Antibiotic Treatment Strategies Research Articles

Prevalence and Antibiogram of Escherichia coli Isolated from Children Under Five Years of Age Presented with Acute Diarrhoea: Cross Sectional Study from a Tertiary Care Centre in South India

Aim: The study aimed to analyze the prevalence and antibiogram of E. coli isolated from stool sample cultures collected from children below five years of age who were presented with acute diarrhoea in a tertiary care centre. Background: Multidrug-resistant strains of diarrheagenic E. coliremain a major public health concern for greater morbidity and mortality. Antibiotic resistance and susceptibility patterns of E. coli were found to vary with geographical location. Objective: To determine the prevalence and antibiogram of E. coli isolated from cultures of diarrhoea stool samples collected from children below five years of age from laboratory records. Methods: A cross-sectional study was designed to analyze the report on stool culture of children (aged below five years) presented with acute diarrhea during the period between 2017 and 2020. The prevalence of E. coli and its antibiogram were analyzed. The data were subjected to statis-tical analysis. Results: A total of 245 diarrhoea stool samples results were analyzed. E. coli was confirmed in 176 samples (72%). More number of isolates (51/176, 28.9%) were found in children below one year of age with male dominance. Amoxicillin resistance was found in all the E. coli strains isolated with no significant difference (p=0.2233) between genders and age groups below and above one year. A significant difference (p=0.0001) was found between male and female chil-dren of age below and above one year for cefotaxime and ciprofloxacin resistance. Polymyxin B (72%) followed by imipenem (69%) sensitivity was exhibited by the isolated E. coli strains. Conclusion: E. coli isolates were more sensitive to polymyxin B and imipenem while they were most resistant to amoxicillin. Effective antibiotic treatment strategies should be developed to control E. coli infections in children.

Triggerable biomaterials‐based osteomyelitis theranostics

AbstractThe emergence of multidrug‐resistant bacteria poses a significant challenge in the treatment of osteomyelitis, rendering traditional antibiotic treatment strategies inadequate in terms of achieving a complete cure. In recent years, triggerable biomaterial‐based, antibiotic‐free osteomyelitis treatment strategies have rapidly evolved, demonstrating excellent bactericidal effects. Triggerable biomaterials‐based osteomyelitis theranostics encompass physical signal response strategies and host immune modulation approaches. These strategies can be effective against drug‐resistant bacteria, circumventing the gradual acquisition of resistance that often accompanies traditional antibiotic treatment. Additionally, the inherent physical properties of the triggerable biomaterials facilitate the precise imaging of osteomyelitis. There is no doubt that triggerable biomaterial‐mediated, antibiotic‐free therapies are emerging as a trend, which is critically important in combating multidrug‐resistant bacteria‐induced osteomyelitis. In this review, we summarize the latest advances in osteomyelitis treatment strategies from both pathogen‐directed and host‐directed perspectives. The design regimens and specific action mechanisms of triggerable biomaterial‐based nanoplatforms are also clarified. Finally, we outline the challenges faced by various antibiotic‐free therapies and provide an outlook on the prospects for synergistic interactions.

Microbiota-Based Live Biotherapeutic Products for Clostridioides Difficile Infection- The Devil is in the Details.

Clostridioides difficile infection (CDI) remains a significant contributor to healthcare costs and morbidity due to high rates of recurrence. Currently, available antibiotic treatment strategies further disrupt the fecal microbiome and do not address the alterations in commensal flora (dysbiosis) that set the stage for CDI. Advances in microbiome-based research have resulted in the development of new agents, classified as live biotherapeutic products (LBPs), for preventing recurrent CDI (rCDI) by restoring eubiosis. Prior to the LBPs, fecal microbiota transplantation (FMT) was available for this purpose; however, lack of large-scale availability and safety concerns have remained barriers to its widespread use. The LBPs are an exciting development, but questions remain. Some are derived directly from human stool while other developmental products contain a defined microbial consortium manufactured ex vivo, and they may be composed of either living bacteria or their spores, making it difficult to compare members of this heterogenous drug class to one another. None have been studied head-to head or against FMT in preventing rCDI. As a class, they have considerable variability in their biologic composition, biopharmaceutic science, route of administration, stages of development, and clinical trial data. This review will start by explaining the role of dysbiosis in CDI, then give the details of the biopharmaceutical components for the LBPs which are approved or in development including how they differ from FMT and from one another. We then discuss the clinical trials of the LBPs currently approved for rCDI and end with the future clinical directions of LBPs beyond C. difficile.

