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Background: Although several conditions and specific risk factors have been associated with stillbirth (SB), in most of the cases it is difficult to identify the definitive etiopathology and cause of death. Specifically, the role of infections in SB is still debated. Our aim was to study maternal, placental, and fetal tissues in cases of SB in order to define the causative link between infections and fetal death, through a multidisciplinary clinical audit. Methods: Between 2014 and 2022, microbiological investigations on maternal, placental and fetal samples of SB cases were performed according to a standardized protocol including serology, cultures, and molecular biology. Autopsies and placental examination were mandatory in all SB cases. Results: A total of 182 cases of SB were investigated. Bacteria were detected in 22.2% of vaginal swabs, 65% of placental biopsies, 29% of fetal blood, and 14.1% of oropharyngeal swabs. Vaginal and oropharyngeal swabs were positive for urogenital mycoplasmas in 25.2% and 8.6%, respectively. Positive results of microbiological investigations, in association with histological features suggestive of infection, were observed in six cases, indicating that fetal death was likely related to a bacterial infection. In one case, a high SARS-CoV-2 load was found in the placenta of a SB due to placental abruption. Conclusions: Infections were likely associated with fetal death in 3.8% of cases. Thus, in developed countries, an infection, defined when positive microbiological findings are associated with histological evidence of organ damage, is a minor contributory factor in SB. [ABSTRACT FROM AUTHOR]

Objectives: The main aim of this study was to describe the epidemiology of infected non-unions (INUs) managed at an Infectious Disease (ID) referral centre and to investigate the factors associated with treatment failure. Methods: This was an observational retrospective study on adult patients with INUs managed between 2012 and 2018 at the ID Unit of the IRCCS Azienda Ospedaliero-Universitaria di Bologna, an Italian ID referral centre for bone and joint infections. Patients were observed for at least 24 months. Those who achieved clinical success were compared with those who experienced clinical failure; to identify factors associated with treatment failure, we performed a univariate and multivariate logistic regression analysis. Results: Overall, 78 patients were included. A total of 57/78 (73%) were males; their median age was 43 (IQR 34–56) years; their median Charlson index was 0 (IQR 0–2); 32/78 (41%) reported a history of an open fracture; the non-union most frequently involved the leg. Polymicrobial infection was found in 23/78 cases (29%); the most common microorganisms were coagulase-negative staphylococci (n = 47) and Staphylococcus aureus (n = 35). At 24-month follow-up from index surgery, 16/78 patients had experienced clinical failure: 13 (16.6%) presented with persistence of local signs of infection and 3 (3.8%) had undergone amputation. Logistic regression analysis of risk factors for clinical failure identified body mass index (BMI) (aOR 1.15; 95% CI 1.03–1.28, p = 0.01) and MRSA infection (aOR 5.35; 95% CI 1.06–26.92, p = 0.04) as factors associated with clinical failure. Conclusions: Given that a standardized management of antibiotic therapy is initiated by an expert ID consultant team, BMI and MRSA infection are associated with worse outcomes among patients with INUs. [ABSTRACT FROM AUTHOR]

Purpose: Acute appendicitis (AA), classified as non-complicated acute appendicitis (NCAA) and complicated acute appendicitis (CAA), is the most common cause of abdominal pain in children requiring surgical treatment. If the first-line treatment for NCAA is to be debated between conservative management and surgery, authors find a consensus in choosing surgery as the first step for CAA in children. In the case of patients with CAA undergoing surgery, a broad-spectrum antibiotic therapy should be administered to reduce the risk of post-operative complications (POC). The rise in antibiotic resistance requires a review of recent data regarding bacterial species involved in AA. The primary aim of our study was to investigate the clinical effectiveness of different antibiotic protocols in patients undergoing surgery for CAA. The secondary aim was to verify the antibiotic's in vitro effectiveness based on cultural examinations. Methods: A retrospective and prospective study was conducted on all patients operated on at our pediatric surgery department for CAA from January 2017 to January 2023. The following data were collected: age at surgery, sex, surgical technique, duration of the procedure, antibiotic therapy, duration of the hospital stay, cultural examination of peritoneal effusion, and POC. Results: We divided the patients enrolled (n = 182) into three groups of antibiotic protocols; only one group resulted in a statistically significant lower rate of POC. Different pathogens were isolated (Enterobacteriaceae, non-fermentative Gram-negative bacilli, anaerobes, Gram-positive cocci), and the in vitro rate of antimicrobial sensitivity varied from 40% to 94% in the three groups of patients. Conclusions: Based on cultural examinations, our study showed a high rate of inadequacy regarding the therapy with amoxicillin + clavulanic acid despite a low rate of complications. Radical surgery seems to be the best way to reduce complications in children with CAA. [ABSTRACT FROM AUTHOR]

