Scientific letter
Ceftobiprole, a new option for multidrug resistant microorganisms in the outpatient antimicrobial therapy setting
Ceftobiprole, una nueva opción de tratamiento para microorganismos multirresistentes en el ámbito del tratamiento antimicrobiano domiciliario
Luis Eduardo López-Cortésa,
, Laura Herrera-Hidalgob, Virginia Almadanac, María Victoria Gil-Navarrob, on behalf of the DOMUS OPAT Group 1
Corresponding author
a Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena/CSIC/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain
b Unidad de Gestión Clínica de Farmacia, Hospital Universitario Virgen del Rocío/CSIC/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain
c Unidad Clínica de Neumología, Hospital Universitario Virgen Macarena, Seville, Spain
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1 => array:3 [ "nombre" => "Laura" "apellidos" => "Herrera-Hidalgo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Virginia" "apellidos" => "Almadana" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "María Victoria" "apellidos" => "Gil-Navarro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:2 [ "colaborador" => "on behalf of the DOMUS OPAT Group" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena/CSIC/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Gestión Clínica de Farmacia, Hospital Universitario Virgen del Rocío/CSIC/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad Clínica de Neumología, Hospital Universitario Virgen Macarena, Seville, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Ceftobiprole, una nueva opción de tratamiento para microorganismos multirresistentes en el ámbito del tratamiento antimicrobiano domiciliario" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Ceftobiprole is a broad spectrum fifth-generation cephalosporin. Ceftobiprole is approved in several European countries for the treatment of community-acquired pneumonia and hospital-acquired pneumonia, excluding ventilator-associated pneumonia. Respiratory infections in patients with bronchiectasis have special characteristics because they are frequently caused by <span class="elsevierStyleItalic">Haemophilus influenzae</span>, <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>, respiratory viruses, and less frequently, <span class="elsevierStyleItalic">Moraxella catarrhalis</span>, <span class="elsevierStyleItalic">Staphylococcus aureus</span>, and Enterobacteriaceae.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> The high number of exacerbations leads to high antibiotic pressure. Ceftobiprole is stable for up to 24<span class="elsevierStyleHsp" style=""></span>h at 25<span class="elsevierStyleHsp" style=""></span>°C and protected from light, which allows for potential administration in OPAT.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">2,3</span></a> There is limited experience and research data of its use at home. The specific characteristics of our OPAT programme have been described previously.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 32-year-old male patient diagnosed with cystic fibrosis at the age of 5 (homozygous for the CFTR gene with the delta-F508 mutation) and colonized with multidrug-resistant (MDR) <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>, and methicillin-susceptible <span class="elsevierStyleItalic">Staphylococcus aureus</span> (MSSA) since 1995. A bipulmonary transplant was performed in October 2019 (8 months previously) with multiple subsequent complications. Mucoid phenotype <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> resistant to quinolones, piperacillin-tazobactam, aminoglycosides, ceftazidime, cefepime, and carbapenems was isolated in a sputum culture three months before. Susceptibility to ceftazidime/avibactam, ceftobiprole, and ceftolozane/tazobactam are not test routinely in our hospital. The patient was admitted at the beginning of June 2020 with fever and respiratory symptoms. Procalcitonin and C-reactive protein were compatible with a bacterial aetiology. Nevertheless, a cytomegalovirus serology and viral load were requested to rule out possible reactivation. Blood and sputum cultures were taken, without making identification. Urinary antigens for <span class="elsevierStyleItalic">Legionella</span> and <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> were negative. Empirical treatment was started with piperacillin-tazobactam 4<span class="elsevierStyleHsp" style=""></span>g every 8<span class="elsevierStyleHsp" style=""></span>h, with no improvement after three days. A CT scan showed alveolar infiltrates compatible with an infectious cause. Taking into account the resistance pattern of <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>, we decided to start empirical treatment with ceftobiprole 500<span class="elsevierStyleHsp" style=""></span>mg over 2<span class="elsevierStyleHsp" style=""></span>h, every 8<span class="elsevierStyleHsp" style=""></span>h. Within 48<span class="elsevierStyleHsp" style=""></span>h, the patient became afebrile, the respiratory parameters improved, and acute phase reactants normalized. Since the patient was clinically stable, it was proposed that he continue antibiotic therapy at home in our OPAT programme. Ceftobiprole was prepared daily, diluted in 0.9% saline solution at a concentration of 3<span class="elsevierStyleHsp" style=""></span>mg/mL, then refrigerated. The antibiotic solution was administered by electronic pump over 2<span class="elsevierStyleHsp" style=""></span>h every 8<span class="elsevierStyleHsp" style=""></span>h. Three days after being discharged, the patient became asymptomatic, and ceftobiprole was stopped after 7 days of therapy. He showed no adverse events and no changes in the control analysis carried out at home. We examined him in the pneumology clinic one month later, with no clinical incidents. After 3 months of follow-up by telephone, he has shown no new episodes of infection.