Recent advances in colorectal cancer genetics and diagnostics

Children with cancer treated with chemotherapy are susceptible to bacterial infections and serious infectious complications. However, fever and neutropenia can also result from other causes, for which no antibiotic treatment is needed. In the past decades attempts have been made to stratify the heterogeneous group of pediatric cancer patients with fever and neutropenia into high- and low-risk groups for bacterial infections or infectious complications. Strategies for risk assessment have resulted in treatment regimens with early discharge or even no hospital admission at all, and/or treatment with oral or no antibiotics. We will provide a historical overview of the changing approach to low-risk fever and neutropenia, and we will also try to identify clear and objective parameters for risk assessment strategies and illustrate their relationship to innate immunity. In the future, new insights into genetic susceptibility on neutropenic fever might be of use in children with cancer with fever and neutropenia.     

Antibiotics and growth factors in the management of fever and neutropenia in cancer patients

The association of neutropenia and infection continues to be a major cause of morbidity and mortality in cancer patients receiving myelosuppressive chemotherapy. Prompt hospitalization and initiation of empirical intravenous broad-spectrum antibiotics has been the standard of care during the past three decades. Recently, risk-assessment models have been developed that allow the identification of febrile neutropenic patients that are at low risk for medical complications and mortality. New treatment strategies are being evaluated in this low-risk patient population to safely reduce toxicity, decrease costs, and improve quality of life. These include early shift from intravenous therapy to oral antibiotics, immediate initiation of oral empiric treatment, early hospital discharge, or outpatient care. A risk-based approach should also be applied to the use of colony-stimulating factors in this setting. Growth factors should not be routinely administered to neutropenic patients with uncomplicated febrile episodes. However, recent data support their use in populations with high-risk neutropenic fever.     

Clinical research in febrile neutropenia in cancer patients: Past achievements and perspectives for the future

Febrile neutropenia (FN) is responsible for significant morbidity and mortality. It can also be the reason for delaying or changing potentially effective treatments and generates substantial costs. It has been recognized for more than 50 years that empirical administration of broad spectrum antibiotics to patients with FN was associated with much improved outcomes; that has become a paradigm of management. Increase in the incidence of microorganisms resistant to many antibiotics represents a challenge for the empirical antimicrobial treatment and is a reason why antibiotics should not be used for the prevention of neutropenia. Prevention of neutropenia is best performed with the use of granulocyte colony-stimulating factors (G-CSFs). Prophylactic administration of G-CSFs significantly reduces the risk of developing FN and consequently the complications linked to that condition; moreover, the administration of G-CSF is associated with few complications, most of which are not severe. The most common reason for not using G-CSF as a prophylaxis of FN is the relatively high cost. If FN occurs, in spite of prophylaxis, empirical therapy with broad spectrum antibiotics is mandatory. However it should be adjusted to the risk of complications as established by reliable predictive instruments such as the Multinational Association for Supportive Care in Cancer. Patients predicted at a low level of risk of serious complications, can generally be treated with orally administered antibiotics and as out-patients. Patients with a high risk of complications should be hospitalized and treated intravenously. A short period of time between the onset of FN and beginning of empirical therapy is crucial in those patients. Persisting fever in spite of antimicrobial therapy in neutropenic patients requires a special diagnostic attention, since invasive fungal infection is a possible cause for it and might require the use of empirical antifungal therapy.     

Novel and innovative strategies to treat ventilator-associated pneumonia: optimizing the duration of therapy and nebulizing antimicrobial agents

Ventilator-associated pneumonia (VAP) is responsible for approximately half of the infections acquired in the intensive care unit (ICU) and represents one of the principal reasons for prescribing antibiotics in this setting. Because unnecessary prolongation of antimicrobial therapy and insufficient dosing of antibiotics at the site of infection in patients with true bacterial infection may lead to the selection of multidrug-resistant microorganisms without improving clinical outcome, efforts to reduce the duration of therapy and optimize pulmonary penetration of antimicrobial agents are warranted. An 8-day regimen can probably be standard for patients with VAP. Possible exceptions to this recommendation include immunosuppressed patients, those whose initial antimicrobial treatment was not appropriate for the causative microorganism(s), and patients whose infection was caused by very difficult-to-treat microorganisms and had no improvement in clinical signs of infection. Nebulizing concentration-dependent antibiotics such as aminoglycosides during mechanical ventilation can markedly increase tissue penetration in foci of pneumonia as compared with intravenous administration. The superiority in terms of pulmonary penetration and antibacterial efficacy of this route of administration was demonstrated in a model of ventilated piglets with and without bronchopneumonia.     

