Previous Antibiotic Research Articles

P-1575. Trends in antibiotic resistance in community-acquired urinary tract infections among children - a retrospective descriptive nation-wide study

Abstract Background Urinary tract infection (UTI) is one of the most common bacterial infections in children. Early antibiotic treatment may prevent complications. Empirical treatment requires up-to-date knowledge of the local epidemiology. This study aims to describe trends in resistance rates in community-acquired UTI`s between 2017-2022, assess whether current recommendations for empirical treatment are valid and identify risk factors for resistance. Methods Data was collected retrospectively from the computerized system of Maccabi Health Services for all children under 18 years-old diagnosed with a UTI in 2017 and 2022 and analyzed using chi-square test and regression models. Results A total of 240,122 urinary samples were included in the study. The most common isolated pathogen was Escherichia coli (78%); there was a slight but significant increase in extended-spectrum beta-lactamases (ESBL) incidence for all Gram-negative Enterobacteriaceae from 6% in 2017 to 8% in 2022, (P-value 0.001). Higher incidence (12%) was detected among Klebsiella isolates compared to E. coli (8%). Aminoglycosides resistance rates increased from 5% to 6% (P-value 0.001). The most impressive increase was in resistance to Fluoroquinolones from 7% to 23% (P-value 0.001). Female gender, younger age, previous antibiotic treatment and urinary tract abnormalities were associated with an increased resistance rate. Conclusion The increased resistance rate observed for most pathogens and antibiotics was statistically significant, nevertheless, due to small absolute changes, the recommendations for empirical antibiotic treatment in Israel are still valid. Fluoroquinolones, which are not recommended as empirical treatment, should be avoided due to high levels of resistance. Disclosures Shirley Shapiro Ben David, MD, GSK: Lecturer|Pfizer: Grant/Research Support|Pfizer: Lecturer

Clostridioides difficile infection diagnosis

Clostridioides difficile is a Gram-positive, spore-forming anaerobic enteropathogen responsible for a wide spectrum of clinical diseases ranging from mild diarrhoea to pseudomembranous colitis. It is the first cause of healthcare-associated diarrhoeas, but community-associated Clostridioides difficile infections (CDI) are increasingly reported in patients without the common risk factors (age > 65 years, previous antibiotic treatment). The main C. difficile virulence factors are toxins A (TcdA) and B (TcdB), and in some cases the binary toxin. The CDI incidence has increased in Europe since the early 2000s, then decreased to reach approximately 4 cases/10,000 patients/days. C. difficile should be tested only in diarrheal stools. Children less than 3 years old are frequently colonized, therefore CDI diagnosis should be carried out only in specific cases (outbreak, Hirschsprung disease). No stand-alone method can be used for the CDI diagnosis. The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) recommends a two-step algorithm with a sensitive screening test (molecular assay or glutamate dehydrogenase immunochromatographic assay). If the screening test is negative, the CDI diagnosis can be ruled out. If the screening test is positive, a second highly specific test should be used, such as toxin A/B immunochromatographic assay.

Clinical Profile and Antibiotic Susceptibility Patterns of Cronobacter sakazakii in the Northern Region of Oman

Abstract Background: Cronobacter sakazakii is an opportunistic pathogen that mostly affects neonates, infants, and elderly people with weakened immune systems. No study has reported the frequency and antibiotic susceptibility patterns of C. sakazakii from Oman, and thus this study was conducted to fill this gap in the literature. Materials and Methods: This single-center retrospective study included C. sakazakii isolates identified from different clinical samples of patients treated at Sohar Hospital, Oman, between January 2017 and December 2023. Bacterial identification and antibiotic susceptibility testing were done using the VITEK II automated microbiological system in accordance with the Clinical Laboratory Standards Institute (CLSI) guidelines. Results: A total of 185 C. sakazakii isolates were included, most commonly from patients aged >60 years (42.7%) and <1 year (11.4%). C. sakazakii strains had high susceptibility (>80%) to most of the tested antibiotics; however, for beta-lactam antibiotics, it ranged from 0% to 50%. Approximately 26.5% of the strains were multidrug resistant. Independent risk factors for increased frequency of multidrug-resistant strains were urinary catheterization (P = 0.002), surgery (P = 0.021), previous antibiotic therapy (P = 0.047), and critical care unit admission (P = 0.048). About one-fifth of the patients experienced life-threatening C. sakazakii infections such as septicemia (15%) and pneumonia (4.7%). All deaths due to septicemia occurred in the >60 years (n = 12) and <1 year (n = 4) age groups. Conclusions: Cronobacter sakazakii isolates from the North Batinah region of Oman were most frequently isolated from elderly and infant patients and had high antibiotic susceptibility; however, the significant resistance against beta-lactams suggests their low effectiveness. The high number of multidrug-resistant strains coupled with the independent risk factors suggests the need for following stricter antibiotic stewardship protocols and infection control practices.

