Association between inappropriate empirical antimicrobial therapy and mortality in gram-negative bloodstream infections in patients with febrile neutropenia and hematological malignancy.

BACKGROUND AND OBJECTIVE: Inappropriate initial antimicrobial therapy has been associated with high mortality in patients with gram-negative bacilli bloodstream infections during febrile neutropenia following chemotherapy for hematological malignancies. The aim of this study is to determine this association in our hospital. METHODS: A single center, retrospective, cohort study of bloodstream infection due to gram-negative bacilli and febrile neutropenia was conducted. Clinical characteristics, microbiological etiology, antimicrobial resistance profile, empirical and targeted antibiotic therapy, intensive care unit admission, persistent bacteremia and mortality were analyzed. RESULTS: Of the 171 episodes of bloodstream infection due to gram-negative bacilli, empirical antimicrobial therapy was inappropriate in 43 episodes (25.1 %). There was a significant difference in mortality at 7 and 30 days between patients who received appropriate versus inappropriate empirical treatment (4.6 % versus 13.9 %, p = 0.04; 15.6 % versus 32.5 %, p = 0.016). Inappropriate empirical treatment (RR, 2.97 [95 % CI, 1.01-8.74]), shock at the time of febrile neutropenia diagnosis (RR, 6.5 [95 % CI, 1.83-23.05]) carbapenem-resistant microorganism (RR, 3.73 [95 % CI, 1.14-12.24]) and persistent bacteremia (RR, 84.6 [95 % CI, 11.3-629.4]) were associated with an increased mortality at 7 and 30 days. In the multivariate analysis, shock (RR, 4.85 [95 % CI, 2.10-11.65]) and persistent bacteremia was independently associated with increased 30-day mortality, but inappropriate empirical antimicrobial therapy was not an independent prognostic determinant (RR, 1.66 [0.53-4.82]). CONCLUSION: Shock at the time of febrile neutropenia diagnosis contributes to mortality in patients with gram-negative bacilli bloodstream infection, in this scenario, appropriate empirical antimicrobial therapy should be encouraged.

Efficacy of extended infusion of ß-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients (BEATLE): a randomised, multicentre, open-label, superiority clinical trial.

OBJECTIVES: The efficacy of extended infusions (EI) of ß-lactam antibiotics for optimising outcomes in febrile neutropenia is unclear. We assessed whether the administration of ß-lactams was more effective in EI than in intermittent infusion (II) for the treatment of febrile neutropenia. METHODS: We performed a randomised, open-label, superiority clinical trial of patients with febrile neutropenia at four Spanish university hospitals. Patients undergoing haematopoietic stem cell transplantation or with acute leukaemia receiving chemotherapy who required empirical antibiotic treatment for febrile neutropenia were randomly assigned (1:1) to receive EI of ß-lactam or II after a first dose in bolus. The choice of antipseudomonal ß-lactam was left to the discretion of the attending physician. The primary endpoint was treatment success at day 5, defined as defervescence without modifying the antibiotic treatment. Secondary endpoints included adverse events, attainment of the pharmacokinetic/pharmacodynamic target of 50, 75 and 100%ƒuT>MIC, and 30-day mortality. RESULTS: Between November 19, 2019 and June 22, 2022, 295 patients we screened for eligibility, of whom 150 were randomly assigned to receive EI (n=77) or II (n=73) of the antipseudomonal ß-lactam of choice. In the intention-to-treat analysis, treatment success at day 5 was achieved in 39/77 patients (50.6%) receiving EI versus 46/73 patients (63.0%) receiving II (risk difference -12.4%; 95% confidence interval, -29.4 to 4.7, p=0.17). The pharmacokinetic/pharmacodynamic targets of 75 and 100% ƒuT>MIC for empirical treatment were achieved more frequently in the EI group. No statistically-significant differences were found between groups in terms of adverse events or 30-day mortality. CONCLUSIONS: Our findings do not support the routine use of empirical EI of ß-lactams in febrile neutropenia. Further studies should consider the clinical heterogeneity of febrile neutropenia and focus on patients with sepsis/septic shock and microbiologically documented infections, particularly those with infections caused by microorganisms less susceptible to ß-lactams.

