Systematic review on efficacy and safety of empirical versus pre-emptive antifungal therapy among children with febrile neutropenia reveals paucity of data.

BACKGROUND: Two approaches are used to manage invasive fungal disease (IFD) in febrile neutropenic patients viz. empirical therapy (without attempting to confirm the diagnosis), or pre-emptive therapy (after screening tests for IFD). OBJECTIVE: This systematic review was undertaken to compare these approaches in children. METHODS: We searched PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, CINAHL, Clinical Trial Registries and grey literature, for randomized controlled trials (RCT) comparing empirical versus pre-emptive antifungal therapy in children with FN suspected to have IFD. We used the Cochrane Risk of bias 2 tool for quality assessment, and evaluated the certainty of evidence using the GRADE approach. RESULTS: We identified 7989 citations. Stepwise screening identified only one relevant RCT that administered empirical (n = 73) or pre-emptive (n = 76) antifungal therapy. There were no significant differences in all-cause mortality (RR 1.56, 95% CI: 0.46, 5.31), IFD mortality (RR 1.04, 95% CI:0.15, 7.20) and other clinically important outcomes such as duration of fever, duration of hospitalization and proportion requiring ICU admission. There were no safety data reported. The number of days of antifungal therapy was significantly lower in the pre-emptive therapy arm. The certainty of evidence for all outcomes was 'moderate'. CONCLUSIONS: This systematic review highlighted the paucity of data, comparing empirical versus pre-emptive antifungal therapy in children with febrile neutropenia having suspected invasive fungal disease. Data from a single included trial suggests that both approaches may be comparable in research settings. Robust trials are warranted to address the gap in existing knowledge about the optimal approach in clinical practice.

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.

Application of the Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to guide the empiric antibiotic treatment of febrile neutropenia in oncological paediatric patients: experience from two paediatric hospitals in Northern Italy.

BACKGROUND: Guidelines about febrile neutropenia in paediatric patients are not homogeneous; the best empiric treatment of this condition should be driven by local epidemiology. The Weighted-Incidence Syndromic Combination Antibiogram (WISCA) addresses the need for disease-specific local susceptibility evidence that could guide empiric antibiotic prescriptions based on outcome estimates of treatment regimens obtained as a weighted average of pathogen susceptibilities. This study developed a WISCA model to inform empirical antibiotic regimen selection for febrile neutropenia (FN) episodes in onco-haematological paediatric patients treated at two Italian paediatric tertiary centres. METHODS: We included blood cultures from patients with a bloodstream infection and neutropenia admitted to the Paediatric Haematology-Oncology wards in Padua and Genoa Hospitals from 2016 to 2021. WISCAs were developed by estimating the coverage of 20 antibiotics as monotherapy and of 21 combined regimens with a Bayesian probability distribution. RESULTS: We collected 350 blood cultures, including 196 g-negative and 154 g-positive bacteria. Considering the most used antibiotic combinations, such as piperacillin-tazobactam plus amikacin, the median coverage for the pool of bacteria collected in the study was 78%. When adding a glycopeptide, the median coverage increased to 89%, while the replacement of piperacillin-tazobactam with meropenem did not provide benefits. The developed WISCAs showed that no monotherapy offered an adequate coverage rate for the identified pathogens. CONCLUSIONS: The application of WISCA offers the possibility of maximizing the clinical utility of microbiological surveillance data derived from large hospitals to inform the choice of the best empiric treatment while contributing to spare broad-spectrum antibiotics.

Bacterial Isolates and Characteristics of Children With Febrile Neutropenia on Treatment for Cancer at a Tertiary Hospital in Western Kenya.

