Nosocomial Pneumonia Research Articles

P-1758. Evaluation of Real-Life Application of Multi-plex PCR Pneumonia Film-array Panel as an Antibiotic Stewardship Tool, a Prospective Investigation

Abstract Background Selecting empiric antibiotics (abx) for community-acquired and hospital-acquired pneumonia (CAP, HAP) on admission can be challenging, given the variety of possible pathogens. Per IDSA guidelines, broad spectrum antibiotic(s) are recommended, based on pneumonia type, risk of prior abx exposure/drug resistance, and disease severity. In this study, by using the BioFire® multi-plex PCR film-array (FA) on sputa, we prospectively investigated the time to pathogen identification in CAP and HAP, time to providing optimal abx, and types of change this strategy allowed. Methods Single center, prospective, observational study from January 1, 2021 to January 31, 2024. All admitted patients with CAP or HAP, with satisfactory sputa or bronchioalveolar lavage (BAL) cultures, were considered for inclusion by the Antimicrobial Stewardship service (ASP), whereby FA was performed on the sample. Exclusion criteria consisted of poor sample (≥ 10 epithelial cells/lpf), sputa previously ordered within 7 days, concurrent non-pneumonia infections and non-infectious pulmonary conditions. FA results and its respective abx recommendations were communicated to the patient’s clinician by ASP. Results 148 samples met study criteria (Table 1). FA detected bacterial pathogens in 65% (n=96) and viruses in 16% (n=23) (Table 2). FA resulted in 2.9 hours (H) [IQR 1.75-2.87] after gram stain, whereas time to culture finalization was 90.5 H [IQR 45-82] (Figure 1). An average of 2 empiric abx days were saved per case [IQR 1-2]. Time to first modification of abx was 6.1 H [IQR 0.15-2.9]. 84% of abx courses were modified due to ASP intervention from FA, of which 86% resulted in de-escalation of empiric abx (Figure 2). 62% (n=92) had no growth on culture, and of those cases, 48% (n=44) had pathogen detected by FA. 50% (n=74) of bacterial culture results were congruent to FA, 19% (n=28) were partially congruent, with more bacteria detected on FA than culture. Timeline Conclusion FA reduced time to pathogen identification compared to traditional culture in CAP and HAP, allowing ASP to provide rapid interventions to optimize abx treatment and save days of less optimal empiric abx. FA detected more pathogens compared to culture, including when negative, leading to abx changes in majority of cases. FA serves as a valuable tool for ASP. Type of Intervention Disclosures All Authors: No reported disclosures

P-822. Unraveling the Landscape of Staphylococcus aureus Bloodstream Infection: Insights from a Single-Center Study

Abstract Background Staphylococcus aureus significantly impacts human health, with global prevalence ranging from 13% to 74% and 37% in India. By delving into the intricacies of this bloodstream infection, we aim to provide valuable insights into its manifestations, risk factors, and antibiotic sensitivities, crucial for guiding tailored treatment strategies and optimizing patient outcomes. Methods Between February 2022 and January 2024, a prospective observational study was conducted at AIIMS, Jodhpur, India, encompassing all blood culture-positive Staphylococcus aureus patients, with comprehensive collection of clinical, epidemiological, microbiological, and outcome data. Results In our study, we observed a diverse demographic distribution among Staphylococcus aureus bloodstream infection cases. The most common age group affected was 1-20 years, comprising 29.82% of cases, followed closely by individuals aged 21-40 years (24%), 41-60 years (23.27%), and those over 60 years old (22.91%). Clinical manifestations varied, with Hospital-Acquired Pneumonia (HAP) being the most common syndrome at 31.27%, followed closely by Central Line-Associated Bloodstream Infection (CLABSI) at 27.27%. Other prevalent syndromes included Community-Acquired Pneumonia (CAP; 17.45%), Bone & Joint infections (22.54%), Meningitis (10.18%), Urinary Tract Infection (UTI; 2.54%), Skin and Soft Tissue Infections (SSTI; 4%), and Endocarditis (4%). Regarding Staphylococcus aureus strain types, Methicillin-Sensitive Staphylococcus aureus (MSSA) constituted the majority of cases at 55.64%, followed by Methicillin-Resistant Staphylococcus aureus (MRSA) at 42.54%, and Vancomycin-Resistant Staphylococcus aureus (VRSA) at 1.82%. Among the recorded outcomes, the majority of patients (78.54%) showed improvement following treatment, while 16.36% of patients succumbed to the infection. Additionally, 5.09% of patients were lost to follow-up. Conclusion Despite progress, many patients succumbed or were lost, highlighting the need for vigilant monitoring and enhanced treatments. Our study underscores the urgency to improve outcomes and curb Staphylococcus aureus infections. Disclosures All Authors: No reported disclosures

P-287. Risk factors for Pseudomonas aeruginosa in ICU-Related Respiratory Infections. An analysis from the European Network for ICU-Related Respiratory Infections (ENIRRIs) study

