Combination of Amikacin and either Ampicillin or Cephalotin as Initial Treatment of Febrile Neutropenic Patients

ABSTRACT. A prospective, randomized trial of two antibiotic combinations (amikacin plus either ampicillin or cephalotin) was performed on 39 consecutive episodes of fever in 30 patients with neutropenia and hematological malignancy. Infections were documented as the cause of fever in 37 episodes (95%): in 21 episodes (54%) bacteria or a virus (n=1) were isolated, and in 16 (41% of all episodes) the infection was documented clinically but no pathogen was isolated. The most frequently isolated bacteria were Staph, aureus (38% of all strains), E. coli (13%), and Pseudomonas aeruginosa (13%). Bacteremia occurred in 18% of the febrile episodes. Improvement followed treatment with the combination amikacin plus ampicllin in 73% of 19 cases, and with amikacin plus cephalotin in 55% of 20 cases (p>0.05), giving a total Improvement rate of 64%. Failure of therapy was seen in episodes caused by multiple bacteria or Pseudomonas infections. Mild signs of nephrotoxicity were noted in 13% during both regimens. Audiograms were normal in all but two patients who showed slight high-frequency hearing loss. A second infection occurred in 7 episodes (18%). Thus, the combination of amikacin plus ampidllin was as efficient (but less expensive) as amikacin plus cephalotin in the initial treatment of febrile episodes in neutropenic patients with hematological malignancies.     

A prospective study of infections in lung cancer patients admitted to the hospital

STUDY OBJECTIVES: To determine the type of infections occurring in hospitalized patients with lung cancer. DESIGN: Prospective cohort study. SETTING: Department of internal medicine in a cancer hospital. PATIENTS: All patients with lung cancer who were hospitalized for any cause and who acquired infections at the time of admission or during the hospital stay between January 1997 and February 2001. INTERVENTIONS: None. RESULTS: Two hundred seventy-five patients with lung cancer had 435 episodes of fever and/or microbiologically or otherwise documented infection. Two hundred eighteen patients (79.3%) presented with non-small cell lung carcinoma, while 49 patients (17.8%) had small cell lung cancer. The majority of the infections occurred in the tracheobronchial tree (56%). There were 38 episodes of bacteremia or fungemia, and the primary site of infection was identified in 18 cases (47%). Microbiologically documented infections accounted for 61% of the infectious episodes, and included a total of 312 microorganisms. The most frequent pathogens were Gram-negative bacteria (64%), followed by Gram-positive bacteria (25%) and fungi (8%). The predominant Gram-negative bacteria were Haemophilus influenzae and Moraxella catarrhalis. Staphylococcus aureus, Streptococcus pneumoniae, coagulase-negative staphylococci, and Enterococcus faecalis essentially represented the Gram-positive bacteria. No multiresistant bacteria were observed. Bacteria were susceptible to most of the antibiotics classically administered for their treatment. CONCLUSIONS: The predominant site of infection in patients with lung cancer is the tracheobronchial tree, with S pneumoniae, S aureus, H influenzae, Escherichia coli, Pseudomonas aeruginosa, and M catarrhalis as the principal pathogens.     

Prospective evaluation of procalcitonin in adults with febrile neutropenia after haematopoietic stem cell transplantation

Serum procalcitonin (PCT) levels have been proposed as a new discriminative marker for bacterial and fungal infections. We analysed the diagnostic relevance of PCT in febrile episodes of neutropenic adult patients after haematopoietic stem cell transplantation (HSCT). PCT was determined prospectively in 92 febrile episodes, classified according to the final diagnosis as: neutropenic fever of unknown origin (n = 51), microbiological (n = 26) or clinical (n = 5) documented infection and non-infectious febrile episodes (n = 10). On first day of fever, mean (+/- SD) PCT level was 0.3 ng/ml (0.2) in neutropenic fever of unknown origin, 0.5 ng/ml (0.7) in microbiologically confirmed infections, 0.2 ng/ml (0.2) in clinically documented infections and 1.7 (4.2) in non-infectious fever (P = not significant). Five days after the antibiotic therapy was started, fever persisted in 29 neutropenic episodes (32%). Cases that were eventually diagnosed with invasive aspergillosis had PCT values significantly higher [10.1 ng/ml (6.7)] than all remaining groups (P = 0.027; Kruskal-Wallis). Our analysis indicates that the PCT level on first day of fever did not facilitate the differential diagnosis of neutropenic febrile episode. However, when fever persisted for more than 5 d, PCT values > or = 3 ng/ml had a high sensitivity and specificity for the diagnosis of invasive aspergillosis.     

