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1.
BMC Infect Dis ; 20(1): 365, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448204

RESUMO

BACKGROUND: Mycobacterium fortuitum complex is a group of rapidly growing nontuberculous mycobacteria (NTM) associated with skin and soft-tissue infections after surgery or trauma. Treatment of NTM is challenging, due to resistance to multiple antimycobacterial agents. Bedaquiline is a diarylquinoline that inhibits mycobacterial ATP-synthase. The drug has recently been approved for the treatment of multidrug-resistant tuberculosis and evidence of its in vitro efficacy against NTM, including Mycobacterium fortuitum complex, has been published. CASE PRESENTATION: A 20-year-old Caucasian woman with chronic skin and soft tissue infection in the lower leg following a traffic accident in Vietnam underwent a tedious journey of healthcare visits, hospital admissions, empiric antimicrobial treatments, surgical debridement and plastic reconstruction before definite diagnosis of Mycobacterium fortuitum complex-infection was established by culture from a tissue biopsy and targeted antimycobacterial therapy was administered. Histopathological examination revealed granulomatous purulent inflammation, which strongly supported the diagnosis. Genotypic identification was performed and broth microdilution for susceptibility testing showed macrolide resistance. Five weeks of induction treatment with intravenous amikacin, imipenem / cilastin, and oral levofloxacin was administered, followed by all-oral treatment with bedaquiline combined with levofloxacin for four months, which was well-tolerated and led to persistent healing with scars but without signs of residual infection. CONCLUSIONS: Bedaquiline is a promising novel agent for NTM treatment, although clinical data are limited and trials evaluating efficacy, safety, and resistance of bedaquiline are required. To our knowledge, this is the first reported case of successful in vivo use of bedaquiline for a skin and soft tissue infection caused by Mycobacterium fortuitum complex.


Assuntos
Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium fortuitum/efeitos dos fármacos , Dermatopatias Bacterianas/tratamento farmacológico , Pele/lesões , Infecções dos Tecidos Moles/tratamento farmacológico , Amicacina/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Humanos , Imipenem/uso terapêutico , Levofloxacino/uso terapêutico , Macrolídeos/efeitos adversos , Macrolídeos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium fortuitum/genética , Lesões dos Tecidos Moles/microbiologia , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Vietnã , Adulto Jovem
2.
BMC Infect Dis ; 20(1): 258, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32234012

RESUMO

BACKGROUND: Mycobacterial species other than Mycobacterium tuberculosis and Mycobacterium leprae are generally free-living organisms and Mycobacterium simiae is one of the slowest growing Non-tuberculous mycobacteria. This is the first case report of Mycobacterium simiae infection in Sri Lanka and only very few cases with extrapulmonary manifestation reported in the literature. CASE PRESENTATION: A 24-year-old, previously healthy Sri Lankan male presented with generalized lymphadenopathy with discharging sinuses, evening pyrexia, weight loss, poor appetite and splenomegaly. Lymph node biopsies showed sheets of macrophages packed with organisms in the absence of granulomata. Ziehl Neelsen, Wade Fite and Giemsa stains revealed numerous red coloured acid-fast bacilli within foamy histiocytes. Slit skin smear for leprosy was negative and tuberculosis, fungal and bacterial cultures of the lymph node and bone marrow did not reveal any growth. Later he developed watery diarrhea and colonoscopy revealed multiple small polyps and ulcers throughout the colon extending up to the ileum, Which was confirmed to be due to cytomegalovirus confirmed by PCR and successfully treated with ganciclovir. Positron emission tomography scan guided biopsies of the gut and lymph nodes confirmed presence of mycobacterial spindle cell pseudo-tumours and PCR assays revealed positive HSP65. The culture grew Mycobacterium Simiae. Flow cytometry analysis on patient's blood showed extremely low T and B cell counts and immunofixation revealed low immunoglobulin levels. His condition was later diagnosed as adult onset immunodeficiency due to anti- interferon - gamma autoantibodies. He was initially commenced on empirical anti-TB treatment with atypical mycobacterial coverage. He is currently on a combination of daily clarithromycin, ciprofloxacin, linezolid with monthly 2 g/kg/intravenous immunoglobulin to which, he had a remarkable clinical response with complete resolution of lymphadenopathy and healing of sinuses. CONCLUSIONS: This infection is considered to be restricted to certain geographic areas such as mainly Iran, Cuba, Israel and Arizona and this is the first case report from Sri lanka. Even though the infection is mostly seen in the elderly patients, our patient was only 24 years old. In the literature pulmonary involvement was common presentation, but in this case the patient had generalized lymphadenopathy and colonic involvement without pulmonary involvement.


