The frequency, epidemiology and risk factors of bloodstream infections in febrile neutropenic patients with hematologic malignancies

Yıl 2021, , 438 - 445, 22.12.2021

Çiğdem Erol , Nuran Sarı , Şahika Zeynep Akı , Esin Şenol

https://doi.org/10.18663/tjcl.1002878

Öz

Aim: Bacteremia is considered as the most significant cause of mortality and morbidity in febrile neutropenic patients. The epidemiology and risk factors might differ among institutions and over the time period. The aim of this study is to evaluate the frequency, epidemiology and factors predictive of bacteremia in neutropenic patients in a university hospital in Ankara between November 2007 and November 2008.
Material and Methods: 177 febrile neutropenic episodes of 115 patients with hematological malignancies were included in this study. Cases were defined as patients with bloodstream infection and controls were the patients without bloodstream infections. We evaluated the cases and controls for the risk factors, complications and mortality rates. Microorganisms isolated from blood samples and their susceptibility patterns were also analysed.
Results: The prevalence of bacteremia was 61%, 42.6% of them were catheter related and mortality rate was 12.4%. Bloodstream infections are more common in the patients with uncontrolled underlying disease and long term severe neutropenia. Duration of severe neutropenia (neutrophile count <100/ mm3), underlying hematologic malignancy, stem cell transplantation, relapsing or refractory disease, presence of central venous catheter and presence of mucositis were significant predictive factors for bacteremia. Presence of central venous catheter and relapsing or refractory disease were independent risk factors. Candidemia and gram negative bacteremia were significantly associated with higher mortality rates. Gram-positive microorganisms were the most common isolates (76.8%) with the predominance of coagulase negative staphylococci (63.6%) with methicillin resistance rate of 64%. The most frequent gram-negative pathogen was Escherichia coli with quinolon resistance rate of 82.1%.
Conclusion: Monitorization for the epidemiology of bacteremia and prediction of significant factors associated with bacteremia in febrile neutropenic patients are considered to be important for the choice of initial antibiotic therapy.

Anahtar Kelimeler

Febrile neutropenia, bloodstream infection, risk factors

Febril nötropenik hastalarda bakteriyemi sıklığı, risk faktörleri ve epidemiyolojisi

Öz

Amaç: Kan dolaşımı infeksiyonları febril nötropenik hastalarda, ciddi morbidite ve mortalite ile seyretmektedir. Farklı merkezler arasında ve aynı merkezde yıllar içerisinde bakteriyemi epidemiyolojisi ve risk faktörleri değişiklikler göstermektedir. Bu çalışmanın amacı Kasım 2007-Kasım 2008 tarihleri arasında Ankara’da bir üniversite hastanesinde bakteriyemi sıklığını, risk faktörlerini ve epidemiyolojisini belirlemektir.
Gereç ve Yöntemler: Çalışmamızda 115 hematolojik maligniteli hastada gelişen 177 febril nötropeni atağı ve 108 kan dolaşımı enfeksiyonu incelenmiştir. Olgular kan dolaşımı enfeksiyonu gelişen, kontrol grup ise gelişmeyen hasta grubu olarak tanımlanmıştır. Olgular ve kontroller risk faktörleri, komplikasyonlar ve mortalite oranları yönünden karşılaştırılmış; izole edilen mikroorganizmalar ve duyarlılık paternleri incelenmiştir.
Bulgular: Epizodlarının %61’inde bakteriyemi gelişmiş, bunların %42.6’sı kateterle ilişkili bulunmuş ve atak ilişkili mortalite hızı %12.4 saptanmıştır. Altta yatan malignitesi kontrol altında olmayan, uzun süreli derin nötropenisi olanlarda bakteriyemi daha yüksek oranda izlenmiştir. Kök hücre nakil ünitesinde yatmak, altta yatan malignite tanıları, nakil uygulama türünden bağımsız olarak kök hücre nakli varlığı, malignite evresi, santral venöz kateter, mukozit ve ishal varlığı kan dolaşımı enfeksiyonu gelişimi ile ilişkili bulunmuş; altta yatan malignite evresi ve santral venöz kateter varlığı bağımsız risk faktörleri olarak tanımlanmıştır. En sık etkenleri olarak gram-pozitif bakteriler (%76.8); bunlar içinde de en sık koagülaz negatif stafilokoklar (%63.6) saptanmıştır. Metisilin direnci koagülaz negatif stafilokoklarda %64 bulunmuştur. Gram-negatif bakteriler içerisinde ise en sık Escherichia coli izole edilmiştir. Escherichia coli izolatlarında kinolon direnci %82.1 saptanmıştır.
Sonuç: Sonuç olarak febril nötropenik hastalarda kan dolaşımı enfeksiyonu sıklığının, risk faktörlerinin ve epidemiyolojisinin izlemi, her merkezin kendi empirik tedavi yaklaşımını belirleyebilmesi için önemlidir.

