Case report
Rhodococcus equi infection as inaugural manifestation of idiopathic CD4+ lymphopenia: A rare entity and a therapeutic challenge
A. Alvesa,
, E. Silvaa, T. Teixeirab, C. Figueiredob, A. Lameirãoc, M. Vanzellera, C. Ribeiroa
Corresponding author
a Pulmonology Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Rua Conceição Fernandes, 4434-502 Vila Nova de Gaia, Portugal
b Infectious Diseases Unit of Internal Medicine Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Rua Conceição Fernandes, Portugal
c Department of Clinical Pathology, Centro Hospitalar de Vila Nova de Gaia/Espinho, Rua Conceição Fernandes, Portugal
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Schneider, Felipe V.C. Machado, Antenor Rodrigues, Raquel P. Hirata, Daniele C. Dala Pola, Mariana P. Bertoche, Letícia F. Belo, Ana Carolina dos Reis Andrello, Jéssica Fonseca, Leandro C. Mantoani, Karina C. Furlanetto, Fabio Pitta" "autores" => array:12 [ 0 => array:2 [ "nombre" => "Lorena P." "apellidos" => "Schneider" ] 1 => array:2 [ "nombre" => "Felipe V.C." "apellidos" => "Machado" ] 2 => array:2 [ "nombre" => "Antenor" "apellidos" => "Rodrigues" ] 3 => array:2 [ "nombre" => "Raquel P." "apellidos" => "Hirata" ] 4 => array:2 [ "nombre" => "Daniele C. Dala" "apellidos" => "Pola" ] 5 => array:2 [ "nombre" => "Mariana P." "apellidos" => "Bertoche" ] 6 => array:2 [ "nombre" => "Letícia F." "apellidos" => "Belo" ] 7 => array:2 [ "nombre" => "Ana Carolina dos Reis" "apellidos" => "Andrello" ] 8 => array:2 [ "nombre" => "Jéssica" "apellidos" => "Fonseca" ] 9 => array:2 [ "nombre" => "Leandro C." "apellidos" => "Mantoani" ] 10 => array:2 [ "nombre" => "Karina C." 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"apellidos" => "Alves" "email" => array:1 [ 0 => "adelaide.pereira.alves@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "E." "apellidos" => "Silva" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "T." "apellidos" => "Teixeira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "C." "apellidos" => "Figueiredo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "A." "apellidos" => "Lameirão" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "M." "apellidos" => "Vanzeller" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "C." "apellidos" => "Ribeiro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Pulmonology Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Rua Conceição Fernandes, 4434-502 Vila Nova de Gaia, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Infectious Diseases Unit of Internal Medicine Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Rua Conceição Fernandes, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Clinical Pathology, Centro Hospitalar de Vila Nova de Gaia/Espinho, Rua Conceição Fernandes, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1545 "Ancho" => 1500 "Tamanyo" => 223169 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Sites of <span class="elsevierStyleItalic">Rhodococcus equi</span> infection. (A) Lung as a consolidation in the left pulmonary field on posteroanterior X-ray; (B) lung as a mass on the periphery of the left upper lobe on chest computed tomography; (C) trachea as a protruding lesion leading to obstruction of about 50% of the lumen; (D) brain as an abscess in the left parasagital occipitoparietal location on magnetic resonance.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Rhodococcus equi (R. equi)</span> is a facultative intracelular gram-positive coccobacillus which primarily causes zoonotic infection.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> This bacteria is becoming an emerging opportunistic agent in humans.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> As far as we know, we present the first case of <span class="elsevierStyleItalic">R. equi</span> infection in a patient with idiopathic T-CD4<span class="elsevierStyleSup">+</span> lymphopenia (ICL), a rare condition defined by the repeated presence of a T-CD4<span class="elsevierStyleSup">+</span> lymphocyte count <300<span class="elsevierStyleHsp" style=""></span>cells/mm<span class="elsevierStyleSup">3</span> or less than 20% of total T cells without evidence of human immunodeficiency virus (HIV) infection or other condition that might lead to decreased T-CD4<span class="elsevierStyleSup">+</span> counts.