Broad Spectrum Research Articles

Antibiotic Appropriateness for Urinary Tract Infections in Children.

We examined local prescribing patterns across the entire treatment course for children treated for uncomplicated urinary tract infection (UTI) to determine opportunities for antibiotic stewardship initiatives. We conducted a retrospective review of emergency department and inpatient encounters for febrile and afebrile UTI in a children's hospital from 2021 to 2022. An antibiotic spectrum ranking was established, and providers' choices were assessed for appropriateness on the basis of the individuals' urine culture (UCx). Groups were stratified by fever presence and compared using χ2, Fisher's exact, and Mann-Whitney U tests. Of 172 encounters (83% emergency department), 99 (58%) had a positive UCx. Eighty (80%) grew Escherichia coli, with 67 (84%) being susceptible to cefazolin (minimum inhibitory concentration ≤16 mg/L). There were 229 antibiotic regimens and 39 (17%) were appropriate. Inappropriate antibiotic choices included unnecessary use of broad-spectrum antibiotics and misdiagnosed UTI. Grouping by encounter, at least 1 dose of a third cephalosporin was given in 51% of encounters, and 80% of these received it unnecessarily because of UTI misdiagnosis or suitability of a narrower-spectrum antibiotic. The median prescribed antibiotic duration was 7 days (interquartile range 7-10). Of 73 encounters with UCx growing mixed flora or a nonuropathogen, only 29 (40%) had antibiotics discontinued. Confirmed UTI was associated with fever and nitrite positivity. Our study revealed high prevalence of inappropriate antibiotics, particularly unnecessary prescribing of third cephalosporin, prescriptions not supported by laboratory data, and prolonged treatment courses. Our results identify factors that can be used to support UTI treatment pathways and ensure antibiotic stewardship.

Umbilical Amniotic Tissue Graft as an Alternative Approach for Eyelid Reconstruction After Necrotizing Fasciitis Debridement

A 54-year-old female with myelodysplastic syndrome on chemotherapy presented with 10 days of periocular erythema and edema worsening on oral antibiotics. Computed Tomography scan showed periorbital soft tissue swelling without postseptal extension or abscess. Intravenous broad-spectrum antibiotics were administered. However, she developed necrosis of the upper eyelid requiring aggressive debridement. Nine days after debridement, the defect measuring 5.5 × 3 cm was covered using an umbilical amniotic tissue graft (AmnioGuard, BioTissue, Miami, FL). At postoperative week 4, 5-fluorouracil was injected to prevent the shortening of anterior lamella. At postoperative week 20, the graft had dissolved and been replaced by regenerated skin. Final eyelid exam demonstrated normal eyelid elevation and minimal lagophthalmos. Herein, we present a case of umbilical amniotic membrane as a substrate graft to support the healing of the eyelid defect by secondary intention.

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.

Excitation and manipulation of super cavity solitons in multi-stable passive Kerr resonators

We report on the theoretical analysis as well as the numerical simulations about the nonlinear dynamics of cavity solitons in a passive Kerr resonator operating in the multistable regime under the condition of a sufficiently strong pump. In this regime, the adjacent tilted cavity resonances might overlap, thus leading to the co-existence of combinatory states of temporal cavity solitons and the extended modulation instability patterns. The cavity in the regime of multistablity may sustain distinct families of cavity solitons, vividly termed as super cavity solitons with much higher intensity and broader spectra if compared with those in the conventional bi-stable regime. The description of such complex cavity dynamics in the multstable regime requires either the infinite-dimensional Ikeda map, or the derived mean-field coupled Lugiato-Lefever equations by involving multiple contributing cavity resonances. With the latter model, we revealed the existence of different orders of super cavity solitons, whose stationary solutions were obtained by using the Newton-Raphson algorithm. Along this line, with the continuation calculation, we have plotted the Hopf / saddle-node bifurcation curves, thus identifying the existing map of the stable and breathing (super) cavity solitons. With this defined parameter space, we have proposed an efficient method to excite and switch the super cavity solitons by adding an appropriate intensity (or phase) perturbation on the pump. Such deterministic cavity soliton manipulation technique is demonstrated to underpin the multi-level coding, which may enable the large capacity all-optical buffering based on the passive fiber ring cavities.

Broad-Spectrum Engineered Multivalent Nanobodies Against SARS-CoV-1/2.

