Febrile Neutropenia in Patients with Solid Tumors Undergoing Intravenous Chemotherapy.

INTRODUCTION: Febrile neutropenia (FN) is a potentially life-threatening complication of systemic chemotherapy (CT) that often requires hospital admission. Delay in diagnosis and treatment are associated with higher morbidity and mortality. OBJECTIVE: We aimed to determine the factors that influence FN episodes outcomes in the emergency room (ER). METHODS: This was a retrospective study of all FN episodes (with a collected blood culture [BC]) that occurred between 2012 and 2016 at our institution. FN was defined as a temperature ≥38°C and an absolute neutrophil count (ANC) <1,000/µL, expected to decrease to <500/µL in the following week. RESULTS: Between 2012 and 2016, there were 173 FN episodes in 153/1,947 patients treated with intravenous CT. Most of these episodes (n = 121, 70%) were diagnosed in the ER, 29 in the outpatient clinic, and 23 as inpatients. In the ER, the median time was 36 min from hospital nurse triage to medical observation, and 52 min from medical observation to complete blood count specimen collection. There was a positive BC in 33 FN episodes, 72% with Gram-negative bacteria. A total of 160 FN episodes led to hospital admission and 13 were treated as outpatients. Mortality associated with the FN episode was 15% and an ANC <100/µL was predictive of increased mortality. CONCLUSION: This study confirms that FN is a serious and common complication of IV CT which must be diagnosed and treated promptly. Profound neutropenia was the only predictive factor of mortality.

Contribution of specific pathogens to bloodstream infection mortality in neutropenic patients with hematologic malignancies: Results from a multicentric surveillance cohort study.

Bloodstream infection (BSI) remains a serious complication in patients with hematologic malignancies and neutropenia. The risk factors for mortality after BSI and the contributions of BSI pathogens to mortality remain incompletely understood. We evaluated first BSI among adult neutropenic patients undergoing high-dose chemotherapy for hematologic malignancies in the setting of (a) an early disease stage of autologous (auto-HSCT) or allogeneic (allo-HSCT) hematopoietic stem cell transplantation or (b) for acute leukemia. Risk factors for intensive care admission and all-cause mortality were analyzed by multivariable logistic regression 7 and 30 days after onset of the first BSI in the first neutropenic episode. Between 2002 and 2015, 9080 patients met the study inclusion criteria, and 1424 (16%) developed BSIs, most of them during the first week of neutropenia. Mortality during neutropenia within 7 days and 30 days after BSI onset was 2.5% and 5.1%, respectively, and differed considerably between BSI pathogens. Both 7-day and 30-day mortalities were highest for Pseudomonas aeruginosa BSI (16.7% and 26.7%, respectively) and lowest for BSI due to coagulase-negative Staphylococcus spp. (CoNS) and Streptococcus spp. BSI pathogens were independently associated with 7-day mortality included P aeruginosa, Klebsiella spp., Enterobacter spp., Serratia spp., and enterococci. Only gram-negative BSI and candidemia were associated with admission to intensive care within 7 days after BSI onset. BSI caused by P aeruginosa continues to carry a particularly poor prognosis in neutropenic patients. The unexpected association between enterococcal BSI and increased mortality needs further study.

Primary peg-filgrastim prophylaxis versus filgrastim given "on demand" for neutropenia during therapy with cladribine for hairy cell leukemia.