Considering kidney stones and the bidirectional relationship between nephrolithiasis and urinary Tract Infection (UTIs): a systematic review of the literature on cause and effect

Urinary tract infections (UTIs) and kidney stones also known as nephrolithiasis, it have complicated and reciprocal interaction that makes both conditions worse. We conducted an extensive study to ascertain the connection between “kidney stone disease (KSD)” and recurrent “Urinary Tract Infection (UTIs)”, as well as to evaluate the impact of kidney stone treatment on UTI resolution. We found that there is a strong correlation between KSD and UTI in several studies after evaluating 15 publications. Though the technique resolves UTIs, there is conflicting information about the likelihood of recurrence following kidney stone removal surgery. Our understanding of the potential role of bacteria in the genesis of "metabolic" stones can improve with the aid of vitro research. Our study shows that KSD and UTIs coexist and have an influence on one another. Consequently, individuals with a history of urinary tract infections (UTIs) or other risk factors can be advised to pursue prophylactic measures such kidney stone removal, regardless of the kind of stone. A stone culture test should be conducted to determine the specific bacteria causing the UTI to reduce the likelihood of recurring episodes and to enable more precise and effective antibiotic treatment strategy.

Clostridioides difficile Infection: Diagnosis and Treatment Challenges.

Clostridioides difficile is the most important cause of healthcare-associated diarrhea in the United States. The high incidence and recurrence rates of C. difficile infection (CDI), associated with high morbidity and mortality, pose a public health challenge. Although antibiotics targeting C. difficile bacteria are the first treatment choice, antibiotics also disrupt the indigenous gut flora and, therefore, create an environment that is favorable for recurrent CDI. The challenge of treating CDI is further exacerbated by the rise of antibiotic-resistant strains of C. difficile, placing it among the top five most urgent antibiotic resistance threats in the USA. The evolution of antibiotic resistance in C. difficile involves the acquisition of new resistance mechanisms, which can be shared among various bacterial species and different C. difficile strains within clinical and community settings. This review provides a summary of commonly used diagnostic tests and antibiotic treatment strategies for CDI. In addition, it discusses antibiotic treatment and its resistance mechanisms. This review aims to enhance our current understanding and pinpoint knowledge gaps in antimicrobial resistance mechanisms in C. difficile, with an emphasis on CDI therapies.

Deciphering complex antibiotic resistance patterns in Helicobacter pylori through whole genome sequencing and machine learning.

Helicobacter pylori (H.pylori, Hp) affects billions of people worldwide. However, the emerging resistance of Hp to antibiotics challenges the effectiveness of current treatments. Investigating the genotype-phenotype connection for Hp using next-generation sequencing could enhance our understanding of this resistance. In this study, we analyzed 52 Hp strains collected from various hospitals. The susceptibility of these strains to five antibiotics was assessed using the agar dilution assay. Whole-genome sequencing was then performed to screen the antimicrobial resistance (AMR) genotypes of these Hp strains. To model the relationship between drug resistance and genotype, we employed univariate statistical tests, unsupervised machine learning, and supervised machine learning techniques, including the development of support vector machine models. Our models for predicting Amoxicillin resistance demonstrated 66% sensitivity and 100% specificity, while those for Clarithromycin resistance showed 100% sensitivity and 100% specificity. These results outperformed the known resistance sites for Amoxicillin (A1834G) and Clarithromycin (A2147), which had sensitivities of 22.2% and 87%, and specificities of 100% and 96%, respectively. Our study demonstrates that predictive modeling using supervised learning algorithms with feature selection can yield diagnostic models with higher predictive power compared to models relying on single single-nucleotide polymorphism (SNP) sites. This approach significantly contributes to enhancing the precision and effectiveness of antibiotic treatment strategies for Hp infections. The application of whole-genome sequencing for Hp presents a promising pathway for advancing personalized medicine in this context.

Natural Experiments as a Study Method in Spinal Trauma Surgery: A Systematic Review.

