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PubMed2000

Resistance of Rhodococcus equi to acid pH.

Rhodococcus equi is an important gram-positive intracellular facultative pathogen in foals of less than 3 months of age, that causes suppurative bronchopneumonia, lymphadenitis and/or enteritis. The disease in young foals mainly occurs in spring and summer when weather conditions are favorable for survival and multiplication of the bacteria in the environment. R. equi is widespread in the environment of horsebreeding farms: it has been isolated from the soil of paddocks and from the feces of adult horses and foals. Aerosol infection via dust of paddocks seems to be the major route of foal infections. The molecular mechanisms associated with the pathogenesis are not well understood and little is known about the markers or factors associated with virulence of R. equi. However, the discovery of a large plasmid in virulent strains and its association with virulence in mice and in young foals was reported. In this report, we studied the acid resistance of virulent R. equi in comparison with its avirulent plasmid-free isogene.

Hydrogen-Ion Concentration↗
PubMed1996

Transfer of a CD4+ Th1 cell line to nude mice effects clearance of Rhodococcus equi from the lung.

Rhodococcus equi, and intracellular respiratory pathogen, causes sever e granulomatous pneumonia in humans with AIDS and in young horses. Pulmonary clearance of R. equi requires functional CD4+ T cells and gamma interferon (IFN-gamma) expression from bronchial lymph node cells. The purpose of this study was to investigate whether R. equi-specific CD4+ Th1 cells could effect clearance of R. equi from the lung. Adoptive transfer of a clearance of R. equi from the lungs. In contrast, mice transfused with a R. equi-specific CD4+ Th2 cell line expressed interleukin-4 but not IFN-gamma mRNA, failed to clear pulmonary infection, and developed granulomas in the lung. Control mice, which did not receive cells, did not produce IFN-gamma or interleukin-4 and developed small pulmonary granulomas. These results clearly show that a Th1 response is sufficient to effect pulmonary clearance of R. equi.

Animals↗
PubMed1992

Distribution and antimicrobial susceptibility of Rhodococcus equi from clinical specimens.

Rhodococcus equi, an unusual gram positive aerobic actinomycete, was first described as a respiratory pathogen of livestock in 1923. Reports of human clinical illness have emphasized R. equi as a cause of invasive pulmonary infection in severely immunocompromised patients and, recently, have implicated it as a cause of pneumonia, bacteremia and disseminated infection in HIV-infected patients. To determine the distribution of R. equi we evaluated 107 isolates referred to the Centers for Disease Control (CDC) during the period January 1973 through December 1990. The sites of these 107 isolates (101 patient and 6 animal isolates) were: blood (32 isolates), sputum (30), lung tissue (13) and other site (32). Before 1983, when the first R. equi isolate from an HIV-infected patient was received, CDC received a total of 52 patient isolates. In addition, during this 10 year period, R. equi isolates were received from more than one site from only one patient. However, during the two year period 1989-1990, we identified 8 patients with underlying HIV infection and R. equi pneumonia who accounted for 29 of 35 (83%) R. equi patient isolates; 6 of these patients also had bacteremia and three died with disseminated R. equi infection. No isolates were resistant to amoxicillin-clavulanate, ampicillin-sulbactam, gentamicin or imipenem, and few (less than 5%) isolates were resistant to erythromycin, rifampin, tetracycline, and trimethoprim-sulfamethoxazole. These results suggest that HIV-infected patients, in particular, are predisposed to develop invasive pulmonary, fatal disseminated R. equi infection (or both), and appropriate antimicrobial susceptibility testing of clinical isolates may improve the effectiveness of therapy of R. equi-infected patients.

Actinomycetales Infections↗
PubMedDate not supplied

[Emergent pathologies: Rhodococcus equi infection in the acquired immunodeficiency syndrome].

Rhodococcus equi is an intracellular facultative, gram-positive, partially acid-fast, cocco-bacillary microorganism of increasing importance as a pathogen in severely immunocompromised HIV-positive patients. Rhodococcus equi may cause invasive pulmonary infection, bacteremia and disseminated infection. Rhodococcus equi is easily cultured from blood or sputum on standard media, but is frequently regarded as a contaminant. Delay in establishing a definite diagnosis may result in a poor outcome in most cases. Treatment in humans is not standardized. Surgical intervention may be beneficial in selected cases.