Assuntos
Síndromes de Imunodeficiência/imunologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium/patogenicidade , Autoanticorpos/sangue , Ciprofloxacino/uso terapêutico , Claritromicina/uso terapêutico , Humanos , Biópsia Guiada por Imagem , Interferon gama/sangue , Linfonodos/microbiologia , Linfadenopatia/etiologia , Masculino , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/patologia , Tomografia por Emissão de Pósitrons , Sri Lanka , Adulto Jovem
4.
BMC Infect Dis ; 20(1): 232, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32188404

RESUMO

BACKGROUND: The most common infection in patients positive for anti-interferon-gamma autoantibodies (anti-IFN-γ AAbs) is disseminated nontuberculous mycobacterial (dNTM) infection. Here, we report a rare case of triple infection caused by Cryptococcus, varicella-zoster virus (VZV), and nontuberculous mycobacterium in a patient with anti-IFN-γ AAbs. CASE PRESENTATION: A 53-year-old Thai man presented with a progressively enlarging right cervical mass with low-grade fever and significant weight loss for 4 months. He also developed a lesion at his left index finger. A biopsy of that lesion showed granulomatous inflammation with yeast-like organisms morphologically consistent with cryptococcosis. Serum cryptococcal antigen was positive. Histopathology of a right cervical lymph node revealed chronic granulomatous lymphadenitis, and the lymph node culture grew Mycobacterium abscessus. One month later, he complained of vision loss in his left eye and subsequently developed a group of painful vesicles at the right popliteal area of S1 dermatome. Lumbar puncture was performed and his cerebrospinal fluid was positive for VZV DNA. His blood test for anti-HIV antibody was negative. Anti-IFN-γ AAbs was positive, but test for anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF AAbs) was negative. He was treated with amphotericin B plus fluconazole for cryptococcosis; a combination of amikacin, imipenem, azithromycin, and levofloxacin for dNTM infection; and, intravenous acyclovir for disseminated VZV infection. After treatment, our patient's fever and cervical lymphadenopathy were subsided, and his vision and visual acuity were both improved. CONCLUSIONS: This is the first case of triple infection with cryptococcosis, VZV, and dNTM in a patient who tested positive for anti-IFN-γ AAbs and negative for anti-GM-CSF AAbs. This case will increase awareness and heighten suspicion of these infections in patients with the described presentations and clinical characteristics, and this will accelerate diagnosis and treatment.


Assuntos
Criptococose/tratamento farmacológico , Síndromes de Imunodeficiência/complicações , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Aciclovir/uso terapêutico , Anfotericina B/uso terapêutico , Autoanticorpos , Coinfecção , Criptococose/microbiologia , Fluconazol/uso terapêutico , Herpesvirus Humano 3/imunologia , Humanos , Interferon gama/imunologia , Linfadenopatia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus , Infecção pelo Vírus da Varicela-Zoster/tratamento farmacológico
5.
BMC Infect Dis ; 20(1): 215, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164551

