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BACKGROUND: Granulocyte transfusions for patients with prolonged neutropenia and severe infections has been a controversial practice. Previous studies suggest a benefit of high-dose granulocyte transfusions (≥0.6 × 109/kg), although, until recently, the consistent production of high-dose units has been challenging. Here, we present our experience and results utilizing high-dose granulocyte transfusions at a large, tertiary academic medical center for the treatment of infections in adult, neutropenic patients. STUDY DESIGN/METHODS: A retrospective chart review (2018-2021) was conducted for all patients who received high-dose granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. Gathered parameters included patient demographics, clinical history, infection status, dose, clinical outcomes, pre- and post-absolute neutrophil count (ANC), and transfusion times including time between granulocyte collection, administration, and posttransfusion ANC count. Gathered parameters were summarized using descriptive statistics, outcomes were assessed utilizing Kaplan-Meier curves/log-rank/regression testing. RESULTS: Totally 28 adult, neutropenic patients refractory to antimicrobial agents and/or G-CSF received a total of 173 granulocyte concentrates. Median ANC increased from 0.7 × 109/L pre-transfusion to 1.6 × 109/L posttransfusion. The mean granulocyte yield was 77.4 × 109 resulting in an average dose per kilogram of 0.90 × 109 ± 0.30 × 109 granulocytes. Composite day 42 survival and microbial response was 42.9% (n = 12/28) without significant adverse reactions. DISCUSSION: Here, we demonstrate the successful and safe implementation of high-dose granulocyte transfusions for neutropenic patients. Given the rapid and consistent production, distribution, and improved granulocyte quality, further investigations to determine the clinical efficacy of G-CSF primed granulocyte transfusions is now possible.

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INTRODUCTION: Autologous stem cell transplantation (ASCT) is a well-established consolidation treatment for many hematologic cancers which delivers prolonged survival. A subset of patients' adequate stem cell harvest is not achievable with a solitary use of granulocyte colony-stimulating agents (G-CSF). Generally, chemomobilization is employed for patients failing G-CSF and its most feared complication febrile neutropenia (FN). MATERIALS AND METHODS: Here, we aimed to investigate the impact of the FN in chemomobilization on apheresis outcomes and engraftment. One hundred and eighty-three patients with the diagnosis of lymphoma or myeloma who underwent chemomobilization between 2015 and 2020 were included in the study. RESULTS: Forty-three patients experienced FN. All patients received G-CSF. All myeloma patients were mobilized with 4 g/m2 cyclophosphamide, but it was heterogeneous for lymphoma patients. The precollection blood counts, harvested CD34+ hematopoietic stem cells (HSCs)/kg, apheresis count, and engraftment durations were recorded. Preapheresis leukocyte and platelet were lower in the FN group (P = 0,004 and P = 0,001). Peripheral CD34 HSCs and total harvested CD34 HSCs were similar among groups (P = 0.25 and P = 0.9). More apheresis was needed in the FN group, but it was not significant (P = 0.07). Undergoing ASCT was similar (P = 0.7); however, platelet and neutrophil engraftment durations were slower in the FN group (P = 0.05 and P = 0.001). CONCLUSION: Harvesting sufficient CD34+ HSCs from patients with FN is still feasible; however, FN treatment should begin promptly, and further apheresis sessions may be required.

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Neutropenic enterocolitis (NEC), also referred to as typhlitis, is a condition associated with a high mortality risk and primarily manifests in immunocompromised patients. It is characterized by ulceration, edema, and hemorrhage affecting the bowel wall. The underlying cause of NEC is postulated as an immunocompromised condition that facilitates bacterial infiltration through compromised bowel mucosa. The high mortality rate is attributable to bowel necrosis, culminating in perforation and sepsis. This report describes a case involving a patient with metastatic seminoma who exhibited seizure-like activity, fever, Streptococcus gallolyticus bacteremia, and NEC. The patient underwent treatment involving broad-spectrum antibiotics and filgrastim. The patient's neutropenia resolved leading to discharge on oral antibiotics. The case reported is unique, as it links NEC to Streptococcus gallolyticus and seminoma. Streptococcus gallolyticus has not been previously associated with NEC.

