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Osteomyelitis of the pelvis caused by Rhodococcus equi in a two-year-old horse.

A 2-year-old female Quarter Horse was evaluated for hind limb lameness, fever (40 degrees C [104 degrees F]), and lethargy of 2 weeks' duration. Hypoproteinemia characterized by hypoalbuminemia and hyperfibrinogenemia was detected. Abdominal ultrasonography revealed thickening of the right dorsal colon wall. Treatment was instituted for putative right dorsal coliis. Lameness evaluation localized signs of pain to the lumbar vertebrae or pelvis. Radiography performed with the horse standing and nuclear scintigraphy revealed no abnormalities. Ventrodorsal pelvic radiography revealed a focal area of bony lysis and proliferation involving the cranial portion of the pubic symphysis. Aspiration yielded purulent exudate containing Rhodococcus equi, which was susceptible to erythromycin. Treatment included surgical debridement of the abscess and oral administration of erythromycin and rifampin. The horse's hind limb lameness completely resolved within 20 days. Infections of the pubic symphysis should be considered when lameness localized to the pelvis is associated with fever and an inflammatory leukogram.

Actinomycetales Infections↗

Foal-related risk factors associated with development of Rhodococcus equi pneumonia on farms with endemic infection.

OBJECTIVE: To identify foal-related risk factors associated with development of Rhodococcus equi pneumonia among foals on farms with endemic R. equi infection. DESIGN: Prospective case-control study. ANIMALS: 220 foals at 2 equine breeding farms in Texas during a 2-year period. PROCEDURE: Information collected for each dam included age, time housed on the farm prior to parturition, whether there were any peripartum illnesses, parity, and health of previous foals. Information collected for each foal included breed, sex, gestational age, month and year of birth, location of birth, type of flooring and bedding in stall, postpartum management and preventive health care, passive immunity status, supplementation of immunoglobulins, exposure to other farms or foals affected with R. equi pneumonia, stall and pasture exposure, commingling with other mare-foal pairs, age at weaning, and whether the foal developed R. equi pneumonia. RESULTS: 32 of the 220 (15%) foals developed R. equi pneumonia, of which 4 (13%) died. Foals at 1 of the 2 farms and foals born during the second year of the study were more likely to develop R. equi pneumonia. Foal-related factors that were examined were not significantly associated with risk of R. equi pneumonia in multivariate analyses. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that there are farm- and year-related effects on the risk that foals will develop R. equi pneumonia. Other foal-related factors significantly associated with R. equi pneumonia were not identified.

Actinomycetales Infections↗

Farm characteristics and management practices associated with development of Rhodococcus equi pneumonia in foals.

OBJECTIVE: To identify farm characteristics and management practices associated with development of Rhodococcus equi pneumonia in foals. DESIGN: Prospective case-control study. ANIMALS: 5230 foals on 138 breeding farms with 9136 horses. PROCEDURE: During 2003, participating veterinarians provided data from 1 or 2 farms with > or =1 foal with R equi pneumonia and unaffected farms. Data from affected and unaffected farms were compared by use of logistic regression analysis. RESULTS: A number of variables relating to farm size and desirable management practices were significantly associated with increased odds of farms being affected with R equi pneumonia. By use of multivariate logistic regression, affected farms were determined significantly more likely to have raised Thoroughbreds, housed > or =15 foals, used concrete floors in foaling stalls, and tested foals for passive transfer of immunity than unaffected farms. These results remained significant even after accounting for exposure of foals to other breeding farms during the first month of life. Conclusions and Clinical Relevance-Breeding farms with large acreage and a large number of mares and foals have greater odds of being affected by R equi pneumonia. Clinical relevance of associations with Thoroughbred breed and concrete flooring in foaling stalls remains uncertain. Desirable management factors commonly used on farms were not effective for controlling or preventing development of R equi pneumonia. This finding indicates a need to focus on host factors that influence disease development.

Actinomycetales Infections↗

Septic pleuritis and abdominal abscess formation caused by Rhodococcus equi in a foal.