Abstract Background Nosocomial low respiratory infections (nLRTIs) represent a significant complication prevalent among patients who require admission to the intensive care unit (ICU). Gram-negative microorganisms are related to nLRTIs, such as ventilator-associated pneumonia (VAP), ventilator-associated tracheobronchitis (VAT), ICU-acquired pneumonia (ICU-HAP), and hospital-acquired pneumonia (HAP). Pseudomonas aeruginosa (PA) is frequently identified among nLRTIs; however, not all patients with nLRTI may require antipseudomonal treatment and this is not clear in the literature. This study aims to describe the characteristics and principal outcomes of patients with confirmed PA nLRTI. Table 1. Characteristics of patients with Pseudomonas aeruginosa identification Vs Non-Pseudomonas aeruginosa identification. Methods This prospective cohort was conducted in 12 countries over two continents from 9th May 2016 until 16th August 2019. Characteristics and outcomes of nLRTI’s patients admitted to the ICU were collected. All patients were tested to find microbiological-causing agents. Patients with confirmed isolation for PA were compared to patients with non-PA isolation. The Mam Whitney and Chi-squared were used to compare the group's proportions depending on their distribution. Table 2. Bivariate analysis for risk factors associated with Pseudomonas aeruginosa Results 1059 patients with nLRTIs who underwent testing for microbiological diagnosis were included, 14.4% patients had confirmed infection by PA. 74% were male with a median age of 64 (49-73) years old. The principal diagnosis among patients with PA was VAP. The principal comorbidities were diabetes and heart disease, followed by COPD. The most frequent complication was septic shock, followed by acute kidney injury. There were differences among the comorbidities, complications and outcomes among the groups (Table 1). However, there were no differences in mortality (Table 1 - Figure 1). VAT and VAP diagnosis, COPD Gold D and AKI on the 1st day were associated with a high risk of infection by PA (Table 2). Figure 1. Sankey diagram showing mortality outcome. Pseudomonas aeruginosa Vs. Non-Pseudomonas aeruginosa LRTI-diagnosed patients who were admitted to the ICU. Conclusion This multi-country study found some important risk factors associated with PA in nLRTI patients. Differences among groups were notorious; diabetes and COPD comorbidities are more frequent among PA nLRTI patients. Finally, PA infection increases the length of stay of patients. Further studies are needed to confirm these findings. Disclosures All Authors: No reported disclosures

511. Activity of Sulbactam-durlobactam and Standard-of-Care Antibiotics against Acinetobacter baumannii-calcoaceticus complex isolates acquired from Hospitalized Patients in the United States (2023 – 2024)

Abstract Background Acinetobacter baumannii-calcoaceticus complex (ABC) isolates are responsible for severe infections, such as bacteremia, healthcare-associated pneumonia, and skin and soft tissue infections. Sulbactam-durlobactam is a FDA-approved targeted β-lactam-β-lactamase inhibitor combination antibiotic developed to treat infections caused by ABC. This study aims to evaluate the in vitro activity of sulbactam-durlobactam and clinically utilized antibiotics against ABC strains with a predominance of carbapenem resistance.Table 1.Susceptibility test results of sulbactam-durlobactam and comparator agents against Acinetobacter baumannii-calcoaceticus complex isolates Methods 164 ABC isolates in addition to de-identified data including patient location at the time of culture and culture source were submitted by 11 geographically dispersed U.S medical centers in 2023 and 2024. Susceptibility tests for sulbactam-durlobactam (durlobactam fixed concentration of 4 mg/L), and comparator agents were conducted by manual broth microdilution and interpreted according to CLSI M100Ed34 standards. Carbapenem-resistant ABC (CRAB) was defined by phenotypic resistance to meropenem (MIC ≥8 mg/L). Results ABC isolates were primarily cultured from respiratory sources (57%), followed by blood (19%) and urine (11%). Of the 164 isolates, majority were isolated from non-ICU patients (n=102; 62%) versus ICU (n=62; 38%). The MIC50 and MIC90 values of the sulbactam component of ampicillin-sulbactam for all isolates was 8 and 32 mg/L, respectively resulting in a susceptibility rate of 40.8%. The addition of durlobactam to sulbactam decreased the MIC50 and MIC90 by 2-doubling dilutions to 1 and 4 mg/L and increased the susceptibility rate to 94.5%. The MIC50/90 and susceptibility rates for all other antimicrobial agents are shown in Table 1. Notably, a majority of isolates were CRAB (n=122; 74.4%) and among these isolates, sulbactam-durlobactam MIC50, MIC90, and %S was 2, 4 mg/L, and 92.6%, respectively. Conclusion Sulbactam-durlobactam demonstrated potent in vitro activity against a contemporary challenge set of clinical ABC isolates, including carbapenem-resistant isolates among hospitalized patients in the United States. This study highlights the important role of sulbactam-durlobactam, relative to other clinically utilized agents for the treatment of infections caused by ABC isolates. Disclosures Amanda Harrington, PhD, Beckman Coulter: Advisor/Consultant|bioMeriuex: Advisor/Consultant|bioMeriuex: Grant/Research Support|Bio-Rad: Advisor/Consultant|Day Zero: Advisor/Consultant|Selux Diagnostics: Grant/Research Support Wesley D. Kufel, Pharm.D., BCPS, BCIDP, Merck & Co.: Grant/Research Support|Shionogi, Inc: Grant/Research Support Lars Westblade, PhD, Accelerate Diagnostics, Inc: Grant/Research Support|bioMerieux, Inc: Grant/Research Support|Element Materials Technology: Grant/Research Support|Hardy Diagnostics: Grant/Research Support|Roche Molecular Systems, Inc.: Advisor/Consultant|Roche Molecular Systems, Inc.: Grant/Research Support|Selux Diagnostics, Inc.: Grant/Research Support|Shionogi, Inc: Advisor/Consultant|Talis Biomedical: Advisor/Consultant David P. Nicolau, PharmD, CARB-X: Grant/Research Support|Innoviva: Grant/Research Support|Innoviva: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria|Venatorx: Grant/Research Support Tomefa E. Asempa, PharmD, FDA/CDER: Grant/Research Support|Paratek: Grant/Research Support|Shionogi: Grant/Research Support|Spero: Grant/Research Support|VenatoRx: Grant/Research Support

