Rhodococcus equi infection in non-HIV-infected patients. Two case reports and review


Corresponding author and reprint requests: Claudio Farina, Servizio di Microbiologia, Ospedali Riuniti, Largo Barozzi, 1-24128 Bergamo, Italy Tel: +39.35.269505 Fax: +39.35.269666


Objective: To review two recent cases in HIV-negative subjects in the light of literature reports (52 patients without HIV infection till 1994).

Method: Epidemiology (animal contacts, risk factors, year, country), clinical presentation, diagnostic methods (X-ray, tomography, microbiological techniques), therapeutic approach (antibiotics, surgery) and outcome were evaluated on the basis of clinical literature reports.

Results: Tumors constituted an important predisposing factor and less frequently hepatobiliary pathology, rheumatologic diseases, iatrogenic causes, psychiatric pathology and trauma. Exposure to animals was reported by 55% of the patients. Pneumonia and pleurisy, without preferential localization, were detected in 50% of the patients. Etiologic diagnosis was usually obtained after an invasive collection. Combined medical therapy and surgery were required by 27.8% of the patients, and 16.7% of the patients died.

Conclusions: In recent years the number of Rhodococcus equi cases has been rising also in HIV-negative patients. The infection is ubiquitous. Accurate diagnosis and the prompt selection of the most appropriate therapy depend on close cooperation between clinicians and microbiologists.


Bacteria of the genus Rhodococcus are Gram-positive microorganisms, obligate aerobes, mesophilic, chemoorganotrophic, immobile, partially alcohol/acid fast (in certain stages of their growth cycle), with a mycelium which can break up into bacillary or coccoid elements. They were first reported in 1889 when Zopf described a microorganism initially referred to as rhodochrous, meaning pink-tinged; this term is no longer used [1]. Rhodococcus has been assigned to various genera: Corynebacterium, Gordona, Mycobacterium, Nocardia, etc. However, in 1974 Tsukamura suggested the current denomination used for the genus, comprising the telluric species rhodochrous (subsequently considered a type species) [2]. Good-fellow, in the fifth edition of Bergey's Manual of Systematic Bacteriology, rendered official the term nocardioform actinomycetes, covering many bacterial genera, including Rhodococcus [3].

The first description of R. equi as an animal pathogen, causing pyogranulomatous pulmonitis in foals, dates back to 1923 [4]. The first human case, however, was reported much later, by Golub et al., in 1967, who described it in an immunodepressed patient [5]. By 1986 [6] there had been numerous reports of R. equi infection in patients with pathologies related to human immunodeficiency virus (HIV). Fifty-two cases have been described in patients who were negative for HIV [7–44]. Our observation of two cases of R. equi infection in patients without HIV infection suggested a review of the epidemiologic, clinical and diagnostic data on this increasingly frequent infection.


A 68-year-old woman, resident in a country area, reported contact with farmyard animals and horses. The patient had been diagnosed as having non-Hodgkin's lymphoma 17 years earlier, and had received repeated cycles of chemo- and radiotherapy. In June 1992 she presented an erythematous infiltrative lesion near the umbilicus, close to an area of recent radiotherapy; it had partially regressed in response to amoxycillin and clavulanic acid, but had then rapidly progressed, causing an abscess. Although the patient was given diaminocillin, 1,200,000 U every 2 weeks, as an outpatient, and erythomycin 1 g twice-daily for 10 days, with daily topical application of polyvinylpyrrolidone iodine, the abscess spontaneously discharged after 1 month, leaving a sinus. She was admitted to hospital with fever (40.2°C), and empirical antibiotic therapy was started with sulbactam/ampicillin 2 g twice-daily. Her erythrocyte sedimentation rate (ESR) was 80 mm/h and she had peripheral neutrophilia (WBC 2740/mm3, neutrophils 81%). Serologic tests found no HIV antibodies.