SARS-CoV-2 Omicron sublineages escape most preclinical/clinical neutralizing antibodies in development, suggesting that previously employed antibody screening strategies are not well suited to counteract the rapid mutation of SARS-CoV-2. Therefore, there is an urgent need to screen better broad-spectrum neutralizing antibody. In this study, a comprehensive approach to design broad-spectrum inhibitors against both SARS-CoV-1 and SARS-CoV-2 by leveraging the structural diversity of nanobodies is proposed. This includes the de novo design of a fully human nanobody library and the camel immunization-based nanobody library, both targeting conserved epitopes, as well as the development of multivalent nanobodies that bind nonoverlapping epitopes. The results show that trivale B11-E8-F3, three nanobodies joinedtandemly in trivalent form, have the broadest spectrum and efficient neutralization activity, which spans from SARS-CoV-1 to SARS-CoV-2 variants. It is also demonstrated that B11-E8-F3 has a very prominent preventive and some therapeutic effect in animal models of three authentic viruses. Therefore, B11-E8-F3 has an outstanding advantage in preventing SARS-CoV-1/SARS-CoV-2 infections, especially in immunocompromised populations or elderly people with high-risk comorbidities.

7964 Manipulation of the Gut Microbiome Using Antibiotics Is Associated With Sex-Specific Reductions in Systemic Testosterone Levels in Rats

Abstract Disclosure: G. Parodi: None. G. Leite: None. W. Morales: None. S.R. Weitsman: None. G.M. Barlow: None. M. Sanchez: None. M. Pimentel: None. M. Villanueva-Millan: None. M. Pimentel: None. R. Mathur: None. The gut microbiome has impacts on metabolic endocrine and reproductive functions. It is known that specific bacteria can impact host metabolism by synthesizing, secreting, and/or metabolizing sex-related hormones. However, the impacts of gut bacterial biosynthesis and/or metabolism of steroids on host metabolism and reproduction have not been fully addressed. In this study we challenged the gut microbiome of wild-type male and female rats with broad-spectrum antibiotics and examined the effects on circulating testosterone levels. Methods: Male (M) and female (F) Sprague-Dawley rats (8 weeks old) were housed with phytoestrogen-free bedding and received a phytoestrogen-free diet with water from glass bottles. Rats were given a combination of vancomycin (0.5g/L), ampicillin (1g/L), neomycin (1g/L), and metronidazole (1g/L) in their water for 8 days, and then returned to normal drinking water for another 13 days. Control rats were given normal water throughout the study. Serum and stool samples were collected before the start of antibiotics (baseline), on day 8 of antibiotics (AbxD8), and at 13 days post-removal of antibiotics (PAbxD13). Stool total DNA was extracted with the MagAttract PowerSoil DNA KF kit and quantified on a Qubit. Circulating testosterone levels were analyzed on a Luminex platform. Paired-ANOVA test was used to determine changes in testosterone levels in each group over time. Results: A total of 31 rats (M=16, F=15) received antibiotics, and 28 (M=14, F=14) were controls. Antibiotic exposure resulted in significant decreases in total stool DNA quantity in both male and female exposed rats relative to controls on AbxD8 (P<0.0001), which returned to baseline levels by PAbxD13. Antibiotic exposed male rats had a continuous decrease in testosterone levels throughout the timepoints collected (baseline: 5.78±2.74 ng/mL, AbxD8: 3.11±2.46 ng/mL, PAbxD13: 2.55±1.80 ng/mL, P=0.0027), however, in control male rats, circulating testosterone levels remained stable throughout the timepoints analyzed (baseline: 3.81±1.73 ng/mL, AbxD8: 3.72±1.12 ng/mL, PAbxD13: 3.92±3.38 ng/mL, P=0.49). There was no effect on circulating testosterone levels in female rats, with both groups, control and exposed, following the same cyclical pattern throughout the timepoints analyzed. Conclusions: Antibiotic depletion of the gut microbiome is associated with changes in systemic levels of testosterone in rats. These changes are sex-specific, and only detected in males. These results suggest a potential involvement of the gut microbiome in testosterone metabolism that is sex-specific. Presentation: 6/1/2024

