Optimal Antimicrobial Therapy Research Articles

Meningitis in Children: Still a Can't-Miss Diagnosis.

Although vaccination and antimicrobial treatment have significantly impacted the frequency and outcomes of meningitis in children, meningitis remains a critical can't-miss diagnosis for children, where early recognition and appropriate treatment can improve survival and neurologic outcomes. Signs and symptoms may be nonspecific, particularly in infants, and require a high index of suspicion to recognize potential meningitis and obtain the cerebrospinal fluid studies necessary for diagnosis. Understanding the pathogens associated with each age group and specific risk factors informs optimal empirical antimicrobial therapy. Early treatment and developmental support can significantly improve the survival rates and lifelong neurodevelopment of children with central nervous system infections.

Distribution of Nosocomial Pathogens and Antimicrobial Resistance among Patients with Burn Injuries in China: A Comprehensive Research Synopsis and Meta-Analysis.

Over the past decade, numerous studies have described the types of pathogens and their antibiotic resistance patterns in patients with burn injuries in China; however, the findings have generally been inconsistent. We conducted a literature search and meta-analysis to summarize the infection spectra and antimicrobial resistance patterns in patients with burn injuries. We searched the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, China Biomedical Literature, Wanfang, and Weipu databases for relevant articles published between January 2010 and December 2023. The DerSimonian-Laird random-effects model was used to estimate the proportions and 95% confidence intervals (CIs) of pathogens among Chinese patients with burn injuries. Meta-regression analyses were performed to explore differences in the proportions of pathogens among different subgroups and their resistance patterns. This study was registered with PROSPERO (CRD42024514386). The database searches yielded 2017 records; after removing duplicates and conducting initial screening, 219 articles underwent full-text screening. Ultimately, 60 studies comprising a total of 62,819 isolated strains reported the proportions of pathogens in patients with burn injuries and were included in this meta-analysis. Meta-analyses were conducted on 18 types of pathogens. The most common pathogens causing infections in Chinese patients with burn injuries were Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Staphylococcus epidermidis. Similar results were observed in the subgroup analysis focusing on wound infections. Since 2015, there has been a significant decrease in the proportion of Pseudomonas aeruginosa (R2 = 4.89%) and a significant increase in the proportion of Klebsiella pneumoniae (R2 = 9.60%). In terms of antibiotic resistance, there has been a significant decrease in the resistance of Staphylococcus aureus to multiple antibiotics and an increasing trend in the resistance of Klebsiella pneumoniae. We systematically summarized the epidemiological characteristics and antibiotic resistance patterns of pathogens among individuals suffering from burns in China, thus providing guidance for controlling wound infections and promoting optimal empirical antimicrobial therapy. The observed high levels of antibiotic resistance underscore the need for ongoing monitoring of antibiotic usage trends.

Culture-negative periprosthetic joint infections: Do we have an issue?

Culture-negative periprosthetic joint infection (PJI) poses a significant challenge in clinical settings. The lack of information on causative organism(s) leads to uncertainties regarding the choice of antimicrobial treatment, which can potentially adversely influence the outcome. Recent advances in molecular-based diagnostic methods have the potential to address the difficulties associated with culture-negative PJIs. These technologies offer a solution to the existing clinical dilemma by providing identification of pathogens and guiding appropriate antimicrobial treatment.In this narrative review, we provide information regarding: 1) incidence and risk factors for culture-negative PJI; 2) the optimal antimicrobial therapy and duration of treatment for culture-negative PJI; 3) outcome comparison between culture-positive and culture-negative PJI; and 4) utilization of novel molecular diagnostic methods in culture-negative PJI, including pathogen identification, and the implementation of an antibiotic stewardship program.

Microbiological diagnosis of pleural infections: a comparative evaluation of a novel syndromic real-time PCR panel.

