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With the spread of antibiotic resistance in pediatric urinary tract infections (UTIs), more patients are likely to be started empirically on antibiotics to which pathogens are later found to be resistant (discordant therapy). However, in-vivo effectiveness may be different from in-vitro susceptibility. Aims of this study were to describe clinical outcomes of discordant empirical treatments in pediatric UTIs and to investigate risk factors associated to treatment failure. This observational, retrospective study was conducted on children hospitalized for febrile UTIs with positive urine culture and started on discordant empirical therapy. Failure rates of discordant treatments and associated risk factors were investigated. A total of 142/1600 (8.9%) patients were treated with inadequate empirical antibiotics. Clinical failure was observed in 67/142 (47.2%) patients, with no fatal events. Higher failure rates were observed for combinations of penicillin and beta-lactamase inhibitors (57.1%). Significant risk factors for failure of discordant treatment were history of recurrent UTIs (95% CI: 1.13–9.98, OR: 3.23, p < 0.05), recent use of antibiotics (95% CI: 1.46–21.82, OR: 5.02, p < 0.01), infections caused by Pseudomonas aeruginosa (95% CI: 1.85–62.10, OR: 7.30, p < 0.05), and empirical treatment with combinations of penicillin and beta-lactamase inhibitors (95% CI: 0.94–4.03, OR: 1.94, p = 0.05). This study showed that discordant empirical treatments may still be effective in more than half of pediatric UTIs. Clinical effectiveness varies between different discordant antibiotics in pediatric UTIs, and patients presenting risk factors for treatment failure may need a differentiated empirical approach.

Background: Community-acquired pneumonia (CAP) is one of the leading causes of death worldwide. Antibiotic stewardship program (ASP) has been implemented to improve rational and responsible antibiotic use by encouraging guideline adherence. Objective: This retrospective observational before–after study aimed to evaluate whether the ASP may improve guideline adherence, antibiotic exposure, and clinical outcomes in patients hospitalized due to CAP in Hungary. Methods: The study was conducted at a pulmonology department of a tertiary care medical center in Hungary. The ASP implementation consisted of written and published guidelines available to all professionals, continuous supervision, and counseling services on antibiotic therapies at an individual level, with the aim of ensuring compliance with CAP guidelines. Overall guideline adherence (agent selection, route of administration, and dose), clinical outcomes (length of stay and 30-day mortality), antibiotic exposure, and direct costs were compared between the two periods. Fisher’s exact test and t -test were applied to compare categorical and continuous variables, respectively. P -values below 0.05 were defined as significant. Results: Significant improvement in overall CAP guideline adherence (30.2%), sequential therapy (10.5%), and a significant reduction in the total duration of antibiotic therapy (13.5%) were observed. Guideline non-adherent combination therapies with metronidazole decreased significantly by 28.1%. Antibiotic exposure decreased by 7.2%, leading to a significant decrease in direct costs (23.6%). Moreover, the ASP had benefits for clinical outcomes, and length of stay decreased by 13.5%. Conclusion: The ASP may play an important role in optimizing empirical antibiotic therapy in CAP having a sustained long-term effect.

Infective endocarditis is very uncommon in children; however, when it does arise, it can lead to severe consequences. The biggest risk factor for paediatric infective endocarditis today is underlying congenital heart defects. The most common causative organisms are Staphylococcus aureus and the viridans group of streptococci. The spectrum of symptoms varies widely in children and this produces difficulty in the diagnosis of infective endocarditis. Infective endocarditis in children is reliant on the modified Duke criteria. The use of blood cultures remains the most effective microbiological test for pathogen identification. However, in blood culture–negative infective endocarditis, serology testing and IgG titres are more effective for diagnosis. Imaging techniques used include echocardiograms, computed tomography and positron emission tomography. Biomarkers utilised in diagnosis are C-reactive protein, with recent literature reviewing the use of interleukin-15 and C-C motif chemokine ligand for reliable risk prediction. The American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines have been compared to describe the differences in the approach to infective endocarditis in children. Medical intervention involves the use of antimicrobial treatment and surgical interventions include the repair and replacement of cardiac valves. Quality of life is highly likely to improve from surgical intervention.Conclusion: Over the past decades, there have been great advancements in clinical practice to improve outcomes in patients with infective endocarditis. Nonetheless, further work is required to better investigative and manage such high risk cohort. What is Known:• The current diagnostic techniques including ‘Duke’s criteria’ for paediatric infective endocarditis diagnosis• The current management guidelines utilised for paediatric infective endocarditisWhat is New:• The long-term outcomes of patients that underwent medical and surgical intervention• The quality of life of paediatric patients that underwent medical and surgical intervention