Blood cultures of samples taken on the first and fifth day in hospital and of purulent material from the periumbilical fistula were positive for R. equi. On the basis of in vitro antibiotic sensitivity testing results, the patient was treated with pefloxacin 400 mg twice-daily, until she was discharged on day 15.

Three months later the patient presented an unexpected fever again, and despite treatment with teicoplanin 400 mg, she died at home. No autopsy was done.


A 50-year-old man with chronic active hepatitis (HCV-Ab positive) received an orthotopic heart transplant with continuous normothermal potassium retroper-fusion for New York Heart Association (NYHA) class IV dilatatory myocardiopathy. During surgery, five epicardial pacemaker wires were positioned, three ventricular and two atrial. The patient subsequently received cyclosporin A.

In the immediate postoperative phase he suffered vascular shock from peripheral vasoplegia, and hyperthermia (39.5°C). Blood cultures were all negative. On day 15 he presented fever (38°C) and complained of spontaneous pain and pain on palpation in the left parasternal area, localized to the mid-zone, but radiating to the left shoulder. Inspection of the surgical wound showed nothing noteworthy and there was no appreciable sternal displacement. There was neutrophil leukocytosis (WBC 9980/mm3, neutrophils 76.4%), and his ESR was 112 mm/h. The atrial pacemaker wires and one ventricular wire were removed, and culture grew R. equi. Blood cultures were negative.

Symptoms regressed spontaneously and by day 20 the patient no longer had fever. However, on day 30 he still had some slight redness and swelling at the lower third of the surgical wound, causing pain at the left sternal margin. A scan with labeled leukocytes showed an accumulation at this site. The patient was therefore treated with ciprofloxacin, 500 mg twice-daily. Computer scan (tomodensitometry) of the mediastinum showed an oval low-density area, about 15 mm in diameter, within the anterolateral wall of the right ventricle; this was not easy to interpret, and culture of seropurulent matter sampled from the medioproximal region of the sternal wound gave no bacterial growth.

The patient later suffered herpes zoster infection in the left cervicobrachial region and Legionella pneumophila infection.

Serologic tests before surgery and during follow-up gave negative results for HIV antibodies.


Blood samples were inoculated into BACTEC Plus 26 and 27 flasks (Becton Dickinson, Diagnostic Instrument Systems, Sparks, MD, USA); signs of growth were evident after 72 h of incubation at 35°C. Subculture of these samples, like the first culture of pus, incubated in a CO2-enriched atmosphere for 24 h, yielded small colonies (diameter 1 to 2 mm), smooth, glossy and moderately mucous, convex with regular edges, and tending to confluence after 48 to 72 h.

Microscopic examination showed pleiomorphic Gram-positive coccobacilli, and no spores. API Coryne kits (Bio-Mérieux s.a., Marcy l'Etoile, France) detected the following enzymatic activities: nitratoreductase, alkaline phosphatase, alpha-glucosidase, urease, and catalase; there was no carbohydrate fermentation capacity. The strains had myristate lipase (C14) activity, tested by the Bio-Mérieux API ZYM system. On the basis of these biochemical features, and the gross and microscopic appearance of the colonies, the microorganism was identified as R. equi.

The isolates were tested for antibiotic sensitivity by the agar diffusion method according to NCCLS procedures. Both strains were resistant to penicillin, first-generation cephalosporins and clindamycin, but sensitive to macrolides, quinolones, vancomycin, third-generation cephalosporins, piperacillin and imipenem.


Bacteria of the genus Rhodococcus are saprophytes found in earth and vegetation, where they break down organic plant substances, in fresh and salt water, and in the intestinal contents of mammals, mainly herbivores, and hematophage arthropods [45]. Some species of Rhodococcus are phytopathogens; others cause infection in herbivores (horses, sheep and cattle), pigs and fish; others have been isolated from human respiratory material [3].

