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Critically ill cancer patients with influenza (H1N1) infection in the intensive care unit in Greece Panagiotis Poulikakos, Anastasia Tsispara, Panagiota Vartzeli & Maria Zakka Department of Intensive Care Unit, Metaxa Cancer Hospital, Piraeus, Greece To the Editor, During the season 2013–2014, Greece suffered an influenza epidemic that resulted in 145 fatalities [1]. We retrospectively analyzed patients with cancer who were infected with influenza and hospitalized in our intensive care unit (ICU) from September 2013 to June 2014. Our department is a six-bed ICU in a cancer hospital. Diagnosis was based on an influenza-like clinical syndrome along with a positive real time RT-PCR testing of oropharyngeal swab for influenza virus. Six patients, four women and two men, 26–71 years old (median age 53.5), fulfilled our criteria (Supplementary Table I, available online at http:// informahealthcare.com/doi/abs/10.3109/0284186X. 2014.974830). Two patients suffered from multiple myeloma, one of whom had autologous stem cell transplantation five years ago, but had subsequently relapsed. Four patients had solid tumors – one had breast cancer, one ovarian cancer and two had sarcoma. Three of the patients with solid tumors had metastatic disease. All patients received chemotherapy within three weeks prior to ICU admission and one with sarcoma received additionally autologous stem cell transplantation. Notably, none of the patients had been vaccinated for the seasonal flu. Upon admission all patients had a ratio of PaO2/ FiO2  100 with bilateral infiltrations on chest x-ray and two patients were neutropenic. All patients received oseltamivir 48 h after their symptoms began. All had positive oropharyngeal swab for H1N1pdm09 and received care with invasive mechanical ventilation, antibiotic coverage, vasopressors and/or inotrops, and four patients received steroids. Oseltamivir was prescribed at a dose of 75mg q12h for all patients and two had their dose increased to 150mg q12h. Length of stay in the ICU ranged from 2 to 45 days (median 5 days). Thirty-day mortality was 83.3% (5 patients) and ICU mortality was 100%. All patients died from respiratory tract infection and multiple organ failure. Three patients suffered superinfection, two of those had transient

clinical improvement and died after 45 and 17 days, respectively. The patient that died after 45 days, while on clinical improvement, managed to receive chemotherapy (bortezomide and dexamethasone) for multiple myeloma. One patient was bacteremic since eight days prior to his admission and died on his second day in the ICU despite receiving directed antibiotic treatment. Among our critically ill cancer patients infected with influenza, no one survived to discharge. Other authors have also published mortality rates up to 100% [2,3] in similar populations that required invasive mechanical ventilation. Alarmingly, none of the patients was vaccinated for seasonal influenza and all received delayed oseltamivir treatment. Current guidelines recommend vaccination for all adult cancer patients, except those receiving anti-B-cell antibodies or intensive chemotherapy, since these two patient categories cannot mount an adequate serologic response [4,5]. Thus, consideration of influenza vaccination should accompany cancer diagnosis and antecede immunosuppressive treatment if feasible. From the few available data, vaccination rates for influenza in Greece are not high and for this, misconceptions about the gravity of influenza and the safety of vaccination have been implicated [6,7]. Additionally during the year 2013–2014 in Greece there was a shortage of vaccines substantial enough to shift guidance towards early use of antiviral drugs [8]. We cannot emphasize strongly enough that timely vaccination and targeted information on influenza prevention and treatment may prevent future fatalities in cancer patients.­­

Acknowledgments We are grateful to Dr Anastasios Grivas (Metaxa Hospital, Greece), Dr Christos Pleros (Chania General Hospital St George) and Dr. Anastasia Tikhonova (New York University, USA) for critical

Correspondence: P. Poulikakos, Department of Intensive Care Unit, Metaxa Cancer Hospital, Piraeus, Greece. E-mail: [email protected] (Received 26 September 2014; accepted 3 October 2014) ISSN 0284-186X print/ISSN 1651-226X online © 2015 Informa Healthcare DOI: 10.3109/0284186X.2014.974830

1082 P. Poulikakos et al. reading of the manuscript. Also we would like to thank the medical team that cared for the patients. We would like to especially thank the nursing stuff for their efforts to provide optimal care to the patients and at the same time make the ICU a friendly environment.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. References [1] Hellenic Center for Disease Control & Prevention: Annual epidemiological report on influenza for the season 2013–2014. Available from: http://goo.gl/Bjl4NT [cited 2014 Oct 30]. [2] Snyder E, Cardenas-Turanzas M, Perego C, Erfe R, Chemaly RC, Price KP, et  al. Respiratory failure in cancer patients with influenza A (H1N1) is associated with poor prognosis. Critical Care 2011;15(Suppl 1):P222.

Supplementary material available online Supplementary Table I available online at http:// informahealthcare.com/doi/abs/10.3109/0284186X. 2014.974830.

[3] Hajjar LA, Mauad T, Galas FR, Kumar A, da Silva LF, Dolhnikoff M, et  al. Severe novel influenza A (H1N1) infection in cancer patients. Ann Oncol 2010;21:2333–41. [4] Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58:e44–100. [5] Berglund A, Willén L, Grödeberg L, Skattum L, Hagberg H, Pauksens K. The response to vaccination against influenza A(H1N1) 2009, seasonal influenza and Streptococcus pneumoniae in adult outpatients with ongoing treatment for cancer with and without rituximab. Acta Oncol 2014;53: 1212–20. [6] Mavros MN, Mitsikostas PK, Kontopidis IG, Moris DN, Dimopoulos G, Falagas ME. H1N1v influenza vaccine in Greek medical students. Eur J Public Health 2011;21: 329–32. [7] Rachiotis G, Mouchtouri VA, Kremastinou J, Gourgoulianis K, Hadjichristodoulou C. Low acceptance of vaccination against the 2009 pandemic influenza A(H1N1) among healthcare workers in Greece. Euro Surveill 2010;15:pii.19486. [8] European Centre for Disease Prevention and Control. Seasonal influenza 2013–14 in the EU/EEA countries. Stockholm: ECDC; 2014.

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