Antimicrobial Therapy In Patients Research Articles

Clinical Predictors of Bacteremia Outcome After Initial Empirical Antimicrobial Therapy in Patients with Hematological Malignancies: A Retrospective Analysis.

We performed a retrospective analysis to investigate the clinical predictors of bacteremia outcome involving Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) after initial empirical antimicrobial therapy among hematological malignancy cases. This retrospective study was conducted between April 2018 and April 2023. All bloodstream infections (BSIs) caused by E. coli and K. pneumoniae in hospitalized hematological malignancy (HM) patients were identified. Data on patient demographics, clinical characteristics, empirical antimicrobial treatment, outcomes and the antimicrobial susceptibility were collected from medical records. Multivariate analyses were utilized to assess the risk factors for all-cause mortality within 28 days and carbapenem resistance. Optimal cutoffs for continuous predictive variables were evaluated by receiver operating characteristic (ROC) curve analysis. Among 61 individuals diagnosed with bacteremia, 39 cases were caused by E. coli bacteremia, while the remaining 22 were identified as K. pneumoniae bacteremia. Out of these, there were 10 cases of carbapenem-resistant Enterobacteriaceae (CRE) and 12 cases resulted in all-cause mortality within 28 days. Analysis indicated that Pitt score was an independent risk factor for mortality and a cut-off of 2.5 was a reliable predictor with 83.3% sensitivity and 85.7% specificity, respectively. Impaired mental status and elevated body temperature exceeding 38.6°C as well as a procalcitonin (PCT) level over 8.24 ng/mL on the third day (d3) after antimicrobial treatment were identified as independent risk factors for predicting carbapenem resistance. We found that Pitt score with a cut-off of 2.5 was a reliable predictor for mortality within 28 days in HM bacteremia cases. Impaired mental status and elevated temperature exceeding 38.6°C as well as a procalcitonin (PCT) level over 8.24 ng/mL on d3 after antimicrobial treatment were identified as predictive risk factors to carbapenem resistance.

Molecular antimicrobial susceptibility testing in sepsis.

Rapidly detecting and identifying pathogens is crucial for appropriate antimicrobial therapy in patients with sepsis. Conventional diagnosticmethods have been a great asset to medicine, though they are timeconsuming and labor intensive. This workwill enable healthcare professionals to understand the bacterial community better and enhance their diagnostic capacity by using novel molecular methods that make obtaining quicker, more precise results possible. The authors discuss and critically assess the merits and drawbacks of molecular testing and the added value of these tests, including the shift turnaround time, the implication for clinicians' decisions, gaps in knowledge, future research directions and novel insights or innovations. The field of antimicrobial molecular testing has seen several novel insights and innovations to improve the diagnosis and management of infectious diseases.

152. Impact of BioFire FilmArray Blood Culture Identification Panel 2 (BCID2) and Antimicrobial Stewardship Interventions on Time to Optimal Antimicrobial Therapy in Patients with Positive Blood Cultures

Abstract Background Delayed treatment of bloodstream infections is associated with increased morbidity and mortality. Conventional methods for organism identification and susceptibility data from blood cultures can take about 2-5 days. Technological advancements in gene-based polymerase chain reaction tests amplify DNA targets from positive blood cultures and can shorten the identification time of certain organisms and resistance genes, aiding in earlier optimization of antimicrobial therapy. Methods This pre/post quasi-experimental, single center study was conducted 6 months prior to and 6 months after implementation of the BCID2 panel. Patients with at least 1 positive blood culture with an organism on the BCID2 panel were included in the study. One hundred twenty-five patients were included in the pre-BCID2 arm and 114 patients in the BCID2 arm. In the BCID2 panel group, real-time alerts were received by the antimicrobial stewardship team (AST) and recommendations were made to providers. The primary outcomes were time to pathogen identification, effective therapy, and optimal therapy. Results Demographic characteristics were similar in both groups. A higher percentage of patients with multiple risk factors for bacteremia were identified in the pre-BCID2 arm (36.8% vs 20.2%). The mean time to pathogen identification (60 hrs vs 30 hrs; P < 0.0001) and time to optimal therapy (61.4 hrs vs 44.6 hrs; P=0.001) were shorter in the BCID2 arm compared to the pre-BCID2 arm. Patients in the BCID2 arm had an overall trend toward decreased mean time to effective therapy compared with the pre-BCID2 arm (17.5 hours vs. 14 hours; P=0.18). Subgroup analysis of blood cultures with vancomycin-resistant Enterococcus spp., ESBL-producing organisms, and Candida glabrata met statistical significance in all three primary outcomes. The BCID2 arm had a 21.9 hr. reduction in time to pathogen ID (49.6 v. 27.7; P=0.02), 38.9 hr. reduction in time to effective therapy (66.9 vs. 28; P=0.013), and a 54.5 hr. reduction in time to optimal therapy (89.3 vs 34.8; P=0.046). Overall, 99% of recommendations from the AST were accepted by providers. Primary Outcome Results Time to pathogen ID, Time to Effective Therapy, Time to Optimal Therapy Secondary Outcomes 1 Total length of stay, ICU length of stay, Microbiologic Cure Secondary Outcomes 2 30 day Mortality and Recurrent bacteremia Conclusion Implementation of the BCID2 panel significantly decreased time to pathogen identification and optimal therapy in patients with bacteremia. Disclosures All Authors: No reported disclosures

