Empiric Broad-spectrum Antibiotics Research Articles

Association between Delayed Broad-Spectrum Gram-negative Antibiotics and Clinical Outcomes: How Much Does Getting It Right with Empiric Antibiotics Matter?

Clinicians often start unnecessarily broad-spectrum empiric Gram-negative antibiotics out of the concern that delaying effective therapy could lead to a worse clinical outcome. This study examined the consequences of delayed initiation of broad-spectrum Gram-negative antibiotics. In a retrospective cohort of adult inpatients from 928 US hospitals, we compared clinical outcomes after (1) empiric narrow-spectrum antibiotics escalated to broad-spectrum antibiotics (delayed broad-spectrum therapy, DBT) and (2) empiric broad-spectrum antibiotics continued for at least 5 days (early broad-spectrum therapy, EBT) using Win Ratios. DBT and EBT patients were matched on hospital, admitting diagnosis, and propensity scores incorporating 28 clinical variables. The outcome of interest was a ranked composite of mortality, readmission, and adverse drug events. Out of 746,880 inpatients, 82,276 (11%) received DBT and 664,604 (89.0%) received EBT. Among the 67,046 with DBT who were matched to 67,046 with EBT, mortality was 8.7% after DBT and 9.5% after EBT (p=0.022), readmission was 10.5% after DBT and 11.8% after EBT (p<0.0001), and the rate of adverse drug events was 8.4% after DBT and 7.2% after EBT (p<0.0001). Among matched patients, clinical outcomes were superior after DBT than after EBT (win-ratio 1.06; p < 0.0001). On average, among a large sample of adult inpatients who ultimately received broad-spectrum antibiotic therapy, delaying initiation of a broad-spectrum antibiotic was not associated with worse outcomes. Though broad-spectrum empiric therapy is undoubtedly sometimes warranted, this finding challenges the common belief that is it safer to err towards overly broad-spectrum empiric antibiotic therapy.

Prevention and Management of Infectious Complications in Pediatric Patients With Cancer: A Survey Assessment of Current Practices Across Children's Oncology Group Institutions.

While clinical practice guidelines (CPGs) for pediatric oncology infection prophylaxis and management exist, few data describe actual management occurring at pediatric oncology centers. An electronic survey querying infection management practices in nontransplant pediatric oncology patients was iteratively created by the Children's Oncology Group (COG) Cancer Control and Supportive Care Infectious Diseases Subcommittee and sent to leaders at all COG institutions, limiting each site to one response to represent their institution. The response rate was 57% (129/227 institutions). Many sites reported utilizing COG-endorsed CPGs for antibacterial (76%) and antifungal prophylaxis (74%), and fever and neutropenia (FN, 64%). Most institutions reported using antimicrobial prophylaxis for patients with acute myeloid leukemia (88% antibacterial, 100% antifungal) and relapsed acute lymphoblastic leukemia (82% antibacterial, 95% antifungal). Definitions of fever, phagocyte recovery, and antibiotic duration in febrile patients varied. Most institutions administer empiric broad-spectrum antibiotics for nonneutropenic fever, although 14% reported withholding antibiotics based on initial clinical status or risk stratification tools. Most respondents reported (70%) admitting FN patients for at least 48 h, however 15% have low-risk FN protocols allowing outpatient management. FN patients remain admitted on antibiotics through count recovery in 50% of institutions, whereas the others employed various early discharge/early antibiotic discontinuation strategies. There is often consistency but also substantial variability in reported antimicrobial prophylaxis strategies and management of patients with fever and represents an opportunity for implementation studies to standardize application of CPG recommendations and randomized trials to advance evidence where knowledge gaps exist.