RESUMO

BACKGROUND: The poorly known mycobacterial species Mycobacterium monacense is a rapidly growing non-tuberculous mycobacterium that was first described in 2006 (Reischl et al., Int J Syst Evol Microbiol 56:2575-8, 2006); it has been reported that its isolation is usually associated with skin and lung infections, especially in immunosuppressed patients (Hogardt et al., Jpn J Infect Dis 61:77-8, 2008; Taieb et al., J Hand Surg Am 33:94-6, 2008; Therese et al., Lung India 28:124-6, 2011; Shojaei et al., Ann Lab Med 32:87-90, 2012; Romero et al., New Microbes New Infect 10:112-5, 2016 ). The clinical significance of Mycobacterium monacense is not yet fully understood. Here, we report the first isolation of Mycobacterium monacense from the blood culture of a patient in China with severe pneumonia. CASE PRESENTATION: On June 26, 2018, a 38-year-old man was admitted to the intensive care unit with breathing difficulty. One day prior, he was discovered with his face immersed in a small pond (non-chlorinated water) and with limb convulsions. He had undergone craniocerebral surgery after trauma 5 years earlier, which left him with epilepsy as a sequela. Bilateral diffuse ground-glass opacity was found in the lungs on chest X ray and chest CT image at admission. The result of the HIV serology test of the patient was negative. The patient was diagnosed with severe pneumonia. Drug-susceptible Klebsiella pneumoniae and Candida glabrata were isolated in the BALF, and yellow-pigmented colonies were isolated from blood cultures of the patient. The strain isolated from blood was identified by 16S rDNA sequencing as Mycobacteria monacense, which is a rapidly growing mycobacterium (RGM). The patient was treated with a combination of cefoperazone sulbactam, linezolid and voriconazole for 10 days, and the symptoms improved. During the one-year follow-up time, the patient did not relapse. CONCLUSIONS: We report the first case of M. monacense isolated from blood cultures in a patient with severe pneumonia, which provided evidence that the environmental microorganism possessed pathogenic characteristics.


Assuntos
Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium/isolamento & purificação , Pneumonia Bacteriana/microbiologia , Adulto , Hemocultura , Cefoperazona/uso terapêutico , China , DNA Ribossômico/genética , Humanos , Linezolida/uso terapêutico , Masculino , Mycobacterium/genética , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Sulbactam/uso terapêutico , Voriconazol/uso terapêutico
6.
Int J Infect Dis ; 92S: S46-S50, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32114200

RESUMO

Non-tuberculous mycobacteria (NTM) are ubiquitous dwellers of environmental niches and are an established cause of natural and nosocomial infections. The incidence of NTM infections is rising owing to a growing population of immunocompromised and vulnerable individuals, complex medical and surgical procedures, as well as increased awareness and diagnostic capabilities. The prevalence of different NTM varies between continents, regions, and countries. The true global burden of pulmonary and extrapulmonary disease is unknown and estimates are subject to under and/or over-estimation. Diagnosis requires confirmation by isolation of NTM along with clinical and radiological criteria, which may be suboptimal at all levels. Susceptibility testing is complex and clinical breakpoints are not available for many of the drugs. Frequently, NTM infections are not considered until late in the course of disease. Improved and rapid detection of tuberculosis cases in high-burden countries has, however, also brought NTM infections into the limelight, and has identified a need for research efforts towards rapid diagnostic tests and the identification of biomarkers to monitor the treatment response in patients with NTM infections.


Assuntos
Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Biomarcadores , Doenças Transmissíveis Emergentes/diagnóstico , Doenças Transmissíveis Emergentes/tratamento farmacológico , Doenças Transmissíveis Emergentes/microbiologia , Humanos , Incidência , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas/isolamento & purificação , Prevalência
8.
Int J Infect Dis ; 93: 208-210, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32105768

RESUMO

Talaromyces (formerly Penicillium) marneffei, a dimorphic fungus, is the most common opportunistic pathogen in human immunodeficiency viruses (HIV)-positive patients, but it rarely appears in HIV-negative individuals. Previously, in 2014, we reported the case of an HIV-negative Chinese woman with disseminated T. marneffei infection within an osteolytic lesion. Subsequently, she was followed up for 6 years, and we present an updated report of her clinical condition during the follow-up period. She presented with T. marneffei infection relapse and nontuberculous mycobacterium (NTM) infection. Laboratory tests showed anti-interferon-gamma (anti-IFN-γ) autoantibody-positive. Antifungals and anti-NTM treatment successfully improved her symptoms and laboratory results. This case highlights the type of infectious diseases that occurs as a result of immunodeficiency syndrome associated with anti-IFN-γ autoantibody.