Ceftazidime as initial therapy in febrile patients with acute leukemia during induction chemotherapy. Leukemia Group of Middle Sweden.

We studied the efficacy of ceftazidime as initial monotherapy in 82 adult patients with acute leukemia who developed 123 febrile episodes during induction chemotherapy. 88% of the patients survived their febrile episode(s), whereas 10% died of infection. When assessed at 72 h after initiation of treatment (early evaluation), 43/123 episodes (35%) had been successfully treated with ceftazidime. These 43 favourable responses were seen in 15/47 (32%) microbiologically documented infections, 20/46 (43%) clinically defined infections, and 8/30 (27%) fever of unknown origin (FUO). At the resolution of fever (late evaluation) 115 episodes were evaluable, and 48% had responded successfully to ceftazidime. Successful treatment was most frequently observed in FUO, 18/29 (62%). In contrast, only 19/44 (43%) microbiologically documented infections and 18/42 (43%) clinically defined infections were cured during ceftazidime treatment. In bacteremia the response rate was only 8/26 (31%). Thus, this study shows that although ceftazidime can be safely used for initial empirical monotherapy in neutropenic leukemia patients, the need for therapy modification is high and few patients with serious infections are cured with ceftazidime alone.     

Urinary albumin excretion and its relationship to C-reactive protein and proinflammatory cytokines in patients with cancer and febrile neutropenia

The aim of the study was to evaluate urinary albumin excretion (UAE) in cancer patients with neutropenic fever and to correlate UAE with the acute-phase response and secretion of proinflammatory cytokines. UAE and serum values of C-reactive protein (CRP), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha) were measured in 32 consecutive cancer patients during episodes of neutropenic fever. UAE increased during fever reaching a peak level 36 h after the onset of fever. CRP, IL-6 and TNF-alpha had peak levels within the first 24 h. UAE correlated significantly with CRP, IL-6 and TNF-alpha. UAE was higher in patients with microbiologically documented infections than in patients with unexplained fever at the time of fever development, whereas UAE was similar in patients with either microbiologically or clinically documented infections. The results suggest a glomerular leakage of albumin secondary to an activated inflammatory response in neutropenic patients with fever. UAE may be a simple and sensitive test in monitoring the acute response to infection in the neutropenic patient.     

Imipenem-cilastatin for empirical therapy in neutropenic patients with fever: an open study in patients with hematologic malignancies

In adult neutropenic patients with hematological malignancies, we explored imipenem-cilastatin as empirical antibiotic therapy in a dose of 500 mg four times daily. Changing to second-line treatment was only resorted to if clinical deterioration, new infections or recurrence of fever occurred. A clinically or microbiologically documented infection was apparent in 115 of 150 episodes studied (76.7%). Imipenem-cilastatin was successful in 70.7% of all episodes and in 67.8% of all proven infections. Modification was necessary and successful in 22.0% of all episodes. 11 patients died while still febrile, 6 of them by infection (4%) and 5 because of progressive disease (3.3%). Imipenem-cilastatin is safe initial therapy in neutropenic febrile patients.     

Prospective screening by a panfungal polymerase chain reaction assay in patients at risk for fungal infections: implications for the management of febrile neutropenia

Invasive fungal infections are a major cause of mortality in neutropenic cancer patients. To determine whether a polymerase chain reaction (PCR)-based assay enabled the identification of patients at risk for invasive fungal infections, a prospective monitoring once per week was performed during 92 neutropenic episodes in patients receiving chemotherapy for acute leukaemia or high-dose therapy followed by allogeneic or autologous stem cell transplantation, with the investigators blinded to clinical and microbiological data. PCR positivity was documented in 34 out of 92 risk episodes. All patients developing proven invasive fungal infection were found PCR positive, and PCR was found to be the earliest indicator of invasive fungal infection preceding clinical evidence by a mean of 5.75 d (range 0-14 d). In febrile neutropenic patients without a prior history of invasive fungal infection, a sensitivity of 100% and a specificity of 73% of the PCR assay for the development of proven or probable invasive fungal infection was documented. In conclusion, panfungal PCR performed prospectively once a week enabled the identification of patients at high risk for invasive fungal infections.     

