Febrile Episodes Research Articles

Advanced Strategies for Hemorrhage Management in Cesarean Sections An In-Depth Procedural Guide

Over the past five decades, there has been a substantial global increase in cesarean section rates. Unfortunately, the incidence of maternal morbidity following cesarean delivery remains notably high, reaching levels as elevated as 36%. Among the prevalent complications are febrile episodes (25%), hemorrhage (4%), hematoma formation (4%), and urinary tract infections (3%). Obstetric hemorrhage, in particular, stands out as a leading cause of maternal mortality worldwide. Excessive bleeding, defined as a blood loss exceeding 1000 ml during cesarean sections, is frequently underestimated, yet it is documented in over 5-10% of such procedures. While conservative management, including vaginal packing and the administration of uterotonic agents, is effective in many instances, persistent hemorrhage may necessitate specific surgical interventions. Therefore, a comprehensive understanding of the procedural steps for managing bleeding during cesarean sections is crucial to mitigating maternal mortality. This review article aims to consolidate various techniques employed to control hemorrhage during cesarean deliveries.

Erysipelothrix rhusiopathiae-associated bloodstream infection in a patient with systemic lupus erythematosus: a case report and literature review

Introduction. Systemic human infections caused by Erysipelothrix rhusiopathiae have been increasingly reported especially within immunocompromised hosts and those with significant occupational exposure to livestock and aquatic animals. We report a case of E. rhusiopathiae bacteraemia in a patient with systemic lupus erythematosus (SLE) and present a literature review on clinical outcomes and microbiologic diagnosis for this organism. Case presentation. A 43-year-old female patient was reporting a 1-month history of intermittent fevers. She recently increased her immunosuppression medication for her underlying SLE on the advice of her rheumatologist. The patient sustained a finger laceration from butchering cattle meat 2 weeks after the onset of her initial symptoms, with worsening index finger swelling and increased febrile episodes. Two weeks post-injury, multiple blood cultures were drawn, and each isolated Gram-positive bacilli. Given her recurrent intermittent fevers, there was a concern for ongoing infection, and therefore, intravenous vancomycin was started with prompt referral to an outpatient parenteral antibiotic therapy clinic. The Gram-positive bacillus was confirmed as E. rhusiopathiae via matrix-assisted laser desorption/ionization-time of flight analysis. Given intrinsic resistance to vancomycin, vancomycin was switched to intravenous ceftriaxone as targeted antimicrobial therapy for 2 weeks. Reassuringly, there was no echocardiographic evidence of infective endocarditis, warranting the prolonged treatment course. Post-treatment, she remained symptom-free with the resolution of joint symptoms and fevers. Conclusion. Our report illustrates a case of E. rhusiopathiae bacteraemia from an immunodeficient host, with prompt microbiologic diagnosis and intervention with appropriate antimicrobial coverage. Literature reflects the rarity of this infection, predilections to specific susceptible hosts and the importance of raising awareness of zoonotic infections.

Frequency and Clinical Outcomes of Respiratory Infections in Children with Cancer Presenting with Febrile Illness

Objectives Fever is a known complication in pediatric cancer patients when on chemotherapy for which prompt initiation of empiric antibiotics is the single most important life-saving intervention. Nearly two-thirds of all children are treated without identifying the source of fever. Molecular diagnostics can improve management of febrile episodes and reduce unnecessary antibiotic use. The purpose of our study was to evaluate the pathogenic etiology of febrile episodes and analyze their clinical characteristics. Materials and Methods We conducted a prospective observational study at our tertiary care institution from January 2019 to March 2020, to identify the etiology of febrile episodes with or without neutropenia in pediatric cancer patients and to study their clinical outcomes. Results Forty febrile episodes were observed among 27 patients over a period of 15 months. The mean age group was 5 years. In 28 febrile episodes without a focus (70%), a respiratory organism (virus, bacteria, or coinfection) was detected. Rhinovirus was the most common single respiratory isolate (47.36%), followed by Streptococcus pneumoniae (21.05%) and six episodes had multiple viral isolates (21.42%). There was no prolonged hospitalization, need for intensive care unit or oxygen requirement, or mortality. The most common antibiotic used in empiric management was piperacillin–tazobactam. Aminoglycosides were added when there was a clinical suspicion of resistant organism. Conclusion Around 70% of febrile episodes without a focus or documented infection in cancer children had a respiratory pathogen identified in nasopharyngeal swab. Molecular diagnostics greatly enhances diagnostic sensitivity and thereby individualizes the management of febrile illness in these children.