Development and validation of artificial intelligence models to predict urinary tract infections and secondary bloodstream infections in adult patients

BackgroundTraditional culture methods are time-consuming, making it difficult to utilize the results in the early stage of urinary tract infection (UTI) management, and automated urinalyses alone show insufficient performance for diagnosing UTIs. Several models have been proposed to predict urine culture positivity based on urinalysis. However, most of them have not been externally validated or consisted solely of urinalysis data obtained using one specific commercial analyzer. MethodsA total of 259,187 patients were enrolled to develop artificial intelligence (AI) models. AI models were developed and validated for the diagnosis of UTI and urinary tract related-bloodstream infection (UT-BSI). The predictive performance of conventional urinalysis and AI algorithms were assessed by the areas under the receiver operating characteristic curve (AUROC). We also visualized feature importance rankings as Shapley additive explanation bar plots. ResultsIn the two cohorts, the positive rates of urine culture tests were 25.2% and 30.4%, and the proportions of cases classified as UT-BSI were 1.8% and 1.6%. As a result of predicting UTI from the automated urinalysis, the AUROC were 0.745 (0.743–0.746) and 0.740 (0.737–0.743), and most AI algorithms presented excellent discriminant performance (AUROC > 0.9). In the external validation dataset, the XGBoost model achieved the best values in predicting both UTI (AUROC 0.967 [0.966–0.968]) and UT-BSI (AUROC 0.955 [0.951–0.959]). A reduced model using ten parameters was also derived. ConclusionsWe found that AI models can improve the early prediction of urine culture positivity and UT-BSI by combining automated urinalysis with other clinical information. Clinical utilization of the model can reduce the risk of delayed antimicrobial therapy in patients with nonspecific symptoms of UTI and classify patients with UT-BSI who require further treatment and close monitoring.

Switch to oral antibiotics in Gram-negative bacteraemia: a randomized, open-label, clinical trial

ObjectivesTo evaluate the safety and efficacy of switching from intravenous (IV) to oral antimicrobial therapy in patients with Enterobacterales bacteraemia, after completion of 3–5 days of microbiologically active IV therapy. MethodsA multicentre, open-label, randomized trial of adults with monomicrobial Enterobacterales bacteraemia caused by a strain susceptible to ≥1 oral beta-lactam, quinolone, or trimethoprim/sulfamethoxazole. Inclusion criteria included completion of 3–5 days of microbiologically active IV therapy, being afebrile and haemodynamically stable for ≥48 hours, and absence of an uncontrolled source of infection. Pregnancy, endocarditis, and neurological infections were exclusion criteria. Randomization, stratified by urinary source of bacteraemia, was to continue IV (IV Group) or to switch to oral therapy (Oral Group). Agents and duration of therapy were determined by the treating physicians. The primary endpoint was treatment failure, defined as death, need for additional antimicrobial therapy, microbiological relapse, or infection-related re-admission within 90 days. Non-inferiority threshold was set at 10% in the 95% CI for the difference in the proportion with treatment failure between the Oral and IV Groups in the modified intention-to-treat population. The protocol was registered at ClinicalTrials.gov (NCT04146922). ResultsIn the modified intention-to-treat population, treatment failure occurred in 21 of 82 (25.6%) in the IV Group, and 18 of 83 (21.7%) in the Oral Group (risk difference –3.7%, 95% CI –16.6% to 9.2%). The proportions of subjects with any adverse events (AE), serious AE, or AE leading to treatment discontinuation were comparable. DiscussionIn patients with Enterobacterales bacteraemia, oral switch, after initial IV antimicrobial therapy, clinical stability, and source control, is non-inferior to continuing IV therapy.

Determinants of Inadequate Empiric Antimicrobial Therapy in ICU Sepsis Patients in Al-Madinah Al-Munawwarah, Saudi Arabia: A Comparison of Artificial Neural Network and Regression Analysis.