Pyogenic liver abscess: an unusual cause of preterm delivery

Background: Pyogenic liver abscess (PLA) is a rare and serious clinical entity during pregnancy, particularly in tropical regions where infectious diseases predominate. Fever is the most common symptom, but the diagnosis is often delayed due to its rarity and the overlap of symptoms with other tropical diseases. Clinical case: We report the case of a 29-year-old pregnant woman at 28 weeks of gestation presenting with altered consciousness, fever, and right hypochondrial pain. Initial investigations revealed intrauterine fetal death and a hepatic abscess. Management included intravenous antibiotics and surgical drainage after unsuccessful percutaneous aspiration. Despite maternal recovery, the fetal prognosis was poor, with intrauterine fetal death. Discussion: Prompt diagnosis and multidisciplinary management are crucial in managing PLA during pregnancy. Imaging techniques such as ultrasonography are pivotal for diagnosis, while empiric broad-spectrum antibiotics combined with drainage provide effective treatment. Conclusion: Although rare, PLA should be considered in pregnant women presenting with fever, especially in tropical regions. Early diagnosis and treatment are vital to minimize maternal and fetal complications. Keywords: Pyogenic liver abscess, preterm delivery, intrauterine fetal death, pregnancy complications, tropical infections.

Empiric gram-negative antibiotics usage among critically ill patients across 13 ICUs of Nepal: A retrospective cohort study

Background This study aims to investigate the associations between patient characteristics and the receipt of empiric broad-spectrum gram-negative antimicrobials among adult patients admitted to ICUs in Nepal. Methods A retrospective cohort study was conducted in 13 ICUs in Nepal between January 1st, 2020, and December 31st, 2022. Empiric antibiotic use was defined as receiving gram-negative antibiotics within the first two days of ICU admission without evidence of infection from culture. Patient characteristics between patients receiving narrow-spectrum antibiotics and broad-spectrum gram-negative antibiotics were compared. Continuous variables were compared using mean and standard deviation, with mean differences and 95% confidence intervals calculated. Categorical variables were compared using the chi-square test. A multi-level multivariable regression model assessed the relationship between selected variables and broad-spectrum antibiotic usage, treating admitting ICU as a random factor. Results Among 12,349 eligible patients, 8720 (70.6%) received Empiric gram-negative antibiotics. Of those, 3240 (37.15%) received empiric narrow-spectrum gram-negative antibiotics, and 5480 (62.8%) received Empiric broad-spectrum gram-negative antibiotics. Patients receiving broad-spectrum gram-negative antibiotics were older (57.4 vs 53.8 yrs); had higher mean heart rates (97.3 vs 89.5 bpm), respiratory rates (24 vs 21.9), a fraction of inspired oxygen ( 50% vs 40%), blood sugar levels (163.4 vs 153.9 mg/dl), total leucocyte counts (12,685 vs 10,647 cells/cu mm) and serum creatinine (2.06 vs 1.03 umol/l) compared to narrow spectrum antibiotics. Similarly, patients receiving broad-spectrum gram-negative antibiotics had lower systolic blood pressure (122.6 vs 126.5 mm Hg), partial pressure of oxygen (96.7 vs 105.3), and pH ( 7.33 vs 7.36) compared to narrow-spectrum antibiotics. On multivariable regression; patients with readmission, cardiac support, and mechanical ventilation were more likely to receive broad-spectrum antibiotics. Conclusion The rate of empiric broad-spectrum gram-negative antibiotics usage in intensive care units is significantly high and associated with features of increased severity of illness.

“Unmasking the Uncommon”: A case series of multi-drug resistant Elizabethkingia meningoseptica causing late-onset sepsis and meningitis in preterm neonates