A 3-month-old female Arabian horse was evaluated because of fever, respiratory distress, lethargy, and decreased appetite of 5 days' duration. Pleural effusion was diagnosed on the basis of ultrasonographic and radiographic examinations. Cytologic examination of pleural fluid collected via thoracocentesis revealed septic inflammation; bacteriologic culture of a sample of that fluid yielded Rhodococcus equi. A large intra-abdominal mass adjacent to the body wall was identified ultrasonographically. A specimen of the mass was collected via aspiration; the specimen was identified cytologically as purulent exudate that contained large numbers of rod-shaped bacteria, which confirmed abdominal abscess formation. Bacteriologic culture of a sample of the exudate also yielded R. equi. The foal was treated with azithromycin (10 mg/kg [4.5 mg/lb], PO, q 24 h for 5 days then q 48 h) and rifampin (5 mg/kg [2.3 mg/lb], PO, q 12 h) for 8 weeks and metronidazole (15 mg/kg [6.8 mg/lb], PO, q 8 h) for 3 weeks. Clinically, the foal responded to antimicrobial treatment within 2 weeks. At 8 weeks after the initial evaluation, ultrasonographic examination of the foal revealed resolution of the pleural effusion and abdominal abscess. In foals, R. equi infection typically results in pyogranulomatous pneumonia, and pleural effusion is an uncommon clinical sign. The combination of azithromycin and rifampin appears to be an effective treatment for R. equi infection in foals.

Abdominal Abscess↗

Intracranial abscess caused by Rhodococcus equi infection in a foal.

CASE DESCRIPTION: A 4-month-old Missouri Fox Trotter colt was examined for a 5-week history of head tilt after treatment for suspected pulmonary Rhodococcus equi infection. CLINICAL FINDINGS: Computed tomography revealed osteolysis of the occipital, temporal, and caudal portion of the parietal bones of the left side of the cranium. A soft tissue mass compressing the occipital region of the cerebral cortex and cerebellum was associated with the osteolytic bone. TREATMENT AND OUTCOME: A rostrotentorial-suboccipital craniectomy approach was performed to remove fragmented occipital bone, debulk the intracranial mass, and obtain tissue samples for histologic examination and bacterial culture. All neurologic deficits improved substantially within 3 days after surgery. Bacterial culture of the resected soft tissue and bone fragments yielded R equi. CLINICAL RELEVANCE: Intracranial surgery in veterinary medicine has been limited to dogs and cats; however, in select cases, extrapolation of surgical techniques used in humans and small animals can assist with intracranial procedures in horses.

Actinomycetales Infections↗

Evaluation of nasotracheal aspiration as a diagnostic tool for Rhodococcus equi pneumonia in foals.

The reliability of preparing bacteriological cultures from nasotracheal aspirates of foals routinely in order to diagnose R. equi pneumonia in foals was studied by isolating Rhodococcus equi from specimens obtained from 96 foals by nasotracheal aspiration with a silicon catheter. Results were compared with specimens obtained from 21 foals by transtracheal aspiration (percutaneous tracheal puncture). These 117 foals showed clinical signs of respiratory tract infection at sampling. R. equi was isolated from 14 of 21 (66.7%) specimens by transtracheal aspiration and from 59 of 96 (61.4%) specimens by nasotracheal aspiration, 649 of 655 isolates (99.1%) from the 73 positive specimens were virulent R. equi, and the culture-positive foals were diagnosed as having R. equi pneumonia. To assess the contamination of aspirates by organisms from the nasopharynx, the results of R. equi isolation from nasal swabs obtained from 56 of the 96 foals were compared to those obtained by nasotracheal aspiration from the same foals. R. equi was isolated from 2 of the 56 nasal swabs: one from a tracheal aspirate was positive, and the other was not. These results suggest that the nasotracheal aspiration technique, which is noninvasive and not associated with complications, could be used as an alternative to the transtracheal aspiration method, especially for the diagnosis of R. equi pneumonia in foals.

Actinomycetales Infections↗

Study of serum amyloid A concentrations as a means of achieving early diagnosis of Rhodococcus equi pneumonia.