BACKGROUND: Major advances in the treatment of patients with hairy cell leukemia (HCL) have been made following the introduction of purine analogues. The major significant short-term toxicity of cladribine therapy are neutropenia and neutropenic fever (NF) which may be life-threatening. AIM: In this retrospective study, we compared the incidence and duration of neutropenia and hospitalization in patients with HCL treated with cladribine followed by peg-filgrastim as primary prophylaxis versus daily filgrastim given "on demand" according to absolute neutrophil count (ANC). METHODS: Medical records of patients with HCL diagnosed and followed in 12 medical centers in Israel during 1985-2015 were examined for details of disease at diagnosis. The efficacy of peg-filgrastim and filgrastim was assessed by evaluating the incidence of neutropenia (ANC < 1.0 × 10 [9]/L), number and length of hospitalizations, and number of days from the last day of therapy to recovery of ANC to >1.0 × 10 [9]/L. RESULTS: The study population included 202 patients with HCL, 159 of whom (80.7%) were treated with cladribine; 78 patients (49%) required hospitalization for the administration of broad-spectrum antibiotics due to NF. Twenty-eight (19%) patients were treated with peg-filgrastim as primary prophylaxis, while 74 (64%) received filgrastim "on demand" due to neutropenia. Median length of hospitalization, and nadir duration were 8 and 18 days respectively (p = 0.71, p = 0.44). CONCLUSIONS: Infectious complications post-cladribine treatment remain high. No difference was found in terms of incidence of NF, number of febrile days, and nadir duration in patients receiving primary peg-filgrastim prophylaxis compared to filgrastim given on demand. Both approaches are justifiable, and the choice remains at the physician's discretion.

Venetoclax in patients with acute myeloid leukemia refractory to hypomethylating agents-a multicenter historical prospective study.

Patients with acute myeloid leukemia (AML) who progress after exposure to hypomethylating agents (HMA) have a dismal prognosis. We hypothesized that the addition of venetoclax, a BCL-2 inhibitor, to AML patients who previously failed HMA might overcome resistance. Adult patients (≥ 18 years) with AML were eligible if leukemia relapsed after, or was refractory to HMA. In general, in addition to venetoclax, patients continued HMA or other low-intensity therapies. Patients who previously underwent allogeneic hematopoietic cell transplantation (HCT) were also eligible. Data were analyzed in November 2018. Twenty-three patients were treated between October 2016 and October 2018 and were eligible for this study. Median age was 76 years and 6 patients had leukemia that relapsed post allogeneic HCT. None of the patients experienced tumor lysis syndrome and toxicities were as expected and manageable. Febrile neutropenia was the most common toxicity (78% of patients). Median hospitalization time was 13 days. Forty-three percent of the patients achieved CR/CRi. Overall survival (OS) was 74% at 6 months and median OS in patients who achieved remission was 10.8 months. Higher number of blasts in both bone marrow and peripheral blood was associated with lower chances of CR, while higher WBC, LDH, and bone marrow or peripheral blasts were associated with increased mortality rate. The addition of venetoclax to patients with HMA-refractory AML may result in a substantial anti-leukemic activity, specifically in those achieving complete remission. This should be further tested in a well-designed prospective trial.

DCEP as a bridge to ongoing therapies for advanced relapsed and/or refractory multiple myeloma.

There is limited data describing dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) in relapsed refractory multiple myeloma (RRMM). We reviewed 65 patients with RRMM receiving DCEP between 2005 and 2017 in two Melbourne Hospitals. Patients had received a mean of three prior treatment lines (range, 1-11). The mean number of cycles of DCEP was two (range, 1-4). Overall response rate (ORR) was 55% whilst 19% achieved MR and SD. Median overall survival (OS) was 9.6 months. Those bridged to autologous stem cell transplant (ASCT) had significantly improved OS compared to those who were not (median 32.8 vs. 10.7 months, p=.0004). Significant treatment-related mortality (TRM) was observed (9.7%), mostly attributable to grade 3-4 neutropenia and febrile neutropenia. Mandatory use of G-CSF is, therefore, warranted to prevent septic complications. In heavily pretreated RRMM, DCEP is an effective bridge to definitive therapy but in the absence of the latter, its value is questionable.

FACTORS ASSOCIATED WITH TREATMENT OUTCOME OF PEDIATRIC CANCERPATIENTS ADMITTED WITH FEBRILE NEUTROPENIA IN TIKURANBESSA SPECIALIZED TEACHING HOSPITAL, ADDIS ABABA, ETHIOPIA.