In the management of sepsis, providing adequate empiric antimicrobial therapy is one of the most important pillars of sepsis management. Therefore, it is important to evaluate the adequacy of empiric antimicrobial therapy (EAMT) in sepsis patients admitted to intensive care units (ICU) and to identify the determinants of inadequate EAMT. The aim of this study was to evaluate the adequacy of empiric antimicrobial therapy in patients admitted to the ICU with sepsis or septic shock, and the determinants of inadequate EAMT. The data of patients admitted to the ICU units due to sepsis or septic shock in two tertiary healthcare facilities in Al-Madinah Al-Munawwarah were retrospectively reviewed. The current study used logistic regression analysis and artificial neural network (ANN) analysis to identify determinants of inadequate empiric antimicrobial therapy, and evaluated the performance of these two approaches in predicting the inadequacy of EAMT. The findings of this study showed that fifty-three per cent of patients received inadequate EAMT. Determinants for inadequate EAMT were APACHE II score, multidrug-resistance organism (MDRO) infections, surgical history (lower limb amputation), and comorbidity (coronary artery disease). ANN performed as well as or better than logistic regression in predicating inadequate EAMT, as the receiver operating characteristic area under the curve (ROC-AUC) of the ANN model was higher when compared with the logistic regression model (LRM): 0.895 vs. 0.854. In addition, the ANN model performed better than LRM in predicting inadequate EAMT in terms of classification accuracy. In addition, ANN analysis revealed that the most important determinants of EAMT adequacy were the APACHE II score and MDRO. In conclusion, more than half of the patients received inadequate EAMT. Determinants of inadequate EAMT were APACHE II score, MDRO infections, comorbidity, and surgical history. This provides valuable inputs to improve the prescription of empiric antimicrobials in Saudi Arabia going forward. In addition, our study demonstrated the potential utility of applying artificial neural network analysis in the prediction of outcomes in healthcare research.

Efficacy of antimicrobial therapy in patients with uncomplicated acute colonic diverticulitis: an updated systematic review and meta-analysis.

The need for antimicrobial therapy for uncomplicated acute diverticulitis of the colon remains controversial. We conducted a systematic review of the efficacy of antimicrobial agents against this disease, including new randomized controlled trials (RCTs) reported in recent years, and evaluated their efficacy using a meta-analytic approach. RCTs were searched using PubMed, EMBASE, Google Scholar, Cochrane Library, Ichushi-Web, and eight registries. Keywords were 'colonic diverticulitis', 'diverticulitis', 'antimicrobial agents', ''antibiotics, 'complication', 'abscess', 'gastrointestinal perforation', 'gastrointestinal obstruction', 'diverticular hemorrhage', and 'fistula'. Studies with antimicrobial treatment in the intervention group and placebo or no treatment in the control group were selected by multiple reviewers using uniform inclusion criteria, and data were extracted. Prevention of any complication was assessed as the primary outcome, and efficacy was expressed as risk ratio (RR) and risk difference (RD). A meta-analysis was performed using 5 RCTs of the 21 studies that were eligible for scrutiny in the initial search and which qualified for final inclusion. Three of these studies were not included in the previous meta-analysis. Subjects included 1039 in the intervention group and 1040 in the control group. Pooled RR = 0.86 (95% confidence interval, 0.58-1.28) and pooled RD = -0.01 (-0.03 to 0.01) for the effect of antimicrobial agents in reducing any complications. Recurrences, readmissions, and surgical interventions did not significantly show the efficacies of using antimicrobial agents. A meta-analysis of recently reported RCTs did not provide evidence that antimicrobial therapy improves clinical outcomes in uncomplicated acute diverticulitis of the colon.

Optimization of Empirical Antimicrobial Therapy in Enterobacterales Bloodstream Infection Using the Extended-Spectrum Beta-Lactamase Prediction Score.

Clinical tools for the prediction of antimicrobial resistance have been derived and validated without examination of their implementation in clinical practice. This study examined the impact of utilization of the extended-spectrum beta-lactamase (ESBL) prediction score on the time to initiation of appropriate antimicrobial therapy for bloodstream infection (BSI). The quasi-experimental cohort study included hospitalized adults with BSI due to ceftriaxone-resistant (CRO-R) Enterobacterales at three community hospitals in Columbia, South Carolina, USA before (January 2010 to December 2013) and after (January 2014 to December 2019) implementation of an antimicrobial stewardship intervention. In total, 45 and 101 patients with BSI due to CRO-R Enterobacterales were included before and after the intervention, respectively. Overall, the median age was 66 years, 85 (58%) were men, and 86 (59%) had a urinary source of infection. The mean time to appropriate antimicrobial therapy was 78 h before and 46 h after implementation of the antimicrobial stewardship intervention (p = 0.04). Application of the ESBL prediction score as part of an antimicrobial stewardship intervention was associated with a significant reduction in time to appropriate antimicrobial therapy in patients with BSI due to CRO-R Enterobacterales. Utilization of advanced rapid diagnostics may be necessary for a further reduction in time to appropriate antimicrobial therapy in this population.