PURPOSE: This study aimed to identify the patient characteristics of children with febrile neutropenia, the associated bacterial organisms, and their sensitivity patterns. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted at the Moi Teaching and Referral Hospital (MTRH) pediatric oncology ward, from June 2021 to April 2022. A total of 110 children who developed fever and neutropenia during chemotherapy were enrolled. Blood samples for culture were collected aseptically. Patient characteristics were presented in frequency tables. Antimicrobial sensitivity patterns were plotted in tables against the bacterial isolates cultured. Chi-square/Fisher's exact test was used to determine any association between patient characteristics, bacterial growth, and antimicrobial sensitivity. RESULTS: The majority (n = 66; 60%) were males. The median age was 6.3 years (standard deviation, 3.7). The majority of patients 71 (64.5%) had hematologic malignancies, the most common being AML. There was a significant association between severity of neutropenia and hematologic malignancies (P = .028). In total, 31/110 (28.2%) blood cultures were positive for bacterial growth. Gram-positive bacteria were more frequent (n = 20; 58.1%). The most common organism was Escherichia coli (n = 6; 18.2%), followed by Staphylococcus aureus (n = 5; 15.2%). All the isolates were sensitive to linezolid and vancomycin and also showed good sensitivity toward meropenem (n = 10/11; 90.9%). High resistance to cephalosporins was noted with ceftriaxone (n = 5/6; 83.3%), cefepime (n = 4/7; 57.1%), and ceftazidime (n = 3/4; 75%). CONCLUSION: The most common malignancy associated with febrile neutropenia was AML. Gram-positive bacteria were the most common isolates. There was high resistance to cephalosporins.

Clinical Utility of Stepwise Bronchoalveolar Lavage Fluid Analysis in Diagnosing and Managing Lung Infiltrates in Leukemia/Lymphoma Patients With Febrile Neutropenia.

PURPOSE: Febrile neutropenia (FN) is a serious complication in hematologic malignancies, and lung infiltrates (LIs) remain a significant concern. An accurate microbiological diagnosis is crucial but difficult to establish. To address this, we analyzed the utility of a standardized method for performing bronchoalveolar lavage (BAL) along with a two-step strategy for the analysis of BAL fluid. PATIENTS AND METHODS: This prospective observational study was conducted at a tertiary cancer center from November 2018 to June 2020. Patients age 15 years and older with confirmed leukemia or lymphomas undergoing chemotherapy, with presence of FN, and LIs observed on imaging were enrolled. RESULTS: Among the 122 enrolled patients, successful BAL was performed in 83.6% of cases. The study used a two-step analysis of BAL fluid, resulting in a diagnostic yield of 74.5%. Furthermore, antimicrobial therapy was modified in 63.9% of patients on the basis of BAL reports, and this population demonstrated a higher response rate (63% v 45%; P = .063). CONCLUSION: Our study demonstrates that a two-step BAL fluid analysis is safe and clinically beneficial to establish an accurate microbiological diagnosis. Given the crucial impact of diagnostic delays on mortality in hematologic malignancy patients with FN, early BAL studies should be performed to enable prompt and specific diagnosis, allowing for appropriate treatment modifications.

Prophylactic pegfilgrastim reduces febrile neutropenia in ramucirumab plus docetaxel after chemoimmunotherapy in advanced NSCLC: post hoc analysis from NEJ051.

Ramucirumab plus docetaxel (RD) can cause febrile neutropenia (FN), which frequently requires the prophylactic administration of pegfilgrastim. However, the effects of prophylactic pegfilgrastim on FN prevention, therapeutic efficacy, and prognosis after RD have not been fully evaluated in patients with advanced non-small-cell lung cancer (NSCLC). Two hundred and eighty-eight patients with advanced NSCLC who received RD as second-line therapy after platinum-based chemotherapy plus PD-1 blockade were included. Patients were divided into groups with and without prophylactic pegfilgrastim, and adverse events, efficacy, and prognosis were compared between both groups. Of the 288 patients, 247 received prophylactic pegfilgrastim and 41 did not. The frequency of grade 3/4 neutropenia was 62 patients (25.1%) in the pegfilgrastim group and 28 (68.3%) in the control group (p < 0.001). The frequency of FN was 25 patients (10.1%) in the pegfilgrastim group and 10 (24.4%) in the control group (p = 0.018). The objective response rate was 31.2% and 14.6% in the pegfilgrastim and control groups (p = 0.039), respectively. The disease control rate was 72.9% in the pegfilgrastim group and 51.2% in the control group (p = 0.009). Median progression free survival was 4.3 months in the pegfilgrastim group and 2.5 months in the control group (p = 0.002). The median overall survival was 12.8 and 8.1 months in the pegfilgrastim and control groups (p = 0.004), respectively. Prophylactic pegfilgrastim for RD reduced the frequency of grade 3/4 neutropenia and febrile neutropenia and did not appear to be detrimental to patient outcome RD.Clinical Trial Registration Number: UMIN000042333.

