Early Initiation Of Effective Therapy Research Articles

The 7-year follow-up of the Hungarian BICAMS validation cohort implies that cognitive performance may improve in multiple sclerosis patients.

Cognitive impairment (CI) is a frequent symptom of multiple sclerosis (MS) and has a great impact on the patients' quality of life, so screening is essential. The brief international cognitive assessment for multiple sclerosis (BICAMS) was developed for this purpose. However, longitudinal data is lacking with the use of the battery. This study is to assess the performance of patients after 5 and 7 years of the original BICAMS validation study and to identify any influencing factors. BICAMS was used to measure cognitive function of 52 relapsing-remitting MS patients (RRMS) from the original validation study after 5 years (n = 43) and again, after 7 years (n = 42). Patients filled out the fatigue impact scale (FIS) and multiple sclerosis quality of life-54 (MSQoL-54) questionnaire, and we evaluated expanded disability status scale (EDSS). There was an improvement in the BVMT-R and the CVLT-II assessments at both the 5-year (p<0.001 and p=0.025) and the 7-year retest (p<0.001 and p=0.002). The prevalence of CI significantly decreased at the 5-year mark (p=0.021) but remained stable after that. There was no deterioration in MSQoL scores during the study. The basic cognitive performance is the most important influencing factor, but the duration of the disease, the EDSS score, and the escalation of the therapy also affect the cognitive scores. This is the longest longitudinal study utilizing the BICAMS battery, reinforcing its feasibility as a clinical screening tool. It seems that cognitive performance may improve in the long term and early initiation of effective therapy may influence this outcome.

2779. Early Administration of Ceftazidime-Avibactam for Carbapenem-Resistant Enterobacterales Is Associated with Improved Clinical Success

Abstract Background Carbapenem-resistant Enterobacterales (CRE) are a significant public health threat. Ceftazidime-avibactam (CZA) retains activity against most carbapenemase-producing CRE and demonstrates favorable health outcomes compared to historically best available therapy. While early initiation of effective therapy is critical in serious infections, the impact of time to CZA initiation on CRE infection-related outcomes has yet to be assessed. Aim: to evaluate clinical outcomes of patients with CRE infections receiving early vs. late CZA as the first active β-lactam. Methods Multicenter, retrospective cohort of hospitalized adult patients from 2019-2022 with culture-positive CRE and infectious symptoms receiving early vs. late CZA as the first active β-lactam. Early and late CZA were defined as CZA administration within or after 48 hours of index culture collection, respectively. Primary outcome was a composite of clinical success defined as i) the absence of all-cause mortality or microbiological recurrence requiring therapy within 30 days from the end of CZA therapy and ii) continued infectious symptoms during CZA therapy. Results In total, 174 patients were included (≤48 hours n=52, &amp;gt;48 hours n=122). Median (IQR) age was 61 (53, 73) years and 56.3% were male. ICU admission rates were similar between early vs. late CZA (73.1% vs. 72.1%; P=0.921). Most common infection sources were respiratory (59.8%) and skin and skin structure (9.2%). Klebsiella pneumoniae was the most common CRE isolated (66%). The overall median (IQR) of CZA MIC was 2 (1,4). and there was no difference in the receipt of package insert CZA doses in the first 48 hours of CZA therapy between the early vs. late groups, respectively (1.9% vs. 5.2%; P=0.311). In total, 40/52 (76.9%) early and 68/122 (55.7%) late CZA patients met the clinical endpoint of clinical success (P&amp;lt; 0.001). The early and late CZA groups demonstrated similar ICU length of stay (LOS) (26 [9, 46] vs. 22 [12, 40]; P=0.431, respectively). Table 1. Baseline and Clinical Characteristics Conclusion In hospitalized adult patients with CRE infections, CZA administration within 48 hours of culture collection was associated with a higher rate of clinical success compared to CZA administered after 48 hours. Further studies in a larger patient cohort are warranted to verify these results. Disclosures Wesley D. Kufel, Pharm.D., BCPS, BCIDP, AAHIVP, Merck: Grant/Research Support Bryan White, PharmD, BCPS, BCIDP, Gilead Sciences: Advisor/Consultant Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Merck, Paratek, Shionogi, Entasis, La Jolla, T2 Biosystems: Advisor/Consultant

An All-in-One Highly Multiplexed Diagnostic Assay for Rapid, Sensitive, and Comprehensive Detection of Intraocular Pathogens

Intraocular infections are sight-threatening conditions that can lead to vision loss. Rapid identification of the etiologies plays a key role in early initiation of effective therapy to save vision. However, current diagnostic modalities are time consuming and lack sensitivity and inclusiveness. We present here a newly developed comprehensive ocular panel designed to improve diagnostic yields and provide a tool for rapid and sensitive pathogen detection. Experimental laboratory investigation. A panel containing 46 pathogens and 2 resistance/virulence markers that are commonly detected in intraocular infections was developed. Genomic targets were scrutinized for stretches predicted to be specific for a particular species while being conserved across different strains. A set of primers for sample enrichment, and two 50mer NanoString compatible probes were then designed for each target. Probe-target hybrids were detected and quantified using the NanoString nCounter SPRINT Profiler. Diagnostic feasibility was assessed in a pilot clinical study testing samples from infectious retinitis (n=15) and endophthalmitis (n=12) patients, for which the etiologies were confirmed by polymerase chain reaction (PCR) or culture. Analytical studies demonstrated highly sensitive detection of a broad spectrum of pathogens, including bacteria, viruses, and parasites, with limits of detection being as low as 2.5 femtograms per reaction. We also found excellent target specificity, with minimal cross-reactivity detected. The custom-designed NanoString ocular panel correctly identified the causative agent from all clinical specimens positive for a variety of pathogens. This highly multiplexed panel for pathogen detection offers a sensitive, comprehensive, and uniform assay run directly on ocular fluids that could significantly improve diagnostics of sight-threatening intraocular infections.

