Antibiotics

Antibiotic overuse poses a critical global health concern, especially in low- and middle-income countries (LMICs) where access to quality healthcare and effective regulatory frameworks often fall short. This issue necessitates a thorough examination of the factors contributing to antibiotic overuse in LMICs, including weak healthcare infrastructure, limited access to quality services, and deficiencies in diagnostic capabilities. To address these challenges, regulatory frameworks should be implemented to restrict non-prescription sales, and accessible point-of-care diagnostic tools must be emphasized. Furthermore, the establishment of effective stewardship programs, the expanded use of vaccines, and the promotion of health systems, hygiene, and sanitation are all crucial components in combating antibiotic overuse. A comprehensive approach that involves collaboration among healthcare professionals, policymakers, researchers, and educators is essential for success. Improving healthcare infrastructure, enhancing access to quality services, and strengthening diagnostic capabilities are paramount. Equally important are education and awareness initiatives to promote responsible antibiotic use, the implementation of regulatory measures, the wider utilization of vaccines, and international cooperation to tackle the challenges of antibiotic overuse in LMICs. Full article

Campylobacter spp., particularly C. jejuni and C. coli, are major food safety concerns, transmitted to humans mainly via contaminated poultry meat. In a previous study, we found that some commercial broiler farms consistently produced Campylobacter-free flocks while others consistently reared Campylobacter-colonized flocks, and significant differences in the gut microbiota compositions between the two types of farm categories were revealed. Therefore, we hypothesized that gut microbiota influences Campylobacter colonization in poultry and that the microbiota from Campylobacter-free flocks may confer colonization resistance to Campylobacter in the chicken intestine. In this study, two fecal microbiota transplantation (FMT) trials were performed to test the hypothesis. Newly hatched chicks were given FMT via oral gavage of the cecal content of Campylobacter-free adult chickens (treatment groups) or PBS (control groups) before the feed consumption. Approximately two weeks after the FMT, the birds were challenged with C. jejuni either by oral gavage (trial 1) or by co-mingling with Campylobacter-colonized seeder birds (trial 2) to evaluate the potential protective effect of the FMT. Cecal contents were collected (3 times, 5 days apart) to determine the Campylobacter colonization levels via culture and microbiota compositions via 16S rRNA gene sequencing. FMT reduced cecal Campylobacter colonization significantly (log₁₀ 1.2–2.54 CFU/g) in trial 1 but not in trial 2, although FMT significantly impacted the diversity and compositions of the gut microbiota in both trials. Several genera, such as Butyricimonas, Parabacteroides, Parasutterella, Bilophila, Fournierella, Phascolarctobacterium, and Helicobacter, had increased abundance in the FMT-treated groups in both trials. Furthermore, Campylobacter abundance was found to be negatively correlated with the Escherichia and Ruminococcus_torques_group genera. These findings indicate that even though FMT with adult cecal microbiota can positively affect the subsequent development of the gut microbiota in young broilers, its inhibitory effect on Campylobacter colonization varies and appears to be influenced by the challenge models. Full article

FTIR (Fourier transform infrared spectroscopy) is one analytical technique of the absorption of infrared radiation. FTIR can also be used as a tool to characterize profiles of biomolecules in bacterial cells, which can be useful in differentiating different bacteria. Considering that different bacterial species have different molecular compositions, it will then result in unique FTIR spectra for each species and even bacterial strains. Having this important tool, here, we have developed a methodology aimed at refining the analysis and classification of the FTIR absorption spectra obtained from samples of Staphylococcus aureus, with the implementation of machine learning algorithms. In the first stage, the system conforming to four specified species groups, Control, Amoxicillin induced (AMO), Gentamicin induced (GEN), and Erythromycin induced (ERY), was analyzed. Then, in the second stage, five hidden samples were identified and correctly classified as with/without resistance to induced antibiotics. The total analyses were performed in three windows, Carbohydrates, Fatty Acids, and Proteins, of five hundred spectra. The protocol for acquiring the spectral data from the antibiotic-resistant bacteria via FTIR spectroscopy developed by Soares et al. was implemented here due to demonstrating high accuracy and sensitivity. The present study focuses on the prediction of antibiotic-induced samples through the implementation of the hierarchical cluster analysis (HCA), principal component analysis (PCA) algorithm, and calculation of confusion matrices (CMs) applied to the FTIR absorption spectra data. The data analysis process developed here has the main objective of obtaining knowledge about the intrinsic behavior of S. aureus samples within the analysis regions of the FTIR absorption spectra. The results yielded values with 0.7 to 1 accuracy and high values of sensitivity and specificity for the species identification in the CM calculations. Such results provide important information on antibiotic resistance in samples of S. aureus bacteria for potential application in the detection of antibiotic resistance in clinical use. Full article

