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• W3048696092 abstract "Febrile neutropaenia (FN) is defined as an oral temperature of >38.3°C or two consecutive readings of >38.0°C for 2 h and an absolute neutrophil count (ANC) of <0.5 × 109/l, or expected to fall below 0.5 × 109/l. Despite major advances in prevention and treatment, FN remains one of the most frequent and serious complications of cancer chemotherapy (ChT). It is a major cause of morbidity, healthcare resource use and compromised treatment efficacy resulting from delays and dose reductions of ChT. Mortality from FN has diminished steadily, but remains significant. Most standard-dose ChT regimens are associated with 6–8 days of neutropaenia, and FN is observed in ∼8 cases per 1000 patients receiving cancer ChT. FN is responsible for considerable morbidity as 20%–30% of patients present complications that require in-hospital management, with an overall in-hospital mortality of ∼10%. The mean cost per hospitalisation in Western countries is ∼13 500€ (15 000 US$). There is a clear relationship between the severity of neutropaenia (which directly influences the incidence of FN) and the intensity of ChT. Currently, the different regimens are classified as producing a high risk (>20%), an intermediate risk (10%–20%) or a low risk (<10%) of FN. It has been shown that several factors, other than ChT itself, are responsible for increasing the risk of FN and its complications. Among them, age plays a major role [II, III] with older patients having a higher risk of FN following ChT, with worse morbidity and mortality rates. Other factors having a similar role are as follows:•advanced disease,•history of prior FN,•no antibiotic prophylaxis or granulocyte colony-stimulating factor (G-CSF) use [III, IV],•mucositis,•poor performance status and/or•cardiovascular disease [III, IV]. The risk of FN and its complications increases when one or several co-morbidities are present in the patient. These considerations will be instrumental in deciding whether a ChT-treated patient should receive primary prophylaxis to decrease the potential risk of FN. In the case of FN, prognosis is worst in patients with proven bacteraemia, with mortality rates of 18% in Gram-negative and 5% in Gram-positive bacteraemia [for bacteraemias due to coagulase-negative Staphylococcus (CNS) only, no attributable mortality has been reported] [1.Klastersky J. Ameye L. Maertens J. et al.Bacteraemia in febrile neutropenic patients.Int J Antimicrob Agents. 2007; 30: S51-S59Google Scholar]. The presence of a focal site of presumed infection (e.g. pneumonia, abscess, cellulitis) also makes the outcome worse. Mortality varies according to the Multinational Association of Supportive Care in Cancer (MASCC) prognostic index (Table 1): lower than 5% if the MASCC score is ≥21, but possibly as high as 40% if the MASCC score is <15 [2.Klastersky J. Paesmans M. Rubenstein E.B. et al.The Multinational Association for Supportive Care in Cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients.J Clin Oncol. 2000; 18: 3038-3051Google Scholar].Table 1MASCC febrile neutropaenia risk indexCharacteristicsScoreBurden of illness: no or mild symptoms5Burden of illness: moderate symptoms3Burden of illness: severe symptoms0No hypotension (systolic BP > 90 mmHg)5No chronic obstructive pulmonary disease4Solid tumour/lymphoma with no previous fungal infection4No dehydration3Outpatient status (at onset of fever)3Age <60 years2Patients with scores ≥21 are at low risk of complications. Points attributed to the variable ‘burden of illness’ are not cumulative. The maximum theoretical score is therefore 26 [2.Klastersky J. Paesmans M. Rubenstein E.B. et al.The Multinational Association for Supportive Care in Cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients.J Clin Oncol. 2000; 18: 3038-3051Google Scholar]. Reprinted with permission. © 2000 American Society of Clinical Oncology. All rights reserved.BP, blood pressure. Open table in a new tab Patients with scores ≥21 are at low risk of complications. Points attributed to the variable ‘burden of illness’ are not cumulative. The maximum theoretical score is therefore 26 [2.Klastersky J. Paesmans M. Rubenstein E.B. et al.The Multinational Association for Supportive Care in Cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients.J Clin Oncol. 