Background: Currently, the escalation of microbial resistance poses a significant global challenge. Children are more susceptible to develop infections and therefore are prescribed antibiotics more frequently. The overuse and misuse of antibiotics in pediatric patients can play a considerable role in developing microbial resistance. Accordingly, many policies, including research into new antibiotic agents have been recommended to combat microbial resistance. Recent developments in novel antibiotics have shown promising results against multi-drug resistant (MDR) and extensive drug resistance (XDR) pathogens. However, as pediatric patients are typically excluded from the clinical trials of new medications, labeling and information about approved antibiotics should be improved. This study aimed to evaluate antibiotics having been introduced to the market in the last decade focusing on pediatric population. Methods: This study reviewed the published literatures on novel FDA-approved antibiotics released between 2010 and 2022. Results: Finally, seven newly approved antibiotics including ceftaroline fosamil, ceftazidime-avibactam, ceftolozane-tazobactam, ceftobiprole, imipenem-cilastatin-relebactam, meropenem-vaborbactam, and tedizolid were considered in the present review-article. All relevant data extracted from literatures, were discussed in different subtitles of "Pharmacology", "Mechanism of action", "Indication", "Dosage regimen and pharmacokinetic and pharmacodynamic properties", "Dosage adjustment in renal/liver failure", "Resistance pattern", and "Adverse drug events". Conclusion: This study reviewed available data on seven new antibiotic agents and their pharmacodynamic and pharmacokinetic properties, with a particular focus on their use in pediatric patients. The information presented in this review will be useful for healthcare professionals in selecting appropriate antibiotics for pediatric patients and for researchers in achieving the ideal therapeutic regimens.

Background: Our multi-institutional healthcare system had a higher-than-expected surgical site infection (SSI) rate. We aimed to improve our peri-operative antibiotic administration process. Gap analysis identified three opportunities for process improvement: standardized antibiotic selection, standardized second-line antibiotic agents for patients with allergies, and feedback regarding antibiotic administration compliance. Hypothesis: Implementation of a multifaceted quality improvement initiative including a near-real-time pre-operative antibiotic compliance feedback tool will improve compliance with antibiotic administration protocols, subsequently lowering SSI rate. Methods: A compliance feedback tool designed to provide monthly reports to all anesthesia and surgical personnel was implemented at two facilities, in September 2017 and December 2018. Internal case data were tracked for antibiotic compliance through June 2021, and these data were merged with American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) data at the case level to provide process and outcome measures for SSIs. Implementation success was evaluated by comparing protocol compliance and risk-adjusted rates of superficial and deep SSI before and after the quality improvement implementation. Results: A total of 20,385 patients were included in this study; 11,548 patients in the pre-implementation and 8,837 in the post-implementation groups. Baseline patient and operative characteristics were similar between groups, except the post-implementation group had a higher median expected SSI rate (2.2% vs. 1.6%). Post-implementation, antibiotic protocol compliance increased from 86.3% to 97.6%, and superficial and deep SSIs decreased from 2.8% to 1.9% (p < 0.001). The odds of superficial and deep SSI in patients in the post-implementation group was 0.69 (0.57, 0.83) times the odds of superficial and deep SSI in pre-implementation patients while adjusting for age, gender, diabetes mellitus, American Society of Anesthesiologists Physical Status (ASA) classification, wound class, smoking, and chronic obstructive pulmonary disease (COPD). Observed-to-expected ratios of superficial and deep SSI decreased from 0.82 to 0.48 after the intervention. Conclusions: Surgical antibiotic prophylaxis standardization and providing near-real-time individualized feedback resulted in sustained improvement in peri-operative antibiotic compliance rates and reduced superficial and deep SSIs.