During the COVID-19 pandemic, patients in need of neurosurgical care suffered. Elective procedures were postponed, and emergency care visits decreased. Healthcare-associated ventriculitis (HAV) is a serious problem in children, with poor outcomes and frequent relapses. Our objective was to describe the clinical characteristics and the factors associated with a first HAV in children during two years of the pandemic. A retrospective cross-sectional study was performed from January 2021 to December 2022. The inclusion criteria were patients who developed a first HAV after a primary cerebrospinal fluid diversion procedure. The controls included patients without a first infection. Intraoperative and clinical data were extracted from medical records. A total of 199 CSF diversion surgeries were registered. A first infection occurred in 17 patients (8.5%), including 10 with external ventricular drain (EVD) and 6 with ventricular shunts. Gram-positive cocci were identified in 70.6%. Six patients recovered uneventfully, eight had relapse or superinfections, and three eventually died. Twenty patients were included as controls. Factors associated with a first infection were a younger age (median 9 vs. 102 months, p < 0.01), malnutrition (23.5% vs. 0%, p = 0.03), and an EVD placement (58.8% vs. 10%, p = 0.03). None of the intraoperative factors showed statistically significant differences. The rate of HAV was high. Most cases presented in children <1 year and with an EVD. Full article

Glycolipids are biocompatible and biodegradable amphiphilic compounds characterized by a great scientific interest for their potential applications in various technological areas, including pharmaceuticals, cosmetics, agriculture, and food production. This report summarizes the available synthetic methodologies, physicochemical properties, and biological activity of sugar fatty acid ester surfactants, with a particular focus on 6-O-glucose, 6-O-mannose, 6-O-sucrose, and 6′-O-lactose ones. In detail, the synthetic approaches to this class of compounds, such as enzymatic lipase-catalyzed and traditional chemical (e.g., acyl chloride, Steglich, Mitsunobu) esterifications, are reported. Moreover, aspects related to the surface activity of these amphiphiles, such as their ability to decrease surface tension, critical micelle concentration, and emulsifying and foaming ability, are described. Biological applications with a focus on the permeability-enhancing effect across the skin or mucosa, antimicrobial and antifungal activities, as well as antibiofilm properties, are also presented. The information reported here on sugar-based ester surfactants is helpful to broaden the interest and the possible innovative applications of this class of amphiphiles in different technological fields in the future. Full article