P-823. Navigating Staphylococcus aureus Bloodstream Infections in Pediatrics: A Comprehensive Analysis

Abstract Background Staphylococcus aureus bacteraemia poses substantial morbidity and mortality risks in children, with infection rates ranging from 1.5 to 3.5 per 1000 hospitalizations. Diagnosis and management of Staph. aureus is challenging. This study aims to delineate the spectrum of Staph. aureus bloodstream infections (BSI) in paediatric patients, aiding in the development of more effective management strategies. Methods Conducted at AIIMS, Jodhpur, India, from February 2022 to January 2024, this prospective observational study gathered clinical and microbiological data from 82 patients with Staphylococcus aureus BSI. Results In this study, the most commonly affected age group was children under 5 years, constituting 39.02% of cases, followed by those aged 11 to 15 years (31.71%), 16 to 20 years (17.07%), and 6 to 10 years (12.19%). In the observed clinical syndromes, the most common was bone and joint infections, affecting 34.15% of patients, followed by healthcare-associated pneumonia (HAP) at 30.49%. Meningitis was observed in 13.41% of cases, while community-acquired pneumonia (CAP) accounted for 17.07%. Central line-associated bloodstream infections (CLABSI) were reported in 7.32% of patients, with skin and soft tissue infections (SSTI) noted in 3.66% of cases. Urinary tract infections (UTI) represented the least common, affecting 1.22% of patients. Methicillin Resistant Staphylococcus aureus was present in 54.88% of cases, followed by Methicillin Sensitive Staphylococcus aureus at 40.24%, and Vancomycin Resistant Staphylococcus aureus at 4.88%. In terms of outcomes, the majority of patients, constituting 75.61%, experienced improvement in their condition. Unfortunately, 21.95% of patients succumbed to the infection, while a small proportion, accounting for 2.44%, were lost to follow-up. Conclusion MRSA underscores the challenges posed by antimicrobial resistance. Our comprehensive analysis of Staphylococcus aureus bloodstream infection reveals multifaceted challenges in its management.. Disclosures All Authors: No reported disclosures

Innovative Antibiotic Therapies for Carbapenem-Resistant Gram-Negative Bacterial Infections: Clinical Efficacy, Safety, and Comparative Studies

This review provides an overview of recent research and advancements in infection prevention and the treatment of drug-resistant bacterial diseases. Cefiderocol, a novel siderophore cephalosporin, has demonstrated effectiveness against carbapenem-resistant bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. Clinical trials, including APEKS-NP and CREDIBLE-CR, affirm its efficacy for hospital-acquired pneumonia (HAP) but highlight concerns over increased mortality due to severe renal complications. Cefiderocol has shown superior outcomes in complicated urinary tract infections (cUTI) compared to imipenem–cilastatin. A comparison of colistin monotherapy versus combination therapy with meropenem for carbapenem-resistant infections revealed no significant improvement in clinical outcomes with combination therapy but noted delays in resistance development. Colistin–rifampicin combination therapy showed potential benefits for colistin-resistant Acinetobacter baumannii, although results were not statistically significant. SPR206, a polymyxin derivative, and durlobactam, a β-lactamase inhibitor, show promise in addressing these resistant strains, with durlobactam demonstrating efficacy in combination with sulbactam and imipenem–cilastatin. Additional studies investigated antibiotic strategies for resistant infections, including cefoperazone–sulbactam versus combination therapy with tigecycline, and examined infection-prevention strategies in surgical settings, comparing chlorhexidine–alcohol and povidone–iodine. This research highlights the importance of optimizing treatment regimens and infection-control measures across various healthcare settings, including neonatology and surgical care.

P-2081. Prototype Assay for Detection of Carbapenem-Resistant Acinetobacter baumannii Complex (CRABC)

