Factors reported in the literature associated with inappropriate prescribing of antimicrobials include physicians with less experience, uncertain diagnosis, and patient caregiver influences on physicians’ decisions. Monitoring antimicrobial resistance is critical for identifying emerging resistance patterns, developing, and assessing the effectiveness of mitigation strategies. Improvement in prescribing antimicrobials would minimize the risk of resistance and, consequently, improve patients’ clinical and health outcomes. The purpose of the study is to delineate factors associated with antimicrobial resistance, describe the factors influencing prescriber’s choice during prescribing of antimicrobial, and examine factors related to consequences of inappropriate prescribing of antimicrobial. A cross-sectional study was conducted among healthcare providers (190) in six tertiary hospitals in the Eastern province of Saudi Arabia. The research panel has developed, validated, and piloted survey specific with closed-ended questions. A value of p < 0.05 was considered to be statistically significant. All data analysis was performed using the Statistical Package for Social Sciences (IBM SPSS version 23.0). 72.7% of the respondents have agreed that poor skills and knowledge are key factors that contribute to the inappropriate prescribing of antimicrobials. All of the respondents acknowledged effectiveness, previous experience with the antimicrobial, and reading scientific materials (such as books, articles, and the internet) as being key factors influencing physicians’ choice during antimicrobial prescribing. The current study has identified comprehensive education and training needs for healthcare providers about antimicrobial resistance. Using antimicrobials unnecessarily, insufficient duration of antimicrobial use, and using broad spectrum antimicrobials were reported to be common practices. Furthermore, poor skills and knowledge were a key factor that contributed to the inappropriate use and overuse of antimicrobials, and the use of antimicrobials without a physician’s prescription (i.e., self-medication) represent key factors which contribute to AMR from participants’ perspectives. Furthermore, internal policy and guidelines are needed to ensure that the antimicrobials are prescribed in accordance with standard protocols and clinical guidelines. Full article

A single-center cross-sectional study was conducted to describe the use of ceftaroline in a large teaching hospital in Northern Italy, during a period also including the first months of the coronavirus disease 2019 (COVID-19) pandemic. The primary objective was to describe the use of ceftaroline in terms of indications and characteristics of patients. A secondary objective was to describe the rate of favorable clinical response in patients with bloodstream infections (BSI) due to methicillin-resistant Staphylococcus aureus (MRSA-BSI) receiving ceftaroline. Overall, 200 patients were included in the study. Most of them had COVID-19 (83%, 165/200) and were hospitalized in medical wards (78%, 155/200). Included patients with COVID-19 pneumonia were given empirical ceftaroline in the suspicion of bacterial co-infection or superinfection. Among patients with MRSA-BSI, ceftaroline was used as a first-line therapy and salvage therapy in 25% (3/12) and 75% (9/12) of cases, respectively, and as a monotherapy or in combination with daptomycin in 58% (7/12) and 42% (5/12) of patients, respectively. A favorable response was registered in 67% (8/12) of patients. Improving etiological diagnosis of bacterial infections is essential to optimize the use of ceftaroline in COVID-19 patients. The use of ceftaroline for MRSA-BSI, either as a monotherapy or in combination with other anti-MRSA agents, showed promising rates of favorable response. Full article

Cefiderocol is a new cephalosporin displaying against extensively resistant (XDR) Gram-negative bacteria. We report our experience with cefiderocol-based combination therapies as “rescue” treatments in immunocompromised or critically ill patients or in patients with post-surgical infections who had failed previous regimens. A total of 13 patients were treated from 1 September 2020 to 31 March 2021. In total, 5/13 (38%) patients were classified as critically ill, due to severe COVID-19 lung failure; 4/13 (31%) patients had post-surgical infections and 4/13 (31%) had severe infections in immunocompromised subjects due to solid organ transplantation (2/4) or hematological malignancy (2/4). Overall, 10/13 infections were caused by carbapenem-resistant Acinetobacter baumannii, one by KPC-positive ceftazidime/avibactam-resistant Klebsiella pneumonia and two by Pseudomonas aeruginosa XDR. Based on clinical, microbiological and hematobiochemical evaluation, cefiderocol was associated with different companion drugs, particularly with fosfomycin, high-dose tigecycline and/or colistin. Microbiological eradication was achieved in all cases and the 30-day survival rate was 10/13; two patients died due to SARS-CoV-2 lung failure, whereas one death was attributed to subsequent infections. No recurrent infections within 30 days were reported. Finally, we hereby discuss the therapeutic potential of cefiderocol and the possible place in the therapy of this novel drug. Full article