Background. Rifampicin is a pillar in the treatment of periprosthetic joint infection (PJI). However, rifampicin resistance is an increasing threat to PJI treatment. This study explores the incidence of rifampicin-resistant bacteria over time in a Swedish tertiary referral centre and the association of rifampicin resistance with infection-free survival after PJI. Methods. The study included 238 staphylococcal PJIs treated between 2001 and 2020 for which susceptibility data for rifampicin were available. Data on causative bacteria, rifampicin resistance, treatment, and outcome were obtained. Kaplan–Meier survival analysis and Cox regression modelling estimated the infection-free cumulative survival and adjusted hazard ratios (HRs) for the risk of treatment failure. Results. Rifampicin-resistant causative bacteria were identified in 40 cases (17%). The proportion of rifampicin-resistant agents decreased from 24% in 2010–2015 to 12% in 2016–2020. The 2-year infection-free survival rates were 78.6% (95% CI, 66.4–93.1%) for the rifampicin-resistant group and 90.0% (95% CI, 85.8–94.4%) for the rifampicin-sensitive group. Patients with PJI caused by rifampicin-resistant bacteria had an increased risk of treatment failure (adjusted HR, 4.2; 95% CI, 1.7–10.3). Conclusions. The incidence of PJI caused by rifampicin-resistant bacteria did not increase over the past 20 years. The risk of treatment failure in PJI caused by rifampicin-resistant bacteria is more than four times that caused by rifampicin-sensitive bacteria, highlighting the importance of limiting the development of rifampicin resistance. Full article

Oritavancin (ORI) is a semisynthetic lipoglycopeptide approved as a single 1200 mg dose intravenous infusion for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by Gram-positive organisms in adults. The pharmacokinetic/pharmacodynamic (PK/PD) linear kinetic profile and long terminal half-life (~393 h) of ORI make it therapeutically attractive for the treatment of other Gram-positive infections for which prolonged therapy is needed. Multidose regimens are adopted in real-world clinical practice with promising results, but aggregated efficacy data are still lacking. A comprehensive search on PubMed/Medline, Scopus, Cochrane and Google Scholar databases was performed to include papers published up to the end of January 2023. All articles on ORI multiple doses usage, including case reports, with quantitative data and relevant clinical information were included. Two reviewers independently assessed papers against the inclusion/exclusion criteria and for methodological quality. Differences in opinion were adjudicated by a third party. From 1751 potentially relevant papers identified by this search, a total of 16 studies met the inclusion criteria and were processed further in the final data analysis. We extracted data concerning clinical response, bacteriologic response, mortality and adverse events (AEs). From the 16 included papers, 301 cases of treatment with multidose ORIs were identified. Multidose regimens comprised an initial ORI dose of 1200 mg followed by 1200 mg or 800 mg subsequent doses with a varying total number and frequency of reinfusions. The most often treated infections and isolates were osteomyelitis (148; 54.4%), ABSSSI (35; 12.9%) and cellulitis (14; 5.1%); and MRSA (121), MSSA (66), CoNS (17), E. faecalis (13) and E. faecium (12), respectively. Clinical cure and improvement by multidose ORI regimens were observed in 85% (231/272) and 8% (22/272) patients, respectively. Multidose ORI was safe and well tolerated; the most frequent AEs were infusion-related reactions and hypoglycemia. A multidose ORI regimen may be beneficial in treating other Gram-positive infections besides ABSSSIs, with a good safety profile. Further studies are warranted to ascertain the superiority of one multidose ORI scheme or posology over the other. Full article

Antimicrobial stewardship (AMS) programs are part of the key activities that contribute to reducing antimicrobial resistance (AMR). Good knowledge, attitudes, and practices (KAP) among healthcare professionals (HCPs) are essential to improving future antimicrobial use and reducing AMR, which is a priority in Ghana. A multicenter cross-sectional survey was conducted in six public hospitals in Ghana among key HCPs to assess their level of KAP towards AMS using a validated self-administered electronic questionnaire. Data analyses included descriptive and inferential statistics using STATA version 14. Overall, 339 out of 355 HCPs responded to the questionnaire, giving a response rate of 95.5%. Most responders were nurses (n = 256, 78.2%), followed by medical doctors (n = 45, 13.3%). The study recorded both poor knowledge (8.9%) and practice levels (35.4%), as well as a good attitude (78.8%) towards AMS. Ongoing exposure to AMS structured training, exposure to continuous professional development training on AMS in the previous year, and the number of years of working experience were predictors of the HCPs’ level of knowledge (aOR = 3.02 C.I = 1.12–8.11), attitude (aOR = 0.37 C.I = 0.20–0.69) and practice (aOR = 2.09 C.I =1.09–3.99), respectively. Consequently, concentrated efforts must be made to address current low levels of knowledge and poor practices regarding AMS among HCPs in Ghana as part of ongoing strategies in the National Action Plan to reduce AMR. Full article

(1) Background: Understanding the physicians’ knowledge, attitudes, and antimicrobial prescribing behavior is a crucial step towards designing strategies for the optimal use of these agents. (2) Methods: A cross-sectional online survey was conducted among clinicians across India between May and July 2022 using a self-administered questionnaire in English comprising 35 questions pertaining to demographic characteristics, knowledge, attitude, and practices domains. (3) Results: A total of 544 responses were received from 710 physicians contacted. Sixty percent of participants were males, with mean age of 34.7 years. Mean ± Standard Deviation scores for knowledge, attitude, and practices domains were 8 ± 1.6, 20.2 ± 3.5, and 15.3 ± 2.1, respectively. Higher scores were associated with basic [odds ratio (95% Confidence Interval), p value: 2.95 (1.21, 7.2), 0.02], medical and allied sciences [2.71 (1.09, 6.67), 0.03], and central zone [3.75 (1.39, 10.12), 0.009]. A substantial proportion of dissatisfactory responses were found regarding hospital antibiograms, antibiotics effective against anaerobes, WHO AWaRe (access, watch, and reserve) classification of antibiotics, and the role of infection prevention and control (IPC) measures in the containment of antimicrobial resistance (AMR). (4) Conclusions: There is a need to sensitize and educate clinicians on various issues related to antimicrobial use, such as antibiograms, double anaerobic cover, IPC practices, and guideline-based recommendations, to curb the AMR pandemic. Full article

Acute pancreatitis (AP) is an acute inflammation of the pancreas caused by the activation of digestive enzymes in the pancreatic tissue. The main causes of AP are cholelithiasis and alcohol abuse; less commonly, it can be caused by drugs, with a prevalence of up to 5%. Causal associations between drugs and pancreatitis are largely based on case reports or case series with limited evidence. We reviewed the available data on drug-induced AP, focusing on antimicrobial drugs and antivirals, and discussed the current evidence in relation to the classification systems available in the literature. We found 51 suspected associations between antimicrobial and antiviral drugs and AP. The drugs with the most evidence of correlation are didanosine, protease inhibitors, and metronidazole. In addition, other drugs have been described in case reports demonstrating positive rechallenge. However, there are major differences between the various classifications available, where the same drug being assigned to different probability classes. It is likely that the presence in multiple case reports of an association between acute pancreatitis and a drug should serve as a basis for conducting prospective randomized controlled trials to improve the quality of the evidence. Full article

Hospital wastewater is a recognized reservoir for resistant Gram-negative bacteria. This study aimed to screen for carbapenemase-producing Escherichia coli and Klebsiella pneumoniae and their resistance determinants in two hospital effluents of Ouagadougou. Carbapenem-resistant E. coli and K. pneumoniae were selectively isolated from wastewater collected from two public hospitals in Ouagadougou, Burkina Faso. Bacterial species were identified via MALDI-TOF mass spectrometry. Carbapenemase production was studied phenotypically using antibiotic susceptibility testing via the disk diffusion method. The presence of carbapenemases was further characterized by PCR. A total of 14 E. coli (13.59%) and 19 K. pneumoniae (17.92%) carbapenemase-producing isolates were identified with different distributions. They were, respectively, bla_NDM (71.43%), bla_VIM (42.86%), bla_IMP (28.57%), bla_KPC (14.29%), bla_OXA-48 (14.29%); and bla_KPC (68.42%), bla_NDM (68.42%), bla_IMP (10.53%), bla_VIM (10.53%), and bla_OXA-48 (5.26%). In addition, eight (57.14%) E. coli and eleven (57.89%) K. pneumoniae isolates exhibited more than one carbapenemase, KPC and NDM being the most prevalent combination. Our results highlight the presence of clinically relevant carbapenemase-producing isolates in hospital effluents, suggesting their presence also in hospitals. Their spread into the environment via hospital effluents calls for intensive antimicrobial resistance (AMR) surveillance. Full article