Impact of posaconazole prophylaxis and antifungal treatment on BAL GM performance in hematology malignancy patients with febrile neutropenia: a real life experience.

BACKGROUND: Diagnostic accuracy of galactomannan measurements is highly variable depending on the study population, diagnostic procedures, and treatment procedures. We aimed to evaluate the effect of posaconazole prophylaxis and empiric antifungal treatment upon diagnostic accuracy of GM measurements in bronchoalveolar lavage (BAL), bronchial lavage (BL), and serum in hematological malignancy population. METHODS: Patients hospitalized in a single tertiary care center with hematologic malignancies undergoing fiberoptic bronchoscopy (FOB) with a preliminary diagnosis of IPA were retrospectively included. RESULTS: In all the study population (n = 327), AUC for BAL, BL, and serum GM were as follows: 0.731 [0.666-0.790], 0.869 [0.816-0.912], and 0.610 [0.540-0.676] with BL samples having the best diagnostic value. GM measurements in patients under posaconazole prophylaxis (n = 114) showed similar diagnostic performance. While specificity was similar between patients with and without posaconazole prophylaxis, sensitivity of GM measurements was lower in patients with prophylaxis. Analyses with patient classified according to antifungal treatment at the time of FOB procedure (n = 166) showed a decreased diagnostic accuracy in serum GM and BAL GM measurements related with the duration of treatment. However, BAL, BL, and serum GM measurements presented similar sensitivity and specificity in higher cut-off values in longer durations of antifungal treatment. CONCLUSION: Our study shows that posaconazole prophylaxis and active short-term (3 days) antifungal treatment do not significantly affect overall diagnostic performance of GM measurements in bronchoalveolar lavage and bronchial lavage samples. However, using different cut-off values for patients receiving active treatment might be suggested to increase sensitivity.

Dissecting bloodstream infections in febrile neutropenic patients with hematological malignancies, a decade-long single center retrospective observational study (2009-2019).

BACKGROUND: The use of ill-suited antibiotics is a significant risk factor behind the increase in the mortality, morbidity, and economic burden for patients who are under treatment for hematological malignancy (HM) and bloodstream infections (BSI). Such unfitting treatment choices intensify the evolution of resistant variants which is a public health concern due to possible healthcare-associated infection spread to the general population. Hence, this study aims to evaluate antibiograms of patients with BSI and risk factors associated with septicemia. METHODS: A total of 1166 febrile neutropenia episodes (FNE) among 513 patients with HM from the National Center for Cancer Care and Research (NCCCR), Qatar, during 2009-2019 were used for this study. The socio-demographic, clinical, microbial, and anti-microbial data retrieved from the patient's health records were used. RESULTS: We analyzed the sensitivity of gram-negative and gram-positive bacilli reported in HM-FN-BSI patients. Out of the total 512 microorganisms isolated, 416 (81%) were gram-negative bacteria (GNB), 76 (15%) were gram-positive bacteria (GPB) and 20 (4%) were fungi. Furthermore, in 416 GNB, 298 (71.6%) were Enterobacteriaceae sp. among which 121 (41%) were ESBL (Extended Spectrum Beta-Lactamase) resistant to Cephalosporine third generation and Piperacillin-Tazobactam, 54 (18%) were Carbapenem-resistant or multidrug-resistant organism (MDRO). It's noteworthy that the predominant infectious agents in our hospital include E. coli, Klebsiella species, and P. aeruginosa. Throughout the study period, the mortality rate due to BSI was 23%. Risk factors that show a significant correlation with death are age, disease status, mono or polymicrobial BSI and septic shock. CONCLUSION: Decision pertaining to the usage of antimicrobials for HM-FN-BSI patients is a critical task that relies on the latest pattern of prevalence, treatment resistance, and clinical outcomes. Analysis of the antibiogram of HM-FN-BSI patients in Qatar calls for a reconsideration of currently followed empirical antibiotic therapy towards better infection control and antimicrobial stewardship.