Piperacillin–Tazobactum Plus Amikacin Versus Ceftazidime Plus Amikacin as Empirical Therapy for Fever in Neutropenic Patients with Hematological Malignancies

Infections are one of the main cause of death in cancer patients particularly when granulocytopenia is present. A number of drugs have been used for the treatment of neutropenic patients with fever. Most published literature has shown piperacillin–tazobactum in combination with amikacin to be significantly more effective than ceftazidime plus amikacin in empirical treatment of febrile episodes in patients with neutropenia. In view of the reported literature we have tried this combination in our febrile neutropenic patients with haematological malignancies at PGIMS Rohtak. It was an open randomized trial. Patients were divided into two groups of 20 each. In the first group (group A) piperacillin–tazobactum (4 + 0.5 g 6 hourly) with single daily dose of amikacin 20 mg/kg was given. In the second group (group B) ceftazidime 40 mg/kg every 8 hourly with single daily dose of amikacin 20 mg/kg was given. The most common site of infection was blood followed by urinary tract, respiratory tract and oral cavity. 13 (65%) patients in group A and 12 (60%) patient in group B showed clinical success. In our study however in our patients a better response was seen in patients with piperacillin–tazobactum + amikacin (65% vs. 60%). So it is recommended that piperacillin–tazobactum + amikacin should be given in febrile neutropenic patients with haematological malignancies.     

A 12-month fever surveillance study in a veterans' long-stay institution

This report describes a 12-month fever surveillance survey in a 258-bed veterans long-term care institution. There were 128 episodes of fever (one episode per 24 patient-months); 114 were studied. Lower respiratory tract infections were most frequent, 36 (32%), with 26 (23%) urinary tract infections. Streptococcus pneumoniae was the most common pathogen in the chest infections and Proteus mirabilis the most common of the urinary tract infections. In 40 (35%) there was no evidence of a lower respiratory tract, urinary tract, or other bacterial infection. Most recovered rapidly, many with no specific treatment. There was a 16% mortality associated with the febrile episodes.     

Predictive factors of septic shock and mortality in neutropenic patients

Neutropenia is a major risk factor for developing a serious infection. Bacteremia still causes significant mortality among neutropenic patients with cancer. The purpose of this study was to identify risk factors for septic shock and for mortality in neutropenic patients with leukemia and bacteremia. Consecutive samples from 20 patients with acute myeloid leukemia and bacteremia were studied during a 1 year period (January-December 2003). All patients received empirical antibiotic therapies for febrile episodes using ceftazidime plus amikacin. About 110 neutropenic febrile episodes were noted: clinically documented 14.54%, microbiologically documented 16.36% and fever of unknown origin 69.09%. Gram-negative organism caused eight febrile episodes: Pseudomonas (5), Klebsiella (3). Gram-positive organism caused 10 episodes: Staphylococcus (6), Streptococci (2), Enterococci (2). Pulmonary infection accounted for 25% of clinically documented infections. About 14 of the 110 febrile episodes were associated with septic shock causing mortality in 7 patients. In a univariate analysis variables associated with septic shock were: pulmonary infection (OR = 17, p = 0.001), serum bicarbonate < 17 mmol/l (OR = 68, p < 0.001) and serum lactate >3 mmol/l (OR = 62, p < 0.001). Variables associated with mortality were: pulmonary infection (OR = 83, p < 0.001) and serum bicarbonate < 17 mmol/l (OR = 61, p < 0.001). In a multivariate analysis two variables were associated with septic shock: pulmonary infection (OR = 5, p = 0.043) and serum lactate >3 mmol/l (OR = 10, p = 0.003). An elevated serum lactate (>3 mmol/l) and low serum bicarbonate ( < 17 mmol/l) at the onset of bacteremia are useful biomarkers in predicting septic shock and mortality in neutropenic patients.     

A pilot study of piperacillin and ciprofloxacin as initial therapy for fever in severely neutropenic leukemia patients.