2000; 18: 3038-3051Google Scholar]. Reprinted with permission. © 2000 American Society of Clinical Oncology. All rights reserved. BP, blood pressure. Positive microbiological detection rates by standard blood cultures vary depending on whether or not patients have received prophylactic antibiotics. Overall, bacteraemia can be detected in ∼20% of patients with FN; this obviously helps to further adjust antibiotic therapy. It is crucial to understand that different centres experience different patterns of frequency of causative pathogens. Consequently, these guidelines are intended for use alongside appropriate local antimicrobial policies adapted to the epidemiology of the centre. Over the last few decades, a shift has occurred from FN associated mainly with Gram-negative bacteria to FN associated with Gram-positive organisms. At the present time, most centres report Gram-positive and Gram-negative bacteraemia in 50% of patients with FN, although centres that do not use fluoroquinolone prophylaxis report a predominance of Gram-negative bacteria. An increase in antibiotic-resistant strains has been noted, such as extended spectrum &bgr;-lactamase (ESBL)—producing Gram-negative bacteria, vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). Increasing numbers of infections with fluconazole-resistant Candida strains (e.g. Candida krusei and Candida glabrata) have also been reported [3.Moghnieh R. Estaitieh N. Mugharbil A. et al.Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis.Front Cell Infect Microbiol. 2015; 5: 11Google Scholar]. Antimicrobials (first non-absorbable antibiotics and later, co-trimoxazole) have been used for a long time for the prevention of episodes of FN in ChT-treated patients. This approach has been somewhat successful, but has also led to the emergence of resistant strains, limiting its efficacy. Since the 1990s, fluoroquinolones have been used extensively for chemoprophylaxis. Most studies have shown that fluoroquinolones reduce the incidence of infection and, in some studies, also the infection-related mortality, but at the expense of the emergence of quinolone-resistant strains. This should, in the end, render the prophylaxis useless; moreover, these strains jeopardise the use of fluoroquinolones as a therapy of FN in low-risk patients, as will be discussed elsewhere. For all of these reasons, the use of antimicrobials, including fluoroquinolones, should be discouraged. Guidelines from the EORTC (European Organisation for Research and Treatment of Cancer) and American Society of Clinical Oncology (ASCO) recommend that clinicians limit the use of antibacterial prophylaxis to patients at high risk for FN; others recommend the mere avoidance of such practices for the prevention of FN. The most recent update of the Cochrane meta-analysis still recommended the use of ciprofloxacin or levofloxacin in cancer patients undergoing intensive ChT [4.Gafter-Gvili A. Fraser A. Paul M. Leibovici L. Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients.Ann Intern Med. 2005; 142 ([Erratum, Ann Intern Med 2006; 144:704]): 979-995Google Scholar]. Several meta-analyses indicate that primary prophylaxis with G-CSF (i.e. G-CSF administered immediately after cycle 1 of ChT) reduces the risk of FN by at least 50% in patients with solid tumours without significantly affecting tumour response or overall survival [I] [5.Clark O.A. Lyman G.H. Castro A.A. et al.Colony-stimulating factors for chemotherapy-induced febrile neutropenia: a meta-analysis of randomized controlled trials.J Clin Oncol. 2005; 23: 4198-4214Google Scholar, 6.Cooper K.L. Madan J. Whyte S. et al.Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis.BMC Cancer. 2011; 11: 404Google Scholar, 7.Kuderer N.M. Dale D.C. Crawford J. Lyman G.H. Impact of primary prophylaxis with granulocyte colony-stimulating factor in febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review.J Clin Oncol. 2007; 25: 3158-3167Google Scholar]. Most guidelines recommend that G-CSF be administered prophylactically if the risk of FN is >20% for all planned cycles of treatment [I, A]. Classifications of the risk according to the type of ChT have been published and updated [8.Aapro M.S. Bohlius J. Cameron D.A. et al.2010 Update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours.Eur J Cancer. 2011; 47: 8-32Google Scholar]. For patients with an intermediate risk (10%–20%), it is important to consider the patient's age and particularly any coexisting morbidities, as already mentioned [8.Aapro M.S. Bohlius J. Cameron D.A. et al.2010 Update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours.Eur J Cancer. 2011; 47: 8-32Google Scholar, 9.Smith T.J. Khatcheressian J. Lyman G.H. et al.2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline.J Clin Oncol. 