Elizabethkingia meningoseptica is an uncommon nosocomial pathogen that causes meningitis, pneumonia, and sepsis in neonates and in immunocompromised individuals. It exhibits resistance to many commonly employed first-line antibiotics used to treat gram-negative pathogens. Herein, we present three cases of late-onset sepsis with multi-drug resistant (MDR) Elizabethkingia meningoseptica in high-risk neonates. Case 1 was a one-day-old preterm low-birth-weight infant who presented with respiratory distress syndrome and septic shock. The patient was intubated and administered empirical broad-spectrum antibiotics and antifungal agents. Blood culture grew Candida krusei, hence Amphotericin B was initiated. Repeat blood culture on day 27 showed gram-negative bacilli, identified as Elizabethkingia meningoseptica by MALDI-TOF . Antibiotic susceptibility testing (AST) revealed resistance to Piperacillin/Tazobactam, but sensitivity to Vancomycin, Levofloxacin, and Minocycline. IV Vancomycin was administered, which resulted in clinical improvement and negative blood culture results. Case 2 was an eleven-day-old preterm, low-birth-weight baby who presented with fever. Initial investigations revealed normal complete blood counts (CBC) parameters and elevated CRP levels. Blood and CSF cultures isolated Elizabethkingia meningoseptica with a similar AST pattern. Intravenous Ciprofloxacin was initiated with clinical improvement and negative follow-up blood cultures. Case 3 was a one-day-old preterm baby, appropriate-to-gestational age, presenting with respiratory distress syndrome. The infant was intubated and started on inotropic support and intravenous antibiotics. Blood cultures on day 4 showed Elizabethkingia meningoseptica and Vancomycin was started. Follow-up cultures on days 6 and 14 grew Acinetobacter baumannii. A combination of Levofloxacin and Colistin was added, and blood cultures were negative after seven days, with clinical improvement. Elizabethkingia meningoseptica is a significant cause of hospital-acquired infections, especially in Neonatal Intensive Care Unit (NICU), leading to outbreaks. Clinicians must have a high degree of suspicion of E. meningoseptica for gram-negative bacilli causing sepsis and meningitis in high-risk patients. Recent technological advances have enabled accurate speciation to guide therapy and reduce morbidity and mortality rates.

Silent Devastation: Acute Marchiafava-Bignami Disease Unmasked by Chronic Alcoholism in a 24-Year-Old Male: A Case Report

Marchiafava-Bignami disease (MBD) is an uncommon condition that is mainly linked to prolonged alcoholism and nutritional deficits. It is characterised by necrosis and demyelination of the corpus callosum. Due to its rarity and vague clinical signs, this disorder can frequently be misdiagnosed. It manifests as a range of neurological symptoms, from altered awareness to motor impairments. We present a 24-year-old man in this case report who has a history of intravenous drug use, chronic alcohol intake, and recent binge drinking.He presented with a 10-day history of constipation, vomiting, and a high-grade continuous fever. Over two days, the patient’s condition deteriorated into a drowsy state with abdominal pain.On examination, the patient was drowsy but arousable, with stable vital signs except for hypertension. Neurological findings indicated reduced deep tendon reflexes, hypotonia, and neck stiffness. A systemic workup revealed normal brain CT findings, however, diffusion limitation was seen in the corpus callosum's splenium on MRI, along with mild oedema and T2/FLAIR hyperintensity. The lumbar puncture showed lymphocytic predominance, low CSF glucose, and elevated protein levels suggestive of a possible CNS infection. The differential diagnosis included Marchiafava-Bignami disease (MBD) and cytotoxic lesions of the corpus callosum (CLOCCs).The patient was managed with intravenous steroids, empirical antitubercular therapy (ATT), broad-spectrum antibiotics, and supportive care, including airway protection via intubation. Despite the late diagnosis, the clinical history of chronic alcoholism, recent binge, and imaging findings confirmed MBD. Early recognition and treatment of this disorder can improve neurological outcomes. The present study emphasises how crucial it is to take MBD into account when making a differential diagnosis for alcohol-related encephalopathies, especially in individuals who have neurological decline and prolonged alcohol consumption.

Impact of EUCAST Rapid Antimicrobial Susceptibility Testing (RAST) on optimal antimicrobial therapy in gram-negative bloodstream infections

ObjectivesTo evaluate the possible impact of RAST on optimal antimicrobial therapy via de-escalation or escalation, and to determine the reduction in antibiotic susceptibility reporting time with RAST. MethodsIn this single-center, prospective descriptive study, RAST was performed on clinical blood cultures containing E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii isolates. Very major error, major error, and categorical agreements with VITEK 2 were analyzed. ResultsOne hundred and three isolates were included in the study, out of which 29.1 % were carbapenem-resistant and 36.9 % were multidrug-resistant according to VITEK 2. Categorical agreement of the RAST method with standard antimicrobial susceptibility test (AST) was > 90 % at 6 h, except for piperacillin/tazobactam. Antibiotic revision could be carried out in 79.6 % of the patients either by de-escalation (61.2 %) or escalation (18.4 %) for optimal therapy based on the RAST 6 h result. RAST could provide carbapenem-sparing therapy in 24 % of patients. Reduction in antibiotic susceptibility reporting time was 41.5 h (38.8 to 63.2, median (IQR)). ConclusionsRAST can provide early antibiotic revision in a majority of patients with significantly reduced antibiotic susceptibility reporting time. Six hours is the shortest optimal time for antibiotic revision with RAST. In countries where empirical broad-spectrum antibiotics are prevalent due to high antibiotic resistance pressure, RAST should be proposed primarily in de-escalation and carbapenem-sparing strategies.