Anahtar Kelimeler

Febril nötropeni, kan dolaşımı infeksiyonu, risk faktörleri

Kaynakça

• [1] Pennington JE. Fever, neutropenia and malignancy: a clinical syndrome in evolution. Cancer 1977; 39: 1345-9.
• [2] Akova MÇBN. Nötropenik hastalarda infeksiyonlar. In: Topçu AW SG, Doğanay M, editor. Enfeksiyon Hastalıkları ve Mikrobiyolojisi: Nobel Tıp Kitabevleri; 2008. p. 641-50.
• [3] Toussaint E, Bahel-Ball E, Vekemans M, Georgala A, Al-Hakak L, Paesmans M, et al. Causes of fever in cancer patients (prospective study over 477 episodes). Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2006; 14: 763-9.
• [4] Blijlevens NM, Donnelly JP, de Pauw BE. Empirical therapy of febrile neutropenic patients with mucositis: challenge of risk-based therapy. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2001; 7: 47-52.
• [5] Viscoli C, Cometta A, Kern WV et al. Piperacillin-tazobactam monotherapy in high-risk febrile and neutropenic cancer patients. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2006; 12: 212-6.
• [6] Oliveira AL, de Souza M, Carvalho-Dias VM et al. Epidemiology of bacteremia and factors associated with multi-drug-resistant gram-negative bacteremia in hematopoietic stem cell transplant recipients. Bone marrow transplantation. 2007;39:775-81.
• [7] Grubu* FNÇ. Febril Nötropenik Hastalarda Tanı ve Tedavi Kılavuzu. Flora 2004; 9: 5-28. [8] Büyüktuna SA, Saba R, Gözel MG et al. Secondary infections after cytotoxic chemotherapy in patient with hematological malignancies. Journal of infection in developing countries 2017; 11: 521-6.
• [9] Nørgaard M, Larsson H, Pedersen G, Schønheyder HC, Sørensen HT. Risk of bacteraemia and mortality in patients with haematological malignancies. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2006; 12: 217-23.
• [10] Marron A, Carratalà J, González-Barca E, Fernández-Sevilla A, Alcaide F, Gudiol F. Serious complications of bacteremia caused by Viridans streptococci in neutropenic patients with cancer. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2000; 31: 1126-30.
• [11] Bodey GP, Buckley M, Sathe YS, Freireich EJ. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Annals of internal medicine 1966; 64: 328-40.
• [12] Velasco E, Thuler LC, Martins CA, Dias LM, Gonçalves VM. Risk factors for bloodstream infections at a cancer center. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 1998; 17: 587-90.
• [13] Vento S, Cainelli F. Infections in patients with cancer undergoing chemotherapy: aetiology, prevention, and treatment. The Lancet Oncology 2003; 4: 595-604.
• [14] Niscola P, Romani C, Cupelli L, Scaramucci L, Tendas A, Dentamaro T, et al. Mucositis in patients with hematologic malignancies: an overview. Haematologica 2007; 92: 222-31.
• [15] Talcott JA, Siegel RD, Finberg R, Goldman L. Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 1992; 10: 316-22.
• [16] Elting LS, Rubenstein EB, Rolston KV, Bodey GP. Outcomes of bacteremia in patients with cancer and neutropenia: observations from two decades of epidemiological and clinical trials. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 1997; 25: 247-59.
• [17] Britt MR, Schleupner CJ, Matsumiya S. Severity of underlying disease as a predictor of nosocomial infection. Utility in the control of nosocomial infection. Jama 1978; 239: 1047-51.
• [18] Hamalainen S, Kuittinen T, Matinlauri I, Nousiainen T, Koivula I, Jantunen E. Severe sepsis in autologous stem cell transplant recipients: microbiological aetiology, risk factors and outcome. Scandinavian journal of infectious diseases 2009; 41: 14-20.
• [19] Collin BA, Leather HL, Wingard JR, Ramphal R. Evolution, incidence, and susceptibility of bacterial bloodstream isolates from 519 bone marrow transplant patients. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2001; 33: 947-53.
• [20] Worth LJ, Slavin MA, Brown GV, Black J. Catheter-related bloodstream infections in hematology: time for standardized surveillance? Cancer 2007; 109: 1215-26.
• [21] Howell PB, Walters PE, Donowitz GR, Farr BM. Risk factors for infection of adult patients with cancer who have tunnelled central venous catheters. Cancer 1995; 75: 1367-75.
• [22] Offidani M, Corvatta L, Olivieri A et al. Infectious complications after autologous peripheral blood progenitor cell transplantation followed by G-CSF. Bone marrow transplantation 1999; 24: 1079-87.
• [23] Cordonnier C, Buzyn A, Leverger G et al. Epidemiology and risk factors for gram-positive coccal infections in neutropenia: toward a more targeted antibiotic strategy. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2003; 36: 149-58.
• [24] Velasco E, Byington R, Martins CA, Schirmer M, Dias LM, Gonçalves VM. Prospective evaluation of the epidemiology, microbiology, and outcome of bloodstream infections in hematologic patients in a single cancer center. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 2003; 22: 137-43.
• [25] Klastersky J, Ameye L, Maertens J et al. Bacteraemia in febrile neutropenic cancer patients. International journal of antimicrobial agents 2007; 30: 51-9.
• [26] Almyroudis NG, Fuller A, Jakubowski A et al. Pre- and post-engraftment bloodstream infection rates and associated mortality in allogeneic hematopoietic stem cell transplant recipients. Transplant infectious disease : an official journal of the Transplantation Society 2005; 7: 11-7.
• [27] Wisplinghoff H, Reinert RR, Cornely O, Seifert H. Molecular relationships and antimicrobial susceptibilities of viridans group streptococci isolated from blood of neutropenic cancer patients. Journal of clinical microbiology 1999; 37: 1876-80.
• [28] Paul M, Gafter-Gvili A, Leibovici L et al. The epidemiology of bacteremia with febrile neutropenia: experience from a single center, 1988-2004. The Israel Medical Association journal : IMAJ. 2007; 9: 424-9.
• [29] Rolston KV, Yadegarynia D, Kontoyiannis DP, Raad, II, Ho DH. The spectrum of Gram-positive bloodstream infections in patients with hematologic malignancies, and the in vitro activity of various quinolones against Gram-positive bacteria isolated from cancer patients. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 2006; 10: 223-30.