AIDS-Related Opportunistic Infections↗
PubMed1995

Case reports: pericarditis and lymphadenitis due to Rhodococcus equi.

Most patients with Rhodococcus equi infection are immunocompromised by either HIV infection, malignancy, or medication. Diagnosis is frequently missed or delayed because the organisms, resembling diphtheroids on smears, may be regarded as contaminants. Their clinical, pathologic, histochemical, and microbiologic resemblance to mycobacteria can result in misdiagnosis. Two cases were seen recently in our institution. R. equi pericarditis developed in a 29-year-old woman with failed renal transplant and R. equi axillary lymphadenitis developed in an asymptomatic 27-year-old man. These patients are important because the former is the first reported case of R. equi pericarditis, and the second case was unusual because of the absence of immunocompromise.

Actinomycetales Infections↗
PubMedDate not supplied

Variations in equid SLC11A1 (NRAMP1) genes and associations with Rhodococcus equi pneumonia in horses.

Rhodococcus equi is an important intracellular pathogen of horses, most commonly causing chronic, suppurative bronchopneumonia in foals. Although most foals likely are exposed to environmental R. equi within the 1st few days of life, only some develop R. equi pneumonia, and the basis of differences in susceptibility among foals currently is unknown. In this study, we investigated solute carrier family 11 member 1 (SLC11A1) gene sequences in the 5' untranslated region, exon 1, and a portion of intron 1 for variations in 3 equid species (horse, donkey, zebra) and compared variants within 3 independent horse breeding farms for associations with R. equi pneumonia by use of an age-matched case-control design. Seven novel variants in the 5'untranslated region were identified as specific for one or both of the non-horse equid species sampled. In addition, a single novel horse variant in the 5'untranslated region, -57C/T, was identified in 4 breeds. The -57C/T variant was found on 2 of the 3 farms with endemic R. equi pneumonia, representing 2 different horse breeds. Significant allelic and genotypic associations with susceptibility to R. equi pneumonia were observed for the -57C/T variant in foals from these farms. Although the functional impact of this novel variant remains to be determined, this study represents an important step in our understanding of natural resistance to R. equi foal pneumonia and other intracellular bacterial diseases affecting equids.

Actinomycetales Infections↗
PubMed2004

Bacteremia due to Rhodococcus equi--a case report.

Rhodococcus equi (R. equi) primarily causes zoonotic infections affecting grazing animals and is an unusual cause of infection in immunocompetent human beings. We report a case of bacteremia due to R. equi a rare isolate in a child suffering from protein energy malnutrition

Actinomycetales Infections↗
PubMed1999

Modulation of cytokine response of pneumonic foals by virulent Rhodococcus equi.

The ability of Rhodococcus equi to induce pneumonia in foals depends on the presence of an 85- to 90-kb plasmid. In this study, we evaluated whether plasmid-encoded products mediate virulence by modulating the cytokine response of foals. Foals infected intrabronchially with a virulence plasmid-containing strain of R. equi had similar gamma interferon (IFN-gamma) and interleukin-12 (IL-12) p35 but significantly higher IL-1beta, IL-10, IL-12 p40, and tumor necrosis factor alpha (TNF-alpha) mRNA expression in lung tissue compared to foals infected with the plasmid-cured derivative. IFN-gamma mRNA expression levels in CD4+ T lymphocytes isolated from bronchial lymph nodes (BLN) were similar for the two groups of R. equi-infected foals on day 3 postinfection. However, on day 14, in association with pneumonia and marked multiplication of virulent R. equi but with complete clearance of the plasmid-cured derivative, IFN-gamma mRNA expression in BLN CD4+ T lymphocytes was significantly (P < 0.001) higher in foals infected with the plasmid-cured derivative. These results suggests an immunomodulating role for R. equi virulence plasmid-encoded products in downregulating IFN-gamma mRNA expression by CD4+ T lymphocytes.

Actinomycetales Infections↗
PubMed1992

An assay to quantitate the binding of Rhodococcus equi to macrophages.