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

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

Empiric gram-negative antibiotics usage among critically ill patients across 13 ICUs of Nepal: A retrospective cohort study

Background This study aims to investigate the associations between patient characteristics and the receipt of empiric broad-spectrum gram-negative antimicrobials among adult patients admitted to ICUs in Nepal. Methods A retrospective cohort study was conducted in 13 ICUs in Nepal between January 1st, 2020, and December 31st, 2022. Empiric antibiotic use was defined as receiving gram-negative antibiotics within the first two days of ICU admission without evidence of infection from culture. Patient characteristics between patients receiving narrow-spectrum antibiotics and broad-spectrum gram-negative antibiotics were compared. Continuous variables were compared using mean and standard deviation, with mean differences and 95% confidence intervals calculated. Categorical variables were compared using the chi-square test. A multi-level multivariable regression model assessed the relationship between selected variables and broad-spectrum antibiotic usage, treating admitting ICU as a random factor. Results Among 12,349 eligible patients, 8720 (70.6%) received Empiric gram-negative antibiotics. Of those, 3240 (37.15%) received empiric narrow-spectrum gram-negative antibiotics, and 5480 (62.8%) received Empiric broad-spectrum gram-negative antibiotics. Patients receiving broad-spectrum gram-negative antibiotics were older (57.4 vs 53.8 yrs); had higher mean heart rates (97.3 vs 89.5 bpm), respiratory rates (24 vs 21.9), a fraction of inspired oxygen ( 50% vs 40%), blood sugar levels (163.4 vs 153.9 mg/dl), total leucocyte counts (12,685 vs 10,647 cells/cu mm) and serum creatinine (2.06 vs 1.03 umol/l) compared to narrow spectrum antibiotics. Similarly, patients receiving broad-spectrum gram-negative antibiotics had lower systolic blood pressure (122.6 vs 126.5 mm Hg), partial pressure of oxygen (96.7 vs 105.3), and pH ( 7.33 vs 7.36) compared to narrow-spectrum antibiotics. On multivariable regression; patients with readmission, cardiac support, and mechanical ventilation were more likely to receive broad-spectrum antibiotics. Conclusion The rate of empiric broad-spectrum gram-negative antibiotics usage in intensive care units is significantly high and associated with features of increased severity of illness.

Descending necrotizing mediastinitis secondary to an oral phlegmon: a case report

Background: Rare complications of odontogenic infection can lead to a life-threatening and fatal consequence of descending necrotizing mediastinitis The mortality rate is still between 20 and 40 percent despite improvements in surgical care, diagnostic imaging, and antibiotics. This case report presents a case of descending necrotizing mediastinitis as a secondary complication of oral phlegmon. Case Presentation: A 51-year-old male patient presented with chief complaints of swelling and pain in the lower right jaw. The patient underwent incision drainage and submandibular dissection which obtained 100 cc of pus and necrotic tissue that originated from submandibular and sublingual region. Laboratory examination showed leukocytosis, in addition the X-ray photo and CT-scan supported diagnosis of mediastinitis. The patient was assessed with oral phlegmon post re-incision drainage and descending necrotizing mediastinitis with jugular vein rupture in the area of infection. The patient received intravenous steroids, fluids, analgesia and broad-spectrum empirical antibiotics. The patient's condition has improved afterwards. Conclusion: Descending necrotizing mediastinitis is rare but has a serious complication of oral phlegmon therefore the principal management surgical drainage, antibiotics, and airway management needs to be performed accordingly.