</p><p id="par0015" class="elsevierStylePara elsevierViewall">To our knowledge this is the first case report providing a clinical and safety evaluation of ceftobiprole in OPAT. The stability of the drug using an elastomeric pump has not been tested.</p><p id="par0020" class="elsevierStylePara elsevierViewall">A history of colonization or infection with resistant gram-negative bacilli in the previous 12 months, previous hospitalization with exposure to broad-spectrum antibiotics, and cystic fibrosis, among others, have been reported in the literature to increase the risk of resistant gram-negative bacilli. A recently published consensus statement based on a Delphi survey of expert opinion recommends the use of empirical therapy against resistant gram-negative bacilli, including <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>, in patients with any of these risk factors.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> Ceftobiprole could be a good option in this scenario due to its broad spectrum of activity. There are no recommendations in cases without improvement using an initial antipseudomonal beta-lactam in the absence of an aetiological diagnosis. In such cases, the strategy should be based on previous clinical experience and local epidemiological data. One study reported the activity of ceftobiprole against a large set of clinical isolates obtained from hospitalized patients in the United States in 2016 that caused serious infections, including pneumonia, in which 72.7% of 1,017 isolates of <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> were susceptible to ceftobiprole.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> In an unpublished observational study including respiratory, skin, genitourinary tract, body fluid, and gastrointestinal clinical isolates from Europe isolated in 2018, the rate of susceptibility to ceftobiprole in 376 <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> isolates ranged from 59% to 76.3%.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> In the presented case, ceftazidime/avibactam and ceftolozane/tazobactam would have been good empirical treatment options against <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>. The decision to use ceftobiprole was taken in the absence of precise data on susceptibility data to <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> in our setting, considering its high activity against MSSA and MRSA, and the possibility to be used in OPAT.</p><p id="par0025" class="elsevierStylePara elsevierViewall">More data are needed to demonstrate the safety and efficacy of ceftobiprole and specific use in the outpatient setting.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">A list of the authors DOMUST OPAT Group is provided in the appendix.</p>" "identificador" => "fn0005" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:2 [ 0 => array:3 [ "apendice" => "<p id="par0030" class="elsevierStylePara elsevierViewall">Rafael Luque Márquez (Hospital Universitario Virgen del Rocío), Elena Fraile-Ramos (Hospital Universitario Virgen del Rocío), Juan Manuel Carmona-Caballero (Hospital Universitario Virgen del Rocío), Lola Navarro Amuedo (Hospital Universitario Virgen del Rocío), and Julia Praena (Hospital Universitario Virgen del Rocío).</p>" "etiqueta" => "Appendix. DOMUS OPAT Group authors" "identificador" => "sec0005" ] 1 => array:3 [ "apendice" => "<p id="par0035" class="elsevierStylePara elsevierViewall">LELC has served as scientific advisor for Novartis, speaker for MSD, Pfizer, Angelini, ViiV, Gilead and Correvio, and has served as trainer for MSD and ViiV. The rest of authors have no conflicts of interests to declare.</p>" "titulo" => "Conflicts of interest" "identificador" => "sec0010" ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0035" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of community-acquired pneumonia in immunocompromised adults: a consensus statement regarding initial strategies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.A. Ramirez" 1 => "D.M. 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Redder" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:2 [ "titulo" => "30th European Congress of Clinical Microbiology & Infectious Diseases" "serieFecha" => "2020" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/0213005X/0000004000000007/v3_202210180618/S0213005X21001841/v3_202210180618/en/main.assets" "Apartado" => array:4 [ "identificador" => "8691" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Cartas científicas" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/0213005X/0000004000000007/v3_202210180618/S0213005X21001841/v3_202210180618/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213005X21001841?idApp=UINPBA00004N" ]
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| 2023 October | 93 | 12 | 105 |
| 2023 September | 28 | 4 | 32 |
| 2023 August | 43 | 5 | 48 |
| 2023 July | 95 | 11 | 106 |
| 2023 June | 66 | 5 | 71 |
| 2023 May | 81 | 8 | 89 |
| 2023 April | 83 | 5 | 88 |
| 2023 March | 70 | 27 | 97 |
| 2023 February | 16 | 10 | 26 |
| 2023 January | 1 | 0 | 1 |
| 2022 December | 1 | 0 | 1 |
| 2022 November | 4 | 2 | 6 |
| 2022 October | 23 | 4 | 27 |
| 2022 September | 34 | 12 | 46 |
| 2022 August | 146 | 51 | 197 |
| 2022 March | 0 | 2 | 2 |
| 2021 October | 0 | 2 | 2 |
| 2021 September | 0 | 6 | 6 |
| 2021 August | 0 | 4 | 4 |
| 2021 July | 0 | 2 | 2 |
Show all
