—  SPECIALTY CONFERENCE  —

Infectious Disease Pathology

Case 2 - Rhodococcus Equi Pneumonia
as the Presenting Feature in a HIV Positive Aids Patient

Margie A. Scott
Central Arkansas Veterans Healthcare System and
University of Arkansas for Medical Sciences
Little Rock, Arkansas


Click on each slide thumbnail image for an enlarged view
Clinical History
A 34-year old divorced mechanic presented to the emergency room with a 3 to 4 week history of malaise, fever, non-productive cough, left sided chest pain and night sweats. The patient recalls recent exposure to a friend's child who was diagnosed with "walking pneumonia." Past medical history was positive only for degenerative joint disease of the knee (ACL tear) and two bouts of "pink eye" in the past year. The patient lives in a rural area and enjoys outdoor activities such as hunting, rodeos and horseshows, but recalls no unusual exposures to wildlife, ticks or insects. The patient reports being HIV and PPD negative at time of military discharge. On physical examination there was mild fever of 99.9 F, BP 123/73, pulse 120, respiratory rate 20, and chest was clear to auscultation. Laboratory: WBC 7.3, Hgb 13.3, Hct 38.8, Plt 251, Basic metabolic panel and UA were normal. Chest X-ray was positive for a LUL infiltrate, 6.7cm maximum dimension with focal cavitation, very suspicious for TB. The patient was admitted with respiratory isolation precautions, started on broad-spectrum antibiotic therapy, a PPD and control were placed and the infection control team was notified. Blood and sputum samples were collected for bacterial, fungal and mycobacterial cultures. Serologic studies for Hepatitis C, Hepatitis B and HIV were obtained. The patient left the hospital AMA on hospital day 2, with the PPD and control noted as "no induration." The patient returned to the emergency room one week later with progressive respiratory symptoms and was admitted for pulmonary consultation, CT scan and bronchoscopy. The TB skin test was noted as "negative" by the patient. AFB smears were negative and previously obtained cultures were negative to date. CT scan confirmed the LUL density with three areas of early cavitation as well as a focal infiltrate in the RUL and mild hilar adenopathy. No additional abnormalities were identified. A transbronchial biopsy and BAL were obtained for work-up.


Case 2 - Figure 1 - Chest radiograph showing a left upper lobe infiltrate with focal cavitation. Read as suspicious for tuberculosis
Case 2 - Figure 2 - Transbroncial biopsy was non-contributory and does not reflect lesional sampling.


Case 2 - Figure 3 - BAL cell block, inflammatory process with a predominance of histiocytes and neutrophils.
Case 2 - Figure 4 - BAL cell block, some histiocytes show eosinophilic cytoplasm. (Gram stain, not shown, demonstrated rare gram-positive coccobacilli of Rhodococcus equi.

Histologic & Culture Findings
Sections of the transbronchial biopsy are non-contributory, and do not reflect lesional sampling. The BAL cell block shows a distinct inflammatory process with a predominance of histiocytes and neutrophils. Scattered histiocytes have an enhance eosinophilic cytoplasmic appearance on Hematoxylin&Eosin which increases with Periodic-Acid-Schiff staining. Scattered intracellular gram positive coccobacilli are identified; acid fast stains are negative. Follow-up cultures were positive for Rhodococcus equi with successful isolation and identification from the Lowenstein-Jensen slant. Sensitivities performed on 5% RBC enriched Mueller-Hinton agar using standard Kirby-Bauer method, show the organism to be sensitive to rifampin, vancomycin, erythromycin, tetracycline, imipenem, cefepime, clindamycin, tobramycin, amikacin, ciprofloxicin, levofloxicin and sulfa/trimethoprim. (noted in report: There are no NCCLS standards for sensitivity testing of this organism; sensitivities are compared to those reported within the literature; antimicrobial therapy should be coordinated with infectious disease specialist consultation)