Background: Despite the availability of new options (ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam and cefiderocol), it is still very difficult to treat infections caused by metallo-β-lactamase (MBLs)-producers resistant to aztreonam. The in vitro efficacy of aztreonam in association with avibactam, vaborbactam or relebactam was evaluated on a collection of MBL-producing Enterobacterales, MBL-producing P. aeruginosa and highly drug-resistant S. maltophilia. Methods: A total of fifty-two non-duplicate MBL-producing Enterobacterales, five MBL-producing P. aeruginosa and five multidrug-resistant S. maltophila isolates were used in this study. The minimum inhibitory concentrations (MICs) of aztreonam, meropenem-vaborbactam and imipenem-relebactam were determined by Etest^® (bioMérieux, La Balme-les-Grottes) according to EUCAST recommendations. For aztreonam-avibactam, aztreonam-vaborbactam and aztreonam-relebactam associations, the MICs were determined using Etest^® on Mueller-Hinton (MH) agar supplemented with 8 mg/L of avibactam, 8 mg/L of vaborbactam and 4 mg/L of relebactam. The MICs were interpreted according to EUCAST guidelines. Results: The susceptibility rates of aztreonam-avibactam, aztreonam-vaborbactam and aztreonam-relebactam with a standard exposure of aztreonam (1g × 3, IV) were 84.6% (44/52), 55.8% and 34.6% for Enterobacterales and 0% for all combinations for P. aeruginosa and S. maltophila. The susceptibility rates of aztreonam-avibactam, aztreonam-vaborbactam and aztreonam-relebactam with a high exposure of aztreonam (2g × 4, IV) were 92.3%, 78.9% and 57.7% for Enterobacterales, 75%, 60% and 60% for P. aeruginosa and 100%, 100% and 40% for S. maltophila. Conclusions: As previously demonstrated for an aztreonam/ceftazidime-avibactam combination, aztreonam plus imipenem-relebactam and aztreonam plus meropenem-vaborbactam might be useful options, but with potentially lower efficiency, to treat infections caused by aztreonam-non-susceptible MBL-producing Gram-negative strains. Full article

Bone and joint infections (BJI) require prolonged antimicrobial treatment, leading to lengthy hospitalizations, high costs, the risk of nosocomial infections, and the development of antimicrobial resistance. Dalbavancin is a novel semisynthetic lipoglycopeptide approved for the treatment of adults and children with acute bacterial skin and skin structure infections. This narrative review aims to summarize the characteristics of dalbavancin and the current scientific evidence regarding its clinical efficacy and safety in the treatment of BJI. A literature search until June 2023 was performed to identify all published research about the role of dalbavancin in the management of BJI. Due to its unique pharmacokinetics characterized by prolonged half-life, high bactericidal activity against most Gram-positive bacteria, a good safety profile, and high tissue penetration, dalbavancin can be a valuable alternative to the treatment of BJI. Clinical studies have shown its non-inferiority compared to conventional therapies in BJI, offering potent activity against key pathogens and an extended dosing interval that may shorten hospitalization. In conclusion, dalbavancin represents a promising treatment option for BJI with a favorable safety profile, but further research in both adults and particularly children, who are ideal candidates for long-acting antibiotics, is necessary to evaluate the role of dalbavancin in BJI. Full article

