(BQ) Part 2 book Haematology in critical care - A practical handbook has contents: Haematopoietic stem cell transplantation, delivering chemotherapy on intensive care, neonatal anaemia, approach to thrombocytopenia, haematological emergencies,.... and other contents.
5 Section Approach to White Cell Problems 20 c h a p t e r 20 Infectious Complications in the Immunosuppressed Patient Tim Collyns1 and Elankumaran Paramasivam2 Leeds Teaching Hospitals Trust, St James’s University Hospital, Leeds, UK St James’s University Hospital, Leeds, UK 1 2 Introduction Neutropenic fever Patients with many haematological disorders have an increased susceptibility to infections This may be due to disruption of the patient’s host defences by the underlying condition and/or the subsequent haematological treatment Some examples are listed in Table 20.1; however, the spectrum of infectious diseases which may be involved varies with the type and severity of the haematological condition and the associated therapy [1–3] It is also related to the infectious agents which are circulating in the patient’s surrounding environment and community and to which they have been exposed to Depending on the haematological disease, patients may present with more than one infectious complication, either concurrently or consecutively Patients may require critical care level support due to the systemic sequelae of an infection, or they may acquire certain infections while in the critical care environment This chapter outlines some of the more common scenarios in the critical care setting and approaches to their diagnosis and successful management Infectious complications contribute significantly to the overall morbidity and mortality of haematological diseases; hence, there will usually be local guidelines in place which should be consulted as required This is the archetype of an infectious complication in the setting of haematological diseases Standard, internationally applied definitions are available (Table 20.2), but there may be local variation in interpretation of both neutropenia and fever [1, 2, 4] Diagnostic criteria for assessing sepsis severity are also outlined in Table 20.2 [5, 6] The National Institute for Health and Clinical Excellence (NICE) in the UK has recently issued guidance for the prevention and management of neutropenic sepsis – in which the criteria for a diagnosis of sepsis includes a fever greater than 38°C alone, while neutropenia is defined as the patient’s neutrophil count being equal to, or less than, 0.5 × 109/L [4] Neutropenic fever often arises in those with haematological malignancy undergoing chemotherapy The absence of neutrophils, coupled with disruption of skin and mucosal barriers, predispose the patient to infection The risk is inversely proportional to the absolute count, and 10–20% of patients with a neutrophil count less than 0.1 × 109/L will have a bloodstream infection Fever is an early, albeit non-specific, sign of infection, although classic symptoms and signs may be reduced or absent [1, 2] Only 20–30% of neutropenic fevers are due to clinically identified infection [2] The aetiology of likely infecting organisms varies with length of neutropenia, previous or current antimicrobial Haematology in Critical Care: A Practical Handbook, First Edition Edited by Jecko Thachil and Quentin A Hill © 2014 John Wiley & Sons, Ltd Published 2014 by John Wiley & Sons, Ltd 125 126 Iron overload (e.g thalassaemias) and/or iron chelator therapy such as desferrioxamine Sickle cell disease Multiple myeloma Chronic lymphocytic leukaemia (CLL) Acute leukaemias Asplenic/functionally hyposplenic Lymphopenia/impaired cellular immunity Hypogammaglobulinaemia/impaired humoral immunity Neutropenia Viral infections HSV reactivation Bacterial infections (see also Table 20.3) Gut translocation: Enterobacteriaceae (coliforms) Line associated: staphylococci Fungal infections Candida species Aspergillus species, most common Aspergillus fumigatus (other moulds) Encapsulated bacteria: principally Streptococcus pneumoniae, also Haemophilus influenzae, Neisseria meningitidis Sinopulmonary infections, +/− septicaemia Herpesviruses, respiratory viruses Listeria monocytogenes, Nocardia species Mycobacteria: Mycobacterium tuberculosis and non-tuberculous Cryptococcus species, P jirovecii Toxoplasma gondii reactivation Encapsulated bacteria, principally S pneumoniae, also H influenzae, Capnocytophaga spp.; parasite infections, malaria, babesiosis If neutropenic, see preceding text Patients with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) may be functionally neutropenic, i.e detectable but ineffective neutrophils Acute lymphocytic leukaemia (ALL): Pneumocystis Hypogammaglobulinaemic – see preceding text CLL treatment (e.g alemtuzumab, MabCampath®): wide range, including Pneumocystis, CMV reactivation Functionally hypogammaglobulinaemic – see preceding text If neutropenic – see preceding text Functionally hyposplenic – see preceding text