Abstract Background Carbapenem-resistant Acinetobacter baumannii complex (CRABC) is recognized as an urgent/critical antimicrobial resistance (AMR) threat, causing hospital-acquired and ventilator-associated pneumonia (HAP/VAP) and bacteremia. Due to limited treatment options, there is an urgent need for novel targeted antibiotics against CRABC. As these drugs become available, their timely and appropriate use will require the rapid identification of patients with CRABC infection. We evaluated the performance of a prototype assay for the rapid detection of CRABC directly from bronchoalveolar lavage (BAL), sputum/endotracheal aspirate (S/ETA), and positive blood culture (PBC) samples. Methods A prototype assay was designed for the qualitative detection of A. baumannii complex (ABC) harboring the most prevalent associated carbapenemase genes (blaOXA-23, blaOXA-24, blaOXA-58, and/or blaNDM). The prototype assay was developed for use on the high-throughput cobas® 5800/6800/8800 Systems with a defined oligo pool and positive control. A total of 452 BAL, 681 S/ETA, and 392 PBC samples (including prospective, archived, and contrived specimens) were tested by the prototype assay and compared with routine microbiology for ABC detection and the Unyvero Hospitalized Pneumonia or BCU panel for carbapenemase detection. Discrepant resolution was performed using the BioFire® FilmArray® Pneumonia or BCID Panel and/or the Streck ARM-D® Kit, OXA assay, depending on the type of discrepancy. Results After resolution of discrepant results, the overall percentage agreement, positive percent agreement, and negative percent agreement between the prototype assay and the comparator methods (culture/nucleic acid amplification tests [NAATs]) was 97.1%, 98.5%, and 96.5%, respectively, for BAL; 99.3%, 100%, and 99.1%, respectively, for S/ETA; and 99.2%, 100%, and 99.1%, respectively, for PBC. Conclusion This prototype assay exhibited a high percentage agreement for the detection of CRABC in BAL, S/ETA, and PBC samples when compared to culture/NAATs. A future assay based on this prototype could be evaluated in a clinical trial to establish its utility in facilitating timely and appropriate antibiotic selection for patients with HAP/VAP or bacteremia caused by CRABC. Disclosures Brian Lee, MD, GE Healthcare: Stocks/Bonds (Public Company)|Invitae: Stocks/Bonds (Public Company)|Merck: Stocks/Bonds (Public Company)|OPKO Health: Stocks/Bonds (Public Company)|Roche Diagnostics Solutions: Employment|Roche Diagnostics Solutions: Stocks/Bonds (Public Company)|Spero Therapeutics: Stocks/Bonds (Public Company) Natacha Martins Sorenson, PhD, Roche Diagnostics Solutions: Employment|Roche Diagnostics Solutions: Stocks/Bonds (Public Company) Hai Nguyen, n/a, Roche Diagnostics Solutions: Employment Arrash Moghaddasi, n/a, Roche Diagnostics Solutions: Employment Aishwarya Sathish, n/a, Roche Diagnostics Solutions: Employment Patrick Lin, n/a, Roche Diagnostics Solutions: Employment Kyle C. Cady, PhD, Roche Diagnostics Solutions: Employment|Roche Diagnostics Solutions: Stocks/Bonds (Public Company)

P-1499. Patient Characteristics and Clinical Outcomes Associated with Meropenem/Vaborbactam Treatment in Carbapenem-Resistant Enterobacterales Pneumonia

Abstract Background Carbapenem-resistant Enterobacterales (CRE) are a major public health threat due to increasing prevalence and limited effective treatment options. Meropenem/vaborbactam (M/V) is a beta-lactam/beta-lactamase inhibitor agent designed to treat CRE. There is a paucity of data related to patient characteristics and associated outcomes with the utilization of M/V in pneumonia due to CRE. The objective of this study was to describe real-world experience with M/V in this setting. Methods This is a retrospective, observational, multicenter, cross-sectional study of patients ≥ 18 years old who received M/V for ≥ 72 hours for clinically-diagnosed hospital-acquired (HAP) or ventilator-associated pneumonia (VAP) due to CRE between 6/2020-2/2024. The primary outcome was clinical success, defined as resolution or improvement in signs/symptoms of infection and without the need for additional therapy. The secondary outcomes included 30-day mortality, 30-day microbiologic recurrence, 30-day symptomatic recurrence and adverse drug reaction(s). Results Sixty-two patients were included from six U.S. medical centers. The mean age (standard deviation [SD]) was 58.2 (15.4) years; patients were predominantly male (71.0%) and Caucasian (58.1%). At time of culture collection, the mean (SD) APACHE II score was 22.1 (7.8) and most patients (78.0%) were admitted to the intensive care unit. Klebsiella pneumoniae was the predominant species isolated in culture (43.5%). Notably, 65.6% were diagnosed with VAP, 32.3% had a COVID-19-related hospitalization and 29.0% developed secondary bacteremia. Patients received a median (interquartile range [IQR]) of 7.2 (6.1-12.0) days of M/V, with 21.0% receiving systemic combination therapy. Clinical success was achieved in 69.4% of patients and 30-day mortality occurred in 33.9%. Microbiologic and symptomatic recurrence occurred in 11.2% and 8.1% of cases, respectively. One patient experienced Clostridioides difficile infection attributed to the use of M/V. Conclusion Our study demonstrates promising clinical success with the use of M/V for treatment of pneumonia. Larger, comparative studies are needed in this population to identify patient factors associated with clinical success and assess M/V’s efficacy compared to other available therapies. Disclosures Kaylee E. Caniff, PharmD, BCIDP, T2Biosystems: Honoraria Kevin W. Garey, PharmD, MS, Acurx: Grant/Research Support Tamara Krekel, PharmD, BCPS, BCIDP, Merck Inc: Honoraria Wesley D. Kufel, Pharm.D., BCPS, BCIDP, Merck & Co.: Grant/Research Support|Shionogi, Inc: Grant/Research Support Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Advisor/Consultant|Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Grant/Research Support|Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Speaker

Modeling and simulation of distribution and drug resistance of major pathogens in patients with respiratory system infections