Facing Clostridioides difficile infection in a resource - Limiting setting.

An HIV- positive patient with Kaposi's sarcoma and undergoing chemotherapy, had been on antibiotic therapy for around 14 days with ceftriaxone and imipenem. He was admitted with a 5-day evolution of watery diarrhea followed by rectorrhagia. His CD4 level was 226 cells/ mm3. Colonoscopy was done with visualization of scattered pseudomembranes separated by areas of healthy mucosa, covering the entire intestine. Due to low resources the diagnosis of Clostridioides difficile (C.D) infection was proposed and treatment with oral metronidazole were made. Diarrhea improved after 5 days of treatment. Endoscopic findings were suggestive of CD infection. Other less common causes of pseudomembranous colitis, were unlikely according to clinical history. The probability of CD infection increased due the combination of risk factors such as HIV immunosuppression, chemotherapy, antibiotic therapy and endoscopic findings. The lack of Polymerase chain reaction, enzyme immunoassay for CD glutamate dehydrogenase antigen and toxins A and B was a diagnosis limitation. All these diagnostic tools were not available in the hospital. Oral vancomycin is the treatment of choice, however it was not available in the hospital, so treatment with oral metronidazole was made and the previous antibiotics used were discontinued. The patient progressed with clinical improvement.

Analysis of the dynamics of transition from non-colonization to colonization and Staphylococcus aureus bacteremia in hemodialysis patients using Markov models.

Background Hemodialysis patients are frequently colonized by Staphylococcus aureus, leading to severe infections with high mortality rates. However, little is known about transition from non-colonization to colonization or bacteremia over time. The aim was to analyze the behavior of S. aureus colonization, identifying the probability of transition from non-colonized to colonized state or bacteremia, and the influence of specific covariates. Methods The study was conducted in a dialysis unit associated with a tertiary care hospital in Medellín between October 2017 and October 2019. An initial measurement was taken to evaluate S. aureus colonization, and follow-up measurements were performed 2 and 6 months later. Bacteremia evolution was monitored for 12 months. A two-state recurrent continuous-time Markov model was constructed to model transition dynamics from non-colonization to S. aureus colonization in hemodialysis patients. Subsequently, the model was applied to a third state of bacteremia. Results Of 178 patients on hemodialysis, 30.3% were colonized by S. aureus. Transition intensity from non-colonization to colonization was three times higher (0.21; CI: 0.14-0.29) than from colonization to non-colonization (0.07; CI: 0.05-0.11). The colonization risk increased in patients with previous infections (HR: 2.28; CI: 0.78-6.68), hospitalization (HR: 1.29; CI: 0.56-2.99) and antibiotics consumption (HR: 1.17; CI: 0.53-2.58). Mean non-colonized state duration was 10.9 months, while in the colonized state was 5.2 months. In the 3-state model, it was found that patients colonized were more likely to develop S. aureus infection (13.9%). Conclusion A more likely transition from non-colonization to colonization was found, which increases with factors such as previous infection. In addition, the development of bacteremia was more likely in colonized than in non-colonized patients. These results underline the importance of surveillance and proper management of S. aureus colonization to prevent serious complications, such as bacteremia, and improve prognosis in this vulnerable population.

Assessing the role of environment in Pseudomonas aeruginosa healthcare-associated bloodstream infections: a one-year prospective survey

ObjectiveTo prospectively investigate the role of hospital environment in Pseudomonas aeruginosa (Pa) nosocomial bloodstream infections (BSIs) during one year in a tertiary-care hospital. MethodsClinical records of patients presenting Pa-BSIs after >48h of hospitalization were investigated to confirm the nosocomial character of BSIs and identify the way of entry and risk factors. Environmental investigations were performed to track Pa source/reservoir along the pathway of cares. Clinical and environmental strains were compared by whole-genome sequencing to identify the path of contamination from hospital environment to patients. Results53 episodes of BSIs in 49 patients were considered as nosocomial, mostly involving men (73%), with an average age of 62.4, immunosuppressed in over 40% of cases, and after previous antibiotic therapy in almost 92% of cases. BSIs occurred after 27 days of hospitalization on average. The main routes of entry were urinary (30%, on indwelling catheters for 2/3 of cases) and cutaneous (17%, catheter-related in almost 80% of cases). Pa was found in 16/49 investigations, representing 34 positive samples, including 54% of sink traps, 23% of water and 20% of tap aerators. An epidemiological link was established between environmental and clinical strains only for 8 patients representing 15% of nosocomial BSIs. ConclusionThe hospital environment usually considered as the main source of Pa healthcare-associated infections was identified as responsible of nosocomial BSIs for only 15% of patients. Since the implementation of water and hospital environment management, one can hypothesize that Pa has become a community-acquired pathogen with a nosocomial expression in infection.