The heterogeneous syndrome of non-infectious causes of persistent fever in neutropenic patients with hematologic malignancy: another opportunity for stewardship?

Although occult fungal, viral and multidrug-resistant bacterial infections can cause persistent fever in neutropenic patients with hematologic cancer, a variety of non-infectious entities should be considered in case-by-case basis in the context of negative diagnostic workup for infection.

NEWS, NEWS2, and qSOFA accuracy in predicting sepsis-related mortality in acute myeloid leukemia: a retrospective single-center analysis.

Acute myeloid leukemia (AML) treated with intensive chemotherapy carries a high risk of severe infection. The development of reliable assessment tools to promptly identify patients at risk of developing critical illness is essential to prevent delays in intensive care unit (ICU) admission. This study evaluated the accuracy of quick Sequential Organ Failure Assessment (qSOFA) score, National Early Warning Score (NEWS), and NEWS2 score in predicting ICU admission and sepsis-related mortality in this population. A retrospective analysis was conducted, including 365 episodes of febrile neutropenia in 126 patients. The results showed that all three scores-qSOFA, NEWS, and NEWS2-demonstrated good accuracy for all outcomes, with area under the receiver-operating characteristic curve values for sepsis-related mortality of 0.812, 0.858, and 0.848, respectively. In addition, the scores exhibited excellent accuracy in predicting ICU admission and the composite outcome of ICU admission or sepsis-related mortality. To our knowledge, this is the first study to evaluate the accuracy of NEWS in a population of patients with AML who did not undergo stem cell transplantation. These findings suggest that NEWS and NEWS2 are effective tools for identifying patients with AML at high risk of clinical deterioration during febrile neutropenia, supporting their use in clinical practice.

Rates of febrile neutropenia and its causes in the real world.

Aim: Characterize febrile neutropenia in the real-world and explore potentially modifiable risk factors.Patients & methods: Characteristics of patient presenting with febrile neutropenia after systemic cancer treatment were investigated, with a thorough evaluation of potential risk factors.Results: The rate of febrile neutropenia requiring hospitalization was comparable with clinical trials (mean absolute difference 2%, 95% CI: -1-4%; p = 0.29). The in-hospital mortality rate was 6%. Most cases resulted from low-risk regimens (50%) and 18.2% presented no apparent risk factors. 42.4% of patients presented modifiable factors potentially involved in the occurrence of febrile neutropenia.Conclusion: Febrile neutropenia rate in contemporary real-world evidence is comparable with clinical trials. Appropriate G-CSF administration and avoidance of potentially harmful drug-interactions represent potential areas for improvement.

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Procalcitonin Level Monitoring in Antibiotic De-Escalation and Stewardship Program for Patients with Cancer and Febrile Neutropenia.