Benefits and Safety of Empiric Antibiotic Treatment Active Against KPC-Producing Klebsiella pneumoniae for Febrile Neutropenic Episodes in Colonized Children with Acute Leukemia—An 8-Year Retrospective Observational Study

In children with acute leukemia (AL), the mortality rate from Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bloodstream infection (KPC-KpBSI) exceeds 50%, highest when active treatment is delayed. Neutropenic KPC-K. pneumoniae carriers are at high risk of KPC-KpBSI, and preemptive empiric antibiotic treatment (EAT) of febrile neutropenic episodes (FNEs) active against KPC-K. pneumoniae may reduce this mortality. We conducted an 8-year (2014–2021) retrospective observational study of 112 febrile neutropenic episodes (FNEs) in 32 children with AL who were KPC-K. pneumoniae carriers: standard EAT for 39 FNEs and active EAT for 73 FNEs (52 ceftazidime/avibactam (CAZAVI)-based and 21 colistin-based combinations, and 5 CAZAVI monotherapy). Successful outcomes (survival from FNE) were observed in 94%; seven were fatal, with four due to infectious causes. KPC-KpBSIs caused 10/112 FNEs, 10/20 g-negative BSIs, and 3 deaths. The mortality rate of KPC-KpBSI was 30%. Active EAT was successful in 97% of the FNEs, compared to 87% with standard EAT. All deaths from KPC-KpBSI occurred in patients who received standard EAT, while none occurred with active EAT. KPC-KpBSI mortality rate with initial inactive treatment was 60%. CAZAVI-based EAT was successful in all FNEs, with a higher success rate without any modification compared to colistin-based EAT, where nephrotoxicity occurred in 14%. Therefore, active EAT, mainly a CAZAVI-based combination, was effective, safe, and associated with low overall and KPC-KpBSI-related mortality.

A constant contact community-based epidemiological investigation (C3EI) as part of malaria elimination demonstration project, Mandla district, Madhya Pradesh, India

BackgroundIn India, an increase in malaria cases by 21% (223,961 cases) has been reported between 2022 and 2023. Madhya Pradesh ranks 10th in malaria burden, with Mandla district selected for the Malaria Elimination Demonstration Project (MEDP) to demonstrate the feasibility of malaria elimination in a hard-to-reach, tribal-dominated, and hilly forested district. A Constant Contact Community-based Epidemiological Investigation (C3EI) was undertaken by continuous engagement with the community for real-time data collection, mapping of malaria cases, identification of risk factors, and monitoring of intervention outcomes designed to drive effective strategies for malaria elimination.MethodsThe study mapped 1,143,126 individuals from 248,825 households in the year 2017 in Mandla district for constant contact surveillance. Fortnightly household visits were conducted to inquire about febrile episodes, with on-spot diagnosis and treatment. Data collection was done using the SOCH mobile application, and analysis using R.ResultsThe constant contact household surveillance revealed that out of 956,795 individuals, 230,780 (24.12%) unique individuals reported one or more febrile episodes, with a total of 322,577 febrile episodes and 490 malaria episodes (RDT positive). Males had a higher risk of malaria infection than females (OR = 2.62; p < 0.0001). The cumulative incidence of malaria was highest among children aged 5–15 years and pregnant women. Multiple episodes of malaria infections were more common in adults over 30 years. The incidence of malaria per 100,000 persons gradually declined from 26.13 in 2018 to 11.18 in 2020, with the highest incidence during the monsoon season.ConclusionThe C3EI presents a new strategy suitable for disease elimination programmes. Implementing C3EI-type longitudinal studies in elimination projects holds promise for generating data to expedite malaria elimination efforts because the unit of observation is a ‘household’. Such a comprehensive approach allows identification in the gaps in case management for prompt interventions at the household-level.

A practical approach to febrile cancer patients: Diagnostic stewardship in Oncology units

Introduction Cancer and cytotoxic chemotherapy used for its treatment predispose to severe and often fatal infections. Prompt diagnosis and timely antibiotic therapy are crucial, with delays in therapy initiation having high mortality. Complete blood count (CBC) is an inexpensive, standardized, and preliminary investigation for the management and follow-up of cancer patients with diagnostic and prognostic value. Method We studied the types of infections associated with various cancers treated with chemotherapy, their etiologies and susceptibility patterns, and the hematological profile of these patients as predictors of infection. Results A total of 21 patients (12 solid and 9 hematological malignancies) presented with 31 febrile episodes. White Blood cell count (2079 cells/cu. mm), percentage of neutrophils (52.9%), absolute neutrophil (137.5 cells/cu. mm), and platelet count (1,77,507 cells/cu. mm) were significantly lower in the 11 patients with febrile neutropenia. The absolute lymphocyte count (412.7 cells/cu. mm) was reduced with a strikingly low Neutrophil-to-lymphocyte ratio (NLR) (6.07) in patients with neutropenia. Laboratory and radiological evidence were present in 14/15 episodes of hematological malignancies (p-0.218) whereas unexplained clinical sepsis was common in solid malignancies (p-0.0202). The majority of documented infections were bacterial, caused by gram-negative bacilli, often showing multi-drug resistance. Infectious etiologies were identified in 71.4% of the patients with febrile neutropenia for &gt;5days. Bacterial infections developed within 2 days of neutropenia, whereas viral and fungal infections manifested in prolonged neutropenia. Multi-site infections and higher mortality rates were observed in patients with febrile neutropenia. (p&lt;0.04) Conclusion Febrile neutropenia is a common complication among patients receiving chemotherapy for cancer, with an increased risk of morbidity and mortality. Early, rapid, and accurate diagnosis is key to prompt intervention. Hematological parameters such as Total Leukocyte count, platelet count, NLR, and Platelet-to-lymphocyte ratio are promising biomarkers in conjunction with morphological changes in neutrophils, thus proving that CBC and peripheral smears are simple, easily available, cost-effective, and highly dependable screening tools, especially in resource-poor settings.