Characterization of middle ear microbiome in otitis media with effusion in Hungarian children: Alloiococcus otitidis may potentially hamper the microbial diversity

IntroductionAlthough otitis media with effusion (OME) is a common cause of hearing impairment in children, little is known about its microbiological background. We aimed to analyse the microbiome of the middle ear fluid (MEF) in OME to identify microbiological, demographic and environmental factors that may potentially influence the middle ear microbiome. In addition, we aimed to compare the results of conventional culture techniques and PCR-based methods. Methods39 samples from children with OME were investigated using conventional culture and 16S rRNA sequencing. Bioinformatic analyses were carried out to assess the microbial communities and their association with clinical data. ResultsBy conventional culture technique bacteria could be cultured in 33 % of the MEF samples; the most frequent bacterium was Haemophilus influenzae, followed by Staphylococcus species, Cutibacterium acne, and Streptococcus species. The 16S rRNA analysis showed that Alloiococcus was the most abundant bacterium, followed by Haemophilus, Streptococcus. and Sphingobium.A “High Alloiococcus group” with significantly lower and a “Low Alloiococcus group” with significantly higher alpha and beta diversity could be defined. Children born by Caesarean sections had lower beta and Shannon diversity than patients born by natural birth. Breastfeeding for at least six months showed a negative correlation with alpha diversity. Age, previous antibiotic treatment, parental smoking, duration of symptoms, existence of siblings, did not alter the significantly bacterial composition of MEF samples and there were no significant differences in regard to alpha or beta diversity. ConclusionThe conventional culture technique and 16S rRNA results were not congruent. Remarkably, Alloiococcus could not be cultured at all, even by 16S rRNA analysis the presence of Alloiococcus seems to be important. Based on our results, A. otitidis possibly impacts the diversity of middle ear microbiome in children with OME. However, further studies are required to determine the role of A. otidis in middle ear pathologies.

Surgical Site Infections: Risk Factors for Multiple Antibiotic Resistance in Abdominal Surgery

INTRODUCTION. Multidrug-resistant (MDR) organisms are increasingly becoming a major surgical site infection (SSI); however, the clinical outcomes and risk factors associated with resistant pathogens in general surgery remain poorly understood.THE AIM of the present research is to study the risk factors and consequences of infections in patients with SSI caused by antibiotic resistant pathogens with MDR.MATERIAL AND METHODS. A single-center, retrospective case-control study was carried out. The results of the examination and treatment of 50 patients with SSI + MDR, who made up the main group, and two control groups — non-MDR SSI and no SSI, 50 patients each, were analyzed. A total of 38 risk factors were used: pre- and surgical criteria, clinical, biochemical, instrumental data, postoperative complications and treatment features. The microbial landscape was studied in SSI+MDR. Single- and multivariate analysis was carried out, binary and multinomial logistic regression was performed. P-values <0.05 were considered significant at 95% CI.RESULTS. Significant risk factors were as follows: previous hospitalization, previous antibiotic therapy, terms of preoperative stay of the patient in the department, emergency surgery, class of surgery, decrease in the ratio of ALP/ ALPI, MEI and EMFC (p<0.01); elevated ASA score, obesity, low levels of plasma proteins and albumin, (p<0.05). Among the pathogens, there were more gram-negative enterobacteria (61%) than gram-positive ones (30.5%). Escherichia coli (36.3%) was the most commonly found bacterium, followed by Enterococcus faecium (9.09%), Morganella morganii (7.58%), Staphylococcus aureus (6%), and Pseudomonas aeruginosa (6%). In SSSI, Staphylococcus spp. prevailed. (>80%); in DSSI — Echerichia, Acinetobacter (>70%); and in OSSSI — Enterobacter spp., Acinetobacter and Citrobacter (>90%). SSI+MDR were characterized by serious surgical complications (Clavien Dindo Classification grade 3–5), wound dehiscences and OSSSI, reoperations (p<0.05).CONCLUSION. 1. The primary risk factors for multiple antibiotic resistance were as follows: previous hospitalization, previous antibiotic therapy, the duration of the patient’s preoperative stay in the department, emergency surgery, surgery class, reduced ALP/ALPI ratio, MEI and EMFC. In addition to the above, the following were also of great importance: increased ASA score, obesity, low plasma proteins, albumin.2. When identifying risk factors for multiple antibiotic resistance in surgical patients, the development of severe postoperative complications, sepsis and multiple organ failure can be predicted.3. Perioperative medical and preventive measures require a multidisciplinary approach involving the microbiologist, pharmacologist, immunologist, nutrition specialist, and other expert consultants.

