Case report
Community-associated methicillin-resistant Staphylococcus aureus infection in Portugal
Pneumonia da comunidade por Staphylococcus aureus resistente à meticilina em Portugal
R. Nazaretha,
, J. Gonçalves-Pereiraa,d, A. Tavaresc, M. Miragaiac, H. de Lencastrec,e, J. Silvestrea,d, P. Freitasa, E. Gonçalvesb, F. Martinsb, V. Mendesa, C. Tapadinhasa,d, P. Póvoaa,d
Corresponding author
a Unidade Polivalente de Cuidados Intensivos, Hospital São Francisco Xavier, CHLO, Lisboa, Portugal
b Laboratório de Microbiologia, Hospital São Francisco Xavier, CHLO, Lisboa, Portugal
c Laboratório de Genética Molecular, Instituto de Tecnologia Química e Biológica (ITQB), Oeiras, Portugal
d CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal
e Laboratory of Microbiology, The Rockefeller University, New York, NY, USA
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Outbreaks have been described in different settings in the community.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> A high prevalence was found in patients with SSTI,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> namely intravenous drug users in North America,<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,13</span></a> as well as in the UK.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Initially, most of CA-MRSA isolates were only resistant to β-lactams, associated with the smallest types (IV and V) of the staphylococcal cassette chromosome <span class="elsevierStyleItalic">mec</span> (SCC<span class="elsevierStyleItalic">mec</span>).<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> However, in recent years there has been increased resistance to other antibiotic classes.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> It frequently carries Panton–Valentine leukocidin (PVL) gene, an exotoxin causing leukocyte destruction and tissue necrosis, increasing severity of infections, especially pneumonia, with higher mortality rate.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">At present, the predominant CA-MRSA clones in the USA are USA300 (ST8-IVa) and USA400 (ST1-IV),<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> particularly USA300, which is widely disseminated in the community and hospitals,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> whereas in Europe and Australia, the most relevant are the European clone (ST80-IVc)<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> and the Southwestern Pacific clone (ST30-IV),<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> respectively.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Skin and soft tissue infections are the most common manifestations of CA-MRSA, but serious invasive infections, namely pneumonia, are also described.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> In a large USA study only 2% of CA-MRSA infections were pneumonia.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">We describe the first documented case of CA-MRSA infection in Portugal, of a patient with severe necrotizing pneumonia complicated with bilateral empyema.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Case presentation</span><p id="par0040" class="elsevierStylePara elsevierViewall">A 33-year-old homeless Armenian man, who had been living in Portugal for seven years, with a past medical history of chronic B and C hepatitis and active parenteral drug abuse came to the emergency department (ED) with a 5-day history of right pleuritic chest pain and, in the previous two weeks, non-quantified fever and purulent sputum.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The chest X-ray showed a lower bilateral pulmonary infiltrate and right-sided pleural effusion. HIV-check (4th generation ELISA method) was positive. A community-acquired pneumonia (CAP) with parapneumonic effusion was diagnosed and the patient was discharged on amoxicillin/clavulanate.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Two days later he returned to the ED with worsening symptoms. He was febrile, tachycardic and tachypneic, with pulse oxygen saturation of 95% on room air and had diminished breath sounds on the right hemithorax. Arterial blood gases revealed arterial partial pressure of oxygen (PaO<span class="elsevierStyleInf">2</span>) of 67.3<span class="elsevierStyleHsp" style=""></span>mmHg. Laboratory tests showed elevated C-reactive protein (35.4<span class="elsevierStyleHsp" style=""></span>mg/dL, which 2 days earlier had been 15.6<span class="elsevierStyleHsp" style=""></span>mg/dL) and leucocytosis (14.5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/μL; neutrophils 94%). No acid-fast bacilli were found on sputum smear (three samples). The patient was admitted to the Infectious Diseases ward. Clarithromycin was added and, since he had markedly depressed immunological state (46 CD4 T-cells/μL, 10.3% with viral load >180,000<span class="elsevierStyleHsp" style=""></span>copies/mL), prophylactic therapy with trimethoprim–sulfamethoxazole was initiated. In the following 2 days, his clinical condition rapidly deteriorated with acute respiratory failure needing invasive mechanical ventilation. He was transferred to the intensive care unit (ICU).