2006; 24: 3187-3205Google Scholar, 10.Sung L. Nathan P.C. Alibhai S.M. et al.Meta-analysis: effect of prophylactic hematopoietic colony-stimulating factors on mortality and outcomes of infections.Ann Intern Med. 2007; 147: 400-411Google Scholar]. An algorithm for the decisions about primary prophylactic G-CSF use is presented in Figure 1. Besides this approach, G-CSF can be considered in patients with reduced bone marrow reserve due to extensive radiotherapy [III] or patients who are neutropaenic in the context of HIV infection [II]. Recent meta-analysis of randomised, controlled trials [11.Wang L. Baser O. Kutikova L. et al.The impact of primary prophylaxis with granulocyte colony-stimulating factors on febrile neutropenia during chemotherapy: a systematic review and meta-analysis of randomized controlled trials.Support Care Cancer. 2015; 23: 3131-3140Google Scholar] and experience in real-world settings [12.Mitchell S. Li X. Woods M. et al.Comparative effectiveness of granulocyte colony-stimulating factors to prevent febrile neutropenia and related complications in cancer patients in clinical practice: a systematic review.J Oncol Pharm Pract. 2016; 22: 702-716Google Scholar] confirm the outstanding (>50% success) of primary prophylaxis with filgrastim or pegfilgrastim. With most ChT used for the treatment of common tumours, the risk of FN is maximal during the first course; thus, it makes sense to recommend primary prophylaxis for the patients at risk rather than to systematically resort to secondary prophylaxis. Secondary prophylaxis (i.e. G-CSF given for a course of ChT following a course with FN) is indicated if dose reduction below threshold or delay of ChT is not desirable (e.g. treatment with a curative intent). There are few complications associated with G-CSF administration; the most common adverse effect is minor or moderate bone pain that can usually be handled with standard analgesics. Use 5 &mgr;g/kg/day of G-CSF subcutaneously (s.c.) 24–72 h after the last day of ChT until sufficient/stable post-nadir ANC recovery (achieving a target ANC of >10–109/l is not necessary). Pegfilgrastim, injected s.c. as a single dose of either 100 &mgr;g/kg (individualised) or of a total dose of 6 mg (general approach), is considered equally effective [I, A]. The equivalent dose of filgrastim is 5 &mgr;g/kg/day for ∼10 days. There are no adequate data for reduced numbers or days or alternate days of G-CSF instead of standard, neither for use on day 1 instead of on day 2. EMA/FDA approved biosimilars can be considered. The therapy of acute leukaemias, autologous and allogeneic stem cell transplantations (TPLs) leads to higher risks of FN and potentially lethal complications [13.Hämäläinen S. Kuittinen T. Matinlauri I. et al.Neutropenic fever and severe sepsis in adult acute myeloid leukemia (AML) patients receiving intensive chemotherapy: causes and consequences.Leuk Lymphoma. 2008; 49: 495-501Google Scholar]. The incidence of FN in high-risk situations is as follows:•common during autologous and allogeneic peripheral blood stem-cell (PBSC) TPLs and bone marrow TPL, during graft failure,•in 35%–48% of acute myeloid leukaemia (AML) cases at diagnosis and•in 13%–30% during acute lymphoblastic leukaemia (ALL) induction ChT. FN-related mortality is described as follows:•0%–10% in autologous TPL,•highly variable in allogenic TPL,•80% during graft failure,•20%–26% during the first 2 months in AML and•2%–10% during induction ChT of ALL. Success in FN management requires prompt recognition of, and reaction to, potential infection. It is vital to educate outpatients to monitor their symptoms, including body temperature, and to provide clear written instructions on when and how to contact the appropriate service in the event of concerns. In addition, effective written local policies are essential to ensure a rapid response whenever FN is suspected. Some patients may present with FN at the Emergency Department, and in this situation, clear protocols must again be in place to manage these patients appropriately. The first administration of therapy should be given in the hospital within 1 h from the admission of a patient with FN. Delay in antibiotic administration has been associated with significant prolongation of the hospital stay and increased mortality. As already mentioned, the spectrum of infection in cancer patients is different from place to place and changes over time; therefore, paying attention to local epidemiology is crucial [14.Nesher L. Rolston K.V. The current spectrum of infection in cancer patients with chemotherapy related neutropenia.Infection. 