Background: Cancer treatment is associated with variable degrees of myelosupression. Infection is often a life-threatening complication of chemotherapy-induced neutropenia, and it is also considered an oncologic emergency. Febrile neutropenia is a common, costly and potentially fatal complication in oncology. Objective: To assess factors affecting treatment outcome of cancer patients with chemotherapy induced febrile neutropenia. Method: We conducted a review of records of pediatric patients hospitalized and treated for chemotherapy-induced febrile neutropenia from January 1, 2013 to December 31, 2013 and met the selection criteria. Result: A total of 60 patients (36 males and 24 females) fulfilled the selection criteria. Twelve of them died while in hospital. The mean (SD) age of patients who died was 4.78 (±2.48) years and the mean (SD) hospital stay before death was 20.2 (±5.26) days. Ten children had hematologic malignancy and two had a solid tumor. Ten of the 12 patients had an absolute neutrophil count of less than 100/mm3 (p=0.008, OR=20.3) and a platelet count of less than 50,000/mm3. Six of the 10 children (10%) had sepsis. Patients with profound neutropenia, platelet count of less than 50,000 and sepsis were more likely to die (P=0.048, OR=7). Conclusion: The result of this study showed that absolute neutrophil count of less than 100/mm3, platelet count of less than 50,000/mm3 and a diagnosis of sepsis were factors affecting outcome patients with febrile neutropenia. Careful evaluation of these factors and assessing severity of patients' clinical condition at time of admission can be useful for triaging children with febrile neutropenia.

Infection-related complications during treatment for childhood acute lymphoblastic leukemia.

Background: Comprehensive studies on neutropenia and infection-related complications in patients with acute lymphoblastic leukemia (ALL) are lacking. Patients and methods: We evaluated infection-related complications that were grade ≥3 on National Cancer Institute's Common Terminology Criteria for Adverse Events (version 3.0) and their risk factors in 409 children with newly diagnosed ALL throughout the treatment period. Results: Of the 2420 infection episodes, febrile neutropenia and clinically or microbiologically documented infection were seen in 1107 and 1313 episodes, respectively. Among documented infection episodes, upper respiratory tract was the most common site (n = 389), followed by ear (n = 151), bloodstream (n = 147), and gastrointestinal tract (n = 145) infections. These episodes were more common during intensified therapy phases such as remission induction and reinduction, but respiratory and ear infections, presumably viral in origin, also occurred during continuation phases. The 3-year cumulative incidence of infection-related death was low (1.0±0.9%, n = 4), including 2 from Bacillus cereus bacteremia. There was no fungal infection-related mortality. Age 1-9.9 years at diagnosis was associated with febrile neutropenia (P = 0.002) during induction and febrile neutropenia and documented infection (both P < 0.001) during later continuation. White race was associated with documented infection (P = 0.034) during induction. Compared with low-risk patients, standard- and high-risk patients received more intensive therapy during early continuation and had higher incidences of febrile neutropenia (P < 0.001) and documented infections (P = 0.043). Furthermore, poor neutrophil surge after dexamethasone pulses during continuation, which can reflect the poor bone marrow reserve, was associated with infections (P < 0.001). Conclusions: The incidence of infection-related death was low. However, young age, white race, intensive chemotherapy, and lack of neutrophil surge after dexamethasone treatment were associated with infection-related complications. Close monitoring for prompt administration of antibiotics and modification of chemotherapy should be considered in these patients.

[Mortality of hematology-oncology patients with neutropenia in intensivecare]. / Letalität hämatoonkologischer Patienten in Neutropenie auf der Intensivstation.

BACKGROUND: Febrile neutropenia remains one of the most common reasons for hospital admission of patients with underlying oncologic disease. These patients have an up to 10-fold increased risk of developing sepsis, which often leads to these patients being transferred to the intensive care unit (ICU). The survival of neutropenic patients with sepsis in particular has improved in recent years, due to advanced therapy in intensive care (surviving sepsis campaign); however few large international studies of neutropenic cancer patients in the ICU are available. METHODS: In a retrospective study, 59 episodes of neutropenic cancer patients in the internal medicine ICU at the University Hospital of Cologne over a period of 2 years were analyzed. RESULTS: Pneumonia with or without sepsis are the main admission diagnoses of neutropenic cancer patients in the ICU. The mortality rate of these patients is very high (50.8 %). Pneumonia and sepsis, stem cell transplantation, mechanical ventilation, and acute renal failure with or without dialysis are correlated with mortality. CONCLUSION: Cancer patients should be admitted immediately to the ICU if they have signs of sepsis for early monitoring and treatment. Neutropenic patients have an increased risk for infectious complications and a risk for sepsis with higher mortality rates.