Assuntos
Coinfecção/diagnóstico , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Micoses/diagnóstico , Talaromyces , Antifúngicos/uso terapêutico , Autoanticorpos , Feminino , Seguimentos , Humanos , Interferon gama/imunologia , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/imunologia , Micoses/complicações , Micoses/tratamento farmacológico , Micoses/imunologia , Osteólise , Recidiva
9.
Sci Rep ; 10(1): 928, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31988293

RESUMO

Infections caused by Mycobacterium abscessus are increasing in prevalence in cystic fibrosis patients. This opportunistic pathogen's intrinsic resistance to most antibiotics has perpetuated an urgent demand for new, more effective therapeutic interventions. Here we report a prospective advance in the treatment of M. abscessus infection; increasing the susceptibility of the organism to amoxicillin, by repurposing the ß-lactamase inhibitor, relebactam, in combination with the front line M. abscessus drug imipenem. We establish by multiple in vitro methods that this combination works synergistically to inhibit M. abscessus. We also show the direct competitive inhibition of the M. abscessus ß-lactamase, BlaMab, using a novel assay, which is validated kinetically using the nitrocefin reporter assay and in silico binding studies. Furthermore, we reverse the susceptibility by overexpressing BlaMab in M. abscessus, demonstrating relebactam-BlaMab target engagement. Finally, we highlight the in vitro efficacy of this combination against a panel of M. abscessus clinical isolates, revealing the therapeutic potential of the amoxicillin-imipenem-relebactam combination.


Assuntos
Amoxicilina/farmacologia , Compostos Azabicíclicos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Imipenem/farmacologia , Mycobacterium abscessus/efeitos dos fármacos , Inibidores de beta-Lactamases/farmacologia , Amoxicilina/uso terapêutico , Compostos Azabicíclicos/metabolismo , Compostos Azabicíclicos/uso terapêutico , Sítios de Ligação , Cefalosporinas/metabolismo , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Imipenem/uso terapêutico , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium abscessus/enzimologia , Plasmídeos/genética , Inibidores de beta-Lactamases/metabolismo , beta-Lactamases/genética , beta-Lactamases/metabolismo
10.
Infection ; 48(2): 165-171, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31098926

RESUMO

PURPOSE: Extrapulmonary infections due to M. xenopi, particularly osteoarticular localizations, are rare. The purpose of this paper is to describe a case of prosthetic hip infection and to review the published literature on cases of M. xenopi osteoarticular infections. METHODS: Literature search was performed in the following databases: MEDLINE (PubMed), Embase, Central (the Cochrane Library 2019, Issue 1), LILACS (BIREME) (Latin American and Caribbean Health Science Information database) and Clinical Trials databases (14th August 2018). We included all case reports and case series on adult patients diagnosed with bone or joint infection by M. xenopi for whom the treatment and outcome were specified. RESULTS: We retrieved 30 cases published between 1982 and 2012, among which 25 (83.3%) were reported from Europe. The two most common infection sites were spine (12/30, 40%) and knee (9/30, 30%). Risk factors for infection were previous invasive procedures (11/30, 36.7%), autoimmune disease (8/30, 26.7%), AIDS (4/30, 13.3%) and other comorbidities (2/30, 6.7%); five patients had no past medical history. All patients were treated with antibiotic combinations, but composition and duration of regimens hugely varied. Surgical intervention was performed in 16 patients (53.3%). Only 11 patients obtained full recovery of articular mobility after treatment. CONCLUSION: This work highlights the difficulties in diagnosing and treating M. xenopi osteoarticular infections. Globally, evidence supporting the best practice for diagnosis and treatment of this infection is scanty.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium xenopi/fisiologia , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Idoso , Artroplastia de Quadril/efeitos adversos , Humanos , Imagem por Ressonância Magnética , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnóstico por imagem , Infecções Relacionadas à Prótese/diagnóstico por imagem , Resultado do Tratamento
11.
J Craniofac Surg ; 31(1): 278-282, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31842068

RESUMO

Ventricular shunt infections caused by nontuberculous mycobacteria are uncommon, and those caused by Mycobacterium abscessus are particularly rare. This mycobacterium is intrinsically resistant to first-line anti-tuberculous drugs and is considered the most pathogenic of the atypical, rapidly growing mycobacteria. Given the paucity of reported M. abscessus ventricular shunt infections, the appropriate surgical treatment for these cases, especially in the pediatric setting, has yet to be described. The authors present a 4-year-old male with history of intraventricular hemorrhage resulting in hydrocephalus who presented with an M. abscessus ventricular shunt infection that disseminated to the skin and soft tissue of the entire shunt tract. Despite aggressive antimicrobial therapy, several shunt exchanges, and numerous incisions and debridements of separate infected tract areas, the patient's clinical course was prolonged by multiple relapses and re-admissions. Only after opening and debriding the entire length of the infected tract, which measured 100 cm and extended from the scalp to the groin, and months of intrathecal antibiotics did CSF and tissue culture results become negative, and the entire tract was able to be closed. This article describes the management of the second-encountered pediatric M. abscessus shunt infection along with the management of the 4 previously reported cases. In addition, it highlights the vital role of early, aggressive surgical debridement to achieve infection eradication.