Diagnosis and management of bacterial infections in decompensated cirrhosis

Bacterial infections are one of the most frequent complications in cirrhosis and result in high mortality rates.Patients with cirrhosis have altered and impaired immunity,which favours bacterial translocation.Episodes of infections are more frequent in patients with decompensated cirrhosis than those with compensated liver disease.The most common and life-threatening infection in cirrhosis is spontaneous bacterial peritonitis followed by urinary tract infections,pneumonia,endocarditis and skin and soft-tissue infections.Patients with decompensated cirrhosis have increased risk of developing sepsis,multiple organ failure and death.Risk factors associated with the development of infections are severe liver failure,variceal bleeding,low ascitic protein level and prior episodes of spontaneous bacterial peritonitis (SBP).The prognosis of these patients is closely related to a prompt and accurate diagnosis.An appropriate treatment decreases the mortality rates.Preventive strategies are the mainstay of the management of these patients.Empirical antibiotics should be started immediately following the diagnosis of SBP and the first-line antibiotic treatment is third-generation cephalosporins.However,the efficacy of currently recommended empirical antibiotic therapy is very low in nosocomial infections including SBP,compared to community-acquired episodes.This may be associated with the emergence of infections caused by Enterococcus faecium and extended-spectrum β-lactamaseproducing Enterobacteriaceae,which are resistant to the first line antimicrobial agents used for treatment.The emergence of resistant bacteria,underlines the need to restrict the use of prophylactic antibiotics to patients with the greatest risk of infections.Nosocomial infections should be treated with wide spectrum antibiotics.Further studies of early diagnosis,prevention and treatment are needed to improve the outcomes in patients with decompensated cirrhosis.     

Autoimmune Thrombozytopenie, Neutropenie und H?molyse

Autoantibodies reduce the life span of platelets, granulocytes, and red blood cells. This may result in thrombocytopenia with bleeding, in neutropenia with infection, and in anemia, respectively. Immune-hemocytopenias can manifest as primary disease without another cause, or they are associated with other underlying morbidities such as autoimmune diseases, lymphoproliferative diseases, immune defects, or viral infections. Diagnosis is confirmed by laboratory tests showing autoantibodies against the respective blood cells. Indication for treatment is the clinical manifestation of symptoms: bleeding in autoimmune thrombocytopenia, infections in neutropenia, and symptomatic anemia, respectively. Especially in case of thrombocytopenia patients should not be treated because of abnormal laboratory values, only. To date steroids are the basic treatment in autoimmune thrombocytopenia and hemolytic anemia, while prophylactic antibiotics are the main treatment in autoimmune neutropenia. Growth factors like the new thrombopoietin receptor agnonists in autoimmune thrombocytopenia or G-CSF in autoimmune neutropenia, and anti-CD20 antibodies are new options for treatment.     

Neutropenia during combination therapy of interferon alfa and ribavirin for chronic hepatitis C

Interferon therapy of hepatitis C causes a decrease in neutrophil counts, and neutropenia is a common reason for dose adjustment or early discontinuation. However, it is unclear whether neutropenia caused by interferon is associated with an increased rate of infection. In this study, we assessed factors associated and clinical consequences of neutropenia before and during interferon therapy of chronic hepatitis C. A total of 119 patients with chronic hepatitis C treated with the combination of interferon alfa and ribavirin were analyzed. In these studies, neutropenia was not used as an exclusion or dose modification criterion. In multivariate analysis, only black race was associated with baseline neutropenia. During treatment, neutrophil counts decreased by an average of 34%. Among 3 blacks with baseline neutropenia without cirrhosis or splenomegaly, there was little or no decrease in neutrophil counts (despite typical decreases in platelet and lymphocyte counts). Documented or suspected bacterial infections developed in 22 patients (18%), but in no patient with neutropenia. United States population estimates suggest that 76,000 blacks with hepatitis C have neutrophil counts below 1,500 cells/microL and might be denied therapy if this exclusion criterion was generally applied. In conclusion, neutropenia is frequent during treatment of hepatitis C with interferon and ribavirin, but it is not usually associated with infection. Constitutional neutropenia, which is common among blacks, should not exclude patients from therapy with interferon as these patients usually have minimal further decreases in neutrophil counts on therapy and are not excessively prone to bacterial infections.     