Background: The correlation between pre-operative serum pre-albumin and surgical site infection (SSI) has been the focus of many studies. However, existing literature presents conflicting evidence on this association. Therefore, this meta-analysis was conducted to determine the significance of low serum pre-albumin as a prognostic factor SSI, and to assess the potential utility of pre-albumin in predicting SSI. Methods: A comprehensive literature search and analysis was conducted in PubMed, Web of Science, Cochrane of Library, Scopus, Embase, and Google Scholar databases through August 2022 to identify studies reporting low pre-operative serum pre-albumin levels in patients undergoing surgery and their association with SSIs. The pooled risk estimates were shown in odds ratio with 95% confidence interval. The random effect model was used according to the test of heterogeneity among studies. Subgroup analyses and sensitivity analyses were performed to identify the possible sources of heterogeneity. This meta-analysis was prospectively registered in the PROSPERO database (number: CRD42022376167). Results: Nine studies involving 5,306 patients were eligible. The results demonstrated an association between low pre-operative serum pre-albumin levels and a higher probability of developing SSI (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.28-3.26). Conclusions: Our findings suggest that low serum pre-albumin level may serve as an independent and valuable predictor of SSI. These results provide important insights for clinicians in identifying high-risk patients and implementing preventive measures.

Background: There is increasing recognition of extensive crosstalk between programmed cell death pathways (PCDPs), such as apoptosis, pyroptosis, and necroptosis, resulting in a highly redundant system responsive to a breadth of potential pathogens. However, because pyroptosis and necroptosis propagate inflammation, these redundancies also present challenges for therapeutic control of dysregulated hyperinflammation seen in cytokine storm (CS) generated organ dysfunction. Hypothesis: We hypothesize that the conversion of existing knowledge regarding apoptosis, pyroptosis, and necroptosis into a computational model can enhance our understanding of the crosstalk between PCDPs via simulation experiments of microbe interactions and experimental interventions. Materials and Methods: Literature regarding apoptosis, pyroptosis, and necroptosis was reviewed and transposed into an agent-based model, the programmed cell death agent-based model (PCDABM). Computational experiments were performed to simulate the activation of various PCDPs as seen by differing microbes, specifically: influenza A virus (IAV), enteropathic Escherichia coli (EPEC), and Salmonella enterica (SE). The potential protective value of PCDP crosstalk was evaluated by silencing either pyroptosis, necroptosis, or both. Computational experiments were also performed simulating the effect of potential therapies blocking tumor necrosis factor (TNF) and interleukin (IL)-1. Results: The PCDABM was implemented in the agent-based modeling toolkit NetLogo. Computational experiments of infection with IAV, EPEC, and SE reproduced cross-activation of PCDPs with effective microbial clearance. Simulations of anti-TNF and anti-IL-1 did not reduce the aggregated amount of inflammation-generated system damage, the surrogate for CS-generated tissue damage. Conclusions: Redundancies have evolved in host PCDPs to maintain protection against a wide range of pathogens. However, these redundancies also challenge attempts at dampening the pathogenic hyperinflammatory state of CS using therapeutic immunomodulation. Integrative simulation models such as the PCDABM can aid in identifying potentially targetable inflection points to mitigate CS while maintaining effective host defense.

Background: Severity scoring systems are used widely to predict prognosis in managing various diseases and to tailor the treatment of patients in a personalized way, not in a general concept, by making a risk assessment. This study examines the importance of the Temperature-Neutrophils-Multiple Organ Failure (TNM) scoring system, a new scoring system, in evaluating the prognosis in patients with Fournier gangrene (FG). Patients and Methods: Patients who were operated on with the diagnosis of FG in our clinic between 2012 and 2022 were analyzed with a single-center cross-sectional retrospective study design. Demographic data (age, gender), pre-operative evaluation, body temperature, neutrophil ratio, presence of multiple organ failure, TNM score, and post-operative survival data were recorded. The patients were grouped as those with post-operative hospital mortality (group 1) and without (group 2). Results: The study included 167 patients. Twenty-two (13.2%) of the patients were in group 1 and 145 (86.8%) were in group 2. According to the TNM score, the frequency of stage 3-4 was higher in group 1 than in group 2 (p < 0.001). Patients ≥65 years of age had a 4.80 (95% confidence interval [CI], 1.87-12.29) times greater mortality risk than patients <65. Patients with comorbid disease had a 4.56 (95% CI, 1.47-14.14) times greater risk of mortality than patients without. Patients with TNM scores 3-4 had a 9.38 (95% CI, 3.01-29.28) times greater risk of exit than patients with scores 1-2. Conclusions: The TNM system is a new scoring system that is created quickly using simple laboratory and clinical data in patients with FG and is useful in predicting mortality. Therefore, its clinical use will benefit FG and other deep soft tissue infections.

Background: Early initiation of broad-spectrum antibiotic agents is a cornerstone of the care of necrotizing skin and soft tissue infections (NSTI). However, the optimal duration of antibiotic agents is unclear. We sought to characterize antibiotic prescribing patterns for patients with NSTI, as well as associated complications. Patients and Methods: Using an NSTI registry, we characterized antibiotic use at a quaternary referral center. Kaplan-Meier analyses were used to describe overall antibiotic duration and relative to operative source control, stratified by presence of other infections that independently influenced antibiotic duration. Factors associated with successful antibiotic discontinuation were identified using logistic regression. Results: Between 2015 and 2018, 441 patients received antibiotic agents for NSTI with 18% experiencing a complicating secondary infection. Among those without a complicating infection, the median duration of antibiotic administration was 9.8 days (95% confidence interval [CI], 9.2-10.5) overall, and 7.0 days after the final debridement. Perineal NSTI received fewer days of antibiotic agents (8.3 vs. 10.6) compared with NSTI without perineal involvement. White blood cell (WBC) count and fever were not associated with failure of antibiotic discontinuation, however, a chronic wound as the underlying infection etiology was associated with greater odds of antibiotic discontinuation failure (odds ratio [OR], 4.33; 95% CI, 1.24-15.1). Conclusions: A seven-day course of antibiotic agents after final operative debridement may be sufficient for NSTI without any secondary complicating infections, because clinical characteristics do not appear to be associated with differences in successful antibiotic discontinuation.

Background: To understand the differences between patients with diabetes mellitus and obese patients with respect to the occurrence of peri-prosthetic joint infection (PJI) after lower-extremity joint arthroplasty as well as to identify differences in PJI occurrence at different time periods. Patients and Methods: The Cochrane Library, CINAHL, MEDLINE, and PubMed were searched for literature published between January 2000 and July 2022. Our targets were studies involving patients with PJI who had already been diagnosed as having diabetes mellitus or being obese before receiving lower-extremity joint arthroplasty. Analysis was performed using Comprehensive Meta-Analysis Software (CMA) Version 3 (Biostat, Inc., Englewood, NJ, USA). Results: A total of 53,522 patients with diabetes mellitus and 360,018 obese patients were included. The forest plot for patients with and without diabetes mellitus indicated that patients with diabetes mellitus were more likely to contract PJIs than were patients without diabetes mellitus (odds ratio, 1.84; 95% confidence interval [CI], 1.56-2.16) and that no differences existed among early, delayed, and late PJI occurrence in patients with diabetes mellitus. The forest plot for obese and non-obese patients indicated that obese patients were more likely to contract PJIs than were non-obese patients (odds ratio, 1.86; 95% CI, 1.53-2.14) and that among obese patients, early PJI occurrence was higher than was late PJI occurrence. In addition, the mixed model indicated that obese patients were more likely to develop early PJIs than were patients with diabetes mellitus. Conclusions: Patients with diabetes mellitus and obese patients were more likely to develop PJIs than were patients without diabetes mellitus and non-obese patients, and that obese patients were more likely to develop early PJIs than late PJIs. Also, obese patients were more likely to develop early PJIs than patients with diabetes mellitus.