Resistance Pattern of Acinetobacter baumannii in Hospitalized Patients

Background: One of the most prevalent bacteria in nosocomial infections is Acinetobacter baumannii. Misuse of antibiotics has resulted in an increase in A. baumannii multidrug-resistant (MDR) strain resistance. To assess the resistant gene pattern of MDR A. baumannii, empirical antibiotic therapy is required. In order to do this, the current study used a genotypic diagnostic technique to assess the resistance gene pattern of MDR A. baumannii that was collected from hospitalized patients. A. baumannii has resistance mechanisms against broad-spectrum antibiotics, including β-lactamases, efflux pumps, and aminoglycosides, altering targets, permeability shifts, and enzyme modifications. Efforts have been made to target plant-derived compounds and a combination of antibiotics and phytocompounds to circumvent resistance mechanisms. Many studies have been conducted on plant extract-synthesised nanoparticles. Additionally, we projected contemporary techniques to investigate insights into the mechanisms of action of antibiotics, such as multi-omics analysis. The data implied that A. baumannii putative antibiotic pathways would result in a different approach to treating A. baumannii infections. One of these resilient pathogens is A. baumannii, which is becoming more common in hospitals, resistant to treatment, and linked to higher death rates. Notwithstanding its clinical importance, little is known about this pathogen's behavior outside of hospitals. Additionally, unknown are its virulence factors. Consequently, our goal in this review is to provide light on the most recent findings about the ecological niches, microbiological characteristics, and antibiotic resistance profiles of A. baumannii. According to recent research, this bacterium is found in an increasing number of environmental niches, such as soils, treatment plants, and rivers.

8227 Complex Case of Myxedema Coma Complicated by Cardiac Arrest in a Geriatric Patient with Multiple Comorbidities

Abstract Disclosure: M. Parvez: None. L. Makahleh: None. S. Nagpal: None. A. Kavarthapu: None. V. Vedantam: None. Introduction: This case report details a rare instance of cardiac arrest in a patient with myxedema coma, a severe form of hypothyroidism. It highlights the diagnostic and therapeutic challenges in managing such complex endocrine emergencies. Case Presentation: A 70-year-old female with a history of hypothyroidism, type 2 diabetes, atrial fibrillation, pacemaker implantation, and COPD presented with a 3 day history of progressive lethargy and weakness. EMS found her with critically low blood glucose level of 20. History and Examination revealed non-compliance with thyroid medication and myxedematous features including moon-like facies, periorbital edema, generalized edema, elevated JVP, and cold extremities with sluggish capillary refill. In the ER, she was hypotensive, labs showed a significantly elevated TSH level of 30.55 (0.45-4.5), free T3 level of 1.2 (2.3-4.2), free T4 level of 1.12 (0.93-1.70), high lactate, metabolic acidosis, renal impairment, and liver enzyme elevation. These findings, coupled with the clinical presentation, led to the diagnosis of myxedema coma. The patient's critical state was further complicated by distributive shock, shock liver and oliguric AKI. Management included sodium bicarbonate infusion for severe acidosis, IV hydrocortisone, IV levothyroxine, and broad-spectrum antibiotics. Amiodarone was discontinued due to its potential contribution to acute liver injury and hypothyroidism. Despite interventions, she developed acute respiratory failure, requiring intubation and norepinephrine for low mean arterial pressure. Her renal function improved with pressor support, and her lactic acidosis resolved. She recovered quickly and was subsequently extubated. After stabilization, she was switched to oral levothyroxine and discharged. Shortly after discharge, she returned again with generalized weakness, confusion, and dysuria. ER evaluation revealed lethargy, hypotension, hypoglycemia, severe metabolic acidosis, and a UTI. She tested positive for Influenza. While in the ER, she had cardiac arrest, presenting with agonal breathing and PEA. CPR was initiated, achieving ROSC after two rounds and one dose of epinephrine. She was treated again with IV levothyroxine, and IV antibiotics. She recovered well and was discharged to rehab facility with re-education on compliance. Conclusion: This case exemplifies the complexity and challenges in managing a geriatric patient with multiple comorbidities, particularly in the context of myxedema coma. The intricate interplay of endocrine, cardiovascular, respiratory, and infectious complications necessitated a multifaceted and dynamic therapeutic approach. This case underscores the importance of compliance, vigilant monitoring, prompt recognition of complicating factors, and the need for a coordinated multidisciplinary approach in managing similar cases. Presentation: 6/2/2024

7964 Manipulation of the Gut Microbiome Using Antibiotics Is Associated With Sex-Specific Reductions in Systemic Testosterone Levels in Rats

