Empirical Therapy Research Articles

Quantifying aminoglycoside resistance in extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales clinical isolates: a retrospective cohort study.

Aminoglycoside resistance is frequently detected in extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-PE), questioning the appropriateness of aminoglycosides as empiric therapy in patients with suspected ESBL-PE infections. Therefore, we aimed to evaluate the frequency of aminoglycoside resistance in patients harbouring ESBL-PE and identify patient-related risk factors associated with aminoglycoside resistance to facilitate early detection of at-risk patients. This retrospective single-centre cohort study included hospitalised patients aged ≥18 years with an ESBL-PE-positive sample between January 2016 and December 2018. Aminoglycoside resistance was defined according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints for Enterobacterales for the current year of testing. Five hundred forty-four patients met the eligibility criteria, of which 240 (44.1%) harboured aminoglycoside-resistant ESBL strains. Identification of ESBL-Klebsiella pneumoniaewas significantly associated with aminoglycoside resistance (odds ratio [OR] = 2.64, 95% confidence interval [CI] = 1.65-4.21, p <0.001) and an international travel history within the past 12 months was marginally associated with aminoglycoside resistance (OR = 1.51, 95% CI = 0.95-2.42, p = 0.084). In a low ESBL endemicity setting, aminoglycoside resistance in patients harbouring ESBL-PE is common, especially ESBL-K. pneumoniae, and needs to be considered in clinicians' decision-making regarding empiric therapy regimens.

Towards an update on the antimicrobial use in Adult Care Units in Brazil: insights from multi-hospital prevalence study.

Introduction. Efforts to understand the burden of antibiotic use in low- and middle-income countries such as Brazil are essential for developing strategies that are effective and appropriate in the context of endemic multidrug-resistant organisms.Aim. This study aims to determine antimicrobial-prescribing practices among patients hospitalized in intensive care units (ICUs) for adults in Brazil.Methodology. A 1-day point prevalence multicentre survey was conducted in 58 adult ICUs across the five regions of Brazil. The institutions were categorized according to their type and size. Detailed antimicrobial prescription data were prospectively provided to all patients hospitalized on the day of data collection.Results. A total of 620 patients were included in the study, of whom 63.9% were receiving at least one antimicrobial. Of these, 34.6% were treated for an infection, but only 39.9% of the cases were based on microbiological criteria. Empirical treatment was applied to 72.3% of the patients. Significant differences in antibiotic usage were observed across the different hospitals included in the study. Overall, treatment was most commonly directed towards pneumonia (51.8%) and bloodstream infections (29.6%). Glycopeptides (19.4%) and carbapenems (18.5%) were the most prescribed in teaching hospitals, while in non-teaching hospitals, carbapenems (17.8%) and broad-spectrum cephalosporins (16.8%) were most frequently used.Conclusion. Our study reveals alarming data on antibiotic use in adult ICUs in Brazil, with high frequencies of severe healthcare-associated infections acquired in these units, where patients are frequently subjected to empirical treatment.

Rocky Mountain Spotted Fever Encephalitis and "Starry Sky" Pattern on MRI: A Case Report.

Rocky Mountain Spotted Fever (RMSF) is a tick-borne disease caused by Rickettsia rickettsii (R. rickettsii). RMSF presents after a tick bite with fever, rash, and headache but can also cause more serious neurological manifestations. We report a case of RMSF encephalitis presenting with altered sensorium and rapid progression to coma, fever, and petechial rash, and an magnetic resonance imaging (MRI) brain notable for a "starry sky" pattern. A 61-year-old woman presented with confusion and fever and was diagnosed with a urinary tract infection. Two days later, she became comatose. MRI brain revealed lacunar infarcts in the right centrum semiovale and splenium of the corpus callosum. Lumbar puncture was notable for neutrophilic pleocytosis and elevated protein with negative bacterial and viral cultures. Empiric meningitis therapy was initiated, and she was transferred to our institution. On transfer, she was febrile, comatose, and had a diffuse petechial rash. Repeat MRI brain demonstrated diffuse, innumerable punctate foci of diffusion restriction with susceptibility-weighted signal attenuation throughout cerebral hemispheres in a "starry sky" pattern. Skin biopsy revealed perivascular lymphocytic infiltrates. Serologic RSMF antibody titers were obtained, and doxycycline was initiated for presumed RMSF encephalitis. The family opted to pursue palliative measures, given no clinical improvement. RSMF titers and postmortem PCR from brain tissue were positive for R. rickettsii. This case report highlights the clinical presentation of RMSF encephalitis. RMSF encephalitis should be suspected in a patient presenting with encephalopathy, fever, petechial rash, and MRI brain findings of diffuse punctate foci of diffusion restriction and susceptibility-weighted signal attenuation in a "starry-sky" pattern.