Systematic review. To determine if the natural experiment design is a useful research methodology concept in spinal trauma care, and to determine if this methodology can be a viable alternative when randomized controlled trials are either infeasible or unethical. A Medline, Embase and Cochrane database search was performed between 2004 and 2023 for studies comparing different treatment modalities of spinal trauma. All observational studies with a natural experiment design comparing different treatment modalities of spinal trauma were included. Data extraction and quality assessment with the MINORS criteria was performed. Four studies with a natural experiment design regarding patients with traumatic spinal fractures were included. All studies were retrospective, one study collected follow-up data prospectively. Three studies compared different operative treatment modalities, whereas one study compared different antibiotic treatment strategies. Two studies compared preferred treatment modalities between expertise centers, one study between departments (neuro- and orthopedic surgery) and one amongst surgeons. For the included retrospective studies, MINORS scores (maximum score 18) were high ranging from 12-17 and with a mean (SD) of 14.6 (1.63). Since 2004 only four studies using a natural experiment design have been conducted in spinal trauma. In the included studies, comparability of patient groups was high emphasizing the potential of natural experiments in spinal trauma research. Natural experiments design should be considered more frequently in future research in spinal trauma as they may help to address difficult clinical problems when RCT's are infeasible or unethical.

Effect of early antibiotic treatment strategy on prognosis of acute pancreatitis

BackgroundAntibiotic use in the early stages of acute pancreatitis is controversial. The purpose of this study was to investigate the effect of early antibiotic application on the prognosis of acute pancreatitis (AP).Materials and methodsClinical data of patients with primary AP admitted to our emergency ward within 72 hours of onset were retrospectively collected from January 2016 to December 2020. We classified patients with acute pancreatitis according to etiology and disease severity, and compared the differences in hospital stay, laparotomy rate, and in-hospital mortality among AP patients who received different antibiotic treatment strategies within 72 hours of onset.ResultsA total of 1134 cases were included, with 681 (60.1%) receiving early antibiotic treatment and 453 (39.9%) not receiving it. There were no significant differences in baseline values and outcomes between the two groups. In subgroup analysis, patients with biliary severe acute pancreatitis (SAP) who received early antibiotics had lower rates of laparotomy and invasive mechanical ventilation, as well as shorter hospital stays compared to those who did not receive antibiotics. In logistic regression analysis, the early administration of carbapenem antibiotics in biliary SAP patients was associated with a lower in-hospital mortality rate. Early antibiotic use in biliary moderate-severe acute pancreatitis (MSAP) reduced hospital stays and in-hospital mortality. Quinolone combined with metronidazole treatment in biliary mild acute pancreatitis (MAP) shortened hospital stays. Early antibiotic use does not benefit patients with non-biliary AP.ConclusionStrategies for antibiotic use in the early stages of AP need to be stratified according to cause and disease severity.

PP118 The Value Of New Antibiotic Treatment Strategies In Zhejiang Province, China

IntroductionThe rising antimicrobial resistance (AMR) and the difficulty in developing new antibiotics are causing a global public health problem. This analysis aims to better understand the clinical and economic value of new antibiotic treatment strategies, in order to inform clinical and antibiotic formulary decisions.MethodsWe applied a published and validated dynamic disease transmission and cost-effectiveness model of AMR with a 10-year time horizon and discount rate of five percent to evaluate the clinical and economic outcomes of introducing a new antibiotic, namely, Ceftazidime/Avibactam (CAZ-AVI) for treating AMR infections in Zhejiang Province, China. Together with piperacillin-tazobactam (pip/taz) and meropenem, we explored the impact of six treatment strategies across three common infections (complicated intra-abdominal infection (cIAI), hospital-acquired/ventilator-associated pneumonia (HAP/VAP) and infections with limited treatment options (LTO)), and pathogens (Escherichia coli, Klebsiella spp., and Pseudomonas aeruginosa). These treatment strategies included (i) current treatment strategy (pip/taz and meropenem, no CAZ-AVI), (ii) CAZ-AVI at the third line, (iii) CAZ-AVI at the second line, (iv) CAZ-AVI at the first line, (v) first line diversity (i.e., equal pip/taz and CAZ-AVI at the first line; meropenem at the last line) and (vi) all-lines diversity (pip/taz, meropenem and CAZ-AVI used randomly and only once). The data with a total of 10,905 patients were collected from a tier-3 hospital from 2018 to 2021.ResultsUnder the current treatment strategy, the hospital length of stay (LOS) and costs over ten years were estimated to be 1,588,763 days and CNY3,898,198,802 (USD559,781,348), respectively, associated with 142,999 quality-adjusted life-years (QALYs) lost, resulting in the resistance of pip/taz and meropenem being 42.0 percent and 49.9 percent respectively. In contrast, the other five treatment strategies all have shown improved outcomes, among which the “all-lines diversity” carried the greatest benefit, saving CNY1,646.04 (USD236.37) for each additional QALY gained, with the net monetary benefit being CNY24,727,102,215 (USD3,550,811,878).ConclusionsIntroducing CAZ-AVI had positive impact on clinical and economic outcomes for treating AMR, and diversifying early the antibiotics might yield the best benefits.