Combination of a Rapid Diagnostic Assay and Antimicrobial Stewardship Intervention for Gram-Negative Bacteremia.

Traditional blood cultures for gram-negative bacteremia can take up to 72 hours or more to return results, prolonging the duration of empiric broad-spectrum intravenous antibiotics. The Accelerate Pheno system provides rapid identification and susceptibilities for blood cultures in gram-negative bacteremia. Current data on its clinical utility are mixed overall, so the system requires further research. A multicenter, retrospective quasi-experimental study was conducted comparing the Accelerate Pheno rapid diagnostic system with antimicrobial stewardship intervention and traditional blood cultures alone. A total of 264 patients with blood cultures with gram-negative bacteria growth were included in the final analysis (102 pre-intervention, 162 post-intervention). The antimicrobial stewardship team made 364 recommendations in 152/162 (93.8%) patients in the post group. Duration of intravenous therapy was shorter (P < .001) for the post-intervention group (median, 4.0 days) compared with the pre-intervention group (median, 7.5 days). Hospital length of stay was also shorter (P < .001) for the post-intervention group (median, 5.1 days) compared with the pre-intervention group (median, 7.0 days). Readmission rates within 30 days were reduced (P = .042) post-intervention (13.0%) compared with pre-intervention (22.6%). In the post-intervention group, a larger proportion of patients were transitioned to oral therapy at any point (126/162, 77.8%) compared with pre-intervention (62/102, 60.8%; P < .001). These results suggest that the Accelerate Pheno system, with active review and intervention by a multidisciplinary antimicrobial stewardship team, is a useful tool in improving both patient-centric and antimicrobial stewardship outcomes.

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.

Subdural empyema—a rare complication of chronic otitis media: a case report

BackgroundSubdural empyema is an extremely rare and fatal intracranial complication of chronic otitis media. Due to its rarity and vague symptoms, it is often diagnosed late if not completely missed; specially in developing countries where the diagnostic modalities are hardly available or accessible. To the best knowledge of the authors, this is a preliminary reported case of subdural empyema as a complication of chronic otitis media in Eritrea. It aims to provide vital information on the clinical presentation, preferred diagnostic modalities, and the proper management of such cases.Case reportAn 8 years old female patient from the Rashaida ethnic group presented with fever, right ear purulent discharge, right post-auricular swelling, and altered mental status. Prior to her admission, she had history of recurrent purulent discharge from her right ear for almost 2 years, and had been diagnosed with chronic otitis media. Upon admission her GCS was 13/15 which later on deteriorated to be 3/15 on day 3. MRI was done and showed a right fronto-tempo-parietal subdural empyema with mass effect, shifting the midline to the left. She was immediately started on empirical broad-spectrum antibiotics. After the diagnosis was made, craniotomy was done, and 30 ml of pus was removed from the subdural space. Culture and sensitivity of the pus obtained intraoperatively was done but produced no yield. Hence, she was continued on the empirically started antibiotics. The patient’s condition was well improved by post-operative day 4.ConclusionIt is important to have a high index of suspicion of intracranial complications in patients with history of chronic otitis media or other otologic complaints, who present with neurologic manifestations. Subdural empyema still being uncommon even among the intracranial complications of COM, it is often missed. Hence, timely diagnosis with MRI, immediate surgical evacuation of the empyema along with the prolonged administration of broad-spectrum antibiotics is highly recommended.

Early stoppage of empirical antibiotic therapy at clinical improvement in paediatric leukaemia patients with high-risk febrile neutropenia (ESAT-HR-FN study): Study protocol of a single centre investigator initiated randomised open label non-inferiority trial