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Chronic disseminated candidiasis (CDC) is a severe but rarely seen fungal infection presenting in patients with hematologic malignancies after a prolonged duration of neutropenia. A high index of suspicion is required to diagnose CDC as standard culture workup is often negative. While tissue biopsy is the gold standard of diagnosis, it is frequently avoided in patients with profound cytopenias and increased bleeding risks. A presumptive diagnosis can be made in patients with recent neutropenia, persistent fevers unresponsive to antibiotics, imaging findings of hypoechoic, non-rim enhancing target-like lesions in the spleen and liver, and mycologic evidence. Here, we describe the case of an 18-year-old woman with relapsed B-cell acute lymphoblastic leukemia treated with re-induction chemotherapy who subsequently developed CDC with multi-organ involvement. The diagnosis was made based on clinical and radiologic features with positive tissue culture from a skin nodule and hepatic lesion. The patient was treated for a total course of 11 months with anti-fungal therapy, most notably amphotericin B and micafungin, and splenectomy. After initial diagnosis, the patient was monitored with monthly CT abdomen imaging that showed disease control after 5 months of anti-fungal therapy and splenectomy. The diagnosis, treatment, and common challenges of CDC are outlined here to assist with better understanding, diagnosis, and treatment of this rare condition.

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Invasive fungal diseases (IFDs) still represent a relevant cause of mortality in patients affected by hematological malignancies, especially acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) undergoing remission induction chemotherapy, and in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Mold-active antifungal prophylaxis (MAP) has been established as a standard of care. However, breakthrough IFDs (b-IFDs) have emerged as a significant issue, particularly invasive aspergillosis and non-Aspergillus invasive mold diseases. Here, we perform a narrative review, discussing the major advances of the last decade on prophylaxis, the diagnosis of and the treatment of IFDs in patients with high-risk neutropenic fever undergoing remission induction chemotherapy for AML/MDS and allo-HSCT. Then, we present our single-center retrospective experience on b-IFDs in 184 AML/MDS patients undergoing high-dose chemotherapy while receiving posaconazole (n = 153 induction treatments, n = 126 consolidation treatments, n = 60 salvage treatments). Six cases of probable/proven b-IFDs were recorded in six patients, with an overall incidence rate of 1.7% (6/339), which is in line with the literature focused on MAP with azoles. The incidence rates (IRs) of b-IFDs (95% confidence interval (95% CI), per 100 person years follow-up (PYFU)) were 5.04 (0.47, 14.45) in induction (n = 2), 3.25 (0.0013, 12.76) in consolidation (n = 1) and 18.38 (3.46, 45.06) in salvage chemotherapy (n = 3). Finally, we highlight the current challenges in the field of b-IFDs; these include the improvement of diagnoses, the expanding treatment landscape of AML with molecular targeted drugs (and related drug-drug interactions with azoles), evolving transplantation techniques (and their related impacts on IFDs' risk stratification), and new antifungals and their features (rezafungin and olorofim).

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High-dose cyclophosphamide (HD-Cy) (3 g/m2) plus granulocyte colony-stimulating factor (G-CSF) is a very effective regimen for peripheral blood stem cell (PBSC) mobilization. Unfortunately, it is associated with an increased risk of neutropenic fever (NF). We analyzed the effect of NF on PBSC apheresis results and the efficacy of prophylactic antibiotics for the prevention of NF associated with HD-Cy plus G-CSF for PBSC mobilization in patients with newly diagnosed multiple myeloma (MM). First, patients were divided into NF ( +) and NF ( -) groups according to whether they suffered from NF during mobilization. Second, we divided patients into an antibiotic prophylaxis group and a nonantibiotic prophylaxis group according to whether antibiotic prophylaxis was used during the mobilization period. Our study showed that NF( +) patients (n = 44) had lower CD34 + cell dose collection (median 2.60 versus 5.34 × 106/kg, P < 0.001) and slower neutrophil engraftment and platelet engraftment (median 11 versus 10 days, P = 0.002, and median 13 versus 11 days, P = 0.043, respectively) than NF( -) patients (n = 234). Of note, the nonantibiotic prophylaxis group patients (n = 30) had a 26.7% incidence of NF. In the patients receiving antibiotic prophylaxis (n = 227), the incidence was reduced to 9.3% (P = 0.01). The antibiotic prophylaxis patients had higher CD34 + cell collection (median 5.41 versus 2.27 × 106/kg, P < 0.001) and lower hospitalization cost of mobilization ($ median 3108.02 versus 3702.39, p = 0.012). Thus, our results demonstrate that NF is associated with lower CD34 + cell collection and that antibiotic prophylaxis can reduce the incidence of NF and improve stem cell mobilization and collection outcomes, which reduces the hospitalization cost of mobilization.

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The incidence of invasive fungal infections (IFIs) has increased in recent years as a result of increasing the incidence of hematologic malignancies (HMs). IFIs, as the opportunistic diseases, are the most important concern in these patients with a high mortality rate. These infections are one of the leading causes of morbidity and mortality in HM patients and an important factor in increasing the costs of patients' management because of the prolonged hospitalization and the inevitable need to use antifungal agents. Due to the changes in the pattern of organisms causing IFIs, unavailability of effective and safe antifungal drugs, and high rate of drug resistance as well as lack of fast and accurate diagnostic methods, these infections have become a serious and life-threatening problem necessitating effective prevention and treatment strategies using suitable antifungal agents, especially in high-risk patients. The aim of the present study was to review the pathogens causing various types of IFIs, diagnostic methods, and novel prophylactic and therapeutic antifungal regimens in HM patients according to the new published studies and clinical trials.

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Sweet syndrome (SS) is a rare inflammatory disorder characterized by the rapid onset of a characteristically tender rash, fever, and other systemic symptoms. These manifestations are often mistaken for an infection that is not responding to antimicrobials, especially in immunocompromised hosts. We present the case of a 44-year-old woman who developed SS following induction chemotherapy for newly diagnosed acute myeloid leukemia (AML). She exhibited a painful rash on the anterior chest, which spread centrifugally, along with neutropenic fever unresponsive to broad-spectrum antimicrobials. Biopsy of the rash revealed a dense neutrophilic infiltrate within the dermis, confirming the diagnosis of SS. The patient was subsequently treated with systemic steroids with prompt resolution of fevers and improvement of her rash. This case highlights that SS can manifest with a robust neutrophilic infiltrate, even in the context of neutropenia stemming from chemotherapy. SS serves as a crucial consideration in hematologic malignancies, particularly AML, when patients present with fever and cutaneous eruptions. Prompt recognition followed by systemic steroid therapy often leads to symptom resolution.

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Aplastic anemia (AA) is a hematopoietic stem cell (HSC) disorder characterized by the loss of HSCs, bone marrow failure, and peripheral pancytopenia. AA is classified as very severe (VSAA), severe (SAA), or non-severe (NSAA) based on the severity criteria. This classification system has implications for the prognosis and treatment options offered to patients. The prognosis of AA has improved over the past several decades with the advancements in supportive care, HSC transplant (HCT), and immunosuppressive therapy (IST). In this report, we present the case of a 26-year-old male diagnosed with VSAA after presenting with severe neutropenia and fever. The patient ultimately underwent HSC transplantation.