Empiric antibiotic treatment for periprosthetic joint infections: a national survey in The Netherlands.

Early periprosthetic joint infection (PJI) is generally treated by means of debridement, antibiotics and implant retention (DAIR). Subsequently, empiric antibiotic therapy is commenced directly after surgery which is important for the successful treatment of PJI. The aim of this study is to evaluate current nationwide empiric antibiotic treatment regimens for PJI in the Netherlands. An electronic 15-question survey addressing the empiric antibiotic treatment strategy for PJI following THA or TKA was sent to orthopaedic surgeons in all Dutch hospitals in April 2019. Orthopaedic surgeons active in every single Dutch orthopaedic hospital (n=69) were approached. At least one surgeon in every hospital completed the survey (100% response rate). A protocol dictating the empiric antibiotic treatment following DAIR was used in 87% (60 hospitals). Among all hospitals, 72% (50 hospitals) used antibiotic monotherapy and 28% (19 hospitals) used combination therapy. Cefazolin was the most commonly used regimen in centres opting for monotherapy (42%, 29 hospitals). Similar regimens were used for the empiric treatment of suspected early PJI after revision surgery and for acute hematogenous PJI. In septic patients, combination therapy was preferred (64%). 81% (56 hospitals) incubated tissue biopsies for a minimum of 10 days whereas 16% (9 hospitals) indicated an incubation period of 7 days or less. Even in a small country such as the Netherlands there seems to be no uniformity regarding empiric antibiotic treatment for PJI. Increased uniformity regarding empiric treatment could be an important first step in improving PJI treatment.

Mortality Risk and the Clinical Outcome of Carbapenem-Resistant Enterobacteriaceae Carriers with Neutropenia: A Matched Case-Control Study

Patients with hematologic diseases are often accompanied by immunodeficiency, treatments as well as the disease itself can lead to granulocyte deficiency. Patients with granulocyte deficiency are under the high risk of infection. In recent years, the rate of Carbapenem-resistant Enterobacteriaceae (CRE) infection has gradually increased. Treatment options of CRE infection is limited, and effective anti-infection treatment is usually delayed, leading to the death of patients due to infection. CRE screening can provide clinical evidence for early detection of CRE by clinicians, thereby formulating antimicrobial treatment strategies. However, whether the initial empirical treatment covering CRE can improve the adverse outcomes of patients still lacks a definitive conclusion. We collected clinical data on patients with neutropenia who also undergoing CRE screening between January 2017 and December 2022. To further analyze the impact of CRE positivity on patient mortality risk and the clinical effectiveness of initial empirical treatment for CRE, we conducted two case-cohort studies with clinical baseline data matching. In total, we performed 3529 fecal CRE screenings from 664 patients. Out of these, 345 screenings from 135 patients tested positive for CRE. We identified 16 different strains, with the most common being Klebsiella pneumoniae (184/345), followed by Escherichia coli (76/345). To determine the influence of CRE positivity on patient mortality rates, we conducted a 1:2 case matching based on age, gender, diagnosis, and medical history of CRE-positive patients (Table 1). The results showed that in the overall analysis, CRE positivity, age over 60, and male gender were adverse factors influencing mortality. However, in the subgroup analysis of CRE-positive patients, no adverse factors affecting mortality were observed. To further assess the impact of CRE positivity on patient infection outcomes, we defined the initial antibiotic treatment strategies for a total of 4,872 infection events in screened patients. We divided them into the following groups: the empirical treatment group without CRE results (n=3,954), the empirical treatment group not covering CRE (n=122), and the CRE based empirical treatment group (n=796). The CRE based empirical treatment group had a higher success rate in initial empirical treatment compared to the group without covering CRE (65.5% vs. 59.0%). To further investigate the differences in initial empirical treatment success rates and 30-day mortality rates between patients in the CRE-based empirical treatment group and empirical treatment group without CRE covering, we performed 1:2 case matching for clinical baseline data on age, sex, diagnosis, past history, and disease status at infection according to the clinical characteristics of the CRE-based anti-infection treatment group. The results indicated that there were no significant differences in initial empirical treatment success rate and 30-day mortality rate between the CRE-based empirical treatment group and case-matched controls. In conclusion, diagnosing and treating patients with CRE infection presents significant challenges. Early screening for CRE and empirical treatment targeting CRE can increase the success rate of initial empirical treatment in CRE-positive patients.