Abstract Disclosure: G. Parodi: None. G. Leite: None. W. Morales: None. S.R. Weitsman: None. G.M. Barlow: None. M. Sanchez: None. M. Pimentel: None. M. Villanueva-Millan: None. M. Pimentel: None. R. Mathur: None. The gut microbiome has impacts on metabolic endocrine and reproductive functions. It is known that specific bacteria can impact host metabolism by synthesizing, secreting, and/or metabolizing sex-related hormones. However, the impacts of gut bacterial biosynthesis and/or metabolism of steroids on host metabolism and reproduction have not been fully addressed. In this study we challenged the gut microbiome of wild-type male and female rats with broad-spectrum antibiotics and examined the effects on circulating testosterone levels. Methods: Male (M) and female (F) Sprague-Dawley rats (8 weeks old) were housed with phytoestrogen-free bedding and received a phytoestrogen-free diet with water from glass bottles. Rats were given a combination of vancomycin (0.5g/L), ampicillin (1g/L), neomycin (1g/L), and metronidazole (1g/L) in their water for 8 days, and then returned to normal drinking water for another 13 days. Control rats were given normal water throughout the study. Serum and stool samples were collected before the start of antibiotics (baseline), on day 8 of antibiotics (AbxD8), and at 13 days post-removal of antibiotics (PAbxD13). Stool total DNA was extracted with the MagAttract PowerSoil DNA KF kit and quantified on a Qubit. Circulating testosterone levels were analyzed on a Luminex platform. Paired-ANOVA test was used to determine changes in testosterone levels in each group over time. Results: A total of 31 rats (M=16, F=15) received antibiotics, and 28 (M=14, F=14) were controls. Antibiotic exposure resulted in significant decreases in total stool DNA quantity in both male and female exposed rats relative to controls on AbxD8 (P<0.0001), which returned to baseline levels by PAbxD13. Antibiotic exposed male rats had a continuous decrease in testosterone levels throughout the timepoints collected (baseline: 5.78±2.74 ng/mL, AbxD8: 3.11±2.46 ng/mL, PAbxD13: 2.55±1.80 ng/mL, P=0.0027), however, in control male rats, circulating testosterone levels remained stable throughout the timepoints analyzed (baseline: 3.81±1.73 ng/mL, AbxD8: 3.72±1.12 ng/mL, PAbxD13: 3.92±3.38 ng/mL, P=0.49). There was no effect on circulating testosterone levels in female rats, with both groups, control and exposed, following the same cyclical pattern throughout the timepoints analyzed. Conclusions: Antibiotic depletion of the gut microbiome is associated with changes in systemic levels of testosterone in rats. These changes are sex-specific, and only detected in males. These results suggest a potential involvement of the gut microbiome in testosterone metabolism that is sex-specific. Presentation: 6/1/2024

8248 Glucocorticoid Induced Adrenal Crisis Masked By Metastatic Lung Carcinoma

Abstract Disclosure: N. Abrahimi: None. A. Abrahimi: None. Background: Chronic glucocorticoid use of three weeks or longer can cause hypothalamic-pituitary-adrenal axis inhibition by negative feedback, causing adrenal suppression. (1) Adrenal crisis is diagnosed by an acute clinical decompensation, persistent hypotension that resolves with high dose steroid administration. (2) Adrenal crisis is precipitated by several causes such as illness, dehydration, trauma, emotional distress and sometimes due to no identifiable cause. (2) Clinical Case: 64-year-old male past medical history of lung carcinoma metastatic to mediastinum who presented to the hospital with tachycardia. On presentation, patient was tachycardic, tachypneic, and hypotensive. Labs significant for WBC 22, Na+ 129, K+ 3.2, Cr 3.4. Patient received 2.5 L bolus of NS and was given one dose of azithromycin due to concern for sepsis. After fluid resuscitation, hypotension and tachycardia resolved. Presenting symptoms included ongoing nausea, decreased appetite and malaise for several weeks. Repeat labs post fluid resuscitation showed resolution of leukocytosis, improvement of AKI, and repletion of electrolytes. CT chest abdomen pelvis showed questionable pneumonia, however, consolidations were difficult to distinguish from known malignant masses. Clinical picture was not consistent with pneumonia and so additional antibiotics were held. Several hours later, blood pressure decreased, and patient began requiring vasopressors. Cefepime was started given concern for septic shock. Nearly 48 hours after initiation of broad-spectrum antibiotics hypotension persisted and patient remained on vasopressors. Given clinical decline, etiology of shock was reconsidered. Patient reported daily prednisone use over the last several months for COPD management. Given high clinical suspicion of adrenal crisis in setting of chronic steroid use and glucocorticoid withdrawal, patient was started on hydrocortisone 100 mg every 8 hours. Shortly after initiation of stress dosed steroids, the patient was successfully weaned off vasopressors with complete resolution of hypotension. Conclusion: Presentation and symptoms of adrenal insufficiency and crisis including nausea, anorexia, fatigue, malaise, hypotension and electrolyte abnormalities are nonspecific, can go unrecognized and be masked by other disease processes, such as metastatic cancer. (1) Adrenal crisis is life threatening and must be diagnosed and treated early to prevent mortality. (2) Therefore, adrenal crisis should always be on the differential in patients who present with shock.

