Empirical Therapy Research Articles

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

Enhancing antimicrobial management: A 5–year retrospective analysis of urinary pathogen susceptibility at a tertiary care centre from January 2018 to December 2022

Objective: The study aims to collect data on prevalence and antibiotic susceptibility patterns of uropathogens in a hospital in India, and to analyze any changes that have occurred over the past 5 years. Methods: This retrospective study was conducted over 5 years at Lady Hardinge Medical College & Associated Hospitals, New Delhi. Urine samples from patients who attended outpatient department or were admitted with diagnosis of urinary tract infection (UTI) were included in this study. Samples were cultured and tested to identify bacteria and determine antibiotic susceptibility using the Kirby-Bauer disc diffusion method. Results: A total of number of 151395 urine specimens were collected from January 2018 to December 2022. The prevalence of UTI was 7.5% (11372/151395) with the majority of patients being aged above 40 years (19.3%). The prevalence was higher in females (12.7%) as compared to males (3.2%). Escherichia (E.) coli was the predominant pathogen, accounting for 59.8% of cases, followed by Klebsiella spp. at 18.9%, and Enterococcus spp. at 8.3%. Gram-negative bacteria accounted for 89.5% of the isolates and exhibited good susceptibility to aminoglycosides and piperacillin-tazobactam, but showed resistance to fluoroquinolones. Methicillin-resistant Staphylococcus aureus (MRSA) was present in 35% of Staphylococcus (S.) aureus isolates with high susceptibility to glycopeptides and nitrofurantoin. Conclusions: The data suggest the need for careful selection of empirical therapy due to increasing resistance patterns. The stringent use of antimicrobial agents is pivotal to the control of antimicrobial resistance. Antibiotic susceptibility data contributes to tailoring the antibiotic stewardship programs to local needs.

The clinical application of metagenomic next-generation sequencing in immunocompromised patients with severe respiratory infections in the ICU.

Early targeted antibiotic therapy is crucial for improving the prognosis of immunocompromised patients with severe respiratory infections (SRIs) in the intensive care unit (ICU). Metagenomic next-generation sequencing (mNGS) has shown significant value in pathogen detection, but research on lower respiratory tract microorganisms remains limited. This study enrolled 234 patients with SRIs in the ICU, and individuals were categorized into immunocompromised and immunocompetent groups. We compared the diagnostic performance of mNGS using bronchoalveolar lavage fluid (BALF) with conventional microbiological tests (CMTs) and analyzed the value of mNGS in immunocompromised patients with SRIs in the ICU. Among all patients, the pathogenic microorganism detection rate of mNGS was higher than that of CMTs (94.02% vs 66.67%, P < 0.05), both in the immunocompromised group (95.0% vs 58.75%, P < 0.05) and the immunocompetent group (93.51% vs 71.43%, P < 0.05). mNGS detected more pathogens than CMTs did (167 vs 51), identifying 116 organisms that were missed by CMTs. The proportion of antibiotic regimen adjustments based on mNGS results was significantly higher compared to CMTs in both the immunocompromised (70.00% vs 17.50%, P < 0.05) and immunocompetent groups (48.70% vs 15.58%, P < 0.05). In the immunocompromised group, patients who had their antibiotic treatment adjusted on mNGS results had improved prognosis, with significantly lower ICU mortality (8.93% vs 50%, P < 0.05) and 28-day mortality rates (30.36% vs 68.75%, P < 0.05) than CMTs. In the immunocompetent group, no statistically significant differences were observed in ICU mortality or 28-day mortality (20.00% vs 33.33%, P > 0.05; 42.67% vs 45.83%, P > 0.05). mNGS shows significant value in detecting pathogens in immunocompromised patients with SRIs in ICU. For immunocompromised patients who respond poorly to empirical treatment, mNGS can provide an etiological basis, helping adjust antibiotic regimens more precisely and thereby improving patient prognosis.