Surveillance of fever and neutropenia episodes at Yeolyan Hematology and Oncology Center in Armenia

Abstract Background Fever and neutropenia frequently occur as complications in pediatric patients with malignancies, significantly escalating morbidity and mortality if not appropriately addressed. We implemented a fever registry to identify patient factors and outcomes associated with fever in patients undergoing treatment at our facility. Methods We conducted a single-center prospective observational study at the Pediatric Cancer and Blood Disorders Center of Armenia. All patients aged 0-21 years with a malignancy diagnosis and developing fever and neutropenia between June 25 and November 20, 2023, were included. Variables collected included age, gender, date and time of fever onset, patient symptoms, time to antibiotic administration, identified microbiologic and clinical infections, and subsequent outcomes, including mortality and requirement for critical care level interventions. Data were entered in Microsoft Excel 2016 and analyzed using descriptive statistical methods. Results Sixty-one patient episodes in 36 patients met the inclusion criteria. Of these, 22% of episodes had fever at home. The most common malignancy was acute leukemia, specifically B-ALL (21/61), followed by T-ALL (9/61), AML (7/61), and mixed T- and B-type (1/61). Eight out of 61 fever episodes occurred in patients with relapsed disease. The median time-to-antibiotics was 100 minutes (max: 24 hours 40 minutes) in patients developing fever outside the hospital; for inpatient cases, the median time-to-antibiotics was 30 minutes (max: 6 hours 45 minutes). The time-to-antibiotics was longer for patients experiencing fever at home compared to those in inpatient settings (p=0.043). 21% of patient episodes were pretreated, however 11 out of 61 patient episodes (18%) had a positive blood culture. Of 13 total positive cultures, ten were obtained at the time of the patient’s presentation. The most common pathogens identified were Staphylococcus spp. (8/13) including coagulase-negative (3/8), and Klebsiella spp. (3/13). Polymicrobial-positive cultures were observed during two fever and neutropenia episodes. During 35 episodes, patients presented with no complaints except for general weakness. Among the identified sources of infection (20/61), central-line-related bloodstream infections (n=6), bacteremia (n=5), and Clostridiodes difficile colitis (n=5) were the most common. One febrile neutropenia episode resulted in death (1.6%). Conclusion In summary, over 75% of episodes were observed among patients with hematologic malignancies, and localizing symptoms were absent in half of episodes at presentation. We have identified opportunities for quality improvement in time to administration of antibiotics in outpatient fever episodes. The adaptation of an electronic-based medical record system will simplify the tracking process for a febrile episode.

Implementation of a Nurse-Initiated Antibiotic Time-Out (NATO) in Childhood Cancer Patients in Central America

Abstract Background Children with cancer are at high risk for infection and frequently require antimicrobials. Antimicrobial stewardship (AMS) interventions can mitigate toxicity and development of antibiotic resistance yet the pharmacy and infectious diseases specialists who usually perform AMS are often absent in global settings. We report our experience testing a novel intervention to shift the antibiotic timeout to nurses in six pediatric oncology units in Central America. Methods The Nurse-initiated Antibiotic Timeout (NATO) is a scripted conversation between nurses and physicians to reevaluate antibiotic appropriateness after 48 to 72 hours of empiric use for febrile neutropenia. First, we performed a baseline assessment of AMS capacity using the WHO Practical Toolkit for AMS Programmes checklist. Based on these results, sites tailored a generic implementation plan emphasizing educational and documentation tools and iterative PDSA (Plan-Do, Study-Act) cycles to improve implementation and effectiveness outcomes. Results All sites collected antimicrobial use data for a minimum of two months. Four sites then piloted NATO, producing change ideas, including changes to documentation tools, antimicrobial decision categories, communication processes, and times. From August 2022 – October 2023, NATO was performed in 53.4% of febrile neutropenia episodes in the three sites reporting data. Sites had substantial NATO performance rate variation from month to month. Sites reported changes in antimicrobial therapy in 47% of episodes after a 6-month period (Figure 1). Conclusion The difference in performance rate of NATO underscores the importance of real-time reporting to adjust AMS implementation strategies. The change ideas developed by each site differed, however, core tools emerged, which will support AMS in other global settings. Next steps include comparing antimicrobial use pre- and post-intervention and determining a sustainability and scalability plan. Figure 1. Incidence of change in antibiotic therapy over time.