Invasive fungal disease in patients with cancer in a tertiary care pediatric hospital

Abstract Background In the last two decades, the raise in invasive fungal diseases (IFD) has been associated with increased morbidity and mortality in immunosuppressed hosts. Its incidence varies between 2 to 21% and depends on the host´s underlying disease, the intensity of immunosuppressive treatment and the presence of comorbidities. The aim of this study is to describe the epidemiological, clinical and microbiological characteristics of IFD in patients with hematology-oncology disease. Methods Retrospective, descriptive study. Patients under 18 years of age with acute leukemias, lymphomas and solid tumors with a diagnosis of proven IFD (according to EORTC-MSG 2019 criteria) were included during the period from January 2020 to November 2023 in a tertiary care pediatric hospital. Results During the study period, 304 patients were under follow-up. 14 episodes of proven IFD were identified in 13 patients.The median age was 120 months. Male sex predominated (69.2%). The recognized factors associated were neutropenia (69.2%), use of corticosteroids in the last 3 months (61.5%) and use of previous antibiotics (92.3%). The most common underlying disease was Acute Lymphoblastic Leukemia (ALL) in 11 cases (78.5%), of which 3 were in relapse. The 21.4% of the episodes occurred in solid tumors (1 osteosarcoma of the tibia, 1 abdominal germ cell tumor, 1 neuroblastoma). Patients receiving primary prophylaxis for filamentous fungi were 3/14 (21.4%), according to the European Conference on Infections in Leukemia (ECIL-8). All received voriconazole. The fungal isolates identified were: 1 Rhizopus spp. (eye biopsy, paranasal sinuses) 1 Penicillum spp. (lung biopsy), 1 Exserohilum rostratum (skin biopsy), 1 Trichophyton asahii (blood cultures), 1 Purpuracillum lilacinus (skin biopsy), 1 Aspergillus fumigatus (Bronchoalveolar lavage, BAL),: 3 Candida parapsilosis (blood cultures), 1 Candida tropicalis (blood cultures), 1 Candida spp (blood cultures), 1 Malassezia (BAL). The patients with invasive molds infections were six, all of them with pathological chest tomography. Galactomannans (GM) were positive in 66% (4/6). BAL with positive GM was performed in 2 of them. The primary focus were: cutaneous (3/6), pulmonary (2/6) and orbital-rhinosinusal (1/6). Regarding IFD due to yeast fungi: all Candida infections were associated with central venous catheters fungemia. Malassezia infection presented with pulmonary involvement. Fungal co-infection was observed in 1 patient with documentation of Aspergillus fumigatus in BAL and Candida tropicalis in blood and urine cultures. Empirical antifungal therapy was liposomal amphotericin in 76.9 % of the patients. Two patients died (15.4%) at 30 days of follow-up. Conclusion Early diagnosis and timely antifungal therapy represent the main strategies to increase the survival of patients with IFD. Antifungal prophylaxis is postulated as an effective prevention measure and its indication should be defined according to the patient’s characteristics and the incidence of IFD at the treating center. We consider that patients with suspected IFD and clinical focus should undergo the corresponding tissue biopsy for culture, histological evaluation, and molecular biology, to direct the appropriate treatment. Candida species represent the most frequent isolates, however, Aspergillus and Rhizopus infections are associated with higher morbidity and mortality.

Risk factors for multidrug-resistant bacteria in critically ill children and MDR score development.