REASONS FOR PERFORMING STUDY: Prognosis of Rhodococcus equi pneumonia can be challenging because the course of the disease is often insidious and overt clinical signs are subtle. Early diagnosis is considered desirable because it may offer the chance of more successful implementation of treatment and, thereby, improved outcome. Serological tests have previously failed to be accurate for early detection or diagnosis. Measurement of serum amyloid A (SAA) prior to and at the time of clinical signs was therefore chosen in order to assess its potential clinical use. OBJECTIVE: To determine whether SAA concentrations differentiate foals affected with R. equi pneumonia from unaffected foals, either prior to the onset of disease or at the time of onset of clinical signs. HYPOTHESIS: SAA concentrations are significantly higher among foals that develop R. equi pneumonia than in foals from the same environment that remain clinically unaffected. METHODS: Serum samples were obtained from 212 foals 7-14 days and 196 foals 21-28 days post partum, and from affected foals and age-matched controls at the time of onset of signs of pneumonia. SAA concentration was determined for each sample. RESULTS: There were no significant differences between SAA concentrations of foals with R. equi and clinically unaffected foals during the 2 periods of examination or at the time of onset of clinical signs of R. equi pneumonia. CONCLUSIONS: Concentrations of SAA are variable among foals with R. equi pneumonia and cannot be used reliably either as an ancillary diagnostic tool or to screen for early detection of disease during the first month post partum. POTENTIAL RELEVANCE: Bimonthly monitoring concentration of SAA is not useful as a screening test for early detection of R. equi pneumonia and does not facilitate diagnosis of this disease when used according to the protocol of this study.

Actinomycetales Infections↗

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

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.

Actinomycetales Infections↗

Rhodococcus equi--an easily missed opportunistic pathogen.

Over the last 10 years Rhodococcus equi has been identified as an important, albeit very rare, opportunistic pathogen. As the number of patients immunocompromised from HIV infection grows, this microorganism will likely become of increasing clinical importance. Infection with R. equi is usually insidious, causing progressive pulmonary disease that is typically pleural based at the time of microbiological diagnosis. As in the case we present, the clinical and microbiological diagnoses may be significantly delayed, either by the common pitfalls encountered in the laboratory identification of R. equi, or by the failure to recognize the pathogenic potential of the isolate. R. equi infection should be suspected in immunocompromised patients with pneumonia, when a pure or predominant growth of aerobic, non-sporeforming gram-positive bacilli is found on cultures of bronchoalveolar lavage fluid and other pulmonary pathogens have been excluded.

Actinomycetales Infections↗

Rhodococcus equi infection in HIV-positive subjects: a retrospective analysis of 24 cases.

Rhodococcus equi causes a rare infection in immunocompromised hosts. We describe 24 cases of infection in patients with AIDS-related complex (ARC)/acquired immunodeficiency syndrome (AIDS). Pneumonia was always the first manifestation of R. equi infection, but extrapulmonary involvement was also observed. The main sources of bacteria were sputum, bronchial washings and blood. The strains isolated were mainly susceptible to erythromycin, vancomycin, teicoplanin, rifampicin, imipenem and aminoglycosides. Initial treatment should involve an intravenously administered antibiotic combination therapy including imipenem or vancomycin or teicoplanin, followed by orally administered maintenance combination therapy. Drug combinations should be investigated for serum bactericidal activity in vitro. Surgery does not increase survival time and should only be performed in cases that do not respond to antibiotic treatment. Presumptive risks of infection (contact with horses or farm dust, or cohabiting with people affected by R. equi infection) were present in more than 50% of patients. This finding, and the frequency of bacteria in the sputum, are not sufficient proof of transmission between humans, but do suggest the need for respiratory isolation of patients affected by R. equi pneumonia.

AIDS-Related Complex↗

Rhodococcus equi pneumonia in patients infected with the human immunodeficiency virus. Report of 2 cases and review of the literature.

Rhodococcus equi is a cause of lung infection in immunosuppressed hosts. Since the start of the HIV epidemic, 76 cases of R. equi lung infection (MEDLINE 1985-96) affecting this population have been described. We report 2 additional cases and review the clinical data, radiological findings, treatment and outcome of these 78 patients. The mean age of these patients was 33 y; 69 were male. 71 met the criteria for AIDS (CDC 1993). Fever and cough were the presenting complaints in the majority of patients (84.3%). A single cavitary lung lesion in the upper lobes was the most common radiological finding (57.7%), although multiple cavitations, alveolar infiltrates and pleural effusion were also found. Treatment usually was based on synergistic antibiotic combinations for a long period of time determined on an individual basis. Surgery was performed only in 11 patients. Death attributable directly to R. equi infection is low (15.4%), however only half of the patients (53.8%) were completely cured. We conclude that R. equi infection should be strongly considered in any HIV patient who presents with cavitary lesions in the lung, especially if mycobacteria are not identified. Treatment must be based on synergistic antibiotic combinations, and surgery relegated to cases of chronic single cavitary lesions not responding to antibiotics.

