Clinical significance, antimicrobial susceptibility and molecular identification of Nocardia species isolated from children with cystic fibrosis

ABSTRACT Nocardia is an opportunistic pathogen that causes respiratory infections in immunocompromised patients. The aim of this study was to analyze the epidemiology, clinical significance and antimicrobial susceptibility of Nocardia species isolated from eight children with cystic fibrosis. The isolated species were identified as Nocardia farcinica, Nocardia transvalensis, Nocardia pneumoniae, Nocardia veterana and Nocardia wallacei. N. farcinica was isolated in three patients and all of them presented lung affectation with a chronic colonization and pneumonia. N. farcinica showed resistance against gentamicin, tobramycin, cefotaxime, but was susceptible to trimethoprim-sulfamethoxazole and amikacin. N. transvalensis, which was isolated from two patients, showed an association with chronic colonization. N. transvalensis was resistant to tobramycin and amikacin, but susceptible to ciprofloxacin, trimethoprim-sulfamethoxazole and cefotaxime. N. veterana, N. pneumoniae and N. wallacei were isolated from three different patients and appeared in transitory lung colonization. N. veterana and N. pneumoniae were susceptible to imipenem, trimethoprim-sulfamethoxazole, amikacin, tobramycin, and cefotaxime. N. wallacei was resistant to amikacin, tobramycin, imipenem, and trimethoprim-sulfamethoxazole and susceptible to ciprofloxacin and cefotaxime. All the isolates were identified up to species level by 16S rRNA gene sequencing. The presence of Nocardia in the sputum of patients with cystic fibrosis is not always an indication of an active infection; therefore, the need for a treatment should be evaluated on an individual basis. The detection of multidrug-resistant species needs molecular identification and susceptibility testing, and should be performed for all Nocardia infections.

A case of atypical nocardia asteroides sclerouveitis resistant to fourth-generation fluoroquinolones / Um caso atípico de esclero-uveíte por Nocardia Asteroides resistente a fluorquinolona de quarta-geração

ABSTRACT We describe an unusual case of Nocardia spp scleritis in a health girl resistant to topical fourth-generation fluoroquinolones. Clinically, there was only partial response of the scleritis to initial therapy. Treatment was changed to meropenem intravenously and topical amikacin. Following several weeks of antibiotic treatment, the patient's infection resolved but her vision was reduced to no light perception. Nocardia asteroides must be considered as a possible agent in cases of necrotizing scleritis in patients without a clear source. Antibiotic sensitivity testing has a definitive role in view of the resistance to these new medications.

RESUMO Nós descrevemos um raro caso de esclerite por Nocardia spp em uma criança sadia resistente a utilização tópica de fluorquinolona de quarta-geração. Clinicamente, a paciente apresentou apenas uma resposta parcial do quadro de esclerite a terapêutica inicial. O tratamento foi então modificado para meropenem intravenoso e amicacina tópica. Após várias semanas de tratamento com antibiótico, o quadro infeccioso regrediu porém a visao da pacientes evoluiu para perda da percepção luminosa. Em casos de esclerite necrotizante em pacientes sem fatores de risco aparente é necessário considerer a Nocardia Asteroides como possível agente causador. Os testes de sensibilidade medicamentosa apresentam importância significativa em virtude do aparecimento de resistência aos novos medicamentos.

Long-term treatment of persistent disseminated Nocardia cyriacigeorgica infection

In this paper a disseminated persistent Nocardia cyriacigeorgica infection in an immunocompetent patient is described. The patient's long-term treatment, as well as its implications for managing similar cases in the future, is emphasized. Presenting with high fever, multiple nodules, and ulcerative cutaneous lesions of body sites, the patient was treated with various antimicrobials. Under combined therapy, empyema and arthritis, leading to disseminated nocardiosis, were seen. The overall treatment course was 28 months. It can be concluded that the choice of the antibiotics and optimal duration of treatment are uncertain; therefore the treatment of nocardiosis requires expertise.

Nocardia abscessus brain abscess in an immunocompetent host

Nocardia brain abscesses typically occur in immunocompromised patients. Most cases of nocardiosis are caused by the Nocardia asteroides complex and Nocardia brasiliensis. Here, we present a patient with a Nocardia abscessus brain abscess. The diagnosis was confirmed by DNA sequencing, and the organism was susceptible to linezolid, clarithromycin, ceftriaxone, imipenem, tobramycin, amikacin, minocycline and sulfamethoxazole. The patient was successfully treated medically in combination with surgical excision

Management of post-operative Nocardia endophthalmitis.