</p><p id="par0055" class="elsevierStylePara elsevierViewall">In the ICU a bilateral thoracocentesis was performed, revealing two large-volume empyemas. The chest CT scan showed right lung consolidation. Methicillin-resistant <span class="elsevierStyleItalic">S. aureus</span> was recovered from pleural fluid, bronchoalveolar lavage (BAL) and blood cultures. The microorganism was susceptible to vancomycin, with <span class="elsevierStyleItalic">in vitro</span> minimum inhibitory concentration (MIC) of 2<span class="elsevierStyleHsp" style=""></span>μg/mL (Etest<span class="elsevierStyleSup">®</span>) and resistant to ciprofloxacin, erythromycin and clindamycin; it was also susceptible to linezolid (MIC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>μg/mL), teicoplanin (MIC<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.5<span class="elsevierStyleHsp" style=""></span>μg/mL), gentamicin (MIC<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.5<span class="elsevierStyleHsp" style=""></span>μg/mL) and trimethoprim–sulfamethoxazole (MIC<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>μg/mL). Vancomycin was started by continuous infusion adjusted to maintain serum levels of 20–25<span class="elsevierStyleHsp" style=""></span>mg/L. No improvement was noted after 7 days. A transesophageal echocardiogram excluded endocarditis.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Cultures were repeated revealing persistence of MRSA on BAL and tracheal secretions, with the same pattern of susceptibility. The hypothesis of CA-MRSA was suggested and linezolid IV was started. After a 10-day course there was complete clinical resolution.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The molecular characterization of the isolates was done by pulsed-field gel electrophoresis,<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a><span class="elsevierStyleItalic">spa</span> typing,<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> multilocus sequence typing<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> and SCC<span class="elsevierStyleItalic">mec</span> typing and subtyping.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26,27</span></a> The presence of PVL was also assessed.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> The etiological agent was identified as CA-MRSA belonging to the USA300 epidemic clone (ST8-IVa, t008, PVL positive).</p><p id="par0070" class="elsevierStylePara elsevierViewall">The patient had a long ventilator course. A tracheostomy was performed on the 21st day. He was discharged from ICU on the 56th day and from hospital on the 179th day.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusions</span><p id="par0075" class="elsevierStylePara elsevierViewall">This is the first published case report of a CA-MRSA identified in Portugal, which led to a rare infection, necrotizing pneumonia with empyema.</p><p id="par0080" class="elsevierStylePara elsevierViewall">The isolated CA-MRSA belongs to the epidemic clone USA300, which is wide spread in the USA, where it is also found in a hospital environment, being reported as the most common agent of SSTI.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> It has also been isolated in Europe,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> but there were no prior cases reported in Portugal.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Most CA-MRSA infected patients reported have recent or concomitant influenza-like illness and/or recent antimicrobial exposure,<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> which was not the case with our patient. Nor did he have any other recognised risk factors for HA-MRSA, such as recent hospital admission, observation in a health care centre or recent antibiotic therapy. However, he was a homeless man with intravenous drug abuse habits, so in this context he could have had prior MRSA SSTI or exposure to another infected person. Not all cases have an identified risk factor like this one.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Necrotizing pneumonia associated with PVL producing strains has a high mortality rate that can reach 75%.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> In a series of 24 patients with CA-MRSA pneumonia, all patients with PVL producing strains died, compared with 47% of PVL non-producing strains (increased risk of 1.56).<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> In another larger study, which included 50 patients with pneumonia caused by PVL producing CA-MRSA, the overall mortality was 56%.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> In our patient, CA-MRSA had elevated <span class="elsevierStyleItalic">in vitro</span> MIC to vancomycin and resistance to several antibiotic classes. Clinical deterioration may be explained by an increase in PVL levels, which can occur with sub-inhibitory concentrations of oxacillin and vancomycin.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> In contrast, even sub-inhibitory concentrations of clindamycin and linezolid were shown to reduce PVL levels,<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> probably by inhibition of protein synthesis, which may explain the therapeutic success in our patient. Finally, others have shown that patients not responding to vancomycin frequently got better with the association of linezolid and rifampicin.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> There are few available guidelines and no randomized clinical studies for comparing the different antibiotic therapies.</p><p id="par0095" class="elsevierStylePara elsevierViewall">The recovery of a multidrug-resistant USA300 isolate from a drug user is worrying because of the high rate of transmission in this specific population,<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> causing concerns about possible increased rates of this agent in community-acquired infections in Portugal.</p><p id="par0100" class="elsevierStylePara elsevierViewall">This report underlines the importance of CA-MRSA as a potential pathogen of severe CAP and the need to reinforce epidemiological surveillance. CA-MRSA infections do not cause specific signs or symptoms. However, it is crucial that attending clinicians and hospital microbiology laboratories have a high suspicion index to CA-MRSA when MRSA is isolated from patients with no risk factors for HA-MRSA but who have skin and soft tissue infections or pneumonia with a marked toxic and necrotizing component. Control efforts aimed at preventing the spread of the infection are feasible and can ultimately be successful.