Impact of a Pediatric Emergency Medicine Pharmacist, Institutional Guideline, and Electronic Order Set on Empiric Antimicrobial Use for Febrile Neutropenia.

OBJECTIVES: This study evaluated the difference in appropriateness of antimicrobial selection in pediatric patients with febrile neutropenia (FN) after implementation of an institutional guideline, a dedicated pediatric emergency medicine (EM) pharmacist, and an electronic order set. METHODS: This was a retrospective cohort study that included febrile patients aged younger than 18 years who were at risk of neutropenia, as defined by our institutional algorithm. Charts were evaluated for inclusion by searching for patients who presented to the emergency department (ED) between February 2018 and January 2022 who had International Classification of Diseases, Tenth Revision (ICD-10) codes for patients at risk of FN. Three independent groups were compared before, during, and after interventions. A historical control group (group 1), postdedicated EM pharmacist and institutional guideline cohort (group 2), and postdedicated EM pharmacist, institutional guideline, and electronic order set cohort (group 3) were compared. Secondary outcomes included time from registration in the ED to administration of the first dose of empiric antimicrobials, days to defervescence, pediatric intensive care unit length of stay, and hospital length of stay. RESULTS: Seventy-eight charts were reviewed for inclusion. Among those included (n = 38), there was an increase in appropriate use of antimicrobials from 71% to 92% to 100% ( P = 0.1534) between group 1, group 2, and group 3, respectively. In addition, the interventions in this study lead to an overall decrease in the median time from registration to first dose of antibiotics from 142 minutes to 72 minutes ( P = 0.1370). CONCLUSIONS: This study demonstrated the positive impact a pediatric EM pharmacist along with an institutional guideline and an electronic order set have on appropriate antimicrobial selection in pediatric FN patients. Institutions should consider multipronged approaches to improve the selection and time to administration of appropriate empiric antimicrobials in the ED.

Safety of Procalcitonin Guided Early Discontinuation of Antibiotic Therapy among Children Receiving Cancer Chemotherapy and Having Low-Risk Febrile Neutropenia: A Randomized Feasibility Trial (ProFenC Study).

In low-risk febrile neutropenia (LR-FN), the safety of early discontinuation of empiric antibiotics without marrow recovery is not well established. This study aimed to evaluate the safety of procalcitonin (PCT) guided early discontinuation of antibiotics in LR-FN. In this trial, children with LR-FN with an afebrile period of at least 24 h, sterile blood culture, and negative/normalized PCT were randomized at 72 h of starting antibiotics into two groups: intervention arm and standard arm. The antibiotics were stopped in the intervention arm regardless of absolute neutrophil count (ANC), while in the standard arm, antibiotics were continued for at least 7 days or until recovery of ANC (>500/mm3). The primary objective was to determine the treatment failure rates, and the secondary objective was to compare the duration of antibiotics and all-cause mortality between the two arms. A total of 46 children with LR-FN were randomized to either the intervention arm (n = 23) or the standard arm (n = 23). Treatment failure was observed in 2/23 (8.7%) of patients in the intervention arm compared to 1/23 (4.3%) in the standard arm [RR: 2 (95% CI: 0.19-20.6); p = 0.55]. The median duration of antibiotics in the intervention arm and standard arm were 3 days vs 7 days (P= <0.001). There was no mortality in this study. PCT-guided early discontinuation of empirical antibiotics in LR-FN is feasible. There was no significant difference observed in treatment failure between the early discontinuation of antibiotics vs standard therapy. The total duration of antibiotic exposure was significantly lesser in the discontinuation arm. Further, larger multicenter studies are needed to confirm the finding of this study.