Assuntos
Desbridamento/efeitos adversos , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus/fisiologia , Derivação Ventriculoperitoneal/efeitos adversos , Antibacterianos/uso terapêutico , Pré-Escolar , Humanos , Hidrocefalia/etiologia , Masculino , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico
12.
Proc Natl Acad Sci U S A ; 117(1): 629-634, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31871194

RESUMO

Antibiotic resistance in bacteria is typically conferred by proteins that function as efflux pumps or enzymes that modify either the drug or the antibiotic target. Here we report an unusual mechanism of resistance to macrolide-lincosamide antibiotics mediated by mycobacterial HflX, a conserved ribosome-associated GTPase. We show that deletion of the hflX gene in the pathogenic Mycobacterium abscessus, as well as the nonpathogenic Mycobacterium smegmatis, results in hypersensitivity to the macrolide-lincosamide class of antibiotics. Importantly, the level of resistance provided by Mab_hflX is equivalent to that conferred by erm41, implying that hflX constitutes a significant resistance determinant in M. abscessus We demonstrate that mycobacterial HflX associates with the 50S ribosomal subunits in vivo and can dissociate purified 70S ribosomes in vitro, independent of GTP hydrolysis. The absence of HflX in a ΔMs_hflX strain also results in a significant accumulation of 70S ribosomes upon erythromycin exposure. Finally, a deletion of either the N-terminal or the C-terminal domain of HflX abrogates ribosome splitting and concomitantly abolishes the ability of mutant proteins to mediate antibiotic tolerance. Together, our results suggest a mechanism of macrolide-lincosamide resistance in which the mycobacterial HflX dissociates antibiotic-stalled ribosomes and rescues the bound mRNA. Given the widespread presence of hflX genes, we anticipate this as a generalized mechanism of macrolide resistance used by several bacteria.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana/genética , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium abscessus/fisiologia , Subunidades Ribossômicas Maiores de Bactérias/metabolismo , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Lincosamidas/farmacologia , Lincosamidas/uso terapêutico , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Mutação , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium smegmatis/efeitos dos fármacos , Mycobacterium smegmatis/fisiologia , Biossíntese de Proteínas/efeitos dos fármacos , Domínios Proteicos/genética , RNA Bacteriano/metabolismo , RNA Mensageiro/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo
13.
BMJ Case Rep ; 12(12)2019 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-31818890

RESUMO

We present a case of a 28-year-old woman who came to medical attention after noticing a breast mass associated with an overlying eroded plaque of the skin. A core biopsy of the breast mass was negative for malignancy but demonstrated granulomatous inflammatory changes. Acid-fast bacilli and Gomori methenamine-silver stains were negative for microorganisms. The patient was diagnosed with presumptive idiopathic granulomatous mastitis and started on oral steroids. Her symptoms progressed. Tissue culture from a repeat biopsy grew Mycobacterium mucogenicum The patient responded well to combination oral antimicrobial therapy.


Assuntos
Mastite Granulomatosa/diagnóstico , Mycobacteriaceae , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Dermatopatias Bacterianas/microbiologia , Infecções dos Tecidos Moles/microbiologia , Adulto , Claritromicina/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Dermatopatias Bacterianas/diagnóstico , Dermatopatias Bacterianas/tratamento farmacológico , Infecções dos Tecidos Moles/diagnóstico , Infecções dos Tecidos Moles/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
14.
BMJ Case Rep ; 12(12)2019 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-31818891