BackgroundRespiratory tract infections (RTIs) are one of the leading causes of morbidity and mortality worldwide. The increase in antimicrobial resistance in respiratory pathogens poses a major challenge to the effective management of these infections.ObjectiveTo investigate the distribution of major pathogens of RTIs and their antimicrobial resistance patterns in a tertiary care hospital and to develop a mathematical model to explore the relationship between pathogen distribution and antimicrobial resistance.MethodsFive hundred patients with RTIs were included in the study and 475 bacterial strains were isolated from their respiratory specimens. Antimicrobial susceptibility testing and analysis of influencing factors were performed. A mathematical model was developed to simulate the relationship between pathogen distribution and drug resistance.ResultsThe most common pathogens were Streptococcus pneumoniae (30%), Haemophilus influenzae (20%), Pseudomonas aeruginosa (15%), Staphylococcus aureus (10%) and Klebsiella pneumoniae (10%). The distribution of pathogens varied according to age group and type of RTIs, with higher proportions of Pseudomonas aeruginosa and Staphylococcus aureus in hospital-acquired and ventilator-associated pneumonia. Isolated pathogens showed high and increasing rates of resistance to commonly used antibiotics. Model simulations suggest that a shift in the distribution of pathogens toward more resistant strains may lead to a significant increase in overall resistance rates, even if antibiotic use patterns remain unchanged.ConclusionThis study emphasizes the importance of regular monitoring of respiratory pathogen distribution and antimicrobial resistance patterns and the need for a comprehensive approach to managing RTIs, including implementation of antibiotic stewardship programs, infection control measures, and development of new therapies.

P-422. Incidence, Risk Factors, Etiology, and Clinical Outcomes of Pneumonia in Adults with Cancer at a Tertiary Care Centre: a One Year Prospective Cohort Study

Abstract Background Pneumonia is an important cause of morbidity, mortality, hospital admission, and healthcare-associated costs in cancer patients. We investigated the incidence, risk factors, etiology, and clinical outcomes of pneumonia in adults with cancer admitted to the ICU in Tata Medical Center Kolkata from October 2022 to September 2023.Figure 1:Monthly Trend in Case Identification Methods We conducted a prospective cohort study involving two groups with malignancy admitted to the ICU: one with pneumonia and one without. Pneumonia was identified by clinical and radiological features. Incidence was calculated as the proportion of patients in the ICU who developed pneumonia in one year. Community-acquired (CAP), healthcare-associated (HAP), and ventilator-associated pneumonia (VAP) were defined by NHSN and HAI Surveillance in India guidelines. Relative risks were calculated and logistic regression performed to assess risk factors for pneumonia and mortality; and clinical outcomes were compared using Z-tests on STATA-17.Figure 2:Kaplan-Meier Plot for the survival analysis for patients with or without pneumonia Results 355 individuals with pneumonia and 356 without were enrolled among 2279 in-patients. The incidence of pneumonia was 15.6% (95% CI: 14.1-17.1%). 51.8% were CAP and 48.2% were HAP. 17.9% of HAP (7.3% of all pneumonia) was VAP. Hematological malignancies (RR=2.08), diabetes (1.31), COPD (1.78), renal dysfunction (1.73), neutropenia (1.83), smoking (1.28), chemotherapy (2.01), radiotherapy (1.56), immunotherapy (1.61), and bone marrow transplantation (2.05) increased risk for pneumonia. 258 (72.7%) cases had a positive microbiology. Of these, 123 were polymicrobial (47.7%), termed “coinfections/ superadded infections” (table 1). All-cause 90-day mortality (39.2%), mean length of hospital stay (18.6 days), ICU stay (10.9 days), and mechanical ventilation (2 days) were higher in patients with pneumonia than those without (p< 0.05, figure 2). CAP (RR=1.42), hematological malignancies (1.59), renal dysfunction (1.51), neutropenia (1.74), chemotherapy (1.60), immunotherapy (1.55), days of ICU stay (logit OR=1.04), days of mechanical ventilation (logit OR=1.03), and co-infections/ superadded infections (logit OR=1.82) increased risk of death in pneumonia.Table 1:Etiology of pneumonia with positive microbiology segregated by type of pneumonia. The denominator corresponds to the number of cases in each category that had positive microbiology. Conclusion Pneumonia in cancer patients admitted to the ICU is associated with worse clinical outcomes.Table 2:Clinical Outcome in patients with or without pneumonia Disclosures All Authors: No reported disclosures

P-424. Challenges in Developing a Non Ventilator Hospital-Acquired Pneumonia Surveillance System

Abstract Background Pneumonia has been identified as the leading cause of hospital-acquired infections (HAI) with Non Ventilator Hospital-Acquired Pneumonia (NVHAP) making up the majority of cases. The ambiguity of definitions and subjective diagnostic criteria make defining and tracking NVHAP cases a challenge. We attempted to duplicate a previously validated electronic medical record (EMR) based NVHAP surveillance systems at a Midwest Academic Medical Institution. Defining NV HAP Inclusion criteria for NVHAP. Methods Using previously established criteria a surveillance system was designed to determine possible cases of NVHAP using data from our institution’s EMR (Table 1). Institutional review board approval was obtained, and the surveillance system was retrospectively applied to adult patients hospitalized throughout 2023 at two Midwest academic hospitals. A validation study was conducted to compare ten percent of cases reported by the NVHAP surveillance system to that of a single physician reviewer. Interim analysis was conducted in instances of inclusion criteria failure to allow for refinement of the NVHAP surveillance system. Results The NVHAP surveillance system generated a list of 425 possible NVHAP events in 2023. Single reviewer analysis of 20 patients revealed 12 patients who did not meet CDC pneumonia criteria and three that did not meet all inclusion criteria: two for lack of chest imaging within 48 hours of recorded oxygen deterioration event and two with no documentation of new antibiotic administration. Additional lists of 338, 322, and 76 NVHAP episodes were generated after coding changes were implemented with repeat interim analysis demonstrating further issues with adherence to inclusion criteria and errors with reproducibility of data extraction. Conclusion The development of a NVHAP surveillance system would allow an objective way to track this significant HAI. Potential models exist for creating such a system. However, multiple challenges are still present from determining EMR specific coding for complex medical issues, such as oxygen deterioration events, to reproducibility of electronic extracted data. Our efforts show that even when attempting to replicate validated methodologies site specific challenges will pose significant barriers to the development of EMR based NVHAP surveillance systems. Disclosures Kelly Cawcutt, MD, MS, BD: Advisor/Consultant|BMJ: Honoraria