OBJECTIVE: Serial procalcitonin (PCT) monitoring has been adopted to supplement clinical judgement and help guide antibiotic therapy as part of antimicrobial stewardship programs. PCT levels peak 24 to 48 h after infection onset and decline with infection resolution. We explored the role of PCT as an infection biomarker for guiding antibiotic therapy in cancer patients hospitalized for febrile neutropenia. DESIGN: Prospective randomized study. METHODS: Patients were enrolled between October 2021 and August 2023 and received empiric intravenous broad-spectrum antibiotics (IVBSA) for at least 48 h. PCT was measured at baseline and 48-72 h after IVBSA initiation. PCT drop 48-72 h after IVBSA initiation was defined as a reduction of 30% from baseline or a PCT level < 0.25 ng/mL. De-escalation was defined as a switch from IVBSA to oral or simplified once-daily IV therapy. RESULTS: Of the 89 patients with available PCT levels, 53 (60%) had a PCT drop, most of whom (79%) underwent IVBSA de-escalation. Compared with patients without a PCT drop, patients with a PCT drop had a higher de-escalation rate at 72 h (71% vs. 45%; p = 0.003) and a shorter median antibiotic duration (55 h vs. 98 h; p = 0.004). Patients with bacteremia had a significantly higher median PCT level than those without bacteremia (2.35 ng/mL vs. 0.370 ng/mL, p = 0.013). CONCLUSIONS: In patients with cancer and febrile neutropenia, a PCT drop was associated with earlier therapy de-escalation and shorter antibiotic duration. PCT monitoring may be useful in antimicrobial stewardship initiatives in this patient population. CLINICAL TRIALS IDENTIFIER: NCT04983901.

Sarcopenia as a predictive factor for febrile neutropenia during induction chemotherapy in head and neck squamous cell cancer.

OBJECTIVE: Febrile neutropenia (FN) is the most serious toxicity in patients with head and neck squamous cell carcinoma (HNSCC) treated with induction chemotherapy (IC). Although it is well-known that sarcopenia is a risk factor for severe toxicity of (chemo)radiotherapy, the data on the association between sarcopenia and FN during IC in HNSCC patients is rare. This study determined the impact of sarcopenia on FN during IC. METHODS: IC-treated patients with HNSCC were enrolled in this study. Skeletal muscle mass (SMM) at the C3 vertebral body was used to define sarcopenia from computed tomography (CT) scans. To determine the predictive effect of low SMM on FN, logistic regression analysis was performed. RESULTS: In this study, 71 patients were included, of whom 28 had low SMM and 14 experienced FN. In multivariate analysis, low SMM and high CRP were the independent predictive factors for FN. The combination index of sarcopenia and CRP showed a greater odds ratio than sarcopenia alone suggesting a more significant predicting indicator. CONCLUSIONS: Sarcopenia defined by CT imaging is associated with FN in patients with HNSCC treated with IC. The combination of sarcopenia and high CRP is a more significant risk factor, and it helps determine patients at risk of FN during IC.

Human pegivirus -1 (HPgV-1) RNA frequency and genotype distribution in pediatric oncology patients with febrile neutropenia.

Human Pegivirus-1, typically regarded as a commensal virus, exhibits high prevalence in humans. Its frequency and impact on oncologic pediatric patients with febrile neutropenia (FN), a frequent chemotherapy complication, remains unexplored. In this study, we assessed HPgV-1 RNA prevalence in pediatric patients experiencing FN. Blood samples were collected from 30 children, 15 presenting FN and 15 comprising a control group of either undergoing treatment or in remission. Overall, HPgV-1 RNA was detected in 23.3 % of samples (26.7 % among FN patients and 20.0 % among those under treatment or in remission). Phylogenetic analysis unveiled HPgV-1 genotype 2 predominance among these samples, the most prevalent strain circulating in Brazil. Our findings prompt crucial inquiries into the role of HPgV-1 RNA in FN: is it an incidental finding and if it can influences this clinical entity? Further investigation is imperative to elucidate HPgV-1 implications in vulnerable patients cohorts, potentially informing new approaches and understanding viral dynamics in immunocompromised populations.

Efficacy and safety of same-day versus next-day administration of PEG-rhG-CSF for the prophylaxis of chemotherapy-induced neutropenia and febrile neutropenia in patients with breast cancer: a retrospective cohort study.