Antimicrobial Resistance of Uropathogenic Escherichia coli in Outpatient Cases at Baeza Basic Hospital, Ecuador

Introduction: Bacterial resistance to antibiotics is one of the current major public health issues, as these compounds constitute a primary tool for controlling and treating bacterial infections. Objective: To determine the bacterial resistance of uropathogenic Escherichia coli in outpatient individuals attending the Microbiology Laboratory of Baeza Basic Hospital (BBH) during the period January-December 2023. Methodology: An observational, descriptive, and cross-sectional study was conducted to describe the antimicrobial resistance characteristics of uropathogenic Escherichia coli during the period January-December 2023. Results: We analyzed 169 positive urine culture results from outpatient individuals of both sexes, varying ages, with a diagnosis of urinary tract infection. The most frequently isolated microorganisms were Escherichia coli (80.1%), followed by Enterococcus faecalis (3.8%) and Proteus mirabilis (3.3%). Regarding antimicrobial resistance profiles expressed as a percentage for E. coli, they were as follows: ampicillin (70.8%), nalidixic acid (53.7%), amoxicillin + clavulanic acid (48.8%), trimethoprim + sulfamethoxazole (44.0%), and ciprofloxacin (34.3%). 12.4% of E. coli were extended-spectrum beta-lactamase (ESBL) producers. The sensitivity of E. coli to nitrofurantoin was 92.1%, ampicillin-sulbactam 90.4%, and fosfomycin 87.1%. Conclusions: The recommended empirical first-line treatment is nitrofurantoin, fosfomycin, and as second-line options, cephalexin and cefuroxime for uncomplicated urinary tract infections. Based on this information, it is proposed to develop a Clinical Guide for the treatment of uncomplicated urinary tract infections in the study areaarea.

Antimicrobial Resistance of Uropathogenic Escherichia coli in Outpatient Cases at Baeza Basic Hospital, Ecuador

Introduction: Bacterial resistance to antibiotics is one of the current major public health issues, as these compounds constitute a primary tool for controlling and treating bacterial infections. Objective: To determine the bacterial resistance of uropathogenic Escherichia coli in outpatient individuals attending the Microbiology Laboratory of Baeza Basic Hospital (BBH) during the period January-December 2023. Methodology: An observational, descriptive, and cross-sectional study was conducted to describe the antimicrobial resistance characteristics of uropathogenic Escherichia coli during the period January-December 2023. Results: We analyzed 169 positive urine culture results from outpatient individuals of both sexes, varying ages, with a diagnosis of urinary tract infection. The most frequently isolated microorganisms were Escherichia coli (80.1%), followed by Enterococcus faecalis (3.8%) and Proteus mirabilis (3.3%). Regarding antimicrobial resistance profiles expressed as a percentage for E. coli, they were as follows: ampicillin (70.8%), nalidixic acid (53.7%), amoxicillin + clavulanic acid (48.8%), trimethoprim + sulfamethoxazole (44.0%), and ciprofloxacin (34.3%). 12.4% of E. coli were extended-spectrum beta-lactamase (ESBL) producers. The sensitivity of E. coli to nitrofurantoin was 92.1%, ampicillin-sulbactam 90.4%, and fosfomycin 87.1%. Conclusions: The recommended empirical first-line treatment is nitrofurantoin, fosfomycin, and as second-line options, cephalexin and cefuroxime for uncomplicated urinary tract infections. Based on this information, it is proposed to develop a Clinical Guide for the treatment of uncomplicated urinary tract infections in the study areaarea.