Clinical metagenomic sequencing of plasma microbial cell-free DNA for febrile neutropenia in patients with acute leukaemia

ObjectivesTo evaluate the diagnostic performance and clinical impact of metagenomic next-generation sequencing (mNGS) of plasma microbial cell-free DNA (mcfDNA) in febrile neutropenia (FN). MethodsIn a 1-year, multicentre, prospective study, we enrolled 442 adult patients with acute leukaemia with FN and investigated the usefulness of mNGS of plasma mcfDNA for identification of infectious pathogens. The results of mNGS were available to clinicians in real time. The performance of mNGS testing was evaluated in comparison with blood culture (BC) and a composite standard that incorporated standard microbiological testing and clinical adjudication. ResultsIn comparison with BC, the positive and negative agreements of mNGS were 81.91% (77 of 94) and 60.92% (212 of 348), respectively. By clinical adjudication, mNGS results were categorized by infectious diseases specialists as definite (n = 76), probable (n = 116), possible (n = 26), unlikely (n = 7), and false negative (n = 5). In 225 mNGS-positive cases, 81 patients (36%) underwent antimicrobials adjustment, resulting in positive impact on 79 patients and negative impact on two patients (antibiotics overuse). Further analysis indicated that mNGS was less affected by prior antibiotics exposure than BC. DiscussionOur results indicate that mNGS of plasma mcfDNA increased the detection of clinically significant pathogens and enabled early optimization of antimicrobial therapy in patients with acute leukaemia with FN.

Management of Patients with Suspected or Confirmed Antibiotic Allergy: Executive Summary of Guidelines from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Allergy and Clinical Immunology (SEAIC), the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Intensive Medicine and Coronary Care Units (SEMICYUC).

Suspected or confirmed antibiotic allergy is a frequent clinical circumstance that influences antimicrobial prescription and often leads to the avoidable use of less efficacious and/or more toxic or costly drugs than first-line antimicrobials. Optimizing antimicrobial therapy in patients with antibiotic allergy labels has become one of the priorities of antimicrobial stewardship programs in several countries. These guidelines aim to make recommendations for the systematic approach to patients with suspected or confirmed antibiotic allergy based on current evidence. An expert panel (11 members of various scientific societies) formulated questions about the management of patients with suspected or confirmed antibiotic allergy. A systematic literature review was performed by a medical librarian. The questions were distributed among panel members who selected the most relevant references, summarized the evidence, and formulated graded recommendations when possible. The answers to all the questions were finally reviewed by all panel members. A systematic approach to patients with suspected or confirmed antibiotic allergy was recommended to improve antibiotic selection and, consequently, clinical outcomes. A clinically oriented, 3-category risk-stratification strategy was recommended for patients with suspected antibiotic allergy. Complementary assessments should consider both clinical risk category and preferred antibiotic agent. Empirical therapy recommendations for the most relevant clinical syndromes in patients with suspected or confirmed ß-lactam allergy were formulated, as were recommendations on the implementation and monitoring of the impact of the guidelines. Antimicrobial stewardship programs and allergists should design and implement activities that facilitate the most appropriate use of antibiotics in these patients.

A multifaceted strategy to optimize pharmacokinetics of antimicrobial therapy in patients with hospital-acquired infections-a monocentre quality improvement project.

We assessed the efficacy of a quality improvement programme to optimize the delivery of antimicrobial therapy in critically ill patients with hospital-acquired infections (HAI). Before-after trial in a university hospital in France. Consecutive adults receiving systemic antimicrobial therapy for HAI were included. Patients received standard care during the pre-intervention period (June 2017 to November 2017). The quality improvement programme was implemented in December 2017. During the intervention period (January 2018 to June 2019), clinicians were trained to dose adjustment based on therapeutic drug monitoring and continuous infusion of β-lactam antibiotics. The primary endpoint was the mortality rate at day 90. A total of 198 patients were included (58 pre-intervention, 140 intervention). The compliance with the therapeutic drug monitoring-dose adaptation increased from 20.3% to 59.3% after the intervention (P < 0.0001). The 90-day mortality rate was 27.6% in the pre-intervention period and 17.3% in the intervention group (adjusted relative risk 0.53, 95%CI 0.27-1.07, P = 0.08). Treatment failures were observed in 22 (37.9%) patients before and 36 (25.7%) patients after the intervention (P = 0.07). Recommendations for therapeutic drug monitoring-dose adaptation and continuous infusion of β-lactam antibiotics were not associated with a reduction in the 90-day mortality rate in patients with HAI.