Background: Little is known about the recent trends in antibiotic and phytopharmaceutical prescribing for acute upper (URIs) and lower respiratory tract infections (LRIs) in children and adolescents. Therefore, this study investigated changes in the prescription of antibiotics and phytopharmaceuticals in children diagnosed with acute URIs and LRIs in pediatric practices in Germany in 2013, 2018, and 2022. Methods: The present retrospective study included children aged 2–12 years diagnosed with acute URIs or LRIs in one of 180 pediatric practices in 2013, 2018, and 2022. The URIs included nasopharyngitis, sinusitis, pharyngitis, tonsillitis, laryngitis and tracheitis, and upper respiratory infections of multiple and unspecified sites, while the LRIs corresponded to bronchitis. The primary outcomes were the proportion of children being prescribed antibiotics and the proportion of those being prescribed phytopharmaceuticals. Results: A total of 120,894 children were diagnosed with acute URIs or LRIs in 2013 compared to 116,844 in 2018 and 127,821 in 2022. The prevalence of antibiotic prescription decreased for all diagnoses between 2013 and 2022. This decrease was statistically significant for both 2013–2018 and 2018–2022 for nasopharyngitis, pharyngitis, and bronchitis. Meanwhile, there was a significant increase in the use of phytopharmaceuticals for all diagnoses between 2013 and 2018. The prevalence of phytopharmaceutical prescription decreased slightly between 2018 and 2022, but this decrease was generally not statistically significant. Conclusions: The prescription of antibiotics has decreased and that of phytopharmaceuticals has increased in children diagnosed with acute URIs and LRIs in Germany over the last decade. More data are needed to corroborate these findings in other settings. Full article

Bacterial biofilms on orthopedic implants are resistant to the host immune response and to traditional systemic antibiotics. Novel therapies are needed to improve patient outcomes. TRL1068 is a human monoclonal antibody (mAb) against a biofilm anchoring protein. For assessment of this agent in an orthopedic implant infection model, efficacy was measured by reduction in bacterial burden of Staphylococcus aureus, the most common pathogen for prosthetic joint infections (PJI). Systemic treatment with the biofilm disrupting mAb TRL1068 in conjunction with vancomycin eradicated S. aureus from steel pins implanted in the spine for 26 of 27 mice, significantly more than for vancomycin alone. The mechanism of action was elucidated by two microscopy studies. First, TRL1068 was localized to biofilm using a fluorescent antibody tag. Second, a qualitative effect on biofilm structure was observed using scanning electron microscopy (SEM) to examine steel pins that had been treated in vivo. SEM images of implants retrieved from control mice showed abundant three-dimensional biofilms, whereas those from mice treated with TRL1068 did not. Clinical Significance: TRL1068 binds at high affinity to S. aureus biofilms, thereby disrupting the three-dimensional structure and significantly reducing implant CFUs in a well-characterized orthopedic model for which prior tested agents have shown only partial efficacy. TRL1068 represents a promising systemic treatment for orthopedic implant infection. Full article

Mucormycosis is an opportunistic infection affecting mainly immunocompromised hosts. Infection in immunocompetent patients is rare, but may occur typically in trauma or burn victims. We report on a previously healthy young man suffering devastating trauma from an agricultural accident with the subsequent development of a multifocal mucormycosis. Diagnosis was achieved by cultures obtained from non-healing wounds, some of them even covered by a macroscopic mold formation. Specific treatment was initiated soon after the preliminary results indicated mucormycosis. Aggressive surgical therapy, with concomitant use of systemic posaconazole and topical amphotericin B in a combination treatment, led to the elimination of the fungal infection. The remaining deep tissue defects were consequently reconstructed by a muscle flap and skin graft autotransplantation with a good overall outcome, which would not have been possible without the complete remission of mucormycosis. This case study presents the successful use of a combination treatment with systemic posaconazole and topical amphotericin B and underlines the importance of timely and aggressive surgical therapy. Full article