We studied the efficacy of piperacillin and ciprofloxacin as initial parenteral therapy in 41 adult patients with leukemia who developed 47 febrile episodes during severe neutropenia following chemotherapy. 40 patients (98%) survived their febrile episode(s), whereas 1 patient died of infection. When assessed at 72 h after initiation of treatment (early evaluation), 24/47 episodes (51%) had been successfully treated. These 24 favourable responses were seen in 15/24 (63%) microbiologically documented infections and 9/19 (47%) fever of unknown origin (FUO). At the resolution of fever (late evaluation) 46 episodes were evaluable, and 28 (61%) had responded successfully to piperacillin and ciprofloxacin. Successful treatment was most frequently observed in microbiologically defined infections, 18/23 (78%). Three of 5 (60%) Gram-positive, 11/12 (92%) Gram-negative and 1 of 2 mixed bacteremias were successfully treated. In contrast, only 10/19 (53%) FUO and none of 4 clinically defined infections had responded. Thus, this pilot study indicates that piperacillin and ciprofloxacin may be a safe and effective combination for the treatment of febrile episodes in severely neutropenic leukemia patients, which merits further investigation in randomized trials.     

Bloodstream infections in febrile neutropenic patients at a tertiary care center in Lebanon: a view of the past decade.

OBJECTIVES: Previous studies from Lebanon have shown Gram-negative organisms to be the predominant agents in febrile neutropenic patients. The objective of this study was to evaluate the most current epidemiological trends among patients with neutropenic fever. METHODS: This prospective observational cohort study, the largest to date in the country, was conducted at the American University of Beirut Medical Center between January 2001 and December 2003, with the objective of describing the characteristics of patients with neutropenic fever and to assess temporal trends. RESULTS: We included 177 episodes of neutropenic fever. The most common underlying malignancy was lymphoma (42.4%). Gastrointestinal and abdominal infections were predominant (31.6%) and 23.7% of cases represented fever of unknown origin. Gram-negative organisms were responsible for 78.8% (26/33) of bloodstream infections compared to 33.3% (11/33) with Gram-positive organisms. The in-hospital mortality rate in this study (12.1%) was considerably lower than in previous years. CONCLUSIONS: Gram-negative organisms are persistently predominant in our center. In a developing country like Lebanon with limited resources, lower mortality rates commensurate with worldwide reports were successfully achieved in this high-risk patient population. Protocols and guidelines should be adapted to the characteristics of individual institutions to ensure delivery of appropriate care to febrile neutropenic patients.     

Oral ciprofloxacin plus colistin: prophylaxis against bacterial infection in neutropenic patients. A strategy for the prevention of emergence of antimicrobial resistance

Following a 2-year study, the combination of oral ciprofloxacin and colistin has been used continuously for 10 years without the emergence of resistance. During a 2-year period (1987-1989), we compared ciprofloxacin + colistin (CIP + COL) with neomycin + colistin (NEO + COL) in a randomized trial--combinations chosen because of the potential for prophylaxis of Gram-negative infection by ciprofloxacin, with colistin given to reduce the risk of emergence of resistance. Sixty-four patients with similar demographics in each arm were evaluable for efficacy analysis. Patients on CIP + COL had a significantly lower proportion of neutropenic days with fever (P < 0.001) and neutropenic days on intravenous antibiotics (P < 0.001) than patients on NEO + COL. A total of 54 (15 bacteriologically documented) pyrexial episodes occurred in patients on CIP + COL and 77 (41 bacteriologically documented) in patients on NEO + COL. Only two Gram-negative bacterial infections occurred in the CIP + COL arm compared with 16 in the NEO + COL arm. No Staphylococcus aureus infections occurred in the CIP + COL group compared with 10 in the other patients. Two CIP-resistant Gram-negative bacilli were isolated from patients on CIP + COL compared with 13 NEO-resistant Gram-negative bacilli from patients on NEO + COL. Following a subsequent decade of unchanged use of this prophylactic strategy in neutropenic patients, a 2-year follow-up study between 1 January 1998 and 31 December 1999 showed 66 significant infections during 700 [corrected] neutropenic episodes. Thirty-five of the 111 (31%) isolates were ciprofloxacin-resistant, involving 5% of the neutropenic episodes [corrected].     

A multi-centre prospective study of febrile neutropenia in Norway: microbiological findings and antimicrobial susceptibility

The urgent need to treat presumptive bacterial or fungal infections in neutropenic patients has meant that initial therapy is empiric and based on the pathogens most likely to be responsible, and drug resistance. The traditional empirical treatment in Norway has been penicillin G and an aminoglycoside, and this combination has been criticized over recent y. We wished to analyse the microbiological spectrum and susceptibility patterns of pathogens causing bacteraemia in febrile neutropenic patients. This was a prospective multicentre study. During the study period of 2 y, a total of 282 episodes of fever involving 243 neutropenic patients was observed. In 34% of episodes bacteraemia was documented. Overall, 40% of the episodes were caused by Gram-positive organisms, 41% by Gram-negative organisms and 19% were polymicrobial. The most frequently isolated bacteria were Escherichia coli (25.6%), a- and non-haemolytic streptococci (15.6%), coagulase-negative staphylococci (12.4%) and Klebsiella spp. (7.4%). None of the Gram-negative isolates was resistant to gentamicin, meropenem, ceftazidime or ciprofloxacin. Only 5 coagulase-negative staphylococci isolates were resistant to both penicillin G and aminoglycoside. The overall mortality rate was 7%, and 1.2% due to confirmed bacteraemic infection.     

