Antibiotics For Febrile Neutropenia Research Articles

Approach to febrile neutropenia in patients undergoing treatments for hematologic malignancies.

Febrile neutropenia (FN) is common among hematologic malignancy patients, including recipients of hematopoietic cell transplantation (HCT) and cellular therapies such as chimeric antigen receptor (CAR)-T-cell therapy. Prompt empiric antibiotic use has been the mainstay for decades but a "one-size-fits-all" approach is no longer broadly accepted, as treatment-related infectious risk are more understood. Growing antimicrobial resistance is an increasing clinical challenge. Evolving strategies on de-escalation of broad-spectrum antibiotics in FN without identified infection are areas of particular interest.

The Value of Metagenomic Next-Generation Sequencing in Hematological Malignancy Patients with Febrile Neutropenia After Empiric Antibiotic Treatment Failure.

BackgroundIt was crucial to use empirical antibiotics in febrile neutropenia (FN) patients. However, most patients still died from infection due to poor efficacy. Metagenomic next-generation sequencing (mNGS) is a rapid microbiological diagnostic method. The value of mNGS in patients with FN remains to be studied, especially after empiric antibiotic treatment.MethodsWe retrospectively analyzed the differences between mNGS and the traditional methods in 192 patients with hematological malignancies who have received empiric antibiotic treatment. Samples were collected when patient had chills or half an hour before peak body temperature. And we compared the differences between FN and non-FN patients, mainly including types of pathogens and the diagnostic value of different pathogens.ResultsDespite receiving empirical treatment, the pathogen detection rate of mNGS was significantly higher than the traditional method (80.21% vs 25.00%, P<0.001). And it has obvious advantages in detecting mixed pathogens infection (80.21% vs 4.17%, P<0.001). Then, we found that mNGS saw more pathogens in the FN than in the non-FN group, especially fungus. 21/33 (63.63%) of FN patients was diagnosed with fungal infections. The fungal detection rate in FN was significantly higher than non-FN group (32.35% vs 12.22%, P=0.001). Besides, the sensitivity of mNGS was higher than the traditional methods in both FN and non-FN group (P<0.001), but no significant difference in specificity (P>0.05). In the FN group, empiric antibiotic treatment of 46/102 (45.10%) patients did not treat all the pathogens detected by mNGS. After adjusting the antimicrobial regimen according to the results of mNGS, the effective rate at 72 hours and 7 days was 22/46 (47.83%) and 24/102 (52.17%), respectively.ConclusionmNGS had a significant impact on the diagnosis of infection and the second-line antimicrobial therapy in FN. mNGS plays a more important role in FN patients, especially in the diagnosis of fungal infections.PurposeFirstly, we compared the difference between mNGS and the traditional methods in the diagnosis of infection. Secondly, we assessed the value of mNGS in FN patients by comparing it with non-FN patients, including types of pathogens and the diagnostic value of different pathogens. In order to show that mNGS plays a more important role in FN.

Understanding mortality among hematology oncology patients identified from hospital administrative data.

215 Background: Hospital administrative data has large ramifications for quality of care and quality improvement projects. Unexpected inpatient mortality among patients with a hematology/oncology (H/O) diagnostic related group (DRG) is not widely studied and reported. We sought to investigate the unexpected inpatient mortality rate among cancer patients who were admitted to a large, urban, tertiary care safety net teaching hospital. Methods: We obtained the hospital’s adjusted mortality rate and evaluated the subset of specific observed/expected deaths ratio (O/E) of patients with a primary H/O diagnosis. We reviewed each case that was identified as an unexpected inpatient mortality from 2016 to 2018. A chart abstraction tool was designed for data abstraction that included demographics, location of admission, comorbid conditions, if mortality was expected, if documentation was reflective of the severity of the illness. Two independent reviewers abstracted each chart. A third reviewer assessed each case to make a final determination regarding expected mortality based on medical complexity and if documentation was reflective of severity of illness. Results: On review of the inpatient mortality data, the O/E for the H/O diagnostic related group (DRG) from Vizient was 1.14. Twenty two cases were identified as having an unexpected death. Among those cases, 23% of patients were transferred from an outside hospital, and 23% of patients did not have a known cancer diagnosis on admission. In the majority of cases, initial documentation did not accurately reflect severity of illness and/or specialists in hematology or oncology were not consulted at time of diagnosis. We noted the majority of patients were not followed by a hematologist/oncologist within the hospital system (63.6%). In 55% of patients, the cause of death was acute respiratory failure, and 14% of patients had an Advance Directive/DNAR in the chart prior to admission. Delayed antibiotics in febrile neutropenia and a missed blood transfusion reaction were among causes of unexpected deaths. Conclusions: Hospital generated data reported that mortality among H/O patients was greater than projected, however careful chart review of each case demonstrated a significant number of cases that were expected but the severity of illness was not documented properly to account for the death. Templates for proper documentation using the Vizient mortality variables is a key area to lower unexpected inpatient mortality.

