Wednesday, June 15, 2011

Sepsis in Children with Oncohematological Malignancies

Though the use of aggressive treatment protocols that combine chemotherapy, radiation, and surgery, the prognosis for patients with childhood malignancies has improved substantially. However, these intensive treatment regimens can cause life-threatening complications, the

most prominent of which are infections that result from treatment-associated immunosuppression.

Historically, sepsis and septic shock in pediatric oncology patients have carried a poor prognosis. Earlier studies, however, used a variety of criteria to define sepsis and septic shock, and most included relatively small numbers of children. Some studies even excluded patients who had received bone marrow transplants (BMT).

Sepsis is a leading cause of death in critically ill patients despite the use of modern antibiotics and resuscitation therapies. The septic response is an extremely complex chain of events involving inflammatory and anti-inflammatory processes, humoral and cellular reactions and circulatory abnormalities. The diagnosis of sepsis and evaluation of its severity is complicated by the highly variable and non-specific nature of the signs and symptoms of sepsis. However, the early diagnosis and stratification of the severity of sepsis is very important, increasing the possibility of starting timely and specific treatment.

A rapid microbiological diagnosis could therefore confirm an infectious cause of fever and aid in the choice of a specific therapy. Among the infectious causes, bacteria and fungi are the leading threats, with high infection-related mortality rate, especially for polymicrobial infections and moulds. The current gold standard for the detection of bacterial pathogens in blood is blood culture. However, all blood culture systems suffer from several limitations, such as lack of rapidity and low sensitivity, especially when the patient has already received antibiotics and when fastidious micro-organisms are involved. From this perspective, the diagnosis of bloodstream infections could prove really challenging in oncohaematological patients, who routinely receive prophylactic antibiotics and whose blood cultures therefore often remain negative. Even after the detection of growth in cultured blood (usually not before 6–12 h of incubation), conventional blood cultures require at least a further 24–48 h for the definitive identification of the pathogen and the evaluation of its sensitivity to antibiotics. Other parallel approaches are therefore needed, and among them well-designed molecular assays could prove really useful. Several molecular techniques have already been successfully used in routine microbiology laboratories for direct detection of viral, bacterial, mycotic and protozoan pathogens. However, their use on whole blood samples for detection of sepsis has been hampered by several factors, including insufficient sensitivity, presence of PCR inhibitors in blood, and the difficulty of setting up an assay capable of detecting a wide range of potential pathogens.

Another advance in diagnosis of sepsis is the use of biomarkers. Biomarkers can have an important place in this process because they can indicate the presence or absence or severity of sepsis. A biomarker is defined as ‘‘a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.’’.

Beside rapid diagnosis of sepsis, other potential uses of biomarkers include roles in prognostication, guiding antibiotic therapy, evaluating the response to therapy and recovery from sepsis, differentiating Gram-positive from Gram-negative microorganisms as the cause of sepsis, predicting sepsis complications and the development of organ dysfunction (heart, kidneys, liver or multiple organ dysfunction). However, the exact role of biomarkers in the management of septic patients remains undefined. C-reactive protein (CRP) has been used for many years but its specificity has been challenged. Procalcitonin (PCT) has been proposed as a more specific and better prognostic marker than CRP, although its value has also been challenged. It remains difficult to differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome, and there is a continuous search for better biomarkers of sepsis.

In the present chapter we will try to explore the occurrence of sepsis in children with oncohematological disorders under chemotherapy with emphasis on rapid diagnosis and recent therapy.

Keywords: Sepsis, Oncohematological malignancies, biomarkers, children.

No comments: