Febrile Episodes Research Articles

Efficacy and safety of a colostrum- and Aloe vera-based oral care protocol to prevent and treat severe oral mucositis in patients undergoing hematopoietic stem cell transplantation: a single-arm phase II study

Oral mucositis is one of the worst effects of the conditioning regimens given to patients undergoing hematopoietic stem cell transplantation. It is characterized by dry mouth, erythema, mucosal soreness, ulcers, and pain, and it may impact patient outcomes. Bovine colostrum and Aloe vera contain a wide variety of biologically active compounds that promote mucosal healing. A non-randomized phase II study was designed to assess the safety and efficacy of a combined bovine colostrum and Aloe vera oral care protocol to prevent and to treat severe oral mucositis in transplant patients. Two commercially available products were given to patients in addition to the standard protocol: Remargin Colostrum OS® mouthwash and Remargin Colostrum Gastro-Gel® taken orally. Forty-six (78.0%) patients experienced oral mucositis, 40 (67.8%) developed mild–moderate forms, and 6 (10.2%) severe ones. Comparing the study group’s outcomes with those of a homogeneous historical control group, severe oral mucositis decreased significantly (10.2% vs. 28.4%; P < 0.01), as did its duration (0.5 ± 1.9 vs. 1.5 ± 3.0 days; P < 0.01). Febrile neutropenia episodes (69.5% vs. 95.1%; P < 0.01) and duration (4.0 ± 4.7 vs. 6.2 ± 4.5 days; P < 0.01) also decreased. These findings show that the experimental protocol seems effective in preventing severe forms of oral mucositis. However, a randomized controlled trial is necessary to confirm this.

PFAPA Syndrome: Clinical, Laboratory and Therapeutic Features in a Single-Centre Cohort.

ObjectiveThe aim of this study is to describe a group of Romanian children with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome.MaterialsThis consisted of 39 children diagnosed with PFAPA syndrome according to Thomas’ criteria (eight patients with an age at diagnosis <1 year and 31 patients with an age at diagnosis >1 year).MethodsRetrospective analysis of the patients with PFAPA syndrome was focused on clinical features, laboratory findings and therapeutic methods. Comparison between the two groups divided by age at onset was also investigated.ResultsMedian age at onset was 1.58 years, and median age at diagnosis was 2.97 years. The mean interval between episodes was 35.5 days and the mean duration per febrile episode was 4.1 days. The median diagnosis delay was 2.42 years. The patients presented pharyngitis (100%), adenitis (94.8%) and aphthous lesions (66.7%). The frequency of febrile attacks was higher in children with an age at diagnosis under 1 year (p = 0.0287). Younger age was associated with the presence of aphthae. The mean value of C-reactive protein (CRP) was 7.9mg/dl and the mean value of leucocytes was 14,839/mm3. In 95% of patients given oral corticosteroids, remission of symptoms was reported within 24 h. In three patients, tonsillectomy was performed with complete remission of the disease.ConclusionWe present a cohort of children with PFAPA syndrome, with clinical and laboratory features similar to those described in the literature. Febrile attacks had a higher incidence in children with younger age at the onset of the disease. The patients had a favorable response to corticosteroids.

Adjuvant Treatment for Protocadherin 19 (PCDH19) Syndrome.

Protocadherin 19 (PCDH19) syndrome is inherited as an X-linked pattern and affects mainly females. This syndrome is caused by a mutation in the PCDH19 gene encoding for the protocadherin protein. It is characterized by refractory seizures during febrile episodes with neuropsychiatric manifestations. There is no consensus on the treatment of PCDH19. We conducted a literature review to investigate the main drugs used for this syndrome, and to evaluate the best possible course of adjuvant treatment for these patients. We used an advanced PubMed search strategy with the following inclusion criteria: a) full-text papers, b) English Language, and c) studies conducted in humans. Exclusion criteria: a) literature reviews, b) systematic reviews, and c) metanalysis. We gathered 26 observational papers to conduct this literature review on clobazam and bromide which have been shown to reduce seizures by 50%. Corticosteroids improved neurological symptoms during the episodes in a few patients. Nevertheless, they recurred after a few months. Preliminary results of ganaxolone, which is still under study, demonstrated a reduction of 60% in seizure episodes. A ketogenic diet has been studied to treat several refractory epilepsies, including PCDH19; it has promising results as effective adjuvant therapy in the resolution of status epilepticus, suggesting it could be used as part of the treatment in early childhood. Stiripentol was given as adjuvant therapy in a patient with PCDH19 epilepsy resulting in the most extended period of seizure-free episodes, but more studies must be performed to assess its efficacy.

A Study to Assess the Management of Febrile Neutropenia in Oncology Patients in a Tertiary Care Hospital

Background: The cytotoxic chemotherapy is the mainstay treatment of cancer and it is usually complicated with infections. Appropriate antibiotics and other supportive medications must be started immediately as bacterial infections may progress with the absence of granulocytes. Improved outcomes can be seen with empirical administration of broad-spectrum antibiotics and they remain as the standard of care. Patients with intermediate-risk for Febrile Nuetropenia (FN) (10%-20%) need to be evaluated for additional patient risk factors, after assessment, patients who present with at least one of the risk factors for FN is recommended for treatment with a G-CSF. Methodology: Our study was a retrospective cohort single centered observational study carried out randomly in 104 patients in the oncology department of Lourdes hospital, Cochin Data of the patients were collected from Mediware system, medical records and Statistical software SPSS were used for analysis of the data. Results: In our study febrile neutropenia was managed using antimicrobials, of which antibiotics and antifungals prescribed were 12.09% and 1.97% respectively and with granulocyte-colony stimulating factors (G-CSFs) (6.15%). Principally used empirical monotherapy was meropenem sulbactum / meropenem (n = 48) which was followed by piperacillin tazobactum (n=18) and cefoperazone sulbactum (n=15) This study had a leading prescription of Cyclophosphamide containing chemotherapy regimens which led to neutropenia. Breast cancer patients accounts the majority of febrile neutropenic episodes despite of receiving GCSF prophylaxis. The most common type of cancer patients who are suffering from neutropenia were breast cancer. The compliance with National Comprehensive Cancer Network (NCCN) guidelines were analyzed in that we can see 84.6% patients had partial compliance and 14.4% patients had full compliance. Conclusion: A total of 66 patients received both antibiotics and G-CSF treatment however 13 patients and 25 patients were managed only with G-CSF and antibiotic therapy respectively. This study had a leading prescription of Cyclophosphamide containing chemotherapy regimens which led to neutropenia. These regimens were used mainly in breast cancer patients. Breast cancer patients accounts the majority of febrile neutropenic episodes despite of receiving GCSF prophylaxis. The most common type of cancer patients who are suffering from neutropenia were breast cancer. The NCCN guidelines, majority of patients showed partial compliance(86.6%) and about (14.4%) showed full compliance.

Respiratory Viral Infections in Pediatric Acute Leukemia Patients Presenting with Febrile Neutropenia in a Tertiary Hospital in Ankara, Turkey

Background: The prevalence and roles of respiratory viral pathogens in pediatric acute leukemia patients with febrile neutropenia is not well understood and laboratory tests to detect viral agents are not a routine practice in the investigation of these patients.Patients and methods: The medical records of 50 neutropenic episodes in pediatric acute leukemia patients in the Hacettepe University Children’s hospital, Ankara-Turkey, were reviewed. Blood samples were obtained for blood culture, aspergillus antigen and other routine tests. Nasopharyngeal aspirate samples were collected and transferred to the laboratory in a viral transport medium. Therapy for febrile neutropenia was initiated according to our institution’s protocols.Results: Fifty (50) consecutive febrile neutropenic episodes in 44 pediatric ALL and AML patients were included in the study between 1st October 2009 and 31st August 2010. Microbiologically documented infections were found in 36% of the episodes, clinically documented infections in 16% of the episodes and 48% of the episodes were accepted as Fever of Unknown Origin. Twenty-two percent (22%) of the microbiologically documented infections were due to viral agents, 56 % were due to Gram positive bacteria, 21% were due to Gram negative bacteria (E. coli) and only one episode of fungemia was documented.Conclusions: Fever of Unknown Origin constituted nearly 50% of the febrile neutropenic episodes in this study despite the availability of advanced laboratory diagnostic methods. Among the episodes with microbiologically documented infections, bacterial pathogens were especially common. Presenting complaints like cough and rhinorrhea are not specific to a viral etiology and care should be taken not to miss potentially threatening bacterial pathogens in such episodes.

Differentiating flare and infection in febrile lupus patients: Derivation and validation of a calculator for resource constrained settings.

