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Objective: To report clinical and microbiological features and response to treatment in HIV patients with Rhodococcus equi infection., Design: Retrospective study., Setting: Inpatients admitted to two Infectious Diseases Departments in a community-based hospital., Patients: A total of 12 HIV-positive patients with R. equi infection., Main Outcome Measures: Clinical status, radiological finding, microbiological, haematochemical and immunological tests, and response to treatment., Results: Twelve patients (11 men, six injecting drug users) were diagnosed with R. equi infection. Fever and cough were the principal clinical signs on presentation. Mean CD4+ count at the time of diagnosis was 47.67 x 10(6)/l (SD, 49.2 x 10(6)/l). In 58.3% of the cases the diagnosis of R. equi infection followed the appearance of an AIDS-defining illness. The most frequent radiological findings were cavitary lesions (41.7%) and lung consolidation (33.3%). In 83% of cases, R. equi was isolated from blood and in 33.3% cases from sputum. Test of chemosensitivity showed sensitivity to vancomycin (100%), teicoplanin (100%), ceftriaxone (80%), erythromycin (71%) and ciprofloxacin (66%). Clinical response alone with the disappearance of the presenting signs was observed in nine of the 12 cases (75%); complete response was observed in two cases. Seven patients died with a mortality rate of 58.3% and a mean survival of 5.75 months (SD, 6.48 x 10(6)/l)., Conclusions: R. equi should be considered in the differential diagnosis of pulmonary of disseminated infections in patients with HIV infection. Blood culture may be the most sensitive means of diagnosis. Other studies are needed to determine the most effective choice and duration of antibiotic therapy.

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.

Four isolates of Rhodococcus equi, from pneumonic foals, and containing the 85 kb virulence plasmid, a porcine isolate containing an 80 kb plasmid, and their plasmid cured derivatives, were examined for 239 phenotypic properties in an attempt to find characters other than the virulence-associated protein (VapA) which might be encoded by the virulence plasmid in organisms grown at 37 degrees C. Tests chosen included those which have previously given variable results for R. equi isolates, since such variability might be attributed to plasmid curing, and characteristics which have been described as properties of plasmids of Rhodococcus species other than R. equi. Tests included cadmium resistance, Congo red binding, resistance to 26 antibiotics, conventional clinical microbiological tests, utilization of 95 different carbon sources, enzymatic activities in API ZYM, fluorogenic assays for exo- and endopeptidase, glycosidase activities, and testosterone degradation. Apart from production of VapA by foal isolates, no phenotypic property was identified in the plasmid-positive isolates. Phenotypic characteristics of R. equi that have not been described before, and might be useful in identification were: metabolism of N-acetyl-beta D-glucopyranoside, alpha- and beta-hydroxybutyric, alpha-ketobutyric and N-acetyl-glutamic acids, of methylpyruvate, heptanoate, nonanoate and stearate esters; exopeptidase activity against alanine-alanine-tyrosine, alanine-phenylalanine-lysine, glycine-arginine, lysine-alanine, and valine-glycine-alanine; endopeptidase activity against arginine and methionine; and hydrolysis of bis-phosphate ester.

Using a broth microdilution technique, the in vitro susceptibility of bacterial isolates from the equine respiratory tract to trimethoprim, sulfadoxine, sulfadimethoxine, and combinations of these compounds was determined. The bacterial strains (n = 88) isolated recently from horses with respiratory symptoms belonged to the following species: Streptococcus equi subsp. zooepidemicus (n = 34), Streptococcus equi subsp. equi (n = 22), Staphylococcus aureus (n = 9), Klebsiella pneumoniae (n = 7), Rhodococcus equi (n = 4), Pseudomonas spp. (n = 3) and Escherichia coli (n = 3). In addition, two isolates of Enterobacter spp. and one isolate of Streptococcus equisimilis, Staphylococcus intermedius, Proteus mirabilis and Serratia marcescens were examined. For determination of susceptibility of an organism the following minimal inhibitory concentrations (MIC) were fixed as limiting values: Trimethoprim < or = 0.5 microgram/ml, sulfadoxine < or = 32 micrograms/ml, sulfadimethoxine < or = 32 micrograms/ml, trimethoprim/sulfadoxine < or = 0.5/32 micrograms/ml, trimethoprim/sulfadimethoxine < or = 0.5/32 micrograms/ml. As expected, Rhodococcus-equi-isolates were resistant to the antimicrobials tested. However, most of the clinically more common isolates showed a high degree of susceptibility to the combinations. The fractional inhibitory concentration (FIC) indices indicated synergism of the combination-partners in a wide range. According to these in vitro results, application of trimethoprim/sulfonamide combinations for the initial therapy of equine respiratory tract infections can be recommended.