2014; 42: 5-13Google Scholar]. A detailed history should be taken including the nature of the ChT given, prior prophylactic antibiotics, concomitant steroid use, recent surgical procedures and the presence of allergies. To guide therapy, it is important to check the clinical record for past positive microbiology, in particular previous presence of antibiotic-resistant organisms or bacteraemia. An initial assessment (Table 2) of circulatory and respiratory function, with vigorous resuscitation where necessary, should be followed by careful examination for potential foci of infection. Signs and symptoms of infection in neutropaenic patients can be minimal, particularly in those receiving corticosteroids, or in elderly patients who often may present with a confusional state.Table 2Initial assessment and investigations1Note the presence of indwelling i.v. catheters2Symptoms or signs suggesting an infection focus: Respiratory system Gastrointestinal tract Skin Perineal region/genitourinary discharges Oropharynx Central nervous system3Knowledge of previous positive microbiology results by checking clinical records4Routine investigations: Urgent blood testing to assess bone marrow, renal and liver function Coagulation screen C-reactive protein Blood cultures (minimum of two sets) including cultures from indwelling i.v. catheter Urinalysis and culturea Sputum microscopy and culturea Stool microscopy and culturea Skin lesion (aspirate/biopsy/swab) Chest radiograph5Further investigations (profound/prolonger neutropaenia/following allografts) High-resolution chest CT (if pyrexial despite 72 h of appropriate antibiotics) Bronchoalveolar lavagei.v., intravenous; CT, computed tomography.aUrinalysis, sputum and stool cultures only in case of suspected focus of infection at these sites. Open table in a new tab i.v., intravenous; CT, computed tomography. aUrinalysis, sputum and stool cultures only in case of suspected focus of infection at these sites. Vigilance is required in patients at risk for FN who present unwell, are hypotensive (compared with the known previous blood pressure readings), with a low-grade temperature or afebrile, as they may be developing Gram-negative septicaemia, requiring prompt treatment. Urgent full blood counts, to ascertain the ANC along with other investigations listed in Table 2, are crucial in guiding early management. Two sets of blood cultures from a peripheral vein and any indwelling venous catheters should be taken as well as specimens for microbiological testing from any suspected sites of infection, before the prompt institution of empirical broad-spectrum antimicrobial therapy. Urinary tract infections have to be suspected even in asymptomatic patients with a past history of such infections. The vast majority of FN cases, as managed according to the algorithm set out in Figure 2, respond promptly to empirical therapy, suffering no major complications. A number of instruments have been developed in attempts to predict these low-risk cases where complications are not likely. The most widely used instrument, the MASCC index, allows the clinician to rapidly assess, on just a clinical basis, the risk of a patient with FN. The MASCC score has been prospectively validated in several studies. The criteria and weighting scores are listed in Table 1. Low-risk cases are those scoring ≥21. The serious medical complication rate in low-risk cases is estimated to be 6% and the mortality rate to be below 1%. If an obvious focus of infection is apparent, antibacterials should be tailored accordingly. A recent review has concluded that inpatient oral antibacterial therapy can be safely substituted for conventional intravenous (i.v.) treatment in some low-risk FN patients, namely those who•are haemodynamically stable,•do not have acute leukaemia or evidence of organ failure and•do not have pneumonia, an indwelling venous catheter or severe soft tissue infection [I, A]. Precise criteria were not defined as they varied between the trials reviewed. Single-agent quinolones (moxifloxacin) were not inferior to combinations (quinolone with amoxicillin plus clavulanic acid), but the latter are preferred given the rise in Gram-positive FN episodes. Oral quinolone therapy should not be used in patients who have taken a quinolone antibacterial as prophylaxis. The safety of early change to oral combinations in afebrile patients after 48 h on i.v. therapy is supported in the review and preferred by many physicians. Some low-risk patients may be treated with outpatient parenteral regimens. The possibility of exclusive oral outpatient management for low-risk FN cases has become increasingly appealing on the grounds of the patient's convenience, economy [15.Elting L.S. Lu C. Escalante C.P. et al.Outcomes and cost of outpatient or inpatient management of 712 patients with febrile neutropenia.J Clin Oncol. 2008; 26: 606-611Google Scholar] and reduction in the incidence of nosocomial infections. There is also evidence to support an early discharge policy in these low-risk cases once they have become clinically stable, symptomatically better and there is evidence of fever lysis after a minimum of 24 h in hospital [II, B], and provided that there is an adequate understanding of the risks and that patient surveillance is available [16.Freifeld A. Marchigiani D. Walsh T. et al.A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during cancer chemotherapy.N Engl J Med. 1999; 341: 305-311Google Scholar, 17.Innes H. Lim S.L. Hall A. et al.Management of febrile neutropenia in solid tumours and lymphomas using the Multinational Association for Supportive Care in Cancer (MASCC) risk index: feasibility and safety in routine clinical practice.Support Care Cancer. 