Antimicrobial resistance and healthcare-associated infections (HAIs) are major health concerns in the pediatric intensive care unit (PICU). Device-associated HAIs (DA-HAIs) produced by multidrug-resistant (MDR) bacteria are especially worrying, as they can lead to an inappropriate empirical antibiotic therapy, worsened outcomes and increased mortality. The MDR score was designed to enable the prompt identification of patients at high risk of developing an MDR infection. This was a single-center, prospective, observational study, conducted between January 2015 and December 2022, including PICU patients with a microbiologically confirmed DA-HAI. Demographic, clinical characteristics and outcomes were compared between patients with a DA-HAI caused by MDR and non-MDR-associated DA-HAI, and a risk score for multi-resistance was designed. In total, 257 DA-HAI cases were included, 86 (33.46%) caused by an MDR microbe. In the univariate analysis, comorbidity (p = 0.002), previous MDR colonization (p < 0.001), previous surgery (p = 0.018), and previous antibiotic therapy (p = 0.009) were more frequent among MDR-associated DA-HAI (MDR DA-HAI). In addition, days from device insertion to infection and from PICU admission (p < 0.005) to infection were longer in patients with MDR. In the multivariate analysis, previous comorbidity (OR 2.201), previous MDR colonization (OR 5.149), and PICU length of stay longer than 9days (OR 1.782) were independently associated with MDR-DA-HAI. Using these three independent risk factors for MDR, a risk score was created: the MDR score. Three risk groups were obtained: low risk (0-2 points), intermediate risk (3-7 points), and high risk (8-12 points). Seventy-one patients with MDR-DA-HAI (82.6%) were classified in the intermediate or high-risk group, with a global sensitivity of 82.6%. The specificity in the high-risk group was 91.8%, and 81.0% of patients who were stratified into the low-risk group had non-MDR-associated infections, so they were correctly classified. Conclusions: The MDR score can be a useful tool to stratify patients in risk groups for MDR-DA-HAI. It may help to guide the choice of empirical therapy, leading to early optimization and avoiding delays in establishing appropriate treatment. This study reinforces the importance of stratifying patients based on their individual risk profile for MDR infection.

Hospitalized patients on proton pump inhibitors for stress ulcer prophylaxis have a higher risk of Clostridioides difficile infection compared with those on histamine-2 receptor antagonists

Previous studies on Clostridioides difficile infection (CDI) in proton pump inhibitor (PPI) users generally enrolled a heterogeneous population and did not include a control group of histamine H2 receptor antagonists (H2RAs) users or adjust for confounding variables, such as previous antibiotics. It is uncertain whether hospitalized patients using PPIs for stress ulcer prophylaxis (SUP) are at a higher risk of CDI compared with those using H2RAs. This study aimed to compare the association between CDI and the usage of antisecretory drugs (ASDs): PPIs and H2RAs, for SUP among hospitalized patients, and the impact of the duration of their use on CDI. In this nationwide population-based cohort study using the Taiwan National Health Insurance Database, hospitalized patients using ASDs for SUP were identified between 2017 and 2018. A total of 63,266 and 69,269 individuals were included in the PPI and H2RA groups, respectively. The primary endpoint was a 90-day monitoring of CDI occurrence. The incidences of CDI were 1.6/10,000 and 0.5/10,000 person-days in the PPIs and H2RAs groups, respectively. After adjusting for confounding factors, the risk of infection in the PPIs group remained significantly higher than in the H2RAs group (hazard ratio (HR), 2.49; 95% confidence interval (CI), 1.63-3.81). In the subgroup analysis, during hospitalization, the risk of CDI for patients using high-risk antibiotics or admitted to the intensive care unit (ICU), as well as patients with immunodeficiency, using PPIs for SUP, was higher than using H2RAs. Furthermore, the risk of CDI was higher in patients using ASDs for durations >14 days than in those using them for <7 days (adjusted HR, 3.66; 95% CI, 2.34-5.75). The risk of occurrence CDI for hospitalized patients using PPIs for SUP was higher than using H2RAs. It is recommended not to exceed 14 days of any gastric ASDs for SUP during hospitalization, especially for patients who have used high-risk antibiotics, have been admitted to the ICU, or have immunodeficiency.

Atypical gouty tophus masquerading as a foreign body granuloma

Subcutaneous nodular lesions in a patient with significantly elevated inflammatory markers always raise the possibility of infectious diagnoses such as atypical infection, pyogenic abscess, mycobacterial infection, and malignancy. Definitive diagnosis requires tissue biopsy and histopathologic examination. The atypical presentation of a foreign body granuloma with concurrent intraoperative findings supports the diagnosis of gouty arthritis.We report a case of a 67-year-old man who presented with an inflammatory nodular lesion on the left elbow that was initially suspected to have an infectious cause. Histopathologic examination of the nodular tissue later revealed that the patient had a foreign body granuloma due to urate crystal deposition. The atypical appearance of the gouty arthritis, the low serum urate level, the negative crystal identification in the synovial fluid, and the markedly elevated inflammatory markers, which did not respond to the previous antibiotic and steroid therapy, raised the suspicion of atypical infection in this case.