[Management of febrile neutropenias in adolescents and young adults: Differences of practice between adult and pediatric units]. / Gestion des aplasies fébriles chez les adolescents et jeunes adultes: différences de pratiques entre secteurs adultes et pédiatriques.

INTRODUCTION: Adolescents and young adults (AYA, 15-25years old) with cancer are treated either in adult or pediatric units. Management of febrile neutropenia (FN) is different between these units. Monitoring rules and indications of hospitalization are often stricter in pediatrics. This study evaluates if these differences influence the occurrence of complications. METHODS: The medical records of AYA patients treated in our institution in the Euro-E-W-I-N-G99 protocol between 01/09/2000 and 31/05/2013 were retrospectively analyzed. We studied febrile neutropenias occurring after VIDE courses, during the induction period. RESULTS: Forty-four patients were included (18 from adult units, 26 from pediatrics). Median age at inclusion was 19.6. After 260 courses of VIDE, we observed a median of 2 FN per adult and 3 per pediatric patient (P=0.2). Hospitalization occurred in median 1.5 time per adult and 3 per pediatric patient (P=0.008). Median cumulated length of stay was 4.5days for adults versus 16 days for pediatric patients (P=0.008). There was no significant difference for survival, number of documented infections, transfusions, dose modifications, chemotherapy delay, need for intensive care, infection after post-induction surgery. CONCLUSION: AYA treated in adult services are less frequently hospitalized for FN with no difference in morbi-mortality. Homogeneous recommendations could be made for these patients, whatever the units they are treated in.

Can mortality of cancer patients with fever and neutropenia be improved?

PURPOSE OF REVIEW: Neutropenic fever is the most common infective complication in patients receiving cytotoxic chemotherapy, and may result in severe sepsis, septic shock and mortality. Advancements in approaches to empiric antimicrobial therapy and prophylaxis have resulted in improved outcomes. Mortality may, however, still be as high as 50% in high-risk cancer populations. The objective of this review is to summarize factors associated with reduced mortality in patients with neutropenic fever, highlighting components of clinical care with potential for inclusion in quality improvement programs. RECENT FINDINGS: Risks for mortality are multifactorial, and include patient, disease and treatment-related factors. Historically, guidelines for management of neutropenic fever have focused upon antimicrobial therapy. There is, however, a recognized need for early identification of sepsis to enable timely administration of antibiotic therapy and for this to be integrated with a whole of systems approach within healthcare facilities. Use of Systemic Inflammatory Response Syndrome criteria is beneficial, but validation is required in neutropenic fever populations. SUMMARY: In the context of emerging and increasing infections because of antimicrobial-resistant bacteria in patients with neutropenic fever, quality improvement initiatives to reduce mortality must encompass antimicrobial stewardship, early detection of sepsis, and use of valid tools for clinical assessment. C-reactive protein and procalcitonin hold potential for inclusion into clinical pathways for management of neutropenic fever.

Adrenomedullin--A New Marker in Febrile Neutropenia: Comparison With CRP and Procalcitonin.