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PURPOSE: Neutropenia, defined as a number of neutrophils in patients' blood specimen lower than 1500 cells/µm3, is a common adverse event during myelosuppressive oncological chemotherapy, predisposing to febrile neutropenia (FN). Patients with coexisting moderate-to-severe chronic kidney disease (CKD) have an increased risk of FN, included in the guidelines for the primary prophylaxis of FN. However, this does not include mild kidney function impairment with estimated glomerular filtration rate (eGFR) 60-89 ml/min/1.73 m2. This prospective study analyzed the risk of neutropenia in patients on chemotherapy without indication for the primary prophylaxis of FN. METHODS: The study enrolled 38 patients starting chemotherapy, including 26 (68.4%) patients aged 65 years or more. The median duration of follow-up was 76 days. The methodology of creatinine assessment enabled the use of the recommended CKD-EPI formula for identifying patients with a mild reduction of glomerular filtration. RESULTS: Sixteen (42.1%) patients developed at least G2 neutropenia without episodes of FN. Only five (13.1%) patients had eGFR < 60 ml/min/1.73 m2, while 15 (62.5%) eGFR < 90 ml/min/1.73 m2. The relative risk of neutropenia in patients with impaired eGFR was over six times higher than in patients with eGFR > 90 ml/min/1.73 m2 (RR = 6.08; 95%CI:1.45-27.29; p < 0.01). CONCLUSIONS: Our observation indicates that even a mild reduction in eGFR is a risk factor for the development of neutropenia and a potential risk factor for FN. Authors are advised to check the author instructions for the journal they are submitting to for word limits and if structural elements like subheadings, citations, or equations are permitted.

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BACKGROUND: The use of fluoroquinolones to prevent infections in neutropenic patients with cancer or undergoing hematopoietic stem cell transplantation (HSCT) is a controversial issue, with international guidelines providing conflicting recommendations. Although potential benefits are clear, concerns revolve around efficacy, potential harms, and antimicrobial resistance (AMR) implications. DISCUSSION: Fluoroquinolone prophylaxis reduces neutropenic fever (NF) bloodstream infections and other serious bacterial infections, based on evidence from systematic reviews, randomized controlled trials, and observational studies in adults and children. Fluoroquinolone prophylaxis may also reduce infection-related morbidity and healthcare costs; however, evidence is conflicting. Adverse effects of fluoroquinolones are well recognized in the general population; however, studies in the cancer cohort where it is used for a defined period of neutropenia have not reflected this. The largest concern for routine use of fluoroquinolone prophylaxis remains AMR, as many, but not all, observational studies have found that fluoroquinolone prophylaxis might increase the risk of AMR, and some studies have suggested negative impacts on patient outcomes as a result. CONCLUSIONS: The debate surrounding fluoroquinolone prophylaxis calls for individualized risk assessment based on patient characteristics and local AMR patterns, and prophylaxis should be restricted to patients at the highest risk of serious infection during the highest risk periods to ensure that the risk-benefit analysis is in favor of individual and community benefit. More research is needed to address important unanswered questions about fluoroquinolone prophylaxis in neutropenic patients with cancer or receiving HSCT.

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Scedosporium sinusitis is an opportunistic fungal infection that is difficult to treat due to its inherent resistance to many antifungal agents. Infections may cause both localized or disseminated disease usually in skin and soft tissues. Immunocompetent persons are typically unaffected and disseminated disease occurs in immunocompromised hosts. Scedosporiumis a common hyaline mold causing sinopulmonary disease in those with hematologic malignancies and neutropenia. A 38-year-old Caucasian male with a medical history significant for HIV with intermittent treatment compliance, high-grade diffuse large B cell lymphoma (DLBCL) on chemotherapy, and hemophagocytic lymphohistiocytosis (HLH) presented with right-sided facial pain and fever. Maxillofacial computed tomography (CT) showed thickening and opacification of the sphenoid and maxillary sinuses concerning for fungal sinusitis. Endoscopic transsphenoidal debridement showed fungal growth of Scedosporium and the patient's blood cultures were ultimately negative. The patient underwent debridement of fungal sinusitis as well as right medial maxillectomy and ethmoidectomy. A three-month course of voriconazole was started and completed with weekly liver enzyme tests to monitor medication side effects. He has since been observed well as an outpatient with his oncologist after three months loss to follow-up and his infection has resolved.