8411 Ectopic ACTH-dependent Cyclical Cushing’s Syndrome- the Art of Hide-and-seek

Abstract Disclosure: H. Mon: None. A. Kapoor: None. S. Qureshi: None. M. Martineau: None. K. Meeran: None. Case report: A 72-years-old lady was admitted with hypokalaemia, hyperglycaemia with metabolic alkalosis with background hypertension, type2 diabetes, osteoporosis and right-sided breast cancer treated with chemotherapy and radiotherapy 3years ago. She was previously seen in Endocrinology Clinic for similar episode and deemed not having Cushing’s or Conn’s syndrome on workup. During this admission, although there was no obvious Cushingoid appearance, there was refractory hypokalaemia. On further exploration, there were previous admissions with similar episodes in UK and in her home country, within the same year, a few months apart. Therefore, endocrinology workup was conducted for suspected cyclical Cushing’s syndrome. It demonstrated raised 24-hour urinary free cortisol of 5643 nmol/24hour (reference range 0-164 nmol/24hours), unsuppressed low dose dexamethasone suppression test with cortisol level of 800 nmol/L and increased ACTH level of 429 ng/L. MRI (pituitary) showed no pituitary lesion with probable empty sella and CSF filled. However, CT (thorax) showed enlarging lesion (previously from 1cm to 1.6cm) in the left lower lobe, concerning lung metastasis or primary lung malignancy. PET scan showed left lower lobe nodule having low-grade activity with likelihood of indolent malignancy and appearances of physiologic adrenal hyperplasia. Management: Given persistently high cortisol levels during admission with ongoing hyperglycaemia and refractory hypokalaemia, metyrapone was started and titrated accordingly. Her clinical condition including potassium and cortisol levels effectively responded to metyrapone. Gallium scan was booked for detail localization with ongoing lung MDT (multidisciplinary team meeting) and neuroendocrine tumour MDT.However, after starting metyrapone, she had type 1 respiratory failure, not responding to initial antibiotics. After excluding other possible respiratory aetiologies, empirical treatment for Pneumocystosis pneumonia (PCP) was initiated, after which blood test for Beta-D-glucan was found out to be significantly raised, supporting the presumptive diagnosis. Conclusion: Our case highlighted the following interesting points 1. diagnostic challenges, due to the fluctuating nature of cyclical Cushing’s syndrome, presenting with recurrent hypokalaemia. 2. the interesting nature of likely ACTH-dependent cyclical Cushing’s syndrome, progressing into florid Cushing’s syndrome, with efficacy to metyrapone 3. rare and compelling combination of 3 conditions of Cyclical Cushing’s syndrome, being ectopic ACTH-dependent and complicated by Pneumocystosis pneumonia (PCP). Presentation: 6/1/2024

Trends in antimicrobial resistance amongst Salmonella Typhi in Bangladesh: A 24-year retrospective observational study (1999-2022).

Rising antimicrobial resistance (AMR) in Salmonella Typhi restricts typhoid treatment options, heightening concerns for pan-oral drug-resistant outbreaks. However, lack of long-term temporal surveillance data on AMR in countries with high burden like Bangladesh is scarce. Our study explores the AMR trends of Salmonella Typhi isolates from Bangladesh, drawing comparisons with antibiotic consumption to optimize antibiotic stewardship strategies for the country. The typhoid fever surveillance from 1999 to 2022 included two pediatric hospitals and three private clinics in Dhaka, Bangladesh. Blood cultures were performed at treating physicians' discretion; cases were confirmed by microbiological, serological, and biochemical tests. Antibiotic susceptibility was determined following CLSI guidelines. National antibiotic consumption data for cotrimoxazole, ciprofloxacin, and azithromycin was obtained from IQVIA-MIDAS database for comparison. Over the 24 years of surveillance, we recorded 12,435 culture-confirmed typhoid cases and observed declining resistance to first-line drugs (amoxicillin, chloramphenicol, and cotrimoxazole); multidrug resistance (MDR) decreased from 38% in 1999 to 17% in 2022. Cotrimoxazole consumption dropped from 0.8 to 0.1 Daily defined doses (DDD)/1000/day (1999-2020). Ciprofloxacin non-susceptibility persisted at >90% with unchanged consumption (1.1-1.3 DDD/1000/day, 2002-2020). Low ceftriaxone resistance (<1%) was observed, with slightly rising MIC (0.03 to 0.12 mg/L, 1999-2019). Azithromycin consumption increased (0.1 to 3.8 DDD/1000/day, 1999-2020), but resistance remained ≤4%. Our study highlights declining MDR amongst Salmonella Typhi in Bangladesh; first-line antimicrobials could be reintroduced as empirical treatment options for typhoid fever if MDR rates further drops below 5%. The analysis also provides baseline data for monitoring the impact of future interventions like typhoid conjugate vaccines on typhoid burden and associated AMR.