Background: Surgical site infections (SSIs) have been associated with increases in terms of costs, hospital stay, morbidity, and mortality. We aimed to assess trends in SSIs monitored through 10 years of surveillance activities in our region, and to describe mortality attributable to SSIs in the two most frequently monitored surgical procedures: colorectal surgery and hip arthroplasty. Methods: A retrospective cohort study was conducted among the 42 hospitals participating in the surveillance network of our region in northern Italy. All colorectal and hip arthroplasty procedures performed between January 1st, 2010, and December 31st, 2019, and monitored through the surveillance system were included in the study. Surgical site infection rates, overall mortality, case fatality rates (CFR), and mortality attributable to SSIs were evaluated overall and by year of participation in the surveillance program. Results: In total, 11,417 colon surgery and 20,804 hip arthroplasty procedures were included. Among colon surgery procedures, SSI rates decreased from 9.21% in 2010 to 5.7% in 2019. A significant decreasing trend was found for overall mortality (p = 0.008), which progressively decreased from 4.96% in 2010 to 2.96% in 2019. Among hip arthroplasty procedures, no significant trend emerged for SSI and mortality rates. Considering the 10-year period, the CFR was 6.62% and 3.7% for SSIs after colon surgery and hip arthroplasty procedures, respectively. Conclusions: The impact of SSIs on the clinical outcomes of patients undergoing surgery highlights the importance of SSI surveillance.

Background: Although oral hygiene in patients in the intensive care unit (ICU) has been shown to reduce hospital-associated infections, baseline and progressive oral health are often not reported because of lack of a standardized tool. The Oral Health Risk Assessment Value Index (OHRAVI) is a comprehensive oral assessment validated by dental providers. This study hypothesizes that non-dental providers can use OHRAVI in trauma ICU patients with minimal training and acceptable inter-rater reliability (IRR). Patients and Methods: Dentulous adult patients in the ICU at a level 1 trauma center were scored, excluding those with severe orofacial trauma. The eight categories of the OHRAVI were scored 0 to 3 (best to worst) with summed total and index (average) score. Index scores 1 or less need routine oral care; greater than 1-2 require moderate care; and greater than 2-3 require extensive oromaxillofacial care. Inter-rater reliability was assessed by two to three raters with Krippendorff's α (≥0.80 for good and ≥0.667 for acceptable). Results: Eighty-four ratings were completed across 34 patients, with 16 patients (47%) scored by all three raters. Ten patients (29%) had an index score <1. The average index score for patients was 1.28 (median, 1.34; range, 0.63-2). Krippendorff's α for index score was 0.86. For individual categories, α ranged from 0.44 to 1, with six of the eight categories achieving an α ≥ 0.667. Conclusions: With minimal training, non-dental providers were able to use OHRAVI with a good IRR for index score and an acceptable/good IRR for most individual categories. This novel, simple, comprehensive oral health score could help standardize oral assessment and facilitate future studies of peri-operative oral hygiene interventions.

Background: Pediatric acute appendicitis (PAA) involves a substantial consumption of health and economic resources. The identification of serum biomarkers that may help predict the post-surgical evolution of these patients is a field of great interest. Patients and Methods: This was a prospective, observational substudy within the Biomarkers for the Diagnosis of Appendicitis in Pediatrics (BIDIAP) cohort aimed at evaluating the association between post-surgical increase in serum IL-6 and different outcomes related to the clinical evolution of children operated on for PAA. Sixty-nine children with a confirmed diagnosis of acute appendicitis and both pre-operative and post-operative serum IL-6 were included in the study. Three multivariable-adjusted linear regression models were fitted to analyze the association between an increase of >10% in post-operative serum IL-6 level with the length of stay, the number of post-operative emetic episodes, and the onset of oral feeding. Two multivariable-adjusted logistic regression models were fitted to assess the association of the same exposure with the indication of antibiotherapy at discharge and with positivity in peritoneal fluid culture. Results: Thirteen children showed an increase of >10% in the post-operative serum IL-6 value (group 1) whereas 56 showed only a minor increase, or no change (group 2). After accounting for potential confounders, children in group 1 had a mean of three-day longer hospital stay (difference, 3.33; 95% confidence interval [CI], 0.57-6.09) and higher odds of a positive result in peritoneal fluid culture (odds ratio [OR], 37.43; 95% CI, 1.02-1361.28) than children in group 2. Conclusions: An increase of >10% in post-operative serum IL-6 value could predict longer hospital stay and higher odds of positive peritoneal fluid culture. Future prospective studies are needed to replicate these findings and to broaden the range of biomarkers that could predict the post-operative evolution of children operated on for PAA.