In this study, we aimed to determine serum adrenomedullin levels and compare them with levels of C-reactive protein (CRP) and procalcitonin (PCT). Cancer patients aged 0-18 years who experienced febrile neutropenia attacks were included in the study. Adrenomedullin, CRP, and PCT were analyzed at admission, day 3, and days 7-10 later. Fifty episodes of febrile neutropenia that developed in 37 patients were analyzed in this study. The mean age of the patients was 7.5 ± 4.7 (1-18) years. The patients had leukemia (73%), solid tumors (19%), and lymphoma (8%). The percentages of the patients in the clinically documented infection (CDI), fever of unknown origin (FUO), sepsis, and microbiological documented infection (MDI) categories were 34%, 34%, 20%, and 12%, respectively. During the study period, four patients were lost. In the MDI group, adrenomedullin levels on day 3 were significantly higher than those in the CDI and FUO groups. PCT levels were significantly higher in the sepsis group than those in the CDI group at admission, day 3, and days 7-10. In the sepsis group, PCT levels on days 7-10 days were significantly higher than those in the sepsis group. PCT values from the deceased patients on days 7-10 were significantly higher than those from patients who survived. CRP levels did not differ significantly among the febrile neutropenia groups. First, in our study, adrenomedullin was used as a biomarker in the febrile neutropenia episodes of children with cancer. Among adrenomedullin, CRP, and PCT, procalcitonin demonstrates the highest correlation with the severity of infection.

Capecitabine pattern of usage, rate of febrile neutropaenia and treatment related death in asian cancer patients in clinical practice.

BACKGROUND: Oral capecitabine is increasingly replacing intravenous 5-fluorouracil in many chemotherapy regimens. However, data on the risk of febrile neutropaenia (FN) and treatment related death (TRD) with the drug remain sparse outside of clinical trial settings despite its widespread usage. This study aimed to determine these rates in a large cohort of patients treated in the University of Malaya Medical Centre (UMMC). MATERIALS AND METHODS: We reviewed the clinical notes of all patients prescribed with oral capecitabine chemotherapy for any tumour sites in University Malaya Medical Centre (UMMC) from 1st January 2009 till 31st June 2010. Information collected included patient demographics, histopathological features, treatment received including the different chemotherapy regimens and intent of treatment whether the chemotherapy was given for neoadjuvant, concurrent with radiation, adjuvant or palliative intent. The aim of this study is to establish the pattern of usage, FN and TRD rates with capecitabine in clinical practice outside of clinical trial setting. FN is defined as an oral temperature >38.5°or two consecutive readings of >38.0° for 2 hours and an absolute neutrophil count <0.5 x 109/L, or expected to fall below 0.5 x 109/L (de Naurois et al., 2010). Treatment related death was defined as death occurring during or within 30 days of last chemotherapy treatment. RESULTS: Between 1st January 2009 and 30th June 2010, 274 patients were treated with capecitabine chemotherapy in UMMC. The mean age was 58 years (range 22 to 82 years). Capecitabine was used in 14 different tumour sites with the colorectal site predominating with a total of 128 cases (46.7%), followed by breast cancer (35.8%). Capecitabine was most commonly used in the palliative setting accounting for 63.9% of the cases, followed by the adjuvant setting (19.7%). The most common regimen was single agent capecitabine with 129 cases (47.1%). The other common regimens were XELOX (21.5%) and ECX (10.2%). The main result of this study showed an overall FN rate of 2.2% (6/274). The overall TRD rate was 5.1% (14/274). The FN rate for the single agent capecitabine regimen was 1.6% (2/129) and the TRD rate was 5.4% (7/129). All the TRDs were with single agent capecitabine regimen were used for palliative intent. CONCLUSIONS: Oral capecitabine is used widely in clinical practice in a myriad of tumour sites and bears a low risk of febrile neutropaenia. However, capecitabine like any other intravenous chemotherapeutic agent carries a significant risk of treatment related death.

Impact of time to antibiotics on outcomes of chemotherapy-induced febrile neutropenia.

