Zambian HIV Guidelines:: Rhodococcus equi

	Zambia HIV National Guidelines
	Introduction HIV Counseling and Testing Sexually Transmitted Infections (STIs) General Principles of Antiretroviral Therapy for Chronic HIV Infection in Adults and Adolescents When to Start ARV Therapy for Chronic HIV Infection in Adults and Adolescents Initial Regimen for ARV Therapy Adherence Baseline evaluation and Monitoring Calculations: Ideal Body Weight, Body Mass Index and Creatinine Clearance ARV Therapy for Individuals with Tuberculosis Co-Infection Adverse Effects and Toxicity Immune Reconstitution Inflammatory Syndrome (IRIS) Changing or Stopping ART Treatment Failure Stopping ARV Therapy Post Exposure Prophylaxis Cotrimoxazole Prophylaxis WHO Staging in Adults and Adolescents Nutrition Care and Support Palliative Care in HIV and AIDS
	Guide Editors
	Editor In Chief Joel E. Gallant, MD, MPH Pharmacology Editor Paul Pham, PharmD, BCPS Zambia Guideline Team Peter Mwaba MMed PhD FRCP Alywn Mwinga MMed Isaac Zulu MMed MPH Velepie Mtonga MMed Albert Mwango MBChB Jabbin Mulwanda MMed FCS

Pathogens>Bacteria>

Rhodococcus equi

Eric Nuermberger, MD
02-14-2008

Organism has been isolated from soil and animal feces in Zambia.
No published data on incidence of infection in Zambia, but several cases in HIV+ pts reported from Uganda and Zimbabwe.
Not commonly diagnosed in Zambia due to similarities with clinical TB presentation and difficulties with Cx and identification of the organism.
Rx: vancomycin not generally available, so could use PO regimen mentioned below: rifampin + either macrolide, tetracycline or fluoroquinolone.

Zambia Information Author: David Riedel, M.D.

MICROBIOLOGY

Pleomorphic gram-positive bacillus, weakly acid-fast
Grows well on ordinary media, but may be mistaken as diphtheroid contaminant
Rarely isolated from healthy persons, suspect immunosuppressive condition
Soil inhabitant; infection typically via inhalation, but may be via inoculation or ingestion
Recognized equine pathogen, but only 20-30% of infected humans have contact with horses

CLINICAL

CXR: unilobar nodular infiltrate or consolidation, often upper lobe, frequently cavitates, TB mimic; may see multilobar involvement or pleural effusion
High-resolution chest CT also may show ground-glass opacities, centrilobular nodules or tree-in-bud appearance
Dx may require invasive procedure, but blood Cx positive in up to 2/3 of HIV+ pts
Histopathology: dense histiocytic infiltrate with necrosis, intracellular bacteria; may see PAS+ macrophages or malakoplakia (histiocytic aggregates with basophilic cytoplasmic inclusions laminated with calcium, iron)
2/3 of R. equi infections are in HIV+ pts; CD4 typically <100
Mortality 55% in pre-HAART era
Rare OI, incidence: 3/1000 in hospitalized AIDS pts

SITES OF INFECTION

Lung: most common site (approx 80%); often insidious fever, cough, fatigue, weight loss
Cutaneous: nodule, abscess, ulcer at inoculation site or with disseminated disease
Musculoskeletal: osteomyelitis, septic arthritis, psoas abscess
Adenitis: cervical, mesenteric
Less common: nodule or abscess in brain, liver, spleen, kidney, prostate after dissemination
DDx: TB, other mycobacterial infections, fungal infections, actinomycosis, nocardiosis, lung abscess, lung cancer, lymphoma, metastatic neoplasm

TREATMENT

General Principles

No treatment standard established
Susceptibility testing recommended to guide therapy and to investigate treatment failures
Combination therapy strongly recommended to prevent emergence of resistance
Begin with 2-3 parenteral agents for 2-4 wks, then change to two-drug oral regimen for at least 6 mos and 1-2 mos beyond resolution of disease
In largest series (ref 2), mostly pre-HAART era, 43% died of the disease or progressed despite treatment, only 15% cured
For pts with AIDS, relapse occurs frequently enough that lifelong suppressive therapy with 1-2 oral agents is recommended beyond treatment of active disease unless immune reconstitution achieved
HAART confers survival benefit
Consider surgical drainage or resection of large cavities or abscesses should in those who fail to respond to ABx