Acquired Immunodeficiency Syndrome↗

Further sequence analysis of the DNA regions with the Rhodococcus 20S proteasome structural genes reveals extensive homology with Mycobacterium leprae.

The sequence of the respective DNA regions downstream of the 20S proteasome structural genes prcB1A1 (6 kb) and prcB2A2 (3.3 kb) of Rhodococcus erythropolis NI86/21 were determined. A highly conserved gene organization was observed between the two clusters which differed significantly in G + C content (68.8% versus 62.6%). Several ORFs were homologues of putative genes previously identified by genomic sequencing of the equivalent DNA in the related nocardioform actinomycete, Mycobacterium leprae, and thought to be specific for this pathogen. Three ORFs (ORF8(1), ORF8(2), ORF12[1]) without a counterpart in M. leprae were found. No significant homology to known sequences including proteasome-related gene products was detected, except for ORF9(1) and ORF9(2) which display a high level of sequence identity with a partially sequenced ORF in Streptomyces chrysomallus. These downstream ORFs also show a significant level of sequence homology with the ORF6(1) and ORF6(2) which are located upstream of the proteasome structural genes in the respective clusters.

Amino Acid Sequence↗

Cloning of an ORF with homology to Mycobacterium echA1, encoding the enoyl-CoA hydratase, in Rhodococcus fascians.

An open reading frame encoding a polypeptide of significant homology (55.7% identity) with the enoyl-CoA hydratase encoded by the gene echA1 from Mycobacterium tuberculosis has been found in the genome of the plant-pathogen bacteria Rhodococcus fascians strain NRRL-B-15096. Sequence alignments showed that it possesses several conserved blocks common to E. coli, M. tuberculosis and human mitochondria. One of such blocks includes a glutamate residue located at position 149, corresponding to the glutamate 139 of Escherichia coli. This glutamate was previously shown to be the catalytic residue of enoyl-CoA hydratase in the multienzyme complex of fatty acid oxidation from E. coli. Our results provide additional information on the conserved domains of this enzyme. Significant homologies in other genome regions between R. fascians and M. tuberculosis confirm their phylogenetic relationship.

Amino Acid Sequence↗

Rhodococcus equi and Arcanobacterium haemolyticum: two "coryneform" bacteria increasingly recognized as agents of human infection.

Rhodococcus equi and Arcanobacterium haemolyticum, formerly classified in the genus Corynebacterium, are members of the loosely defined taxon "coryneform" bacteria. Although they are the etiologic agents of distinct human infections, both organisms are frequently overlooked, which results in missed or delayed diagnoses. R. equi, long known as an important pathogen of immature horses, has become in the past three decades an opportunistic pathogen of severely immunosuppressed humans. Most cases are secondary to HIV infection. When specifically sought in throat swab cultures, A. haemolyticum is found responsible for 0.5% to 2.5% of bacterial pharyngitis, especially among adolescents. These two microorganisms represent a spectrum of disease in humans: from a mild, common illness to a rare life-threatening infection. Each organism elaborates lipid hydrolyzing enzymes (cholesterol oxidase by R. equi and sphingomyelinase D by A. haemolyticum) that are toxic to animals and humans and damaging to mammalian cell membranes. The participation of the cytotoxins in pathogenicity is discussed. Greater awareness of the properties of these two bacteria may promote faster, more accurate diagnoses and better clinical management.

Actinomycetales↗

Vaccine-associated systemic Rhodococcus erythropolis infection in farmed atlantic salmon Salmo salar.

In 7 instances between 2000 and 2003, clinical investigation of populations of fresh- and seawater-reared, vaccinated, Atlantic salmon Salmo salar suffering total losses of between 0.1 and 35 % revealed infection with a Gram-positive rod-shaped bacterium. The isolations were geographically widespread, occurring in both Norway and Scotland. In all cases, a Gram-positive bacterium, subsequently identified as Rhodococcus erythropolis, was isolated in pure culture. Infections, although systemic, were focused within the peritoneal cavity. While initial attempts to reproduce the disease by intraperitoneal injection of unvaccinated Atlantic salmon failed, Koch's postulates were subsequently fulfilled in fish vaccinated with a commercially available oil-adjuvanted vaccine.

