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Case report: Rhodococcus equi pneumonia in a patient infected by the human immunodeficiency virus.

Rhodococcus equi, a facultative intracellular bacterium, is a common cause of pulmonary infection in farm animals, especially foals. Pulmonary and disseminated infection caused by this organism is occasionally seen in humans, especially in patients whose cell-mediated immunity has been altered by glucocorticoids or cytotoxic chemotherapy. Not surprisingly, the organism may cause serious disease in human immunodeficiency virus (HIV)-infected humans whose T cell-dependent immune system has been profoundly suppressed. This report describes an HIV infected patient with Rhodococcus equi pneumonia and reviews nine additional HIV-infected patients. Treatment in humans is not standardized. Studies in foals indicate that erythromycin and rifampin together are the treatment of choice. The patient in this report responded to this treatment briefly before relapsing and dying of the infection.

Actinomycetales Infections↗

Clinical manifestations, diagnosis, treatment, and prevention of Rhodococcus equi infections in foals.

Since the 1986 Rhodococcus equi workshop, there have been major breakthroughs in understanding the epidemiology of, the virulence of, and the immune response to, this intriguing pathogen. However, with the exception of the use of hyperimmune plasma for the prevention of the disease (Martens et al., 1989; Madigan et al., 1991) the clinical aspects of R. equi infections have essentially remained unchanged. This article reviews the various clinical manifestations and summarizes recent advances in diagnosis, treatment and prevention of R. equi infections in foals.

Actinomycetales Infections↗

HIV-infected patient with a Rhodococcus equi pneumonia.

The case history of a HIV patient with a pulmonary infect of Rhodococcus equi is presented. He recovered after prolonged treatment with antibiotics and lobectomy. The Rhodococcus equi infection was the presenting symptom of his impaired immune status caused by HIV infection.

AIDS-Related Opportunistic Infections↗

In vitro production of tumor necrosis factor-alpha, interleukin-6 and interleukin-8 from normal human peripheral blood mononuclear cells stimulated by Rhodococcus equi.

The capability of heat-killed Rhodococcus equi organisms to induce in vitro release of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8 from normal human mononuclear cells as well as the secretion kinetics of these inflammatory cytokines over a 48 h period were evaluated. Results show that normal human mononuclear cells are efficiently triggered to secrete TNF-alpha, IL-6 and IL-8 following R. equi stimulation according to a different kinetics. In particular, release of IL-B was already maximally expressed after 2 h of stimulation, while TNF-alpha amounts progressively increased in a time-dependent fashion. Finally, IL-6 secretion reached peak levels as soon as 18 h of incubation. Taken together, these data point out that monocyte-derived cytokines may play an important role in the immunological control of R. equi infection in immunocompetent people.

Cells, Cultured↗

[Diagnosis and therapy of Rhodococcus equi infection in the horse].

Infection with Rhodococcus equi is an important cause of pneumonia in foals, but other organ systems may also be affected. The intracellular presence of R. equi and the formation of granulomatous and suppurative inflammatory tissue mean that prolonged treatment is needed. The pharmacological properties of the combination of erythromycin and rifampicin have improved the survival of foals infected with R. equi; however, erythromycin can cause adverse reactions in foals and mares, which has prompted the search for alternative therapies. The combination of azithromycin or clarithromycin with rifampicin seems to be a promising alternative. However these combinations are expensive and adverse effects remain to be determined, especially in the dams of treated foals. Thus correct diagnosis and appropriate use of drugs are essential for the treatment of R. equi infection in foals.

Actinomycetales Infections↗

Penicillin-binding proteins of Rhodococcus equi: potential role in resistance to imipenem.