7762 A Unique Case Of Sepsis-Driven Bilateral Adrenal Hemorrhages In A Patient With HIT

Abstract Disclosure: A. Siddiqui: None. B. Shalit: None. H. Nadeem: None. Z. Khan: None. D. Pinkhasova: None. Introduction: Bilateral adrenal hemorrhages, commonly seen in the setting of sepsis as Waterhouse Friderichsen syndrome, is a rare life-threatening condition. This process is driven by the release of bacterial endotoxins leading to the activation of coagulation, fibrinolysis, and proinflammatory pathways. It is by a similar process that now non-septic hypercoagulable states, including heparin-induced thrombocytopenia (HIT), factor V Leiden and protein C resistance are also being recognized as etiologic for bilateral adrenal hemorrhaging. The following case demonstrates a combination of the two etiologies leading to adrenal insufficiency from bilateral adrenal hemorrhages. Clinical Case: A 48-year-old male presented to the emergency department with right upper quadrant pain, dyspnea, and a low-grade fever. Laboratory results indicated leukocytosis with a predominance of neutrophils. Initial computed tomography imaging revealed a 4 x 3.5 cm right lower lobe multi-loculated lung abscess and multiple right lower lobe segmental/subsegmental pulmonary emboli. The patient was started on a heparin drip and empiric antibiotics. Infectious disease was consulted to help determine the etiology of the lung abscess. Extensive workup including sputum, blood, fungal cultures, and acid-fast bacillus smear testing were negative. The patient improved on routine broad-spectrum antibiotics and was planned to be transitioned to a direct oral anticoagulant until serial imaging revealed incidental bilateral 4 cm adrenal hemorrhages. Endocrinology was emergently consulted; a random cortisol level was drawn and found to be low at 2.7 (3-17 µg/dL) with an elevated Adrenocorticotropic hormone (ACTH) level of 114 (6 - 50 pg/mL) indicative of primary adrenal insufficiency. The patient subsequently became hypotensive and was started on stress-dose steroids. Upon further investigation, the patient was found to be thrombocytopenic, and hematology was involved. Based on his 4T score of 5, concern was raised for HIT and argatroban was initiated. Moreover, the patient was eventually stabilized for discharge with close follow-ups with endocrinology, infectious disease, and hematology as an outpatient. Conclusion: There have been 17 reported cases of bilateral adrenal hemorrhaging in the setting of HIT uniformly presenting with complete hemodynamic collapse. This case serves as even more unique given the added component of sepsis. Both sepsis and HIT respectively have been well established to pose individual risk for developing bilateral adrenal hemorrhages. Hence, we hope to highlight the importance of exploring all potential causes of adrenal insufficiency in the setting of bilateral adrenal hemorrhaging and emphasize the harms of anchoring to a single etiology. Presentation: 6/3/2024

A-257 Revolutionizing Fungal Infection Diagnosis: A Sensitive, Cost-Effective, and Time-Efficient Solution

Abstract Background Fungal infection detection is essential for optimizing therapeutic strategies, preventing complications, enhancing overall health, and alleviating the financial burden, and preventing transmission. According to the CDC, fungal illness resulted in 75,000 hospital admissions and 9 million outpatient visits annually, with 7,199 deaths predicted in the United States in 2021. The rising prevalence of fungal infections, influenced by factors such as population expansion and evolving treatment strategies poses a growing challenge to achieving an early and accurate diagnosis. There is the crucial need for improved detection methods to promptly identify various fungal infections, including Candida species, spanning from skin issues to potentially fatal systemic diseases, ultimately reducing associated morbidity and mortality. Severe and profound infections with life-threatening potential are common in individuals with compromised immune systems and those who are hospitalized. This risk is notably elevated among patients with organ transplants, immunosuppressive treatments, diabetes, recent broad-spectrum antibiotic usage, catheter utilization, and extended hospitalization periods. Our advancement seeks to introduce innovative methods leveraging carbon-based nanomaterials for the detection of fungal infections, offering distinct advantages including cost-effectiveness, ease of operation, and time efficiency compared to conventional techniques. Methods Our technology utilizes carbon-based nano materials, a promising advancement in nanotechnology to detect fungal infections, especially Candida manifestations. The samples are brought into contact with pre-probed carbon-based nano materials sensors maintained at a specific annealing temperature, facilitating nucleic acid hybridization. Subsequently, alterations in the carbon nanotube's electrical signal are observed, indicating a change in conductivity. This change can allow for the measurement of a voltage difference across a continuous flow of electricity, correlating with the concentration of targets present in the sample, thereby enabling the detection of specific microorganisms. No change was noticed in electrical properties of carbon-based nano material when negative experiments were conducted. Results The initial findings showed the presence of specific microorganisms within the sample in less than 15 minutes with carbon-based nano materials sensors. Comparative analysis of the electrical signal magnitude values obtained from carbon nanotube measurements against the corresponding CT values from quantitative PCR (qPCR) provides insights into the correlation between the electrical readouts and molecular quantification, offering a comprehensive evaluation of the nanotube-based detection system's performance in diagnostics procedure. Conclusions Unlike conventional blood culture and qPCR, our technology, delivers outcomes with heightened sensitivity, cost-effectiveness, and time efficiency. Our team's uncomplicated sample collection method notably reduces the intricacies of sample preparation, enabling the proper disposal of both the sample container and sensor part without requiring disassembly. Enhanced sensitivity, coupled with the economical and rapid detection capabilities of advanced technologies like carbon-based nano materials, is a promising alternative for the accurate and efficient diagnosis of fungal infections. Consequently, the implementation of such technology not only enhances diagnostic efficiency but also contributes to better patient outcomes through prompt and targeted therapeutic interventions.