Post-operative Nocardia endophthalmitis has an aggressive course and poor visual prognosis. It often masquerades as severe post-operative uveitis or toxic anterior segment syndrome due to the absence of vitreous involvement resulting in a delay in diagnosis. The poor prognosis in Nocardia endophthalmitis is due to severe intra-ocular inflammation which may lead to phthisis. Therefore, treatment with corticosteroids after appropriate antibiotics have been initiated may improve the outcome. This is an interventional case report highlighting the typical features of Nocardia endophthalmitis, which when diagnosed early and managed medically with antibiotics and steroids, resulted in an excellent visual outcome in our patient.

Successful treatment of pulmonary Nocardia farcinica infection with linezolid: case report and literature review

Nocardia infection is rare but potentially fatal. Therapy of Nocardia infection remains difficult. Linezolid, a novel oxazolidinone antibiotic, has proven to be effective, but clinical data are limited. Here we describe a case of a 45-year-old man with pulmonary N. farcinica infection following a liver transplantation. The initial therapy was trimethoprim-sulfamethoxazole, which showed no effect. According to susceptibility test, linezolid was administered with clearly improving the patient's condition. The treatment was stopped for anemia as drug related adverse event, and the therapy lasted for as long as 5 months. At the end of treatment clinical cure was confirmed and anemia reversed after discontinuation of linezolid. We also analyzed the clinical data of previously published reports by literature review, focusing on the efficacy and safety of linezolid treatment for Nocardia infection.

Nocardiosis linfocutánea por Nocardia brasiliensis / Lymphocutaneous nocardiosis due to Nocardia brasiliensis

La nocardiosis linfocutánea es una de las formas clínicas de nocardiosis cutánea, producida en la mayoría de los casos por Nocardia brasiliensis. Puede ser difícil de diagnosticar sin una alta sospecha clínica, debido a su semejanza con otras enfermedades que pueden presentarse con patrones linfocutáneos. Los pacientes con nocardiosis cutánea tienen a menudo una historia previa de traumatismo cutáneo, ya sea herida punzante, picadura de insecto o abrasiones contaminadas. Se comunica un caso de nocardiosis linfocutánea primaria en una paciente inmunocompetente, de 33años.

Nocardiosis cutánea y sus formas clínicas / Cutaneous nocardiosis and its various presentations

La nocardiosis cutánea es una dermatosis infecciosa poco frecuente, que puede presentarse tanto en individuos inmunocompetentes como en inmunocomprometidos. A continuación se describen tres pacientes de sexo masculino inmunosuprimidos, en tratamiento con corticoesteroides, que presentaron diferentes formas clínicas de nocardiosis cutánea.

Cutaneous nocardiosis is a rare opportunistic infection found in bothimmunocompromised and immunocompetent patients. We describe three male immunocompromised patients who exhibited diff erent clinical forms of cutaneous nocardiosis. All of them were under corticosteroid regimen.

Primary sternal osteomyelitis caused by Nocardia nova: case report and literature review

A 51 year old woman without significant past medical history or risk factors for Nocardia infection developed primary Nocardia nova sternal osteomyelitis with mediastinal abscess, diagnosed with open biopsy. She required prolonged antibiotic therapy and had a favorable outcome. Primary sternal osteomyelitis develops in the absence of a contiguous focus of infection, as opposed to secondary sternal osteomyelitis, which is usually a complication of sternotomy. Staphylococcus aureus probably still is the most common cause of both forms of sternal osteomyelitis. Nocardia species invade humans usually through the respiratory tract and can cause a variety of localized infections through the hematogenous route. Pulmonary involvement may or may not coexist. Immunosuppressed patients are more prone to infection by Nocardia species, although cases involving seemingly immunocompetent patients are not rare. This is the first reported case in the English literature of primary sternal osteomyelitis due to Nocardia nova or any other Nocardia species.

Disseminated nocardiosis with psoas abscess in a patient with AIDS: first reported case

Psoas muscle abscess is an uncommon infection that have been diagnosed increasingly in the last years. We present a case of a patient with advanced human immunodeficiency virus infection who developed a disseminated infection due to Nocardia asteroides sensu stricto type VI with psoas abscess. To our knowledge no other cases of Nocardia psoas abscess in the setting of HIV infection have been reported in the literature.

O abscesso do músculo psoas é uma infecção pouco comum que tem sido diagnosticada de maneira crescente nos últimos anos. Apresentamos um caso de paciente com infecção avançada pelo vírus da imunodeficiência humana (HIV) que desenvolveu uma infecção disseminada por Nocardia asteroides senso estrito tipo VI, com abscesso no psoas. Em nosso conhecimento, não foram relatados na literatura outros casos de abscesso do psoas por Nocardia, no contexto da infecção por HIV.