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Case description</span><p id="par0010" class="elsevierStylePara elsevierViewall">In April 2017, a 69-year-old never smoker male presented to the emergency department with cough, left pleuritic thoracalgia and fever during the previous month. He was a retired driver who owned a farm with several animals. Past medical history included hypothyroidism treated with levothyroxine and chronic hepatitis B under entecavir. He had undergone lower left lobectomy in 2004 for a pulmonary mass, but histology of the operative specimen suggested an infectious etiology and the patient received no further treatment or follow-up.</p><p id="par0015" class="elsevierStylePara elsevierViewall">On admission, he had peripheral oxygen saturation of 97% on room air and decreased respiratory sounds in the left pulmonary field.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Blood test revealed white blood cells count of 10<span class="elsevierStyleHsp" style=""></span>030/μL (83.3% neutrophils and 7.5% lymphocytes) and C-reactive protein of 14.7<span class="elsevierStyleHsp" style=""></span>mg/dL. Chest X-ray revealed a pleural-based consolidation in the left pulmonary field (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A) which was characterized by contrast-enhanced chest computed tomography (CT) showing a 67<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>41<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>24<span class="elsevierStyleHsp" style=""></span>mm mass on the periphery of the left upper lobe (LUL) with heterogeneous contrast uptake and hypodense areas suggestive of necrosis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The diagnosis of necrotizing pneumonia was established and the patient was hospitalized. Urine was negative for pneumococcal and <span class="elsevierStyleItalic">Legionella</span> antigens. Blood cultures were collected. Intravenous amoxicillin/clavulanic acid and azithromycin were started. Bronchofibroscopy and bronchoalveolar lavage (BAL) were conducted without endobronchial lesions. <span class="elsevierStyleItalic">R. equi</span> was isolated in both blood cultures and BAL. Antimicrobial susceptibility test (AST) showed sensitivity to imipenem and levofloxacin and intermediate sensitivity to ceftriaxone and ciprofloxacin. Treatment was adjusted for a combination of rifampicin and levofloxacin. Although sensitivity to rifampicin could not be tested, it was included due to its intracellular action and because it is a first choice drug.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,5</span></a> The patient underwent transthoracic aspiration biopsy of the LUL lesion that excluded malignancy and showed signs of <span class="elsevierStyleItalic">R. equi</span> infection, namely, histiocyte foci with granulomatous configuration, necrosis and coccoid elements in the macrophage cytoplasm. The diagnosis of necrotizing pneumonia by <span class="elsevierStyleItalic">R. equi</span> with hematogenous dissemination was established. Central nervous system, cardiac, abdominal and cutaneous involvement were excluded. HIV and human T-lymphotropic infections were ruled out. Further extensive work-up to detect any other immunodeficiency condition was made leading to the diagnosis of ICL with an initial T-CD4<span class="elsevierStyleSup">+</span> lymphocyte count of 28<span class="elsevierStyleHsp" style=""></span>cells/μL.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The patient was discharged after two weeks of intravenous treatment with rifampicin and levofloxacin and instructed to continue oral antibiotic treatment at home.</p><p id="par0035" class="elsevierStylePara elsevierViewall">After one month, blood cultures were negative and radiological improvement was documented with a significant reduction in the LUL mass. After six months of treatment, bronchofibroscopy revealed persistence of <span class="elsevierStyleItalic">R. equi</span> in BAL, albeit with significant reduction in the number of colonies.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In April 2018, nearly one year after starting treatment, the patient developed stridor. Rigid bronchoscopy showed obstruction of the lumen of the lower third of the trachea in about 50% due to a protruding lesion (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C) in which endoscopic treatment was conducted. Tracheal lesion biopsy revealed chronic inflammation with intracellular bacteria, malakoplakia and no signs of malignancy. Relapse of <span class="elsevierStyleItalic">R. equi</span> infection was assumed based on these histopathological findings, but since microbiological isolation was not obtained it was not possible to determine AST. Other potential recurrence sites were investigated leading to the diagnosis of an asymptomatic small brain abscess in magnetic resonance without indication for surgical treatment (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>D). A new antibiotic regimen was started with ertapenem, gentamycin and linezolide according to the literature.