Hemophagocytic Lymphohistiocytosis (HLH)

HLH is a reactive process resulting from prolonged and excessive antigen-presenting cell activation [1]. Hemophagocytosis is a hallmark of activated macrophages/histiocytes. The predominant clinical findings of HLH are fever (often hectic and persistent), cytopenia, hepatitis, and splenomegaly. A case of HLH in a 32-year-old female with no past medical history was presented in the current paper. She was admitted to the medical department with a fever and thrombocytopenia for evaluation. After failure to respond to a brief course of empiric antibiotics, the patient was extensively investigated and finally diagnosed with HLH (bone marrow aspiration showed occasional hemophagocytes). She was started on steroids but, failed to respond and so immunosuppressant drugs were added to the therapy.

The epidemiology of gram-negative bacteremia in Lebanon: a study in four hospitals

IntroductionGram-negative bacteremia is a life-threatening infection with high morbidity and mortality. Its incidence is rising worldwide, and treatment has become more challenging due to emerging bacterial resistance. Little data is available on the burden and outcome of such infections in Lebanon.MethodsWe conducted this retrospective study in four Lebanese hospitals. Data on medical conditions and demographics of 2400 patients diagnosed with a bloodstream infection based on a positive blood culture were collected between January 2014 and December 2020.ResultsMost bacteremias were caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, with the more resistant organisms being hospital-acquired. Third-generation cephalosporin and quinolone resistance was steady throughout the study, but carbapenem resistance increased. Mortality with such infections is high, but carbapenem resistance or infection with Pseudomonas or Acinetobacter species were significant risk factors for poor outcomes.ConclusionThis is the first multi-center study from Lebanon on gram-negative bacteremia, resistance patterns, and factors associated with a poor outcome. More surveillance is needed to provide data to guide empirical treatment for bacteremia in Lebanon.

Retrospective validation study of a machine learning-based software for empirical and organism-targeted antibiotic therapy selection.

This study is registered with ClinicalTrials.gov as NCT06174519.

Population pharmacokinetic modeling of ceftriaxone in cerebrospinal fluid in children: should we be using once- or twice-daily dosing for meningitis?

Guidelines for bacterial meningitis in children recommend intravenous ceftriaxone 50 mg/kg (max 2 g) twice daily (BD) or 100 mg/kg (max 4 g) once daily (OD), leaving the decision regarding the dose frequency to the prescriber. We investigated the cerebrospinal fluid (CSF) penetration of ceftriaxone to evaluate whether one dosing regimen is superior. Unbound ceftriaxone concentrations were measured in serum and CSF samples from children aged 0-18 years treated with ceftriaxone if there was a sample remaining after clinical tests were performed. A serum-CSF population pharmacokinetic model was developed using non-linear mixed-effects modeling. The once- and twice-daily dosing regimens were simulated, and the probability of target attainment (PTA) was determined for maintaining a CSF concentration above a minimum inhibitory concentration (MIC) of 1 mg/L for common meningitis pathogens and 4 mg/L for Staphylococcus aureus for 100% of the dosing interval. Sixteen serum and 87 CSF samples were collected from 98 children (age range 0.1-18.5 years). The final two-compartment serum-CSF model included a renal maturation function with weight scaling on clearance and volume of distribution. The estimated serum:CSF uptake was 20.1%. For MIC 1 mg/L, the 24 h PTA was higher for OD (88%) compared with BD (53%) dosing, although both achieved a 100% PTA at steady state. For S. aureus (MIC 4 mg/L), neither dosing regimen was sufficient. Our findings support the use of a 100 mg/kg once daily regimen for empirical treatment of bacterial meningitis due to earlier achievement of the pharmacodynamic target. Neither dosing regimen was adequate for S. aureus meningitis.

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.

Gas gangrene with Clostridium septicum in a neutropenic patient.