Background and rationaleFebrile neutropenia (FN) is one of the major causes of early mortality among children undergoing induction chemotherapy for haematological malignancies. FN occurs in up to 80 % of the children undergoing intensive chemotherapy and FN specific mortality is as high as 10 %. The management of high-risk FN (HR-FN) is by early initiation of broad-spectrum empirical antibiotic therapy (EAT) which is continued till blood count recovery. Adverse effects of prolonged EAT among children without proven infective focus have questioned the rationale behind the duration of EAT. The non inferiority of early stoppage of EAT in patients with low-risk FN (LR-FN) when afebrile for 48 h, irrespective of marrow recovery, is proven among adults and children. However, there is paucity of data regarding the same in children with HR-FN. This study aims to determine whether early discontinuation of EAT in children with HR-FN without proven infective focus who become afebrile and awaiting marrow recovery, would reduce antibiotic duration and their adverse effects without any negative consequences for patients. ObjectiveTo compare the rates of recurrent fever in paediatric patients (2–18 years) with HR-FN when EAT is continued till marrow recovery (control group) versus when stopped early at defervescence irrespective of marrow recovery (study group). MethodologyThis is the study protocol of a phase 3, single centre, randomized, open label, non-inferiority clinical trial. The primary outcome is the rate of fever recurrence among patients with HR-FN, when EAT is stopped early irrespective of marrow recovery (study group) and will be compared to the rate of fever recurrence on continuation of EAT till marrow recovery which is defined as an absolute neutrophil count (ANC) ≥ 500/mm3 (control group). Secondary outcomes include the comparison of duration of antibiotic use, mortality rates, hospital re-admission rates, requirement of multiple broad-spectrum antibiotics, therapeutic anti-fungal usage and need for organ support between the study and the control groups. A total of 280 children with acute leukaemia undergoing EAT for grade 3 or severe FN (ANC <500/μL) without clinico-laboratory evidence of infective foci are being randomized in the ratio of 1:1 between the study and the control group after defervescence for 48 h. The patients will be followed up for primary outcome (fever recurrence) till the end of induction period (day 35) or recovery of ANC ≥500/mm3 whichever is earlier. Expected outcomeESAT-HR FN study is the first large phase 3 randomised study to assess the impact of early stoppage of EAT irrespective of marrow recovery among a homogenous paediatric cohort of HR-FN in the setting of induction chemotherapy for acute leukaemia. This study will be seminal in addressing the duration of EAT in HR-FN among children without infective foci and if proven to be non-inferior this strategy will help to reduce the adverse effects from prolonged antibiotic use, the emergence of drug resistance, decrease hospital stay length and overall health care costs.

Bloodstream infections due to multi-drug resistant bacteria in the emergency department: prevalence, risk factors and outcomes-a retrospective observational study.

Multidrug-resistant organisms (MDROs) are prevalent in patients admitted to the Emergency Department (ED) and increase the risk of inappropriate empirical antibiotic therapy. Risk stratification for MDRO infection is essential to early identify patients requiring empirical broad-spectrum antibiotic therapy, but it remains challenging for emergency physicians. This study aimed to evaluate prevalence, risk factors, and outcomes of patients admitted to the ED with a bloodstream infection (BSI) caused by MDROs. A retrospective observational study enrolling all consecutive adult patients admitted with a BSI to the ED of Niguarda Hospital, Italy, from January 2019 to December 2021 was performed. 757 patients were enrolled, 14.1% with septic shock. 156 (20%) patients had a BSI caused by MDRO: extended-spectrum beta-lactamase (ESBL) producing Enterobacterales were the most prevalent followed by methicillin-resistant Staphylococcus aureus (MRSA). Risk factors for BSI due to MDRO and specifically for ESBL were chronic renal failure (OR 2.2; 95%CI 1.4-3.6), nursing home residency (OR 4.4; 95%CI 1.9-10.2) and antibiotic therapy in the last 90-days (OR 2.6; 95%CI 1.7-4), whereas for MRSA were dialysis (OR 12.3; 95%CI 1.8-83), antibiotic therapy and/or hospital admission in the past 90-days (OR 3.6; 95%CI 1.2-10.6) and ureteral stent or nephrostomy (OR 7.8; 95%CI 1.5-40.9). Patients with BSI due to MDRO had a higher rate of inappropriate empirical antibiotic therapy (50%) and longer length of stay, but no higher in-hospital mortality. Among patients admitted to the ED with a BSI, MDROs are frequent and often associated with inappropriate empirical antibiotic therapy. Specific updated risk factors for MDRO may help clinicians to better identify patients requiring a broader antibiotic therapy in the ED, while awaiting microbiological results.