Use of Data from a Fever Registry (FEVEREG) to Identify Quality Improvement Opportunities in a Third-Level Hospital in Panama

Abstract Background Infectious diseases in childhood cancer patients are frequent and increase the morbimortality of these patients. Hospital del Niño doctor José Renán Esquivel initiated data collection in a registry of fever and neutropenia (FEVEREG) to evaluate outcomes and management of these diseases and identify opportunities for quality improvement. The objective of this study is to describe data collected to date. Methods Data was collected through a data collection instrument (CRF) using Trial Master platform. It was analyzed with R Data Analytics (version 4.3.2) and descriptive statistics summarized. Only patients who were admitted due to the febrile episode or were hospitalized when fever started were included. Results From Sept 2021 to October 2023, we captured 138 episodes in 70 patients, with a mean age of 8 years (range 0-15) and a similar percentage of female and male patients. The most common diagnosis was acute lymphoblastic leukemia (57.14%) and the episodes occurred more during the induction phase (24%) and in patients with a relapse protocol (31.5%). The time of administration of the antibiotic varied depending on the patient location at fever onset. 44% of outpatients (46/105) received the first dose of antibiotic more than 4 hours after the onset of fever, while hospitalized patients received this dose in the first hour in 64% of cases (21/33). Time from registration of outpatients until the first dose of antibiotic was an average of 71 minutes, with 60% of the patients receiving the antibiotic during the first 60 minutes. In 45.8% of the episodes, a blood culture was taken before starting the antibiotic. The febrile neutropenia algorithm was followed on 64.5% of the days evaluated, with the main cause of deviation being treatment to the focus of infection (55%) followed by clinical decision (41%). Bacteremia occurred in 26% of episodes (20/78) and 14% of episodes had documented viral infection (11/78). The most frequently isolated bacteria in blood was Pseudomonas aeruginosa (13/33, 39.3%). Approximately 4% of the episodes (6/138) were admitted to the intensive care unit and died, half from septic shock and half from progressive disease. The average length of hospital stay was 12 days. Conclusion Data from FEVEREG has suggested opportunities for quality improvement in time to antibiotics and use of guideline compliant antibiotics (antimicrobial stewardship).

Early Fever in Allogeneic Stem Cell Transplantation: Are Presepsin and YKL-40 Valuable Diagnostic Tools?

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a lifesaving treatment but carries a high infection risk. Diagnosing infections remains challenging due to the limited accuracy of standard biomarkers. Methods: This single-center study aimed to evaluate presepsin (PSP) and YKL-40 as infection biomarkers in febrile patients during the allo-HSCT pre-engraftment phase. Biomarker levels were prospectively measured in 61 febrile episodes from 54 allo-HSCT patients at admission, representing baseline levels, and then at Day 1, 3, 5, and 7 following fever onset. The diagnostic value was compared to that of procalcitonin (PCT). Results: PSP showed fair diagnostic value on Day 1 (AUC 0.656; 95% CI: 0.510-0.802) and Day 3 (AUC 0.698; 95% CI: 0.559-0.837). YKL-40 did not provide any significant diagnostic value across measured time points. PCT outperformed PSP and YKL-40, particularly on Day 3 (AUC 0.712; 95% CI: 0.572-0.852). When combining biomarkers, the best model for predicting infection used PSP > 3.144 ng/mL and PCT > 0.28 μg/L on Day 3, resulting in R2 of about 31% (p < 0.001). Conclusions: Neither test showed sufficient discriminative power for early infection to recommend their use as individual diagnostic tools in clinical practice.