Gas gangrene is a rare presentation of a necrotizing fasciitis, caused by Clostridium perfringens, C. septicum and other clostridial species. With its rapid progression it is a potentially life-threatening infection, that poses as a challenge in the clinical management requiring an interdisciplinary approach.Here we present a 62-year-old woman, who developed neutropenic fever while undergoing chemotherapy for triple negative breast cancer. She presented with a high fever, reporting little pain in her left thigh accompanied by redness and induration locally. Subsequently the patient developed pain and redness of the back of the left hand. The initial findings suggested cellulitis and immediate empiric treatment with intravenous meropenem was started. Despite the antibiotic treatment the patient rapidly developed septic shock along with progression of the local infection. Emergency surgical debridement revealed extensive necrosis of the soft tissues including extensive myonecrosis of the thigh. On the left hand an extensive debridement was performed, the left lower limb could not be preserved and exarticulation of the left hip was required. Microbiologically C. septicum was isolated in different samples, confirming gas gangrene. As there was no local entry portal on the skin, hematogenous seeding from intestinal translocation in this neutropenic patient was suspected. The empiric antibiotic treatment was tailored to intravenous penicillin and complemented with clindamycin for toxin inhibition. Following radical debridement and antibiotic treatment, the patient could be stabilized. After repetitive debridement wound closure was achieved and the patient was discharged for rehabilitation. Antibiotic treatment was continued for four weeks.This rare case of gas gangrene in a neutropenic patient shows the complexity in the diagnostic and therapeutic management of necrotizing soft tissue infections in immunocompromised patients. It particularly highlights the importance of an interdisciplinary management with fast recognition of the disease and rapid, if needed radical, surgical debridement as well as tailored antibiotic treatment for a successful outcome.

Risk factors for multidrug-resistant bacteria in critically ill children and MDR score development.

Antimicrobial resistance and healthcare-associated infections (HAIs) are major health concerns in the pediatric intensive care unit (PICU). Device-associated HAIs (DA-HAIs) produced by multidrug-resistant (MDR) bacteria are especially worrying, as they can lead to an inappropriate empirical antibiotic therapy, worsened outcomes and increased mortality. The MDR score was designed to enable the prompt identification of patients at high risk of developing an MDR infection. This was a single-center, prospective, observational study, conducted between January 2015 and December 2022, including PICU patients with a microbiologically confirmed DA-HAI. Demographic, clinical characteristics and outcomes were compared between patients with a DA-HAI caused by MDR and non-MDR-associated DA-HAI, and a risk score for multi-resistance was designed. In total, 257 DA-HAI cases were included, 86 (33.46%) caused by an MDR microbe. In the univariate analysis, comorbidity (p = 0.002), previous MDR colonization (p < 0.001), previous surgery (p = 0.018), and previous antibiotic therapy (p = 0.009) were more frequent among MDR-associated DA-HAI (MDR DA-HAI). In addition, days from device insertion to infection and from PICU admission (p < 0.005) to infection were longer in patients with MDR. In the multivariate analysis, previous comorbidity (OR 2.201), previous MDR colonization (OR 5.149), and PICU length of stay longer than 9days (OR 1.782) were independently associated with MDR-DA-HAI. Using these three independent risk factors for MDR, a risk score was created: the MDR score. Three risk groups were obtained: low risk (0-2 points), intermediate risk (3-7 points), and high risk (8-12 points). Seventy-one patients with MDR-DA-HAI (82.6%) were classified in the intermediate or high-risk group, with a global sensitivity of 82.6%. The specificity in the high-risk group was 91.8%, and 81.0% of patients who were stratified into the low-risk group had non-MDR-associated infections, so they were correctly classified. Conclusions: The MDR score can be a useful tool to stratify patients in risk groups for MDR-DA-HAI. It may help to guide the choice of empirical therapy, leading to early optimization and avoiding delays in establishing appropriate treatment. This study reinforces the importance of stratifying patients based on their individual risk profile for MDR infection.

AI Algorithms for Modeling the Risk, Progression, and Treatment of Sepsis, Including Early-Onset Sepsis—A Systematic Review

Sepsis remains a significant contributor to neonatal mortality worldwide. However, the nonspecific nature of sepsis symptoms in neonates often leads to the necessity of empirical treatment, placing a burden of ineffective treatment on patients. Furthermore, the global challenge of antimicrobial resistance is exacerbating the situation. Artificial intelligence (AI) is transforming medical practice and in hospital settings. AI shows great potential for assessing sepsis risk and devising optimal treatment strategies. Background/Objectives: This review aims to investigate the application of AI in the detection and management of neonatal sepsis. Methods: A systematic literature review (SLR) evaluating AI methods in modeling and classifying sepsis between 1 January 2014, and 1 January 2024, was conducted. PubMed, Scopus, Cochrane, and Web of Science were systematically searched for English-language studies focusing on neonatal sepsis. Results: The analyzed studies predominantly utilized retrospective electronic medical record (EMR) data to develop, validate, and test AI models to predict sepsis occurrence and relevant parameters. Key predictors included low gestational age, low birth weight, high results of C-reactive protein and white blood cell counts, and tachycardia and respiratory failure. Machine learning models such as logistic regression, random forest, K-nearest neighbor (KNN), support vector machine (SVM), and XGBoost demonstrated effectiveness in this context. Conclusions: The summarized results of this review highlight the great promise of AI as a clinical decision support system for diagnostics, risk assessment, and personalized therapy selection in managing neonatal sepsis.