168 Characterization of the Culturable Fraction of Bovine Ocular Microbiota and Its in Vitro Antimicrobial Activities Against Pinkeye Pathogens

Abstract Pinkeye, clinically known as infectious bovine keratoconjunctivitis (IBK), is considered one of the most important ocular diseases in cattle, causing an estimated $226 million in annual losses to U.S. cow-calf producers. While Moraxella bovis is considered the principal IBK pathogen, Moraxella bovoculi has also been associated with the pathogenesis of IBK. Thus, these Moraxella species are often the target for antibiotic and/or vaccine-based treatment and prevention strategies. Despite extensive use of antibiotics, IBK infections are challenging to treat, highlighting the increased need for an antibiotic-alternative approach to control IBK. Recent evidence suggests that the microbial community associated with the bovine oculus is important for eye health, and that the ocular microbiota can be a target for enhancing disease resistance against IBK in cattle. The objectives of this study were to characterize the ocular microbiota of healthy and IBK infected cattle using sequencing and culturing techniques, and to isolate and screen commensal ocular isolates for their antimicrobial activity against M. bovis and M. bovoculi. Ocular swabs (n = 64) were collected using eSwabs from cattle diagnosed with IBK or without IBK (healthy control) before antibiotic treatment from beef herds across North Dakota. Swabs were plated onto four different agar plates (blood, Columbia blood, MRS and multi-sliced agar plates), and cultured aerobically and anaerobically. A total of 658 bacterial isolates were obtained via culturing and cryopreserved. Taxonomic identification was performed on a subset of banked isolates (n = 277) by near full-length sequencing of the 16S rRNA gene. These isolates taxonomically belong to 6 different bacterial phyla: Bacillus (42%), Firmicutes (27%), Actinomycetota (13%), Pseudomonadota (11%), Actinobacteria (5%), and Proteobacteria (2%). A total of 55 different genera were identified with Bacillus (25%), Streptococcus (13%), Staphylococcus (10%), Moraxella (6%), Macrococcus (5%), Paenibacillus (3%), Caldibacillus (3%), and Rummeliibacillus (3%) being the most dominant genera. Next, a subset of these commensal isolates (n 53) were screened for their growth inhibition against M. bovis and M. bovoculi using an agar slab method. Among the screened isolates, 6 isolates showed inhibition against M. bovis and M. bovoculi with zones of inhibition ranging from 12 mm to 28 mm. Ocular isolates identified as Weizmannia coagulans (43Y-MRSC), Lentillactobacillus buchneri (23D-MRSA) and Paenibacillus polymyxa (785-WCF) exhibited relatively strong inhibition against both Moraxella isolates. Scanning electron microscopy revealed noticeable structural and morphological damages in M. bovis and M. bovoculi cells due to Weizmannia coagulans culture-supernatant treatment. Overall, our results indicate that ocular mucosa of beef cattle is inhabited by relatively rich and diverse culturable bacterial communities, and that some ocular commensals can inhibit IBK pathogens. This suggests the potential for the development of bacterial therapeutics based on commensal ocular bacteria to mitigate IBK in cattle.

Efficacy of Intravenous Colistin Monotherapy Versus Colistin Combined With Meropenem in Patients With Multidrug-Resistant Infections: A Retrospective Observational Study.