An Homage to Two Explorers of Uncharted Cancer Waters

An Homage to Two Explorers of Uncharted Cancer Waters

A nonrandomized study on compliance with IDSA guidelines on the choice and dosing of empiric antibiotics for patients with febrile neutropenia after implementation of a new Computerized Physician Order Entry (CPOE).

48 Background: More than 80% of patients with hematologic malignancies and 10-50% of patients with solid tumors are expected to experience fever after one cycle of chemotherapy. Studies have shown all-cause mortality to be 15% higher in cancer patients with febrile neutropenia than comparably matched patients without febrile neutropenia and compliance for choice of empiric antibiotics in febrile neutropenia to be as low as 56%. Methods: We conducted a retrospective chart review of patients who presented with febrile neutropenia to our institution for one year prior to and after implementation of a CPOE set. Data was collected on basic demographics, oncological diagnosis, labs, choice of antibiotics and dosing frequency. Awareness sessions were conducted among admitting staff following the initial retrospective analysis followed by implementation of a CPOE set in order to improve guideline concordant management of febrile neutropenia patients. The IDSA risk was assessed based on the above data and the pre and post order set compliance with IDSA guidelines were compared. Fisher’s exact test was applied to assess the percentage of compliance before and after implementation of the order set, with significance set at two-sided p value &lt; 0.05. Results: Among the patients managed before order set, 15 of the total 26 (58%) were found to be non compliant with IDSA guidelines in terms of either antibiotic choice or dosing frequency. A post order set analysis showed that only 7/27 (26%) were non compliant with IDSA guidelines. The Fisher exact test showed a statistically significant value of 0.0267 (p &lt; 0.05). Conclusions: Education and implementation of a CPOE order set showed significant improvement in compliance with IDSA guidelines for management of febrile neutropenia. Based on the data from our study an IDSA concurrent institutional guideline for management of febrile neutropenia was formulated and further efforts are under way to incorporate results in our new EMR order set entries.[Table: see text]

Procalcitonin-guided protocol is not useful to manage antibiotic therapy in febrile neutropenia: a randomized controlled trial.

Febrile neutropenia (FN) requires immediate use of antibiotics (ATB), and procalcitonin (PCT) is proven to be useful in guiding antibiotic therapy in different settings. This study investigated the use of PCT as a guide for the duration of ATB in FN. A randomized controlled trial was carried out from January-December 2010. A total of 62 hematological adult patients with FN were randomized, in 1:1 ratio, into two groups: (1) PCT group: length of ATB guided by institutional protocol plus PCT dynamics, and (2) control group: duration of ATB in accordance with institutional protocol. There was no difference between groups regarding the use of ATB for the first episode of fever (HR 1.14, 95% CI 0.66-1.95, p = 0.641), with equivalent median duration of ATB therapy (PCT group 9.0days and control group 8.0days, p = 0.67), and median number of days without ATB (0days, IQR 0-2days for both groups, p = 0.96). We observed no difference in clinical cure rate (p = 0.68), infection relapse (p = 1.0), superinfection (p = 0.85), length of hospitalization (p = 0.64), and mortality at 28days (p = 0.39) and at 90days (p = 0.72). Considering the cut-off of 0.5ng/ml, PCT was correlated with bacteremia (sensitivity of 51.9% and specificity of 76.5%). In this randomized controlled trial, adding a PCT-guided protocol to the standard recommendations did not reduce the use of antibiotics in febrile neutropenia, although no apparent harm was caused. PCT proved to be a marker of bacteremia in this setting.

Colony-stimulating factors for chemotherapy-induced febrile neutropenia.