Evaluation of the quickmic system in the rapid diagnosis of Gram-negative bacilli bacteremia.

The rapid diagnosis of antibiotic sensitivity in Gram-negative bacilli is of paramount importance in clinical microbiology, particularly in cases of bacteremia. The escalating challenge of antimicrobial resistance underscores the need for expeditious antibiotic susceptibility diagnostics to guide empirical antibiotic therapy effectively. In light of this, we present our study that evaluates the QuickMIC System, a recently developed rapid diagnostic antibiogram. QuickMIC System, offers a novel approach to phenotypic testing, providing information on the activity of 12 antibiotics against key pathogens, including Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae, Proteus spp., Citrobacter spp., and Serratia marcescens. Our investigation involved testing a total of 816 antibiotic/microorganism combinations. The study demonstrated an impressive 99.02% concordance between the QuickMIC System and the reference methods, with only eight discrepancies observed. The time to actionable minimum inhibitory concentration (MIC) ranged between 2 and 4 h, highlighting the system's efficiency in providing rapid results.

Accelerated Agony

Abstract This case report discusses a 39-year-old male with advanced HIV infection presenting with fever, weight loss, and respiratory symptoms, ultimately succumbing to fulminant pulmonary coccidioidomycosis. Despite initial empirical treatment for bacterial pneumonia and Pneumocystis jirovecii, the patient's condition rapidly deteriorated, highlighting the diagnostic challenges posed by this fungal infection, especially in immunocompromised individuals. Diagnostic confirmation was complicated by nonspecific clinical features, overlapping symptoms with other opportunistic infections, and unreliable serological tests. Radiological findings resembled those of other pulmonary infections, further complicating timely diagnosis. Delayed recognition of disseminated coccidioidomycosis contributed to the patient's poor prognosis. Antifungal therapy, primarily azoles, remains the cornerstone of management, with prognosis worsening with additional dissemination sites and advanced HIV illness. This case underscores the importance of considering pulmonary coccidioidomycosis in immunocompromised patients presenting with respiratory symptoms, particularly in endemic regions.

A-282 Purpura fulminans caused by Haemophilus influenzae: case report of unusual etiology

Abstract Background Fulminant purpura is a clinical syndrome characterized by a purplish, ischemic-looking skin rash, commonly accompanied by systemic symptoms ranging from acute febrile syndrome to septic shock. Due to high lethality of possible infectious etiologies, immediate recognition and early initiation of empirical antimicrobial therapy are crucial to ensure better outcomes. Interdisciplinary collaboration among healthcare teams, infectious disease specialists and microbiologists is essential to ensure accurate and early microbiological diagnosis. Methods This work aims to report a case of Haemophilus influenzae-induced purpura fulminans that occurred in Fortaleza-CE, a coastal city in northeastern Brazil, highlighting clinical recognition and microbiological identification, based on review of medical records. Results Case report A 59-year-old man, originally from Germany, was on vacation in Brazil. He presented to emergency medical service with an acute onset of fever, abdominal pain and diarrhea, progressing to decreased level of consciousness and purplish ischemic skin lesions with hemorrhagic bullae on trunk and extremities (Figure 1), with no history of trauma. Upon admission, the blood exams showed bicytopenia - 1900 leukocytes/µL (86% segmented) and 51,000 platelets/µL - and very high C-reactive protein (41.58 mg/dL). Although empirical antimicrobial therapy with vancomycin and piperacillin-tazobactam was initiated, patient progressed to septic shock, hepatic dysfunction, requiring mechanical ventilation, vasopressor support, and renal replacement therapy. Blood cultures from hospital admission were positive after about 14 hours and allowed isolation of small and translucent colonies in Chocolate PVX plate Agar (BioMerieux™). Maldi tof analysis by Vitek MS identified H. influenzae (99.9 % accuracy). Despite prolonged hospitalization due to multiple organ dysfunctions, patient had a positive outcome. Conclusions This case illustrates the importance of immediate recognition of the syndrome coupled with assertive empirical treatment and early microbiological diagnosis for a positive clinical outcome, even in a severe presentation. Multiprofessional approach is essential for accurate and early diagnosis.