A Rhodococcus equi radiobinding assay has been developed using organisms labeled with 3H-uracil. These labeled organisms resemble their unlabeled counterparts with respect to colony morphology, viability, and buoyant density. Bacteria routinely incorporate between 5 x 10(-3) and 5 x 10(-2) counts per minute per colony forming unit (cfu) which in this assay allows the detection of fewer than 0.2 cfu per macrophage. Once incorporated, greater than 90% of the label remains bacterial associated for at least 4 h postlabeling. The majority of the label is trichloroacetic acid precipitable, partitions into the aqueous phase following phenol/chloroform extraction and is ethanol precipitable. RNAse treatment of the ethanol precipitate abolishes label trichloroacetic acid precipitation. This radiolabeling technique has been used to quantitate the attachment of R. equi to both murine peritoneal and equine alveolar macrophages adherent to 13 mm glass coverslips. R. equi binding is dose dependent, saturable, and specific to macrophages. Further, binding is enhanced in the presence of fresh serum. Inhibition of radiolabeled bacterial binding can be obtained by competition with cold R. equi. This radiolabeled binding assay represents a crucial step in identifying the receptors on macrophages involved in the recognition of R. equi and may help to provide information on how macrophages recognize intracellular bacteria in general.

Animals↗
PubMed2004

Nramp1 deletion does not confer susceptibility to Rhodococcus equi infection in mice.

Rhodococcus equi is an intracellular bacterium that causes pneumonia in immunocompromised people and foals. The Nramp1 gene influences susceptibility to a variety of intracellular bacteria (including mycobacterial species), but not to Mycobacterium tuberculosis. In this study, we demonstrate that mice functionally deleted of the Nramp1 gene were not more susceptible to infection with virulent R. equi (ATCC 33701) than wild-type mice. Susceptibility of mice to infection with the intracellular bacterium R. equi is more similar to that of M. tuberculosis than to other intracellular bacteria, including other mycobacteria.

Actinomycetales Infections↗
PubMed1997

[Review of 105 cases of isolation of Rhodococcus equi in humans].

BACKGROUND: Rhodococcus equi (formerly Corynebacterium) has been long considered an exclusively zoopathogenic microbe causing mainly granulomatous pneumonias and lung abscesses in young foals. The aim of this paper was to analyse substantial features of R, equi infections hitherto reported in man. METHODS AND RESULTS: MEDLINE database was searched for relevant reports. When the original source was not obtained the data from reviews were employed. Together, 105 cases of R, equi infection in man were reported. Median age was 35 years with a range from 9 months to 83 years. The male: female ratio was 3.3. Lungs were involved in 72 cases (69%), extrapulmonary abscesses as the only symptom of infection were described in 9 cases, septic state in 7 cases. Clinical outcome was known in 98 cases, being fatal in 41 (42%). Therapy was mentioned in 70 reports, the most often used drugs being erythromycin (30 cases, 12 deaths), rifampicin (19 cases, 7 deaths) and vancomycin (18 cases, 6 deaths). R. equi was isolated from the sputum of 69% patients with the pulmonary involvement. Blood cultures were positive in 35% of cases. Out of total, 49% persons were HIV positive. Median age for HIV positive patients was 32 years with a range from 18 to 71 years, for HIV negative patients 52 years with a range from 9 months to 83 years. There were 97% males in the HIV positive group in contrast to 59% in the HIV negative group (p < 0.01). Lungs were involved in 90% of HIV positive and 48% of HIV negative cases (p < 0.01). Extrapulmonary abscesses as the only sign of infection were seen in 2% of HIV positive persons and in 15% of HIV negative ones (p < 0.05). Outcome was fatal for 60% of the HIV positive hosts and for 28% of the HIV negative individuals (p < 0.01). R. equi was isolated from the sputum of 80% pneumonic HIV positive patients and of 50% of pneumonic patients without HIV infection (p < 0.05). R. equi was detected in the blood of 67% of HIV positive patients and of 33% of HIV negative ones (p < 0.01). CONCLUSIONS: The analysis of published reports shows that whereas R. equi causes mainly pneumonia in persons with HIV infection, in HIV negative individuals extrapulmonary manifestations slightly prevail, most often abscesses, sepsis, eye involvement and wound infections.

AIDS-Related Opportunistic Infections↗
PubMed2000

Cooperation between reactive oxygen and nitrogen intermediates in killing of Rhodococcus equi by activated macrophages.