Nocardiose pulmonar em paciente usuário crônico de corticóides / Pulmonary nocardiosis in a patient who was a chronic corticosteroid user

Nocardiose pulmonar é uma infecção grave e incomum causada pela Nocardia ssp, microorganismos que podem se comportar tanto como oportunistas quanto patógenos primários e que pode se apresentar como desordem aguda ou crônica supurativa. Relata-se o caso de um paciente de 49 anos, portador de púrpura trombocitopênica idiopática em tratamento com corticóides que desenvolveu infecção pulmonar por Nocardia farcinica, isolada em hemocultura. Apesar de tratamento correto com sulfametoxazol-trimetoprim, o paciente morreu após três meses de instituída terapia.

Pulmonary nocardiosis is an infrequent and severe infection caused by Nocardia spp. These are microorganisms that may behave both as opportunists and as primary pathogens, and they may present as either acute or suppurative chronic disorders. We report on the case of a 49-year-old man with idiopathic thrombocytopenic purpura that was being treated with corticosteroids. He developed pulmonary infection due to Nocardia farcinica, which was isolated from blood cultures. Despite correct treatment with trimethoprim-sulfamethoxazole, the patient died three months after this therapy was instituted.

Nocardial infections: report of 22 cases

Twenty-two cases of nocardial infections were diagnosed in our city between 1977- 1998. All patients whose clinical specimens showed Nocardia spp. at Gram stain, which were further confirmed by culture, were selected to be included in the study. Data from patients who were cured were compared with those from patients who died by statistical tests using EPIINFO version 6.04 software. Six isolates were identified as Nocardia asteroides complex, one as Nocardia asteroides sensu stricto and other as Nocardia brasiliensis. We had 17 cases of lung nocardiosis, being one out of them also a systemic disease. Other four cases of systemic nocardiosis were diagnosed: nocardial brain abscesses (one); nocardiosis of the jejunum (one); multiple cutaneous abscesses (one); and a case of infective nocardial endocarditis of prosthetic aortic valve. One patient had a mycetoma by N. brasiliensis. Fifteen (68.2 percent) out of 22 patients were immunosuppressed, being most (93.3 percent) by high-doses corticotherapy. Mortality by nocardial infection was 41 percent; mortality of systemic nocardiosis was 60 percent. Nocardiosis has a bad prognosis in immunosuppressed patients and also in non-immunosuppressed patients if the diagnosis is delayed. We propose that the delay in diagnosis should be examined in larger series to document its influence in the prognosis of the disease.

São apresentados 22 casos de infecção por Nocardia species entre 1977 e 1998, apresentando-se seu quadro clínico e evolução. Todos os pacientes cujos espécimes clínicos mostraram microorganismos sugestivos de Nocardia spp. à coloração de Gram, confirmados posteriormente por cultura, foram incluídos no estudo. Os dados dos pacientes que obtiveram cura foram comparados com aqueles dos pacientes que foram a óbito pelo programa EPIINFO versão 6.04; nível de significância menor que 5 por cento foi considerado estatisticamente significativo. Foram obtidos 22 casos de infecção por Nocardia spp.: seis isolamentos identificados como Nocardia asteroides complex, um como Nocardia asteroides sensu stricto e outro como Nocardia brasiliensis, enquanto os restantes foram identificados como Nocardia spp. Tivemos 17 casos de nocardiose pulmonar (um com disseminação). Tivemos outros quatro casos de nocardiose sistêmica: múltiplos abscessos cerebrais (um); endocardite infecciosa de prótese valvular aórtica (um); nocardiose de intestino delgado (um); abscessos cutâneos múltiplos por Nocardia spp (um). Um paciente apresentou micetoma por Nocardia brasiliensis. Imunossupressão esteve presente em 15 pacientes (68,2 por cento), predominantemente por corticoterapia (93,3 por cento). Nossa mortalidade foi 41 por cento; a mortalidade dos pacientes com nocardiose sistêmica foi de 60 por cento. A nocardiose tem pior prognóstico em pacientes imunossuprimidos e em pacientes com nocardiose sistêmica.

Nocardia infection following phacoemulsification.

Infection of a self-sealing tunnel incision is a rare but vision-threatening complication of cataract surgery. We describe two cases of side port infection following an uneventful phacoemulsification. Nocardia was isolated in one case. Both the cases were worsening on medical treatment and were successfully treated by therapeutic keratoplasty.

Endocarditis infecciosa por nocardia en valvulas nativas aortica y tricuspide / Nocardia endocarditis in aortic and tricuspid native valves

La endocarditis infecciosa por Nocardia en válvula nativa es una infección excepcional, que afecta a pacientes inmunodeprimidos. Presentamos el caso de un varón de 51 años con diagnóstico de endocarditis infecciosa por Nocardia en válvulas nativas aórtica y tricúspide, que recibió terapia antimicrobiana específica y que requirió reemplazo valvular aórtico, con buena evolución clínica en el seguimiento a 6 meses.

Nocardia endocarditis in native valve is an uncommon infection that usually arises in immunodepressed patients. We report a 51-yearold man diagnosed as having Nocardia endocarditis in aortic and tricuspid native valves, which received antimicrobial therapy and required aortic valve replacement. In 6 month follow up the patient remained asymptomatic with good clinical evolution.

