagnosis may be delayed and microbiological detection is challenging. Here, we report a cluster of NTM lymphadenitis experienced in Korean children. METHODS: Subjects under 19 years of age diagnosed with NTM lymphadenitis during November 2016-April 2017 and April 2018 were included. Electronic medical records were reviewed for clinical, laboratory and pathological findings. Information regarding underlying health conditions and environmental exposure factors was obtained through interview and questionnaires. RESULTS: A total of ten subjects were diagnosed during 18 months. All subjects were 8-15 years of age, previously healthy, male and had unilateral, nontender, cervicofacial lymphadenitis for more than 3 weeks with no significant systemic symptoms and no response to empirical antibiotics. Lymph nodes involved were submandibular (n = 8), preauricular (n = 6) and submental (n = 1). Five patients had two infected nodes and violaceous discoloration was seen in seven subjects. Biopsy specimens revealed chronic granulomatous inflammation and acid-fast bacteria culture identified Mycobacterium haemophilum in two cases and NTM polymerase chain reaction was positive in two cases. Survey revealed various common exposure sources. CONCLUSION: NTM lymphadenitis is rare but increasing in detection and it may occur in children and adolescents. Diagnosis requires high index of suspicion and communication between clinicians and the laboratory is essential for identification of NTM.

Late-onset postoperative Mycobacterium haemophilum endophthalmitis masquerading as inflammatory uveitis: a case report.

BACKGROUND: Although atypical mycobacteria had been increasingly found in various ocular infections in the past decades, a slow-growing Mycobacterium haemophilum (M. haemophilum) was scarcely reported. Similar to tuberculous infection, the presentation can masquerade as low-grade granulomatous intraocular inflammation with partial response to corticosteroids. Besides, the special requirements for culture make this pathogen difficult to diagnose. The study aims to report the clinical presentation and notify the awareness of NTM endophthalmitis among clinicians. This is the first case report of late-onset, postoperative M. haemophilum endophthalmitis in the literature. CASE PRESENTATION: A 66-year-old man with non-insulin-dependent diabetes mellitus (NIDDM) manifested chronic granulomatous inflammation in the left eye after multiple glaucoma surgeries. With a diagnosis of noninfectious panuveitis, he was treated with systemic corticosteroids. The inflammation initially responded to therapy although it subsequently worsened and became purulent endophthalmitis. The vitreous cultures grew M. haemophilum. Intraocular and systemic antimicrobial treatments were administered early, but the patient eventually turned blind. CONCLUSIONS: M. haemophilum endophthalmitis is a rare but serious intraocular complication leading to loss of vision or eyeball. Awareness of atypical mycobacterial infections is necessary especially in patients with impaired immune function, previous intraocular surgery, and corticosteroid resistance. Proper laboratory investigations and treatments should be performed. However, due to the rarity of the disease, the development of guidelines for its investigation and therapy is still challenging.

Successful management of Mycobacterium haemophilum lower extremity cutaneous infection in a matched-unrelated donor stem cell transplant recipient.

Nontuberculous mycobacterial infections can often occur in individuals with adequate immune function. Such infections typically have cutaneous involvement and are caused by rapidly growing mycobacterium. Other nontuberculous mycobacteria species, like Mycobacterium haemophilum, almost always present as opportunistic infections occurring in severely immunocompromised hosts. Here, we present a complicated and protracted course of diagnosing M. haemophilum lower extremity cutaneous infection in a matched-unrelated donor stem cell transplant recipient.

Recurrent Mycobacterium haemophilum in a renal transplant recipient.

Mycobacterium haemophilum is a rare isolate of non-tuberculous Mycobacterium which has been reported to affect immunocompromised patients. We report a case of a 32-year-old renal transplant patient with M. haemophilum infection initially involving his left sinus which was treated with appropriate antimicrobial therapy for thirteen months. Two weeks after cessation of antibiotics the infection rapidly recurred in his skin and soft tissues of his hands and feet. This case highlights the difficult diagnostic and therapeutic implications of atypical infections in transplant patients. To our knowledge this is the first reported case of relapsed M. haemophilum infection in a renal transplant recipient.

Clinical manifestations, treatment and outcomes of patients infected with Mycobacterium haemophilum with a focus on immune reconstitution inflammatory syndrome: a retrospective multi-site study.