PURPOSE: The aim of this study was to determine the relationship between the time to antibiotic administration and patients' outcomes of febrile neutropenia (FN). We also investigated the relationship between the time to antibiotics and mortality rates in a subgroup of patients with bacteremia or severe sepsis or septic shock. METHODS: From the Neutropenic Fever Registry, we analyzed 1001 consecutive FN episodes diagnosed from November 1, 2011, to August 31, 2014. Timing cutoffs for antibiotics included the following: ≤1 vs. >1 h, ≤2 vs. >2 h, ≤3 vs. >3 h, and ≤4 vs. >4 h. Multivariate logistic regression was used to adjust for potential confounders in the association between timing intervals and outcomes of FN episodes. RESULTS: The median length of time from triage to antibiotics was 140 min (interquartile range, 110-180 min). At each time cutoff, the time from triage to antibiotic administration was not significantly associated with FN outcomes after adjusting for potential confounders. Antibiotic timing was not significantly associated with complication rates in overall FN episodes. We failed to find a significant relationship between antibiotic timing and mortality in FN episodes with severe sepsis or septic shock or with bacteremia. Procalcitonin concentration and the Multinational Association for Supportive Care in Cancer (MASCC) risk index score were found to be more crucial determinants of outcomes in patients with FN. CONCLUSIONS: The time to antibiotic administration is not a major factor in FN outcomes.

Mortality, length of stay, and health care costs of febrile neutropenia-related hospitalizations among patients with breast cancer in the United States.

PURPOSE: Febrile neutropenia is a potentially life threatening complication of breast cancer chemotherapy associated with a significant amount of morbidity, mortality, and health care resource utilization. Recent data on the national estimates of mortality rate, length of stay, and health care costs among the subpopulation of febrile neutropenia admissions with breast cancer are lacking. METHODS: We used the Nationwide Inpatient Sample database to identify patients with breast cancer hospitalized for febrile neutropenia from 2009 to 2011. We derived data on inhospital mortality rate, length of stay, and mean health care costs and compared it with previous studies. RESULTS: The average inhospital mortality rate during 2009-2011 was 2.6 % (n = 685). Advanced age (≥ 65 years) was found to be significantly associated with a higher odds of mortality (4.4 vs 1.7 %, OR 2.7, 95 % CI 2.3-3.1, p < 0.01). The mean length of stay was 5.7 days (95 % CI 5.5-5.9 days), whereas the mean cost of hospitalization was $37,087 (95 % CI $34,009-$40,165). CONCLUSION: Febrile neutropenia-related hospitalizations continue to account for significant morbidity, mortality, and health care resource utilization among patients with breast cancer. Further efforts should be focused on curtailing the rising health care costs without compromising the quality of care.

Cytidine deaminase polymorphism predicts toxicity of gemcitabine-based chemotherapy.

BACKGROUND: The aim of this study was to ascertain whether single nucleotide polymorphisms of cytidine deaminase (CDA), a key enzyme in the metabolism pathway of gemcitabine, could predict clinical outcomes of cancer patients with gemcitabine-based chemotherapy. METHODS: We searched MEDLINE and EMBASE up to January 2013 to identify eligible studies. A rigorous quality assessment of eligible studies was conducted according to the Newcastle-Ottawa Quality Assessment Scale. For each included study, the overall survival (OS), overall response rate (ORR) and toxicities were extracted and pooled using random-effects model. RESULTS: In total, data from 13 studies were included. CDA 208A>G and CDA 435C>T were not included in quantified synthesis due to limited data. CDA 79A>C polymorphism was not significantly associated with OS; however, patients carrying the variant CDA 79C allele were likely to have a poor survival, hazard ratio (HR)=1.03, 95% CI 0.957-1.27 (AC+CC vs. AA). CDA 79A>C polymorphism did not correlated with ORR, odds ratio (OR)=0.719, 95% CI 0.363-1.425 (AC+CC vs. AA). However, patients with the variant CDA 79C allele would experience more grade ≥ 3 leucopenia (OR=2.933, 95% CI 1.357-6.605) and tended to have more severe neutropenia (OR=1.313, 95% CI 0.157-10.981). CONCLUSIONS: These results suggest that CDA 79A>C polymorphisms is a potential biomarker for toxicity of gemcitabine-based chemotherapy and a CDA testing before gemcitabine administration is preferred.

Risk and Consequences of Chemotherapy-Induced Febrile Neutropenia in Patients With Metastatic Solid Tumors.