Infection with R. equi is of interest in veterinary medicine, occurring almost exclusively in foals, where it frequently causes rapidly progressive suppurative bronchopneumonia, with multiple abscesses, and sometimes colitis and granulomatous mesenteric lymphadenitis. There are occasional reports of ‘tubercular-like’ episodes in pigs and cattle, and in other locations in dogs, cats, reptiles and koala bears [45].

In human pathology Rhodococcus spp. infection is very infrequent. However, in recent years the numbers of cases have been rising, possibly because of increased attention being given to this pathogen, but also because of the rising numbers of patients, especially immuno-depressed ones, exposed to the infection.

About fifty cases of HIV patients infected with R. equi were found in the international literature up to the end of 1994, many of them in Mediterranean countries. R. equi is often the cause of the first opportunistic infection [46–49], especially when the patient's absolute CD4 lymphocyte count is less than 100 mm3. It has thus been suggested that isolation of R. equi is a diagnostic indication of AIDS, and R. equi might be included in CDC classification group 4C1.

R. equi infection in non-HIV patients presents particular epidemiologic and clinical features, and generally the prognosis is better than in seropositive cases [46]. We found 52 cases reported in the literature, covering three decades up to the end of 1994, all HIV negative [5,7–44]. Eight of 54 were observed from 1965 to 1974, 15 in the next decade, and 31 in the years 1985–94.

The infection was diagnosed in 33 males and 21 females (female-to-male ratio 1:1.5), aged from 7 months to 76 years (mean 40, median 40.5 years). The infection was ubiquitous, and the different geographic distribution of the isolates appears to reflect local microbiological practice more than the existence of specific reservoirs: 32 cases were described in North America; 11 were from Europe; five were from Oceania; and the remaining three were from Asia or South America (one from Brazil). Table 1 shows the epidemiologic and clinical features of these cases.

Table 1.  Epidemiological and clinical features of rhodococcosis
PatientAge/sexRisk factorAnimal contactClinical presentation/Clinical diagnosisX-rayCultureAntibioticsSurgeryOutcomeYear/CountryRef.
  1. ALL = acute lymphocytic leukemia; APL = acute promyelocytic leukemia; AML = acute myeloblastic leukemia; CLL = chronic lymphocytic leukemia; CML = chronic myelogenous leukemia; CNS = central nervous system; COPD = chronic obstructive pulmonary disease; HD = Hodgkin's disease; LL = lymphocytic lymphoma; LS = lymphosarcoma; NHL = non-Hodgkin's lymphoma; RC sarcoma = reticulum cell sarcoma; RA = rheumatoid arthritis; BBF = bronchobiliary fistula; LLL = left lower lobe; LUL = left upper lobe; RLL = right lower lobe; RML = right middle lobe; RUL = right upper lobe; LPE = left pleural effusion; PC = pulmonary cavitation; UAP = upper abdominal pain; C = present case; Interst. accent. = interstitial accentuation; sequestr. = sequestrectomy; NK = not known; A = ampicillin; AMC = amoxicillin-clavulanate; AMX = amoxicillin; AZT = aztreonam; C = chloramphenicol; CAZ = ceftazidime; CC = clindamycin; Cef = cefsulodin; CF = cephalexin; CFZ = cephazoline; Cip = ciprofloxacin; CRO = ceftriaxone; CTX = cefotaxime; Clo = cloxacillin; Doxy = doxycycline; E = erythromycin; ETH = ethambutol; FA = fusidic acid; Fu = fucloxacillin; GN = gentamicin; I = iodophor; IMP = imipenem/cilastatin; INH = isoniazid; Lat = latamoxef; Ofl = ofloxecin; P = penicillin; Pef = pefloxacin; RF = rifampin; SAM = sulbactam-ampicillin; SXT = sulphamethoxazole; Tic = ticarcillin; Tin = tinidazole; TMP = trimethoprim; Tob = tobramicin; Va = vancomycin.