Procalcitonin in paediatric cancer patients: its diagnostic relevance is superior to that of C-reactive protein, interleukin 6, interleukin 8, soluble interleukin 2 receptor and soluble tumour necrosis factor receptor II

Sensitive parameters of inflammation are rare in neutropenic cancer patients. In this study, procalcitonin (PCT), C-reactive protein (CRP), interleukin 6 (IL-6), IL-8, the soluble IL-2 receptor (sIL-2R) and the soluble tumour necrosis factor receptor II (sTNFRII) were evaluated for their diagnostic relevance in febrile episodes of cancer patients. Plasma or serum levels of these parameters were determined in neutropenic children with febrile episodes (n = 122) classified according to both the kind of infection [60 cases of fever of unknown origin (FUO), 28 cases of localized infection, 13 cases of pneumonia, 20 cases of bacteraemia, one case of fungaemia] and the World Health Organization (WHO) score of chemotherapy-induced mucositis. At baseline and during the febrile episodes, the highest levels of all parameters were observed in cases of gram-negative bacteraemia. However, in FUO and localized infections, low or only slightly elevated median levels of all parameters were documented. The degree of chemotherapy-induced mucositis did not influence the value of any parameter. In comparison with the other inflammatory parameters, PCT (optimum cut-off level 0.5 microg/l) was a more sensitive and more specific parameter in the diagnosis of high-risk (gram-negative bacteraemia) and low-risk (FUO) episodes, as well as in the sequential assessment of all febrile neutropenic episodes.     

Evolution of the clinical manifestations of infection during the course of febrile neutropenia in patients with malignancy

Summary The impact of a standardized set of diagnostic interventions on the further management of 968 episodes of fever in neutropenic cancer patients who did not respond to initial therapy was assessed prospectively. At the onset of fever, 65% of patients had no additional signs of infection, whereas skin and soft tissue infections were present in 12% and clinical sepsis and gastrointestinal infections in 8% each. After 72h, 41% of the fevers still remained unexplained. New foci of infection emerged in 11% of the cases involving mainly the lungs, skin and soft tissues, and urinary tract. The presence of a lower respiratory tract infection or a microbiologically defined infection of any sort was associated with higher mortality than other types of infection were. Changes in initial antibiotic therapy were, based on the results of the diagnostic measures specified in the protocol in only 15% of the cases.     

Predictive factors of septic shock and mortality in neutropenic patients

Neutropenia is a major risk factor for developing a serious infection. Bacteremia still causes significant mortality among neutropenic patients with cancer. The purpose of this study was to identify risk factors for septic shock and for mortality in neutropenic patients with leukemia and bacteremia. Consecutive samples from 20 patients with acute myeloid leukemia and bacteremia were studied during a 1 year period (January–December 2003). All patients received empirical antibiotic therapies for febrile episodes using ceftazidime plus amikacin. About 110 neutropenic febrile episodes were noted: clinically documented 14.54%, microbiologically documented 16.36% and fever of unknown origin 69.09%. Gram-negative organism caused eight febrile episodes: Pseudomonas (5), Klebsiella (3). Gram-positive organism caused 10 episodes: Staphylococcus (6), Streptococci (2), Enterococci (2). Pulmonary infection accounted for 25% of clinically documented infections. About 14 of the 110 febrile episodes were associated with septic shock causing mortality in 7 patients. In a univariate analysis variables associated with septic shock were: pulmonary infection (OR = 17, p = 0.001), serum bicarbonate < 17 mmol/l (OR = 68, p < 0.001) and serum lactate >3 mmol/l (OR = 62, p < 0.001). Variables associated with mortality were: pulmonary infection (OR = 83, p < 0.001) and serum bicarbonate < 17 mmol/l (OR = 61, p < 0.001).