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,5</span></a> One-year treatment was proposed and a central line was placed allowing outpatient parenteral treatment.</p><p id="par0045" class="elsevierStylePara elsevierViewall">On July 2018 linezolid was replaced by clarithromycin due to myelotoxicity and on January 2019 gentamycin was replaced by doxycycline due to nephrotoxicity and ototoxicity.</p><p id="par0050" class="elsevierStylePara elsevierViewall">On July 2019 the patient was under ertapenem (14 months), clarithromycin (12 months) and doxycycline (7 months) with a favorable clinical response, resolution of cerebral abscess and no evidence of infection recurrence. These antibiotics were discontinued and it was decided to start prophylactic treatment with cotrimoxazole. So far the patient has been under surveillance and has not undergone any further treatment.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">Diagnostic approach of <span class="elsevierStyleItalic">R. equi</span> infection requires high clinical suspicion. Multidisciplinary discussion with microbiology expert is of vital importance since <span class="elsevierStyleItalic">R. equi</span> may be misdiagnosed as a contaminant or other bacteria. Due to its partial alcohol-acid resistance, <span class="elsevierStyleItalic">R. equi</span> infection may lead to misdiagnosis of mycobacteriosis.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,6</span></a><span class="elsevierStyleItalic">R. equi</span> infection may also mimic malignancy since pulmonary nodules or masses may be the radiological manifestation.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> We believe that the lesion treated with lobectomy in 2004 could already correspond to infection by <span class="elsevierStyleItalic">R. equi</span>, since at that time the patient had contact with animals and signs of infection by a supposed atypical mycobacteria on the operative specimen were found. A radical treatment such surgery, the insidious course of the disease and continued contact with animals could explain why the infection only manifested again over ten years later.</p><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">R. equi</span> infection prompted the investigation of an immunosuppressive condition leading to the inaugural diagnosis of ICL. T-CD4<span class="elsevierStyleSup">+</span> cells, mainly Th1 cells, are involved in acquired resistance against facultative intracellular bacteria and increase bactericidal activity of macrophages by producing gamma interferon.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Th1 response seems to be crucial in pulmonary clearance of <span class="elsevierStyleItalic">R. equi</span>.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Recombinant human IL-7 may be a promising therapeutic intervention in ICL, leading to an increase in T-CD4<span class="elsevierStyleSup">+</span> cells in both peripheral blood and tissues.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> It may be questionable to assume the diagnosis of ICL since opportunistic infections may themselves lead to a depression of T-CD4<span class="elsevierStyleSup">+</span> cell count.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Because low T-CD4<span class="elsevierStyleSup">+</span> cell count persisted for over two years after the first analysis and no apparent cause had been determined, the diagnosis of ICL was made by exclusion.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Regarding treatment there are no consensus guidelines. Because acquired resistances are of concern, combination treatment is recommended with two or three antibiotics to which the agent is susceptible and at least one drug should have good intracellular activity.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> First line drugs in humans include rifampicin, levofloxacin, erythromycin, imipenem, vancomycin and aminoglycosides.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> For immunocompromised patients at least six months of antibiotic therapy are advised.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> The placement of a central venous catheter allows intravenous treatment on an outpatient basis, reducing risks of nosocomial infection and costs. Side-effects from multi-drug treatment over such a long period of time may be a concern and should be closely monitored. Antibiotics withdrawal and substitution may be needed, making <span class="elsevierStyleItalic">R. equi</span> infection treatment a dynamic process.