OBJECTIVES: Polyethylene glycol recombinant human granulocyte colony-stimulating factors (PEG-rhG-CSFs) are used to prevent or treat chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). This study aimed to compare the efficacy and safety of same-day versus next-day PEG-rhG-CSF administration following chemotherapy and the effects of 3 mg versus 6 mg dosages. METHODS: We retrospectively analyzed cohort data of patients with breast cancer who underwent chemotherapy and received PEG-rhG-CSF either within 24 h (same-day group) or 24 h (next-day group) after chemotherapy. The incidences of CIN and FN were assessed in each chemotherapy cycle between the two groups. The primary endpoint was the incidence of FN in the first cycle and throughout all cycles. The secondary endpoints included the incidences of various grades of CIN (CIN1-CIN4), antibiotic use, chemotherapy regimen modifications, and overall safety. RESULTS: Among the 2385 chemotherapy cycles with prophylactic PEG-rhG-CSF in 620 patients, 798 and 1587 cycleswere in the same-day and next-day group, respectively. No statistically significant differences were observed in the incidence of FN in the first cycle or across all cycles, CIN1-4, or adverse reactions between the two groups. However, the same-day group exhibited significantly higher rates of antibiotic use (2.88% vs. 0.42%, P = 0.03) and chemotherapy regimen modification (4.68% vs. 1.45%, P < 0.001). Subgroup analysis indicated no differences in outcomes for the 6 mg dosage, but a significantly lower incidence of CIN was observed in the same-day group receiving 3 mg (P = 0.025). CONCLUSIONS: These findings suggest that same-day administration of PEG-rhG-CSF is as effective and safe as next-day administration in preventing FN and CIN during chemotherapy.

Enhancing patient-centered care: a randomized study on G-CSF administration preferences in chemotherapy-induced neutropenia.

PURPOSE: Chemotherapy-induced neutropenia poses a significant risk to cancer patients, with pegfilgrastim being commonly used for its prevention. While pegfilgrastim can be administered via prefilled syringe or pen device, patient preferences and experiences with these delivery methods remain unclear. METHODS: We conducted a prospective, open-label, randomized, observational trial (NCT05910164) at the Rafael Institute, France, comparing patient preferences for pegfilgrastim administration using a prefilled syringe versus a prefilled pen device. Patients undergoing chemotherapy and requiring pegfilgrastim were enrolled and randomized 1:1 to receive either syringe or pen first, with crossover administration. Questionnaires assessed patient preferences, learning experiences, autonomy, pain levels, emotional responses, satisfaction with nursing care, and empowerment. RESULTS: Among 150 randomized patients (mean age 58 years; 69% female), both groups showed a preference for the pen device, with significantly higher mean scores favoring pen administration (4.94 ± 1.70 vs. 4.27 ± 1.84; p = 0.00106). Patients reported significantly lower perceived pain with pen administration and stronger positive emotions compared to syringe use. Satisfaction with nursing care was higher with syringe use. Empowerment levels were similar across groups but significantly stronger when using the pen in complete autonomy. CONCLUSION: A preference for pegfilgrastim administration via the pen device was observed, though this may have been influenced by the administration sequence and the absence of syringe self-administration. The insights gained can help inform clinical decision-making and improve patient-centered care in managing chemotherapy-induced neutropenia. TRIAL REGISTRATION: NCT05910164 on June 15, 2023.

Lesson from COVID-19 outbreak; importance of standard precautions to febrile neutropenia prevention in patients with breast cancer who received adjuvant chemotherapy: a retrospective observational study.