5132 Unraveling the Enigma: A COVID-19 Triggered Revelation of Adult Idiopathic ACTH Deficiency

Abstract Disclosure: K.A. Arao: None. A.E. Gadbois: None. Introduction: Adult idiopathic ACTH deficiency (AIAD) is a rare and potentially life-threatening condition that is frequently misdiagnosed or even missed. We present a case of AIAD in a patient who exhibited altered mental status alongside a COVID-19 infection and was fortunately diagnosed after responding to empiric treatment with oral steroids for another condition. Case Presentation: A 76-year-old man was admitted to the hospital for bilateral leg weakness. His hospital stay was complicated by the development of febrile episodes and delirium. He tested positive for COVID-19, and the rest of infectious work-up yielded negative results. He then received a course of remdesivir. In the evaluation of his delirium, a CT scan of the brain, MRI of the brain, and lumbar puncture with CSF analysis were done, all of which were unremarkable. Initially, the delirium was attributed solely to COVID-19 infection. After consultation with neurology and rheumatology, the patient received empiric treatment with prednisone 5 mg twice daily for possible polymyalgia rheumatica as a cause of his bilateral leg weakness. His mental status significantly improved following steroid administration. With the improvement in symptoms, an AM cortisol test was added on his morning blood tests, revealing a cortisol level of 2.56 mcg/dL with an albumin level of 2.3 g/dL, raising concerns for adrenal insufficiency. An outpatient endocrinology evaluation recommended transitioning from prednisone to physiologic twice-daily dosing of hydrocortisone. An ACTH stimulation test was performed, which peaked at an AM cortisol of 6.1 mcg/dL, with a baseline ACTH level of 4.1 pg/mL. A review of the recent brain MRI showed no pituitary pathology. Other pituitary hormones were normal, and he was eventually diagnosed with AIAD. He was subsequently maintained on physiologic dosing of hydrocortisone, resulting in clinical stability. Discussion: AIAD is characterized by secondary adrenal insufficiency, normal production of other pituitary hormones, and the absence of structural pituitary pathology. The etiology of AIAD remains unknown, with most cases attributed to an autoimmune process. AIAD can have diverse clinical manifestations and may only become more apparent with triggers like infections or illnesses. As in our case, the COVID-19 infection likely unmasked the underlying AIAD, presenting with altered mental status. Identifying AIAD can be challenging, leading to high rates of misdiagnosis and clinical omission. Physicians should consider AIAD when dealing with unexplained altered mental status, as the administration of a simple treatment with steroids can be life-changing. Presentation: 6/3/2024

Atypical Presentation of Congenital Insensitivity to Pain With Anhidrosis Leading to Diagnostic Odyssey.

Congenital insensitivity to pain with anhidrosis (CIPA) (OMIM 256800) is a rare autosomal-recessive condition, also known as hereditary sensory and autonomic neuropathy type IV (HSAN-IV). The most commonly reported features include anhidrosis, intellectual disability, self-mutilation, febrile episodes, impaired temperature perception, recurrent infections and/or autonomic nervous system impairment. Major joint destruction and joint deformity known as Charcot (neuropathic) joints are also seen in CIPA patients attributed to insensitivity to joint pain. We present a case of a 46-year-old female affected with CIPA with a known NTRK1 variant and previously unidentified variant. Minigene reporter constructs were generated encompassing the exon 8 to exon 13 of the NTRK1 gene using the reference sequence and one harboring c.1483 + 5G > A variant identified in our proband. Minigene constructs were transfected into HEK293T cells, and the transcript was analysed for splicing to evaluate the effect of this variant in splicing. The patient (46-year-old female) exhibited right ankle joint deformity around 5 years of age. Patient also experienced lumbar compression and knee damage in adulthood. She had undergone a significant number of evaluations without clear diagnosis. Her presentation lacked many of the common clinical presentations of CIPA, and therefore, the focus of her evaluation was directed towards her unexplained joint deformities. Exome sequencing revealed a known pathogenic variant in NTRK1 (c.851-33T > A:p.? [Intron 7]) and a novel NTRK1 variant (c.1483 + 5G > A:p.? [Intron 11]), which was later re-classified as likely pathogenic. The patient was started on a biologic disease-modifying anti-rheumatic medication (bDMARD) due to a possible inflammatory etiology of her joint deformity. Molecular diagnosis allowed for modification of her treatment and surveillance strategies. Our minigene splicing assay demonstrated that the presence of the c.1483 + 5G > A variant has a negative effect on splicing, supporting the pathogenicity of this novel variant.

Xanthogranulomatous osteomyelitis of pubic bone mimicking neoplasm: a case report and literature review

BackgroundXanthogranulomatous osteomyelitis (XO) is a rare disease characterized radiologically by an osteolytic lesion with cortical expansion or disruption. Differentiating this condition from other osteolytic diseases such as primary or metastatic bone neoplasms is imperative. Several case reports have been published on XO, with previous reports predominantly identifying bacteria such as Pseudomonas or Staphylococcus as causative organisms. However, fungal infection-induced XO has not yet been reported.Case presentationWe present the case of a 23-year-old woman with a tumor-like osteolytic lesion in the pubic bone. The patient had experienced pelvic pain and intermittent febrile episodes for 2 months. Plain radiography revealed an osteolytic lesion in the right pubic tubercle. Magnetic resonance imaging suggested a cystic bone tumor or tubercular infection. Surgical intervention included curettage of the lesion and irrigation with normal saline. Histopathological examination of the specimen revealed abundant foamy histiocytes with inflammatory infiltrates consistent with XO. Culture of the osteolytic lesion confirmed an Aspergillus species infection and antifungal treatment was initiated. At 1-year follow-up, no evidence of local recurrence was observed.ConclusionsAlthough rare, XO requires differentiation from similar conditions and is treated with surgical intervention and targeted medical therapy based on the identified organisms. Clinicians should be mindful that XO can also be induced by fungal infections and that combination antifungal treatments may be beneficial in such cases.