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Immune checkpoint inhibitors (ICIs) as standard of care have revolutionized the treatment of patients with metastatic melanoma. The combination of nivolumab and ipilimumab improves treatment efficacy and prolongs survival compared to monotherapy alone. However, combination therapy is also associated with an increased incidence of adverse events. We report an uncommon yet important case of multi-organ failure in a patient following a single dose of nivolumab plus ipilimumab. A 60-year-old male with a history of ulcerative colitis in remission and metastatic melanoma was admitted on February 25, 2021, for presumed sepsis, after presenting with neutropenic fever. His brain metastases were previously resected on January 14, 2021, and he was started on dexamethasone 4 mg BID for six weeks. On February 11, 2021, he received one dose of nivolumab plus ipilimumab, per the CheckMate-067 protocol. He presented 14 days later with fever, diarrhea, pancytopenia, renal failure, drug-induced hepatitis, and myocarditis. The infectious workup was negative. His neutropenia responded to growth factors. He was diagnosed with interstitial nephritis due to immunotherapy and treated with corticosteroids. His symptoms resolved with concomitant improvement of his renal, hepatic, and cardiac function. He was discharged home in a stable condition. Although these specific immune-related adverse events (irAEs) are uncommon and rarely occur simultaneously, ICIs can trigger non-specific immune system activation, resulting in widespread inflammatory effects. Since irAEs can lead to multi-organ failure, as evidenced in this case, early recognition and institution of high-dose steroids are critical to preventing rapid deterioration. Given that ICI therapy is the standard of care for several cancers and is often studied in clinical trials, increased education on irAE toxicity and updated algorithms on the management of febrile cancer patients are warranted.

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Safe outpatient management of acute leukaemia consolidation cycles may enable substantial savings in admission costs. Safety involves the prompt administration of antibiotics in patients with neutropenic fever. Our unit in a metropolitan tertiary referral hospital analysed a cohort of patients spanning a 10-year period, with two key observations: (i) a high proportion of patients living a substantial distance from hospital and (ii) the high incidence and generally prompt onset of fever after severe neutropenia, suggesting this broad applicability of this approach is unfeasible without addressing travel issues and potentially reducing and/or delaying neutropenic fever with prophylactic antibiotics.

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Background: Mortality rates in patients with haematological malignancies who required intensive care unit (ICU) admission have in the past been high. More recently, however, improved outcomes for critically ill haematological patients have been reported. Objectives: To determine outcomes, average length of ICU stay, and factors associated with mortality in patients with haematological malignancies and neutropenic fever in the multidisciplinary ICU (MICU) at Universitas Academic Hospital (UAH), Bloemfontein, Free State Province, South Africa. Methods: We conducted a retrospective review of medical and laboratory records of all patients admitted to the UAH MICU with haematological malignancies and febrile neutropenia between 2010 and 2019. Results: A total of 182 patients with haematological malignancies were admitted to the MICU between 1 January 2010 and 31 December 2019, of whom 51 (28.0%) fulfilled the inclusion criteria for the study. The median age was 33 years, and 29 patients (56.9%) were female. Most patients had either acute myeloid leukaemia (n=22; 43.1%) or acute lymphocytic leukaemia (n=16; 31.4%), while B-cell lymphoma (n=12; 23.5%) and multiple myeloma (n=1; 2%) were less frequent. The median length of stay in the ICU was 3 days. ICU mortality was 76.5% and hospital mortality 82.4%. Factors associated with mortality included septic shock, vasoactive agent use and mechanical ventilation. Conclusion: Patients with haematological malignancies and febrile neutropenia in the UAH MICU have high ICU and hospital mortality rates. More needs to be done with regard to timeous management of patients with haematological malignancies and septic shock in our setting to improve survival. Study synopsis: This is the first study to report on ICU mortality of adult patients with haematological malignancies and neutropenic sepsis in a tertiary hospital ICU in the Free State. These patients had a high mortality rate. What the study adds. Our study shows that septic shock, vasoactive agent use and mechanical ventilation were associated with increased ICU mortality.Implications of the findings. Strict adherence to infection prevention and control measures in haematology wards is required. Early recognition and treatment of sepsis before it progresses to septic shock is important. ICUs must be designed so that isolation cubicles are readily available to prevent cross-infection of patients.