19/MNonePigs?Fever, neck swelling Cervical lymphadenitisNot doneLymph nod biopsyDoxyNoneCured1965/Denmark7
22/FNoneCatPainless swelling hand OsteomyelitisOsteal reactionSynovial/bone biopsyINH, then E+AMXNoneCured1976/USA18
328/MNoneLaboratory researcherCough, dyspnea, chest pain PneumoniaCavitation (LUL) Multiple nodulesLung biopsyOfl+Cef+Lat, then Ofl+TicNoneCured1987/Japan33
43/FNoneDogsFever, cough, neck swelling Sepsis, cervical lymphadenitisNot doneBloodE, then CTXNoneCuredNK/USA44
538/MNoneNot detectedFever, chills, cough PneumoniaCavitation (LLL)SputumENoneCuredNK/USA44
640/FNoneHorsesArm fracture-dislocation Soft tissue infectionNot donePusVa+RFDrainageCuredNK/Italy42
739/FKidney transplantNot evaluatedFever, chest pain, cough PneumoniaCavitation (LUL)PC pusNoLobectomyCured1971/USA8
845/FKidney transplantPigFever, dyspnea, chest pain, lethargy, cough PneumoniaInfiltrate (LUL)Bronchial biopsy; PC pusAMX, then E+GNNoneDied1975/Australia14
938/MKidney transplantHorsesBurn Burn infectionNot doneSkin biopsyAMXNoneRelapsed (4)1975/N. Zealand20
1030/MKidney transplant/HDCattleAsymptomatic relapse: headache Pneumonia; CNS infect.Cavitation (RLL) Brain abscessesLung nodule pus Brain pusE+TMP-SXT, then C+Va+GNLobectomy DrainageRelapse Cured1980/USA22
1152/MKidney transplantNoneMyalgia, fever, UAP Soft tissue infectionNot reportedParaspinal abscess pusFu+Tob then E+RFDrainageCured1985/N. Zealand32
1264/MKidney transplantNot evaluatedThigh enlargement Osteomyelitis (femur)Lysis metaphysisUrine, muscle necrosisP, then E+Va then E+ TMP-SXTSequestr.Cured1986/USA29
1362/MKidney transplantNot evaluatedFever Pneumonia, pleuritisInfiltrate (RML)Lung autopsyIMP+TobNoneDied1991/Spain39
1442/MHeart transplantDog; horsesFever, cough PneumoniaCavitation (RUL)Lung biopsy, bloodVa+Cip then Cip+AncNoneCured1991/Spain43
1550/MHeart transplantNot detectedFever, sternal wound infection Soft tissue infectionNegativeWiresCipNoneCured1992/ItalyC
1651/MProsthetic valve replacementNot detectedFever EndocarditisNot reportedAortic valve vegetationsP+GNValve replacementCuredNK/UK21
1747/FHDHorsesFever, dyspnea, cough PneumoniaInfiltrate (RUL)Lung biopsy; blood; skinE, then E+TetLobectomyCured1974/USA13
1826/MHDHorse, pigFever, dyspnea, cough Pustular lesions Pneumonia, soft tissue infectionCavitation (RML)Surgical tissue; PC pusP, then ELobectomyCured1975/USA12
1953/FHDNot evaluatedFever SepsisNegativeBone marrowSXTNoneDied1977/USA15
2052/MHDNot evaluatedFever; cough PneumoniaInfiltrate (RML)Bronchial biopsyNot specifiedNoneCured1979/USA16
2134/MHDNot evaluatedFever SepsisInfiltrate (RML)Blood/sputumNot specifiedNoneDied1979/France17
2218/MALLNoneFever PneumoniaInfiltrate (LLL)Bronchial washingOxa, then CC+CNoneDied1974/USA11
236/FALL, myringotomyNot evaluatedFever, cough PneumoniaCavitation (RUL) Nodule (LLL)Lung biopsy, bloodE+RFNoneCured1988/Canada30
249/FALL?Not evaluatedFever SepsisNot reportedBloodNot reportedNoneCured1990/NK34
2568/FNHLHorsesFever, skin abscess Soft tissue infectionNegativePus; bloodSAM, then PefNoneDied1992/ItalyC
