The aerobic actinomycetes are soil-inhabiting microorganisms that occur worldwide. In 1888, Nocard first recognized the pathogenic potential of this group of microorganisms. Since then, several aerobic actinomycetes have been a major source of interest for the commercial drug industry and have proved to be extremely useful microorganisms for producing novel antimicrobial agents. They have also been well known as potential veterinary pathogens affecting many different animal species. The medically important aerobic actinomycetes may cause significant morbidity and mortality, in particular in highly susceptible severely immunocompromised patients, including transplant recipients and patients infected with human immunodeficiency virus. However, the diagnosis of these infections may be difficult, and effective antimicrobial therapy may be complicated by antimicrobial resistance. The taxonomy of these microorganisms has been problematic. In recent revisions of their classification, new pathogenic species have been recognized. The development of additional and more reliable diagnostic tests and of a standardized method for antimicrobial susceptibility testing and the application of molecular techniques for the diagnosis and subtyping of these microorganisms are needed to better diagnose and treat infected patients and to identify effective control measures for these unusual pathogens. We review the epidemiology and microbiology of the major medically important aerobic actinomycetes. Images

The medically important aerobic actinomycetes: epidemiology and microbiology.

Recent isolations of Rhodococcus equi from cavitatory pulmonary disease in patients with AIDS have aroused interest among medical microbiologists in this unusual organism. Earlier isolations from humans had also been in immunosuppressed patients following hemolymphatic tumors or renal transplantation. This organism has been recognized for many years as a cause of a serious pyogranulomatous pneumonia of young foals and is occasionally isolated from granulomatous lesions in several other species, in some cases following immunosuppression. The last decade has seen many advances in understanding of the epidemiology, pathogenesis, diagnosis, treatment, and immunity to infection in foals. The particular susceptibility of the foal is not understood but can be explained in part by a combination of heavy challenge through the respiratory route coinciding with declining maternally derived antibody in the absence of fully competent foal cellular immune mechanisms. R. equi is largely a soil organism but is widespread in the feces of herbivores. Its growth in soil is considerably improved by simple nutrients it obtains from herbivore manure. About one-third of human patients who have developed R. equi infections had contact in some way with herbivores or their manure. Others may have acquired infection from contact with soil or wild bird manure. R. equi is an intracellular parasite, which explains the typical pyogranulomatous nature of R. equi infections, the predisposition to infection in human patients with defective cell-mediated immune mechanisms, and the efficacy of antimicrobial drugs that penetrate phagocytic cells.

Rhodococcus equi: an animal and human pathogen.

Role of Flexible Bronchoscopy in Immunocompromised Patients With Lung Infiltrates

One stop mycology

Rhodococcus equi is an uncommon pathogen in humans that has occasionally been reported to cause infection in individuals with impaired cellular immunity. We summarize 30 previously published reports of human infection with R. equi and describe one additional case in a patient with AIDS. Eleven (35%) of the patients discussed in this report had AIDS or human immunodeficiency virus (HIV) infection, which is emerging as the leading cause of immunosuppression in cases of R. equi infection. Seventy-seven percent of all patients had pneumonia due to R. equi, and the infiltrate frequently cavitated. When HIV-infected patients were compared with those not infected with the virus, symptoms, age, and frequency of pneumonia were similar. Sputum and blood cultures were more likely to be positive in HIV-infected patients. Individuals with HIV infection also had a higher incidence of simultaneous secondary infections and higher mortality than non-HIV-infected patients (54.5% vs. 20%). The rate of survival for all patients was 75% when antibiotics were combined with surgical resection of infected tissue; in comparison, the survival rate among patients receiving antibiotics alone was 61.1%.

Rhodococcus equi infection in patients with and without human immunodeficiency virus infection.