Molecular genetic surveillance based on the identification of borrelia in ixodid ticks

Aim. To improve emergency diagnostic measures and preventive antimicrobial therapy in patients with ixodid tick bites using molecular genetic techniques for identification of Вorrelia spp.Materials and Methods. Borrelia strains were isolated by inoculation of tick suspension on the BSK-H medium. Molecular genetic screening of Вorrelia spp. was performed by real-time polymerase chain reaction (PCR) and sequencing. In total, we examined 4,276 patients including 272 bitten by Ixodes persulcatus and 3,108 bitten by Dermacentor reticulatus. In addition, we investigated blood of 896 patients for molecular signatures of Borrelia spp.Results. Borrelia spp. was detected by PCR in 30.1% of Ixodes persulcatus and 3.2% of Dermacentor reticulatus suspensions. However, detection of Borrelia spp. in blood was rare, reaching only 1.1% in those bitten by Ixodes persulcatus and two cases of Dermacentor reticulatus bites. Genotyping of Borrelia spp. in 8 tick suspensions showed the presence of Borrelia garinii in 1 sample, Borrelia afzelii in 5 samples, Borrelia bavariensis in 1 sample, and Borrelia miyamotoi in 1 sample.Conclusion. Molecular genetic screening showed the significant proportion of Ixodid ticks bearing Borrelia spp., indicating the need in specific antimicrobial therapy.

Specific features of antimicrobial therapy in patients with severe respiratory failure receiving veno-venous extracorporeal membrane oxygenation (ECMO)

In modern medicine, the extracorporeal membrane oxygenation (ECMO) is becoming increasingly common in the treatment of severe respiratory failure. The development of infectious complications in patients receiving ECMO often leads to an increase in the duration of the procedure and significantly increases the risk of death. Dosing of antimicrobials during ECMO remains uncertain and requires further research. Diagnosis of infectious complications during ECMO is a difficult and requires the development of diagnostic protocols and the use of routine microbiological studies. The use of antimicrobials during ECMO could be complicated due to decrease in effective plasma concentration. The adsorption of antibacterial drugs in the ECMO circuit and oxygenator, the use of infusion therapy, the development of hypoalbuminemia, as well as the high incidence of acute renal and hepatic dysfunction in critically ill patients lead to an inevitable change in the volume of distribution and clearance of antibacterial drugs. These conditions require an individual approach to the choice of antimicrobials and optimization of dosing regimens in critically ill patients receiving ECMO.

Identifying the potential impact of a multidisciplinary outpatient antimicrobial therapy program in an area of high social vulnerability.

Outpatient parenteral antimicrobial therapy (OPAT) and complex outpatient antimicrobial therapy (COpAT) are common practice in the management of infectious diseases (IDs). However, providing OPAT/COpAT can pose significant challenges pre- and post-discharge, particularly in vulnerable patient populations. The objective of this study is to assess outpatient complications related to OPAT/COpAT in patients discharged with a home health services referral and to identify pre- and post-discharge intervention opportunities and the associated cost-savings that could be achieved with a multidisciplinary ID team-run OPAT/COpAT program. This is a retrospective cohort study of patients who were discharged with OPAT/COpAT through home health services over a 3-month study period. Data on potential pre-discharge interventions and post-discharge complications were recorded. Medication-related issues were the most common pre-discharge complications, accounting for more than 50% of identified intervention opportunities. More than half of the included patients experienced at least one documented outpatient complication post-discharge with peripherally inserted central catheter-line-related complication (20.7%) being the most common issue. Using previously published cost-estimates, the implementation of a designated pre- and post-discharge OPAT/COpAT program could have saved over $100,000 over the 3-month study period. A multidisciplinary OPAT/COpAT program located in a high social vulnerable area can help reduce complications related to a patient's antimicrobial therapy. Medication-related issues represent a major area for potential intervention. Our findings suggest that a multidisciplinary ID team will have ample opportunities to improve the transition of care, at both pre- and post-discharge, for patients requiring antimicrobial therapy.

Therapeutic Drug Monitoring of Antibiotics Is Needed in the Treatment of Sepsis

The article presents the results of a prospective on e-c enter observational clinical study. The level of therapeutic drug monitoring antibiotics was studied in patients with sepsis. The objective: to assess the impact of pharmacokinetics and pharmacodynamics parameters of the main classes of antibacterial drugs using specific indices to improve the effectiveness of ongoing antimicrobial therapy in patients with sepsis asscoaited with the infectious process with pa n-r esistant nosocomial microflora. Subjects and Methods. A total of 8 patients with sepsis meetiing the criteria of Sepsi s-3 were included. Carbapenems, oxazolidinones, and aminoglycosides were used in the treatment. Concentrations of drugs in blood plasma were studied by hig h-p erformance liquid chromatography with mass spectrometry. Analysis of the effectiveness of treatment was performed on the third day of therapy. Results. The T &gt; MIC index reached 40% of the time interval between the two administrations for MIC for Pseudomonas aeruginosa in only two cases for group II carbapenems. In both cases, high peak concentrations of the drug (19.5 and 35.4 m g/L , respectively) were observed, a low static volume of antibiotic distribution (0.06 l/k g and 0,09 l/k g) and reduced total clearance of the drug (7.18 and 4.11 m l/h r) were noted. The peak concentration of amikacin was low (3.35 m g/l ), while the time to achieve it and the level of static volume distribution (356.5 liters) increased. The peak concentration of linezolid was reduced in all observations and amounted to 4.04 and 3.35 m g/l . The time of its achievement was increased (3.27 and 6.6 hours), the ratio of AU C / M IC was low and made 76.8 and 59.2. The resolution of organ dysfunction and reduction of manifestations of infectious intoxication were noted only in three patients on the third day of observation. Conclusion. Static pharmacokineti c/p harmacodynamic criteria may serve as a guideline for antimicrobial therapy. Limitations in changing the tactics of antimicrobial therapy based on the use instruction nevertheless allow optimizing treatment by controlling the volume of distribution of the drug, presence of renal or hepatic insufficiency that, however, does not guarantee treatment success. The volume of therapeutic drug monitoring of antibiotics sufficient for compilation of static pharmakinetic models, does not meet the requirements of modern intensive care.