Current microbial diagnostics for pleural infections are insufficient. Studies using 16S targeted next-generation sequencing report that only 10%-16% of bacteria present are cultured and that 50%-78% of pleural fluids containing relevant microbial DNA remain culture negative. As a rapid diagnostic alternative suitable for clinical laboratories, we wanted to explore a PCR-based approach. Based on the identification of key pathogens, we developed a syndromic PCR panel for community-acquired pleural infections (CAPIs). This was a pragmatic PCR panel, meaning that it was not designed for detecting all possibly involved bacterial species but for confirming the diagnosis of CAPI, and for detecting bacteria that might influence choice of antimicrobial treatment. We evaluated the PCR panel on 109 confirmed CAPIs previously characterized using culture and 16S targeted next-generation sequencing. The PCR secured the diagnosis of CAPI in 107/109 (98.2%) and detected all present pathogens in 69/109 (63.3%). Culture secured the diagnosis in 54/109 (49.5%) and detected all pathogens in 31/109 (28.4%). Corresponding results for 16S targeted next-generation sequencing were 109/109 (100%) and 98/109 (89.9%). For bacterial species included in the PCR panel, PCR had a sensitivity of 99.5% (184/185), culture of 21.6% (40/185), and 16S targeted next-generation sequencing of 92.4% (171/185). None of the bacterial species present not covered by the PCR panel were judged to impact antimicrobial therapy. A syndromic PCR panel represents a rapid and sensitive alternative to current diagnostic approaches for the microbiological diagnosis of CAPI.IMPORTANCEPleural empyema is a severe infection with high mortality and increasing incidence. Long hospital admissions and long courses of antimicrobial treatment drive healthcare and ecological costs. Current methods for microbiological diagnostics of pleural infections are inadequate. Recent studies using 16S targeted next-generation sequencing as a reference standard find culture to recover only 10%-16% of bacteria present and that 50%-78% of samples containing relevant bacterial DNA remain culture negative. To confirm the diagnosis of pleural infection and define optimal antimicrobial therapy while limiting unnecessary use of broad-spectrum antibiotics, there is a need for rapid and sensitive diagnostic approaches. PCR is a rapid method well suited for clinical laboratories. In this paper we show that a novel syndromic PCR panel can secure the diagnosis of pleural infection and detect all bacteria relevant for choice of antimicrobial treatment with a high sensitivity.

The clinical importance of metagenomic next-generation sequencing in detecting disease-causing microorganisms in cases of sepsis acquired in the community or hospital setting.

Although metagenomic next-generation sequencing (mNGS) is commonly used for diagnosing infectious diseases, clinicians face limited options due to the high costs that are not covered by basic medical insurance. The goal of this research is to challenge this bias through a thorough examination and evaluation of the clinical importance of mNGS in precisely identifying pathogenic microorganisms in cases of sepsis acquired in the community or in hospitals. A retrospective observational study took place at a tertiary teaching hospital in China from January to December 2021. Data on 308 sepsis patients were collected, and the performance of etiological examination was compared between mNGS and traditional culture method. Two hundred twenty-nine cases were observed in the community-acquired sepsis (CAS) group and 79 cases in the hospital-acquired sepsis (HAS) group. In comparison with conventional culture, mNGS showed a significantly higher rate of positivity in both the CAS group (88.21% vs. 25.76%, adj.P < 0.001) and the HAS group (87.34% vs. 44.30%, adj.P < 0.001), particularly across various infection sites and specimens, which were not influenced by factors like antibiotic exposure or the timing and frequency of mNGS technology. Sepsis pathogens detected by mNGS were broad, especially viruses, Mycobacterium tuberculosis, and atypical pathogens, with mixed pathogens being common, particularly bacterial-viral co-detection. Based on the optimization of antimicrobial therapy using mNGS, 58 patients underwent antibiotic de-escalation, two patients were switched to antiviral therapy, and 14 patients initiated treatment for tuberculosis, resulting in a reduction in antibiotic overuse but without significant impact on sepsis prognosis. The HAS group exhibited a critical condition, poor prognosis, high medical expenses, and variations in etiology, yet the mNGS results did not result in increased medical costs for either group. mNGS demonstrates efficacy in identifying multiple pathogens responsible for sepsis, with mixed pathogens of bacteria and viruses being prevalent. Variability in microbiological profiles among different infection setting underscores the importance of clinical vigilance. Therefore, the adoption of mNGS for microbiological diagnosis of sepsis warrants acknowledgment and promotion.

Rapid determination of antimicrobial susceptibility of Gram-negative bacteria from clinical blood cultures using a scattered light-integrated collection device.