Anatomy, Diagnosis, and Clinical Management of Deep Neck Space Infections

Any surgeon providing care to patients with congenital, oncologic, infectious, or traumatic processes impacting the head and neck should have an intimate knowledge of the local anatomy. The complex fascial system in this region results in a series of loosely and tightly bound spaces that can both harbor and/or facilitate the rapid spread of infections through these fascial planes and potential spaces. Deep neck space infections may occur spontaneously from cutaneous, lymphatic, odontogenic, otologic, salivary gland, sinus, and hematogenous sources or develop as the result of surgical/iatrogenic manipulation. These infections are typically polymicrobial, involving a mixture of Gram-positive cocci, Gram-negative rods, and beta-lactam-resistant anaerobes commonly found in the oropharyngeal flora. Other populations, such as immunocompromised or hospitalized patients, are particularly vulnerable to infection by certain opportunistic and antibiotic-resistant pathogens. Understanding the deep neck anatomy is crucial for predicting the spread of infection and guiding treatment strategies. The superficial and deep cervical fascial planes form a series of compartments and spaces including the retropharyngeal, danger, prevertebral, carotid, parapharyngeal, submandibular, sublingual, parotid, masticator, temporal, and infrahyoid spaces. Despite their rarity in the post-antibiotic era, deep neck space infections pose a significant threat as they progress rapidly and can quickly lead to life-threatening complications. Delayed clinical presentation is common due to the compartmentalization by fascial planes, therefore early recognition requires a high index of suspicion, thorough clinical examination, and diagnostic imaging studies, typically contrast-enhanced computed tomography (CECT). Treatment requires a multidisciplinary approach, including advanced airway management, administration of empirical broad-spectrum antibiotics, and surgical drainage when indicated. This review provides a comprehensive overview of deep neck space anatomy and its defining fascial planes, as well as discussions on epidemiology, specific microbiology, clinical presentation, diagnosis, antibiotic selection, and surgical treatment options.

Risk Factors for Therapeutic Failure and One-Year Mortality in Patients with Intramedullary Nail-Associated Infection after Trochanteric and Subtrochanteric Hip Fracture Repair.

Despite the implications of trochanteric and subtrochanteric intramedullary (IM) nail infection for patients with hip fracture, little is known about risk factors for therapeutic failure and mortality in this population. We performed a retrospective observational analysis including patients diagnosed with trochanteric and subtrochanteric IM nail infection at a Spanish academic hospital during a 10-year period, with a minimum follow-up of 22 months. Of 4044 trochanteric and subtrochanteric IM nail implants, we identified 35 cases of infection during the study period (0.87%), 17 of which were chronic infections. Patients with therapeutic failure (n = 10) presented a higher average Charlson Comorbidity Index (CCI) (5.40 vs. 4.21, p 0.015, CI 0.26-2.13) and higher rates of polymicrobial (OR 5.70, p 0.033, CI 1.14-28.33) and multidrug-resistant (OR 7.00, p 0.027, CI 1.24-39.57) infections. Upon multivariate analysis, polymicrobial infection and the presence of multidrug-resistant pathogens were identified as independent risk factors for therapeutic failure. Implant retention was associated with an increased risk of failure in chronic infection and was found to be an independent risk factor for overall one-year mortality in the multivariate analysis. Our study highlights the importance of broad-spectrum empirical antibiotics as initial treatment of trochanteric and subtrochanteric IM nail-associated infection while awaiting microbiological results. It also provides initial evidence for the importance of implant removal in chronic IM-nail infection.

Surgical Management of Extensive Chronic Suppurative Maxillary Osteomyelitis in an Uncontrolled Diabetic Patient – A Comprehensive Case Report

Osteomyelitis is inflammation of the medullary cavities, Haversian system, and adjacent cortex of the bone. It is pernicious to patients when aggressive and invasive. Maxillary osteomyelitis mostly affects individuals with immunocompromised conditions such as uncontrolled diabetes, human immunodeficiency virus infections, and immunosuppressive/chemotherapy, and has potentially fatal outcomes. In diabetic patients, strict glycemic control routinely as well as pre-, intra-, and postoperatively is paramount to prevent as well as cure diabetic maxillary osteomyelitis. We report a case of maxillary osteomyelitis in a female patient with poorly controlled type 2 diabetes mellitus. She complained of multiple mobile teeth and exposed bone in the upper left back tooth region. Clinical, radiographic, and histopathological findings were confirmative of chronic suppurative maxillary osteomyelitis. Sequestrectomy, curettage, and debridement were performed after broad-spectrum empirical antibiotic therapy and correction of raised blood glucose levels within normal limits. At regular follow-ups, there was no evidence of any recurrence or re-infection.