Perfil epidemiológico y microbiológico de la primera infección urinaria en una población pediátrica

Introduction: urinary tract infection (UTI) is the second cause of bacterial infection in children, generates high costs for the health system, may be the first manifestation of urinary tract anomalies and is a risk factor for multiple pathologies. Objective: to characterize the epidemiological and microbiological profile of the first UTI episode in the pediatric population of a referral center in Pereira, Colombia. Methods: a cross-sectional study, conducted during 2016- 2017, including patients aged 2 months to 10 years, with their first UTI episode, based on the American Academy of Pediatrics criteria. Bacterial resistance was defined using current CLSI (Clinical and Laboratory Standards Institute) guidelines. Descriptive statistics and STROBE guidelines were used for reporting this study results. Results: 81 patients were included, 28% were males, most were aged 2 to 12 months (40%), 49% were nitrite-positive, 39% had hematuria and 37% proteinuria, and 87% had a positive Gram stain. Ultrasound imaging revealed urinary tract anomalies in 18%; the most common uropathogens were: Escherichia coli (86%), Proteus mirabilis (5%) and Klebsiella pneumoniae (5%). E. coli showed resistance for trimethoprim-sulfamethoxazole, ampicillin-sulbactam and cephalothin in 51.4%, 32.8% and 17.1%, respectively; 2.8% were extended-spectrum betalactamase/ESBL-positive. The median time of empiric management was 3 days and full treatment was of 10 days. Discussion: high resistance rates were recorded for ampicillin, ampicillin-sulbactam and trimethoprim-sulfamethoxazole, which discourage their use. The sensitivity of E coli to cephalothin and amikacin, reported in this study, favors their use as first empirical therapeutic choices in our setting. Conclusion: ultrasound examination of the urinary tract is recommended in patients experiencing their first febrile UTI episode, due to the high prevalence of urinary anomalies identified.

Malaria Rapid Tests, Febrile Illness Management, and Child Mortality Across Sub-Saharan African Countries

A prompt malaria diagnosis is crucial for the management of children with febrile illness in sub-Saharan African countries, where malaria remains a leading cause of mortality among children younger than 5 years of age. The development and distribution of point-of-care rapid diagnostic tests (RDTs) for malaria has transformed practice, but limited systematic evidence exists on how malaria RDTs have affected the management of febrile illness and mortality for children younger than 5 years of age across sub-Saharan Africa countries. To evaluate the association between the distribution of malaria RDTs and the management of febrile illness and mortality among children younger than 5 years of age in sub-Saharan African countries. This quasi-experimental study used a novel dataset linking malaria RDT distribution to 165 nationally representative household surveys across 35 sub-Saharan African countries with mortality data. The sample comprised approximately 3.9 million child-year observations and approximately 260 000 febrile illness episodes in children younger than 5 years of age between 2000 and 2019. Fixed-effects linear probability models were used to analyze the association between variation in malaria RDTs distributed per child younger than 5 years of age (by country per year) and blood testing, antimalarial drug use, antibiotic use, use of symptomatic treatments, and mortality rates. Variation in the effects of testing and treatment was also assessed across the sub-Saharan African countries that had varying prevalence of malaria. The mortality sample included 1 317 866 children and the fever sample included 256 292 children. The mean age of the children with febrile illness was 2.4 years (SD, 1.3 years) and 49% were female. Each additional malaria RDT distributed per child younger than 5 years of age was associated with an increase of 3.5 percentage points (95% CI, 3.2-3.8 percentage points) in blood testing, an increase of 1.5 percentage points (95% CI, 1.2-1.8 percentage points) in the use of antimalarial drugs, an increase of 0.4 percentage points (95% CI, 0.1-0.6 percentage points) in antibiotic use, and a decrease of 0.4 percentage points (95% CI, 0.1-0.8 percentage points) in the use of treatments for symptoms. Each additional malaria RDT distributed per child younger than 5 years of age was associated with a reduction in child mortality of 0.34 deaths per 1000 child-years (95% CI, 0.15-0.52 deaths per 1000 child-years). The effects of malaria RDT distribution on medication use and child mortality varied across prevalence settings (low vs high) for malaria; there were survival improvements only in areas that had a high prevalence of malaria. Increasing distribution of malaria RDTs was associated with increased blood testing, increased use of antimalarial drugs, and modestly improved survival in children younger than 5 years of age in sub-Saharan African countries. However, malaria RDTs were associated with increases in the rates of antibiotic use that were already high, suggesting that more comprehensive approaches to case management of febrile illness are needed.

