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Risk assessment and microbiological profile of infections in paediatric cancer patients with febrile neutropenia

Latiff Z, Zulkifli SZ, Jamal R

Malays J Pathol, 2002 Dec;24(2):83-9.
PMID: 12887165

Febrile neutropenia is a common and potentially fatal problem encountered in cancer patients undergoing chemotherapy. We carried out an observational study to evaluate the possible risk factors of developing fever amongst neutropenic children with an underlying malignancy. We also looked at the microbiological profile of causative pathogens in patients with febrile neutropenia. During a study period of 1 year, a total of 90 neutropenic episodes were recorded amongst 57 patients who were on treatment and follow-up during the study period. Multivariate analysis showed that factors such as chemotherapy status, underlying disease, existing central venous catheters, presenting white blood cell counts at chemotherapy, use of steroid therapy or hospitalisation at the onset of neutropenia, were not significant risk factors for developing fever during neutropenic episodes. Although the presence of a central venous catheter was associated with a higher risk of developing fever, it did not reach statistical significance (p=0.11). Of the 90 neutropenic episodes, 59 (65.6%) developed fever and 25 of these had positive blood cultures. The causative organisms include gram-negative bacteria (64%), gram positive bacteria (16%) and fungus (20%). Of the gram-negative organisms, Klebsiella spp. predominated (28%) with the extended spectrum beta-lactamase producing strain forming the majority (16%). Amongst those with fungaemia, Candida spp. and Candida tropicalis formed the majority (8% each) of the isolates.

Matched MeSH terms: Neutropenia/epidemiology*
Surveillance study of bacteraemic episodes in febrile neutropenic children

Ariffin H, Navaratnam P, Lin HP

Int J Clin Pract, 2002 May;56(4):237-40.
PMID: 12074201

We prospectively studied the type, frequency and outcome of infections in 513 patients with 762 consecutive episodes of febrile neutropenia (FN) over a five-year period between 1995 and 1999 in a single paediatric oncology unit. The findings were then compared with a similar study carried out in our unit between 1990 and 1994. The types of bacterial isolates and sensitivity patterns were also studied to identify trends and to gauge the suitability of antibiotics chosen for empirical therapy. Bacteraemia was documented in 35.4% of FN episodes, although 70% of patients did not have an obvious site of sepsis. The majority of isolates (61.9%) were gram-negative bacteria, a consistent finding throughout the study period. Resistance to ceftazidime, amikacin and imipenem among gram-negative bacteria was 26.3%, 21.2% and 0.7%, respectively. Methicillin resistance among gram-positive bacteria was 26.3%, while no vancomycin-resistant bacteria were encountered. There were 36 sepsis-related deaths. Factors associated with a fatal outome were prolonged capillary refill time, hypotension, fever above 39 degrees C and pneumonia. Rapid neutrophil recovery was associated with a good prognosis. A change to our current choice of empirical antibiotics for FN, comprising ceftazidime/ceftriaxone and amikacin appears necessary because of the relatively high resistance rates found.

Matched MeSH terms: Neutropenia/epidemiology
Role of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A polymorphisms in irinotecan-induced neutropenia in Asian cancer patients

Jada SR, Lim R, Wong CI, Shu X, Lee SC, Zhou Q, et al.

Cancer Sci, 2007 Sep;98(9):1461-7.
PMID: 17627617

The objectives of the present study were (i) to study the pharmacogenetics of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A in three distinct healthy Asian populations (Chinese, Malays and Indians), and (ii) to investigate the polygenic influence of these polymorphic variants in irinotecan-induced neutropenia in Asian cancer patients. Pharmacokinetic and pharmacogenetic analyses were done after administration of irinotecan as a 90-min intravenous infusion of 375 mg/m(2) once every 3 weeks (n = 45). Genotypic-phenotypic correlates showed a non-significant influence of UGT1A1*28 and ABCG2 c.421C>A polymorphisms on the pharmacokinetics of SN-38 (P > 0.05), as well as severity of neutropenia (P > 0.05). Significantly higher exposure levels to SN-38 (P = 0.018), lower relative extent of glucuronidation (REG; P = 0.006) and higher biliary index (BI; P = 0.003) were found in cancer patients homozygous for the UGT1A1*6 allele compared with patients harboring the reference genotype. The mean absolute neutrophil count (ANC) was 85% lower and the prevalence of grade 4 neutropenia (ANC < or = 500/microL) was 27% in patients homozygous for UGT1A1*6 compared with the reference group. Furthermore, the presence of the UGT1A1*6 allele was associated with an approximately 3-fold increased risk of developing severe grade 4 neutropenia compared with patients harboring the reference genotype. These exploratory findings suggest that homozygosity for UGT1A1*6 allele may be associated with altered SN-38 disposition and may increase the risk of severe neutropenia in Asian cancer patients, particularly in the Chinese cancer patients who comprised 80% (n = 36) of the patient population in the present study.

Matched MeSH terms: Neutropenia/epidemiology
Causative Pathogens of Febrile Neutropaenia in Children Treated for Acute Lymphoblastic Leukaemia

Lam JC, Chai JY, Wong YL, Tan NW, Ha CT, Chan MY, et al.

Ann Acad Med Singap, 2015 Nov;44(11):530-4.
PMID: 27089960

INTRODUCTION: Treatment of acute lymphoblastic leukaemia (ALL) using intensive chemotherapy has resulted in high cure rates but also substantial morbidity. Infective complications represent a significant proportion of treatment-related toxicity. The objective of this study was to describe the microbiological aetiology and clinical outcome of episodes of chemotherapy-induced febrile neutropaenia in a cohort of children treated for ALL at our institution.
MATERIALS AND METHODS: Patients with ALL were treated with either the HKSGALL93 or the Malaysia-Singapore (Ma-Spore) 2003 chemotherapy protocols. The records of 197 patients who completed the intensive phase of treatment, defined as the period of treatment from induction, central nervous system (CNS)-directed therapy to reinduction from June 2000 to January 2010 were retrospectively reviewed.
RESULTS: There were a total of 587 episodes of febrile neutropaenia in 197 patients, translating to an overall rate of 2.98 episodes per patient. A causative pathogen was isolated in 22.7% of episodes. An equal proportion of Gram-positive bacteria (36.4%) and Gram-negative bacteria (36.4%) were most frequently isolated followed by viral pathogens (17.4%), fungal pathogens (8.4%) and other bacteria (1.2%). Fungal organisms accounted for a higher proportion of clinically severe episodes of febrile neutropaenia requiring admission to the high-dependency or intensive care unit (23.1%). The overall mortality rate from all episodes was 1.5%.
CONCLUSION: Febrile neutropaenia continues to be of concern in ALL patients undergoing intensive chemotherapy. The majority of episodes will not have an identifiable causative organism. Gram-positive bacteria and Gram-negative bacteria were the most common causative pathogens identified. With appropriate antimicrobial therapy and supportive management, the overall risk of mortality from febrile neutropaenia is extremely low.

Matched MeSH terms: Chemotherapy-Induced Febrile Neutropenia/epidemiology