Purpose: Intensive cytotoxic chemotherapy increases the risk of infection in patients with cancer by inducing bone marrow suppression and mucosal injury. Febrile neutropenia (FN) is the most important clinical adverse event in patients with cancer receiving cytotoxic chemotherapy. To prevent FN, standard precautions including hand and respiratory hygiene are generally recommended, but the exact effect of non-pharmacologic intervention has not been clearly proven in the clinical setting. We aimed to compare the incidence of FN between the pre-coronavirus disease 19 (COVID-19) era vs. the post-COVID-19 era. Methods: We retrospectively enrolled patients with breast cancer who received an adriamycin and cyclophosphamide (AC) regimen containing adjuvant chemotherapy at Jeju National University Hospital. We compared the incidence of FN between the pre- and post-COVID-19 period and analyzed characteristics of the event and other clinical risk factors. Results: In total, 149 patients were enrolled, including 94 who received AC chemotherapy in the pre-COVID-19 era and 55 who received it in the post-COVID-19 era. Sixteen patients (10.7%) experienced FN. Fourteen (14.9%) and 2 events (3.6%) occurred in pre-COVID-19 and post-COVID-19 eras, respectively. The post-COVID-19 era was the only risk factor for FN (P = 0.032). Conclusion: We found an association between FN occurrence and the COVID-19 outbreak, providing indirect evidence of the importance of non-pharmacological measures to reduce FN risk in patients with breast cancer. Further research is required to confirm the standard precautions for FN prevention in patients with cancer.

Cost of Pegfilgrastim for the Prophylaxis of Chemotherapy-induced Febrile Neutropenia in Patients with Breast Cancer Receiving Perioperative Chemotherapy in Daily Practice in Japan: A Posthoc Analysis in a Single-center Retrospective Study.

This study aimed to estimate the medical costs associated with febrile neutropenia (FN) prophylaxis with pegfilgrastim and evaluate its impact on survival outcomes in daily practice in Japan. In this single-center retrospective study, we obtained data from 296 Japanese patients with breast cancer receiving fluorouracil, epirubicin, and cyclophosphamide (FEC)-100 chemotherapy; the patients were divided into the pegfilgrastim and non-pegfilgrastim groups. We analyzed the median costs of chemotherapy, drugs for all adverse events (AEs) and FN, and hospitalization due to FN. We also assessed the survival outcomes. The pegfilgrastim group showed a significantly higher median total cost (JPY 872320.0 vs. JPY 466715.0, p<0.001). This difference was associated with the prophylactic use of pegfilgrastim. The median costs of the drugs for all AE treatments were JPY 9030.4 and JPY 24690.6, with the non-pegfilgrastim group showing a significantly higher cost (p<0.001). In 11 patients hospitalized for FN management, no significant difference in hospitalization cost was observed between the pegfilgrastim and non-pegfilgrastim groups (JPY 512390.0 vs. JPY 307555.0, p=0.102). No significant difference in the 3-year overall survival was observed between the pegfilgrastim and non-pegfilgrastim groups (79.9% vs. 88.3%, p=0.672). In this study, although the total medical cost in daily practice increased because of primary prophylaxis with pegfilgrastim, the 3-year overall survival was not impacted by the use of pegfilgrastim. Our study data suggested that the primary prophylaxis pegfilgrastim should be used during FEC-100 chemotherapy based on the patient-related FN risk factors, instead of routine use.

Serum Albumin as a Prognostic Biomarker for Febrile Neutropenia Outcome and Complications: A Prospective Observational Trial.

Background: Febrile neutropenia (FN) poses a significant challenge in cancer treatment, with a high incidence among patients undergoing standard therapies. Predicting FN complications and outcomes remains crucial for improving patient management strategies. Biomarkers, including procalcitonin and albumin, have garnered attention for their potential prognostic value in FN. Methods: We conducted a prospective observational study at a tertiary hospital, enrolling 185 adult cancer patients experiencing FN episodes. We assessed serum albumin levels and incorporated them into the Multinational Association for Supportive Care in Cancer (MASCC) risk index to enhance risk stratification. Results: Serum albumin levels displayed promising prognostic utility in febrile neutropenia (FN). They exhibited moderate specificity and sensitivity in predicting mortality during FN and 28-day mortality. Serum albumin levels were significantly associated with gastrointestinal infections, serving as an independent predictor. Integrating serum albumin into the MASCC risk index improved predictive accuracy for FN mortality by 50%, 28-day mortality by 66.67%, and respiratory tract infections by 62.50%, enhancing in this way risk stratification for FN-related complications. Conclusion: Serum albumin emerges as a promising biomarker for prognostication in FN, complementing existing risk assessment frameworks. Its incorporation into the MASCC risk index enhances predictive capabilities, aiding clinicians in identifying high-risk patients promptly. While albumin shows potential in predicting mortality and complications, further research is warranted to optimize sensitivity and specificity, ensuring its clinical utility.