A-253 Antimicrobial Susceptibility Pattern in Escherichia coli Isolated From Community-Acquired Urinary Tract Infections in the era Post-Covid-19

Abstract Background Urinary tract infections (UTI) are one of the most common infectious diseases diagnosed in the community as well as in hospitals. Community-acquired urinary tract infections caused by Escherichia coli represent the largest proportion of infectious diseases affecting women and a significant amount of oral antibiotics are prescribed daily to treat UTI in community outpatient clinics. Having knowledge of regional susceptibility data regarding E. coli is very important for selecting an appropriate empirical antibiotic. This study aimed to report the frequency and antimicrobial susceptibility of E. coli isolated from community-acquired urinary tract infections post-Covid-19 pandemic. Methods This study was a retrospective analysis from January to December 2023 based on the analysis of 24,019 uropathogens isolated from 182 outpatient health centers located in several regions of São Paulo city, Brazil. The urine samples were cultivated onto ChromID™CPS® agar plates by semi-quantitative technique using 1µL disposable loop, incubated at 35-37°C and the colony counting were read after 24h and 48h of incubation. The bacteria identification was performed by MALDI-TOF mass spectrometry (Vitek-MS), and the minimal inhibitory concentrations of antibiotics were determined using the Vitek®2 system, according to the manufacture’s recommendations. Only positive results with one bacterial species and a colony count ≥105 CFU/mL was considered for descriptive analysis. Results Of the 24,019 urine samples tested, 71.44% (17,159/24,019) were identified as Escherichia coli. The major frequency of E. coli infection occurred among women (90.48%) and the main age range was over 60 years (38.57%), while 21-30 comprised 16.5% of cases. The antimicrobial resistance profile for E. coli isolates showed 39.9% (6852/17158) of resistance to ciprofloxacin (MIC, &amp;gt;0.5 mg/L), 34.7% (5,921/17,075) to trimethoprim/sulfamethoxazole (MIC, &amp;gt;0.5 mg/L), 37.5% (6,371/17,002) to Amoxicillin/clavulanate (MIC, &amp;gt;8 mg/L), 8.75% (1,501/17,592) to ceftriaxone (MIC, &amp;gt;1 mg/L), 4.88% (837/17,138) to cefepime (MIC, &amp;gt;4 mg/L), 3.64% (616/16,901) to piperacillin/tazobactam (MIC, &amp;gt;8 mg/L), 11.07% (1,900/17,156) of gentamicin (MIC, &amp;gt;2 mg/L), 0.43% (74/17,158) of amikacin (MIC, &amp;gt;8 mg/L) and 2.23% (377/16,909) of fosfomycin (MIC, &amp;gt;16 mg/L). High-level of susceptibility was detected to carbapenems with 99.94% (10/17159) to ertapenem (MIC, ≤0.5 mg/L) and 99.8% (4/17,159) to meropenem (MIC, ≤2 mg/L). The rate of Extended-spectrum beta-lactamase production was 8.1% (1391/17159). Conclusions This data could be used locally with other related samples, to properly interpret significant resistance patterns and choose the most appropriate antimicrobial for empirical treatment of patients with community-acquired urinary tract infections.

Risk Factors for Empiric Treatment Failure in US Female Outpatients with Uncomplicated Urinary Tract Infection: an Observational Study.