2008; 16: 485-491Google Scholar, 18.Kern W.V. Marchetti O. Drgona L. et al.Oral antibiotics for fever in low-risk neutropenic patients with cancer: a double-blind, multicenter trial comparing single daily moxofloxacin with twice daily ciprofloxacin plus amoxicillin-clavulanic acid combination therapy – EORTC infectious diseases group trial XV.J Clin Oncol. 2013; 31: 1149-1156Google Scholar, 19.Pherwani N. Ghayad J.M. Holle L.M. Karpiuk E.L. Outpatient management of febrile neutropenia associated with cancer chemotherapy: risk stratification and treatment review.Am J Health Syst Pharm. 2015; 72: 619-631Google Scholar]. Patients with FN who are at high risk as assessed by the MASCC criteria (<21), or have high-risk features as judged by the admitting doctor, should be admitted and commenced on broad-spectrum i.v. antibiotics, since the risk of bacterial sepsis is very high [20.Feld R. Bloodstream infections in cancer patients with febrile neutropenia.Int J Antimicrob Agents. 2008; 32: S30-S33Google Scholar]. Local epidemiological bacterial isolate and resistance patterns are crucially important in determining the first-choice empirical therapy, since coverage for MRSA or resistant Gram-negative bacteria may be required [21.Montassier E. Batard E. Gastinne T. et al.Recent changes in bacteremia in patients with cancer: a systematic review of epidemiology and antibiotic resistance.Eur J Clin Microbiol Infect Dis. 2013; 32: 841-850Google Scholar]. A meta-analysis comparing monotherapy (e.g. an anti-pseudomonal cephalosporin like ceftazidime or cefepime, imipenem, meropenem or piperacillin–tazobactam) with combination therapy found equivalent efficacy [I, A] [22.Furno P. Bucaneve G. Del Favero A. Monotherapy or aminoglycoside-containing combinations for empirical antibiotic treatment of febrile neutropenic patients: a meta-analysis.Lancet Infect Dis. 2002; 2: 231-242Google Scholar, 23.Rolston K.V. Bodey G.P. Comment on: empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials.J Antimicrob Chemother. 2006; 58 (author reply: 479–480): 478Google Scholar]. This is less clear in the subsets at high risk of prolonged neutropaenia and those with bacteraemia, where the bactericidal activity and synergistic effect of a &bgr;-lactam antibiotic in combination with an aminoglycoside might be preferable; namely, in case of Pseudomonas aeruginosa sepsis or in centres with known intermediate susceptibility of Gram-negative bacilli to &bgr;-lactams [3.Moghnieh R. Estaitieh N. Mugharbil A. et al.Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis.Front Cell Infect Microbiol. 2015; 5: 11Google Scholar]. Key recommendations about the management of febrile neutropenia are summarised in Table 3.Table 3Key recommendations for the management of FN•FN is observed in ±1% of patients receiving ChT; it is associated with considerable morbidity (20%–30%) and mortality (10%)•FN can be effectively prevented by the use of G-CSFs; it is recommended to use these agents in patients receiving chemotherapies with a >20% risk of developing FN and in those having serious co-morbidities and/or aged >60 years [I, A]•Patients with FN should be assessed for the risk of complications using a validated predictive tool, such as the MASCC score [I, A]•Patients with FN at a low risk of complications can often be treated with oral antibiotics and possibly as outpatients, if adequate follow-up is available [I, A]•Patients with FN at a high risk of complications should be hospitalised and treated without delay with broad spectrum antibiotics; these patients should be closely monitored for instability (pre-shock) [I, A]FN, febrile neutropaenia; ChT, chemotherapy; G-CSF, granulocyte colony-stimulating factor; MASCC, Multinational Association of Supportive Care in Cancer. Open table in a new tab FN, febrile neutropaenia; ChT, chemotherapy; G-CSF, granulocyte colony-stimulating factor; MASCC, Multinational Association of Supportive Care in Cancer. Apart from the standard treatment with broad-spectrum antibacterial agents, there are a number of situations, in clinical practice, that require a specific regimen. The duration of treatment may vary and local antibacterial guidelines should be followed in these circumstances. If a patient has an i.v. catheter, catheter-related infection (CRI) should be suspected, and blood must be cultured from the catheter and peripherally to measure the differential time to positivity (DTTP), which is the difference in time between positivity of results between catheter culture and peripheral blood culture. A DTTP of ±2 h is a highly sensitive and specific indicator of catheter-related bacteraemia [I, A] [24.Seifert H. Cornely O. Seggewiss K. et al.Bloodstream infection in neutropenic cancer patients related to short-term nontunnelled catheters determined by quantitative blood cultures, differential time to positivity, and molecular epidemiological typing with pulsed-field gel electrophoresis.J Clin Microbiol. 