Background: Patients with Systemic Lupus Erythematous (SLE) are at an increased risk of infection and it is often difficult to differentiate between infection and disease activity in a febrile patient with SLE. Methods: Patients with SLE (SLICC criteria) presenting with fever between December 2018 and August 2021 were included. Neutrophil to lymphocyte ratio (NLR), NEUT-x, -y, -z indices, Erythrocyte sedimentation rate (ESR), C-reactive protein(CRP), C3, C4, anti-dsDNA antibodies, and procalcitonin(PCT) were tested in addition to investigations as per the treating physician's discretion. Based on the clinical assessment and laboratory data, the febrile episode was classified into infection, disease flare, or both. Statistical analysis was done using GraphPad prism v8.4.2. A novel composite score was devised and validated with a calculator incorporated is a spreadsheet. The performance of a previously proposed model of duration of fever, CRP, and dsDNA (Beca et al) was evaluated and other models using PCT and NEUT-Z were explored. Results: Among 168 febrile episodes in 166 patients with SLE (25 (19-32) years), 46 were due to infection, 77 due to flare, 43 due to both, and two due to other causes. High SLEDAI 2K (0.001), anti-dsDNA (p = 0.004), and low complements(C3, p = 0.001 and C4, p = 0.001) were characteristic of disease flare, whereas high total leukocyte count (TLC) (p = 0.008), NLR (p = 0.008), NEUT-x (p = 0.001), -y (p = 0.03), -z (p = 0.002), CRP (p = 0.001), and PCT (p = 0.03) were observed with infection. A model using age, TLC, and CRP was devised using 80% of the cohort with an AUC of 0.88 (0.78-0.97) which was validated in the remaining 20% to have an AUC of 0.83(0.60-1.0). The model devised by Beca et al yielded an AUC of 0.74. Use of PCT did not improve the discrimination between flare and infection. A Model of C4 and NEUT-z analyzed in a subset performed well and needs further exploration. Conclusion: A composite score of low cost and routinely available parameters like age, TLC, and CRP gives a good discrimination between infection and flare in a febrile patient with SLE.

Gemcitabine, Cisplatin, and Dexamethasone as a Salvage and Mobilization Chemotherapy Before Autologous Stem Cell Transplantation is Effective and Safe Outpatient Regimen in Relapsed and Refractory Hodgkin Lymphoma Patients

BackgroundSecond line salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the current standard treatment for eligible patients with relapsed and refractory (R/R) Hodgkin lymphoma (HL). Several salvage regimens have been used before ASCT. However the optimal salvage regimen is still unclear. We report outcome of patients with R/R HL treated with gemcitabine, cisplatin, and dexamethasone (GDP) regimen before ASCT in this retrospective study aiming at evaluating efficacy, stem cell mobilization activity and safety of GDP in a real-life setting. Patients and MethodsForty-five patients with R/R HL who were treated with GDP as salvage and mobilization regimen before ASCT were analyzed retrospectively. Peripheral blood stem cells (PBSC) were collected after GDP. All patients underwent ASCT after 2 cycles of GDP. ResultsThirty-six (80%) patients achieved overall response including 24 (53.3%) complete response (CR). PBSC collections were adequate in all patients with a median number of 11.01 × 106/kg CD34+ cells. The most common grade 3/4 hematological adverse events were thrombocytopenia (31.1%) and neutropenia (22.2%). There were no febrile neutropenic episodes. Grade 3 or 4 renal, hepatic, or cardiac toxicity was not observed. The 4 year progression-free survival and overall survival for patients receiving GDP followed by ASCT were 72% and 92%, respectively. ConclusionOur results suggest that GDP is a viable therapeutic option before ASCT with high response rate, favorable toxicity profile and excellent mobilization potential. Applicability of GDP on an outpatient setting also provides advantage over other effective salvage regimens.

Efficacy and Safety of Levofloxacin Prophylaxis During Induction Therapy for Childhood Acute Lymphoblastic Leukemia