Evaluation of the MolecuTech® REBA MTB-XMDR kit for detection of pre-extensively drug-resistant TB.

BACKGROUND: Rapid diagnosis of drug-resistant TB is critical for early initiation of effective therapy. YD Diagnostics in South Korea recently developed the MolecuTech® REBA MTB-XMDR test to rapidly detect multidrug-resistant TB (MDR-TB), pre-extensively drug-resistant TB (pre-XDR-TB) and resistance to second-line injectable drugs (SLIDs) simultaneously using a fully automated test platform. This study aimed to evaluate the MolecuTech® test for the detection of MDR- and pre-XDR-TB, as well as SLID resistance.METHODS: A total of 151 clinical Mycobacterium tuberculosis isolates from South Korea were tested using the MolecuTech test, and the results were analysed by comparing these with phenotypic drug susceptibility testing (pDST) and sequencing.RESULTS: Compared to pDST, the MolecuTech test showed a sensitivity and specificity of respectively 97.7% and 100.0% for rifampicin (RIF), 82.4% and 100.0% for isoniazid (INH), 97.5% and 97.2% for fluoroquinolones (FQs), and 94.0% and 98.8% for SLIDs. Concordances with the sequencing results of each resistance determinant were 99.3% for RIF, 96.7% for INH, 98.7% for FQs and 99.3% for SLIDs.CONCLUSION: The MolecuTech test is an efficient and reliable rapid molecular diagnostic tool for the simultaneous screening of MDR- and pre-XDR-TB.

Feasibility of Direct Sputum Molecular Testing for Drug Resistance as Part of Tuberculosis Clinical Trials Eligibility Screening.

A rapid diagnosis of drug-resistant tuberculosis (TB) is critical for early initiation of effective therapy. Molecular testing with line probe assays (MTBDRplus and MTBDRsl) on culture isolates has been available for some time and significantly reduces the time to diagnosis of drug resistance. However, routine use of this test directly on sputum is less common. As part of enrollment screening procedures for tuberculosis clinical trials conducted in Hanoi, Vietnam, we evaluated the feasibility and performance of line probe assay (LPA) testing directly on sputum samples from 315 participants with no prior history of TB treatment. Test performance characteristics for the detection of rifampin (RIF) and isoniazid (INH) drug resistance as compared to culture-based drug susceptibility testing (DST) reference standard were calculated. LPA demonstrated high sensitivity and specificity for the diagnosis of drug resistance. Scaling up molecular testing on sputum as part of time-sensitive clinical trial screening procedures in high TB burden settings is feasible and will reduce both time to initiation of appropriate therapy and the risk of late exclusions due to microbiologic ineligibility.

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges.

Acinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity. The virulence properties demonstrated by Acinetobacter spp. primarily stem from evasion of rapid clearance by the innate immune system, effectively enabling high bacterial density that triggers lipopolysaccharide (LPS)-Toll-like receptor 4 (TLR4)-mediated sepsis. Capsular polysaccharide is a critical virulence factor that enables immune evasion, while LPS triggers septic shock. However, the primary driver of clinical outcome is antibiotic resistance. Administration of initially effective therapy is key to improving survival, reducing 30-day mortality threefold. Regrettably, due to the high frequency of this organism having an extreme drug resistance (XDR) phenotype, early initiation of effective therapy is a major clinical challenge. Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp. are desperately needed.

Neuromyelitis optica: eine mit Aquaporin-4-Antikörpern assoziierte nosologische Entität

Neuromyelitis optica (NMO; Devic's Syndrome) is an idiopathic, often relapsing, severe inflammatory disorder preferentially affecting optic nerves and spinal cord. The distinction of NMO from multiple sclerosis (MS) as a separate disease entity has been controversally discussed for a long time. Though both diseases show demyelinisation, they differ in typical clinical, imaging and immunopathological findings. The recent identification of serum aquaporin (AQP)-4 antibody clearly separates NMO from MS. In addition, the identification of AQP-4 antibodies supports peripheral humoral autoimmune pathogenesis in NMO and permits early initiation of effective therapy for prevention of attack-related disability.

Ascites due to ovarian hyperstimulation syndrome: A case report and review of literature

Objectives: To report a case of ovarian hyperstimulation syndrome (OHSS), to discuss the differential diagnosis and to give a review of current evidences in diagnosis and management of ovarian hyperstimulation syndrome. Design: A detailed description of a case of OHSS followed by a thorough review of case reports, randomized controlled trials and review articles to assess the current modalities of diagnosis and management of ovarian hyperstimulation syndrome. Results: A 29-year-old female was admitted with dyspnoea and features suggestive of polyserositis. Patient was evaluated for causes of polyserositis. She gave history of ovulation induction and invitro fertilization one week prior to the onset of dyspnoea. With the positive history of invitro fertilization and negative markers for other causes of capillary leak syndrome the patient was diagnosed to have OHSS. She was treated and improved within a week. Conclusion: Diagnosis and management of ovarian hyperstimulation syndrome requires high index of suspicion, prompt investigation and early initiation of effective therapy. With correct diagnosis and early treatment, most patients recover.