The impact of bacterial infections on survival of patients with decompensated cirrhosis

Introduction. Bacterial infection in cirrhotic patients is a severe complication that requires early recognition and specific therapeutic care.Material and methods. In this review the various aspects of diagnosis and management of infections that may impact survival in cirrhosis are analyzed.Results. Active search for infections allows early detection and its treatment with suitable antibiotics has reduced mortality rates in spontaneous bacterial peritonitis, the main infection in patients with decompensated cirrhosis. Other common infections, such as bacteremia and septicemia or urinary tract, lung, skin and soft tissue infections must be thoroughly investigated so that antibiotic treatment can be started early. As intestinal bacterial translocation is one of the most important mechanisms for development of bacterial infections, selective intestinal decontamination is able to prevent these infections in populations at risk. After the first episode of spontaneous bacterial peritonitis, poorly absorbed oral antibiotics, such as quinolones, must be started and continued. Moreover, when there is upper gastrointestinal bleeding, infection prevention should be based on oral administration of quinolones or intravenous administration of cephalosporins, both for seven days, to avoid morbidity and early lethality. With the advent of resistance to commonly used antibiotics and recent reports of multiresistant bacteria, there is a need for stricter control when administering antibiotics to cirrhotic patients.Conclusion. Existing knowledge of therapy and prophylaxis for bacterial infections in cirrhotic patients, which undoubtedly improve survival, should be disseminated and applied in clinical practice for the benefit of the population at large.     

Fungal infections in severe acute pancreatitis

Severe acute pancreatitis (SAP) is associated with significant morbidity and mortality. The majority of deaths related to SAP are the result of infectious complications. Although bacterial infections are most commonly encountered, fungal infections are increasingly being recognized. Candida is the most common fungal infection. The occurrence of fungal infection in patients with acute pancreatitis adversely affects the clinical course, leading to a higher incidence of systemic complications, and possibly mortality as well. Important risk factors for fungal infection in patients with acute pancreatitis include broad-spectrum antibiotics, prolonged hospitalization and surgical/endoscopic interventions, use of total parenteral nutrition, and mechanical ventilation. Patients with higher severity of pancreatitis are at a greater risk. The pathogenesis of fungal infection in patients with acute pancreatitis is multifactorial. Translocation of microorganisms across the gut epithelium, lymphocyte dysfunction, and the virulence of the invading microorganisms play important roles. Histological demonstration of fungi remains the gold standard of diagnosis, but a positive biopsy is rarely obtained. The role of biomarkers in the diagnosis is being investigated. As early diagnosis and treatment can lead to improved outcome, a high index of suspicion is required for prompt diagnosis. Limiting the use of broad-spectrum antibiotics, early introduction of enteral nutrition, and timely change of vascular catheters are important preventive strategies. The role of antifungal prophylaxis remains controversial. Surgical necrosectomy with antifungal therapy is the most widely used treatment approach. Clinical trials on antifungal prophylaxis are needed, and indications for surgical intervention need to be clearly defined.     

Harnwegsinfektionen

Urinary tract infections are the most frequent bacterial infections in humans. They can occur sporadically as acute, recurrent or chronic infections. Infections of the upper and lower urinary tract are differentiated according to the clinical symptoms. Severe complications can develop during pregnancy, in patients with diabetes mellitus and in cases of chronic renal insufficiency. These factors have to be taken into account during decision-making for diagnostic and therapeutic purposes. Urinary tract infections are most often caused by Gram negative bacteria encoding corresponding virulence factors, particularly uropathogenic Escherichia coli (UPEC). The increase in antibiotic resistance impairs the empirical findings of the appropriate therapy. Therefore, urine cultures should be more frequently conducted in order to allow personalized therapy and to increase the knowledge about the local antibiotic resistance situation. Asymptomatic bacteriuria should be principally viewed as colonization of the urinary tract by potentially pathogenic microorganisms but should only be treated during pregnancy, after organ transplantation and before traumatic interventions. Recurrent and chronic infections are mainly promoted by host-specific factors. Relapses can be prevented by administration of antibiotics in reduced dosages and also by non-antibiotic-based strategies with varying degrees of success. More clinical studies are urgently needed to achieve better control of the course of disease.     