PurposeLegionella spp. pneumonia (LP) is a cause of community-acquired pneumonia (CAP) that requires early intervention. The median mortality rate varies from 4 to 11%, but it is higher in patients admitted to intensive care unit (ICU). The objective of this study is to identify predictors of ICU admission in patients with LP.MethodsA single-center, retrospective, observational study conducted in an academic tertiary-care hospital in Pisa, Italy. Adult patients with LP consecutively admitted to study center from October 2012 to October 2019.ResultsDuring the study period, 116 cases of LP were observed. The rate of ICU admission was 20.7% and the overall 30-day mortality rate was 12.1%. Mortality was 4.3% in patients hospitalized in medical wards versus 41.7% in patients transferred to ICU (p < 0.001). The majority of patients (74.1%) received levofloxacin as definitive therapy, followed by macrolides (16.4%), and combination of levofloxacin plus a macrolide (9.5%). In the multivariate analysis, diabetes (OR 8.28, CI 95% 2.11–35.52, p = 0.002), bilateral pneumonia (OR 10.1, CI 95% 2.74–37.27, p = 0.001), and cardiovascular events (OR 10.91, CI 95% 2.83–42.01, p = 0.001), were independently associated with ICU admission, while the receipt of macrolides/levofloxacin therapy within 24 h from admission was protective (OR 0.20, CI 95% 0.05–0.73, p = 0.01). Patients who received a late anti-Legionella antibiotic (> 24 h from admission) underwent urinary antigen test later compared to those who received early active antibiotic therapy (2 [2–4] vs. 1 [1–2] days, p < 0.001).ConclusionsAdmission to ICU carries significantly increased mortality in patients with diagnosis of LP. Initial therapy with an antibiotic active against Legionella (levofloxacin or macrolides) reduces the probability to be transferred to ICU and should be provided in all cases until Legionella etiology is excluded.

In a retrospective cohort study of intensive care unit (ICU) admitted adult patients with suspected or confirmed infection, associations between combination versus mono empirical antibiotic therapy and clinical cure at day 7 as well as mortality at day 7 and 28, were investigated. Patients from the DIANA study were grouped and analysed by combination versus mono antibiotic therapy. Clinical cure was defined as survival and resolution of all signs and symptoms related to the infection. Odds ratios (ORs) were calculated by logistic regression analyses. Of the 1398 included patients, 568 patients (41%) received combination therapy. In total, 641(46%) patients achieved clinical cure and 135 (10%) patients had died as of day 7. There were no significant associations between combination and mono therapy relating to clinical cure and mortality. This study found no differences in clinical cure and mortality between empirical combination versus mono therapy in a large cohort of ICU patients with a suspected infection. •The most common antibiotic therapy was beta-lactam antibiotic therapy in combination with aminoglycosides.•There was no difference in clinical adequacy between combination and monotherapy in patients with positive microbiology.•There was no difference in mortality between combination and monotherapy in ICU patients with a suspected infection.•There was no difference in clinical cure between combination and monotherapy in ICU patients with a suspected infection.