Rhodococcus equi is a gram-positive coccobacillus which, like other members of the order Actinomycetales, is increasingly reported as an opportunistic pathogen in patients with AIDS. The use of combinations of antibiotics that include imipenem (IMP) has been suggested for the treatment of patients infected with R. equi. An antagonism between IMP, meropenem, cefoxitin, ceftriaxone, moxalactam, and oxacillin and other beta-lactams, such as penicillin, amoxicillin, cephalothin, and ticarcillin, was detected in vitro both on Mueller-Hinton agar and in broth for all 10 IMP-susceptible R. equi strains examined. To study the mechanism of the antagonism between beta-lactams, a mutant with decreased susceptibility to IMP (isolate IpR) was selected in vitro from a susceptible clinical isolate of R. equi (isolate IpS). IpR exhibited decreased susceptibility to IMP, meropenem, cefoxitin, ceftriaxone, moxalactam, and oxacillin but not to penicillin, amoxicillin, cephalothin, or ticarcillin. No beta-lactamase was found in IpS, IpS cultured with antagonistic beta-lactams, or IpR strains. Labeling of penicillin-binding proteins (PBPs) revealed four PBPs with molecular masses of ca. 59, 56, 43, and 26 kDa in IpS. In IpR, PBP 3 disappeared and was replaced by PBP 3a of 40 kDa. The 50% saturation of PBP 3 and PBP 3a by the carbapenems correlated with the MICs of these antibiotics, respectively, for IpS and IpR strains. However, PBP 3a was not detected in IpS when IpS was cultured in the presence of beta-lactams, with which antagonism was observed. The present work describes the PBPs of R. equi and reports that IMP resistance in R. equi is related to an altered PBP pattern.

Anti-Bacterial Agents↗

Development of a new selective plating medium for Rhodococcus equi.

A new selective plating medium for Rhodococcus equi containing ceftazidime (20 mg/l) and novobiocin (25 mg/l) on a Mueller-Hinton agar basis is described. It proved to be less inhibitory for R. equi than selective plating media devised earlier and grew only very few other nocardioform bacteria.

Actinomycetales Infections↗

Studies on the rod-coccus life cycle of Rhodococcus equi.

In the present study all 19 Rhodococcus equi cultures isolated from horses and 19 of 22 R. equi cultures isolated from human patients displayed a rod-coccus life cycle after cultivation under defined growth conditions. A bacillary growth could be observed after cultivation of the bacteria in fluid media for 4 h at 37 degrees C, a coccoid morphology after cultivation of the bacteria for 24 h either on sheep blood agar plates or in fluid media. The different morphological features did not significantly influence the typability of the bacteria or the expression of surface proteins including 15-17 kDa virulence proteins. Studies on further surface characteristics revealed a relation between haemagglutinating properties, the surface hydrophobicity and adherence properties of the bacteria to HeLa cells. These properties seemed to be influenced by the cultivation conditions but not by the different morphological forms of the bacteria. A haemagglutination reaction, a hydrophobic surface and an enhanced adherence to HeLa cells could be observed with coccoid bacteria after cultivation in fluid media for 24 h at 37 degrees C but not with coccoid bacteria harvested from sheep blood agar plates or with bacillary bacteria after 4 h growth in fluid media. This difference might possibly be caused by the degree of encapsulation of the bacteria after various cultivation conditions and a subsequent masking effect of the hydrophilic polysaccharide capsule of R. equi.

AIDS-Related Opportunistic Infections↗

Pyogranulomatous skin disease and cellulitis in a cat caused by Rhodococcus equi.

This report describes a case of Rhodococcus equi infection causing pyogranulomatous skin disease and cellulitis in a two-year-old female domestic shorthaired cat. The case differed from previously reported cases in cats in its clinical presentation and in the locations of the lesions, which were similar to those seen in horses. The presence of an intracellular organism was confirmed by cytology and on histopathology. The aetiological diagnosis was confirmed by routine biochemical tests specific for R. equi on a pure isolate obtained from a biopsy specimen. The report also reviews the literature of the documented feline cases and discusses the common pitfalls in the diagnosis of such infections.

Actinomycetales Infections↗

Rhodococcus equi brain abscess in an immunocompetent patient.

Rhodococcus equi brain abscesses usually occur in immunocompromised patients with prolonged and refractory pulmonary infections. Herein we report a case of R. equi brain abscess in a 67-y-old man without immunodepression. Our patient recovered after neurosurgical resection and prolonged antimicrobial therapy with vancomycin and trimethoprim-sulfamethoxazole.