Background Intensive care units frequently contend with infections caused by highly drug-resistant organisms, particularly Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacterales (CRE), which often lead to high mortality rates. Colistin (colomycin) is employed to treat infections, notably extremely drug-resistant (XDR) bacteria. Antibiotic combination treatment is a frequently used tactic in this endeavour. However, the widespread use of antibiotics in synergy could result in the emergence of resistance and a rise in side effects, such as those linked to Clostridium difficile infection. The aim of the study was to assess and contrast the clinical results of intravenous colistin monotherapy with the combination of colistin and meropenem in patients experiencing MDR bacteremia resulting from Acinetobacter Baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacterales (CRE). Methods In this retrospective observational study, an analysis spanning two years, from June 2021 to June 2023, was conducted at a teaching hospital located in Karachi, Pakistan. The research involved the retrospective examination of medical records from 132 patients who had been diagnosed with MDR bacteremia. Patients were divided into two categories based on their treatment regimen, either intravenous colistin monotherapy or intravenous colistin combined with meropenem. Among the 132 patients included in the analysis, 66 underwent colistin monotherapy, while the other 66 received a combination of colistin and meropenem. The primary focus of evaluation in this study centered on the 14-day all-cause mortality, while secondary outcomes encompassed clinical success and microbiologic cure. Results The mean age of patients in both groups was comparable, and there were no noteworthy gender differences. Additionally, the distribution of infection types and the isolated pathogens showed no substantial distinctions between the two groups. The study revealed no statistically significant disparities in 14-day mortality, improvement in Sequential Organ Failure Assessment (SOFA) score, or the proportion of patients who were cured and survived between the two treatment groups. Conclusion The findings from this study lead to the conclusion that there exists no significant disparity in the efficacy of colistin monotherapy compared to the combination of colistin with meropenem in the treatment of MDR bacteremia stemming from Acinetobacter Baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacterales (CRE). The results provide a basis for future research and underscore the significance of ongoing endeavors to refine antibiotic treatment strategies in response to the worldwide issue of antibiotic resistance.

The use of non-invasive stool tests for verification of Helicobacter pylori eradication and clarithromycin resistance.

Clarithromycin resistance of Helicobacter pylori (H. pylori) represents a major challenge in eradication therapy. In this study, we assessed if non-invasive stool tests can be used to verify successful H. pylori eradication and determine clarithromycin resistance. In this prospective study, patients undergoing urea breath testing (UBT) for confirmation of H. pylori eradication were asked to collect the stool as both a dry fecal sample and fecal immunochemical test (FIT). Stool H. pylori antigen testing (SAT) was performed on these samples and assessed for its accuracy in eradication verification. Type and duration of antibiotic treatment were retrospectively collected from patient records and compared with clarithromycin resistance determined by PCR of stool samples. H. pylori eradication information was available for a total of 145 patients (42.7% male, median age: 51.2). Successful eradication was achieved in 68.1% of patients. SAT on FIT samples had similar accuracy for eradication assessment compared to dry fecal samples, 72.1% [95% CI 61.4-81.2] versus 72.2% [95% CI 60.9-81.7]. Clarithromycin resistance rate was 13.4%. H. pylori antigen testing on FIT stool samples to verify H. pylori eradication is feasible and has similar accuracy as H. pylori antigen testing on dry stool samples. Dry stool, but not FIT, was suitable for non-invasive identification of H. pylori clarithromycin resistance by rt-PCR personalizing antibiotic treatment strategies without the need for invasive diagnostics is desirable, as the cure rate of first-line empirical H. pylori treatment remains low.

Supporting Clinical Decisions with Rapid Molecular Diagnostic Pneumonia Panel in Pediatric Intensive Care Unit: Single Center Experience in Turkiye.

Lower respiratory tract infections are the leading cause of morbidity and mortality in children worldwide. It is crucial to promptly conduct diagnostic investigations in order to determine the microbiological cause of pneumonia, since this is necessary to ensure the appropriate delivery of antibiotic therapy to each individual patient. We evaluated the results of a rapid molecular diagnostic pneumonia panel in children with LRTI in a pediatric intensive care unit (PICU). Rapid molecular diagnostic pneumonia panel (BioFire®, FilmArray Pneumonia Panel plus; FA-PP) findings (71 results from 46 children) in a tertiary care PICU between 2019 and 2023 were retrospectively reviewed. At least one bacterial pathogen was detected in 57 cases. A total of 77% of children had underlying conditions. A total of 70.4% of children needed invasive mechanical ventilation and 54.4% had ventilator-associated pneumonia. Pseudomonas aeruginosa (50.8%), Acinetobacter calcoaceticus baumannii complex (42%), and Klebsiella pneumoniae (38.6%) were the most common pathogens detected with the FA-PP. Of the 33 cases diagnosed with VAP, more than one pathogen was identified in 65.9% of cases, with the most commonly identified bacteria being K. pneumoniae (43.1%), P. aeruginosa (38.6%), and Acinetobacter calcoaceticus baumannii complex (31.8%). According to the FA-PP results, the same antibiotic therapy was continued in 39.4% of cases, escalated in 54.5%, and de-escalated in 6.1%. The utilization of the FA-PP has some beneficial effects, including more prompt delivery of findings compared to conventional approaches. Additionally, this approach enables the identification of resistance profiles in children diagnosed with pneumonia in the PICU. Consequently, these test results facilitate the organization of antibiotic treatment strategies, including escalation and de-escalation approaches. The detection of resistance patterns was exclusively determined via the implementation of molecular testing, prompting a reevaluation of the isolation technique in accordance with the obtained data.