BACKGROUND: Mycobacterium haemophilum is a nontuberculous mycobacterium with fastidious in vitro growth requirements and an increasingly reported cause of extrapulmonary disease. Timely diagnosis and management of M. haemophilum infections and the immune reconstitution inflammatory syndromes (IRIS) observed in a subset of patients during treatment remain challenging. METHODS: We conducted a retrospective chart review between January 1, 2010, and January 1, 2022 and identified 26 patients diagnosed with M. haemophilum infection at our institution. We describe their clinical presentation, diagnostic results, management, and outcomes. RESULTS: The majority of patients in our cohort had upper and/or lower extremity skin involvement, were immunosuppressed, and had generally favourable treatment outcomes. All tested M. haemophilum isolates were susceptible in vitro to clarithromycin and trimethoprim-sulfamethoxazole. Moreover, high rates of susceptibility were noted for ciprofloxacin (95%), linezolid (90%), and rifampin (85%). IRIS was identified in 31% of cases and should be considered in patients who develop worsening skin lesions or systemic symptoms following the initiation of effective antimicrobial therapy. Visualisation of acid-fast bacilli on initial tissue stains, a positive mycobacterial blood culture, and rapid de-escalation of tumour necrosis factor-α inhibitors and/or corticosteroids were more frequently encountered among patients in our cohort who developed IRIS. CONCLUSION: M. haemophilum infection should be considered among patients receiving immunomodulatory therapy who develop discoloured or nodular skin lesions involving the extremities, worsening focal arthritis, tenosynovitis, or isolated adenopathy. A heightened awareness of this pathogen's clinical and laboratory characteristics can lead to a timely diagnosis and favourable outcome.

Osteomyelitis due to Mycobacterium haemophilum in an adult renal transplant recipient.

Mycobacterium haemophilum is an increasingly recognized pathogen of the non-tuberculous mycobacteria family that largely infects immunocompromised adults and immunocompetent children. M. haemophilum is a fastidious and slow-growing organism that exhibits preferential growth at lower temperature with iron supplemented media, and therefore most clinical manifestations involve cutaneous infection or musculoskeletal infection of the distal extremities. It is believed that opportunistic infection occurs in immunocompromised hosts when the organism is acquired through environmental exposure. We describe the case of a 71-year-old renal transplant recipient who developed acute M. haemophilum osteomyelitis of the left foot, likely contracted from Epsom salt soaks with contaminated tap water. Outcomes of M. haemophilum infection are generally favorable in the literature. Our patient was treated with local debridement and partial amputation followed by a 3-drug anti-mycobacterial regimen until definitive amputation could be completed.

Case report: Subcutaneous Mycobacterium haemophilum infection in an immunocompetent patient after lipolysis injections.

Mycobacterium haemophilum is a slow-growing, aerobic mycobacterium that acts as a pathogen in immunocompromised adult patients and immunocompetent children. There are only a few rare cases in the literature describing this species as a cause of subcutaneous infections. Here, we describe a subcutaneous infection caused by M. haemophilum in an immunocompetent female after lipolysis injections at an unqualified beauty salon, suggesting that this bacteria can also be a potential causative agent of adverse events in medical aesthetics. In addition, M. haemophilum caused lesions not only at the injection sites and adjacent areas but also invaded distant sections through the subcutaneous sinus tracts. Thus, early diagnosis and appropriate treatment are vital to prevent further deterioration and improve prognosis.

A Systemic Lupus Erythematosus Patient with Cutaneous Mycobacterium haemophilum Infection under Belimumab Treatment: A Case Report.

A 38-year-old female with systemic lupus erythematosus (SLE) initiated belimumab treatment. One month later, she presented with a reddish painful swelling on her right lower leg. She was treated with ceftriaxone and vancomycin. However, novel erythematous papules and indurated nodules appeared on both her lower legs. Skin biopsy revealed microabscess formation with mixed cell granuloma surrounded by inflammatory cell infiltration within the dermis with subcutaneous fat tissue. A large number of acid-fast bacilli were observed with Ziehl-Neelsen staining. DNA sequencing of both the hsp65 and the 16S rRNA sequences showed a 100% match with the corresponding region of Mycobacterium haemophilum. Mycobacterial culture revealed satellite growth enhancement on Middlebrook 7H11 agar plates around a paper strip containing hemin. She was treated with levofloxacin, rifabutin, and ethambutol. Within 13 months, her cutaneous lesions improved markedly without any side effects. The B cell-targeted biologic belimumab, a fully humanized IgG1γ monoclonal antibody that inactivates B lymphocyte stimulator, has been considered to be beneficial for active SLE. However, this therapy could increase the risk for the development of biologic therapy-associated mycobacterial infections, both tuberculosis and nontuberculous mycobacteria infections.

A Cold-Blooded Tiptoer: Nonresolving Cellulitis in an Immunocompromised Patient.

Mycobacterium haemophilum is a nontuberculous mycobacteria (NTM) with a predilection for skin and soft tissue infection (SSTI) in the immunocompromised host. We report a case of disseminated M haemophilum infection initially presenting as a nonresolving subacute cellulitis of bilateral lower extremities. Genetic sequencing was used for final identification, while a commercially available polymerase chain reaction test returned a false-positive result for Mycobacterium intracellulare. Consequently, we highlight the importance of M haemophilum as a major differential diagnosis of SSTI in the immunocompromised host and the need for careful interpretation of rapid diagnostic tests.