266/MCMLNot evaluatedFever, tachypnea, cough PneumoniaInfiltrate (LLL)Pleural fluidCAZ+Net+Oxa, then PDrainageCuredNK/USA37
2773/FCLLNoneFever, cough PneumoniaInfiltrate (RLL)Transtracheal fluidTMP-SXTNoneCured1977/USA15
2864/MLLFarmerCachexia, ascites PleutitisInfiltrate (RLL)Blood/pleural fluidTMP-SXTNoneDied1979/USA22
2936/MAPLHorsesMyalgia, fever SepsisNegativeBloodE+RFNoneCured1990/USA41
3058/MAMLNoneFever SepsisNegativeBlood, catheter tipPef+Tob+VaNoneCured1990/France36
3153/FRC sarcomaNoneFever, vomiting, cough PneumoniaInfiltrate (LLL)Blood; pleural fluidCF+GNNoneDied1974/USA13
3239/MLSHorsesFever, dyspnea, cough PneumoniaCavitation (LUL)PC pus; bloodA+GNNoneDied1971/USA9
3353/MLSFoalsEmpyema, then tentorial herniation Pneumonia; CNS infect.LPEPleural pusA+Clo then A+TobDrainageCured1980/N. Zealand32
3452/FAdenocarcinomaNot detectedFever, vomiting SepsisNegativeBloodAZT+SAMNoneCuredNK/USA44
353/FEpendymoblatomaNot evaluatedFever, cough SepsisInterst·accent.BloodVa + CAZNoneCuredNK/USA37
3662/MTraumaFarmerLeft foot tumorMycetomaNot reportedFoot pus and biopsyTMP+SXTNoneCured1985/Brazil26
379/MTraumaNoneEye pain EndophthalmitisNot reportedVitreous fluidGNVitrectomyCured1985/USA27
3829/MTraumaNot evaluatedCorneal laceration EndophthalmitisNot reportedVitreous fluidCFZ+GNVitrectomyCuredNK/USA31
394/MTraumaNot detectedKnee pain, fever Articular infectionNot doneKnee joint fluidCFZArthrotomyCuredNK/USA44
409/MTraumaNot detectedLymphangitisNot doneWound pusCFNoneCuredNK/USA44
4170/MCOPDNot detectedFever, dyspnea, cough PneumoniaInfiltrate (RUL)Transtracheal fluidINH+ETHNoneUnchanged1977/USA15
4233/FFactitious illnessNot evaluatedFever Sepsis (8 times)Not reportedBloodTMP-SXT+IMPNoneCured1988/Sweden35
4376/FSchizophreniaNot detectedRespiratory distress PneumoniaCavitation (RML)BloodE+GN+RFNoneCuredNK/USA40
4469/MRAFarmerCough, hemoptysis PneumoniaInfiltrate (LLL)Lingular massDoxy+VaNoneCured1985/USA25
4551/FRANoneDyspnea, chest pain PneumoniaCavitation (RUL)SputumCFZ, then INH+RF+ETHNoneDiedNK/USA38
4654/FSarcoidosisCattle, swineHemoptysis, fever PneumoniaCavitation (LUL)Blood and rib biopsyE+RFNoneCured1982/Sweden28
4769/FPoliarthritisNot evaluatedGluteal abscess Soft tissue infectionNot reportedPusNoneNoneCured1981/Germany19
4841/MAlcoholismHorsesFever PeritonitisNegativeAscitesNoNoneCured1985/France23
4956/FAlcoholismNoneFever, chest pain PleuritisLPE, atelectasis (LUL)Pleural fluidA, then RF+INHNoCured1986/USA24
5029/MCirrhosisNot detectedFever, vomiting, diarrhea PneumoniaCavitation (RUL)PC pusEDrainageCured1966/USA5
5120/FCholecystitisHorses, cattleVomiting CholecystitisNegativeMesenteric lymph nodeNoCholecystectomyCured1970/France10
523/FCongenital hepatic fibrosisNot evaluatedFever SepsisNot reportedBloodVa+PNoneCuredNK/USA37
5376/MBBFGardenerDyspnea, cough PneumoniaCystic areas (RLL)Cystic cavity pusAMX+TinDrainageCured1985/N. Zealand32
5453/MEmphysemaLivestockFever, dyspnea, cough PneumoniaCavitation (LUL)Bronchial washCC+E+RF+CRONoneCuredNK/USA44