1998. Association of Infection Recurrence with Oral Step-Down vs Continued Intravenous Antimicrobial Therapy in Patients with Complicated Intra-Abdominal Infection

Abstract Background Complicated intra-abdominal infections (cIAIs) require a combined strategy of source control and antimicrobial therapy. Guidelines recommend initial intravenous (IV) therapy with oral step-down therapy following source control. Due to limited data supporting this strategy, we aimed to evaluate the safety and efficacy of oral step-down antimicrobial therapy in cIAIs after initial IV antimicrobial therapy. Methods This retrospective cohort study included hospitalized patients ≥ 18 years of age diagnosed with a cIAI who received &amp;gt; 7 days of IV therapy during index hospitalization at quaternary hospital from March 2017 to October 2021. Patients were excluded for primary or peritoneal dialysis-related peritonitis, necrotizing pancreatitis, fistulizing inflammatory bowel disease, or upper gastrointestinal tract infection; repeat hospitalization during study period; or transfer from another facility after &amp;gt; 24 hours of care. Patients were assigned into two treatment groups: IV-only or oral step-down therapy. The primary outcome was infection recurrence defined as re-initiation of antimicrobials after a treatment-free period of ≥ 3 days. Secondary outcomes included treatment escalation, repeat source control procedure, treatment-related complications, and all-cause mortality. Results The cohort consisted of 248 patients (199 IV-only and 49 oral step-down). Baseline, infection, and treatment characteristics were similar between groups, except for gender, length of stay, and overall treatment duration (Table 1). Patients receiving IV-only therapy had a shorter median antimicrobial duration than the oral step-down group (13 vs. 23 days; P &amp;lt; 0.001). Infection recurrence occurred in 26 (13.1%) and six (12.2%) patients in the IV-only and oral step-down groups, respectively (P = 0.88). Treatment escalation, repeat source control, and 28-day mortality were similar between groups (Table 1). Oral step-down therapy resulted in more adverse drug events (10.2% vs. 3.0%; P = 0.04). Table 1: Baseline and infection-related characteristics for IV only and oral step-down therapy groups aDefined as: solid organ transplant, hematopoietic stem cell transplant within the last 1 year, long-term high-dose steroids (prednisone &amp;gt;10 mg, or equivalent, for ≥2 weeks), concomitant immunosuppressive medication, or HIV (CD4 count &amp;lt;200 cells/µL) bOther antimicrobials included cephalexin, cefpodoxime, doxycycline, fluconazole, and sulfamethoxazole-trimethoprim cAdverse drug events included dermatologic reactions, gastrointestinal upset, nausea/vomiting, diarrhea, fatigue, thrombocytopenia, and acute kidney injury Conclusion Transition to oral step-down after initial IV antimicrobial therapy may be an alternative strategy for the management of cIAIs; however, larger non-inferiority studies are warranted to confirm the safety and efficacy of this approach. Disclosures James Sanders, PhD, PharmD, Merck &amp; Co., Inc.: Grant/Research Support|Shionogi Inc.: Grant/Research Support Sara Hennessy, M.D., Boston Scientific: Advisor/Consultant Sara Hennessy, M.D., Boston Scientific: Advisor/Consultant.