Neoadjuvant Chemotherapy with Concurrent Letrozole for Estrogen Receptor-Positive and HER2-Negative Breast Cancer: An Open-Label, Single-Center, Nonrandomized Phase II Study (NeoCHAI).

The role of combining neoadjuvant endocrine therapy with conventional chemotherapy remains unclear; therefore, we conducted an open-label, single-center, nonrandomized phase II trial to assess the effect of this combination. Patients with previously untreated stage II or III HR-positive, HER2-negative breast cancer received concurrent letrozole 2.5 mg with standard neoadjuvant chemotherapy. The primary endpoint was pathologic complete response (pCR) at the time of surgery. We used Simon's minimax two-stage design; a pCR rate > 6% was necessary at the first stage to continue. Between November 2017 and November 2020, 53 women were enrolled in the first stage of the trial. Their median age was 49 years (range, 33-63), and 60% of them were premenopausal. Subsequently, 66% and 34% of patients with clinical stages II and III, respectively, were included; 93% had clinically node-positive disease. Two patients (4%) achieved pCR after neoadjuvant chemo-endocrine treatment, which did not satisfy the criteria for continuing to the second stage. The overall response rate was 83%. During the median follow-up of 53.7 months, the 3-year disease-free survival and overall survival rates were 87% and 98%, respectively. Neutropenia was the most common grade 3/4 adverse event (40%), but rarely led to febrile neutropenic episodes (4%). Myalgia (32%), nausea (19%), constipation (17%), heartburn (11%), oral mucositis (9%), and sensory neuropathy (9%) were frequently observed, but classified as grade 1 or 2. No deaths occurred during preoperative treatment. The addition of letrozole to standard neoadjuvant chemotherapy was safe and beneficial in terms of overall response rate, but did not provide a higher pCR rate in locally advanced HR-positive, HER2-negative breast cancer. Further research is needed to enhance neoadjuvant treatment strategies for this cancer subtype.

A practical approach to febrile cancer patients: Diagnostic stewardship in Oncology units

Introduction Cancer and cytotoxic chemotherapy used for its treatment predispose to severe and often fatal infections. Prompt diagnosis and timely antibiotic therapy are crucial, with delays in therapy initiation having high mortality. Complete blood count (CBC) is an inexpensive, standardized, and preliminary investigation for the management and follow-up of cancer patients with diagnostic and prognostic value. Method We studied the types of infections associated with various cancers treated with chemotherapy, their etiologies and susceptibility patterns, and the hematological profile of these patients as predictors of infection. Results A total of 21 patients (12 solid and 9 hematological malignancies) presented with 31 febrile episodes. White Blood cell count (2079 cells/cu. mm), percentage of neutrophils (52.9%), absolute neutrophil (137.5 cells/cu. mm), and platelet count (1,77,507 cells/cu. mm) were significantly lower in the 11 patients with febrile neutropenia. The absolute lymphocyte count (412.7 cells/cu. mm) was reduced with a strikingly low Neutrophil-to-lymphocyte ratio (NLR) (6.07) in patients with neutropenia. Laboratory and radiological evidence were present in 14/15 episodes of hematological malignancies (p-0.218) whereas unexplained clinical sepsis was common in solid malignancies (p-0.0202). The majority of documented infections were bacterial, caused by gram-negative bacilli, often showing multi-drug resistance. Infectious etiologies were identified in 71.4% of the patients with febrile neutropenia for &gt;5days. Bacterial infections developed within 2 days of neutropenia, whereas viral and fungal infections manifested in prolonged neutropenia. Multi-site infections and higher mortality rates were observed in patients with febrile neutropenia. (p&lt;0.04) Conclusion Febrile neutropenia is a common complication among patients receiving chemotherapy for cancer, with an increased risk of morbidity and mortality. Early, rapid, and accurate diagnosis is key to prompt intervention. Hematological parameters such as Total Leukocyte count, platelet count, NLR, and Platelet-to-lymphocyte ratio are promising biomarkers in conjunction with morphological changes in neutrophils, thus proving that CBC and peripheral smears are simple, easily available, cost-effective, and highly dependable screening tools, especially in resource-poor settings.

Incidence of acute transfusion reactions and associated factors among adult blood-transfused patients at Jimma University Medical Center, southwest Ethiopia: A cross-sectional study.