Background. A bloodstream infection (BSI) presents a complex and serious health problem, a problem that is being exacerbated by increasing antimicrobial resistance (AMR).Gap Statement. The current turnaround times (TATs) for most antimicrobial susceptibility testing (AST) methods offer results retrospective of treatment decisions, and this limits the impact AST can have on antibiotic prescribing and patient care. Progress must be made towards rapid BSI diagnosis and AST to improve antimicrobial stewardship and reduce preventable deaths from BSIs. To support the successful implementation of rapid AST (rAST) in hospital settings, a rAST method that is affordable, is sustainable and offers comprehensive AMR detection is needed.Aim. To evaluate a scattered light-integrated collection (SLIC) device against standard of care (SOC) to determine whether SLIC could accelerate the current TATs with actionable, accurate rAST results for Gram-negative BSIs.Methods. Positive blood cultures from a tertiary referral hospital were studied prospectively. Flagged positive Gram-negative blood cultures were confirmed by Gram staining and analysed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, Vitek 2, disc diffusion (ceftriaxone susceptibility only) and an SLIC device. Susceptibility to a panel of five antibiotics, as defined by European Committee on Antimicrobial Susceptibility Testing breakpoints, was examined using SLIC.Results. A total of 505 bacterial-antimicrobial combinations were analysed. A categorical agreement of 95.5 % (482/505) was achieved between SLIC and SOC. The 23 discrepancies that occurred were further investigated by the broth microdilution method, with 10 AST results in agreement with SLIC and 13 in agreement with SOC. The mean time for AST was 10.53±0.46 h and 1.94±0.02 h for Vitek 2 and SLIC, respectively. SLIC saved 23.96±1.47 h from positive blood culture to AST result.Conclusion. SLIC has the capacity to provide accurate AST 1 day earlier from flagged positive blood cultures than SOC. This significant time saving could accelerate time to optimal antimicrobial therapy, improving antimicrobial stewardship and management of BSIs.

Efficacy of single antibiotic therapy versus antibiotic combination in implant-free staphylococcal post-surgical spinal infections: a retrospective observational study

BackgroundPost-surgical spinal infections (pSSIs) are a serious complication of spinal surgeries, with Staphylococcus spp. being one of the most prominent bacteria identified. Optimal antimicrobial therapy for staphylococcal spinal infections without spinal implants is not well documented.MethodsThis single center retrospective 7-year observational study described and compared the outcome (treatment failure or mortality rate one year after diagnosis) of 20 patients with staphylococcal-implant-free pSSI treated with single or combination antibiotics.ResultsMedian duration of treatment was 40 days (IQR 38–42), with 6 days (IQR 5–7) on intravenous antibiotics and 34 days (IQR 30–36) on oral therapy. Four patients (20%) underwent new surgical debridement, all due to surgical failure, and 1 patient died within the first year without significant differences between both treatment group.ConclusionThis study raises the possibility of single antibiotic therapy for patients with implant-free post-surgical spinal infections due to Staphylococcus spp.

The impact of implementation of rapid blood culture identification panels on antimicrobial optimization: a retrospective cohort study.

Determine the impact of limited implementation of a rapid blood culture identification (BCID) panel. Retrospective cohort study. From February to April 2022, positive blood cultures identified via e-Plex BCID (Roche, Carlsbad, CA) were compared to those identified using standard microbial identification techniques. The primary outcomes assessed were time to optimal therapy, time to de-escalation of anti-MRSA (methicillin-resistant Staphylococcus aureus) agents, and time to de-escalation of anti-pseudomonal agents. Additional analysis investigated the impact of the availability of antimicrobial stewardship program support. This study was conducted at Grady Health System, a large metropolitan safety-net hospital in the southeastern United States. A total of 253 blood cultures were included in this study (153 BCID and 100 standard). Blood culture identification use was associated with a reduction in median time to optimal antimicrobial therapy (43.4 vs 72.1 h, P < .001) and median time to de-escalation of anti-MRSA agents (27.7 vs 46.7 h, P = .006), and a trend towards reduction of median time to de-escalation of anti-pseudomonal agents (38.8 vs 54.8 h, P = .07). These reductions persisted when controlling for patient age, sex, intensive care unit status, Charlson Comorbidity Index, and antimicrobial stewardship program availability. Despite restricted use and lack of 24/7 antimicrobial stewardship program availability, BCID panel utilization was associated with earlier initiation of optimal therapy and pathogen identification with subsequent de-escalation of broad-spectrum antimicrobials, as compared to standard antimicrobial techniques. This suggests the potential for benefit from adopting novel diagnostic technologies outside of idealized fully-resourced settings.