PURPOSE: Although studies have evaluated the risk and consequences of febrile neutropenia (FN) among patients receiving cancer chemotherapy in US clinical practice, none have focused on a broad group of patients with metastatic disease. METHODS: A retrospective cohort design and health care claims (2006 to 2011) from private health plans covering a geographically diverse US population of > 30 million persons annually were used. The study population included adults who underwent myelosuppressive chemotherapy for metastatic cancer of the breast (MBC), colon/rectum (MCRC), lung (MLC), ovaries (MOC), or prostate (MPC). For each patient, the first chemotherapy course and each cycle therein, along with each episode of FN and the consequences thereof, were identified. RESULTS: The most common regimens, by cancer type, were paclitaxel (18% of 15,318 patients with MBC); oxaliplatin, fluorouracil, and leucovorin (23% of 16,923 patients with MCRC); carboplatin plus paclitaxel (23% of 21,999 patients with MLC); carboplatin plus paclitaxel (49% of 7,433 patients with MOC); and docetaxel (68% of 4,667 patients with MPC). Across cancers, FN occurred in 13.1% to 20.6% of patients during their chemotherapy course, most often required hospitalization (89% to 94%), and most often occurred in the first cycle (23% to 36%). Among hospitalized patients with FN, mean length of stay ranged from 7.0 to 7.5 days, and inpatient mortality ranged from 3.9% to 10.3%; mean FN-related costs during the cycle ranged from $16,291 to $19,456. CONCLUSION: Among patients receiving myelosuppressive chemotherapy for metastatic cancer in US clinical practice, FN is a frequent complication, associated with significant morbidity, mortality, and economic costs, and should be given careful consideration in the treatment of this population.

Results of a multicenter, controlled, randomized clinical trial evaluating the combination of piperacillin/tazobactam and tigecycline in high-risk hematologic patients with cancer with febrile neutropenia.

PURPOSE: Empiric antibiotic monotherapy is considered the standard of treatment for febrile neutropenic patients with cancer, but this approach may be inadequate because of the increasing prevalence of infections caused by multidrug resistant (MDR) bacteria. PATIENTS AND METHODS: In this multicenter, open-label, randomized, superiority trial, adult, febrile, high-risk neutropenic patients (FhrNPs) with hematologic malignancies were randomly assigned to receive piperacillin/tazobactam (4.5 g intravenously every 8 hours) with or without tigecycline (50 mg intravenously every 12 hours; loading dose 100 mg). The primary end point was resolution of febrile episode without modifications of the initial allocated treatment. RESULTS: Three hundred ninety FhrNPs were enrolled (combination/monotherapy, 187/203) and were included in the intention-to-treat analysis (ITTA). The ITTA revealed a successful outcome in 67.9% v 44.3% of patients who had received combination therapy and monotherapy, respectively (127/187 v 90/203; absolute difference in risk (adr), 23.6%; 95% CI, 14% to 33%; P < .001). The combination regimen proved better than monotherapy in bacteremias (adr, 32.8%; 95% CI, 19% to 46%; P < .001) and in clinically documented infections (adr, 36%; 95% CI, 9% to 64%; P < .01). Mortality and number of adverse effects were limited and similar in the two groups. CONCLUSION: The combination of piperacillin/tazobactam and tigecycline is safe, well tolerated, and more effective than piperacillin/tazobactam alone in febrile, high-risk, neutropenic hematologic patients with cancer. In epidemiologic settings characterized by a high prevalence of infections because of MDR microorganisms, this combination could be considered as one of the first-line empiric antibiotic therapies.

Risk predictors for adverse outcome in pediatric febrile neutropenia: Single center experience from a low and middle-income country.