Analysis of the dynamics of transition from non-colonization to colonization and Staphylococcus aureus bacteremia in hemodialysis patients using Markov models.

Background Hemodialysis patients are frequently colonized by Staphylococcus aureus, leading to severe infections with high mortality rates. However, little is known about transition from non-colonization to colonization or bacteremia over time. The aim was to analyze the behavior of S. aureus colonization, identifying the probability of transition from non-colonized to colonized state or bacteremia, and the influence of some covariates. Methods The study was conducted in a dialysis unit associated with a high complexity hospital in Medellín between October 2017 and October 2019. An initial measurement was taken to evaluate S. aureus colonization, and follow-up measurements were performed 2 and 6 months later. Bacteremia evolution was monitored for 12 months. A two-state recurrent continuous-time Markov model was constructed to model transition dynamics from non-colonization to S. aureus colonization in hemodialysis patients. Subsequently, the model was applied to a third state of bacteremia. Results Of 178 patients on hemodialysis, 30.3% were colonized by S. aureus. Transition intensity from non-colonization to colonization was three times higher (0.21; CI: 0.14-0.29) than from colonization to non-colonization (0.07; CI: 0.05-0.11). The colonization risk increased in patients with previous infections (HR: 2.28; CI: 0.78-6.68), hospitalization (HR: 1.29; CI: 0.56-2.99) and antibiotics consumption (HR: 1.17; CI: 0.53-2.58). Mean non-colonized state duration was 10.9 months, while in the colonized state was 5.2 months. In the 3-state model, it was found that patients colonized were more likely to develop S. aureus infection (13.9%). Conclusion A more likely transition from non-colonization to colonization was found, which increases with factors such as previous infection. In addition, the development of bacteremia was more likely in colonized than in non-colonized patients. These results underline the importance of surveillance and proper management of S. aureus colonization to prevent serious complications, such as bacteremia, and improve prognosis in this vulnerable population.

Risk of emergency hospital admission related to adverse events after antibiotic treatment in adults with a common infection: impact of COVID-19 and derivation and validation of risk prediction models

BackgroundWith the global challenge of antimicrobial resistance intensified during the COVID-19 pandemic, evaluating adverse events (AEs) post-antibiotic treatment for common infections is crucial. This study aims to examines the changes in incidence rates of AEs during the COVID-19 pandemic and predict AE risk following antibiotic prescriptions for common infections, considering their previous antibiotic exposure and other long-term clinical conditions.MethodsWith the approval of NHS England, we used OpenSAFELY platform and analysed electronic health records from patients aged 18–110, prescribed antibiotics for urinary tract infection (UTI), lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), sinusitis, otitis externa, and otitis media between January 2019 and June 2023. We evaluated the temporal trends in the incidence rate of AEs for each infection, analysing monthly changes over time. The survival probability of emergency AE hospitalisation was estimated in each COVID-19 period (period 1: 1 January 2019 to 25 March 2020, period 2: 26 March 2020 to 8 March 2021, period 3: 9 March 2021 to 30 June 2023) using the Kaplan–Meier approach. Prognostic models, using Cox proportional hazards regression, were developed and validated to predict AE risk within 30 days post-prescription using the records in Period 1.ResultsOut of 9.4 million patients who received antibiotics, 0.6% of UTI, 0.3% of URTI, and 0.5% of LRTI patients experienced AEs. UTI and LRTI patients demonstrated a higher risk of AEs, with a noted increase in AE incidence during the COVID-19 pandemic. Higher comorbidity and recent antibiotic use emerged as significant AE predictors. The developed models exhibited good calibration and discrimination, especially for UTIs and LRTIs, with a C-statistic above 0.70.ConclusionsThe study reveals a variable incidence of AEs post-antibiotic treatment for common infections, with UTI and LRTI patients facing higher risks. AE risks varied between infections and COVID-19 periods. These findings underscore the necessity for cautious antibiotic prescribing and call for further exploration into the intricate dynamics between antibiotic use, AEs, and the pandemic.