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 &amp;lt; 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

Identification of microorganisms by a rapid PCR panel from positive blood cultures leads to faster optimal antimicrobial therapy – a before-after study

BackgroundThe BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) detects microorganisms with high accuracy in positive blood cultures (BC) – a key step in the management of patients with suspected bacteraemia. We aimed to compare the time to optimal antimicrobial therapy (OAT) for the BF-FA-BCIP vs. standard culture-based identification.MethodsIn this retrospective single-centre study with a before-after design, 386 positive BC cases with identification by BF-FA-BCIP were compared to 414 controls with culture-based identification. The primary endpoint was the time from BC sampling to OAT. Secondary endpoints were time to effective therapy, length of stay, (re-)admission to ICU, in-hospital and 30-day mortality. Outcomes were assessed using Cox proportional hazard models and logistic regressions.ResultsBaseline characteristics of included adult inpatients were comparable. Main sources of bacteraemia were urinary tract and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7%, for cases and controls, respectively). Median (95%CI) time to OAT was 25.5 (21.0–31.2) hours with BF-FA-BCIP compared to 45.7 (37.7–51.4) hours with culture-based identification. We observed no significant difference for secondary outcomes.ConclusionsRapid microorganism identification by BF-FA-BCIP was associated with a median 20-h earlier initiation of OAT in patients with positive BC. No impact on length of stay and mortality was noted.Trial registrationClinicaltrials.gov, NCT04156633, registered on November 5, 2019.

Impact of Rapid Molecular Diagnostic Technique on Time to Optimal Antimicrobial Therapy and Hospital Outcomes in Pediatric Cancer Patients with Sepsis.

sepsis is a leading cause of morbidity and mortality in pediatric cancer patients. We sought to assess the impact of using rapid molecular diagnostic techniques on time to pathogen identification, early administration of targeted antimicrobial treatment, and hospital outcomes. This prospective study was conducted at the Egyptian National Cancer Institute (1/2018-1/2019) on pediatric cancer patients with suspected sepsis. The cohort was divided into two groups. In one group, blood samples were sent for rapid molecular detection [multiplex-Polymerase Chain Reaction (PCR)] and blood cultures (PCR-group). While only blood cultures were collected for the second group (BC-group). In the entire cohort (n=120), the most common bacteria identified on blood cultures was Escherichia Coli (n=33,27.5%) followed by Klebsiella (n=31,25.8%). Multidrug-resistant bacteria were identified in 63 patients (52.5%). The median turnaround time to initial results was 5 hours in PCR-group (n=60), and 120 hours in BC-group (n=60)(P<0.001). For PCR-group, agreement in pathogen identification between the rapid molecular detection kit (PCR) and blood cultures was noted in 56 patients (93.3%). While the remaining four patients had no bacterial growth on blood cultures. The empirical antibiotic treatment for the PCR-group was modified based on the result of the PCR test. Antibiotic shift, based on blood culture sensitivity results, was done in 29 patients (48%) in PCR-group, compared to 45 patients (75%) in BC-group (P=0.003). Median sepsis episode duration [8-days vs. 10-days,P=0.361), and hospital mortality (42% vs. 50%, P=0.360) were slightly lower in PCR-group. However, this did not reach statistical significance. There was a substantial agreement in pathogen identification between the rapid molecular detection method (PCR) and blood culture results. PCR had a much shorter turnaround time, which allows for earlier start of optimal antimicrobial treatment, and might potentially improve hospital outcomes, which in turn will reduce associated health care costs.

Optimizing pharmacotherapy regimens in adult patients receiving extracorporeal membrane oxygenation: A narrative review for clinical pharmacists

AbstractExtracorporeal membrane oxygenation (ECMO) is a complex therapy aimed at providing mechanical support for patients with severe, life‐threating cardiac and/or respiratory failure. Research has demonstrated variability in pharmacokinetic changes in the critically ill patient population receiving ECMO. There is a need to understand the complexity of these pharmacokinetic changes to provide optimal pharmacotherapeutic regimens thereby maximizing effectiveness and mitigating harm. However, the number of pharmacokinetic studies in patients receiving ECMO remains small, and very few prospective studies have been published addressing optimal analgesic, sedative, or antimicrobial therapy. Anticoagulation is an additional important component of ECMO therapy but the preferred agent as well as dosing and monitoring strategy are unclear. The purpose of this narrative review is to discuss analgesia and sedation, antimicrobial, and anticoagulation management strategies in adult patients receiving ECMO.