Febrile neutropenia is a frequent adverse event experienced by people with cancer who are undergoing chemotherapy, and is a potentially life-threatening situation. The current treatment is supportive care plus antibiotics. Colony-stimulating factors (CSFs), such as granulocyte-CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF), are cytokines that stimulate and accelerate the production of one or more cell lines in the bone marrow. Clinical trials have addressed the question of whether the addition of a CSF to antibiotics could improve outcomes in individuals diagnosed with febrile neutropenia. However, the results of these trials are conflicting. To evaluate the safety and efficacy of adding G-CSF or GM-CSF to standard treatment (antibiotics) when treating chemotherapy-induced febrile neutropenia in individuals diagnosed with cancer. We conducted the search in March 2014 and covered the major electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and SCI. We contacted experts in hematology and oncology and also scanned the citations from the relevant articles. We searched for randomized controlled trials (RCTs) that compared CSF plus antibiotics versus antibiotics alone for the treatment of chemotherapy-induced febrile neutropenia in adults and children. We used the standard methodological procedures expected by The Cochrane Collaboration. We performed meta-analysis of the selected studies using Review Manager 5 software. Fourteen RCTs (15 comparisons) including a total of 1553 participants addressing the role of CSF plus antibiotics in febrile neutropenia were included. Overall mortality was not improved by the use of CSF plus antibiotics versus antibiotics alone (hazard ratio (HR) 0.74 (95% confidence interval (CI) 0.47 to 1.16) P = 0.19; 13 RCTs; 1335 participants; low quality evidence). A similar finding was seen for infection-related mortality (HR 0.75 (95% CI 0.47 to 1.20) P = 0.23; 10 RCTs; 897 participants; low quality evidence). Individuals who received CSF plus antibiotics were less likely to be hospitalized for more than 10 days (risk ratio (RR) 0.65 (95% CI 0.44 to 0.95) P = 0.03; 8 RCTs; 1221 participants; low quality evidence) and had more number of participants with a more faster neutrophil recovery (RR 0.52 (95% CI 0.34 to 0.81) P = 0.004; 5 RCTs; 794 participants; moderate quality evidence) than those treated with antibiotics alone. Similarly, participants receiving CSF plus antibiotics had shorter duration of neutropenia (standardized mean difference (SMD) -1.70 (95% CI -2.65 to -0.76) P = 0.0004; 9 RCTs; 1135 participants; moderate quality evidence), faster recovery from fever (SMD -0.49 (95% CI -0.90 to -0.09) P value = 0.02; 9 RCTs; 966 participants; moderate quality evidence) and shorter duration of antibiotics use (SMD -1.50 (95% CI -2.83 to -0.18) P = 0.03; 3 RCTs; 457 participants; low quality evidence) compared with participants receiving antibiotics alone. We found no significant difference in the incidence of deep venous thromboembolism (RR 1.68 (95% CI 0.72 to 3.93) P = 0.23; 4 RCTs; 389 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. We found higher incidence of bone or joint pain or flu-like symptoms (RR 1.59 (95% CI 1.04 to 2.42) P = 0.03; 6 RCTs; 622 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. Overall, the methodological quality of studies was moderate to low across different outcomes. The main reasons to downgrade the quality of evidence were inconsistency across the included studies and imprecision of results. The use of a CSF plus antibiotics in individuals with chemotherapy-induced febrile neutropenia had no effect on overall mortality, but reduced the amount of time participants spent in hospital and improved their ability to achieve neutrophil recovery. It was not clear whether CSF plus antibiotics had an effect on infection-related mortality. Participants receiving CSFs had shorter duration of neutropenia, faster recovery from fever and shorter duration of antibiotics use.

Bloodstream infections in pediatric patients at Cancer Institute, Chennai.

There is paucity of data on the epidemiology of bloodstream infections in pediatric cancer patients from India. Rationale use of antibiotics in febrile neutropenia is important for reducing morbidity and preventing the emergence of drug resistant bacteria. The study was conducted to look at the prevalence of bloodstream bacterial infection and the antibiotic resistance profile at Cancer Institute, Chennai. This was a retrospective study. Data on all blood cultures taken from pediatric cancer patients treated at Cancer Institute, Chennai, during the year 2013 were analyzed. The microbiological profile and sensitivity pattern were analyzed. A total of 1045 blood culture samples were taken, and there were 82/1045 (7.5%) positive blood cultures. Gram-negative organisms accounted for 50/82 (61%) of all positive cultures. Klebsiella pneumoniae (32%) was the most common Gram-negative isolate, and Staphylococcus aureus (93.5%) was the most common Gram-positive. There was high resistance to aminoglycosides and beta-lactam/beta-lactamase inhibitor antibodies. Gram-negative organisms are the predominant bacteria isolated. There is high resistance to first-line combination antibiotics used as empiric therapy for treatment of febrile neutropenia.

Potential economic impact of the 21-gene expression panel according to tumor (T) size in lymph-node-negative (LNN), estrogen-receptor (ER)-positive early breast cancer (BC)

e11518 Background: Use of the 21-gene panel may save costs in patients with LNN, ER-positive BC. Our previous analysis suggests that such would be the case in Brazil (SABCS 2008). However, the impact of the test may vary according to T size. Methods: Using a web-based survey with 30 (of a total of nearly 700) medical oncologists and literature data, we developed a model of direct medical expenses in two hypothetic cohorts (one without and one with access to the 21-gene panel) of Brazilian women with LNN, ER-positive BC, from the perspective of third-party payers. The questionnaire assessed patterns of care relating to chemotherapy (CT) regimens in each T size, type of premedication, use of G-CSF, and use of intravenous antibiotics for febrile neutropenia. Medication and 21-gene panel costs were the manufacturers’ recommended prices at the time of the survey. T size and recurrence score distributions followed those reported by Paik et al (NEJM 2004). CT use in the cohort with no access to the 21-gene panel was modeled according to the survey. In the cohort with access to the test, we assumed that patients with intermediate or high scores would receive CT, whereas patients with low score would not. Results: The table displays the number of patients receiving CT and the costs (CT, premedication, G-CSF, antibiotics, and the 21-gene panel) for two hypothetic cohorts of 100 patients. Conclusions: Our economic analysis suggests that the 21-gene panel overall would be cost-saving in Brazil, from the perspective of third-party payers. However, testing could actually increase direct medical costs in LNN, ER-positive T1 tumors, and decrease costs in T &gt;2 cm. [Table: see text] [Table: see text]

Study devises risk index to identify people with cancer who are at low risk of complication if treated with empiric antibiotics for febrile neutropenia

Study devises risk index to identify people with cancer who are at low risk of complication if treated with empiric antibiotics for febrile neutropenia