399: A CASE OF SEVERE BABESIOSIS REQUIRING EXCHANGE TRANSFUSION

Introduction: Babesiosis is an infection caused by a protozoan that infects human erythrocytes. In the United States, Babesia microti is the most commonly isolated strain transmitted by tick vector (Ixodes scapularis). The severity of infection usually depends on host immune status and Babesia species, ranging from asymptomatic to life-threatening. We describe a case of severe babesiosis requiring exchange transfusion in an elderly but otherwise healthy individual. Description: A previously healthy 90-year-old man presented to the emergency department with a 1-week history of dyspnea and dark-colored urine. Patient reported a tick bite two months prior for which he was empirically treated with doxycycline. On admission, he was afebrile, blood pressure was 130/69 mmHg, heart rate was 84 bpm, and respiratory rate was 22 breaths/min. Physical exam was unremarkable. Labs were notable for serum creatinine 2.70mg/dl, total bilirubin 3.2mg/dl, direct bilirubin 1.6mg/dl, AST 125U/L, ALT 66U/L, hemoglobin 10.1g/dl, and platelets 44k/µL. Peripheral smear showed babesia species without Anaplasma and Ehrlichia, and Lyme serology was negative. Patient was started on intravenous azithromycin and atovaquone and admitted to medical ward. Later that day he became hypotensive with elevated lactate of 3.1mmol/dl. His blood pressure was minimally fluid-responsive. Further labs revealed a haptoglobin < 10, elevated lactate dehydrogenase, and parasitemia of 31.4%. Due to the hypotension with evidence of organ damage, intravascular hemolysis, and high-grade parasitemia, he was transferred to the medical intensive care unit (MICU) for exchange transfusion. In the ICU patient received two rounds of exchange red blood cell transfusion with which parasitemia decreased to 1.4% and hemolysis parameters improved. His blood smear was negative for babesia on hospital day 5 and he was discharged home to complete a 2-week course of azithromycin and atovaquone from the day of negative smear. Discussion: Babesiosis can be life-threatening, especially in elderly, asplenic, and immunocompromised patients. Our case outlines the importance of early institution of exchange transfusion in addition to appropriate antimicrobial therapy in patients with end-organ damage, intra-vascular hemolysis, and high-grade parasitemia for better outcomes.

To what extent does prior antimicrobial therapy affect the diagnostic performance of radiolabeled leukocyte scintigraphy in infective endocarditis?

AimsThis prospective, single-center study sought to assess to what extent there is interference between the hybrid technique of single-photon emission tomography-computed tomography with technetium99m-hexamethylpropyleneamine oxime–labeled leukocytes (99mTc-HMPAO-SPECT/CT) and antimicrobial therapy in patients with infective endocarditis (IE). Methods and resultsDuring the years 2015–2019, we enrolled 205 consecutive adults with suspected IE, all underwent 99mTc-HMPAO-SPECT/CT. The study population was divided into those who had received antimicrobial therapy up to 30 days prior to 99mTc-HMPAO-SPECT/CT (group 1, n = 96) and those who had not (group 2, n = 109). Patients were prospectively observed for 12 ± 10 months. Group 1 presented higher positive predictive values (91.89% vs. 60.00%, = 0.001), and decreased negative predictive values (77.97% vs. 90.54%, P = 0.04). Patients treated with antimicrobial therapy displayed false-negative 99mTc-HMPAO-SPECT/CT results more often [odds ratio (OR), 4.63; 95% confidence interval (CI), 1.41–15.23, P = .01], particularly when intravenous (OR 5.37; 95% CI 1.73–16.62, P = .004), definite (OR 9.43; 95% CI 2.65–33.51, P = .001), and combination antibiotic regimens (OR 8.1; 95% CI 2.57–25.64, P = .001) had been administered. ConclusionPrior antibiotic therapy affects 99mTc-HMPAO-SPECT/CT diagnostic properties. Patients treated with antimicrobial therapy display false-negative 99mTc-HMPAO-SPECT/CT results more often, especially if intravenous, definite, or combination regimens are administered. Graphical abstract▪

PB2261: LINEZOLID AS A SAFE ANTIMICROBIAL AGENT IN THROMBOCYTOPENIC PATIENTS UNDERGOING CHEMOTHERAPY FOR HEMATOLOGIC MALIGNANCIES