Alternative therapy for lymphoma with febrile neutropenia using traditional Chinese medicine: A case report.

INTRODUCTION: Febrile neutropenia is a common complication in patients undergoing chemotherapy for hematologic malignancies and is associated with significant morbidity and mortality. Primary granulocyte colony-stimulating factor (G-CSF) prophylaxis is consistently associated with a notable reduction in the risk of febrile neutropenia. However, the use of G-CSF in patients who are already neutropenic from chemotherapy remains controversial. Studies have shown that 12.9 % of cancer patients incorporate traditional Chinese medicine (TCM) to alleviate chemotherapy side effects in Taiwan; thereby providing an alternative management strategy for febrile neutropenia in cancer patients. CASE PRESENTATION: This is an 18-year-old female with newly diagnosed precursor T-lymphoblastic lymphoma. After chemotherapy, the patient developed febrile neutropenia. Despite the use of antibiotics and G-CSF, the febrile neutropenia persisted for two months. Approximately ten days after the initiation of traditional Chinese medicine decoction with the strategy of tonifying the spleen and stomach, clearing yin fire, and uplifting yang, her absolute neutrophil count (ANC) had gradually increased. Additionally, after two weeks of treatment, her fever subsided. The patient continued with chemotherapy and was discharged in stable condition. DISCUSSION: Antibiotic use aligns with the TCM perspective of an "attack" approach. Conversely, our TCM decoction was designed to raise the ANC by tonifying the spleen and stomach, clearing Yin Fire, and uplifting Yang. Li Dongyuan, one of the four great masters of the Jin Yuan Dynasty, created the formula: Bupiwei Shengyang Sanhuo Decoction that is notable in this regard. The herbs in our decoction have shown hematopoietic and myelosuppression-alleviating effect. For many patients who do not respond adequately to G-CSF alone, integrative treatments involving both TCM and Western medicine can offer additional therapeutic benefits by increasing blood cell counts.

Predictive value of peri-chemotherapy hematological parameters for febrile neutropenia in patients with cancer.

Objective: The aim of this study was to compare hematological parameters pre- and early post-chemotherapy, and evaluate their values for predicting febrile neutropenia (FN). Methods: Patients diagnosed with malignant solid tumors receiving chemotherapy were included. Blood cell counts peri-chemotherapy and clinical information were retrieved from the hospital information system. We used the least absolute shrinkage and selection operator (LASSO) method for variable selection and fitted selected variables to a logistic model. We assessed the performance of the prediction model by the area under the ROC curve. Results: The study population consisted of 4,130 patients with common solid tumors receiving a three-week chemotherapy regimen in Sichuan Cancer Hospital from February 2019 to March 2022. In the FN group, change percentage of neutrophil count decreased less (-0.02, CI: -0.88 to 3.48 vs. -0.04, CI: -0.83 to 2.24). Among hematological parameters, lower post-chemotherapy lymphocyte count (OR 0.942, CI: 0.934-0.949), change percentage of platelet (OR 0.965, CI: 0.955-0.975) and higher change percentage of post-chemotherapy neutrophil count (OR 1.015, CI: 1.011-1.018), and pre-chemotherapy NLR (OR 1.002, CI: 1.002-1.002) predicted an increased risk of FN. These factors improved the predicting model based on clinical factors alone. The AUC of the combination model was 0.8275. Conclusion: Peri-chemotherapy hematological markers improve the prediction of FN.