P-663. Evaluating the Effectiveness of a Real-Time Electronic Alert to Monitor the Duration of Antibiotic Therapy in Hospitalized Pneumonia Patients in the Asian Healthcare Setting

Abstract Background Limiting the duration of antibiotic prescribing to the shortest effective period is recognized as a strategy to mitigate the risk of antibiotic resistance. This study aims to assess the impact of a Real-Time Electronic Alert system designed to monitor the duration of antibiotic therapy in hospitalized pneumonia patients, with the goal of reducing unnecessary antibiotic exposure. Methods The intervention involved the implementation of a dashboard capable of generating real-time alerts whenever hospitalized patients diagnosed with community- or hospital-acquired pneumonia received antibiotics for more than five consecutive days. The study was conducted between December 2022 and January 2024 at two medical college hospitals in South Asia. Alerts generated by the dashboard were regularly reviewed by an antibiotic stewardship (AS) team, who intervened when patients exceeded the guideline-recommended duration of antibiotic therapy for pneumonia without additional clinical indications warranting continued antibiotic use. To evaluate the effectiveness of the intervention, the inappropriate duration of antibiotic therapy was compared before and after the implementation of the dashboard. A similar hospital with comparable patient demographics served as a comparative group. Results During the intervention period, the AS team reviewed a total of 218 patients flagged by the dashboard, resulting in 117 documented interventions. Reasons for lack of intervention included the presence of additional infection diagnoses necessitating prolonged antibiotic therapy, co-infections, and delayed clinical improvement. Post-implementation, the mean excess duration of antibiotic therapy for pneumonia decreased to 0.48 days compared to the pre-implementation mean of 2.13 days. In contrast, the comparative hospital, which did not employ the alert system, experienced a post-intervention mean excess duration of 1.97 days compared to a pre-intervention mean of 2.04 days. Conclusion The pneumonia dashboard represents a potentially valuable stewardship tool for reducing unnecessary antibiotic exposure in pneumonia patients. Disclosures All Authors: No reported disclosures

P-661. Impact of Optimal β-lactam Treatment on the Outcomes of Patients with Pseudomonas Aeruginosa Pneumonia

Abstract Background P. aeruginosa is the most common cause of nosocomial pneumonia and accounts for a large proportion of antibiotic use in the ICU. Despite this, there are limited comparative-effectiveness data for β-lactam agents. Our objective was to compare outcomes of Pseudomonal pneumonia treated with piperacillin-tazobactam (TZP), cefepime (FEP) or meropenem (MEM). Methods We performed a retrospective cohort study of patients who met clinical criteria for pneumonia before (2017-2018) and after (2022-2023) dose optimization protocols were established.The primary outcome was 28-day all-cause mortality with secondary outcomes including 28-day clinical response, 90-day recurrence and development of new β-lactam resistance. Results In preliminary analyses, 118 patients were included; baseline characteristics shown in Figure 1. At diagnosis, 72% required mechanical ventilation and 42% had severe sepsis/shock. TZP was giving as a prolonged infusion (≥3h) throughout the study; 98.3% of patients received FEP or MEM as prolonged infusions after dose optimization, compared to 0% before (Figure 2). Clinical outcomes stratified by definitive treatment are shown in Figure 3. Mortality rates were numerically higher in patients treated with TZP (28.6%) compared to FEP or MEM (22.6%). Rates of treatment emergent resistance ranged from 28.9 – 47.1% across agents. Clinical response rates did not vary across patients before or after dose optimization (Figure 4); however, the 28-day mortality rates was 4.3% lower post-dose optimization of FEP and MEM. Across all patients, 24% died within 28 days of treatment initiation. Among those who survived (n=90), 26% developed recurrent pneumonia or bacteremia within 90 days. Conclusion Our preliminary data suggests that outcomes did not vary significantly between TZP, FEP, or MEM for treatment of P. aeruginosa pneumonia; however, some notable trends were identified, including higher mortality among patients who received TZP and lower mortality among patients receiving optimized doses of FEP or MEM. These data support further investigation through multicenter studies that include a larger number of patients. Consistent with prior reports, recurrent infections and treatment-emergent resistance are common challenges in managing P. aeruginosa pneumonia. Disclosures Erin K. McCreary, PharmD, Abbvie: Advisor/Consultant|Basilea: Advisor/Consultant|Ciadara: Advisor/Consultant|Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|GSK: Honoraria|Melinta: Advisor/Consultant|Merck: Advisor/Consultant|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria Ryan K. Shields, PharmD, MS, Allergan: Advisor/Consultant|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Menarini: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Utility: Advisor/Consultant|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support

Enhancing Patient Safety: Assessing ICU Nurses' Knowledge and Compliance in Ventilator-Associated Pneumonia Prevention at King Fahad General Hospital, Saudi Arabia