[Neutropenia - when is GCSF support indicated?] / Neutropenie ­ wann ist eine GCSF Unterstützung notwendig?

Many systemic treatments used in genitourinary oncology negatively affect haematopoiesis, thus leading to neutropenia. Neutropenic patients are vulnerable to bacterial, and other infections. Often fever is the only symptom in these patients. Neutropenic fever is a major threat for these patients, as it may lead to life-threatening therapy complications that significantly impair the patient's quality of life, Moreover, it may also worsen the prognosis due to therapy delays or necessary dose modifications. Granulocyte colony stimulating factors (GCSF), which can improve neutrophil granulocyte formation, are used both for supportive treatment in febrile neutropenia and for its prophylaxis. The correct indication for such GCSF support depends on the general risk of febrile neutropenia of the therapy used, as well as on individual patient factors and the treatment intent (palliative vs. curative). Based on the current recommendations both of the German and international guidelines, this article aims to provide an up-to-date and practice-oriented overview of the use of GCSF in uro-oncology.

Dose Individualization of Cefepime for Febrile Neutropenia in Patients With Lymphoma or Multiple Myeloma: Implications for Therapeutic Drug Monitoring.

BACKGROUND: Optimal cefepime dosing is a challenge because of its dose-dependent neurotoxicity. This study aimed to determine individualized cefepime dosing for febrile neutropenia in patients with lymphoma or multiple myeloma. METHODS: This prospective study enrolled 16 patients receiving cefepime at a dose of 2 g every 12 hours. Unbound concentrations were determined at 0.5 hours, 7.2 hours [at the 60% time point of the 12 hours administration interval (C7.2h)], and 11 hours (trough concentration) after the first infusion (rate: 2 g/h). The primary and secondary end points were the predictive performance of the area under the unbound concentration-time curve (AUC unbound ) and the effect of unbound cefepime pharmacokinetic parameters on clinical response, respectively. RESULTS: The mean (SD) AUC unbound was 689.7 (226.6) mcg h/mL, which correlated with C7.2h (R 2 = 0.90), and the Bayesian posterior AUC unbound using only the trough concentration (R 2 = 0.66). Although higher exposure was more likely to show a better clinical response, each parameter did not indicate a statistical significance between positive and negative clinical responses ( P = 0.0907 for creatinine clearance (Ccr), 0.2523 for C7.2h, 0.4079 for trough concentration, and 0.1142 for AUC unbound ). Cutoff values were calculated as 80.2 mL/min for Ccr (sensitivity: 0.889, specificity: 0.714), 18.6 mcg/mL for C7.2h (sensitivity: 0.571, specificity: 1.000), and 9.2 mcg/mL for trough concentration (sensitivity: 0.571, specificity: 1.000). When aiming for a time above 100% the minimum inhibitory concentration, both continuous infusion of 4 g/d and intermittent infusion of 2 g every 8 hours achieved a probability of approximately 100% at a minimum inhibitory concentration of 8 mcg/mL. CONCLUSIONS: Therapeutic drug monitoring by sampling at C7.2h or trough can facilitate rapid dose optimization. Continuous infusion of 4 g/d was recommended. Intermittent dosing of 2 g every 8 hours was alternatively suggested for patients with a Ccr of 60-90 mL/min.

Consensus survey on the management of children with chemotherapy-induced febrile neutropenia and at low risk of severe infection.

Our aim was to identify national consensus criteria for the management of children with chemotherapy-induced febrile neutropenia (FN), for evidence-based step-down treatment approaches for patients classified at low risk of severe infection. In 2018, a five-section, 38-item survey was e-mailed to all pediatric hematology and oncology units in France (n = 30). The five sections contained statements on possible consensus criteria for the (i) definition of FN, (ii) initial management of children with FN, (iii) conditions required for initiating step-down therapy in low-risk patients, (iv) management strategy for low-risk patients, and (v) antibiotic treatment on discharge. Consensus was defined by respondents' combined answers (somewhat agree and strongly agree) at 75% or more. Sixty-five physicians (participation rate: 58%), all specialists in pediatric onco-hematology, from 18 centers completed the questionnaire. A consensus was reached on 22 of the 38 statements, including the definition of FN, the criteria for step-down therapy in low-risk children, and the initial care of these patients. There was no consensus on the type and duration of antibiotic therapy on discharge. In conclusion, a consensus has been reached on the criteria for initiating evidence-based step-down treatment of children with FN and a low risk of severe infection but not for the step-down antimicrobial regimen.