Background: Febrile neutropenia (FN) is a common event in patients undergoing high-dose chemotherapy (HD-CT) for hematologic malignancies. Linezolid (LZ) is the first-in-class oxazolidinone antimicrobial agent active against gram-positive bacteria, often administered during FN as treatment for hospital-acquired pneumonia, gram-positive bacteriemia and soft-skin tissue infection. LZ induced thrombocytopenia or delayed platelet recovery are adverse events of concern in patients receiving HD-CT. As of today, few data are available on the safety of LZ in this specific setting. Aims: To retrospectively analyze a cohort of thrombocytopenic patients treated with LZ for FN in a single center, evaluating bleeding risk and impact on PLT recovery time. Methods: The analysis included patients diagnosed with Acute Leukemia (AL), High Grade Lymphomas (HGL) and Multiple Myeloma (MM) treated at our institution, between 2016 and 2021, with LZ for a FN episode during induction chemotherapy or ASCT conditioning. To be enrolled, PLT count at the start of LZ therapy had to be < 50×109/L. Results: A total of 40 FN episodes treated with LZ were identified. 22 occurred during induction therapy for AL and 18 during ASCT conditioning regimens. The median PLT count at the start of LZ therapy was 19×109/L in both groups (range 5-49×109/L in the AL cohort, 5-35×109/L in the ASCT group), while the median treatment duration was 8 days in both groups (range 2-15 days in the AL cohort, 3-12 days in the ASCT cohort). Only one clinically relevant bleeding event was observed in the AL group, while 0 bleeding events were observed in the ASCT group. Resolution of infection (defined as fever resolution, normalization of CRP and blood culture negativization) after the introduction of LZ therapy was observed in 17 (77%) AL patients and 15 (83%) ASCT patients. In the AML group PLT recovery (defined as a stable PLT count ≥20×109/L without the need for PLT transfusion) was observed in 18 (81%) patients with a median time to recovery of 22 days from the start of the chemotherapeutic regimen (range 18-41). PLT recovery was observed in 10 (71%) ASCT patients with a median time to recovery of 35 days from the stem cell infusion (range 13-136). 4 out of 18 patients in the ASCT group started LZ therapy after PLT recovery, and 3 out of 18 patients in the same group died due to the infectious complication that prompted the start of LZ therapy. Median PLT recovery time was not significantly different between patients enrolled in this study and historical controls from our center (AML: median 20 days, p>0.1. ASCT: median 22.5 days, p>0.1). Summary/Conclusion: Our observations support the use of LZ in this setting, as only one relevant bleeding event was observed among the two groups, and no impact on PLT recovery time was noted after comparison with historical data. Our study suggests that LZ is a safe and effective antimicrobial therapy in patients undergoing HD-CT for hematological malignancies. This data needs to be prospectively confirmed in a larger cohort of patients in a multicenter study.

The Role of Urinary Nitrite in Predicting Bacterial Resistance in Urine Culture Analysis Among Patients With Uncomplicated Urinary Tract Infection.

ObjectiveThis study aims to determine the relationship between the presence of urinary nitrite and bacterial resistance to antimicrobial therapy in patients with uncomplicated urinary tract infections.MethodsDuring a six-month time period (April-October, 2020), we reviewed the urine samples of 59 adult outpatients from the Urology Department of Tbilisi State Medical University the First University Clinic with the diagnosis of urinary tract infection. The infecting microorganisms and the presence of urine nitrite were recorded. Resistance rates to the antibiotics were compared between the positive and negative nitrite groups. Chi-squared test was used to perform the statistical analysis using Prism software version 9.3.1 (GraphPad Software, Inc., San Diego, California).ResultsWe examined the correlation between the nitrite-positive and -negative groups with the resistance pattern to ceftriaxone, trimethoprim/sulfamethoxazole (TMP-SMX), ampicillin-sulbactam, fosfomycin, amikacin, doxycycline, cefuroxime, cefotaxime, ceftazidime, and nitrofurantoin.A total of 59 outpatients with a mean age of 37 years met the inclusion criteria between April and October 2020. In the positive and negative nitrite groups, there were 23 and 36 patients, respectively. Three (17.6%) of the 17 gram-positive organisms and 20 (62.5%) of the 42 gram-negative organisms yielded positive nitrite results.In nitrite-positive group, resistance rates to ceftriaxone, TMP-SMX, ampicillin-sulbactam, fosfomycin, amikacin, doxycycline, cefuroxime, cefotaxime, ceftazidime, and nitrofurantoin were 52.2%, 70.8%, 63.5%, 67.7%, 25.8%, 31.9%, 29.6%, 32.5%, 22.5% and 83.8%, respectively. These values in the nitrite-negative group were 6.5%, 41.3%, 60.7%, 72.9%, 49%, 3%, 2.3%, 3.3%, 4.3% and 81.9%, respectively.Highest relative resistance rate was recorded against cefuroxime (12.9), followed by doxycycline (10.6), cefotaxime (9.8), ceftriaxone (8.03), ceftazidime (5.2), TMP-SMX (1.71), ampicillin-sulbactam (1.05), nitrofurantoin (1.02), fosfomycin (0.93), and amikacin (0.53).The most commonly isolated pathogen was Escherichia coli, which was detected in 35 (71%) isolates. Other bacteria commonly found were Proteus spp in five (12%) isolates, Klebsiella spp in two (5%) isolates, and Enterococcus in five (12%) isolates.ConclusionThe findings revealed that out of 10 antibiotics, nitrite-positive groups demonstrated higher resistance only against ceftriaxone, cefuroxime, cefotaxime, and doxycycline. Other antibiotics showed no statistically significant differences in resistance. Furthermore, the highest relative resistance rate was recorded against cefuroxime, whereas amikacin revealed the lowest. Therefore, we suggest physicians to not adjust antibiotic therapy for urinary tract infections (UTIs) based on the presence of nitrite. Urine bacteriology should be ordered.