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Cefepime is widely considered a safe and effective antibiotic, but it can have rare and serious side effects. We present a case of a 33-year-old female patient who developed severe and potentially life-threatening neutropenia after being on cefepime for 25 days. Despite extensive investigations, no other causes of neutropenia could be identified. Discontinuing the medication and administering a single dose of filgrastim produced a rapid and dramatic response. This case highlights the rare but serious risk of cefepime-induced neutropenia and underscores the need for clinicians to remain vigilant for this potential adverse effect. It is important to note that discontinuing the medication can rapidly reverse the effects, making timely recognition and intervention crucial for patient outcomes.

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BACKGROUND: Epidemiology of infectious diseases causing febrile illness varies geographically with human attributes. Periodic institutional surveillance of clinical and microbiological profiles in adding data to updating trends, modulating pharmatherapeutics, signifying possible excessive treatments and risk of drug resistance in post-chemotherapy neutropenic fever (NF) in hematological malignancy (HM) is limited. We aimed to review institutional clinical and microbiological data and explore clinical phenotype pattern groups among data. METHODS: Available data from 372 NF episodes were included. Demographics, types of malignancies, laboratory data, antimicrobial treatments and febrile-related outcome data such as predominant pathogens and microbiological diagnosed infections (MDIs) were collected. Descriptive statistics, two-step cluster analysis and non-parametric tests were employed. RESULTS: The occurrences of microbiological diagnosed bacterial infections (MDBIs; 20.2%) and microbiological diagnosed fungal infections (MDFIs; 19.9%) were almost equal. Gram-negative pathogens (11.8%) were comparable with gram-positive pathogens (9.9%), with gram-negative being slightly predominant. Death rate was 7.5%. Two-step cluster analysis yielded four distinct clinical phenotype pattern (cluster) groups: cluster 1 'lymphomas without MDIs', cluster 2 'acute leukemias MDBIs', cluster 3 'acute leukemias MDFIs' and cluster 4 'acute leukemias without MDIs'. Considerable NF events with antibiotic prophylaxis being not identified as MDI might have cases in low-risk with non-infectious reasons causing febrile reactions that might possibly not require prophylaxis. CONCLUSIONS: Regular institutional surveillance with active parameter assessments to signify risk levels in the post-chemotherapy stage, even prior to the onset of fever, might be an evidence-based strategy in the management of NF in HM.

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BACKGROUND: Chemotherapy-induced febrile neutropenia (FN) is one of the more common oncological emergencies. Despite evidence in the oncology literature suggesting that low-risk cases of FN can be managed safely at home, most patients with FN who present to the emergency department (ED) are admitted. FN risk stratification methods, such as Multinational Association for Supportive Care in Cancer (MASCC) and Clinical Index of Stable Febrile Neutropenia (CISNE) scores, may be useful when considering patient disposition. We sought to address whether the existing body of literature is adequate to support the use of these methods when treating patients with FN in the ED. METHODS: A PubMed search from January 1, 2016 to March 19, 2021 was performed using the following search strategy: "febrile neutropenia" OR (fever AND neutropenia)) AND (emerg* OR outpatient) AND (admit OR admission OR hospitalization). General review articles and case reports were omitted. Each of the articles selected underwent a structured review. RESULTS: The search yielded 371 articles, which were independently screened for relevance by two authors, and 23 articles were selected for inclusion. MASCC score was used in 10 of the identified studies and each of these studies concluded that the score was useful in the ED. Most of the identified studies found that CISNE score had a higher sensitivity than MASCC score (96.7% vs. 32.9%, respectively), but a lower specificity (22.2% vs. 89.5%). CONCLUSIONS: FN risk stratifications tools, such as MASCC and CISNE scores, are supported by the existing literature and may be included as part of the decision-making process when considering patient disposition.