Actinomycetales Infections↗

Acute mediastinitis due to Rhodococcus equi in a patient with human immunodeficiency virus infection.

A patient with human immunodeficiency virus infection developed anterior mediastinitis during antibiotic treatment for empyema due to Rhodococcus equi. This is the first reported case of infection with this organism in this setting. Despite an adequate course of therapy and maintenance treatment with antibiotics to which the isolate of Rhodococcus equi was susceptible in vitro, the patient experienced relapse of the infection into the mediastinum. Clinicians should consider this complication when Rhodococcus equi is present in pleural effusions.

AIDS-Related Opportunistic Infections↗

Tamponade due to Rhodococcus equi in acquired immunodeficiency syndrome.

Infection with Rhodococcus equi has been described as a cause of cavitary pneumonia in AIDS patients. We report such a case, complicated by bacteremia, tamponade, and possible brain and liver abscesses. Medical treatment was successful with pericardiocentesis and antibiotherapy with teicoplanin, gentamicin, clarithromycin, rifampicin, supplemented by empirical treatment of cerebral toxoplasmosis. Antibiotherapy was terminated after 6 months, without relapse 2 months later.

AIDS-Related Opportunistic Infections↗

Production of cholesterol oxidase by Rhodococcus equi No. 23 in a jar fermenter.

Rhodococcus equi No. 23 was grown in a batch fermenter. The effects of cultivation temperature, pH of the culture medium, aeration rate and agitation speed on the production of cholesterol oxidase (CholOx) by the test organism were examined. Results revealed that the cultivation temperature, the pH of the medium, the aeration rate and the agitation speed all affected the production of CholOx by R. equi No. 23. Adjusting the operation variables during the cultivation period increased the production of CholOx effectively and prevented the occurrence of overflow of foam during the fermentation period. A maximum CholOx activity of 0.34 unit/ml with a volumetric production rate of 0.011 unit/h per ml could be achieved in 30 h of cultivation at an aeration rate of 5.0 l/min, if the pH of the culture medium, the cultivation temperature and the agitation speed were controlled at 6.5, 39 degrees C and 200 rev. /min respectively during the first 24 h of cultivation, then shifted to 7.5, 37 degrees C and 300 rev./min respectively.

Bioreactors↗

T-cell response during Rhodococcus equi infection in a murine experimental model.

Rhodococcus equi is a facultative intracellular bacterium that can cause pneumonia in both young horses and immunocompromised humans. In this study, we have tried to determine the T-cell populations that recognize this pathogen during murine infection, as well as the bacterial antigens recognized by these cells. When BALB/c mice were hyperimmunized with a virulent R. equi strain, we did not observe preferential expansion of a particular T-cell subset in their spleens. However, when the splenic T lymphocytes of the hyperimmunized BALB/c mice were cultured in the presence of killed bacteria, we found that alpha/beta CD4+ T cells proliferated and exhibited increased levels of the interleukin-2 receptor (IL2R). In order to ensure antigen specificity, two different controls were included in these experiments: (i) T-cell proliferation and expression of the IL2R in the presence of the major membrane constituent of Bacillus megaterium were studied comparatively with the presence of the R. equi bacterial antigen, and (ii) T-cell proliferation and expression of the IL2R from naive, non-infected mice in the presence of bacterial antigens were compared to those observed in hyperimmunized mice. In our study, the T cells from hyperimmunized mice did not significantly proliferate nor were they activated in the presence of non-related bacterial antigens, and T cells from naive mice were not found to significantly recognize R. equi antigens. When we studied the localization of R. equi antigens that could stimulate the in vitro proliferation and activation of T cells, we found that they were constituents of the bacterial cell wall and the cytoplasm, but they were not excreted in the culture medium. For these experiments, T-cell recognition of the bacterial antigens in hyperimmunized mice was compared to that of naive mice. With T-cell immunoblotting, we found that T-cell proliferation and activation were obtained with proteins having molecular masses of approximately 65, 43, 30, 22-27 and 15-17 kDa. It is noteworthy that among the recognized bacterial antigens, some have been described as being associated with virulence.