In a multivariate analysis two variables were associated with septic shock: pulmonary infection (OR = 5, p = 0.043) and serum lactate >3 mmol/l (OR = 10, p = 0.003). An elevated serum lactate (>3 mmol/l) and low serum bicarbonate (< 17 mmol/l) at the onset of bacteremia are useful biomarkers in predicting septic shock and mortality in neutropenic patients.     

Causes and empirical treatment of fever in HIV-infected adult outpatients, Abidjan, Côte d'Ivoire

OBJECTIVES: In Abidjan, HIV prevalence has been estimated at 20% in outpatients attending community clinics. Documenting causes of fever in HIV-infected adult outpatients may help to improve care in these centres with limited facilities. DESIGN: Prospective study. METHODS: We describe all diagnoses and treatments made during febrile episodes in HIV-infected adults participating in the ANRS 059 trial and followed up in a dedicated outpatient centre. RESULTS: Causes of fever could be identified in half of the 269 febrile episodes. Bacterial diseases were the leading identified cause of fever in all CD4 cell count strata (53, 56 and 43% of identified causes in episodes with CD4 count < 200 x 106/l, 200-499 x 106/l, and >or= 500 x 106/l, respectively), followed by malaria (5, 22, and 38%, respectively). Among febrile bacterial diseases, respiratory tract infections and enteritis accounted for 62% of organ involvement, and Streptococcus pneumoniae and non-typhi Salmonella represented 69% of isolated bacterial strains. In these bacterial episodes, an early empirical antibacterial treatment was associated with shorter duration of hospitalization and fever. In the 19 episodes leading to death (7%), the two leading diagnoses were atypical mycobacteriosis (26%) and acute unexplained fever (21%). Death was associated with the absence of antimalarial treatment in the group of acute unexplained fevers. CONCLUSIONS: African HIV treatment guidelines should take into account the predominant role of bacterial infections and malaria in HIV-infected adult outpatients. Reports from other African settings would be useful to compare experiences in algorithms of empirical early antibacterial and antimalarial treatments.     

Low mortality among patients with spinal cord injury and bacteremia

We reviewed 103 episodes of bacteremia in 93 patients with spinal cord injury who had bacteremia during initial hospitalization (39 patients) or readmission (54 patients) during 1978-1988. Eighteen episodes (18%) were due to polymicrobial infections. Urinary tract infections (47%), infected pressure areas (19%), and pneumonia (9%) were the most frequent primary infections and sources of the bacteremia. The bacteria most frequently associated with urinary tract infections were enterococci (26%), Escherichia coli (26%), Pseudomonas species (20%), and Klebsiella pneumoniae (12%). Bacteria most frequently isolated from patients with infected pressure areas were anaerobes and Staphylococcus aureus. Bacteremia was the cause of death for 8 patients (9%). The urinary tract was identified only once as the source of gram-negative bacteremia in an immunocompetent patient who died. The reason for the low mortality in patients with spinal cord injury is unclear.     

A prospective study on the epidemiology of febrile episodes during chemotherapy-induced neutropenia in children with cancer or after hemopoietic stem cell transplantation.

BACKGROUND: The purpose of our study was to evaluate the incidence and clinical characteristics of febrile episodes during neutropenia following chemotherapy in children with cancer. PATIENTS AND METHODS: A prospective, 3-year single-center observational study of periods of neutropenia was performed. Epidemiology and clinical diagnoses of febrile episodes occurring during the neutropenic periods were evaluated, taking into consideration different categories of anticancer treatment based on the type of tumor and phase of therapy. RESULTS: A total of 703 febrile episodes were observed during 614 (34%) of 1792 neutropenic periods (34%), for a total of 28,001 days at risk, accounting for a rate of 0.76 episodes per 30 days at risk. The highest proportions of neutropenic periods with primary febrile episodes were observed after autologous hemopoietic stem cell transplantation (58%), aggressive treatment for acute leukemia or non-Hodgkin lymphoma (48%), and allogeneic hemopoietic stem cell transplantation (44%); the lowest proportion (9%) was observed during maintenance chemotherapy for acute leukemia (P<.001). The most frequent clinical diagnosis was fever of unknown origin (in 79% of cases), followed by bacteremia (10%); invasive mycosis was diagnosed in only 2% of cases. CONCLUSIONS: The overall incidence of febrile neutropenia and severe infectious complications in children with cancer is low, with differences according to the aggressiveness of chemotherapy. This fact must be considered when designing clinical trials on the management of infectious complications in children with cancer.