Background Ineffective antibiotic therapy increases mortality of acute cholangitis. The choice of antibiotics should reflect local resistance patterns and avoid the overuse of broad-spectrum agents. In this study, we analysed how results of bile and blood cultures and patient data can be used for selection of empirical antibiotic therapy in acute cholangits. Methods Pathogen frequencies and susceptibility rates were determined in 423 positive bile duct cultures and 197 corresponding blood cultures obtained from 348 consecutive patients with acute cholangitis. Patient data were retrieved from the medical records. Associations of patient and microbiological data were assessed using the Chi-2 test and multivariate binary logistic regression. Results In bile cultures, enterobacterales and enterococci were isolated with equal frequencies of approximately 30% whereas in blood cultures, enterobacterales predominated (56% compared to 21% enterococci). Antibiotic resistance rates of enterobacterales were > 20% for fluorochinolones, cephalosporines and acylureidopenicillins but not for carbapenems (< 2%). The efficacy of empirical therapy was poor with a coverage of bacterial bile and blood culture isolates in 51 and 69%, respectively. By multivariate analysis, predictors for pathogen species, antibiotic susceptibility and expected antibiotic coverage were identified. Conclusions In unselected patients treated for acute cholangitis in a large tertiary refferential center, use of carbapenems seems necessary to achieve a high antibiotic coverage. However, by analysis of patient and microbiological data, subgroups for highly effective carbapenem-sparing therapy can be defined. For patients with community-acquired cholangitis without biliary prosthesis who do not need intensive care, piperacillin/tazobactam represents a regimen with an expected excellent antibiotic coverage.

Patients with bacteraemia constitute an useful population for an audit of antibiotic treatments. Empirical antibiotic therapy (EAT) and its reassessment must take into account clinical data and microbiological results. Our aim was to determine the impact of these sequential steps of the therapy on survival. This was a retrospective multicentre study which included patients admitted to emergency departments (ED) for whom blood cultures were positive over a 4-month period. Microbial results were compiled from the database of the laboratories. The relevant information was extracted from the computerized patient’s chart. An efficient EAT was based on antibiotic susceptibility of the bacteria. An effective antibiotic reassessment (AR) was defined as any modification of the EAT. Unfavorable outcome was defined as death of the patient during in-hospital care. Three hospitals and two clinics took part in this study, 169 patients with bacteraemia being included. The diagnosis in ED was undetermined in 21 cases (12%), 35 patients (21%) required intensive care, and 23 died (14%). One hundred and thirty-six patients (80%) received an EAT, the latter being efficient in 107 cases (63%). An effective AR was performed in 116 cases (69%). In multivariate analysis, risks factors for death were: ongoing cancer AOR (adjusted odds ratio) 3.34, undetermined diagnosis in ED: AOR 9.34 and severe sepsis or shock: AOR 6.98. Effective AR was a protective factor: AOR 0.28 [0.09–0.81]. One third of bacteraemic patients in ED did not benefit from AR. Improvement of antimicrobial stewardship should be associated with a higher rate of survival.

Background Antimicrobial resistance (AMR) is a global health threat with millions of deaths annually attributable to bacterial resistance. Effective antimicrobial stewardship programs are crucial for optimizing antibiotic use. This study aims to identify factors contributing to deviations from antibiotic treatment guidelines in hospitalized adults with suspected community-acquired pneumonia (CAP). Methods We conducted a prospective study at Haukeland University Hospital's Emergency Department in Bergen, Norway, from September 2020 to April 2023. Patients were selected from two cohorts, with data on clinical and microbiologic test results collected. We analysed adherence of antibiotic therapy to guidelines for the choice of empirical treatment and therapy duration using multivariate regression models to identify predictors of non-adherence. Results Of the 523 patients studied, 479 (91.6%) received empirical antibiotic therapy within 48 h of admission, with 382 (79.7%) adhering to guidelines. However, among the 341 patients included in the analysis of treatment duration adherence, only 69 (20.2%) received therapy durations that were consistent with guideline recommendations. Key predictors of longer-than-recommended therapy duration included a C-reactive protein (CRP) level exceeding 100 mg/L (RR 1.37, 95% CI 1.18–1.59) and a hospital stay longer than two days (RR 1.22, 95% CI 1.04–1.43). The primary factor contributing to extended antibiotic therapy duration was planned post-discharge treatment. No significant temporal trends in adherence to treatment duration guidelines were observed following the publication of the updated guidelines. Conclusion While adherence to guidelines for the choice of empirical antibiotic therapy was relatively high, adherence to guidelines for therapy duration was significantly lower, largely due to extended post-discharge antibiotic treatment. Our findings suggest that publishing updated guidelines alone is insufficient to change clinical practice. Targeted stewardship interventions, particularly those addressing discharge practices, are essential. Future research should compare adherence rates across institutions to identify factors contributing to higher adherence and develop standardized benchmarks for optimal antibiotic stewardship. Trial registration NCT04660084.