Febrile neutropenia induced by adjuvant radiotherapy for a patient with breast cancer accompanied with reversible splenial lesion syndrome (RESLES, TypeI): a case report.

BACKGROUND: Reversible splenial lesion syndrome (RESLES) is known as a neuro-imaging syndrome with recurrent but reversible lesion of the corpus callosum, characterized by nonspecific but usually mild encephalopathies and specific imaging manifestations.There are few published reports in the field of oncology. CASE PRESENTATION: A 33-year-old female with right breast cancer and with no particular family history was admitted to hospital with high fever and severe headache, after receiving adjuvant radiotherapy. Blood routine test upon admission suggested neutropenia, considering myelosuppression associated with radiotherapy. There were no definite findings of common pathogenic microorganism, and no imaging indication of certain infectious sites other than a likely reversible corpus callosum syndrome suggested by brain MRI, which was relieved after systemic antibiotic therapy and granulocyte colony-stimulating factor injection. CONCLUSIONS: Reversible splenial lesion syndrome is a kind of clinical-imaging syndrome with multiple clinical manifestations and etiologies. This breast cancer patient after postoperative adjuvant radiotherapy develops a complication of RESLES that rings an alarm bell to the oncologists not to easily recognize the corpus callosum lesion as infarction or metastasis. Meanwhile, the potential pathogenic mechanisms need to be explored further.

The role of colonization with resistant Gram-negative bacteria in the treatment of febrile neutropenia after stem cell transplantation.

BACKGROUND: Febrile neutropenia (FN) is a common complication of stem cell transplantation. AIM: To evaluate the frequency of sepsis in patients with FN colonized with resistant Gram-negative bacteria (extended-spectrum ß-lactamase (ESBL)-positive, multidrug-resistant (MDR) Pseudomonas aeruginosa) and the choice of primary antibiotic in colonized patients. METHODS: This retrospective study analysed data from patients undergoing haematopoietic stem cell transplantation from January 2018 to September 2022. Data were extracted from the hospital information system. FINDINGS: Carbapenem as the primary antibiotic of choice was chosen in 10.9% of non-colonized +/-AmpC patients, 31.5% of ESBL+ patients, and 0% of MDR P. aeruginosa patients. Patients with FN and MDR P. aeruginosa colonization had a high prevalence of sepsis (namely 100%, P = 0.0197). The spectrum of sepsis appeared to be different, with Gram-negative bacilli predominating in the ESBL+ group (OR: 5.39; 95% CI: 1.55-18.76; P = 0.0123). Colonizer sepsis was present in 100% of sepsis with MDR P. aeruginosa colonization (P = 0.002), all in allogeneic transplantation (P = 0.0003), with a mortality rate of 33.3% (P = 0.0384). The incidence of sepsis in patients with ESBL+ colonization was 25.9% (P = 0.0197), with colonizer sepsis in 50% of sepsis cases (P = 0.0002), most in allogeneic transplantation (P = 0.0003). CONCLUSION: The results show a significant risk of sepsis in FN with MDR P. aeruginosa colonization, a condition almost exclusively caused by the colonizer. At the same time, a higher risk of Gram-negative sepsis has been demonstrated in patients colonized with ESBL+ bacteria.

Variation in Antibiotic Prescription in High-Risk Febrile Neutropenia in Portuguese Hospitals.

INTRODUCTION: Febrile neutropenia (FN) is a potentially severe entity, particularly in hemato-oncologic patients who have higher incidence of colonization with multidrug-resistant bacteria. Discrepancies among guidelines contribute to divergence in antimicrobial practices. Our objective was to assess the variation of practices in antimicrobial therapy in high-risk FN among Portuguese hematologists. METHODS: We conducted a cross-sectional study through the implementation of an online survey, open to all clinical hematologists in the country. To characterize practice patterns regarding critical elements in FN management, three clinical vignettes were designed to describe typical situations where narrow-spectrum empiric antibiotics (vignette 1), short-course therapy (vignette 2) and de-escalation (vignette 3) could be performed. The remaining questions characterized clinical experience, department size, and differentiation and decision-making process regarding FN antibiotic therapy. RESULTS: The survey yielded 31 responses from 11 hospitals across four regions. All respondents opted for empiric narrow-spectrum antibiotics, 22.6% opted for short-course therapy (mostly senior specialists from larger settings) and 35.5% for de-escalation (mostly young specialists). Availability of an FN protocol seemed to favor both approaches. These findings should be complemented by qualitative assessments of barriers to best practices and should support the need for interventions to improve antibiotic use in febrile neutropenia.