Diversity and antibiotic sensitivity of uropathogens from a regional hospital in Rwanda

Background: Urinary tract infections are a common cause for antibiotic consumption. Empirical treatment is common for community-acquired infections owing to predictability of pathogens. Objectives: Describe sensitivity profiles of uropathogens at a regional hospital in Rwanda. Methods: Hospital-based cross-sectional study in which clean-catch urine samples were analyzed. A two-stage process involving dipstick urinalysis and urine culture was used to identify true infections. The Kirby-Bauer disc diffusion method was used for antibiotic sensitivity analysis as per EUCAST guidelines. Results: Of 198 samples studied, 107 met criterion for UTI with 94 yielding significant growth. Klebsiella pneumoniae (35%), and Escherichia coli (32%) were the most common organisms isolated. Others included Staphylococcal species, Proteus spp, Enterobacter spp and Salmonella. Very high resistance frequencies (above 70%) were observed against amoxycillin, cotrimoxazole, trimethoprim, aztreonam and fosfomycin. Resistance to fluoroquinolones, aminoglycosides and cephalosporins varied between 40-60%. High levels of cross resistance were observed for drugs of the same class. Resistance to the potentiated penicillins, meropenem, cefoxitin and nitrofurantoin were less than 30%. Piperacillintazo bactum performed best with 91% sensitivity against all organisms tested. Conclusion: High levels of resistance were observed for most antibiotics studied. For empirical treatment of community-acquired UTI in our setting, nitrofurantoin remains effective while ciprofloxacin is not. Keywords: Diversity and antibiotic sensitivity; uropathogens; Rwanda.

8158 Transient Blindness In Metformin-Associated Lactic Acidosis

Abstract Disclosure: Y. Abouelkheer: None. A. Nasir: None. M. Ibrahem: None. Transient Blindness in Metformin-associated Lactic Acidosis Background: Metformin-associated lactic acidosis (MALA) is a rare side effect of metformin use. MALA can result in acute transient blindness in patients with severe metabolic derangements. Clinical Case: A 62-year-old woman presented with severe diarrhea, poor oral intake, malaise, and vomiting on a background of metformin-treated type 2 diabetes mellitus. Laboratory investigations showed bicarbonate &amp;lt;2 mmol/L, anion gap 48 mmol/L, lactic acid 20.5 mmol/L, serum osmolality 352 mOsm/kg, negative urine toxicology screen, and positive SARS-CoV-2. In the emergency department, the patient developed sudden onset bilateral vision loss. The examination was remarkable for complete vision loss bilaterally in all fields, associated with minimally reactive pupils and spontaneous ocular movements with an otherwise unrevealing neurological examination. Computed Tomography (CT) of the brain with stroke protocol showed no evidence of acute intracranial process. CT angiogram of the brain and neck showed patent intracranial and cervical vasculature without high-grade stenosis, large vessel occlusion, or aneurysm. While receiving medical management with intravenous fluid resuscitation and sodium bicarbonate supplementation, the patient had a spontaneous return of vision with no additional neurological complications or deficits. The severe metabolic derangements were associated with distributive shock, requiring admission to the intensive care unit for urgent hemodialysis, pressor support, empiric antibiotics, and stress-dose steroids. Shortly after the patient’s only hemodialysis session, we noted the resolution of her critical metabolic disturbances, renal failure, and shock state. Laboratory investigations post-dialysis showed bicarbonate 12 mmol/L, anion gap 36 mmol/L, and lactic acid 10.5 mmol/L. Follow-up MRI showed chronic lacunar infarct of the left basal ganglia, and she was discharged home six days later. Conclusion: Transient blindness in MALA can mimic acute neurovascular events. Prompt correction of metabolic derangements can aid in reversing systemic symptoms and blindness. Reference: DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016;65(2):20-29. doi:10.1016/j.metabol.2015.10.014 Presentation: 6/2/2024

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

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

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.

