Current insights into severe sepsis in cancer patients - Critical Care Science (CCS)
Neutropenia due to myelosuppression by malignant infiltration or that which is more commonly caused by cytotoxic chemotherapy remains the hallmark of immunodeficiency in patients with cancer and is associated with a considerably increased risk for bacterial or fungal infections. In addition to quantitative defects, neutrophils also exhibit various functional defects in chemotaxis, phagocytosis, bactericidal capacity and respiratory burst. The requirements of indwelling long-term central venous access, non-selective cytotoxic activity on dividing cells and poor wound healing account for the frequent impairment in skin and mucosal integrity. Nonetheless, the emergence of new drugs that specifically target lymphocytes has broadened the spectrum of infectious complications to include opportunistic fungal, parasitic and mycobacterial infections, which are observed in patients with lymphoproliferative disorders.(,) Interestingly, even a short course of stress-dose corticosteroids that is commonly applied in cases of severe or refractory circulatory failure is likely to increase the risk of intensive care unit (ICU)-acquired infections in hematological patients with septic shock.() Most importantly, the spectrum of pathogens responsible for severe infections has changed. Multi-resistant Gram-negative bacteria, especially enterobacteriaceae like Klebsiella or Serratia spp. together with Pseudomonas spp. and others have emerged and exert a major impact on the outcomes of immunocompromised patients for whom any delay in adequate antibiotherapy may be extremely harmful.() Extensive prophylaxis with azoles or echinocandins in hematologic patients has led to a shift in the fungal spectrum to more resistant strains and to the emergence of rare fungi.()
In addition, some additional risk factors of infections are potentially involved in patients with malignancies. Cancer patients frequently require red blood cell transfusions. Transfusion-related immunomodulation is likely to confer an additional risk of infectious complications, as suggested by a recent meta-analysis of studies that addressed the transfusion thresholds in various populations.() Furthermore, some inherited individual predispositions that have been previously described in immunocompetent patients might confer an increased susceptibility to severe infections in immunocompromised patients as well. A deficiency in mannose-binding lectin has thus been associated with a higher incidence of severe bacterial and fungal infections in patients with hematological malignancies. Moreover, functional polymorphisms in TLR4 or long pentraxin PTX3 have been associated with an increased risk of invasive aspergillosis in allogeneic stem cell transplant recipients.(–)
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Neutropenia due to myelosuppression by malignant infiltration or that which is more commonly caused by cytotoxic chemotherapy remains the hallmark of immunodeficiency in patients with cancer and is associated with a considerably increased risk for bacterial or fungal infections. In addition to quantitative defects, neutrophils also exhibit various functional defects in chemotaxis, phagocytosis, bactericidal capacity and respiratory burst. The requirements of indwelling long-term central venous access, non-selective cytotoxic activity on dividing cells and poor wound healing account for the frequent impairment in skin and mucosal integrity. Nonetheless, the emergence of new drugs that specifically target lymphocytes has broadened the spectrum of infectious complications to include opportunistic fungal, parasitic and mycobacterial infections, which are observed in patients with lymphoproliferative disorders.(,) Interestingly, even a short course of stress-dose corticosteroids that is commonly applied in cases of severe or refractory circulatory failure is likely to increase the risk of intensive care unit (ICU)-acquired infections in hematological patients with septic shock.() Most importantly, the spectrum of pathogens responsible for severe infections has changed. Multi-resistant Gram-negative bacteria, especially enterobacteriaceae like Klebsiella or Serratia spp. together with Pseudomonas spp. and others have emerged and exert a major impact on the outcomes of immunocompromised patients for whom any delay in adequate antibiotherapy may be extremely harmful.() Extensive prophylaxis with azoles or echinocandins in hematologic patients has led to a shift in the fungal spectrum to more resistant strains and to the emergence of rare fungi.()
In addition, some additional risk factors of infections are potentially involved in patients with malignancies. Cancer patients frequently require red blood cell transfusions. Transfusion-related immunomodulation is likely to confer an additional risk of infectious complications, as suggested by a recent meta-analysis of studies that addressed the transfusion thresholds in various populations.() Furthermore, some inherited individual predispositions that have been previously described in immunocompetent patients might confer an increased susceptibility to severe infections in immunocompromised patients as well. A deficiency in mannose-binding lectin has thus been associated with a higher incidence of severe bacterial and fungal infections in patients with hematological malignancies. Moreover, functional polymorphisms in TLR4 or long pentraxin PTX3 have been associated with an increased risk of invasive aspergillosis in allogeneic stem cell transplant recipients.(-)
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