A Chart Review for Epidemiology and Outcome of Fungal Bloodstream Infections Among Neonates in a Tertiary Care Hospital at North India

Background and Aims The risk of fungal bloodstream infection (BSI) and accompanying mortality in neonates varies widely in between centres depending on the region, the population characteristics and the risk factors. Methods This chart review of neonatal cases with fungal BSI admitted in a tertiary care teaching hospital in North India aimed to comprehensively investigate the epidemiology, profile of fungal species (and their susceptibility to various antifungal agents), risk factors, clinical profile and outcomes in these neonates. The study spanned over a one-year period, from September 2022 to August 2023, included all symptomatic neonates with positive blood cultures for fungal pathogen. Results Over one year, 24 out of 1,174 neonates at risk were diagnosed with fungal BSI, with a cumulative risk of 2.0 per 100 neonates. A peak in cases occurred in February. Candida pelliculosa was the predominant species (75% of isolates), while Candida albicans constituted 4.2%. Most isolates were sensitive to fluconazole, except for some fluconazole-resistant Candida pelliculosa (5.5%) and Candida tropicalis (25.0%), which remained susceptible to amphotericin-B and voriconazole. Around 60% of neonates were preterm, 40% had very low birth weight and 37% were small for gestational age. Nearly all had received prior broad-spectrum antibiotics, with 92% receiving prolonged courses over five days. Respiratory support, including intubation and mechanical ventilation, was used in 83% before onset of fungal sepsis. Intriguingly, all neonates had some invasive device in place for more than seven days. Mortality rate of 25% was observed, with preterm birth and gastrointestinal anomalies contributing to adverse outcomes. Conclusions This study confirms the ongoing shift in trend from albicans to non-albicans Candida infections in our region as well. A seasonal peak of fungal sepsis noted in the month of February hinted at potential seasonal variation or lapses in infection control practices during colder months. The analysis of trends in fungal BSI might hold a significance within neonatal intensive care units (NICUs) for the prompt detection of outbreaks. Simultaneously, understanding and analysing risk factors associated with fungal BSI are essential for targeted prevention.

A Young Female’s Battle with Toxic Epidermal Necrolysis Induced by NSAIDs: A Case Report

Introduction: Stevens-Johnson Syndrome (SJS) is a rare but severe mucocutaneous reaction often triggered by medications or infections, characterized by extensive epidermal detachment and mucosal involvement. This condition poses a high risk of morbidity and mortality, requiring prompt recognition and treatment. Case Presentation: An 18-year-old Asian female from eastern Nepal presented with non-itchy red spots, high fever, and significant discomfort following the administration of ibuprofen for minor sores. She developed extensive skin involvement covering 25% of her body surface area and severe mucosal lesions. Laboratory investigations revealed anemia, leukocytosis, and coagulopathy. She was admitted to the ICU, where she received broad-spectrum antibiotics, corticosteroids, and supportive care. The patient also developed acute kidney injury during treatment but eventually recovered and was discharged after a week. Clinical Discussion: The rapid onset of SJS in this patient reveals the unpredictable nature of drug-induced reactions. Early intervention with a multidisciplinary approach involving dermatology, intensive care, and infectious disease specialists was crucial in managing her condition. Despite the controversy surrounding corticosteroid use in SJS, their administration likely contributed to the rapid improvement in inflammation and skin healing. The case highlights the importance of early recognition, prompt management, and careful monitoring for adverse drug reactions, especially when prescribing medications known to cause SJS. Conclusion: The successful outcome achieved through a multidisciplinary approach provides valuable insights into the effective strategies for handling severe drug reactions, emphasizing that early diagnosis and comprehensive management in patients with SJS is critical.