RESUMO

Mycobacterium c helonae is one of the rapidly growing non-tuberculous mycobacteria that can be isolated from water, soils and aerosols. Localised infections have been reported associated with tattoo parlours, pedicures and cosmetic procedures. But disseminated infection is usually associated with individuals who are immunocompromised, predominantly affecting limbs but sparing abdomen and back. We herein present a case where patient was on immunosuppressive therapy and developed locally severe infection around right ankle. A 69-year-old woman known to rheumatology presents in outpatients with severe pain in right ankle, unable to bear weight, oedematous right foot and lower leg. There was extensive erythematous cellulitic skin rash around right ankle and lower leg. She had background history of systemic lupus erythematosus with previous history of cardiac myositis and left foot drop. She had six cycles of cyclophosphamide for flare of lupus and after last cycle developed this presentation. Skin biopsy was arranged with dermatologist, cultures from which grew M . chelonae She was admitted and started on triple regimen for M . chelonae as per Microbiology guidelines with intention to complete 6-12 months treatment. Patient responded very well to treatment but unfortunately, she died after 5 months on treatment due to other comorbidities and likely cause of death was cardiac arrhythmia.


Assuntos
Hospedeiro Imunocomprometido , Lúpus Eritematoso Sistêmico/imunologia , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium chelonae , Dermatopatias Bacterianas/diagnóstico , Dermatopatias Bacterianas/microbiologia , Idoso , Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Imipenem/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Dermatopatias Bacterianas/complicações , Dermatopatias Bacterianas/tratamento farmacológico , Tobramicina/uso terapêutico , Resultado do Tratamento
15.
Molecules ; 24(24)2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31835481

RESUMO

Mycobacterium abscessus is a rapid-growing, multidrug-resistant, non-tuberculous mycobacterial species responsible for a variety of human infections, such as cutaneous and pulmonary infections. M. abscessus infections are very difficult to eradicate due to the natural and acquired multidrug resistance profiles of M. abscessus. Thus, there is an urgent need for the development of effective drugs or regimens against M. abscessus infections. Here, we report the activity of a US Food and Drug Administration approved drug, thiostrepton, against M. abscessus. We found that thiostrepton significantly inhibited the growth of M. abscessus wild-type strains, subspecies, clinical isolates, and drug-resistant mutants in vitro and in macrophages. In addition, treatment of macrophages with thiostrepton significantly decreased proinflammatory cytokine production in a dose-dependent manner, suggesting an inhibitory effect of thiostrepton on inflammation induced during M. abscessus infection. We further showed that thiostrepton exhibits antimicrobial effects in vivo using a zebrafish model of M. abscessus infection.


Assuntos
Antibacterianos/farmacologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus/efeitos dos fármacos , Tioestreptona/farmacologia , Animais , Antibacterianos/química , Antibacterianos/uso terapêutico , Linhagem Celular , Citocinas/biossíntese , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Mediadores da Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Testes de Sensibilidade Microbiana , Estrutura Molecular , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/metabolismo , Mycobacterium abscessus/classificação , Mycobacterium abscessus/genética , Tioestreptona/uso terapêutico , Peixe-Zebra
16.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(12): 901-906, 2019 Dec 12.
Artigo em Chinês | MEDLINE | ID: mdl-31826533