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Relapse may occur requiring close surveillance. We scheduled hospital medical consultation whenever the patient presented any complaint and every three months with hemogram, serum biochemistry, blood and sputum cultures and chest computed tomography. After relapse with a brain abscess, brain magnetic resonance was performed every three months until its resolution. No further bronchoscopy was performed following endoscopic treatment of tracheal pseudotumor as the patient refused further invasive examinations and remained asymptomatic.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Funding</span><p id="par0075" class="elsevierStylePara elsevierViewall">This case report did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conflicts of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:3 [ "identificador" => "xres1441754" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1315895" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "sec0010" "titulo" => "Case description" ] 4 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 5 => array:2 [ "identificador" => "sec0020" "titulo" => "Funding" ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of interest" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-01-05" "fechaAceptado" => "2020-06-02" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1315895" "palabras" => array:2 [ 0 => "<span class="elsevierStyleItalic">Rhodococus equi</span>" 1 => "Idiopathic CD4<span class="elsevierStyleSup">+</span> lymphopenia" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">We report a case of disseminated infection by <span class="elsevierStyleItalic">Rhodococcus equi</span> as the inaugural manifestation of idiopathic T-CD4<span class="elsevierStyleSup">+</span> lymphopenia. We aim to demonstrate our diagnostic and therapeutic approach and focus on the major dilemmas arising from the lack of scientific evidence regarding best clinical practice of this infection in humans.</p></span>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1545 "Ancho" => 1500 "Tamanyo" => 223169 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Sites of <span class="elsevierStyleItalic">Rhodococcus equi</span> infection. (A) Lung as a consolidation in the left pulmonary field on posteroanterior X-ray; (B) lung as a mass on the periphery of the left upper lobe on chest computed tomography; (C) trachea as a protruding lesion leading to obstruction of about 50% of the lumen; (D) brain as an abscess in the left parasagital occipitoparietal location on magnetic resonance.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "<span class="elsevierStyleItalic">Rhodococcus equi</span>: an animal and human pathogen" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.F. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 7 | 15 |
| 2024 October | 34 | 35 | 69 |
| 2024 September | 57 | 29 | 86 |
| 2024 August | 66 | 56 | 122 |
| 2024 July | 54 | 47 | 101 |
| 2024 June | 66 | 58 | 124 |
| 2024 May | 48 | 42 | 90 |
| 2024 April | 38 | 35 | 73 |
| 2024 March | 48 | 22 | 70 |
| 2024 February | 30 | 19 | 49 |
| 2024 January | 35 | 24 | 59 |
| 2023 December | 25 | 35 | 60 |
| 2023 November | 41 | 42 | 83 |
| 2023 October | 28 | 31 | 59 |
| 2023 September | 33 | 32 | 65 |
| 2023 August | 32 | 26 | 58 |
| 2023 July | 41 | 31 | 72 |
| 2023 June | 42 | 19 | 61 |
| 2023 May | 71 | 27 | 98 |
| 2023 April | 65 | 18 | 83 |
| 2023 March | 112 | 28 | 140 |
| 2023 February | 73 | 18 | 91 |
| 2023 January | 53 | 18 | 71 |
| 2022 December | 98 | 26 | 124 |
| 2022 November | 78 | 34 | 112 |
| 2022 October | 125 | 45 | 170 |
| 2022 September | 95 | 39 | 134 |
| 2022 August | 71 | 37 | 108 |
| 2022 July | 74 | 56 | 130 |
| 2022 June | 112 | 44 | 156 |
| 2022 May | 76 | 37 | 113 |
| 2022 April | 46 | 52 | 98 |
| 2022 March | 54 | 51 | 105 |
| 2022 February | 47 | 37 | 84 |
| 2022 January | 87 | 74 | 161 |
| 2021 December | 50 | 45 | 95 |
| 2021 November | 49 | 35 | 84 |
| 2021 October | 56 | 64 | 120 |
| 2021 September | 43 | 43 | 86 |
| 2021 August | 39 | 42 | 81 |
| 2021 July | 62 | 21 | 83 |
| 2021 June | 47 | 52 | 99 |
| 2021 May | 52 | 60 | 112 |
| 2021 April | 109 | 101 | 210 |
| 2021 March | 63 | 49 | 112 |
| 2021 February | 63 | 34 | 97 |
| 2021 January | 105 | 56 | 161 |
| 2020 December | 45 | 41 | 86 |
| 2020 November | 26 | 24 | 50 |
| 2020 October | 25 | 25 | 50 |
| 2020 September | 41 | 48 | 89 |
| 2020 August | 84 | 37 | 121 |
| 2020 July | 199 | 63 | 262 |
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