Background: Ventilator-associated pneumonia (VAP) is a prevalent cause of morbidity and mortality in intensive care units (ICUs). Defined as a nosocomial pneumonia that occurs more than 48 hours after mechanical ventilation initiation, VAP poses significant clinical challenges. While awareness of evidence-based practices is crucial, a gap often exists between knowledge and actual practice among nursing staff. Enhanced adherence to VAP prevention protocols has been linked to reduced incidence rates. Purpose: This study aims to assess the level of nurses’ knowledge and compliance regarding the prevention of VAP in the intensive care unit of King Fahad General Hospital in Saudi Arabia. Method: A descriptive research design was employed, involving 120 ICU nurses selected through convenience non-probability sampling. Result: A total of 96 participants were recruited in this study. The level of knowledge about VAP prevention among ICU nurses was almost good as there were about 57.3% (n=55) of the nurse participants had a good and adequate information. There was significant statistical difference in the mean knowledge score based on the academic qualification but, there was no statistical difference in mean of compliance based on academic qualification. Conclusion: Insufficient nursing knowledge and compliance about VAP assessment and prevention is a serious safety concern in all healthcare settings. The study highlighted that ICU nurses showed (good) moderate knowledge towards VAP prevention.

Factors Associated with Mortality in Nosocomial Lower Respiratory Tract Infections: An ENIRRI Analysis

Background: Nosocomial lower respiratory tract infections (nLRTIs) are associated with unfavorable clinical outcomes and significant healthcare costs. nLRTIs include hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and other ICU-acquired pneumonia phenotypes. While risk factors for mortality in these infections are critical to guide preventive strategies, it remains unclear whether they vary based on their requirement of invasive mechanical ventilation (IMV) at any point during the hospitalization. Objectives: This study aims to identify risk factors associated with short- and long-term mortality in patients with nLRTIs, considering differences between those requiring IMV and those who do not. Methods: This multinational prospective cohort study included ICU-admitted patients diagnosed with nLRTI from 28 hospitals across 13 countries in Europe and South America between May 2016 and August 2019. Patients were selected based on predefined inclusion and exclusion criteria, and clinical data were collected from medical records. A random forest classifier determined the most optimal clustering strategy when comparing pneumonia site acquisition [ward or intensive care unit (ICU)] versus intensive mechanical ventilation (IMV) necessity at any point during hospitalization to enhance the accuracy and generalizability of the regression models. Results: A total of 1060 patients were included. The random forest classifier identified that the most efficient clustering strategy was based on ventilation necessity. In total, 76.4% of patients [810/1060] received IMV at some point during the hospitalization. Diabetes mellitus was identified to be associated with 28-day mortality in the non-IMV group (OR [IQR]: 2.96 [1.28–6.80], p = 0.01). The 90-day mortality-associated factor was MDRP infection (1.98 [1.13–3.44], p = 0.01). For ventilated patients, chronic liver disease was associated with 28-day mortality (2.38 [1.06–5.31] p = 0.03), with no variable showing statistical and clinical significance at 90 days. Conclusions: The risk factors associated with 28-day mortality differ from those linked to 90-day mortality. Additionally, these factors vary between patients receiving invasive mechanical ventilation and those in the non-invasive ventilation group. This underscores the necessity of tailoring therapeutic objectives and preventive strategies with a personalized approach.

Colistin Use for the Treatment of Multi-Drug-Resistant Gram-Negative Severe Infections in ICU Patients: A Single-Center Study

Background: Colistin is increasingly used to treat severe infections caused by multi-drug-resistant (MDR) bacteria, particularly in critically ill patients. Its effectiveness, especially in monotherapy, remains controversial. This study aimed to evaluate the effectiveness and toxicity of colistin therapy in severe MDR infections. Methods: This retrospective study included patients treated with colistin (CMS) at the ICU. Patients’ treatments were divided into four subgroups: monotherapy vs. combination therapy, empirical vs. targeted therapy, intravenous vs. intravenous plus inhaled therapy, and standard doses with and without a loading dose. The primary outcome was clinical cure. Secondary outcomes included microbiological eradication, survival rate, and drug-related toxicity, particularly acute kidney injury (AKI). Exclusion criteria included Gram-positive infection, inhaled therapy alone, use of colistin <5 days. Results: A total of 150 patients (mean age 60 ± 18 years, APACHE II score 17 ± 10) were included. The most frequent condition was hospital-acquired pneumonia (n = 140, 93.3%). The most common pathogen was MDR Acinetobacter baumannii (n = 146, 97.3%). In most patients, colistin therapy was targeted (n = 113, 75.3%) and combined with other antibiotics (n = 124, 82.7%). Inhaled CMS was added in 47 (31.3%) patients. Mean duration of therapy was 10 ± 4 days. Clinical cure occurred in 64 (42.7%) patients, microbiological eradication in 20 (13.3%). AKI developed in 65 (53.7%) patients. Inhaled CMS improved the clinical cure rates (57.4% vs. 37.0%, p = 0.003). Conclusions: Intravenous CMS was mainly used for MDR Acinetobacter baumannii-related pneumonia. Clinical cure was observed in 42.7% of patients, but renal toxicity was high. Combining intravenous and inhaled CMS may improve outcomes.