Rhodococcus equi is a facultative intracellular bacterium of macrophages which can infect immunocompromised humans and young horses. In the present study, we examine the mechanism of host defense against R. equi by using a murine model. We show that bacterial killing is dependent upon the presence of gamma interferon (IFN-gamma), which activates macrophages to produce reactive nitrogen and oxygen intermediates. These two radicals combine to form peroxynitrite (ONOO(-)), which kills R. equi. Mice deficient in the production of either the high-output nitric oxide pathway (iNOS(-/-)) or the oxidative burst (gp91(phox-/-)) are more susceptible to lethal R. equi infection and display higher bacterial burdens in their livers, spleens, and lungs than wild-type mice. These in vivo observations, which implicate both nitric oxide (NO) and superoxide (O(2)(-)) in bacterial killing, were reexamined in cell-free radical-generating assays. In these assays, R. equi remains fully viable following prolonged exposure to high concentrations of either nitric oxide or superoxide, indicating that neither compound is sufficient to mediate bacterial killing. In contrast, brief exposure of bacteria to ONOO(-) efficiently kills virulent R. equi. The intracellular killing of bacteria in vitro by activated macrophages correlated with the production of ONOO(-) in situ. Inhibition of nitric oxide production by activated macrophages by using N(G)-monomethyl-L-arginine blocks their production of ONOO(-) and weakens their ability to control rhodococcal replication. These studies indicate that peroxynitrite mediates the intracellular killing of R. equi by IFN-gamma-activated macrophages.

Actinomycetales Infections↗
PubMed2001

Evaluation of equine immunoglobulin specific for Rhodococcus equi virulence-associated proteins A and C for use in protecting foals against Rhodococcus equi-induced pneumonia.

OBJECTIVE: To determine whether purified equine immunoglobulin specific for Rhodococcus equi virulence-associated proteins A and C (VapA and VapC) can confer passive protection against R. equi-induced pneumonia in foals. ANIMALS: Twenty-eight 3-week-old mixed-breed pony foals. PROCEDURE: 7 foals received IV injections of equine hyperimmune plasma (HIP) against whole-cell R. equi, and 7 received purified equine immunoglobulin specific for VapA and VapC 1 day prior to intrabronchial infection with R. equi strain 103+. Eleven foals were not treated prior to infection, and 3 control foals were neither treated nor infected. Heart rate, respiratory rate, and rectal temperature were recorded twice daily, and serum fibrinogen concentration and WBC count were determined every other day following infection. Foals were euthanatized 14 days following infection, and lung lesions and concentration of R. equi in lungs were assessed. RESULTS: The onset of clinical signs of pneumonia was significantly delayed in the HIP- and immunoglobulin-treated groups, compared with the untreated infected group. Moreover, pulmonary lesions were less severe in the treated groups, and significantly fewer R. equi organisms were cultured from the lungs of treated foals. CONCLUSIONS AND CLINICAL RELEVANCE: Degree of protection against R. equi-induced pneumonia provided by purified immunoglobulin specific for VapA and VapC was similar to that provided by commercially available HIP. Results not only suggest that immunoglobulin is the primary component of HIP that confers protection against R. equi-induced pneumonia in foals but also indicate that antibodies against R. equi VapA and VapC are protective.

Actinomycetales Infections↗
PubMed1995

Empyema with malakoplakic-like lesions by Rhodococcus equi as a presentation of HIV infection.

Rhodococcus equi (Corynebacterium equi) is an aerobic actinomycetes, well described as a cause of pulmonary infection in different animals as horses, pigs and cows. This pathogen has a coccobacillar aspect and a variable acid-fast stain in tissues. Rare cases of human infection by Rhodococcus species were described, the majority by Rhodococcus equi, especially in patients with immunodeficiency syndrome (AIDS) in advanced stages of the disease. Usually the diagnosis of infections by Rhodococcus species is performed by positive blood or bronchoalveolar lavage cultures. Here we described a case of a pleuro-pulmonary infection by Rhodococcus equi, with malakoplakic-like lesions, that was the first manifestation of AIDS, whose diagnosis was performed by pleural biopsy (acid-fast bacteria with a variable coccobacillar aspect inside macrophages) and pleural fluid culture.