2003; 41: 118-123Google Scholar]. All cases of CRI in the setting of FN require decision-making on the choice and duration of i.v. antibiotics, and the need for catheter removal. When CRI is suspected, and the patient is stable, the catheter should not be removed without microbiological evidence of infection [25.Raad I. Kassar R. Ghannam D. et al.Management of the catheter in documented catheter-related coagulase-negative staphylococcal bacteremia: remove or retain?.Clin Infect Dis. 2009; 49: 1187-1194Google Scholar]. A glycopeptide such as vancomycin should be administered through the line when possible to cover Gram-positive organisms [III, A]. Teicoplanin is a useful alternative as it can be administered once daily as a line lock. Success in treating CRI without removing the catheter depends on the pathogen isolated in the blood cultures. In CRI due to CNS, an attempt at preserving the catheter can be made if the patient is stable [III, B]. Catheter retention does not have an impact on the resolution of CNS bacteraemia but is a significant risk factor for recurrence in those patients in whom the catheter was retained. Removal of the line is indicated in the context of tunnel infections, pocket infections (implanted port system) [III, B], persistent bacteraemia despite adequate treatment, atypical mycobacterial infection and candidaemia. With regard to line infections caused by S. aureus, the literature is divided. The desire to preserve the line must be balanced against the risk of metastatic spread by bloodstream seeding. The recommendation should be to remove the line if at all possible, while recognising that, with careful management, it might be possible to maintain it for a short period. Persistent fever and bacteraemia despite appropriate antibiotics are indications for line removal. If pneumonia in an outpatient is diagnosed either on clinical grounds and/or on the basis of radiological imaging, antibiotic cover may be extended to treat atypical organisms such as Legionella and Mycoplasma by adding a macrolide or a fluoroquinolone antibiotic to a &bgr;-lactam antibiotic [V, D]. Consideration for infection with Pneumocystis jirovecii should be given in patients who present with high respiratory rates and/or desaturate readily off oxygen or on minimal exertion. Predisposing factors include prior corticosteroid therapy, use of immune suppressants after organ TPL and exposure to purine analogues, as well as lack of reliable chemoprophylaxis with co-trimoxazole [26.Kovacs J.A. Masur H. Evolving health effects of Pneumocystis: one hundred years of progress of diagnosis and treatment.JAMA. 2009; 301: 2578-2585Google Scholar]. In high-risk patients with profound prolonged neutropaenia and lung infiltrates, early treatment with a mould-active antifungal agent is recommended. Patients with AML during remission induction ChT and those undergoing allogeneic haematopoietic stem cell TPL with prior conditioning ChT are at risk of invasive fungal infections (namely aspergillosis) due to prolonged and profound neutropaenia [27.Maschmeyer G. Carratalà J. Buchheidt D. et al.Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients (allogeneic SCT excluded): updated guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).Ann Oncol. 2015; 26: 21-33Google Scholar]. Frequent assessment of initial response to antibacterial therapy is essential, and, in the absence of prompt improvement, further investigations are warranted. If invasive aspergillus is suspected, a high-resolution chest computed tomography (CT) scan should be carried out on the same day, looking for typical features such as nodules with halos or ground-glass change, and galactomannan should be measured in serum. If any infiltrate is found, bronchoalveolar lavage should be undertaken if possible. Advice from an infectious diseases (ID) specialist or clinical microbiologist is recommended, and an appropriate therapy against infection with fungi or Pneumocystis species should be" @default.
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• W3048696092 title "Management of febrile neutropaenia: ESMO Clinical Practice Guidelines" @default.
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