SP8.11 The EXTEND trial: EXTENDed antibiotics to improve outcomes in patients with complicated Intra-Abdominal Infection (cIAI)

Abstract Introduction Complicated intra-abdominal infections (cIAI) pose a major challenge in surgical patients. Despite the heterogenous aetiology they have a common disease process, which is bacterial infection of the peritoneal space. Hence, all cIAIs are managed with source control, plus antibiotic therapy. However, there is uncertainty regarding the optimal antibiotic treatment strategy in order to prevent relapse or extra-abdominal spread of infection1. At present, there is no UK guidance on the management of cIAIs2. For other serious infections outside the abdomen microbiologists often advise at least 28-days of antibiotic therapy. Currently the effectiveness of extended duration antibiotics in patients with cIAI is unknown. This trial aims to compare the clinical and cost effectiveness of 28-day duration antibiotics with standard care with respect to rate of treatment failure in patients with cIAIs. Secondary outcomes include complications and quality of life. Method A multicentre, open label, two-arm, parallel group, pragmatic, randomised controlled trial with internal pilot. A total of 1166 consenting adult patients with cIAI will be recruited over 3 years and randomised on a 1:1 basis between 28-days antibiotics and standard care antibiotics. Patients will be recruited from ICUs and hospital in-patient wards across 30 sites. Recruitment commenced September 2022. Trial management and funding EXTEND is sponsored by University of Leeds and hosted by York Trials Unit. It is funded by the NIHR. The Trial Management Group will oversee design and running of the trial. Each site will have a Principal Investigator (PI) with local responsibility. The NIHR Associate PI scheme will be adopted to enable trainees to participate in the trial.

Microbial etiology and antibiotic resistance in urinary tract infections in children; view from an area where antibiotics are overused.

The aim of our study is to determine the uropathogenic causing urinary tract infections (UTIs) and their incidences, assess their antibiotic resistance, and determine an appropriate empirical antibiotic treatment strategy. We retrospectively analyzed the culture and antibiogram results of urine cultures of 49,706 patients aged 1 day to 18 years who applied to Diyarbakır Children's Hospital between March 2018 and October 2022. A total of 4,064 cases meeting the study criteria were recorded. Girls comprised 76.7% of the study population. While reproduction in urine culture was more common in boys in the 0-1 age group, there was a decrease in the number of boys with increasing age, and the most common culture growth was seen in girls in the 5-10 age group (p<0.001). Escherichia coli (E. coli) infections were more common in girls, while non-E. coli infections were more common in boys (p<0.001). Gram-negative bacterial growth in urine cultures was the most common growth type. In descending order, E. coli was grown in 68.1% of all cultures, Klebsiella spp in 12.6%, and Proteus spp in 3.9%. Less commonly, Pseudomonas spp (2.8%), Enterobacter spp (1.5%), and fungi (1.1%) were grown. Antibiotic resistance/sensitivity tests revealed resistance patterns most commonly against ampicillin (73.2%), amoxicillin-clavulanate (57.9%), cefuroxime axetil (46.7%), cefixime (51%), and ceftriaxone (40.5%), and less commonly against meropenem (1.7%), amikacin (2.4%), and nitrofurantoin (9.8%). Escherichia coli showed resistance most commonly against ampicillin (69.8%), amoxicillin-clavulanate (59.7%), and cefixime (51.3%), while non-E.coli bacteria showed resistance most commonly against ampicillin (84.6%), amoxicillin (52.0%), and cefixime (50%). Resistance against nitrofurantoin was lower in E. coli infections than non-E. coli infections, although the difference did not reach statistical significance (3.7% and 27%, respectively; p=0.149). In contrast, resistance against trimethoprim-sulfamethoxazole was more common in E. coli infections than non-E. coli infections, although the difference was not statistically significant (42% and 29.7%, respectively; p=0.093). Our study revealed that resistance has developed at very high rates against many oral and parenteral antibiotics that we use in the treatment of UTIs. If our rate of antibiotic use continues to increase this way, it is predicted that UTIs will, unfortunately, become untreatable with oral antibiotics. This upsetting point reached by our country, which is the state that uses antibiotics the most in Europe, exemplifies the importance of rational antibiotic use for the whole world.