Parenteral agents

Most commonly reported: vancomycin + 1-2 of the following: carbapenem, aminoglycoside or rifampin
Vancomycin 1g IV bid
Amikacin 15 mg/kg IV qd or gentamicin 5-7 mg/kg IV qd
Imipenem 500 mg IV q6h or meropenem 1g IV q8h
Rifampin 600 mg IV qd (not for monotherapy)
Consider fluoroquinolone for pts intolerant to 2 or more of the above agents: moxifloxacin 400 mg IV qd or levofloxacin 750 mg IV qd, or levofloxacin 500 mg IV qd

Oral agents

Most commonly reported: rifampin + either macrolide or tetracycline or fluoroquinolone
Rifampin 600 mg PO qd (not for monotherapy)
Clarithromycin 500 mg PO bid, erythromycin 500 mg PO qid or azithromycin 500 mg PO qd
Minocycline 100 mg PO bid or doxycycline 100 mg PO bid
Moxifloxacin 400 mg PO qd or levofloxacin 500-750 mg PO qd
Other drugs commonly active: TMP/SMX, clindamycin, linezolid

Drug Comments

Drug	Recommendations/Comments
Amikacin	Bactericidal agent that is virtually always active. Good choice for combining with a cell wall-active agent (vancomycin or carbapenem in initial therapy. Substitute cheaper gentamicin if supported by susceptibility testing.
Azithromycin	Erythromycin is most commonly used macrolide in the literature, but azithromycin and clarithromycin are active in vitro, more convenient to take and better tolerated. Clarithromycin is most potent in vitro. Resistance expected to be more likely in patients that develop Rhodococcus infection while receiving these agents for MAC prophylaxis.
Clarithromycin	Erythromycin most commonly used macrolide in the literature, but azithromycin and clarithromycin are active in vitro, more convenient to take and better tolerated. Clarithromycin is most potent in vitro. Resistance expected to be more likely in patients that develop Rhodococcus infection while receiving these agents for MAC prophylaxis.
Imipenem/Cilastatin	Bactericidal agent that is virtually always active and could be included in initial parenteral regimens. Imipenem is carbapenem used most commonly in case reports. However, meropenem appears similarly active and would be favored for CNS infections and patients on dialysis given lower risk of seizures.
Minocycline	The tetracycline with best activity against gram-positive bacteria, although doxycycline also appropriate. These are inexpensive drugs to pair with rifampin for oral therapy once susceptibility is established.
Moxifloxacin	Probably the most potent fluoroquinolone against Rhodococcus although levofloxacin is a reasonable alternatives. Unclear whether newer fluoroquinolones provide any additional benefit over a macrolide or tetracycline to justify their expense. Also, long-term safety profiles of moxifloxacin has not been well established.
Rifampin	Nearly always active and good choice for parenteral and oral combination therapy. Should not be used as monotherapy due to selection of resistant mutants. Many drug interactions with PIs and NNRTIs
Trimethoprim + Sulfamethoxazole	Alternative for oral or parenteral regimens, but use should be supported by susceptibility testing. Resistance expected to be more likely in pts receiving this agent for PCP prophylaxis.
Vancomycin	Virtually always active. Potent activity in mouse model. A recommended agent for initial parenteral regimens.

FOLLOW UP

As with TB, failure to respond to Rx (improved symptoms and CXR) after 2 mos should prompt sputum Cx and susceptibility testing
Recommended treatment duration is at least 6 mos and 1-2 mos after all disease manifestations resolve
Lifelong suppressive therapy recommended for pts w/AIDS unless immune reconstitution achieved

OTHER INFORMATION

Simultaneous OIs are common
2 cases of apparent person-to-person transmission suggest that other immunocompromised pts should not share room with pts with cavitary or sputum Cx-positive disease. Need for airborne isolation unclear.

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