Salmonella osteomyelitis Yersinia spp.; other bacteria may have increased pathogenicity in presence of iron-rich milieu fungal infection (Zygomycetes) Table 20.1 Some specific infections associated with, and/or more severe in, specific conditions [1–3] 127 Haemopoietic stem cell transplant (HSCT) recipients Relative risks vary considerably with source/type of transplant and conditioning regime, as well as underlying disease and previous treatment Allogeneic recipients are more likely to have infectious complications, and be at risk for longer, than autologous recipients In the former, the presence of significant GVHD notably increases the probability of certain infectious complications Conventionally for allogeneic recipients: phases post HSCT Pre-engraftment (day usually to < day 30) Neutropenic: see preceding text (also present post autologous HSCT though usually less prolonged) Early post-engraftment (up to day 100) Lymphopenic – see preceding text Specific risks include CMV reactivation (seropositive recipient and/or donor) Respiratory viruses, including adenovirus BK virus (haemorrhagic cystitis) Aspergillus species and other moulds Pneumocystis T gondii (seropositive recipient) Late post-engraftment (day 100 to reconstitution of immune function – usually around 18 months post allogeneic HSCT but delayed in presence of GVHD/associated treatment) Sinopulmonary infections: S pneumoniae, H influenzae, Pneumocystis, Aspergillus species and other moulds Varicella zoster virus (VZV) (seropositive recipient) 128 section Approach to White Cell Problems Table 20.2 Diagnostic criteria Neutropenic fever Sepsis Severe sepsis Septic shock Refractory septic shock Absolute neutrophil count 30 breaths/min) Significant oedema or positive fluid balance (>20 mL/kg/24 h) Abnormal blood tests: Leukocytosis* (>12 × 109/L) or leukopenia* (14 days) – to allow the administration of certain chemotherapy agents and blood products and facilitate blood sampling [10] These catheters, such as Hickman or Groshong lines, are surgically implanted with a portion in a subcutaneous tunnel A patient requiring critical care level support may also have short-term central venous and/or arterial lines inserted Venous catheters are a significant source of bloodstream infections in the haematology setting [2] The frequency of infection is affected by a number of factors, including the catheter type and site, and the standards of asepsis applied when inserting and using the catheter [10] The hub/lumen is the primary route of organism acquisition by long lines, and hence, these catheter-related bloodstream infections (CRBSIs) are predominantly caused by Gram-positive organisms which colonize the skin, such as coagulasenegative staphylococci, S aureus and corynebacteria (see Table 20.3) [2, 10] Other organisms include Candida species, enterococci, Gram-negative bacilli and rapidly growing mycobacteria [2, 10] Diagnosis History/examination Localizing symptoms/signs may be mild or absent There may be visible purulence or inflammation of skin at the exit site +/− that overlying the subcutaneous tunnel if present Fever +/− rigors may be temporally associated with accessing the line Microbiology • If line being preserved at the time, blood cultures should be taken concurrently from a peripheral vein and via each lumen of the catheter(s) – with similar volume of blood inoculated per bottle If one or more luminal blood cultures flag with positive growth on an automated blood culture machine h or more faster than the peripheral set, this differential time to positivity (DTP) is considered significant and is strongly suggestive of the catheter being the source of infection [2, 5, 10] Quantitative blood cultures are not performed in most routine microbiology laboratories [10] Note that blood cultures positive for S. aureus, coagulase-negative staphylococci or Candida raise the suspicion per se of CRBSI if no alternative clinically apparent source [10] • Exit site swab if exudate present [10] • If catheter is removed and cultured, the growth of greater than or equal to15 cfu from the tip rolled on an agar plate indicates the catheter was (at least) colonized – although this technique doesn’t detect intra-luminal growth [10] 240 section 10 Haematological Emergencies otentiate bleomycin-induced lung injury, even if given p several years later: • Oxygen should be avoided in patients previously exposed to bleomycin unless hypoxic For example, avoid high oxygen doses during clinical procedures and in the peri-operative period • High-dose oxygen should only be used for immediate life-saving indications, and the minimum dose used to maintain oxygen saturations at a lower target range of 88–92% [8] If bleomycin lung injury is suspected, discontinue bleomycin, investigate to exclude infection, optimize fluid balance and consider steroid therapy Radiotherapy Radiation involving lung tissue can cause a pneumonitis but is less likely with a smaller volume irradiated (rare if