Fever of unknown origin in febrile leukopenia

Febrile neutropenia is a syndrome commonly anticipated in patients receiving treatment for cancer. Its management for the last three decades has included the prompt administration of empiric antibacterial therapy, which resulted in a reduction in mortality. Challenges remain the administration of the most appropriate empiric treatment regimen adapted to evolving and changing epidemiology of infections in neutropenic patients and resistance rates; the development of markers of early diagnosis of severe bacterial or fungal infections; the risk stratification of patients; the establishment of targeted empiric (preemptive) antifungal therapy criteria; and the containment of antimicrobial resistance that compromises effective treatment efforts, through effective antibiotic policies and implementation of infection control measures, especially hand hygiene. The need for targeted antimicrobial or antifungal prophylaxis and supportive strategies like the use of growth factors awaits further clarification.     

Changing epidemiology of infections in patients with neutropenia and cancer: emphasis on gram-positive and resistant bacteria.

Over the past 3 decades, considerable changes have occurred in the types of bacteria causing infection in febrile patients with neutropenia and cancer. Twenty years ago, gram-negative bacteria caused approximately 70% of bloodstream infections. As a probable consequence of long-dwelling intravascular devices, fluoroquinolone prophylaxis, and high-dose chemotherapy-induced mucositis, there has been a shift toward gram-positive coccal bacteremia. In most centers today, approximately 70% of bacteremic isolates are gram-positive cocci. Of potential concern is that antimicrobial-resistant gram-positive organisms are becoming increasingly frequent in patients with neutropenia. Fluoroquinolone-resistant Escherichia coli are being isolated from several cancer centers. Several "new" organisms, such as Stomatococcus mucilaginosus, Bacillus cereus, Leuconostoc species, Corynebacterium jeikeium, Rhodococcus species, Stenotrophomonas maltophilia, Moraxella catarrhalis, Burkholderia cepacia, and Bartonella species, now cause infections in these patients. Careful application of infection-control principles, judicious prophylaxis, appropriate evaluation of new antibiotics, and prompt effective therapy will maximize benefits for these patients.     

Gram-positive infections and the use of vancomycin in 550 episodes of fever and neutropenia

STUDY OBJECTIVE: To determine the appropriate role for vancomycin in neutropenic patients with cancer. To review the incidence, types, and outcome of gram-positive infections in a series of neutropenic patients with cancer. DESIGN: Retrospective review. SETTING: Inpatient units of the Medical and Pediatric Oncology Branches of the National Cancer Institute. PATIENTS: Five hundred and fifty consecutive episodes of fever and neutropenia in patients with cancer randomized prospectively on another study to receive either ceftazidime alone or combination antibiotics for initial empirical therapy. INTERVENTION: Intravenous vancomycin (dosage adjusted by serum levels). MEASUREMENTS AND MAIN RESULTS: Gram-positive organisms were the commonest of the bacterial pathogens isolated (63%). Of the 53 gram-positive organisms accounting for primary infections (isolated at initial presentation), there were 36 staphylococcal isolates (19 coagulase-negative and 17 coagulase-positive), 13 streptococcal isolates (8 non-group D and 5 group D), and 4 polymicrobial isolates. Of the 22 secondary gram-positive infections (occurring after institution of initial antibiotics), there were 10 streptococcal isolates (9 group D and 1 non-group D), 7 staphylococcal isolates (6 coagulase-negative and 1 coagulase-positive), and 5 polymicrobial isolates. Vancomycin was used to treat 26 of the 53 primary infections, but was begun only after knowledge of the isolate in 25. Vancomycin was used to treat 17 of the 22 secondary infections, and begun only after knowledge of the isolate in 14. This approach resulted in no treatment failures for the primary infections, and a single microbiological failure for the secondary infections. There was a tendency towards a greater proportion of secondary gram-positive infections in the monotherapy group compared to the combination therapy group (16 of 282 compared with 6 of 268 respectively, P2 = 0.04 by the chi-squared test); but all were treated successfully. CONCLUSION: Vancomycin need not be included in routine empirical therapy for febrile neutropenic patients, but should be added when clinical or microbiological data suggest the need.     

Infection in immunodepressed patients

Infection is an important cause of death in patients receiving cytostatic drugs or with any other impairment of host resistance. Such infections are frequently due to opportunist micro-organisms usually belonging to the endogenous flora of the patient. It is often difficult to obtain an exact diagnosis of the cause and localization of the infection. The problems associated with the prevention of infection are manifold. Exogenous infections can be prevented by proper isolation and a sterile diet. Endogenous infections can only be prevented by eradication of the patient's endogeous flora, so-called decontamination. Special attention should be given to treatment of foci of chronic infection and of the carrier state of certain microorganisms. However, the prophylactic use of antibiotics should be avoided. The curative use of antibiotics should be based on the most probable micro-organism. We consider the inventory of the patient's microflora, repeated weekly, of great help in the choice of antibiotics in cases of septicaemia of unknown aetiology. The initial therapy usually consists of a broad-spectrum combination of antibiotics, which should be bactericidal. When the causative bacteria have been isolated and the sensitivity is known, antibiotic therapy should be adjusted to the narrowest spectrum possible.     