Objectives Ceftazidime/avibactam is a key antibiotic for carbapenemase-producing Enterobacterales (CPE) Gram-negative infections, but current dosing may be suboptimal to grant activity. This study explores the population pharmacokinetics/pharmacodynamics (PK/PD) of continuous infusion (CI) ceftazidime/avibactam for maximizing treatment efficacy in critically ill patients. Methods A retrospective analysis of adult patients receiving CI ceftazidime/avibactam and therapeutic drug monitoring (TDM) of both compounds was performed. Population PK/PD modelling identified the most accurate method for estimating ceftazidime/avibactam clearance based on kidney function and Monte Carlo simulations investigated the relationship between various CI dosing regimens and aggressive joint PK/PD target attainment of ceftazidime/avibactam. Results The European Kidney Function Consortium (EKFC) equation best described kidney function for ceftazidime/avibactam clearance. The findings challenge the current approach of only reducing the ceftazidime/avibactam dose based on kidney function by identifying dose adjustments in patients with augmented kidney function. Our CI ceftazidime/avibactam dosing strategies, adjusted by TDM, showed promise for achieving optimal aggressive joint PK/PD targets and potentially improving clinical/microbiological outcomes against KPC- and OXA-48-producing Enterobacterales. The risk of neurotoxicity associated with these strategies appears acceptable. Conclusions This study suggests that adjusting ceftazidime/avibactam dosing regimen based solely on eCLcr might be suboptimal for critically ill patients. Higher daily doses delivered by CI and adjusted based on TDM have the potential to improve aggressive joint PK/PD target attainment and potentially clinical/microbiological outcomes. Further investigations are warranted to confirm these findings and establish optimal TDM-guided dosing strategies for ceftazidime/avibactam in clinical practice. [ABSTRACT FROM AUTHOR]

Objective To analyse the biliary pharmacokinetics/pharmacodynamics (PK/PD) of continuous infusion (CI) meropenem-vaborbactam (MEM-VBM) in a case series of orthotopic liver transplant (OLT) recipients being treated for Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) related biliary tract infections (BTIs) or as preemptive therapy of KPC-Kp rectal colonization. Methods Critical OLT recipients receiving CI MEM-VBM (2 g/2 g q8h over 8 h) because of KPC-Kp related BTIs or as preemptive therapy of KPC-Kp rectal colonization, having Kehr's tube positioned and undergoing simultaneous therapeutic drug monitoring of MEM and VBM in plasma and bile were retrospectively assessed. Bile-to-plasma ratio of free steady-state concentrations (f Css) of MEM and VBM was used for assessing biliary penetration. Optimal joint MEM-VBM PK/PD target attainment was defined as MEM f Css/MIC ratio >4 coupled with VBM free area under time–concentration curve (f AUC)/threshold concentration (CT) ratio >24. Results Overall, four critical OLT recipients were included. Median bile-to-plasma ratio was 0.32 for MEM (range 0.21–0.79) and 0.40 for VBM (range 0.20–0.77). Biliary MEM-VBM joint PK/PD target attainment was optimal in 3/4 OLT recipients and quasi-optimal in the other one. Conclusions The 1:1 proportion between MEM and VBM concentrations was maintained unchanged in the bile, allowing us to assume that the efficacy of MEM-VBM may be appropriate even in the treatment of BTIs. CI administration was an effective strategy for attaining aggressive biliary joint PK/PD targets against pathogens with an MIC up to 2 mg/L. [ABSTRACT FROM AUTHOR]

Perioperative antibiotic prophylaxis (PAP) in lung transplant recipients (LuTRs) has high heterogeneity between centers. Our aim was to investigate retrospectively the approach to PAP in our center over a 20-year period (2002-2023), and its impact on early postoperative infections (EPOIs) after lung transplantation (LuT). Primary endpoint was diagnosis of EPOI, defined as any bacterial infection including donor-derived events diagnosed within 30 days from LuT. Main exposure variables were type of PAP (combination vs. monotherapy) and PAP duration. We enrolled 111 LuTRs. PAP consisted of single-agent or combination regimens in 26 (25.2%) and 85 (74.8%) LuTR. Median PAP duration was 10 days (IQR 6-13) days. Piperacillin/tazobactam was the most common agent used either as monotherapy (n = 21, 80.7%) or as combination with levofloxacin (n = 79, 92.9%). EPOIs were diagnosed in 30 (27%) patients. At multivariable analysis no advantages were found for combination regimens compared to single-agent PAP in preventing EPOI (OR: 1.57, 95% CI: 0.488-5.068, p: 0.448). The impact of PAP duration on EPOIs development was investigated including duration of PAP =6 days as main exposure variables, without finding a significantly impact (OR:2.165, 95% CI: 0.596-7.863, p: 0.240). Our results suggest no advantages for combination regimens PAP in preventing EPOI in LuTR. [ABSTRACT FROM AUTHOR]