Nocardiose pulmonar e cutânea em paciente usuário de corticosteróide / Pulmonary and cutaneous nocardiosis in a patient treated with corticosteroids

Nocardiose é a infecção localizada ou disseminada causada por bactérias gram positivas do gênero Nocardia. Acomete mais freqüentemente pulmão, pele e sistema nervoso central. Ocorre principalmente em indivíduos com deficiência de imunidade celular e deve ser investigada principalmente quando se tem associação de manifestações respiratórias, cutâneas e neurológicas nesse grupo de pacientes. Relata-se um caso de nocardiose pulmonar e cutânea em paciente usuário de corticosteróide oral para tratamento de bronquiolite obliterante com pneumonia em organização idiopática, que evoluiu com melhora clínico-radiológica após tratamento prolongado com sulfametoxazol-trimetoprim.

Nocardiosis is a localized or disseminated infection caused by gram-positive bacteria of the genus Nocardia. The infection most commonly affects the lungs, skin and central nervous system. Nocardiosis principally occurs in individuals with cellular immunodeficiency and should be considered in the differential diagnosis when such individuals present respiratory, cutaneous or neurological alterations. Herein, we report a case of pulmonary and cutaneous nocardiosis in a patient receiving oral corticosteroids to treat bronchiolitis obliterans accompanied by organizing pneumonia of unknown origin. After long-term treatment with sulfamethoxazole-trimethoprim, the clinical and radiological profile improved.

Actinomicetoma por Nocardia sp: informe de cinco casos tratados con imipenem solo o combinado con amikacina / Actinomycetoma and Nocardia sp: report of five cases treated with imipenem or imipenem plus amikacin

Antecedentes: El tratamiento estándar del actinomicetoma es dapsona con trimetoprim/sulfametoxazol. En casos seleccionados amikacina, estreptomicina, kanamicina, amoxicilina/ácido clavulánico o fosfomicina. El imipenem ha mostrado tener actividad in vitro e in vivo contra algunos actinomicetos; tiene un efecto sinérgico combinado con amikacina. Objetivos: Comunicar la respuesta al tratamiento con imipenem solo o combinado con amikacina en micetomas por Nocardia sp graves o multirresistentes. Material y métodos: Presentamos cinco pacientes con actinomicetoma que habían recibido múltiples tratamientos. Se hospitalizaron tres semanas para recibir imipenem (500 mg cada ocho horas) intravenoso por vía periférica por 21 días. En dos casos se combinó con amikacina. Resultados: Tres pacientes fueron hombres y dos mujeres. En tres casos la localización fue en el dorso, uno de ellos con afección ósea y pulmonar; en un caso hubo afección de la pared abdominal y en otro en la región cervical posterior. La evolución promedio fue de 7.4 años. En dos casos se logró curación clínica y bacteriológica a un año de seguimiento. En el paciente con afección pulmonar también hubo mejoría radiográfica. En el resto de los casos se logró cierre de la mayoría de las fístulas y una disminución importante de la inflamación, aunque hubo presencia de granos con cultivo negativo. Ningún tratamiento provocó efectos colaterales. Conclusiones: El imipenem es un antibiótico de amplio espectro y consideramos que es una buena alternativa para tratar actinomicetomas graves, resistentes al tratamiento habitual o con complicaciones viscerales.

INTRODUCTION: Dapsone with trimethoprim-sulfamethoxazol is currently the standard treatment for actinomycetoma. In select cases, amikacin, streptomycin, kanamycin, amoxicillin/clavulanic acid or phosphomycin may be also added. Imipenem has shown to be effective both in vitro and in vivo against some actinomycetes. Amikacin with Imipenem has a synergistic effect. OBJECTIVES: To report our preliminary findings using imipenem alone or with amikacin for severe or multi-resistant mycetomas due to Nocardia sp. MATERIAL AND METHODS: We present 5 cases of chronic mycetoma infection previously treated with anti-bacterial multidrug regimens. All patients were hospitalized and treated with imipenem 500 mg IV, three times a day for three weeks. Three patients received in addition amikacin. RESULTS: We included 3 male and 2 female patients. The average length of disease duration was 7.4 years. In 3 cases mycetoma was located on the back; one of them involved the rib and the lung. One case was localized in the abdominal wall, and another one involved the posterior side of the cervical region. Two patients achieved clinical and bacteriological cure one year after treatment with Imipenem, and the remaining three displayed clinical improvement, even though grains were observed, cultures where negative. None of the 5 patients studied showed clinical evidence of adverse reactions to Imipenem. CONCLUSIONS: Imipenem is a strong antibiotic and constitutes an important treatment alternative for severe or multi-resistant mycetoma especially for cases with bone and visceral involvement.