Treatment failure (TF) in uncomplicated urinary tract infection (uUTI) increases disease burden and risk of antimicrobial resistance. Identification of risk factors for TF could inform empiric treatment decisions and reduce suboptimal outcomes. To evaluate the incidence of TF to empirically prescribed oral antibiotics and identify risk factors for TF in females with uUTI in the United States (US). This retrospective cohort study used Optum's de-identified Electronic Health Record dataset (January 2017-September 2022). Eligible female patients aged ≥ 12years had ≥ 1 diagnosis of urinary tract infection (UTI) in an outpatient ambulatory/emergency department (ED) setting, ≥ 1 empiric oral antibiotic prescription, and no evidence of complicated UTI (cUTI). TF was defined as having a new/repeat oral antibiotic prescription, IV antibiotic administration or acute UTI diagnosis ≤ 28days following initial empiric oral antibiotic prescription​. Risk factors of TF were selected using LASSO and reported using adjusted risk ratios (aRR) and 95% CIs. Of 376,004 patients with uUTI, 62,873 (16.7%) experienced TF. Incidence of TF was highest in patients with history of antibiotic TF (33.9%) or fosfomycin prescription (30.1%). Significant risk factors of TF included ≥ 3 prior antibiotic prescriptions (aRR [95% CI]: 1.60 [1.56-1.64]); fosfomycin prescription (1.60 [1.38-1.86]); uUTI diagnosis in ED (1.49 [1.46-1.52]), Southern US residence (1.37 [1.35-1.40]), age ≥ 75years (1.35 [1.29-1.41]), recurrent UTI (1.12 [1.10-1.14]) and obesity (1.06 [1.04-1.08]). Incidence of TF to empirically prescribed oral antibiotics for uUTI is considerable. Prior infections requiring antibiotic prescription and location of care are key risk factors for TF in female outpatients with uUTI. Knowledge of these TF risk factors can inform shared-decision making and supplement existing guidance on uUTI treatment.

Vitamin D-Do Diet Recommendations for Health Remain Strong?

How will the scientific community and authoritative bodies define future nutritional requirements for vitamin D? At the International Symposium on Nutritional Aspects of Musculoskeletal Health, the authors debated the strength of current evidence for setting vitamin D intake recommendations from diet: the positive side of the strength of the evidence (PRO) suggests there is a physiological requirement for vitamin D and the opposing view (CON) that in light of negative results from large, recent trials, particularly those with fractures and bone health outcomes, we are left rudderless. Should we provide recommendations based on empiric treatment of vitamin D for most groups and conditions? It is becoming increasingly evident that vitamin D plays a role in many physiological functions and processes associated with long-term human health; however, to what extent are these benefits apparent beyond what is needed for adequate nutritional status, measured as serum 25-hydroxyvitamin D levels, for active calcium absorption? The meeting attendees voted for the PRO vs. CON position at the end of the session.

Association between inappropriate empirical antimicrobial therapy and mortality in gram-negative bloodstream infections in patients with febrile neutropenia and hematological malignancy

Background and objectiveInappropriate initial antimicrobial therapy has been associated with high mortality in patients with gram-negative bacilli bloodstream infections during febrile neutropenia following chemotherapy for hematological malignancies. The aim of this study is to determine this association in our hospital. MethodsA single center, retrospective, cohort study of bloodstream infection due to gram-negative bacilli and febrile neutropenia was conducted. Clinical characteristics, microbiological etiology, antimicrobial resistance profile, empirical and targeted antibiotic therapy, intensive care unit admission, persistent bacteremia and mortality were analyzed. ResultsOf the 171 episodes of bloodstream infection due to gram-negative bacilli, empirical antimicrobial therapy was inappropriate in 43 episodes (25.1 %). There was a significant difference in mortality at 7 and 30 days between patients who received appropriate versus inappropriate empirical treatment (4.6 % versus 13.9 %, p = 0.04; 15.6 % versus 32.5 %, p = 0.016). Inappropriate empirical treatment (RR, 2.97 [95 % CI, 1.01–8.74]), shock at the time of febrile neutropenia diagnosis (RR, 6.5 [95 % CI, 1.83–23.05]) carbapenem-resistant microorganism (RR, 3.73 [95 % CI, 1.14–12.24]) and persistent bacteremia (RR, 84.6 [95 % CI, 11.3–629.4]) were associated with an increased mortality at 7 and 30 days. In the multivariate analysis, shock (RR, 4.85 [95 % CI, 2.10–11.65]) and persistent bacteremia was independently associated with increased 30-day mortality, but inappropriate empirical antimicrobial therapy was not an independent prognostic determinant (RR, 1.66 [0.53–4.82]). ConclusionShock at the time of febrile neutropenia diagnosis contributes to mortality in patients with gram-negative bacilli bloodstream infection, in this scenario, appropriate empirical antimicrobial therapy should be encouraged.

Prospective Observational Study of Microbiology of Infected Diabetic Foot Ulcers in a Tertiary-Care Hospital.