Fiber-optic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) were performed on 67 occasions in 57 immunocompromised patients with symptoms consistent with pulmonary infection. Diagnosis was achieved more often in renal transplant patients than in patients with hematological malignancies (85% versus 28%). Culture (bacteria, virus, fungi), staining and microscopy (bacteria, fungi, Pneumocystis carinii (PC)) and antigen detection by indirect immunofluorescence (cytomegalovirus (CMV), respiratory viruses, PC, Legionella) were used for diagnosis. On 20 occasions transbronchial biopsies with histopathologic examination were performed. In addition, serology comprising the herpes group (HHV-6) and respiratory viruses was done. A microbial diagnosis was obtained on 45% of occasions. The most common pathogens found were CMV (31%) and PC (25%). On 22 (33%) occasions a rapid diagnosis of 1 or more microbial agents was obtained within 24 h by conventional staining or indirect immunofluorescence. The clinical relevance of findings of CMV, HHV-6, and Epstein-Barr virus in BAL by polymerase chain detection on 18, 6 and 3 occasions is discussed. On 4 occasions pathogenic bacteria were found. It was not possible to relate findings of coagulase-negative staphylococci, alpha-streptococci and Candida albicans to the pulmonary infection.

Diagnosis of Pulmonary Infections in Immunocompromised Patients by Fiber-optic Bronchoscopy with Bronchoalveolar Lavage and Serology

Bronchoalveolar lavage (BAL) products from 52 immunocompromised patients with symptoms of pulmonary infection was examined for cytomegalovirus (CMV) by virus isolation, polymerase chain reaction (PCR) and detection of CMV antigen by immunofluorescence or immunoperoxidase staining after short-term incubation in tissue culture and directly in BAL cells. We found that PCR detected all cases positive by virus isolation (15/52 samples) and the result was obtained within 5 h. PCR detected more cases of CMV than did virus isolation (22/52 samples). Positive PCR and negative virus isolation were consistent with probable CMV infection in 3/7 patients when other clinical and laboratory parameters of CMV infection were considered. The negative predictive value of PCR was high; none of 30 patients negative by PCR developed CMV pneumonia within the subsequent 2 months. Detection of CMV antigen after short-term incubation was rapid enough to be used in clinical practice, specific (100%) and with a sensitivity of 60%. D...

Diagnosis of Cytomegalovirus in Bronchoalveolar Lavage by Polymerase Chain Reaction, in Comparison with Virus Isolation and Detection of Viral Antigen

A 51-year-old female farmer was diagnosed as having sarcoidosis. During 4 years of observation, slow radiological progression was observed. Cough then developed, necessitating treatment with corticosteroids. After 28 months of continuous treatment with prednisolone in low doses (5-7.5 mg daily), she suffered fever episodes, recurrent haemoptyses, general malaise and loss of weight. A chest roentgenogram showed a left upper lobe infiltrate, which progressed and finally cavitated, and rib destruction. Despite efforts, including a thoracotomy, 22 months passed before a diagnosis could be made. Blood and sputum cultures and cultures from the destroyed rib showed growth of Rhodococcus equi, a common soil organism which can cause infections in foals and other animals. Treatment with rifampicin and erythromycin was successful. R. equi has been reported to cause infection in patients with neoplastic disease and/or immunosuppression, but the disease might be more common than is suggested by the sparse case reports in the literature, owing to lack of familiarity with the organism, which will tend to be overlooked as a contaminant.

Infection with Rhodococcus equi in a patient with sarcoidosis treated with corticosteroids.

A young woman presented with widespread bilateral infiltrates on chest X-ray and a high fever. Investigations for bacterial, mycobacterial, and fungal infections were negative. A biopsy of the lung showed granulomas, and corticosteroid medication was given on vital indication because of the rapidly progressive disease. There was a dramatic response, with regression of the chest X-ray changes and the fever and the patient was discharged on her own request with a tentative diagnosis of acute sarcoidosis. One month later she was admitted in an alarming state with almost completely consolidated lungs and died a few hours later. Autopsy revealed generalized aspergillosis. Renewed extensive investigation of the earlier lung biopsy revealed hyphae. After her death, the case history of an elder brother was traced and revealed that he had died at early age in a generalized granulomatous disease. Although no definite diagnosis can be made, it seems likely that both siblings suffered from a defect in the immune syst...

Disseminated pulmonary aspergillosis in a previously healthy young woman.

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Diagnosis of Pulmonary Infections in Immunocompromised Patients by Fiber-optic Bronchoscopy with Bronchoalveolar Lavage and Serology

Diagnosis of Cytomegalovirus in Bronchoalveolar Lavage by Polymerase Chain Reaction, in Comparison with Virus Isolation and Detection of Viral Antigen

Infection with Rhodococcus equi in a patient with sarcoidosis treated with corticosteroids.

Disseminated pulmonary aspergillosis in a previously healthy young woman.