Background: Infection related complications represent an important cause of morbidity and mortality in pediatric cancer patients, especially in those receiving chemotherapy. Although antibiotic prophylaxis is used in adult leukemic patients, but it is less practiced in pediatric cancer patients. The aim of this study was to evaluate the efficacy and safety of Levofloxacin prophylaxis to reduce infection which occur during induction phase of chemotherapy among pediatric Acute Lymphoblastic Leukemia (ALL) patients.&#x0D; Materials and methods: This single centered, pilot study in RCT design was conducted in Pediatric HematoOncology Department of Chittagong Medical College Hospital (CMCH). Sixty newly diagnosed ALL patients admitted for chemotherapy were randomly allocated to two groups 30 in each: one group received Levofloxacin prophylaxis (Intervention group) and other group did not receive prophylaxis (Control group). During the whole period of induction, clinical and laboratory features of infection, fever and neutropenia were observed and adverse effects were noted in both groups.&#x0D; Results: In induction phase of chemotherapy of ALL, significantly lower proportion of patients developed fever in the intervention group than in the control group [(18/30, 60.00%) versus (26/30, 86.67%)]. Incidence of infection was significantly less in intervention group compared to control group (60% versus 86.7%, p=0.039). Also, incidence of febrile neutropenia was significantly less in intervention group compared to control group (p=0.039). No major adverse effects were observed in any of the levofloxacin prophylaxis group except only two patients reported mild lower limb pain. &#x0D; Conclusion: It may be concluded from this pilot study that, Levofloxacin prophylaxis in children with ALL during the induction phase of chemotherapy is effective in reducing infection, febrile episodes and febrile neutropenia.&#x0D; JCMCTA 2022 ; 33 (1) : 34-39

P1122: EFFICACY OF ALPELISIB IN PI3K-DRIVEN LANGERHANS CELL HISTIOCYTOSIS

Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm characterized by the accumulation of clonal dendritic cells expressing CD1a and CD207 (Langerin). LCH affects both children and adults and typically ranges from an indolent unifocal form to a progressive multisystemic disease. In the past decade, in depth molecular profiling of LCH as well as other histiocytic neoplasms demonstrated that these diseases are fundamentally dependent on somatic MAPK activating mutations, with the canonical V600E BRAF mutation emerging in more than 50% of LCH patients. Nonetheless, MAPK independent driver mutations were previously reported and anecdotal evidence of successful targeted treatment of various histiocytoses harboring non-canonical drivers such as RET, ALK and CSF1R were previously described in the literature. Aims: To report a case of PI3K driven LCH treated with an isoform specific PIK3CA inhibitor. Methods: Case summary: a 46 year-old mother of 3 presented with complaints of progressive headaches, polydipsia and polyuria. Following a pathological water deprivation test and identification of pituitary stalk thickening on MRI, a diagnosis of central diabetes insipidus (CDI) was established and desmopressin treatment was initiated. However, 10 months following her CDI diagnosis, the patient began to complain of sub febrile episodes of fever and worsening dry cough. Imaging studies including PET/CT disclosed extensive bilateral reticulo-nodular infiltration, nodules with cystic transformation and ground glass opacity, suspicious of pulmonary LCH. Histological examination of a wedge biopsy specimen obtained from the lungs confirmed the diagnosis of LCH and consequent molecular studies identified the M1043V PIK3CA mutation. During her medical investigation, the patient’s conditioned worsened, with new disease foci emerging – including cervical lymphadenopathy and a lytic vertebral lesion involving D11. The patient then received palliative radiotherapy directed at the D11 lytic lesion followed by escalating systemic therapy with single agent Alpelisib, via the Managed Access Program at Novartis. Response to treatment was assessed clinically and using PET/CT. At the molecular level, the effect of Alpelisib was assessed by measuring PTEN expression levels and cell cycle regulating non-coding RNA molecules by using quantitative real-time polymerase chain reaction (qRT-PCR). Results: Treatment with Alpelisib resulted in rapid amelioration of night sweats within 6 days, decrease in back pain within 3 weeks and normalization of all abnormally FDG avid disease foci within 3 months of treatment. The complete metabolic response observed persists currently more than a year following treatment initiation. Treatment with Alpelisib is well tolerated except for a mild increase in HbA1C levels to 6.7%. Moreover, PTEN, the main regulator of the PI3K pathway was found to be upregulated following 3 and 9 months of treatment, in parallel to downregulation of small non-coding RNAs molecules that regulates its expression. Image:Summary/Conclusion: This is the first study demonstrating that the alpha catalytic subunit of PI3K is a targetable non-canonical driver of LCH.

Factors Associated with Gram-Negative Bacteremia and Mortality in Neutropenic Patients with Hematologic Malignancies in a High-Resistance Setting.