Acute transfusion reaction is mainly related to the infusion of blood or blood products resulting at any time within a day of the intervention. It ranges from a non-specific febrile episode to a life-threatening intravascular hemolysis. The severity of the reaction and the degree of morbidity are usually related to the degree of ABO incompatibility and the volume of blood transfused. Therefore, this study aimed to determine the incidence of acute transfusion reactions and its associated factors in Jimma University Medical Center, southwest Ethiopia. Institution-based cross-sectional study was conducted from 1 October to December 30, 2020. A total of 384 transfused patients were followed in this study. Socio-demographic and clinical data were collected through a structured questionnaire. Baseline measurement and 24-hour periodic vital signs monitoring were conducted after each transfusion. Four milliliters of venous blood were drawn after transfusion intervention from each distrusted patient for complete blood count, blood group phenotype, direct antihuman globulin test (DAT), and crossmatching. Data were entered into Epi data version 3.1 and analyzed using Statistical Package for Social Science software (SPSS) version 20. Descriptive statistics, and bivariable and multivariable logistic regression were employed to test the association between independent and dependent variables. A P value ≤ .05 was considered to indicate statistical significance. Acute transfusion reactions were diagnosed in 5.7% of patients, with most of these reactions were febrile nonhemolytic reactions (63.6%) followed by allergic (36.4%) reactions with mild clinical manifestations (27.3%). Transfusion history, transfused blood that was kept for more than 13 days, abortion history, and number of transfused units (≥3 units of blood/blood component) have 3.3, 3.85, 4.2, and 3.9 times greater odds, respectively, besides their significant association with the incidence of acute transfusion reactions. Patients with a history of previous transfusion, abortion, multi-unit transfusion, and patients transfused with blood stored for ≥14 days should be closely monitored. Starting a hemovigilance system of monitoring, collecting, and evaluating data on adverse effects of blood transfusion locally and nationally will decrease the occurrence of acute transfusion reactions.

Clinical Profile of Febrile Neutropenia in Children with Malignancies in a Tertiary Care Hospital: A Prospective Observational Study

Abstract Introduction: Febrile neutropenia is a dreadful complication associated with malignancies. Knowledge of locally prevalent pathogens and their resistance pattern is of paramount importance in guiding antimicrobial therapy. Aims/Objectives: The aim of the study was to identify the common infectious agent, antibiotic susceptibility of culture positive patients, and outcome Methods: We conducted a single-center prospective observational study. Forty-three children with febrile neutropenia episodes admitted in KKCTH, Chennai, were included in the study. The duration of the study was 1 year. Relevant patient and disease specific details were obtained, results were analyzed, and conclusions were drawn. Results: There were 90 episodes of febrile neutropenia. Overall culture positivity was identified in 37 cases (41.11%). Bacteremia (23.3%) was the most common cause of microbiologically documented infection. Gram-positive organisms (60%) were more commonly documented. Among the gram-positive organisms, coagulase-negative Staphylococcus aureus was the predominant isolate followed by Streptococcus. Central line–associated bloodstream infections were documented in 13.33%. Chemo-port removal was done in four children. Three had invasive fungal disease. The majority of the gram-negative isolates were resistant strains. Morbidity was significantly more in gram-negative infections. Overall outcome was good though three children succumbed to sepsis. Conclusion: A vigilant management of illness is essential. Chemo-port carries risk of severe infection. Protocol-based management of catheter-related bloodstream infection (CRBSI) can limit the number of chemo-port removal. Though gram-positive organisms are in the rise, gram-negative organisms are still responsible for significant morbidity. Early initiation of broad-spectrum empirical antibiotics with optimal gram-positive coverage is crucial. Children with suspected fungal infections should be aggressively evaluated and treated. An organized approach is the key in successful management.

Continuous Temperature Telemonitoring of Patients with COVID-19 and Other Infectious Diseases Treated in Hospital-at-Home: Viture® System Validation.

Body temperature must be monitored in patients receiving Hospital-at-Home (HaH) care for COVID-19 and other infectious diseases. Continuous temperature telemonitoring (CTT) detects fever and patient deterioration early, facilitating decision-making. We performed a validation clinical study assessing the safety, comfort, and impact on healthcare practice of Viture®, a CTT system, compared with a standard digital axillary thermometer in 208 patients with COVID-19 and other infectious diseases treated in HaH at the Navarra University Hospital (HUN). Overall, 3258 pairs of measurements showed a clinical bias of -0.02 °C with limits of agreement of -0.96/+0.92 °C, a 95% acceptance rate, and a mean absolute deviation of 0.36 (SD 0.30) °C. Viture® detected 3 times more febrile episodes and revealed fever in 50% more patients compared with spot measurements. Febrile episodes were detected 7.23 h (mean) earlier and modified the diagnostic and/or therapeutic approach in 43.2% of patients. Viture® was validated for use in a clinical setting and was more effective in detecting febrile episodes than conventional methods.