Diabetic foot ulcers (DFUs) are a major cause of morbidity and mortality in people with diabetes mellitus. DFUs are the leading cause of hospitalisation for diabetic patients worldwide, especially in developing countries such as India. This study presents the microbiology profile of DFUs in a tertiary care hospital in the eastern part of India. We conducted a prospective observational study for 150 DFU patients over a period of two years. We took samples from the DFUs of these patients, cultured them, and tested their antimicrobial susceptibility. Most diabetic foot infections (DFIs) in our study patients were caused by Gram-negative bacteria, mainly Escherchia coli(E. coli) (19.3%), Pseudomonas (14%), and Staphylococcus aureus(S. aureus) (12%). The majority of Gram-positive bacteria were susceptible to linezolid, followed by vancomycin and amoxycillin, while the majority of Gram-negative bacteria were susceptible to imipenem and meropenem, followed by ampicillin with sulbactam, amikacin, gentamicin, and ciprofloxacin. Our study revealed that 88.3% of the isolates were monomicrobial. These findings demonstrated the importance of a local antibiogram, a microbiological exam, and antimicrobial susceptibility testing before starting antibiotic treatment for infections caused by DFUs. This protocol is different from the recommended guidelines for using empirical antibiotics.

Acute Hypoxic Respiratory Failure Secondary to Pulmonary Nocardiosis: An Unusual Presentation in the Emergency Department

Background: Nocardiosis, a rare but serious infection caused by Gram-positive, aerobic actinomycetes, primarily affects immunocompromised individuals. This report highlights an uncommon case of pulmonary nocardiosis in an immunocompetent patient leading to acute hypoxic respiratory failure. Case Presentation: A 45-year-old male gardener with no significant past medical history presented with acute dyspnea, pleuritic chest pain, fever, night sweats, and weight loss. Physical examination revealed respiratory distress and hypoxia. Imaging showed bilateral alveolar infiltrates and cavitary lesions. Sputum analysis identified Gram-positive branching filamentous bacteria, and Nocardia species were cultured. HIV test was negative. Management: The patient was admitted to the ICU and treated with high-flow oxygen therapy and empirical antibiotics (trimethoprim-sulfamethoxazole [TMP-SMX] and meropenem). Upon culture results, TMP-SMX was continued, and meropenem was discontinued. The patient showed significant improvement and was discharged on oral TMP-SMX for a six-month course. Discussion: This case underscores the importance of considering pulmonary nocardiosis in acute respiratory failure, even in immunocompetent patients. Early diagnosis and appropriate treatment are crucial for favorable outcomes. Conclusion: Pulmonary nocardiosis can cause severe respiratory symptoms in otherwise healthy individuals. Prompt recognition and treatment are essential to manage this potentially life-threatening condition effectively.

Isavuconazole off-label use as an empirical treatment of invasive fungal infections

Given its good tolerance and broad spectrum, isavuconazole is increasingly used off-label as an empirical therapy of invasive fungal infections. We retrospectively reviewed isavuconazole empirical treatment during a 12-month period in four hospitals. During isavuconazole treatment (n=27), none of the patients had a mycological evidence for fungal infection, but 19% (5/27) developed liver test abnormalities without leading to isavuconazole discontinuation. Isavuconazole could be considered as an off-label empirical therapy only if patients cannot receive caspofungin or liposomal amphotericin B.

Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients (BEATLE): a randomised, multicentre, open-label, superiority clinical trial

ObjectivesThe efficacy of extended infusions (EI) of β-lactam antibiotics for optimising outcomes in febrile neutropenia is unclear. We assessed whether the administration of β-lactams was more effective in EI than in intermittent infusion (II) for the treatment of febrile neutropenia. MethodsWe performed a randomised, open-label, superiority clinical trial of patients with febrile neutropenia at four Spanish university hospitals. Patients undergoing haematopoietic stem cell transplantation or with acute leukaemia receiving chemotherapy who required empirical antibiotic treatment for febrile neutropenia were randomly assigned (1:1) to receive EI of β-lactam or II after a first dose in bolus. The choice of antipseudomonal β-lactam was left to the discretion of the attending physician. The primary endpoint was treatment success at day 5, defined as defervescence without modifying the antibiotic treatment. Secondary endpoints included adverse events, attainment of the pharmacokinetic/pharmacodynamic target of 50, 75 and 100%ƒuT>MIC, and 30-day mortality. ResultsBetween November 19, 2019 and June 22, 2022, 295 patients we screened for eligibility, of whom 150 were randomly assigned to receive EI (n=77) or II (n=73) of the antipseudomonal β-lactam of choice. In the intention-to-treat analysis, treatment success at day 5 was achieved in 39/77 patients (50.6%) receiving EI versus 46/73 patients (63.0%) receiving II (risk difference -12.4%; 95% confidence interval, -29.4 to 4.7, p=0.17). The pharmacokinetic/pharmacodynamic targets of 75 and 100% ƒuT>MIC for empirical treatment were achieved more frequently in the EI group. No statistically-significant differences were found between groups in terms of adverse events or 30-day mortality. ConclusionsOur findings do not support the routine use of empirical EI of β-lactams in febrile neutropenia. Further studies should consider the clinical heterogeneity of febrile neutropenia and focus on patients with sepsis/septic shock and microbiologically documented infections, particularly those with infections caused by microorganisms less susceptible to β-lactams.