Patients with hematological malignancies (HMs) have a substantial incidence of febrile neutropenic episodes. Gram-negative bacteremia (GNB) is still the major cause of these episodes. We evaluated the factors associated with GNB and mortality of bacteremic patients with HMs in a high-resistance setting. We conducted a prospective cohort study from March 2018 to June 2019 with 66 bacteremic and 132 non-bacteremic patients. Regression analyses were used to identify factors associated with GNB and 30-day mortality. The mean age was 53.83±15.21 years, and 129 (65.2%) of the patients were male. In multivariable analysis, factors independently associated with GNB were male gender, duration of hospitalization and neutropenia before the febrile neutropenic episode, leukemias and allogeneic transplant recipients, radiotherapy, receiving glucocorticosteroids, colonization with resistant microorganisms. All-cause mortality and 30-day mortality were 47.0% and 30.3% in cases of GNB, compared to non-bacteremic controls 25.0% and 10.6%, respectively. Sepsis, duration of hospitalization before the febrile neutropenic episode, carbapenem-resistant GNB, and inappropriate empirical antibiotic treatment was found as factors associated with 30-day mortality. Prior antibiotic exposure particularly beta-lactamase inhibitor combinations and carbapenems during the past 30 days was more frequent in the bacteremic group. An increasing trend was observed in multidrug-resistant (MDR) bacteria (p=0.03) and carbapenem-resistant Enterobacterales (p=0.02) over the years. By considering the risk factors associated with GNB and 30-day mortality that we detected in our study among neutropenic patients, a personalized approach for the management of febrile neutropenic patients can be designed by means of an effective antimicrobial stewardship program including the appropriate use of broad-spectrum antibiotics.

Efficacy and Safety of Piperacillin-Tazobactam and Cefepime as Empirical Therapy for Febrile Neutropenic Children with Acute Lymphoblastic Leukaemia (ALL)

Background: Infection is a major clinical challenge in ALL treatment. Prompt administration of empirical antibiotic in febrile neutropenic patients has reduced the mortality. Both Cefepime or Piperacillin-Tazobactam has been used as empirical treatment.&#x0D; Objective: To compare the efficacy and safety between Piperacillin-Tazobactam with Cefepime in febrile neutropenic children with ALL.&#x0D; Materials and methods: This randomized study was conducted from August 2015 to August 2016 in BSMMU. Sixty one episodes of febrile neutropenia in children with ALL, aged 0 to18 years were included in this study. Patients were randomized into two groups. One group received Piperacilln/Tazobactam and another group received Cefepime and data of 60 febrile neutropenic episodes were analyzed.&#x0D; Results: Febrile neutropenic episodes in the Piperacillin/Tazobactam group were 28 and in Cefepime group was 32 episodes and 34(57.63%) were male and 25 (42.37%) female. Median age was 5 years and 38(62.3%) neutropenic episodes were in induction phase. Majority had fever without focus 21(35%). Microorganisms isolated in 13 (21.66%) patients and majority 6 (46.15%) had blood infection. Most of the isolated organisms were Gram negative 11(84.61%). Overall treatment success without modification in the Piperacillin/Tazobactam group was 17(60.7%) and in Cefepime group 18 (56.3%) and that comparison was not statistically significant (p= 0.732). Significant difference was also not found comparing the mean duration of fever, neutropenia and hospital stay.&#x0D; Conclusion: Both Piperacillin/Tazobactam and Cefepime were found effective and safe as an empirical therapy for febrile neutropenic children with ALL.&#x0D; BANGLADESH J CHILD HEALTH 2021; VOL 45 (2) : 83-88

Luc’s Abscess: The Zygomatic Route of Infection from Cholesteatoma

Luc’s abscess is an uncommon complication of otitis media wherein a subperiosteal abscess develops into the temporalis muscle and follows the route of a pneumatized zygoma.1 In uncomplicated cases, surgical drainage and antibiotics are adequate management with mastoidectomy reserved for severe or complicated cases. We report a case of complicated Luc’s abscess presenting with many complications that required multiple surgical interventions. CASE REPORT A 23-year-old man had a three-month history of yellowish, mucoid, foul-smelling left ear discharge associated with multiple episodes of non-projectile watery vomiting (&lt; 1 cup each) and left-sided facial paresis. These symptoms were accompanied by ipsilateral hearing loss, tinnitus and dizziness prompting consult and admission to a secondary hospital. A cranial Computed Tomographic (CT) scan showed a cholesteatoma in the left ear. The facial asymmetry improved, vomiting was resolved with intravenous antibiotics, hydration, and an anti-emetic, and he was subsequently discharged. He continued to have recurrent, foul-smelling left ear discharge and left hemifacial paresis persisted. Left-sided otorrhagia and ipsilateral hemifacial paresis were subsequently associated with left hemifacial swelling, otalgia (VAS of 7/10, described as sharp), and decreased hearing, prompting an outpatient consult with a private ENT specialist. The symptoms persisted despite 7 days of oral ciprofloxacin, this time associated with drowsiness, neck pain and febrile episodes. The patient consulted in our institution and was advised emergency admission. He was admitted drowsy, coherent with GCS 15 (E4V5M6). The left temporal area was edematous and tender, extending to the ipsilateral post-auricular area inferiorly and frontal area superiorly. (Figure 1) Otoscopy revealed yellowish, foul-smelling, copious muco-purulent discharge and near-total perforated left tympanic membrane. The right ear had unremarkable otoscopic findings. Tuning fork tests at 512 Hz were consistent with sensorineural hearing loss in the left ear with House-Brackmann IV facial nerve paresis. Brudzinski and Kernig tests were negative with no signs of dysmetria, dysdiadochokinesia or dysarthria on cerebellar testing. Gram stain and KOH smears of the left ear discharge revealed C fruendii and fungal elements. High resolution temporal bone CT scan showed otomastoid disease on the left with automastoidectomy defect, associated subperiosteal and intracerebral abscess formation on the left, with otherwise unremarkable right temporal bone. (Figure 2)