Impact of Time-to-Antibiotic Delivery in Pediatric Patients With Cancer Presenting With Febrile Neutropenia.

PURPOSE: Febrile neutropenia (FN) in pediatric patients with cancer can cause severe infections, and prompt antibiotics are warranted. Extrapolated from other populations, a time-to-antibiotic (TTA) metric of <60 minutes after medical center presentation was established, with compliance data factoring into pediatric oncology program national rankings. METHODS: All FN episodes occurring at Vanderbilt Children's Hospital (2007-February 2022) and a sample of episodes from Colorado Children's Hospital (2012-2019) were abstracted, capturing TTA and clinical outcomes including major complications (intensive care unit [ICU] admission, vasopressors, intubation, or infection-related mortality). Odds ratios (ORs) were adjusted for age, treatment center, absolute neutrophil count, hypotension presence, stem-cell transplant status, and central line type. RESULTS: A total of 2,349 episodes were identified from Vanderbilt (1,920) and Colorado (429). Only 0.6% (n = 14) episodes required immediate ICU management, with a median TTA of 28 minutes (IQR, 20-37). For the remaining patients, the median TTA was 56 minutes (IQR, 37-90), and 54.3% received antibiotics in <60 minutes. There were no significant associations between TTA (<60 or ≥60 minutes) and major complications (adjusted OR, 0.99 [95% CI, 0.62 to 1.59]; P = .98), and a TTA ≥60 minutes was not associated with any type of complication. Similarly, TTA, when evaluated as a continuous variable, was not associated with a major (OR, 0.99 [95% CI, 0.94 to 1.04]; P = .69) nor any other complication in adjusted analysis. CONCLUSION: There is no clear evidence that a reduced TTA improves clinical outcomes in pediatric oncology FN and thus it should not be used as a primary quality measure.

Febrile neutropenia incidence and the variable toxicity profile between brand and generic docetaxel in the adjuvant treatment of breast cancer with docetaxel and cyclophosphamide regimen.

OBJECTIVE: To assess the incidence of febrile neutropenia without primary granulocyte colony-stimulating factor prophylaxis in patients undergoing chemotherapy with adjuvant docetaxel and cyclophosphamide, and to evaluate the toxicity profile of brand-name docetaxel (Taxotere ® ) and the generic formulation. METHODS: This retrospective study was conducted using data obtained from electronic medical records of patients treated at a Brazilian cancer center. Patients with breast cancer who underwent adjuvant treatment between January 2016 and June 2019 were selected. Data were analyzed using chi-square and Fisher correlation of variables, and multivariate analyses were adjusted for propensity score. RESULTS: A total of 231 patients with a mean age of 55.9 years at the time of treatment were included in the study. The majority (93.9%) had luminal histology, 84.8% were at clinical stage I, and 98.2% had a good performance status. The overall incidence of febrile neutropenia in the study population was 13.4% (31 cases). The use of brand-name docetaxel (Taxotere ® ) was the only factor associated with febrile neutropenia occurrence (OR= 3.55, 95%CI= 1.58-7.94, p=0.002). CONCLUSION: In patients with breast cancer who require treatment with adjuvant docetaxel and cyclophosphamide regimen, the toxicity profile differs between brand-name and generic docetaxel. Regardless of the formulation used, the incidence of febrile neutropenia was less than 20%, which may allow for the omission of primary prophylactic granulocyte colony-stimulating factor use in this setting.

Low utilization of vancomycin in febrile neutropenia: real-world evidence from 4 Brazilian centers.