Malignant blood disorders (Hodgkin's and non-Hodgkin's lymphomas, leukemia and sarcoma) accounted for 17 of 54 of the underlying diseases; solid tumors—adenocarcinoma and ependymoblastoma—accounted for only two cases. Less frequently, there was hepatobiliary pathology resulting from alcoholism, cirrhosis or gallbladder diseases (five cases); rheumatologic diseases—rheumatoid arthritis, polyarthritis and sarcoidosis—accounted for four cases. Iatrogenic causes are becoming more frequent: organ transplant (nine cases), valve replacements and continuous ambulatory peritoneal dialysis (CAPD) (one each).

One patient presented two risk factors—renal transplant and Hodgkin's lymphoma. Two cases had concomitant psychiatric illness, one of them involving self-injury, which suggested a traumatic pathogenic mechanism. Post-traumatic infections thus amounted to six cases, and in these the clinical course was particularly serious, with endophthalmitis and sepsis, or subcutaneous lesions like mycetomas. Two patients had chronic respiratory diseases and six had no identifiable risk factor.

Exposure to animals, possible reservoirs of R. equi, was reported by 22 of the 40 patients who were asked about this. One case of R. equi infection was described in a laboratory technician who, however, had had no contact with experimental animals or microorganisms. It would appear that in most cases—as confirmed by the two we report here—contamination is due to direct contact with R. equi through burns, surgery, or direct trauma, or to the inhalation of bacterial cells with dust or environmental debris, even if no animal reservoir is actually present.

In 27 of the 54 cases, presentation involved the respiratory tract, with pneumonia or, more rarely, pleurisy. Radiologic examination found cavitary progression in 13 of 27 cases, stabilized infiltrates in 12, and atelectasis in one. There seemed to be no preferential localization in the lungs.

Etiologic diagnosis was usually based on specimens obtained invasively (16 of 54 pus or vitreous; 15 out of 54 biopsy). Respiratory specimens were also usually collected invasively: seven by bronchial or pulmonary biopsy, five from pus from cavitation, two from bronchial lavage, four from pleural fluid, and two from transtracheal puncture. In three cases R. equi was isolated from sputum culture, but only in one case was the positive material the basis for diagnosis. Blood and bone marrow cultures were positive in 20 of 53 cases, in 10 of them without confirmation from other positive specimens. One case was diagnosed at autopsy.

Two patients relapsed, one of them four times. One patient, with psychiatric pathology, presented eight successive episodes of sepsis. Fifteen cases (27.8%) required combined medical therapy and surgery; in the remainder, antibiotics, with a variety of long-term regimens, resolved the clinical picture. There were nine deaths (16.7%), usually patients in very poor general condition.

Etiologic diagnosis was often difficult, since R. equi is often dismissed as a contaminant in the sample, and rhodococcosis is rarely considered in differential diagnosis, especially in HIV-negative patients. However, clinical microbiologists and attending physicians should always bear in mind that R. equi is no longer a rare opportunistic microorganisms, particularly after transplants or in leukemia. Accurate diagnosis and the prompt selection of the most appropriate therapy depend on close cooperation between clinicians and microbiologists.