The impact of COVID-19 lockdown measures on rates of febrile neutropenia in a cohort of Irish patients receiving chemotherapy.

e18784 Background: Febrile neutropenia in patients receiving chemotherapy is a life-threatening condition requiring prompt attention. This condition may also result in dose reductions, delays, or discontinuations of chemotherapy which compromise patient outcomes. This study seeks to evaluate the impact of COVID19 “lockdown” public health measures in Ireland on the incidence of febrile neutropenia in patients who were receiving cytotoxic chemotherapy regimens. Methods: All patients receiving chemotherapy at the Bon Secours Hospital Cork who were admitted with neutropenia and fever during two separate time periods were included in the study: 1st April 2018 to 31st March 2019 (“pre-pandemic year”) and 1st April 2020 to 31st March 2021 (“pandemic year”). The pandemic year selected equates to a period of heightened infection control measures in Irish society, featuring public health advice re social distancing, routine mask wearing in public and successive lockdown waves. Retrospective chart review was performed on all patients admitted to the oncology inpatient ward who had blood cultures on admission to determine the number of these patients who were neutropenic at the time of blood culture draw. Similarly, pharmacy records were accessed to determine the number of unique chemotherapy items dispensed in each year in order to establish a rate of febrile neutropenia episodes per 100 chemotherapy items dispensed for each period. The incident rate ratio was calculated using the Exact Poisson Test. Results: During the pre-pandemic year there were 57 individual admissions with febrile neutropenia compared with 32 admissions during the pandemic year. There were 4581 chemotherapy units dispensed during the pre-pandemic year compared to 4628 during the pandemic year. The rate of febrile neutropenia episodes per 100 chemotherapy units dispensed was 1.24 (95% CI 0.94, 1.61) in the pre-pandemic year and 0.69 (95% CI 0.47, 0.98) in the pandemic year. The incident rate ratio is 1.80 (95% CI 1.14, 2.87, two-sided P = 0.007). 9 of 57 (16%) admissions in the pre-pandemic year were associated with positive blood cultures compared with 4 of 32 (13%) in the pandemic year (not significant by Fisher's exact test). Conclusions: Increased precautionary infection control measures during the COVID19 pandemic public health restrictions correlated with a significant reduction in the rate of febrile neutropenia amongst patients receiving cytotoxic chemotherapy. This suggests that there may be a role for similar measures for this patient cohort in the post-pandemic period. Options which patients may consider to employ include social distancing, wearing face-coverings and restricting social contacts while at risk of neutropenia from cytotoxic chemotherapy regimens.

Differentiating probable nitrofurantoin-induced drug fever from antipsychotic-induced hyperthermia in a patient receiving clozapine

Nitrofurantoin (NIT) is a commonly utilized antibiotic for the treatment of UTIs. Although well tolerated, NIT is not without potential adverse reactions. This case report details the observation of probable NIT-induced drug fever in a patient receiving clozapine. A 61-year-old female with treatment-refractory schizoaffective disorder was admitted to a psychiatric unit with paranoia and auditory hallucinations, prompting clozapine initiation during day 1 of hospitalization. Due to worsening hallucinations and anxiety, antibiotic therapy with NIT for a presumed UTI was initiated 8 days after admission. Febrile episodes were observed beginning on hospital day (HD) 9, leading to concern for possible neuroleptic malignant syndrome (NMS), which led to clozapine discontinuation. The patient received a total of 3 doses of NIT with continued fever until discontinuation on HD 10. No further complications were encountered, and clozapine was safely resumed on HD 13. Although sparsely described in the medical literature, occurrences of drug fever attributable to NIT are previously reported. A review of the medical literature identified only 5 previously published articles specific to NIT-induced drug fever, none of which specified interruptions of psychotropic therapy for a patient with acute psychiatric decompensation. This case highlights the differential diagnosis of fever related to NIT in a patient receiving clozapine when NMS was initially suspected.