Ceftobiprole: A therapeutic update.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. The purpose of this therapy update is to highlight new clinical studies comparing ceftobiprole to current therapies and provide evidence for its suggested role in therapeutic management of selected infectious diseases. Antimicrobial resistance continues to be a global health problem, and newer targeted antimicrobials are necessary to combat increasing rates of problematic infections. More specifically, targeted antimicrobials against methicillin-resistant Staphylococcus aureus are needed. Ceftobiprole has been marketed internationally for the treatment of complicated skin and skin structure infections, community-acquired pneumonia, and hospital-acquired pneumonia. While Food and Drug Administration approval was previously pursued for its use in acute bacterial skin and skin structure infections in the US, the Food and Drug Administration issued a complete response letter determining that study data were unreliable and recommended completion of additional studies. In April 2024, ceftobiprole was granted approval for 3 indications in the US based on updated clinical study data. Ceftobiprole is the second fifth-generation cephalosporin to be developed and approved for clinical use. Ceftobiprole has been shown to be safe and effective in treating specific infectious diseases such as bloodstream infections, acute bacterial skin and skin structure infections, and community-acquired bacterial pneumonia. Its use should be considered when targeting infections caused by methicillin-resistant S. aureus where other therapeutic options may be limited. However, additional real-world data on the efficacy of ceftobiprole should be continually monitored as experience in the US increases.

Identification of circulating Tfh/Th subsets as a biomarker of developed hospital-acquired pneumonia.

This study aimed to explore the possible value of follicular helper T (Tfh) cells in hospital-acquired pneumonia (HAP). Flow cytometry was used to measure circulating Tfh and helper T cell (Th) cells in 62 HAP patients and 16 healthy individuals. HAP patients were further categorized into uncontrolled and controlled groups, in accordance with relevant guidelines. Subgroup analyses were additionally conducted based on the pathogen and the presence of bloodstream infections (BSIs) and the incidence of septic shock. Kaplan-Meier survival analysis and ROC analysis were performed to estimate the prognostic value of the combination of Tfh/Th ratios and PCT levels. The Tfh/Th ratio was notably higher in uncontrolled HAP patients than in controls (P<0.05). Specifically, either the Klebsiella pneumoniae (K.p) -positive HAP or BSIs subgroups or septic shock subgroups showed significantly increased Tfh/Th ratios (P<0.05). PCT level in BSIs and septic shock subgroups was significantly increased. However, there were no significant differences in PCT level between K.p-infected and non-K.p-infected patients. So, the Tfh/Th ratio is a good supplement to PCT for distinguishing between the K.p and non-K.p groups. The Tfh/Th ratio also demonstrated a strong correlation with procalcitonin (PCT) levels (P<0.05). Accordingly, the combination of Tfh/Th and PCT could serve as a more effective predictive marker for HAP deterioration and survival prediction. HAP patients with a high Tfh/Th ratio along with high PCT levels had a lower 28-day survival rate. The circulating Tfh/Th ratio, instrumental in gauging the severity of patients with HAP, could be employed as a prognostic biomarker for HAP.

Semi-automated versus fully automated surveillance for non-ventilator hospital-acquired pneumonia: going for the gold when bronze is all there is.

Semi-automated versus fully automated surveillance for non-ventilator hospital-acquired pneumonia: going for the gold when bronze is all there is.

Minimum inhibitory concentrations of antibacterial drugs for Staphylococcus epidermidis strains isolated from the contents of the tracheobronchial tree of newborn children

Introduction. Over the past decades, outstanding progress has been made in caring for extremely premature infants and newborns with severe pathologies. Management of this vulnerable category of patients is associated with the continued risk of developing infectious pathology. In the structure of nosological forms, neonatal sepsis caused by coagulase-negative staphylococci occupies one of the leading positions. There is an increase in the number of antibiotic-resistant strains, including among Staphylococcus epidermidis, a typical representative of the normal microbiocenosis of human skin, so colonization of a premature newborn child who is at the stationary stage of nursing with it is a typical process.Objective. To study changes in the minimum inhibitory concentration of antibacterial drugs for Staphylococcus epidermidis strains isolated from the contents of the tracheobronchial tree of newborn children at the nursing stage in a hospital setting.Material and methods. To assess the statistical significance of the results obtained, the Chisquare test with Yates correction and the Mann-Whitney U test were used. Research results. All strains tested were resistant to cefoxitin. This, in turn, determines resistance to protected penicillins, amoxicillin clavulanate, ampicillin, sulbactam, and cephalosporins of I-IV generations. 44.4% and 87.5% of Staphylococcus epidermidis strains resistant to gentamicin were registered in 2022 and 87.5% in 2024.When comparing the MIC to gentamicin of Staphylococcus epidermidis isolated from TBD, a significant increase in indicators was established in 2024 compared to 2022 (Mann-Whitney U test is 7.5; p&lt;0.05). The proportion of clindamycin-resistant Staphylococcus epidermidis strains is 44.4% in 2022 and 12.5% in 2024 (p = 0.179). &gt; &lt; 0.05). The proportion of clindamycin-resistant Staphylococcus epidermidis strains is 44.4% in 2022 and 12.5% in 2024 (p = 0.179).Conclusion. Thus, the analysis of antibiotic resistance of staphylococci isolated during bacteriological examination of the contents of the tracheobronchial tree demonstrates an increase in the MIC of Staphylococcus epidermidis to gentamicin.The high therapeutic potential of vancomycin, a deep reserve antibiotic for the treatment of congenital and hospital-acquired pneumonia in premature newborns, remains high.