Infectious Complications in the Immunosuppressed Patient

Chapter 20
Infectious Complications in the Immunosuppressed Patient

Tim Collyns¹ and Elankumaran Paramasivam²

¹Leeds Teaching Hospitals Trust, St James’s University Hospital, Leeds, UK
²St James’s University Hospital, Leeds, UK

Introduction

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.

Table 20.1 Some specific infections associated with, and/or more severe in, specific conditions [1–3].

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)
Hypogammaglobulinaemia/impaired humoral immunity	Encapsulated bacteria: principally Streptococcus pneumoniae, also Haemophilus influenzae, Neisseria meningitidis
Hypogammaglobulinaemia/impaired humoral immunity	Sinopulmonary infections, +/− septicaemia
Lymphopenia/impaired cellular immunity	Herpesviruses, respiratory viruses
	Listeria monocytogenes, Nocardia species
	Mycobacteria: Mycobacterium tuberculosis and non-tuberculous
	Cryptococcus species, P. jirovecii
	Toxoplasma gondii reactivation
Asplenic/functionally hyposplenic	Encapsulated bacteria, principally S. pneumoniae, also H. influenzae, Capnocytophaga spp.; parasite infections, malaria, babesiosis
Acute leukaemias	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 leukaemias	Acute lymphocytic leukaemia (ALL): Pneumocystis
Chronic lymphocytic leukaemia (CLL)	Hypogammaglobulinaemic – see preceding text
Chronic lymphocytic leukaemia (CLL)	CLL treatment (e.g. alemtuzumab, MabCampath®): wide range, including Pneumocystis, CMV reactivation
Multiple myeloma	Functionally hypogammaglobulinaemic – see preceding text
Multiple myeloma	If neutropenic – see preceding text
Sickle cell disease	Functionally hyposplenic – see preceding text
Sickle cell disease	Salmonella osteomyelitis
Iron overload (e.g. thalassaemias) and/or iron chelator therapy such as desferrioxamine	Yersinia spp.; other bacteria may have increased pathogenicity in presence of iron-rich milieu fungal infection (Zygomycetes)
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: 3 phases post HSCT
	Pre-engraftment (day 0 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)

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.

Neutropenic fever

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].

Table 20.2 Diagnostic criteria.

Neutropenic fever	Absolute neutrophil count <0.5 × 10⁹/L blood or <1 and expected to fall to <0.5 within the next 48 h
	Single temperature ≥38.3°C (i.e. 101°F) or ≥38°C for 1 h or more
	(NB NICE definitions: ANC < 0.5, temperature > 38°C [4])
Sepsis	Infection (suspected or proven) coupled with deranged parameters indicative of systemic response, including:
	Pyrexia (>38.3°C) or hypothermia (<36°C)
	Tachycardia (>90 beats/min)
	Tachypnoea (>30 breaths/min)
	Significant oedema or positive fluid balance (>20 mL/kg/24 h)
	Abnormal blood tests:
	Leukocytosis* (>12 × 10⁹/L) or leukopenia* (<4)
	Thrombocytopenia* (platelet count <100 × 10⁹/L)
	(*NB often not applicable in haematology patient setting)
	Significantly elevated CRP (or PCT)
	Hyperglycaemia (plasma glucose >7.7 mM/L) without diabetes
	Arterial hypotension (see also severe sepsis)
	Organ dysfunction or tissue perfusion markers (see also severe sepsis)
Severe sepsis	Sepsis with dysfunction or hypoperfusion of organs not primarily infected, e.g. lactic acidosis, oliguria (<30 mL/h or <0.5 mL/kg/h), altered mental state and/or hypotension (systolic pressure < 90 mmHg, mean arterial pressure <70 mmHg or drop of > 40 mmHg from baseline) – which is correctable with fluid resuscitation
	Organ dysfunction can be recorded/monitored using validated scoring systems, such as Multiple Organ Dysfunction (MOD) or Sequential Organ Failure Assessment (SOFA) scores
Septic shock	Sepsis-induced persistent arterial hypotension which requires pressor therapy to correct
Refractory septic shock	Septic shock that lasts >1 h despite the use of pressor therapy

Adapted from [1, 2, 4–6].

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 therapy, as well as with clinical source. It is also influenced by the patient’s setting – whether in the community or in hospital and, if in the hospital, the particular unit’s microflora. Some attributes of the more common bacterial isolates are detailed in Table 20.3.