A systematic review and meta-analysis of antimicrobial resistance knowledge, attitudes, and practices: Current evidence to build a strong national antimicrobial drug resistance narrative in Ethiopia.

Antimicrobial resistance (AMR) is a silent pandemic that has claimed millions of lives, and resulted in long-term disabilities, limited treatment options, and high economic costs associated with the healthcare burden. Given the rising prevalence of AMR, which is expected to pose a challenge to current empirical antibiotic treatment strategies, we sought to summarize the available data on knowledge, attitudes, and practices regarding AMR in Ethiopia. Articles were searched in international electronic databases. Microsoft Excel spreadsheet and STATA software version 16 were used for data extraction and analysis, respectively. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 checklist was followed. The methodological quality of the studies included was assessed by the Joana Briggs Institute critical appraisal checklists. The random-effect meta-analysis model was used to estimate Der Simonian-Laird's pooled effect. Statistical heterogeneity of the meta-analysis was checked through Higgins and Thompson's I2 statistics and Cochran's Q test. Publication bias was investigated by funnel plots, and the regression-based test of Egger for small study effects with a P value < 0.05 was considered to indicate potential reporting bias. In addition, sensitivity and subgroup meta-analyses were performed. Fourteen studies with a total of 4476 participants met the inclusion criteria. Overall, the pooled prevalence of good AMR knowledge was 51.53% [(95% confidence interval (CI): 37.85, 65.21), I2 = 99.0%, P <0.001]. The pooled prevalence of favorable attitudes and good practices were 63.43% [(95% CI: 42.66, 84.20), I2 = 99.6, P <0.001], and 48.85% [(95% CI: 38.68, 59.01), I2 = 93.1, P <0.001] respectively. In conclusion, there is a significant knowledge and practice gap on AMR among the general public, patients, and livestock producers. As a result, we call for greater educational interventions to raise awareness and build a strong national AMR narrative.

Neonatal Meningitis-Causing Escherichia coli Induces Microglia Activation which Acts as a Double-Edged Sword in Bacterial Meningitis.

Bacterial meningitis is a devastating disease occurring worldwide, with up to half of survivors left with permanent neurological sequelae. Neonatal meningitis-causing Escherichia coli (NMEC) is the most common Gram-negative bacillary organism that causes meningitis, particularly during the neonatal period. Here, RNA-seq transcriptional profiles of microglia in response to NMEC infection show that microglia are activated to produce inflammatory factors. In addition, we found that the secretion of inflammatory factors is a double-edged sword that promotes polymorphonuclear neutrophil (PMN) recruitment to the brain to clear the pathogens but, at the same time, induces neuronal damage, which may be related to the neurological sequelae. New neuroprotective therapeutic strategies must be developed for the treatment of acute bacterial meningitis. We found that transforming growth factor-β (TGF-β) may be a strong candidate in the treatment of acute bacterial meningitis, as it shows a therapeutic effect on bacterial-meningitis-induced brain damage. Prevention of disease and early initiation of the appropriate treatment in patients with suspected or proven bacterial meningitis are the key factors in reducing morbidity and mortality. Novel antibiotic and adjuvant treatment strategies must be developed, and the main goal for new therapies will be dampening the inflammatory response. Based on this view, our findings may help develop novel strategies for bacterial meningitis treatment.

P186 Airway clearance in the STOP PEDS pilot study of oral antibiotic treatment strategies for paediatric cystic fibrosis pulmonary exacerbations

Increased frequency of airway clearance therapy (ACT) is a key component of pulmonary exacerbation (PEx) treatment. STOP PEDS (Streamlined Treatment of Pulmonary exacerbations in Pediatrics) was a multicenter, prospective, open-label feasibility study in which oral antibiotic treatment for a mild outpatient pulmonary exacerbation was assigned randomly to either “immediate oral antibiotics” or “tailored therapy” (oral antibiotics started only for pre-specified criteria). Here we report the self-reported frequency of ACT among participants in both arms.