Actinomycetales Infections↗

[Rhodococcus equi infection causing pulmonary malacoplakia in a patient with acquired immune deficiency syndrome].

Rhodococcus equi is a pathogen for some animal species. It can cause opportunistic pulmonary infections in immunocompromised people. The authors describe such an infection that causes malacoplakia in a patient with acquired immunodeficiency syndrome. The likeness between lesions due to Rhodococcus equi and those due to other opportunistic germs as Mycobacterium avium-intracellulare is emphasized.

AIDS-Related Opportunistic Infections↗

H(2)O(2), which causes macrophage-related stress, triggers induction of expression of virulence-associated plasmid determinants in Rhodococcus equi.

The response of the intracellular pathogen Rhodococcus equi to H(2)O(2) treatment, a situation potentially encountered after the oxidative burst of alveolar macrophages, was analyzed. Compared to other bacteria, including Deinococcus radiodurans, R. equi showed exceptionally high resistance to this stress. A proteomic approach showed that four polypeptides present in the wild-type strain (85F) are missing in the plasmid-cured strain 85F(P-), and by using a DNA macroarray, we identified two plasmid-encoded vap genes, vapA and vapG, whose expression was highly induced by H(2)O(2) treatment. Whereas the transcript size of vapA was compatible with a monocistronic mRNA, the transcript of vapG was considerably longer. Rapid amplification of cDNA ends PCRs showed that the transcriptional start sites of the two operons were 69 and 269 nucleotides (nt) upstream of the start codon, respectively. Analysis of these leader sequences revealed the presence of a small open reading frame named podG, which encodes a sequence of 55 amino acids preceded by a putative ribosome binding site sequence in the vapG transcript. Taking this result into account, the untranslated leader of the podG/vapG operon is 87 nt. Alignment of this sequence with the leader sequences of vapA and vapD, genes previously shown to be induced by acid, revealed significant homologies. Since our results showed that vapA, vapD, and vapG are genes highly induced by macrophage-related stresses, their gene products may, within the Vap protein family, play a dominant role inside these phagocytic cells and may be the most promising candidates for vaccination strategies.

5' Untranslated Regions↗

Search for Virulence-Associated Antigens of Rhodococcus equi in Strains Isolated from Patients with Acquired Immunodeficiency Syndrome.

Rhodococcus equi (formerly Corynebacterium equi) are known to be highly virulent, intermediate in virulence, or avirulent correlated with specific virulence-associated antigens identified immunochemically by different molecular weights. The association of virulence antigens with infection of AIDS patients by this organism has not been sufficiently evaluated in Brazil or Italy. The objective of the present study was to search for virulence-associated antigens of 15-to 17-kD and 20-kD in Rhodococcus equi strains isolated from patients with rhodococcal infection and AIDS. Four Brazilian and 9 Italian strains were studied. All isolates were analyzed by gel electrophoresis followed by immunoblotting using specific monoclonal antibodies to identify virulence-associated antigens. The results obtained on gel electrophoresis analyses showed complexing of R. equi components with proteins of molecular weights ranging from 10-to 150-kD. By immunoblotting, a wide diversity in R. equi virulence-associated antigens was detected: 1 of the 4 Brazilian isolates and 2 Italian isolates had the 15-to 17-kD virulence-associated antigen, 3 Brazilian isolates and 1 Italian isolate had the 20-kD virulence-associated antigen, and the other Italian isolates had no virulence-associated antigens. These results indicate that the pathogenicity of R. equi strains for humans does not depend only on the presence of these well established virulence-associated antigens.

Journal Article↗

Rhodococcus equi: fatal pneumonia in a patient without AIDS.

Rhodococcus equi infections are being recognized with greater frequency in immunocompromised patients and the population infected with the human immunodeficiency virus (HIV). R. equi usually causes a progressive pneumonia that may or may not cavitate and is relatively refractory to antibiotic therapy. We report a case of fatal R. equi pneumonia in a normal host.

Actinomycetales Infections↗