AIDS-Related Opportunistic Infections↗
PubMed1996

Serologic responses to Rhodococcus equi in individuals with and without human immunodeficiency virus infection.

Thirty healthy blood donors, 15 workers from horse-breeding farms, 69 human immunodeficiency virus (HIV)-negative persons at risk for HIV infection, 125 HIV-infected subjects without Rhodococcus equi infection, and nine HIV-infected patients with Rhodococcus equi pneumonia were evaluated in order to detect serum antibodies to Rhodococcus equi precipitate-soluble antigen by an enzyme immunoassay (EIA). Whereas EIA values for healthy donors, horse farm workers, individuals at risk for HIV infection, and HIV-positive subjects without Rhodococcus equi infection were comparable, HIV-infected patients with rhodococcal disease had significantly higher Rhodococcus equi antibody levels (p < 0.0001). The clinical outcome of Rhodococcus equi pneumonia was more severe in subjects who had low levels of specific antibodies, whereas patients who recovered had elevated Rhodococcus equi antibody levels over time. Immunoblot studies showed that both Rhodococcus equi-infected patients and foals recognized a protein band of approximately 60 kDa in the Rhodococcus equi precipitate-soluble antigen. On the other hand, the Rhodococcus equi-infected patients did not react with the diffuse 15 to 17 kDa virulence-associated proteins that represent important virulence factors both in mice and horses.

Actinomycetales Infections↗
PubMed2002

[Laryngeal infection by Rhodococcus equi in patient with AIDS].

The Rhodococcus equi is an aerobic gram positive pleomorphic bacillus, that was isolated for the first time like a producer of bronchopneumonia in young horses. Every time more often, it is being recognized as a pathogen in humans, mainly in the immunodepressed population. We described a case, until now exceptional, of laryngeal infection by Rhodococcus equi in a patient with positive serology for the virus of the human immunodeficiency (HIV), and we reviewed some clinical and epidemiological characteristics of the infections by this germ. The treatment is riphampicine and/or erythromycin, being the prognosis bad, because usually they are immunodepressed patients.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Rhodococcus equi: first case in a heart transplant recipient.

Rhodococcus equi is a gram-positive diphtheroid that occasionally affects immunocompromised patients, usually causing a chronic respiratory infection with cavitating pulmonary opacities on chest radiograph that resemble mycobacterial or fungal disease. Etiologic diagnosis presents a number of pitfalls, because Rhodococcus equi isolates mimic many of the characteristics of other microorganisms more familiar to the laboratory staff. The treatment of choice for this disease has not yet been established, and its mortality rate is greater than 50% in individuals with human immunodeficiency virus and 20% to 25% among the remaining patients. We describe here the first case of Rhodococcus equi infection in a heart transplant recipient. Clinical presentation was typical, and treatment with a sensitivity-based combination of antibiotics resulted in resolution of both the clinical and radiologic picture.

Adult↗
PubMed1991

Role of antibody to extracellular proteins of Rhodococcus equi in protection against R. equi pneumonia in foals.

Rhodococcus equi produces two exoenzymes (REE), a cholesterol oxidase in large amounts and a phospholipase C, which cause lysis of sheep red blood cells (SRBC) sensitized with Staphylococcus aureus beta toxin. Two immunization studies were done in foals to determine the role of antibody to REE in protection against R. equi pneumonia. In the first study, three foals (mean age 10 days) were vaccinated four times at 2-week intervals with over 1 million units of partially purified exoenzymes (PREE). In the second study, three foals (mean age 19 days) were administered plasma from an adult horse vaccinated with PREE. Relatively low titres (16-32) of neutralizing antibody were detected in the foals of the former group, and passive transfer of neutralizing antibody (titres 32-64) occurred in the latter. Following immunization, principal foals and an equal number of similarly aged nonimmunized foals were challenged by aerosol with 1 x 10(10) live R. equi per day for 5 consecutive days. No severe clinical pneumonia developed in either group and, with one exception, only minor and resolving lung abscesses developed in these foals. These studies showed that antibody response of foals to immunization with PREE was poor, antibody to PREE did not prevent foals from developing lung abscesses following experimental infection, and that foals even as young as 3 weeks of age may be largely refractory to aerosol challenge with virulent R. equi.

Actinomycetales Infections↗