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Consent</span><p id="par0105" class="elsevierStylePara elsevierViewall">Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of <span class="elsevierStyleItalic">Portuguese Journal of Pulmonology</span>.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Author's contributions</span><p id="par0110" class="elsevierStylePara elsevierViewall">RN drafted the manuscript. PF made substantial contribution by acquisition of data. JGP, JS, VM, CT and PP participated in the sequence alignment and also revised the manuscript critically for important intellectual content. EG and FM performed the microbiological assays and also revised the manuscript. AT, MM and MHL carried out the molecular genetic studies and also made substantial contribution in the manuscript's revision. JPG and PP have given final approval of the version to be published. All authors read and approved the final manuscript.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:2 [ "identificador" => "xres173515" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec161810" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres173514" "titulo" => "Resumo" ] 3 => array:2 [ "identificador" => "xpalclavsec161809" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Background" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case presentation" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Conclusions" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Consent" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Author's contributions" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 10 => array:2 [ "identificador" => "xack44907" "titulo" => "Acknowledgements" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-02-14" "fechaAceptado" => "2011-05-02" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec161810" "palabras" => array:5 [ 0 => "Community-associated" 1 => "MRSA" 2 => "<span class="elsevierStyleItalic">Staphylococcus aureus</span>" 3 => "Necrotizing pneumonia" 4 => "Empyema" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec161809" "palabras" => array:5 [ 0 => "comunidade associada" 1 => "MRSA" 2 => "<span class="elsevierStyleItalic">Staphylococcus aureus</span>" 3 => "pneumonia necrosante" 4 => "empiema" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span> (MRSA) has recently emerged as a cause of community-acquired infections among individuals without risk factors. Community-associated MRSA (CA-MRSA) appears to be more virulent, causing superficial mild skin and soft tissue infections to severe necrotizing fasciitis, and in rare cases, pneumonia.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Community-associated MRSA was first reported in Australia in the early 80s, after almost two decades in the USA, and then in several countries in Europe, Asia and South America. No data exists in Portugal.</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We report the first case of CA-MRSA infection in Portugal, in a young adult with severe necrotizing pneumonia, complicated with bilateral empyema and respiratory failure.</p>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Recentemente assistiu-se à emergência de infeções na comunidade por <span class="elsevierStyleItalic">Staphylococcus aureus</span> meticilina-resistente (MRSA) em indivíduos sem fatores de risco. O MRSA associado à comunidade (CA-MRSA) parece ser mais virulento, causando desde infeções superficiais da pele e tecidos moles até fasceíte necrosante e, raramente, pneumonia.</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">O CA-MRSA foi inicialmente identificado na Austrália no início da década de 80 e, após cerca de duas décadas, surgiu nos EUA e em vários países da Europa, Ásia e América do Sul. Não existe informação disponível acerca da prevalência em Portugal.</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Os autores reportam o primeiro caso de infeção por CA-MRSA em Portugal, num adulto jovem com pneumonia necrotizante grave complicada por empiema bilateral e insuficiência respiratória.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Nazareth R, Infeção por staphylococcus aureus meticilina-resistente da comunidade em Portugal. 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A. Tavares was supported by grant <span class="elsevierStyleGrantNumber" refid="gs0005">SFRH/BD/44220/2008</span> from <span class="elsevierStyleGrantSponsor" id="gs0005">Fundação para a Ciência e a Tecnologia</span>, Lisbon, Portugal.</p>" ] ] ] "idiomaDefecto" => "en" "url" => "/21735115/0000001800000001/v1_201305151555/S2173511511001059/v1_201305151555/en/main.assets" "Apartado" => array:4 [ "identificador" => "9692" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case report" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735115/0000001800000001/v1_201305151555/S2173511511001059/v1_201305151555/en/main.pdf?idApp=UINPBA00004E&text.app=https://journalpulmonology.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173511511001059?idApp=UINPBA00004E" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 8 | 15 |
| 2024 October | 29 | 31 | 60 |
| 2024 September | 29 | 31 | 60 |
| 2024 August | 44 | 44 | 88 |
| 2024 July | 35 | 38 | 73 |
| 2024 June | 25 | 24 | 49 |
| 2024 May | 46 | 33 | 79 |
| 2024 April | 32 | 30 | 62 |
| 2024 March | 34 | 26 | 60 |
| 2024 February | 23 | 23 | 46 |
| 2024 January | 17 | 30 | 47 |
| 2023 December | 17 | 28 | 45 |
| 2023 November | 23 | 29 | 52 |
| 2023 October | 15 | 32 | 47 |
| 2023 September | 14 | 33 | 47 |
| 2023 August | 15 | 24 | 39 |
| 2023 July | 13 | 28 | 41 |
| 2023 June | 6 | 5 | 11 |
| 2023 May | 15 | 23 | 38 |
| 2023 April | 12 | 10 | 22 |
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