PURPOSE: The prompt initiation of a betalactam antibiotic in febrile neutropenic patients is considered standard of care, while the empiric use of vancomycin is recommended by guidelines in specific situations, with a low level of evidence. The objective of this study was to assess the utilization of vancomycin in the management of febrile neutropenia within four Brazilian medical centers that implemented more stringent criteria for its administration. METHODS: A comprehensive retrospective analysis was performed encompassing all instances of febrile neutropenia observed during the period from 2013 to 2019. The primary focus was to identify the reasons for initiating vancomycin therapy. RESULTS: A total of 536 consecutive episodes of febrile neutropenia were documented, involving 384 patients with a median age of 52 years (range 18-86). Chemotherapy preceded febrile neutropenia in 59.7% of cases, while 40.3% occurred after hematopoietic stem cell transplantation. The most prevalent underlying diseases were acute myeloid leukemia (26.5%) and non-Hodgkin's lymphoma (22%). According to international guidelines, vancomycin should have been initiated at the onset of fever in 145 episodes (27%); however, it was administered in only 27 cases (5.0%). Three episodes were associated with Staphylococcus aureus bacteremia, two of which were methicillin resistant. The 15-day and 30-day mortality rates were 5.0% and 9.9%, respectively. CONCLUSIONS: The results of this study underscore the notably low utilization rate of vancomycin in cases of febrile neutropenia, despite clear indications outlined in established guidelines. These findings emphasize the importance of carefully implementing guideline recommendations, considering local epidemiological factors, especially when the strength of recommendation is weak.

Fusariosis in Mexico: A 10-year retrospective series.

Fusarium species represent an opportunistic fungal pathogen. The data in Mexico about Fusarium infections in humans are scarce. Here, we present a retrospective series of patients with a confirmed diagnosis of fusariosis in eight different hospitals in Mexico from January 2010 to December 2019. The diagnosis of proven fusariosis was made according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORT/MSG) criteria. A total of 49 cases were identified in our series. Most patients had burn injuries (49%), and 37% had hematological malignancies. Most patients had fire injuries (40%), followed by electric injuries (8%), febrile neutropenia (10%), and pancytopenia (6%). Patients had skin and soft tissue involvement in 49%, followed by blood culture isolation and biopsies from different sites of the body (lung, sinuses, bone tissue, and eyes). Febrile neutropenia (10%) and fungemia (8%) were the most common clinical syndromes in immunosuppressed patients. Most patients received monotherapy (67%), where voriconazole was used in 30% of the cases, followed by conventional amphotericin B (16%), and lipidic formulations of amphotericin B in 10% (either liposomal amphotericin B or amphotericin B lipid complex). Combination therapy was used in 20% of the cases, and the most common combination therapy was triazole plus any lipidic formulation of amphotericin B (10%). Mortality related to Fusarium infection occurred in 22% of patients. Fusariosis is a serious threat. Burn injuries and hematologic malignancies represent the most common causes of infection in this small series from Mexico.

This study describes the epidemiological characteristics of patients with fusariosis from a multicenter cohort in Mexico. These findings provide information from this invasive fungal disease that threatens different countries in Latin America.

Prophylactic Use Of Levofloxacin During Induction Of Acute Lymphoblastic Leukaemia In Children-Experience From Pakistan.

To assess whether prophylactic use of Levofloxacin would reduce the number of febrile neutropenia episodes during the induction phase, a single-centre, case-control study was carried out. Data was collected prospectively of patients who received Levofloxacin prophylaxis during the induction chemotherapy from September 2019 till October 2020. The cases were compared with historical controls who did not receive antibiotics prophylaxis. A total of 121 patients were enrolled, among which 61 patients were cases, whereas 60 patients were controls. The patients who received Levofloxacin prophylaxis had lower rate of febrile neutropenia episodes than patients who did not receive any prophylaxis (p≤0.01) (odds ratio [OR]:0.23, CI 95%). No significant difference in induction mortality was seen between the two groups (p≤0.14). Levofloxacin prophylaxis reduced the rate of febrile neutropenia episodes among patients, but it did not affect the infection related mortality.