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.

Rhodococcus equi is a gram-positive coccobacillus that appears to be emerging as a pulmonary pathogen in AIDS patients. In four human clinical isolates, two antibiotic resistance phenotypes were found to coexist: one beta-lactam resistant and the other beta-lactam susceptible. In vitro, beta-lactam-resistant mutants were obtained at a frequency of 1 x 10(-5) to 5 x 10(-5) from beta-lactam-susceptible strains on cephalothin-containing plates. Neither beta-lactamase nor plasmid DNA was detected in beta-lactam-resistant or -susceptible strains. The penicillin-binding protein patterns for the two types of strains were identical. Electron microscopy revealed that the beta-lactam-resistant strains possessed cell-surface-associated appendages and produced phage-like particles. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of total cell protein showed at least three additional bands of 42, 39, and 30 kDa found only in the beta-lactam-resistant strains. Testing for virulence in Swiss mice revealed that (i) phage-like-particle-producing strains had lower 50% lethal doses when injected intravenously in euthymic and nude mice than the non-phage-like-particle-producing strains did and (ii) intravenous inoculation of a sublethal dose (5 x 10(6) CFU) in nude mice led to chronic infection by the phage-like-particle-producing bacteria only. Finally, in vitro growth curves indicated that the phage-like-particle-producing strains possessed an ecological selection advantage. These results suggest that, among R. equi human isolates, the antibiotic resistance phenotype is associated with virulence and may be phage mediated.

The pharmacokinetic properties of four erythromycin formulations were compared in six adult horses after administration of single and multiple oral doses. Formulations of erythromycin administered were estolate and phosphate given 37.5 mg/kg every 12 h and 25 mg/kg every 8 h, and stearate and ethylsuccinate given 25 mg/kg every 8 h. Areas under the curve (AUC) and maximum plasma erythromycin concentrations (Cmax) were equal or greater (P > or = 0.05) following administration of erythromycin phosphate and stearate compared with those values following administration of erythromycin estolate or ethylsuccinate. In comparing an 8 h vs. a 12 h dosage interval for multiple doses of erythromycin phosphate or estolate, there were no significant differences observed in AUC(24-28 h), peak-trough plasma concentrations or duration that plasma concentrations exceeded the minimal inhibitory concentration (MIC) for Rhodococcus equi. Comparisons of pharmacokinetic parameters between single and multiple doses were made for each formulation. Differences in Cmax, tmax, or t1/2 beta between single and multiple doses were demonstrated for erythromycin ethylsuccinate and estolate. Based on equivalent plasma antibiotic concentrations, erythromycin phosphate or stearate could be substituted for estolate in the treatment of Rhodococcus equi pneumonia. Furthermore, there was no advantage of an 8-h interval, compared with an interval of 12 h.

Infections of Rhodococcus equi, a well-known pathogen in animals which causes cavitated pneumonia similar to that caused by mycobacteria, were studied in three HIV-infected patients. This microorganism was isolated in the bronchoalveolar washings of two patients and in the sputum of the third. In two patients, Rh. equi represented the first clinical opportunistic manifestation of HIV disease. One patient died of concomitant Pneumocystis infection. The eradication of the microorganism occurred in two out of three patients. It was found that no isolates were resistant to erythromycin, claritromycin, rifampin, vancomycin, teicoplanin, imipenem, gentamycin or azithromycin (MIC values < or = 0.1 microgram/ml). Moreover, the quinolones (ciprofloxacin and ofloxacin) were found to be less effective, whereas neither the beta-lactam antibiotics nor chloramphenicol were effective therapy for this microrganism. At least two antimicrobial agents should be given contemporaneously to treat these infections for a period of up to several months. Our results suggest that the combinations erythromycin + rifampin or imipenem + teicoplanin are the most effective treatments in Rh. equi infections.

Objective: To present a case of Rhodococcus equi (RE) pneumonia and discuss its pathophysiology and treatment., Case Summary: An HIV-positive patient presented with pneumonia. A lung biopsy was performed after sputum and thoracentesis cultures failed to identify a pathogen. The lung biopsy revealed an unidentifiable, diphtheroid-like, gram-positive rod. A bronchoscopy performed five days after the lung biopsy produced the same diphtheroid-like, gram-positive rod. The patient was treated with several injectable antibiotics, but emergence of resistance to two of the antibiotics was suspected. Two weeks after the bacterial isolate was sent to a reference laboratory, it was identified as RE. The patient was discharged on oral antibiotics and experienced no recurrence of RE pneumonia., Conclusions: RE can be difficult to identify in the microbiology laboratory, or it may be assumed to be a colonizing diphtheroid. The isolation of difficult-to-identify, gram-positive rods, or diphtheroids, from a pulmonary source in a patient with decreased cell-mediated immunity should cause one to suspect RE. RE has been noted to develop resistance to beta-lactam antibiotics during therapy. A prolonged course of combination antibiotic therapy directed at the intracellular component of infection is necessary.