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INTRODUCTION: Recent trials have shown early de-escalation of empiric antimicrobial therapy (EAT) in febrile neutropenia has led to less adverse effects with no difference in patient mortality. In 2019, our institution adjusted internal guidelines to de-escalate EAT after 7 days of intravenous anti-pseudomonal therapy in patients with signs of clinical recovery from febrile neutropenia and no evidence of infection. METHODS: This was a retrospective, single-center, observational, cohort study. Eligible patients were adults with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) who received induction chemotherapy and developed febrile neutropenia without documented infection. Patients were separated based on EAT duration: ≤ 9 days and > 9 days. Empiric antimicrobial therapy was defined as the initiation of an anti-pseudomonal beta-lactam. The primary outcome was the difference in number of EAT-free days. Secondary outcomes included fever recurrence, ICU admissions, fever duration, infections post de-escalation, and Clostridioides difficile infection (CDI). RESULTS: Forty-four encounters met inclusion. The EAT ≤ 9 days group had 7 more EAT-free days compared to the EAT > 9 days group (p < 0.001). No between-group differences were identified in terms of fever after EAT discontinuation (p = 0.335), ICU admission (p = 0.498), or CDI (p = 0.498). The EAT > 9 days group experienced longer initial fever (p < 0.001) and received addition of resistant Gram-positive coverage (p = 0.014). More patients receiving EAT > 9 days had a diagnosis of AML (p = 0.001). CONCLUSIONS: Shorter EAT duration did not lead to worse outcomes in patients with AML or ALL who received induction chemotherapy and developed febrile neutropenia without a documented infection source.

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Viridans group streptococci (VGS) bloodstream infection (BSI) in neutropenic patients can be a severe complication. A higher prevalence of vancomycin use has been reported due to reduced susceptibility to penicillin. We aimed to assess the impact on mortality of both penicillin minimal inhibitory concentration (MIC) and the use of vancomycin. We conducted a retrospective multicenter study including consecutive neutropenic patients with VGS BSI between 2007 and 2019. Univariable and multivariable analyses were conducted to evaluate risk factors for mortality, including penicillin susceptibility as an independent variable. Non-susceptibility to penicillin was defined as MIC ≥ 0.25. We included 125 neutropenic patients with VGS BSI. Mean age was 53 years and ~ 50% were women. Overall, 30-day mortality rate was 25/125 (20%), and 41 patients (33%) had a VGS isolate non-susceptible to penicillin. In univariable analysis, no significant association was demonstrated between penicillin non-susceptibility and mortality (9/25, 26% vs. 32/100, 32%, p = 0.81). Among patients with a non-susceptible strain, the use of vancomycin was not significantly associated with mortality (empirical, p = 0.103, or definitive therapy, p = 0.491). Factors significantly associated with increased mortality in multivariable analysis included functional status (ECOG > 1, adjusted odds ratio [aOR] 12.53, 95% CI 3.64-43.14; p < 0.0001); allogeneic transplantation (aOR 6.33, 95% CI 1.96-20.46; p = 0.002); and co-pathogen in blood cultures (aOR 3.99, 95% CI 1.34-11.89; p = 0.013). Among neutropenic hemato-oncological patients with VGS BSI, penicillin non-susceptibility and the use of vancomycin were not associated with mortality. Thus, vancomycin should not be used routinely as empirical therapy in neutropenic patients with suspected VGS BSI.

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