Discovery of Highly Potent Triazole Derivatives with Broad-Spectrum Antifungal Activity Based on Iodiconazole

The widespread use of broad-spectrum antibiotics, the growing number of immunocompromised individuals, and the emergence of drug-resistant strains have resulted in the increasing incidence and mortality of invasive fungal infections. Azole drugs are the primary treatment for invasive fungal infections, and Iodiconazole is a potent azole drug with strong antifungal activity, but its stability is poor. In order to improve stability, a series of triazole compounds containing ethynyl group were designed and synthesized. Most of the compounds showed strong inhibitory activity against pathogenic fungi, among which compound 20l showed excellent inhibitory activity against pathogenic fungi and drug-resistant fungi. Importantly, and the stability of 20l (T1/2 = 30.2 min) was obviously improved compared with Iodiconazole (T1/2 = 4.39 min). In addition, the preferred compound 20l can prevent fungal phase transition and the formation of fungal biofilm, and show satisfactory fungicidal activity. In addition, the compound 20l was almost non-toxic to mammalian HUVEC cell and 293T cell. In vivo pharmacokinetic studies showed that 20l had acceptable pharmacokinetic properties. These results strongly demonstrate that compound 20l was worth further investigation as a potential antifungal inhibitor.

A Mini-Review on the Structural Characteristics and Anticancer Activity of Nagilactones

Abstract: Natural products provide abundant resources for the development of new drugs. Podocarpus nagi is an arbor of Podocarpus L'Hér. ex Persoon. Its fruits, leaves, and roots exhibit a broad spectrum of pharmacological activities (such as antitumor, plant growth regulation, termite killing, and insect larval toxicity), which have been used in Yao folk for a long history. Nagilactone is one of the key components discovered in Podocarpus nagi, which has a variety of structures and a broad spectrum of antitumor activities. In this mini-review, the structures and spectral characteristics, together with the antitumor activities and the structure-activity relationships of nagilactones, are summarized by searching the database in order to provide detailed references for researchers to elucidate and modify their structures.

Escherichia coli, an important Uropathogen: Characteristics and antimicrobial susceptibility pattern at Prof. Dr. I.G.N.G. Ngoerah General Hospital, period January 2020 – December, 2021

Background: Urinary tract infections (UTIs) are among the most common infections globally, often treated empirically with broad-spectrum antibiotics without prior culture and sensitivity testing. This practice has contributed to the rise in antibiotic resistance. Escherichia coli (E. coli) is the primary pathogen in uncomplicated UTIs, accounting for 70–90% of cases. However, other bacteria such as Klebsiella pneumoniae, Proteus mirabilis, and Enterococcus faecalis are also significant, especially in complicated or healthcare-associated UTIs. This study examines the resistance patterns of E. coli in UTI cases. Method: A descriptive cross-sectional study was conducted using secondary data from medical records of UTI patients treated at Prof. Dr. I.G.N.G. Ngoerah General Hospital from January 2020 to December 2021. E. coli isolates were identified, and antibiotic sensitivity tests were performed using the VITEK® 2 compact automatic system, with antimicrobial sensitivity and resistance determined according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Result: Analysis of 639 UTI patients revealed that E. coli exhibited high resistance to cefixime (13.3%), ciprofloxacin (23.8%), and trimethoprim-sulfamethoxazole (35.2%). The highest levels of susceptibility were observed with Tigecycline, Meropenem, and Ertapenem, with rates ranging from 99.2% to 99.8%. The demographic data showed a higher incidence of UTIs in female patients (70.9%) compared to males (29.1%), with the majority of cases occurring in adults (94.52%). Additionally, 52.26% of the E. coli isolates were ESBL-producing strains, complicating treatment options. Conclusion: The study underscores the urgent need for judicious antibiotic use, guided by culture and sensitivity testing, to combat the rising threat of antibiotic-resistant UTIs. Tigecycline, Meropenem, and Ertapenem should be prioritized in treatment protocols for multidrug-resistant cases. Continuous surveillance and the development of new antimicrobial agents are essential to address this escalating public health challenge