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.

Side-chain cleavage of sterol and extracellular cholesterol oxidase activity were investigated using viable cells of R. equi DSM 89-133 immobilized in polyacrylamide gel. In batch culture, immobilized cells were active in side-chain cleavage of cholesterol for more than 30 days. Free or immobilized cells were incapable of side-chain cleavage in the absence of 2,2' dipyridyl; cholesterol oxidase was, however, produced in both the cases. Maximal activity of the immobilized cells was 60 to 70% of the free cells.

Twenty-four foals were confirmed to be infected with Rhodococcus equi on a private stud in Zimbabwe over a two-year period. Six mares had foals which were affected in each of the two years. All the foals were febrile and early cases were detected by this pyrexia. Bronchopneumonia was only clinically detectable in advanced cases. In spite of energetic hygiene measures relating to pasture and housing management, the incidence was higher in the second year (23 per cent of foals born) than in the first (15 per cent of foals born). The mean age of the foals was significantly greater in the second year. The immunological status of some of the foals was obtained from zinc sulphate turbidity tests performed at 24 hours old and all the affected foals so tested were considered to have had effective colostral transfer. Clinically, affected foals showed pyrexia, tachypnoea and tachycardia and many had a scanty purulent nasal discharge. Only one animal had diarrhoea which was attributed to enteric infection with R equi. Diagnosis was confirmed by clinical examination, culture of the organism from tracheal aspirates and thoracic radiography and was supported by significant elevations of plasma fibrinogen and platelet and neutrophil counts in all cases. Anaemia was not a major finding in any case. Rifampicin and erythromycin were administered per os and weight-related doses were continued until plasma fibrinogen and the absolute neutrophil and platelet counts had been persistently normal for two weeks. Supportive radiography was obtained in some cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Rhodococcus equi is a facultative, intracellular, gram-positive coccobacillus increasingly reported as an opportunistic pathogen in human immunodeficiency virus-positive patients. However, the optimal drug regimen for treating R. equi pulmonary or systemic infections is not yet known. Therefore, a model of intravenously infected nude mice with disseminated infection was created to study the efficacy of antibiotics alone or in combination as determined by the reduction of bacterial CFU per gram in the lungs and spleen after 4 and 11 days of treatment. The studied antibiotics possessing low MICs against R. equi strains were amikacin, ciprofloxacin, erythromycin, imipenem, minocycline, rifampin, and vancomycin. Vancomycin, imipenem, and rifampin were the most effective agents in monotherapy. On the other hand, amikacin, ciprofloxacin, erythromycin, and minocycline alone were not active in this model. The most active drug combinations were those including vancomycin. No antibiotic-resistant mutants were selected in vivo with treatment involving any drugs used alone or in combination. Although the treatment recommended until now for R. equi infections is rifampin plus erythromycin, this study suggests that antibiotic combinations which include vancomycin may be the most effective in vivo.

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.

Rhodococcus equi is an intracellular facultative, Gram-positive cocco-bacillary organism of increasing importance as a pulmonary pathogen in HIV-positive patients. This study was carried out to evaluate the optimal antibiotic combinations for treating such infections. Four human R. equi isolates and one reference strain were tested for their susceptibilities to 36 antibiotics. In-vitro the most active antibiotics were amikacin, gentamicin, netilmicin, erythromycin, clarithromycin, roxithromycin, ciprofloxacin, sparfloxacin, rifampicin, vancomycin, teicoplanin, doxycycline, minocycline, imipenem, meropenem and trimethoprim/sulphamethoxazole. The only bactericidal antibiotics were the aminoglycosides, ciprofloxacin, sparfloxacin and vancomycin. As determined by FIC indices, four combinations were synergistic: rifampicin-erythromycin, rifampicin-minocycline, erythromycin-minocycline and imipenem-amikacin. However, no antibiotic combinations were synergistic with the time-kill kinetic method at achievable serum concentrations or at ten-fold and half-fold the MICs. Frequencies of selection of antibiotic-resistant mutants determined at concentrations of five- and ten-fold the MICs ranged from less than 1 x 10(-8) for erythromycin and trimethoprim/sulphamethoxazole to 5 x 10(-4) for amikacin. These results may be of help in selecting the antibiotics for treating infected HIV-positive patients.