Bloodstream infections in neutropenic cancer patients: A practical update

Figures & data

Table 1. Definitions of clinical situations referred to in the text.

	Definition
Antibiotic prophylaxis	Administration of antibiotics to patients without any signs or symptoms of infection with the aim of preventing infectious complications
Bloodstream infection (BSI)	A laboratory-confirmed positive blood culture which can be the consequence of an infection at other body sites (secondary BSI) or not (primary BSI). In case of potential common skin commensals such as coagulase-negative staphylococci, Corynebacterium species other than C. dyphteriae, Bacillus species other than B. anthracis, Micrococcus, etc., at least two consecutive positive blood cultures, drawn in different occasions, are needed ^7
Catheter-related bloodstream infection (CLABSI)	BSI and clinical manifestations of infection in presence of an intravascular device with > 1 positive blood culture from a peripheral vein and no other reliable sources of infection. One of the following should also be present: a positive semiquantitative or quantitative catheter culture; blood culture obtained through catheter positive at least 2 hours earlier than the blood culture drawn peripherally at the same time; quantitative cultures of blood with a ratio of 3:1 cfu/mL of blood (catheter vs. peripheral blood) ^84
Colonization	Presence of bacteria on body surfaces, such as skin or mucosae, without invading or damaging the tissue and without an immune reaction
Empirical antibiotic therapy	Antibiotic treatment given in case of suspected infection before microbiology results are available; the knowledge of the bacteria commonly involved and local epidemiology drive the empirical choice of the drug(s)
Fever	A single oral temperature ≥ 38,3°C (101°F) or as a temperature above 38.0°C (100.4°F) for at least one hour ^8
Mucosal-barrier injury CLABSI (MBI-CLABSI)	Blood culture positive for one of the following intestinal organisms such as Enterobacteriaceae, viridans streptococci, Bacteroides spp., Enterococcus spp., Fusobacterium, Peptostreptococcus, Prevotella or Clostriudium in a neutropenic patient or in a HSCT recipient with severe gastrointestinal graft-versus-host disease or diarrhea ^7
Multidrug-Resistant Gram Negative bacteria	Bacteria which are not susceptible to at least three of the following antimicrobial categories: antipseudomonal penicillins, cephalosporins, carbapenems, aminoglycosides and fluoroquinolones ^13
Neutropenia	A granulocyte count < 500 cells/µL or < 1000 cells/µL with an expected decline greater than or equal to 500 cells/µL over the next 48 hours ^5
Sepsis	A documented or suspected infection plus some of the following criteria: • General parameters: Fever (core temperature > 38.3°C, hypothermia (core temperature < 36°C), Heart rate > 90 or > 2DS the normal value for age, Tachypnea > 30, Altered mental status, Significant edema or positive fluid balance, Hyperglycemia (plasma glucose > 110 mg/dl) in the absence of diabetes. • Inflammatory parameters: Leukocytosis (WBC > 12000 cell/µL), Leukopenia (WBC < 4000 cell/µL), Normal WBC with > 10% of immature forms, CRP or PCT > 2 SD above the normal value. • Hemodynamic parameters: Arterial hypotension (systolic blood pressure < 90 mmHg, mean arterial pressure < 70 mmHg, Systolic blood pressure decrease > 40 mmHg or < 2SD below normal for age, Mixed venous oxygenation > 70%, Cardiac index > 3.5 L/min × m2, • Organ dysfunction parameters: Arterial hypoxemia (PaO2/FiO2 < 300), Acute oliguria (output < 0.5 ml/kg × min), Creatinine increase > 0.5 mg/dL, Coagulation abnormalities (international normalized ratio > 1.5, Activated partial thromboplastin time > 60 s), Ileus, Thrombocytopenia (< 100,000/µL), Hyperbilirubinemia (plasma total bilirubin > 4 mg/dL or 70 mmol/L) • Tissue perfusion parameters: Hyperlactatemia ( > 3 mmol/L), Decreased capillary filling or mottling.

Table 2. The main elements of infection control program.

Main elements	Necessary actions	Practical aspects
Problem recognition	Knowledge of local epidemiology	Reporting regularly the most frequent resistance patterns and the mortality according to these patterns
	Active surveillance for selected resistant bacteria (e.g. MRSA, VRE, CRE, ESBL-E)	Establishing the need for active screening (e.g. only at admission in patients coming from countries with high rate of MDR bacteria, weekly if local transmission is possible, etc.)
	Alerts from microbiology when new MDR bacteria are isolated in the center	Swift reporting from microbiology to clinicians Rapid identification of any nosocomial transmission
	Reporting data on patient's colonization status	Communication of colonization status of infected and colonized patients at discharge or transfer Identifying known MDR carrier patients at re-admission
Infection control measures	Hand Hygiene	Train all staff in hand hygiene Provide access to hand hygiene stations Monitor adherence and provide feedback
	Antiseptic whole body washing and decolonization	The efficacy of chlorhexidine bathing and nasal decolonization has been only reported for MRSA Chlorhexidine bathing is recommended by some guidelines for CRE carriers
	Contact Precautions	Patient isolation in a single room (preferred option) or patient cohorting Staff cohorting if necessary Use of disposable gloves and gowns Clear guidelines for discontinuation of contact precautions
	Antimicrobial stewardship	Optimizing the use of available antibiotics (right dose, right indication) Preferring narrow-spectrum agents Avoiding prolonged treatment courses

Table 3. Clinical data at onset of febrile neutropenia which allow for calculating the risk for severe complications in cancer patients.

MASCC SCORE		CISNE
Clinical Parameters	Score	Eligibility criteria	Clinical Parameters	Score
Burden of illness: no or mild symptoms	5	Adults (≥18 years) No prior hospital admission for any other reason Absence of acute organ failure (renal, cardiac, respiratory) or decompensation of chronic insufficiency Absence of septic shock and hypotension (systolic pressure <90 mmHg) Absence of severe infections No other serious complications, constituting an admission criterion by themselves (pulmonary thromboembolism, arrhythmias, disseminated intravascular coagulation and bleeding) Solid tumor treated with mild-moderate intensity chemotherapy	Eastern Cooperative Oncology Group performance status (ECOG PS) >= 2	2
No hypotension	5		Stress-induced hyperglycemia (SIH)	2
No chronic obstructive pulmonary disease	4		Chronic obstructive pulmonary disease	1
Solid tumor or no previous fungal infection	4		Chronic cardiovascular disease	1
No dehydration	3		Mucositis National Cancer Institute (NCI) grade >= 2	1
Outpatient status	3		Monocytes < 200 microL	1
Burden of illness: moderate symptoms	3
Patient's age <60 years	2

Notes. MASCC, Multinational Association for Supportive Care in Cancer. Points attributed to the “burden of illness” category are not cumulative. The maximal theoretical score is 26. Low-risk patient: score ≥21.

CISNE, the Clinical Index of Stable Febrile Neutropenia. Prognostic categories are defined by the sum of clinical parameters points as low (0 points), intermediate (1–2 points) and high risk (≥ 3 points), with the respective complication rates of 1.1%, 6.2% and 36%.

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