Antimicrobial therapy of febrile complications after high-dose chemo-/radiotherapy and autologous hematopoietic stem cell transplantation--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

Infectious complications occur in 60-100% of patients following high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (HSCT), and are commonly caused by Gram-negative aerobic bacteria (such as Pseudomonas aeruginosa and enterobacteriacea e) and Gram-positive cocci (such as enterococci, streptococci and staphylococci), which should be covered by empiric first-line antibiotic therapy. Less frequently, infections are caused by fungi and anaerobic bacteria, and initial therapy does not necessarily have to cover coagulase-negative staphylococci, oxacillin-resistant S. aureus (MRSA), anaerobic bacteria and fungi. Patients who already receive antibiotics and develop pulmonary infiltrates should immediately be treated with systemic antifungals. Patients with fever and diarrhea or other signs and symptoms of gastrointestinal or perianal infection should be treated with antibiotics covering anaerobic bacteria and enterococci. Clinically stable patients with skin infections or central venous catheter-related infections can be treated with standard empiric antibiotic therapy including a beta-lactam active against Pseudomonas aeruginosa with or without an aminoglycoside, and should only receive glycopeptides if they do not respond to first-line therapy within 72 hours, become clinically unstable, have severe mucositis, or when resistance against the empiric antibiotics is demonstrated. Recombinant hematopoietic growth factors should not be added routinely but may be considered in life-threatening situations such as invasive pulmonary mycoses or sepsis.     

Antibiotic therapy for gram-negative bacteremia.

Although antibiotic therapy is the mainstay of therapy for gram-negative bacillary bacteremia, the amelioration of the underlying conditions, the correction of predisposing factors, the drainage of abscesses, the removal of infected foreign bodies, and adequate supportive care are also of paramount importance for curing the infection and should not be neglected. Beginning in the late 1960s, most of the clinical work on gram-negative infections has focused on the evaluation of new antibiotics. Numerous studies have shown that early, appropriate antibiotic treatment of gram-negative bacteremia significantly improved patients' outcomes and prevented the development of septic shock. Prescribing standard doses of antibiotics does not necessarily mean that therapeutic levels will be reached in all patients, and relapses of infections or breakthrough bacteremias can occur in patients with subinhibitory serum levels of antibiotics. The monitoring of serum concentrations of antibiotic is therefore recommended in critically ill septic patients. Whereas initial studies on the antibiotic treatment of gram-negative bacteremia were carried out in nonneutropenic patients, more recent clinical investigations have been performed almost exclusively in cancer patients with neutropenia. Studies conducted in the 1970s and 1980s among these patients have shown the following: (1) early empirical therapy reduced the mortality of gram-negative bacteremia; (2) therapy with a combination of two antibiotics, be it an extended spectrum penicillin plus an aminoglycoside or a third-generation cephalosporin, has significantly improved patients' outcomes; and (3) triple-drug combinations (i.e., a penicillin plus a cephalosporin plus an aminoglycoside) are not superior to combinations of beta-lactams and aminoglycosides. For the treatment of gram-negative bacteremia, clinicians today have a choice between well-established antibiotic combinations and broad-spectrum single-agent therapy with third-generation cephalosporins or carbapenem antibiotics. Although recent studies suggested that monotherapy could be as effective as combination therapy for the empirical treatment of fever in the neutropenic host, no definitive study has so far unquestionably demonstrated the equivalence of these treatments in patients with gram-negative bacteremias, especially those caused by P. aeruginosa, or in patients with adverse prognostic conditions, such as persistent and profound granulocytopenia. This literature should however be reviewed with great caution. Indeed, only a minority of studies have included a sufficient number of patients to confidently assess the impact of therapy on patients' outcomes. Obviously, small studies can have a significant risk of type II errors, that is, making false-negative conclusions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Oral cefixime is similar to continued intravenous antibiotics in the empirical treatment of febrile neutropenic children with cancer.