Individual health insurance data of antibiotic delivery in previous months as a tool to predict bacterial resistance of urinary tract infection: A prospective cohort study

ObjectivesWe aimed to quantify the individual risk of antimicrobial resistance among patients with community-acquired Escherichia coli urinary tract infection (UTI) according to their antibiotic exposure over the previous 18 months. Patients and methodsFrench patients were prospectively recruited in two centers in 2015–2017. Resistance of isolates to amoxicillin (AMX), amoxicillin-clavulanate (AMC), third-generation cephalosporins (3GC), trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolones (FQ) and fosfomycin (FOS) was analysed according to previous intra-class and inter-class antibiotic exposure documented in health insurance files. ResultsPrevious antibiotic exposure was found in 588 (81.4 %) of the 722 UTI cases analysed (564 patients). Recent exposure (three months before UTI) was associated with stronger intra-class impact on E. coli resistance compared to remote exposure (18 months before UTI) for AMX, AMC, FQ and TMP-SMX, with respective adjusted odds ratios [95 % confidence interval] of 1.63 [1.20–2.21], 1.59 [1.02–2.48], 3.01 [1.90–4.77], and 2.60 [1.75–3.87]. AMX, FQ, and TMP-SMX also showed significant inter-class impact. Resistance to 3GC was not significantly associated with intraclass exposure (adjusted OR: 0.88 [0.41–1.90]). FOS resistance was remarkably low (0.4 %). Duration of the antibiotic-free period required for resistance risk to drop below 10 %, the threshold for empirical use in UTI, was modelled as < 1 month for 3GC, >18 months for AMX and TMP-SMX and uncertain for AMC (5.2 months [2.3 to > 18]) and FQ (17.4 months [7.4 to > 18]). ConclusionsResistance of E. coli causing UTI is partially predicted by previous personal antibiotic delivery.

First-line pembrolizumab for lung cancer in a Spanish real-world study.

e23268 Background: KEYNOTE (KN) 024 trial showed that pembrolizumab significantly improves progression free survival (PFS) and overall survival (OS) in patients with previously untreated advanced non-small cell lung cancer (NSCLC) with a PD-L1 expression ≥ 50% without EGFR/ALK alterations. The main aim of this study is to report the outcomes (PFS and OS) of pembrolizumab in a real life setting. Methods: Multicenter retrospective study in 42 Spanish hospitals. Inclusion period: 01/2016 – 07/2020; cut-off date: 31/12/2021. Demographic, clinical and treatment-related data were retrospectively obtained from patients’ medical files. Statistical analysis was carried out using descriptive metrics and survival analysis techniques (Kaplan-Meier, log-rank test, Cox regression). Results: In our cohort of 1005 patients, 74.5% were males, mean age was 66.4 ± 9.7 and mean BMI 25.6 ± 4.6. The majority were current (35.6%) or former smokers (56.6%), with 11 % of patients with ECOG ≥ 2. Patients with a non squamous histology were 79.5% and 95.2% were classified as IV stage (30.3% had hepatic and/or brain metastases, 49.3% had ≥ 2 metastatic sites). Pembrolizumab dose was mainly fixed (83.1% of patients), while the number of treatment cycles was highly variable. 31.8% received concurrent radiotherapy, while previous corticoid (PCE), antibiotic and proton pump inhibitors (PPI) exposure were 18.2%, 7.7% and 40.7% respectively. With a median follow-up of 6.3 months, median OS and PFSwere 19 (95%CI: 16.2 – 21.3) and 8.7 (95%CI: 7.2 – 10.1) months. Several variables were associated with PFS and OS after univariate survival analysis. Age and previous antibiotic exposure were associated to worse OS but not to PFS. Multivariate analysis showed that ECOG ≥2 (HR 2.7 95%CI 2-3.5) and previous PPI exposure (HR 1.3 95%CI 1.1-1.6) were predictors of poor outcome. Conclusions: In our cohort, pembrolizumab showed lower OS and similar PFS than KN 024. Our results confirm that poor PS (ECOG) is a negative predictive factor for effectiveness. [Table: see text]

Risk factors for Pseudomonas aeruginosa VIM colonization or infection in the ICU: Case-control study

Carbapenem-resistant strains of Pseudomonas aeruginosa (CRPA) have become a major health care concern in many countries, against which anti-infective strategies are limited and which require adequate infection control interventions. Knowing the different modes of transmission of CRPA in intensive care units (ICUs) would be helpful to adapt the means of prevention. The aim of this retrospective case-control study was conducted between January 1, 2017 and February 28, 2022 to identify the risk factors for the acquisition of CRPA in ICUs. During the study period, 147 patients were included (49 cases and 98 controls). Among the 49 patients, 31 (63%) acquired CRPA in clusters and 18 (37%) sporadically. Aunivariate analysis showed that 4 variables were associated with CRPA acquisition, including (1) prior antibiotic prescriptions, (2) admission to rooms 203 and 207, (3) severity of illness at admission, and (4) use of mechanical ventilation. Multivariate analysis identified 3 factors of CRPA acquisition, including admission to room 203 (odds ratio [OR]=29.5 [3.52-247.09]), previous antibiotic therapy (OR=3.44 [1.02-11.76]), and severity of condition at admission (OR=1.02 [1-1.04]). Our study suggests the role of a contaminated environment in the acquisition of CRPA in the ICU, along with antibiotic use.