Actinomycetales Infections↗

Innate immune responses to Rhodococcus equi.

We examined innate immune responses to the intracellular bacterium Rhodococcus equi and show that infection of macrophages with intact bacteria induced the rapid translocation of NF-kappa B and the production of a variety of proinflammatory mediators, including TNF, IL-12, and NO. Macrophages from mice deficient in MyD88 failed to translocate NF-kappa B and produced virtually no cytokines in response to R. equi infection, implicating a TLR pathway. TLR4 was not involved in this response, because C3H/HeJ macrophages were fully capable of responding to R. equi infection, and because RAW-264 cells transfected with a dominant negative form of TLR4 responded normally to infection by R. equi. A central role for TLR2 was identified. A TLR2 reporter cell was activated by R. equi, and RAW-264 cells transfected with a dominant negative TLR2 exhibited markedly reduced cytokine responses to R. equi. Moreover, macrophages from TLR2(-/-) mice exhibited diminished cytokine responses to R. equi. The role of the surface-localized R. equi lipoprotein VapA (virulence-associated protein A), in TLR2 activation was examined. Purified rVapA activated a TLR2-specific reporter cell, and it induced the maturation of dendritic cells and the production of cytokines from macrophages. Importantly, TLR2(-/-)-deficient but not TLR4(-/-)-deficient mice were found to be compromised in their ability to clear a challenge with virulent R. equi. We conclude that the efficient activation of innate immunity by R. equi may account for the relative lack of virulence of this organism in immunocompetent adults.

Adaptor Proteins, Signal Transducing↗

A regulatory effect of the balance between TNF-alpha and IL-6 in the granulomatous and inflammatory response to Rhodococcus aurantiacus infection in mice.

After i.v. inoculation with Rhodococcus aurantiacus, wild-type (WT) mice develop nonnecrotic, epithelioid granulomas. Because a high level of TNF-alpha is observed during the initial phase postinfection, we examined the extent to which TNF-alpha contributes to granulomatous inflammation using TNF-alpha gene-deficient (TNF-alpha(-/-)) mice. Despite a lack of R. aurantiacus proliferation, TNF-alpha(-/-) mice displayed high mortality rates within 5 days postinfection, as well as a high level of IL-6 in their spleens. Histological examination showed an absence of granuloma formation in TNF-alpha(-/-) mice. Pretreatment of TNF-alpha(-/-) mice with rTNF-alpha failed to restore this granuloma formation but accelerated bacterial removal and cellular recruitment. This rTNF-alpha administration also attenuated IL-6 production, resulting in increased survival rates of TNF-alpha(-/-) mice. Heat-killed R. aurantiacus induced in vitro enhanced mRNA expression and production of IL-6 in macrophages and DCs from TNF-alpha(-/-) mice when compared with WT controls, and treatment of TNF-alpha(-/-) mouse cells with rTNF-alpha decreased the IL-6 secretion. Moreover, anti-TNF-alpha or anti-IL-6 treatment increased IL-6 or TNF-alpha production by WT mouse cells, respectively. These data suggest that the production of TNF-alpha and IL-6 can be negatively regulated by each other. Administration of rIFN-gamma to TNF-alpha(-/-) mice caused immature granulomas in livers, and treatment with both rTNF-alpha and rIFN-gamma led to the formation of mature granulomas. Overall, TNF-alpha appears crucial for bacterial clearance, cellular recruitment, and granuloma formation. The balance between TNF-alpha and IL-6 during the early phase of infection controls the development of the inflammatory response to R. aurantiacus infection.

Actinomycetales Infections↗

Caprine vertebral osteomyelitis caused by Rhodococcus equi.

There have been reports of Rhodococcus equi infections in goats in Australia, America and India. In this study, R. equi was isolated from an inflamed vertebra in a Boer goat in South Africa. At autopsy, there was a purulent inflammatory reaction in the 1st cervical vertebra. Histopathologically, a neutrophilic infiltration was encountered in the bone. Aerobic culture of swabs collected from the abscesses yielded R. equi in pure culture that was identified on biochemical tests. R. equi has become important as the cause of an opportunistic infection in people suffering from HIV.

Actinomycetales Infections↗