The proportions and similarities of extended-spectrum β-lactamase (ESBL) producing K. pneumoniae (ESBL-KP) and E. coli (ESBL-EC) carrying multiple ESBL genes is poorly known at our setting. This study investigated the existence of multiple ESBL genes (bla_CTX-M, bla_TEM, and bla_SHV) among ESBL-KP and ESBL-EC concurrently isolated from clinical, colonization, and contamination samples from neonatology units in Mwanza-Tanzania. Twenty and 55 presumptive ESBL-EC and ESBL-KP, respectively, from a previous study archived at −80 °C were successfully recovered for this study. Isolates were screened and confirmed for production of ESBLs by phenotypic methods followed by multiplex PCR assay to determine ESBL genes. All (100%) and 97.3% of presumptive ESBL isolates were phenotypically confirmed by Clinical and Laboratory Standards Institute (CLSI) and modified double-disc synergy methods, respectively. About 93.3% (70/75) of phenotypically confirmed ESBL isolates had at least one ESBL gene, whereby for 62.9% (44/70), all ESBL genes (bla_CTX-M, bla_TEM, and bla_SHV) were detected. Eight pairs of ESBL bacteria show similar patterns of antibiotics susceptibility and ESBL genes. ESBL-KP and ESBL-EC, concurrently isolated from clinical, colonization and contamination samples, harbored multiple ESBL genes. Further, eight pairs of ESBL isolates had similar patterns of antibiotics susceptibility and ESBL genes, suggesting transmission of and/or sharing of mobile genetic elements (MGEs) among ESBL-KP and ESBL-EC. Full article

Probiotics can potentially prevent and treat diseases. We examined the inhibitory activity of bacteriocin-like inhibitory substances (BLISs) from potentially probiotic lactobacilli and streptococci on Candida albicans and non-Candida albicans clinical isolates from women with vulvovaginitis. Using agar well diffusion assays, BLISs inhibited both Candida albicans and non-Candida albicans isolates. The BLIS from L. pentosus isolates had the highest anti-Candida activity (33/45; 73.3%), followed by BLISs from isolates of L. paracasei subsp. paracasei (31/45; 68.9%), L. rhamnosus I (30/45; 66.7%), L. delbrueckii subsp. lactis I (30/45; 66.7%), and S. uberis II (30/45; 66.7%). Upon characterization according to the retained activity under variable physical and chemical conditions, the BLISs showed stability against heat, pH, and surfactants, but were protease-sensitive, which suggests a proteinaceous nature of the active substances. Using crystal violet assays, the BLISs reduced the Candida biofilm biomass significantly as compared to a control group that lacked BLISs. In vivo testing of the antagonistic activity was performed using the Galleria mellonella (G. mellonella) larvae model. BLISs significantly improved survival in G. mellonella larvae treated with Candida isolates on the first, second, and seventh days, as compared to larvae inoculated with Candida only (p < 0.01). The results show that BLISs can be used as biotherapeutic agents in vulvovaginal candidiasis. Full article

Background: Clostridioides difficile infection (CDI) is associated with substantial morbidity and mortality as well as high propensity of recurrence. Systemic antibiotic therapy (SAT) represents the top inciting factor of CDI, both primary and recurrent (rCDI). Among the many strategies aimed to prevent CDI in high-risk subjects undergoing SAT, oral vancomycin prophylaxis (OVP) appears promising under a cost-effectiveness perspective. Methods: A systematic review with meta-analysis and trial sequential analysis (TSA) of studies assessing the efficacy and the safety of OVP to prevent primary CDI and rCDI in persons undergoing SAT was carried out. PubMed and EMBASE were searched until 30 September 2021. The protocol was pre-registered on PROSPERO (CRD42019145543). Results: Eleven studies met the inclusion criteria, only one being a randomized controlled trial (RCT). Overall, 929 subjects received OVP and 2011 represented the comparator group (no active prophylaxis). OVP exerted a strong protective effect for CDI occurrence: odds ratio 0.14, 95% confidence interval 0.04–0.38. Moderate heterogeneity was observed: I² 54%. This effect was confirmed throughout several subgroup analyses, including prevention of primary CDI versus rCDI. TSA results pointed at the conclusive nature of the evidence. Results were robust to a variety of sensitivity and quantitative bias analyses, although the underlying evidence was deemed as low quality. No differences between the two groups were highlighted regarding the onset of vancomycin-resistant Enterococcus infections. Conclusions: OVP appears to be an efficacious option for prevention of CDI in high-risk subjects undergoing SAT. Nevertheless, additional data from RCTs are needed to establish OVP as good clinical practice and define optimal dosage and duration. Full article

A 20-year-old man was admitted to the intensive care unit for septic shock due to Lemierre’s syndrome. It is a rare syndrome that manifests as an upper respiratory infection, although systemic involvement, severe coagulopathy, and multi-organ failure can dangerously complicate the clinical picture. In this syndrome, sepsis-related neuroendocrine dysregulation and microcirculation impairment can have a rapid deleterious progression. Consequently, proper diagnosis, early source control, and appropriate antibiotics administration are mandatory to improve the prognosis. The intensive treatment is aimed at limiting organ damage through hemodynamic optimization. Remarkably, in septic shock due to Lemierre’s syndrome, hemodynamic optimization can be achieved through the synergic effect of norepinephrine, argipressin, and hydrocortisone. Full article