RESUMO

Objective: To investigate the clinical characteristics and drug susceptibility test (DST) of patients infected with different nontuberculous mycobacteria (NTM). Methods: The patients with nontuberculous mycobacterial lung disease (NMLD) in Shanghai Pulmonary Hospital from March 2014 to March 2015 were studied retrospectively by analyzing the clinical characteristics, radiological features and DST results. A total of 201 NMLD patients [male 108, age(58±15) yrs] were enrolled into this study including 48 cases of M. Kansasii [male 13, age (52±16) yrs],46 cases of M. Abscess[male 46, age (57±16) yrs], 92 cases of M. Intracellulare [male 43, age (61±13) yrs], and 15 cases of M. Avium [male 6, age (67±10) yrs]. Clinical data were collected when the diagnosis was made and Chi-square test was used to compare the differences among 4 groups of patients. Bonferroni method was used for further pairwise comparisons. Results: There were significant differences among the 4 groups in the age(χ(2)=6.42, P<0.001) and the gender(χ(2)=49.18, P<0.001) of the patients. The history of bronchiectasis in the groups of M. Kansasii, M. Abscess, M. Intracellulare and M. Avium were 2/48, 31/46, 39/92 and 4/15 cases respectively(χ(2)=41.84, P<0.001). For the Gamma-interferon release assays (ELISA) (IGRA), the positive rate of IGRA in the groups of M. Kansasii, M. Abscess, M. Intracellulare and M. Avium were 83%(40/48), 30%(14/46), 23%(21/92) and 33% (5/15) respectively(χ(2)=50.96, P<0.001). The radiological features were significantly different in tree-in-bud(8/48, 35/46, 36/92 and 4/15 cases respectively, χ(2)=36.48, P<0.001), pleural thickness or mild effusion (21/48, 36/46, 69/92 and 7/15 cases, χ(2)=19.54, P<0.001), bronchiectasis (20/48, 39/46, 78/92 and 10/15 cases, P<0.001) and cavities (38/48, 21/46, 63/92 and 10/15 cases, χ(2)=12.38, P<0.001) among the 4 groups(M. Kansasii, M. Abscess, M. Intracellulare and M. Avium). The drug resistance rates of M. Kansasii to rifampin, ethambutanol and ofloxacin were 10%(5/48), 8%(4/48) and 15%(7/48) respectively; the resistance rates of M.Intracellulare to ethambutanol was 45%(41/92), and the resistance rates of M.Abscess were all over 80% to all anti-TB drugs. The results of pairwise comparisons showed that the male proportion(46/48) and IGRAs positive rate(40/48) of patients with M. Kansasii were higher than those of other groups, and the incidence of bronchiectasis(20/48) and pleural changes(21/48) was lower than those of other groups. The female ratio(33/46), history of bronchiectasis (31/46) and tree-in-bud sign of patients(35/46) with M. Abscess were higher than those of other groups. Conclusions: There were differences in the clinical manifestations and imaging features of 4 common NMLD diseases, which were helpful for clinical differentiation. The patients with M. Kansasii infection were mainly male, with a high IGRA positive rate and fewer lesions of bronchiectasis or pleural changes. Most of the patients with M. Abscess were female, with a previous history of bronchiectasis, and with most of the lesions showing tree-in-bud signs. The NTM species had a high rate of resistance to anti-TB drugs except M. Kansasii.


Assuntos
Antibacterianos/farmacologia , Pneumopatias/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Micobactérias não Tuberculosas/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Farmacorresistência Bacteriana , Etambutol/farmacologia , Feminino , Humanos , Pneumopatias/microbiologia , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas/isolamento & purificação , Ofloxacino/farmacologia , Estudos Retrospectivos , Rifampina/farmacologia , Especificidade da Espécie
17.
BMJ Case Rep ; 12(12)2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31826907

RESUMO

A 66-year-old man was seen in clinic due to concerns of tuberculosis of the right hip. He had a history of urothelial bladder carcinoma, which was treated via transurethral resection followed by intravesicular instillations of Mycobacterium bovis BCG (BCG). A few months later, he developed slowly worsening pain over his prosthetic right hip, and it was recommended he undergo surgical revision. During surgery, joint effusion was noted and synovial fluid was sent for bacterial and mycobacterial cultures, growing an acid-fast bacillus after 3 weeks, identified as Mycobacterium tuberculosis complex via nucleic acid probe. Susceptibility testing revealed resistance to pyrazinamide, which is typically seen in M. bovis PCR confirmed the diagnosis of BCG infection. The patient was treated with isoniazid, rifampin and ethambutol, which he tolerated well. This case highlights the challenges associated with diagnosis and management of this rare complication of a commonly used therapy.


Assuntos
Antibióticos Antituberculose/uso terapêutico , Vacina BCG/efeitos adversos , Isoniazida/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Rifampina/uso terapêutico , Idoso , Artroplastia de Quadril , Vacina BCG/uso terapêutico , Humanos , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnóstico por imagem , Falha de Prótese , Infecções Relacionadas à Prótese/diagnóstico por imagem , Infecções Relacionadas à Prótese/tratamento farmacológico , Resultado do Tratamento
18.
Biomed Res Int ; 2019: 8631563, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31828137