195. Reducing Time to Optimal Antimicrobial Therapy (OAT) for Bloodstream Infections (BSI) due to Gram Positive Cocci (GPC) in Chains Using Rapid Diagnostics Paired with Antimicrobial Stewardship (ASP) Efforts

Abstract Background Rapid microbiology diagnostic results paired with immediate ASP intervention have been shown to decrease time to OAT and improve patient outcomes. For Gram positive (GP) BSI, studies have primarily focused on Staphylococci. However, the value of using rapid diagnostics for GPC in chains is not well studied. With the use of BioFire® FilmArray® Blood Culture Identification 2 (BCID2) to identify GPC in chains, we aimed to compare the time to OAT between pre- and post- implementation. Methods In May 2021, our institution implemented the use of BCID2 for GPC in chains, which detects 5 types of GPC in chains to the species level and the van A/B gene. Positive results were communicated in real time 24/7 to ASP who provided recommendations on OAT to the treatment team. A retrospective chart review compared the pre-implementation cohort (Jan - Sept 2019) to the post-implementation cohort (May 2021 - Jan 2022). The following patients were excluded from analysis: &amp;lt; 18 years of age, presence of polymicrobial infection or Streptococci with unidentified species by BCID2, discharged or deceased before rapid diagnostic result, on comfort measures or left against medical advice within 72 hours of result. The primary study endpoint was time to OAT which was defined as time from positive Gram stain to OAT. Secondary outcomes included percentage of ASP recommendations accepted, length of stay (LOS), and 30-day mortality. Results A total of 199 patients met inclusion criteria, 117 pre-cohort vs. 82 post-cohort. Baseline demographics were similar in both groups with the exception of the post-cohort having a numerically higher Charlson Comorbidity Index (Table 1). The most common sources of the bacteremias were intra-abdominal, skin and soft tissue, and endovascular (Table 2). The primary endpoint, average time to OAT, was 35 hours in the pre-cohort and 18 hours in the post-cohort with a difference of 16.8 hours (95% CI 9.8 – 23.8; p &amp;lt; 0.0001) (Table 3). ASP recommendations were accepted 91% of the time. The median LOS was 9 days (IQR 6 - 21) in the pre-cohort vs. 13 days (IQR 7-32) in the post-cohort (p = 0.07). The 30-day mortality rate was numerically lower in the pre-cohort (6.1% vs. 10.3%; p = 0.79). Conclusion For BSI due to GPC in chains, rapid diagnostics via BCID2 paired with 24/7 ASP led to markedly decreased time to OAT. Disclosures David Peaper, MD, Tangen Biosciences: Stocks/Bonds.

906. Impact of Accelerate Rapid Diagnostic Technology on Time to Optimal Antimicrobial Therapy in Gram Negative Bloodstream Infection

Abstract Background Previous studies at our institution evaluating rapid diagnostic testing (RDT) for blood culture identification (BCID) did not show significant differences in time to optimal antimicrobial therapy for Gram negative bloodstream infections (GNBSI). Recent studies of Accelerate Pheno® system (Accelerate-PS) for blood culture identification and susceptibility have shown significant reduction in time to optimal antimicrobial therapy. This study evaluated the impact of Accelerate-PS compared to BCID RDT on time to optimal antimicrobial therapy for GNBSI. Methods A single center, retrospective, cohort study included adult patients with GNBSI from February 2017 to January 2018 (pre-implementation) and February 2020 to January 2021 (post-implementation). The primary outcome was time to optimal antimicrobial therapy for GNBSI, defined as time from positive blood cultures to time patient received optimal antimicrobial therapy. Secondary outcomes include duration of therapy, rate of antimicrobial-related adverse effects, hospital length of stay, in-hospital mortality, and infection-related readmission. Results The final cohort included 190 patients in pre-implementation group and 179 patients in post-implementation group. Escherichia coli and Klebsiella species were the most common pathogens and urinary tract was the most common source of bacteremia in both groups. More patients in the pre-implementation group had congestive heart failure while more patients in the post-implementation group had peripheral vascular disease. Patients in the post-implementation group had higher Pitt bacteremia scores (1.05 vs. 1.37, P=0.017). Patients in the post-implementation group had significantly shorter time to optimal therapy (mean 60.62 hours vs. 20.17 hours, P&amp;lt; 0.001) and shorter duration of therapy (mean 366.56 vs 310.24 hours, P &amp;lt; 0.001) than in the pre-implementation group. There were no differences in mortality or readmission at 30-days. Conclusion The results of this study indicate that incorporation of Accelerate-PS into microbiology lab workflow significantly reduces time to optimal antimicrobial therapy for GNBSI. Rapid diagnostic testing is a vital component of a robust antimicrobial stewardship program. Disclosures John Schrank, MD, Gilead: Speaker's Bureau.

An Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Determination of 4 β-Lactam Antibiotics, Tazobactam, and Linezolid in Human Plasma Samples.

Optimization of antimicrobial therapy is a challenge in critically ill patients who develop extreme interindividual and intraindividual pharmacokinetic variability. Therapeutic drug monitoring is a valuable tool for maximizing the effect of a drug and minimizing its adverse and unwanted effects. The aim of the current work was to develop and validate an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine multiple antibiotics in clinical plasma samples from critically ill patients; low sample volume and rapid processing of samples were considered the main criteria. A separation method based on an online combination of UHPLC-MS/MS was developed for the simultaneous determination of 4 β-lactam antibiotics (cefepime, meropenem, cefotaxime, and piperacillin), tazobactam, and linezolid in human plasma samples. The volume of plasma sample used for analysis was 20 µL. The developed method was validated according to Food and Drug Administration guidelines. The chromatographic run time was 8 minutes. Calibration curves were linear for concentration ranges of 0.1-100 mcg/mL (r 2 > 0.99) for tazobactam, meropenem, cefotaxime, linezolid, and piperacillin and 1-100 mcg/mL (r 2 > 0.99) for cefepime. The intraday and interday accuracy of the method ranged from 92.4% to 110.7% and 93.6% to 113.3%, respectively. The intraday and interday precision values were ≤17.3% and ≤17.4%, respectively. No interfering and carryover analytes were observed. The developed UHPLC-MS/MS method is an appropriate and practical tool for therapeutic drug monitoring of the selected antibiotics. Owing to its rapidity, requirement of low sample volume, and high selectivity, sensitivity, and reliability, it can be effectively implemented in routine clinical laboratory tests for critically ill patients.

Knowledge, attitude, and perception of community pharmacists towards antimicrobial stewardship in Saudi Arabia: A descriptive cross-sectional study

BackgroundAntimicrobial resistance is of paramount concern globally. Community pharmacists (CPs) play a vital role in supporting judicious antimicrobial use in the community as they are the key healthcare providers at a public level. This study aimed to assess the knowledge, attitude, and perception of CPs towards antimicrobial stewardship at the community level in Saudi Arabia. MethodsA self-administered questionnaire was distributed to all community pharmacies in four major cities of Saudi Arabia. A simple random sampling approach was used to select pharmacies in each chain. ResultsA total of 520 CPs responded to the survey with a response rate of 98.6 %. Most of the pharmacists (n = 479, 92.1 %) accepted that antimicrobial stewardship programs are essential tools to limit injudicious usage of antimicrobials at the community level. Interestingly, very few (n = 105, 21 %) agreed to recommend antibiotics for common illnesses, including upper respiratory tract infections, cold, and flu without a valid prescription. Further, we found a significant role of Saudi health authorities, e.g., Saudi food & drug authorities and the Ministry of Health, in restricting antimicrobials sale in community pharmacies without a valid prescription. ConclusionOur study findings revealed that CPs had good knowledge about antimicrobial stewardship in Saudi Arabia. The CPs play an active role in the optimization of antimicrobial therapy and infections caused by different microbes. Strict policies by the Saudi health care authority regarding the restricted dispensing of antimicrobials are welcomed by the CPs and thus may contribute toward lowering of antimicrobial resistance burden on the patients and Saudi health care authorities.

Getting With the Times: A Review of Peripartum Infections and Proposed Modernized Treatment Regimens

This article provides a review of peripartum infections, including intra-amniotic infection, postpartum endometritis, and postabortal infections. We present a case of postabortal infection to frame the review. The microbiology, pathogenesis, risk factors, diagnosis, and treatment of peripartum infections are reviewed, and a critical appraisal of the literature and available guidelines is provided. There is a focus on discussing optimal antimicrobial therapy for treating these infections.