Clinical Follow-Up
The patient was evaluated for suspected HIV infection based on clinical history and presentation. The HIV positive screen was confirmed by western blot analysis and subsequent viral load studies demonstrated 533,000 viral copies per ml (Log 10 = 5.73c/ml). Lymphocyte subset studies demonstrated an absolute lymphocyte count of 962 (ref: 1000 – 4000); CD 8 suppessors = 64%; CD 4 helpers = 11% with a markedly decreased absolute CD4 cell count of 105 (ref 500 – 1500). HIV Genotyping studies indicted possible resistance to Indinavir (PI), saquinavir (PI), ritonavir (PI), nelfinavir (PI), lamivudine (NRTI), sidovudine (NRTI). The patient was started on lamivudine (NRTI), stavudine (NRTI) and efavirenz (NNRTI) as initial therapy for his HIV infection. He was started on levofloxicin for his Rhodococcus equi pneumonia and prophylactic bactrim was initiated. The patient noted improvement of clinical respiratory symptoms within one week of initiating antibiotics. The patient responded with a greater than two-fold log decrease in HIV viral load and a follow-up chest X-ray performed three months after presentation, demonstrated near complete clearing of the air space disease in the Left Upper Lobe. The patient is tolerating anti-viral and antibiotic therapy well and is to complete a six month course of levofloxicin before considering discontinuation of this antibiotic for his Rhodococcus equi peumonia.

Diagnosis:
Rhodococcus equi pneumonia as the presenting feature in a HIV positive AIDS patient.

Discussion:
Rhodococcus equi (previously Corynebacterium equi) is an opportunistic gram positive weakly acid-fast coccobacillus that resides in the soil and is usually spread to it intended host, horses, via the respiratory route and is known as a common cause of foal pneumonia. Although occasional cases of human direct inoculation infection of the eyes, skins, oral mucosa have been described in the immunocompetent host, these tend to be mild and self-limited. Since the first reported human infection with Rhodococcus equi in 1967, it has become increasingly recognized as an important pathogen in the immunocompromised host. Rhodococcus equi pneumonia characteristically presents with fever, chills, malaise, chronic cough and necrotizing cavitary pneumonia on Chest X-ray. The cavitary lesions vary at presentation from 1 to 8cm in diameter. The clinical danger is its mimicry of tuberculosis and the identification of acid fast bacilli on respiratory specimens obtained for TB culture may result in the initiation of anti-tuberculous therapy. Other sites of infection and presentations documented in the literature include: soft tissue mass, pleural effusion, empyema, pelvic abscess, brain abscess, subcutaneous abscess, paraspinal abscess, osteomyelitis, lymphadenitis, endophthalmitis and fever of unknown origin. Widespread dissemination of infection at autopsy in the immunocompromised host is well documented. As clinicians become more aware of this potential pathogen of the immunocompromised host, outcomes have improved with long term multi-drug, antimicrobial therapy and close follow-up for resolution of symptoms. Rhodococcus equi, in fact, may be the initial presentation of a patient with undiagnosed HIV infection and AIDS.

Histologically, Rhodococcus equi pneumonia is characterized by a dense mixed histiocytic and neutrophilic infiltrate, without formation of giant cells or distinct granulomas. The histiocytes become filled with organisms and take on a brightly eosinophilic appearance in routine Hematoxylin-Eosin stains. These histiocytes further intensify with Periodic-Acid-Shiff (PAS) staining, similar in appearance to the infected histiocytes of Whipple's disease. The organisms stain well with gram stain and silver precipitate stains such as Gomori-methenamine silver, and variably with acid fast stains. In patients with ongoing chronic infection and/or inadequate antimicrobial therapy, the histiocytes become the predominant cell type and may take on a "spindle cell pseudotumor" appearance with the formation of intracytoplasmic laminated inclusions, Michaelis-Gutmann bodies. The spindle cell variant morphology occurring in sites such as a soft tissue mass with minimal necrosis can have a striking pseudosarcomatous appearance. In this setting, malacoplakia with numerous Michaelis-Gutmann bodies help call the attention of the pathologist to the infectious nature of the lesion.

Recognition of culture isolate is often difficult in routine bacterial cultures of respiratory specimens, as the gram stain morphology is 'diphtheriod' in nature and may be dismissed as 'a contaminant' in its early growth stages seen at 72 hours among other respiratory organisms. If isolation occurs during routine bacterial culture work-up, it is usually because the organism grows as a single isolate from a sterile site such as blood, cerebral spinal fluid or deep tissue lesions. It is much easier to recognize this respiratory pathogen as it grows during attempts for mycobacterial isolation. The characteristic salmon-pink colony color is striking in contrast to Lowenstein-Jensen and Sabouraud media; acid fast staining of fresh isolates quickly highlights the acid fast nature of this non-mycobacterial pathogen. It is important that technologists recognize the clinical significance of this opportunistic pathogen and complete the work-up and identification of this pathogen.

Both internists and pathologists should consider Rhodococcus equi within the differential of the immunocompromised patient presenting with chronic cavitary pneumonia, particularly when cultures fail to identify Mycobacteria, Nocardia, Pseudomonas, enterobacteriacea such as Salmonella and fungal organisms.

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