RESUMO

Background: Treatment response for the Mycobacterium abscessus (M. abscessus) lung disease remains far from satisfying. An effective regimen is needed to solve the problem. Methods: We retrospectively reviewed the medical records of all patients with M. abscessus lung disease who received antibiotics regimen at Beijing Chest Hospital Affiliated to Capital Medical University between July 1, 2010, and February 1, 2018. Patients were administered a conventional antibiotics regimen (including macrolide and moxifloxacin, along with an initial 12-week course of low-dose cefoxitin and amikacin) or intensified regimen (including a higher dosage of cefoxitin and linezolid besides conventional drugs), respectively. The time to sputum-culture conversion and proportion of sputum-culture conversion in liquid broth were investigated to evaluate the efficacy and evaluation of safety by performing the classification of adverse events according to the Division of AIDS, National Institute of Allergy and Infectious Disease. Patients were followed for 18 months from baseline. Results: In the conventional regimen group, the sputum conversion rate at 18 months was 29.4% (10/34), and the median time until sputum conversion was 2 months (IQR, 1-2 mo). Furthermore, in the intensified regimen group, the sputum conversion rate was 81.3% (13/16), and the median time until sputum conversion was 1 month (IQR, 1-1 mo). Leukopenia and drug-induced hepatotoxicity occurred more frequently in the intensified regimen group in contrast with the conventional regimen group patients. However, only 1 adverse event in the intensified regimen group was classified as severe adverse event. Conclusions: The intensified regimen could improve sputum conversion of M. abscessus lung disease compared with conventional regimen, but close safety surveillance is necessary to monitor adverse events.


Assuntos
Antibacterianos , Linezolida , Pneumopatias/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium abscessus , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Feminino , Humanos , Linezolida/administração & dosagem , Linezolida/efeitos adversos , Linezolida/uso terapêutico , Pneumopatias/microbiologia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/microbiologia , Estudos Retrospectivos
19.
BMC Infect Dis ; 19(1): 1034, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805893

RESUMO

BACKGROUND: The incidence of Taralomyces marneffei infection in HIV-infected individuals has been decreasing, whereas its rate is rising among non-HIV immunodeficient persons, particularly patients with anti-interferon-gamma autoantibodies. T. marneffei usually causes invasive and disseminated infections, including fungemia. T. marneffei oro-pharyngo-laryngitis is an unusual manifestation of talaromycosis. CASE PRESENTATION: A 52-year-old Thai woman had been diagnosed anti-IFNÉ£ autoantibodies for 4 years. She had a sore throat, odynophagia, and hoarseness for 3 weeks. She also had febrile symptoms and lost 5 kg in weight. Physical examination revealed marked swelling and hyperemia of both sides of the tonsils, the uvula and palatal arches including a swelling of the epiglottis, and arytenoid. The right tonsillar biopsy exhibited a few intracellular oval and elongated yeast-like organisms with some central transverse septum seen, which subsequently grew a few colonies of T. marneffei on fungal cultures. The patient received amphotericin B deoxycholate 45 mg/dayfor 1 weeks, followed by oral itraconazole 400 mg/day for several months. Her symptoms completely resolved without complication. CONCLUSION: In patients with anti-IFN-É£ autoantibodies, T. marneffei can rarely cause a local infection involving oropharynx and larynx. Fungal culture and pathological examination are warranted for diagnosis T. marneffei oro-pharyngo-laryngitis. This condition requires a long term antifungal therapy.


Assuntos
Antifúngicos/uso terapêutico , Laringite/tratamento farmacológico , Micoses/tratamento farmacológico , Faringite/tratamento farmacológico , Talaromyces/patogenicidade , Anfotericina B/uso terapêutico , Autoanticorpos/sangue , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Interferon gama/imunologia , Itraconazol/uso terapêutico , Laringite/microbiologia , Laringite/patologia , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium abscessus/patogenicidade , Micoses/etiologia , Micoses/microbiologia , Faringite/microbiologia , Faringite/patologia , Tailândia
20.
J Korean Med Sci ; 34(46): e302, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31779059

RESUMO

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.


Assuntos
Linfadenite/diagnóstico , Infecções por Mycobacterium não Tuberculosas/patologia , Adolescente , Antibacterianos/uso terapêutico , Criança , Humanos , Linfadenite/tratamento farmacológico , Linfadenite/etiologia , Masculino , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium haemophilum/genética , Mycobacterium haemophilum/isolamento & purificação , Micobactérias não Tuberculosas/genética , Micobactérias não Tuberculosas/isolamento & purificação , RNA Bacteriano/metabolismo
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