#23 Clinical Outcomes with Rapid Gram-Positive Blood Culture Identification in an Academic Pediatric Hospital

Abstract Background BACKGROUND Delays in initiating appropriate antibiotics increases mortality, length of stay, and overall admissions costs in patients with bloodstream infections. Adult studies using rapid diagnostic tests such as the GenMark’s e-Plex Blood Culture Identification (BCID) Panels coupled with Antimicrobial Stewardship Program (ASP) interventions have led to reductions in each of these metrics. Similar data assessing use in the pediatric population are generally lacking. The primary aim of this study was to assess the impact of the GenMark Blood Culture Identification Gram Positive panel (BCID-GP panel) on the time to optimal antimicrobial therapy (OAT) in pediatric patients with positive blood cultures growing gram-positive bacteria (GPB). Method METHOD A 2-year Quality Improvement study of admitted pediatric patients was carried out at UPMC Children’s Hospital of Pittsburgh (CHP) between June 25, 2019 and June 26, 2021. Pre-intervention data (6/25/19 – 6/25/20) was collected retrospectively from the CHP Electronic Medical Record (EMR). During the post-intervention time-period (6/26/20 - 6/26/21), BCID-GP panel was run daily from 6AM to 10 PM on blood cultures with Gram stains revealing GPB. Results were provided to the ASP who generated recommendations and communicated them to the patient’s primary team after reviewing the EMR using a pre-determined algorithm. Statistical analyses were performed using Wilcoxon rank sum test and Chi-squared tests. Results RESULTS 317 and 265 blood cultures with GPB were evaluated in the pre- and post-intervention groups, with median ages of 2.26 and 3.2 years in the 2 groups, respectively. Overall panel accuracy was 97% with gene accuracy of 100%. Percent compliance with ASP recommendations within 12 hours was 89%. The median time to OAT was 48 (range of 0-175), and 33.1 hours (range 0-165) in the pre- and post-intervention groups, respectively (p &amp;lt;0.001). The median time to OAT for patients with MSSA decreased from 65 to 30.5 hours (p &amp;lt;0.001), and 37 to 20 hours (p 0.048) for those with MRSA. Antibacterial therapy was avoided in 42.2% of patients in the post-intervention group when results were interpreted as contaminants, compared with 23.4% in the pre-intervention group with this assessment (p = 0.008). Length of stay and 30-day mortality was similar between groups, 6.1 days vs 6.9 days (p = 0.23) and 3.5% vs 3.4%, (p = 1.00) respectively. Conclusion CONCLUSION Use of BCID-GP panel significantly decreased the time to OAT and avoided initiation of antibiotics in incidences of contamination in our study population. This was also true for positive blood cultures due to MSSA and MRSA. However, significant differences in the length of stay or 30-day mortality were not identified between groups. We did find the overall accuracy, defined as the percentage of BCID panels detected targets confirmed by conventional laboratory culture and gene accuracy, defined as the percent of BCID panels with results detected confirmed by conventional laboratory susceptibility methods, of the panel mirrored with previously published data. We also found ASP recommendations based on the BCID-GP were followed 89% of the time within 12 hours of them being made.

A Diagnostic Stewardship Intervention that Optimizes CNS Infection Management

The introduction of molecular testing has led to more rapid diagnosis and optimization of treatment in the field of infectious diseases. In this volume of The Journal, Messacar et al used a diagnostic stewardship approach to address the role of the FilmArray® Meningitis Encephalitis Panel (MEP), a multiplex CSF PCR, in children with suspected central nervous system infection. After the implementation of pre-test criteria and real-time assistance from an infectious diseases specialist, they found that the use of MEP significantly reduced the time to optimal antimicrobial therapy (28 vs.

Optimal empirical antimicrobial therapy in infective endocarditis.

The case report of left-sided infective endocarditis (IE) in intravenous drug use (IDU) reminds the importance of recognizing peripheral stigmata of IE with subsequent immediate aggressive management.1 However, the management of this patient, including inappropriate the choice of empirical antibiotics and no consideration of valve surgery (given large size of vegetation and systemic embolization), does not seem appropriate. The current literature recommends empirical antimicrobial coverage of methicillin-resistant Staphylococcus aureus (MRSA) and potentially antibiotic-resistant Gram-negative bacilli (including Pseudomonas spp.) in IDU-IE.2–4 A combination of vancomycin plus gentamicin or cefepime covers these bacteria and other potential agents pending culture results.2,3 MRSA, the commonest cause of both right- and left-sided IDU-IE, was not covered in the index case report before the blood cultures were obtained.2–5 Our large IE study, published from the same center (Postgraduate Institute of Medical Education and Research, Chandigarh), also supports the combination of vancomycin and gentamicin for empirical treatment in IDU-IE.6