Empiric oral antibiotic therapy for febrile neutropenic cancer patients has been suggested as a means to decrease hospitalization, but the safety of this approach has not been adequately studied in children. We compared continued iv antibiotic therapy with switching treatment to orally administered cefixime in a group of selected febrile neutropenic children for whom blood cultures were sterile after 48 h of incubation. Two hundred episodes of febrile neutropenia were studied (156 patients), and 100 episodes were randomized to receive each treatment. Failure to respond to therapy was defined by documented or suspected bacterial infection, recurrent fever, or discontinuation of assigned therapy for any reason before neutropenia resolved. Rates of treatment failure were similar in the oral cefixime group (28%) and in the iv antibiotic group (27%; P=1.0). Results support the safety of oral cefixime therapy for low-risk febrile neutropenic children, a therapeutic approach that would facilitate earlier outpatient management and decrease the costs of treatment.     

Improving efficacy of antifungal therapy by polymerase chain reaction-based strategy among febrile patients with neutropenia and cancer.

Early detection of fungal infections in and corresponding early treatment of febrile patients with neutropenia and cancer have been important issues and continue to be major challenges for clinicians. The use of nested PCR to make therapeutic decisions was studied. Sequential blood samples obtained from 42 patients with neutropenia and cancer were tested by nested PCR and culture. Instead of the empirical antifungal therapy strategy, amphotericin B treatment was initiated only for patients who had 2 consecutive positive results by nested PCR. A reduced mortality rate was observed for febrile patients with neutropenia and cancer who had fungal infections. Thus, this strategy, combined with the nested PCR for early detection of fungal infection in febrile patients with neutropenia, may be used as a guideline for antifungal therapy.     

Complications of hematopoietic stem cell transplantation: Bacterial infections

Bacterial infections remain a common complication of hematopoietic stem cell transplantation (HSCT), especially in the pre-engraftment phase. The risk of bacterial infections is mainly related to neutropenia, mucositis, and the presence of vascular lines. Most parts of the world have witnessed a shift in epidemiology toward Gram-negative bacteria; a large proportion of which are resistant to fluoroquinolones, extended-spectrum beta-lactams, carbapenems, and in some units even colistin. Meticulous infection control practices are essential for prevention of bacterial infections in HSCT. The role of routine prophylactic antibiotics is limited in settings with high rates of bacterial resistance. If used, prophylactic antibiotics should be limited to high-risk patients, and the agents are selected based on local resistance profiles. Neutropenic fever is a medical emergency in most HSCT recipients. Prompt clinical evaluation is paramount, along with the intravenous administration of appropriate empiric antimicrobials, typically an antipseudomonal beta-lactam agent. Glycopeptides should only be considered if the patient is hemodynamically unstable or Gram-positive infection is suspected. Additional Gram-negative agents, such as colistin or aminoglycosides, may be added if extensive Gram-negative resistance is expected. To mitigate increasing bacterial resistance, empiric antibiotic regimens should be rationalized or discontinued as soon as possible.     

Elderly haematological patients with chemotherapy-induced febrile neutropenia have similar rates of infection and outcome to younger adults: a prospective study of risk-adapted therapy

We prospectively evaluated 131 consecutive episodes of fever and chemotherapy-induced neutropenia in 85 adults with haematological malignancies to determine whether older patients (aged < 60 years) have different causes of fever and outcome than younger adults (aged < 60 years). Patients were stratified into high-risk and low-risk groups according to previously published criteria. High-risk patients received ceftazidime plus amikacin and low-risk patients received ceftazidime alone. All patients were hospitalized until fever and neutropenia resolved. Ninety one high-risk episodes were documented: 56 occurring in older patients (mean age 69 years) and 35 in younger adults (mean age 45 years). Non-Hodkgin's lymphoma and acute myeloid leukaemia were the most frequent underlying neoplasias in both age groups. Intensity of chemotherapy was similar in both age groups. Mean neutrophil count at entry, median duration of neutropenia, rate of documented infection, incidence of bacteraemia, response to therapy, overall mortality and infectious mortality were similar in the two high-risk age subgroups. The elderly subgroup had a trend to have more Gram-negative infections and the younger patients more Gram-positive infections. In addition, 40 low-risk episodes were registered: 29 in elderly patients (mean age 68 years) and 11 in younger patients (mean age 44 years). Elderly low-risk patients had more concurrent diseases that younger ones (P = 0.124). Mean neutrophil count at entry, median duration of severe neutropenia and rate of response were similar in the two age subgroups. All low-risk patients survived. In conclusion, elderly haematological cancer patients with febrile neutropenia show similar rates of infection and outcome to younger ones.