Background Temporal changes in the microbiological resistance profile have been reported in several life-threatening infections. However, no data have ever assessed this issue in postoperative peritonitis (POP). Our purpose was to assess the rate of multidrug-resistant organisms (MDROs) in POP over a two-decade period and to analyse their influence on the adequacy of empirical antibiotic therapy (EAT). Methods This retrospective monocentric analysis (1999–2019) addressed the changes over time in microbiologic data, including the emergence of MDROs and the adequacy of EAT for all intensive care unit adult patients treated for POP. The in vitro activities of 10 antibiotics were assessed to determine the most adequate EAT in the largest number of cases among 17 antibiotic regimens in patients with/without MDRO isolates. Our primary endpoint was to determine the frequency of MDRO and their temporal changes. Our second endpoint assessed the impact of MDROs on the adequacy of EAT per patient and their temporal changes based on susceptibility testing. In this analysis, the subgroup of patients with MDRO was compared with the subgroup of patients free of MDRO. Results A total of 1,318 microorganisms were cultured from 422 patients, including 188 (45%) patients harbouring MDROs. The growing proportions of MDR Enterobacterales were observed over time ( p  = 0.016), including ESBL-producing strains ( p  = 0.0013), mainly related to Klebsiella spp ( p  < 0.001). Adequacy of EAT was achieved in 305 (73%) patients. Decreased adequacy rates were observed when MDROs were cultured [ p  = 0.0001 vs. MDRO-free patients]. Over the study period, decreased adequacy rates were reported for patients receiving piperacillin/tazobactam in monotherapy or combined with vancomycin and imipenem/cilastatin combined with vancomycin ( p  < 0.01 in the three cases). In patients with MDROs, the combination of imipenem/cilastatin + vancomycin + amikacin or ciprofloxacin reached the highest adequacy rates (95% and 91%, respectively) and remained unchanged over time. Conclusions We observed high proportions of MDRO in patients treated for POP associated with increasing proportions of MDR Enterobacterales over time. High adequacy rates were only achieved in antibiotic combinations involving carbapenems and vancomycin, while piperacillin/tazobactam is no longer a drug of choice for EAT in POP in infections involving MDRO. Graphical Abstract

Community acquired pneumonia is one of the infectious diseases of the lungs with high morbidity and mortality rates. Rapid empirical antibiotic administration is needed to overcome this. Length of stay is one of the clinical outcomes in community acquired pneumonia, but until now there is no clear data related to the length of stay associated with the number of empirical antibiotics given to community acquired pneumonia patients. This study aims to see the difference in the length of stay between monotherapy and polytherapy patients. The research method used was descriptive analytic with a cross-sectional approach with the study sample including patients with a diagnosis of community acquired pneumonia and hospitalized who met the inclusion and exclusion criteria. Data collection was taken from medical record data in one of public hospital Bali in 2019. The collected data were analyzed univariately and bivariately. The results obtained from this study were that there was no difference in the median length of stay between monotherapy and polytherapy patients, both of which had a median of 5 days, while significant differences (p=0.01) were seen in the mean length of hospitalization between patients with monotherapy (4.88±2.14) and polytherapy (7.09±3.39) tested by the mann whitney. Further research is needed to clarify the relationship between the addition of empirical antibiotics and length of stay community pneumonia patients.