What do we know About the Usefulness of 18F-FDG PET-CT for the Management of Invasive Fungal Infection? An International Survey.

BACKGROUND: Recent data support 18F-FDG PET-CT for the management of infections in immunocompromised patients, including invasive fungal infection (IFI). However, its role is not well established in clinical practice. We performed an international survey to evaluate the knowledge of physicians about the usefulness of 18F-FDG PET-CT in IFI, in order to define areas of uncertainty. METHODS: An online survey was distributed to infectious diseases working groups in December 2023-January 2024. It included questions regarding access to 18F-FDG PET-CT, knowledge on its usefulness for IFI and experience of the respondents. A descriptive analysis was performed. RESULTS: 180 respondents answered; 60.5% were Infectious Diseases specialists mainly from Spain (52.8%) and Italy (23.3%). 84.4% had access to 18F-FDG PET-CT at their own center. 85.6% considered that 18F-FDG PET-CT could be better than conventional tests for IFI. In the context of IFI risk, 81.1% would consider performing 18F-FDG PET-CT to study fever without a source and around 50% to evaluate silent lesions and 50% to assess response, including distinguishing residual from active lesions. Based on the results of the follow-up 18F-FDG PET-CT, 56.7% would adjust antifungal therapy duration. 60% would consider a change in the diagnostic or therapeutic strategy in case of increased uptake or new lesions. Uncovering occult lesions (52%) and diagnosing/excluding endocarditis (52.7%) were the situations in which 18F-FDG PET-CT was considered to have the most added value. There was a great variability in responses about timing, duration of uptake, the threshold for discontinuing treatment or the influence of immune status. CONCLUSION: Although the majority considered that 18F-FDG PET-CT may be useful for IFI, many areas of uncertainty remain. There is a need for protocolized research to improve IFI management.

The long-term impact of an antimicrobial stewardship program in febrile neutropenia: an 8 years follow up.

PURPOSE: To describe the long-term effects of an ASP among febrile neutropenia (FN) patients. METHODS: A quasi-experimental study was conducted between 2015 and 2023 at a tertiary care hospital in Istanbul, Türkiye. The ASP was implemented for FN patients, and the effects were assessed before and after the ASP interventions, which included FN clinical pathways and regular multi-disciplinary meetings with relevant healthcare workers. RESULTS: A total of 489 FN episodes of 290 patients were included, 42% were female, and the mean age was 56 years (SD: 15, range: 18-89 years). After the intervention, the rate of appropriate antimicrobial therapy at the levels of starting (p = 0.005), switching (p < 0.001), and de-escalation/discontinuation, (p < 0.001) significantly increased. Another positive impact of the ASP was a significant reduction in candidemia (from 4.88 to 0.74, p = 0.004), as well as a significant reduction in the 90-day mortality rate (from 19 to 5%, p < 0.001). In multivariate analysis, having a gram-negative bloodstream infection, prolonged days with fever, and a high risk for neutropenia were found to be significant predictors of 90-day mortality, while follow-up with ASP significantly reduced mortality. CONCLUSION: Implementation of ASP led to reduced candidemia and LOS without increasing mortality, even in a country with a high rate of antimicrobial resistance. Implementation of sustainable ASP for FN patients is critical in combating antimicrobial resistance.