Association of Previous Antibiotics Use and Kawasaki Disease: A Cohort Study of 106,908 Patients.

Microbial imbalance in the gut from antibiotic use may be an etiologic factor of Kawasaki disease (KD). We aimed to identify the association between the use of antibiotics and the development of KD, considering various antibiotic profiles. A population-based, case-control study was performed using data from the Health Insurance Review and Assessment Service database. Children <5 years of age, who were diagnosed with KD between 2016 and 2019, were identified. Propensity score-matched controls were selected from the general population in a 1:5 ratio. Four separate study cohorts were created according to different periods of antibiotic use: (1) within 28 days and (2) 12 months after birth and (3) within 6 months and (4) 12 months from the index date. Profiles regarding antibiotic use were compared between patients with KD and matched controls. We included 17,818 patients with KD and 89,090 matched controls. Use of antibiotics within 6 months [odds ratio (OR): 1.18; 95% confidence interval (CI): 1.12-1.26] and 12 months (OR: 1.23; 95% CI: 1.14-1.32) from the index date were associated with the development of KD. The association between antibiotic use and KD was most prominent in patients who had received 3 or more types of antibiotics within 12 months from the index date (OR: 1.26; 95% CI: 1.17-1.37). Antibiotic use within the preceding 6 or 12 months was associated with KD. Alteration in gut microbiota due to antibiotic usage might play a role in the development of KD.

Anionic liposome formulation for oral delivery of thuricin CD, a potential antimicrobial peptide therapeutic

Thuricin CD is a two-peptide antimicrobial produced by Bacillus thuringiensis. Unlike previous antibiotics, it has shown narrow spectrum activity against Clostridioides difficile, a bacterium capable of causing infectious disease in the colon. However, peptide antibiotics have stability, solubility, and permeability problems that can affect their performance in vivo. This work focuses on the bioactivity and bioavailability of thuricin CD with a view to developing a formulation for delivery of active thuricin CD peptides through the gastrointestinal tract (GIT) for local delivery in the colon. The results indicate that thuricin CD is active at low concentrations only when both peptides are present. While thuricin CD was degraded by proteases and was unstable and poorly soluble in gastric fluid, it showed increased solubility in intestinal fluid, probably due to micelle encapsulation. Based on this, thuricin CD was encapsulated in anionic liposomes, which showed increased activity compared to the free peptide, maintained activity after exposure to pepsin in gastric fluid and intestinal fluid, was stable in suspension for over 21 days at room temperature and for 60 days at 4 °C, and exhibited no toxicity to epithelial intestinal cells. These findings suggest that an anionic lipid-based nano formulation may be a promising approach for local oral delivery of thuricin CD.

Clinical Picture and Risk Factors for Poor Outcome in Streptococcus pneumoniae Meningitis of Childhood on Three Continents.

Streptococcus pneumoniae meningitis (SpM) remains a major health burden worldwide, particularly in low- and middle-income countries. Identifying the patients at highest risk for mortality and disabling sequelae may reveal potentially avoidable predisposing factors and identify patients most in need of intensive care. We searched for factors that do not require laboratory facilities. This study was a secondary analysis of prospectively collected data from 5 clinical trials of childhood bacterial meningitis on 3 continents between 1984 and 2017. SpM cases were analyzed by study site and predictors for poor outcome (death or severe sequelae) were identified from the whole series, Latin America and Angola. Among a total of 1575 children (age range: 2 months to 15 years), 505 cases were due to pneumococci. Compared to other etiologies, SpM doubled the death rate (33% vs. 17%) and tripled poor outcome (15% vs. 6%). In SpM, Glasgow Coma Score <13 [odds ratio (OR): 4.73] and previous antibiotics in Angola (OR: 1.70) were independent predictors for death. Predictors for poor outcome were age <1 year (OR: 2.41) and Glasgow Coma Score <13 (OR: 6.39) in the whole series, seizures in Latin America (OR: 3.98) and previous antibiotics in Angola (OR: 1.91). Angolan children had a 17-fold increased risk for poor outcome when compared with Finnish children ( P = 0.011). Our study proved the severity of SpM when compared with other etiologies. The outcome was especially poor in Angola. Most patients at risk for poor outcome are easily identified by clinical factors on admission.