The Increasing Trend of Triazole-Resistant Candida from Vulvovaginal Candidiasis.

Candida vaginitis is widely prevalent worldwide and is one of the common gynecological disorders. The aim of this study is to analyze the sensitivity of recurrent vulvovaginal (RVVC) candidiasis to antifungal drugs and its relationship with vaginal microbiota. We Isolated and cultured Candida from RVVC patients, mass spectrometry and broth microdilution method were used to identify and determine MIC values of antifungal drugs. Clinical medical records and vaginal microbiota of RVVC patients were also collected. The main pathogens causing RVVC are predominantly Candida albicans (70.26%), but in recent years, there has been an increasing proportion of Candida glabrata(24.46%). However, only 15.70% of Candida albicans were sensitive to Voriconazole, 35.84% to Fluconazole and 25.60% to Itraconazole. No fluconazole-resistant Candida glabrata was found. Most Candida krusei strains were sensitive to voriconazole (81.80%). More important MIC values of triazoles were increased in Candida species, when exposed to clotrimazole. In addition, we found that the vaginal microecology of candida vaginitis and bacterial vaginitis was significantly different. Triazoles resistant Candida species have emerged, leading to the failure of empirical anti-infective therapy. At the same time, the vaginal microecology of candida vaginitis and bacterial vaginitis was significantly different. In addition, a new breakpoint for Candida from RVVC needs to be established.

Clinical characteristics and prognosis of bloodstream infections with carbapenem-resistant Gram-negative organisms in patients with hematological malignancies: a multicenter case-control study in China

ObjectiveTo investigate clinical characteristics of hematological malignancy (HM) patients with carbapenem-resistant gram-negative organism (CRO) bloodstream infections (BSI) in China, and to elucidate the prognostic risk factors of CRO BSI. MethodsWe conducted a multicenter case-control study of 201 HM patients with CRO BSI between 2018-2020. Antimicrobial susceptibility testing and whole genome sequencing were performed for CRO isolates. Independent risk factors for 28-day crude mortality of were analyzed using Cox proportional hazards regression models. The subgroups of major species were also evaluated. ResultsThe pathogens responsible for CRO BSI in HM patients dominated by ST11 CRKP, ST167 CREC and ST463 CRPA. Most isolates produced carbapenemases with KPC and NDM being the main. CRO isolates had resistance rates to conventional antimicrobials ranging from 55%-100% and poor susceptibility to novel antimicrobials related to carbapenemases and species. The 28-day crude mortality was 24.2%. Non-Hodgkin lymphoma, heart disease, blaKPC-2 positive, empirical antibiotic therapy with linezolid, Pitt bacteremia score >3.5 were risk factors for 28-day mortality and appropriate definitive antibiotic therapy, tigecycline-containing therapy and aminoglycoside-containing therapy were protective factors. blaKPC-2 positive in CRKP and ST463 in CRPA were associated with Pitt bacteremia score > 3.5. Solid tumor and other site infections before BSI were risk factors for ST463 CRPA BSI and Pulmonary infection before BSI was risk factor for KPC-KP BSI. ConclusionsThe antimicrobial resistance of CRO isolates for BSI in HM patients is critical. HM patients with CRO BSI should be treated with appropriate definitive antibiotic therapy based on early clarification of pathology and their antimicrobial susceptibility.