BACKGROUND: Risk stratification of patients with febrile neutropenia (FN) into those at "High Risk" and "Low Risk" of developing complications helps in making decisions regarding optimal treatment, such as whether to treat with oral or intravenous antibiotics, whether to treat as inpatient or outpatient and how long to treat. Risk predictors obtained from Western studies on pediatric FN are unlikely to be relevant to low middle-income country (LMICs). Our study aimed to identify clinical and laboratory parameters predictive of poor outcomes in children with chemotherapy-induced FN in a LMIC. PROCEDURE: Two hundred and fifty consecutive episodes of chemotherapy-induced FN in pediatric (<15 years) patients were analyzed prospectively. Adverse outcomes were defined as per SPOG 2003 FN study as serious medical complications (SMC) due to infection, microbiologically defined infection, and radiologically defined pneumonia (RDP). Variables found to be significant for adverse outcome (P < 0.05) on univariate analysis were selected for multivariate analysis. RESULTS: Five factors that were found to independently predict adverse outcome were (a) previously documented infection in the past 6 months, (b) presence of significant focus of infection, (c) absolute phagocyte count <100/mm3, (d) peak temperature more than 39°C in this episode of FN, and (e) fever lasting more than 5 days during this episode of FN. CONCLUSIONS: Identifying the risk factors for adverse outcome in pediatric FN, which are objective and applicable across LMICs would contribute in developing guidelines for the management of FN in a resource-limited setting.

Factors predicting outcome in high risk febrile neutropenia in patients receiving intensive chemotherapy for acute sleukemia: A prospective, observational study from South India.

BACKGROUND: Outcome of febrile neutropenia (FN) in acute leukemia patients undergoing intensive chemotherapy from India is scanty. MATERIALS AND METHODS: A prospective, observational, single institutional study was conducted to evaluate the clinical features, microbiological aspects, risk factors influencing the outcome of high risk FN during intensive therapy in acute leukemia. RESULTS: Among 115 febrile episodes, though 94 (81.7%) had indwelling central venous catheter (CVC) at the time of diagnosis of FN, infective foci clinically were identified in 70.4% of episodes, with lung as the major site (25.2%) followed by CVC (17.4%). Microbiological documentation was possible in 33% (n = 40) episodes. Gram-negative bacteria isolates were 58.3% and Gram-positive isolates were 41.7% of which Pseudomonas was the predominant Gram-negative and Staphylococcus aureus was the most common Gram-positive isolate. Piperacillin-tazobactam + amikacin were used as first line antibiotic in 93% episodes and second line antibiotics were necessary in 73% episodes. Granulocyte colony stimulating factor was used in 60.9% episodes of high risk FN mostly in acute myeloid leukemia consolidation patients. Eighteen episodes (15.7%) were assigned to have invasive fungal disease. Eleven (9.6%) out of 115 high risk FN had a fatal outcome. Presence of pulmonary infection predicted for fatal outcome (P = 0.02). CONCLUSION: This study reports the outcome of high risk FN in patients with acute leukemia undergoing intensive chemotherapy. Gram-negative isolates are highly sensitive to piperacillin-tazobactum and hence in a cost restraint scenario, carbapenems needs to be judiciously used. Focus of Infection in lungs during FN predicted higher fatal outcomes.

Evaluation of factors associated with prolonged hospital stay and outcome of febrile neutropenic patients receiving chemotherapy: 70 cases (1997-2010).

Febrile neutropenia (FN) is an important sequela in veterinary patients receiving chemotherapy. The purpose of this study was to identify factors associated with prolonged hospital stay and outcome in canine patients developing FN secondary to chemotherapy administration. Medical records of 70 dogs treated for FN at the University of Pennsylvania from 1997 to 2010 were retrospectively evaluated. The mean interval between chemotherapy and hospitalization was 7 days. Two-thirds of treated patients had lymphoma. The majority of patients (70%) received vincristine or doxorubicin prior to the development of FN. Tachycardia at admission, complicating medical issues, G-CSF use and decreasing neutrophil count after admission were associated with prolonged hospital stay. Hypotension and G-CSF use were significantly associated with death in-hospital. Mortality was 8.5%. Identification of factors associated with prolonged hospital stay and mortality in patients with FN may enable the development of risk-adapted treatment guidelines to minimize chemotherapy-associated morbidity and mortality.