The clinical characteristics and risk factors analysis within one week before the onset of necrotizing enterocolitis

There are considerable researches on risk factors for necrotizing enterocolitis (NEC), focusing primarily on the entire course before onset. However, fewer studies address risk factors within the brief period before NEC occurrence. The current study aims to retrospectively analyze the clinical data of NEC patients while focusing on relevant risk factors in the preceding week of NEC onset. Infants born between January 2019 and December 2021 at Suzhou Municipal Hospital and Suzhou University Children’s Hospital with a birth weight < 1500 g or a gestational age < 32 weeks were included. Around 54 NEC patients and 180 controls were recruited in the study. NEC patients satisfying the inclusion criteria formed the case group, while a 1:4 matching principle helped select the control group based on gestational age and birth weight. A statistically significant difference was observed between groups when red blood cell transfusions were compared the week before NEC onset (adjusted OR and 95% CI 2.16 (1.10, 4.24)). Broad-spectrum antibiotic usage before NEC occurrence was significantly lower in the NEC group than in the control group (adjusted OR and 95% CI 0.95 (0.91, 0.99)). A statistically significant difference was observed between groups while comparing patent ductus arteriosus (PDA) (adjusted OR and 95% CI 2.45 (1.23, 4.91)). The indication for packed red blood cell transfusion should be strictly controlled. Moreover, close monitoring of the patient’s condition for NEC occurrence should be conducted within one-week post-transfusion. Accurately identifying infections and using broad-spectrum antibiotics can reduce the incidence of NEC.

Genetic networks suggest Asperger’s syndrome as a distinct subtype of autism spectrum disorders.

BackgroundThe Diagnostic and Statistical Manual of Mental Disorders (DSM-V) issued new diagnostic criteria for autism spectrum disorders (ASD) which resulted in missing the diagnosis of some cases of Asperger’s syndrome (AS). This negatively affected the support received by those affected. In this study, we explored if AS could be biologically stratified from the broader spectrum through a gene co-expression network preservation analysis. MethodsWe analysed the GEO microarray data of 24 individuals with Asperger’s syndrome and 72 individuals with autism. Then, we used a weighted gene co-expression network (WGCNA) pipeline to construct gene co-expression networks. We explored whether these modules share the same co-expression patterns between autism and Asperger’s syndrome using network preservation analysis. ResultsOur results showed that all co-expression modules of autism are preserved into the Asperger’s syndrome. However, three modules of Asperger’s syndrome out of 30 modules were not preserved in autism.Gene enrichment analysis revealed that these modules were involved in chromatin remodelling, immune and neuroinflammatory response, synaptic and neuronal development. Brain enrichment analysis showed significant downregulation of neurodevelopment genes in different brain regions associated with impaired social recognition in Asperger’s syndrome. ConclusionsThe identified genetic and molecular profiles suggest that Asperger’s syndrome, despite sharing numerous similarities with autism, possesses a distinct genetic profile that makes it a distinct subtype of autism. This distinction could have significant implications for the management and treatment strategies tailored to individuals with Asperger’s syndrome.

Antibiotic use in cesarean procedures in developing countries: current practices and improvements

Cesarean delivery, a common surgical procedure worldwide, is associated with a significantly increased risk of postoperative infections compared to vaginal births. This risk is notably higher in developing countries due to varying practices in antibiotic prophylaxis and differences in healthcare settings. This study aims to evaluate the current practices and potential improvements in antibiotic use in cesarean sections within these regions. Our analysis revealed that cesarean sections are performed at an increased rate in developing countries, with infection rates ranging from 10% to 40%, primarily due to inconsistent and often inadequate antibiotic prophylaxis. The most common postoperative infections include endometritis, wound infections, and urinary tract infections, largely influenced by factors such as the timing of antibiotic administration, the choice of antibiotic, and the presence of risk factors like prolonged labor and membrane rupture. The standard practice in many developing countries involves the administration of antibiotics post-cord clamping, which has been challenged by recent studies suggesting that preoperative administration can significantly reduce infection rates without adverse effects on neonatal outcomes. A shift towards a single dose of broad-spectrum antibiotics such as cephalosporins administered 30-60 minutes before incision is recommended based on our findings. This approach aligns with the successful reduction of infectious morbidity observed in developed countries and supports the need for standardized guidelines. Furthermore, our study underscores the importance of healthcare provider education and the establishment of clear protocols for antibiotic prophylaxis in cesarean sections. By adopting these improvements, developing countries can achieve a significant reduction in maternal morbidity and contribute to safer childbirth practices.