Early treatment for Clostridioides difficile infection: retrospective cohort study.

Clostridioides difficile (CDI) is a common cause of infectious diarrhea. The current recommendation is to initiate empirical antibiotic treatment for suspected CDI who have an anticipated delay of confirmatory results or fulminant colitis. This is based on limited clinical trials. The study aims to examine the impact of early treatment on mortality and clinical outcomes. This retrospective cohort study included adult patients with CDI. Early treatment was defined as the initiation of an anti-Clostridioides medication within the first 24h following stool sampling. Outcomes were 30 and 90day mortality, length of hospital stay (LOS), recurrence, and colectomy rate. To address potential bias, propensity score matching followed by logistic regression was performed, P value less than 5% was considered statistically significant. Study cohort consisted of 796 patients; clinical characteristics were balanced following matching. There was no difference, in favor of early treatment, between the groups regarding 30day mortality and 90day mortality with HR of 0.91 (95% CI 0.56-1.47) and 0.7 (95% CI 0.45-1.08), respectively. No statistically significant difference in recurrence rate, ICU admission or colectomy rate was observed. The LOS was shorter in the early-treatment group with 6days vs. 8days. Early treatment for CDI had shortened hospital stay. However, it did not affect clinical outcomes in adult patients.

7988 A Case of Spontaneous Pituitary Hemorrhage in Late Pregnancy

Abstract Disclosure: D. Poudyal: None. G.L. Prince: None. Background: Pituitary apoplexy (PA), caused by hemorrhage into the pituitary gland, is rare. The prevalence in pregnancy is also quite rare, with PA complicating 1 in 10,000 pregnancies. PA usually occurs in patients with pre-existing pituitary adenomas. Spontaneous pituitary hemorrhage (PH) causing PA in the absence of a known adenoma or other precipitating factors is less frequently described. Presenting symptoms of PA are non-specific and can pose diagnostic challenges, yet PA must be managed urgently and decisively due to the risk of life-threatening hormonal deficiencies that can ensue. Physiologic changes in pregnancy pose additional challenges in evaluating and managing patients with possible PA. Here we present a case of spontaneous PH during the third trimester of pregnancy in the absence of pre-existing pituitary pathology or known precipitants. Case presentation: A 31-year-old female, G2P1, with an uncomplicated first pregnancy, presented with acute-onset headache and vision loss at 36 weeks gestation. Her symptoms resolved spontaneously in 45 minutes. MRI brain without contrast showed hemorrhage within the left aspect of the pituitary gland, a mildly displaced infundibulum, but no mass effect on the optic chiasm. MRI brain obtained 1 year prior for headache was unremarkable. Lab work showed an 8AM cortisol of 19 ug/dL (Ref range 3.7 - 19.4 ug/dL), and a total T4 of 11.3 ug/dL (Ref 4.9 - 11.7 ug/dL). Ultimately, interpretation of her cortisol testing was limited by: elevated cortisol-binding globulin in the high-estrogen state of pregnancy, elevated cortisol production by an intact hypothalamic-pituitary-adrenal (HPA) axis during the latter portion of pregnancy, and the lack of validated cutoff values for 8AM serum cortisol levels during pregnancy. In light of these factors and the risk of undiagnosed adrenal insufficiency (AI), she was treated empirically with oral hydrocortisone. Subsequently, she had an uneventful vaginal delivery, supported by stress dosing of her steroids. Postpartum, she had a normal 8AM cortisol level of 14 ug/dL, and she was noted to quickly begin breastfeeding without incident. Conclusion: PA remains a critical diagnosis that cannot be missed in patients presenting with concerning symptoms and signs, in order to identify and treat life-threatening hormonal deficiencies. Pregnancy poses unique challenges in diagnosing hormonal deficiencies such as AI due to normal physiologic changes affecting the HPA axis as well as other pituitary axes. Therefore, the benefit of empiric hydrocortisone treatment likely outweighs any associated treatment risk in cases with consistent symptomatology and radiographic findings. Presentation: 6/2/2024