Febrile Episodes during Chemotherapy Induced Neutropenia in Children with Acute Lymphoblastic Leukemia at Children Hospital –Benghazi 2013-2014

Patients undergoing chemotherapy are vulnerable to infection because of immunosuppression and prolonged hospitalizations. Chemotherapy drugs affect neutrophil production through myelosuppression (1) and low inflammatory response so that fever maybe the manifestation of infection (2).&#x0D; The purpose of this study was to analyze febrile neutropenic episodes associated with infections in the 1st three phases of acute lymphoblastic leukemia (ALL) treatment, document the risk factors affecting morbidity, mortality, treatment and the outcome of treatment.&#x0D; The study was a cross-sectional hospital-based descriptive survey in the Hematology-Oncology Unit at Children’s Hospital. It included all cases of (ALL) who were diagnosed within two years and treated with the Berlin Frankfurt Munich (BFM) protocol who developed fever during a neutropenic period. Data was recorded as gender, age, residence, nationality, number of episodes per patient, treatment phase, admission duration, length of stay (LOS) per episode, symptoms, physical examination and severity of fever. Investigations, the antibiotic used and the outcome were also recorded.&#x0D; A total 27children, males accounting for 63%, 67&lt;5 were included in the study. Febrile neutropenic episodes ranged 1–12. Their peak was in January. 40% were in phase II. LOS range 2-35 days. Fever showed a median of 38.8 °C, higher in phase II and III. Admission and therapy phases were longer in children ˂ 2 years old and in males. The neutrophil median was 270/mm3. Stomatitis was seen in70% of episodes, gastroenteritis in 65%, fever of unknown origin (FUO) in 16%and pneumonias in 15%. 20/23 bacterial infections were Gram-negative. 40% of episodes required a change of antibiotics. The mortality rate was 22%.

Impact of Third-Generation Cephalosporin Resistance on Recurrence in Children with Febrile Urinary Tract Infections.

Background: The purpose of this study was to investigate the association between third-generation cephalosporin resistance and urinary tract infection (UTI) recurrence in patients who underwent voiding cystourethrogram (VCUG). Methods: In this retrospective study, data were obtained from hospitalized pediatric patients who had a first febrile UTI episode and subsequently underwent VCUG. Information based on VCUG was mandatory to identify the presence of vesicoureteral reflux (VUR). A multivariable logistic model was used to identify the risk factors for recurrence. Recurrence was divided into early (90-day) and late (1-year), and sensitivity analyses were performed according to each definition. The estimates of all the statistical models were internally validated using bootstrap samples. Results: A total of 210 patients were included, and the overall recurrence rate of UTI was 26.2% (55 of 210). Third-generation cephalosporin resistance was a significant risk factor for early recurrence (odds ratio: 2.79 [1.08–7.20]) but not for late recurrence. Sensitivity analyses showed that third-generation cephalosporin resistance was a significant risk factor for 60-day recurrence but not for 180-day recurrence. A VUR grade ≥ 3 was identified as a consistent risk factor for both early and late recurrence. Conclusions: Third-generation cephalosporin resistance was a significant risk factor for the early recurrence of pediatric UTI in patients who underwent VCUG.

A prediction model for bacteremia and transfer to intensive care in pediatric and adolescent cancer patients with febrile neutropenia.