Neonatal sepsis is an important cause of morbidity and mortality in neonatal intensive care units (NICUs). Continuous evaluation of antimicrobial resistance (AMR) profiles is advised to implement antimicrobial stewardship (AMS) programs and establish effective empiric antibiotic protocols. AMS may reduce AMR in NICUs and improve sepsis outcomes. In this retrospective observational study, we report data on culture-positive neonatal sepsis, assessing differences after the implementation of an AMS program (2011–2016 vs. 2017–2022). A total of 215 positive bacterial cultures from 169 infants were retrieved, with 79 early-onset (36.7%) and 136 late-onset (63.3%) sepsis episodes. Frequent causative agents for early-onset sepsis were S. agalactiae and E. coli, all susceptible to empiric treatment. Late-onset sepsis was mainly caused by Enterobacterales and S. aureus. Aminoglycosides, cefotaxime, and piperacillin-tazobactam resistance among Enterobacterales was substantially low; S. aureus was mostly susceptible to oxacillin and vancomycin. There were no differences in mortality and multidrug-resistant pathogens rates between the two study periods. There were five episodes of fungal late-onset sepsis, mostly due to C. albicans, of which one was fatal. The microbial distribution pattern and AMR profiles overlapped with other European studies. Because susceptibility patterns are rapidly changing worldwide, with the emerging threat of Methicillin-resistant S. aureus and extended-spectrum beta-lactamases producers, infection prevention and control practices and AMS strategies require continuous optimization to limit selection pressure and AMR escalation. Full article

Our study describes the prevalence and spectrum of enterococci isolated from one-day-old chickens in the Czech Republic, their level of antimicrobial resistance, and the occurrence of multiresistance. Over a 24-month period from 1 August 2021 to 31 July 2023, a total of 464 mixed samples of one-day-old chicken organs were examined during routine inspections at 12 randomly selected poultry farms in the Czech Republic. The samples were processed via cultivation methods and suspected strains were confirmed using the MALDI–TOF Mass Spectrometry method. Antimicrobial susceptibility was determined using the MIC method for eight antimicrobials. A total of 128 isolates (prevalence of 27.6%) representing 4 species of enterococci were isolated, including Enterococcus faecalis, Enterococcus faecium, Enterococcus gallinarum, and Enterococcus hirae, with prevalence rates of 23.3%, 1.5%, 2.2%, and 0.6%, respectively. Susceptibility tests showed a high percentage of susceptible strains among E. faecalis, E. faecium, and E. gallinarum for penicillin-based antibiotics, sulfamethoxazole with trimethoprim, and florfenicol (80–100% susceptible strains). E. hirae was an exception, displaying complete resistance to enrofloxacin (0% susceptible strains) and a high degree of resistance to other tested antimicrobials (33.3% susceptible strains). Among the isolated strains, a total of 16 isolates (12.5%) showed resistance to 3 or more antimicrobials. Complete resistance to all eight antimicrobials simultaneously was observed in four isolates (3.1%). This research shows the possible sources of pathogenic enterococci and their virulence and resistance genes. The findings hold relevance for both veterinary and human medicine, contributing to a better understanding of enterococcal circulation in the human ecosystem and food chain, as well as the development of their resistance and multiresistance. Full article

Prosthetic joint infections (PJI) present a major management challenge for practicing orthopedic surgeons and infectious disease physicians. There are few high-quality data to inform treatment guidelines. The aim of this systematic review was to report the design characteristics and recruitment rates for randomized controlled trials (RCTs) of PJI management. Trials were considered eligible for inclusion if human participants were randomized to any management intervention for PJI. We searched Medline, PubMed, Embase, Web of Science, Cochrane Database, ANZ Clinical Trials Registry, ClinicalTrials.gov, and the EU Clinical Trials Register until the end of May 2023. The systematic review was registered with PROSPERO (CRD42018112646). We identified 15 published RCTs with a total of 1743 participants with PJI. The median (interquartile range [IQR]) number of successfully recruited participants was 63 (38–140), with 0.28 (0.13–0.96) enrolments per site per month. Only four trials (36.4%) achieved the target recruitment. All RCTs applied different primary endpoints and varying definitions of a ‘good’ outcome. Despite recent improvements, PJI RCTs are characterized by slow recruitment and heterogeneous endpoint assessments, which preclude synthesis in a standard meta-analytic framework. To inform international guidelines, future PJI trials should be run as multi-country trials at high-recruiting sites. Full article