An Emerging Threat: A Systematic Review of Endocarditis Caused by Gemella Species.

Infective endocarditis caused by Gemella species is increasingly recognized as an emerging clinical entity. Gemella species are fastidious gram-positive cocci that are typically commensal organisms but can become opportunistic pathogens. This systematic review aimed to provide a comprehensive overview of endocarditis due toGemellaspecies by synthesizing existing evidence. A total of 52 case reports were identified through a rigorous search and selection process. The most prevalent causative species were G. morbillorum (46.3%) and G. haemolysans (25.9%), with a striking male predominance (79.6%). The clinical presentation was largely nonspecific, mirroring typical infective endocarditis. However, the indolent nature of the illness and fastidious growth requirements of Gemella species often led to diagnostic delays. Echocardiography, particularly transesophageal echocardiography, played a crucial role in the diagnosis, enabling the detection of valvular vegetation and the assessment of complications. Management posed significant challenges, including the need for broad-spectrum empirical antibiotic therapy and increasing antimicrobial resistance among Gemella isolates. Surgical intervention was frequently required for severe valvular dysfunction, persistent infection, or embolic complications. Despite advances in diagnosis and treatment, endocarditis due toGemellaspeciesremains associated with significant morbidity and mortality, underscoring the importance of early recognition and multidisciplinary management. This review highlights the emerging clinical significance of Gemella species as causative agents of infective endocarditis and identifies areas for further research.

Group B Streptococcus Meningitis in an Adult Woman with Type 2 Diabetes and Ethmoid Roof Defect. Impact on "frontal" Cognitive Functions.

Community-acquired bacterial meningitis in adults represents one of the most severe infectious diseases worldwide with potentially life-threatening medical complications. Several infectious agents can cause acute meningitis. Although group B Streptococcus is more prevalent in newborns, infection can also lead to meningitis in older adults, particularly those with underlying health issues. A 53-year-old woman with a body mass index of 28.7 kg/m2, type 2 diabetes mellitus, and dyslipidaemia presented to the emergency department of Santa Maria della Stella Hospital (Orvieto, Italy) with confusion, low-grade fever, echolalia, and hyperglycaemia. Computed tomography scans of the brain revealed a hypodensity in the left anterior frontal lobe and an osteodural defect of the rhinobase. Meningitis was suspected and empiric broad-spectrum antibiotic therapy with corticosteroids and insulin were administered while the results of the cerebrospinal fluid analysis confirmed the diagnosis of group B Streptococcus meningitis. Repeat imaging at 48 hours revealed enlargement of the hypodense lesion. The frontal assessment battery indicated deficits in executive functions. Prompt treatment led to rapid clinical improvement. Following the restoration of euglycemic status and hemodynamic stabilization, a follow-up magnetic resonance imaging confirmed the ischaemic lesion and showed cerebrospinal fluid in the sella turcica. The patient was then transferred to neurorehabilitation. The complex interactions among multiple risk factors resulted in an atypical clinical case of group B Streptococcus meningitis, which was promptly treated with empiric antibiotic therapy to mitigate neurocognitive deficits. Group B Streptococcus can cause meningitis in adults with poorly controlled type 2 diabetes mellitus and should be promptly treated with empiric broad-spectrum antibiotics.An osteodural defect of the ethmoid roof together with idiopathic intracranial hypertension may result in empty sella turcica and CSF rhinorrhoea, promoting the dissemination of the pathogen.Meningitis patients with pre-existing diabetic cerebral vasculopathy may develop cerebrovascular complications and cognitive impairments.