Febrile neutropenia (FN) is a common condition in children receiving chemotherapy. Our goal in this study was to develop a model for predicting blood stream infection (BSI) and transfer to intensive care (TIC) at time of presentation in pediatric cancer patients with FN. We conducted an observational cohort analysis of pediatric and adolescent cancer patients younger than 24 years admitted for fever and chemotherapy-induced neutropenia over a 7-year period. We excluded stem cell transplant recipients who developed FN after transplant and febrile non-neutropenic episodes. The primary outcome was onset of BSI, as determined by positive blood culture within 7 days of onset of FN. The secondary outcome was transfer to intensive care (TIC) within 14 days of FN onset. Predictor variables include demographics, clinical, and laboratory measures on initial presentation for FN. Data were divided into independent derivation (2009–2014) and prospective validation (2015–2016) cohorts. Prediction models were built for both outcomes using logistic regression and random forest and compared with Hakim model. Performance was assessed using area under the receiver operating characteristic curve (AUC) metrics. A total of 505 FN episodes (FNEs) were identified in 230 patients. BSI was diagnosed in 106 (21%) and TIC occurred in 56 (10.6%) episodes. The most common oncologic diagnosis with FN was acute lymphoblastic leukemia (ALL), and the highest rate of BSI was in patients with AML. Patients who had BSI had higher maximum temperature, higher rates of prior BSI and higher incidence of hypotension at time of presentation compared with patients who did not have BSI. FN patients who were transferred to the intensive care (TIC) had higher temperature and higher incidence of hypotension at presentation compared to FN patients who didn’t have TIC. We compared 3 models: (1) random forest (2) logistic regression and (3) Hakim model. The areas under the curve for BSI prediction were (0.79, 0.65, and 0.64, P < 0.05) for models 1, 2, and 3, respectively. And for TIC prediction were (0.88, 0.76, and 0.65, P < 0.05) respectively. The random forest model demonstrated higher accuracy in predicting BSI and TIC and showed a negative predictive value (NPV) of 0.91 and 0.97 for BSI and TIC respectively at the best cutoff point as determined by Youden’s Index. Likelihood ratios (LRs) (post-test probability) for RF model have potential utility of identifying low risk for BSI and TIC (0.24 and 0.12) and high-risk patients (3.5 and 6.8) respectively. Our prediction model has a very good diagnostic performance in clinical practices for both BSI and TIC in FN patients at the time of presentation. The model can be used to identify a group of individuals at low risk for BSI who may benefit from early discharge and reduced length of stay, also it can identify FN patients at high risk of complications who might benefit from more intensive therapies at presentation.

Indicaciones para la prevención de infecciones en el paciente inmunocomprometido

A total of 48% to 60% of immunosuppressed patients may have a febrile episode, fever, or established or hidden infection. However, the use of antibiotics as a prophylactic measure continues to be controversial due to the worrying rise in bacterial resistance, changes that occur in the host's microbiota, and drug interactions they may cause. European and American recommendations agree on the choice of fluoroquinolones as prophylaxis in immunosuppressed patients with neutropenia that has been ongoing for more than seven days. In addition to an effective prophylaxis strategy, early diagnosis is fundamental for rapid, effective treatment.

Protocolo diagnóstico y tratamiento empírico de la infección sin focalidad en el paciente neutropénico

Neutropenic patients are at particularly high risk of infection, with fever being the only sign they present with in the majority of cases. An etiological diagnosis is made in just 20% to 30% of febrile episodes. Early diagnosis and effective treatment are crucial for decreasing morbidity and mortality in this population. The treatment of fever in neutropenic patients includes intravenous beta-lactam antibiotics such as cefepime. Multidrug-resistant pathogens are emerging and there are few new anti-infectious agents being developed. Therefore, a rational use of antimicrobial agents is fundamental.

Microbiological profile and antibiotic susceptibility pattern in children with malignancy and febrile neutropenia

Neutropenia that occurs in hematologic malignancies or solid tumors may increase the risk of infection and lead to morbidity and mortality. This study aims to investigate the microbiological profile and antibiotic susceptibility pattern in children with malignancy and febrile neutropenia (FN). A cross-sectional study was conducted from January 2017 to June 2021 using medical records from the pediatric inpatient hematology-oncology ward of Dr. Soetomo General Hospital. The inclusion criteria are children with malignancy aged ≤ 18 years, experiencing a febrile episode of neutropenia, and were examined for blood culture at the onset of FN. A total of 291 children were eligible patients. Out of 291, 65 of them had a bacterial infection from blood cultures. Out of 65, almost 57% were dominated by Gram-negative bacteria (GNB). Gram-positive bacteria (GPB) that are often recognized are Staphylococcus hominis, Staphylococcus epidermidis, and Staphylococcus aureus. Meanwhile, the GNB are Pseudomonas aeruginosa and Klebsiella pneumoniae ESBL+. The majority of GNB is almost 100% resistant to ampicillin meanwhile, GPB also reported resistance to β-lactamase. We found no correlation between microorganism infection and malignancy. GNB and GPB are partially resistant to commonly used antibiotics, especially β-lactamases and ampicillin. Alternative therapies are needed to resolve this matter.