Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) are significant causes of morbidity and mortality. The microbiome plays a significant role in the body's defense against CDI and rCDI. Antibiotics can cause significant injury to the microbiome which leads to an increased risk of CDI and rCDI. Ongoing perturbations of the microbiome perpetuate this risk. Antibiotic treatments for CDI can kill C difficile but also can impact the microbiome. Microbiome therapeutics are effective in restoring the function of the gut microbiota and re-establishing colonization resistance. The field of microbiome therapeutics is evolving with newer, more refined, modalities in development.

Despite stringent infection control measures, Clostridioides difficile infection (CDI) remains a challenge in healthcare settings, partly due to overlooked transmission vectors such as toilet plume bioaerosols.

To systematically quantify the risks associated with CDI transmission via toilet flushing and provide critical insights to inform CDI preventive strategies.

Impaction sampling was used to quantify airborne C. difficile post-flush and high-contact surfaces were swabbed to assess contamination levels, in a controlled toilet environment. A quantitative microbial risk assessment (QMRA) approach was then used to estimate the risk to subsequent users from contamination by a previously colonized individual.

A single flush can release C. difficile into the air, with bioaerosol concentrations up to 29.50 ± 10.52 cfu/m3 and deposit about 8-11 cfu on immediate surfaces. Despite a 4.4 log reduction in bacterial concentration within the toilet bowl post-flush, bacteria persist on its inner walls. Relative humidity increases by approximately 31.28% within the first 10 min post-flush, potentially enhancing the viability and transmission of aerosolized C. difficile. The flush button contact and inhalation-followed-by-ingestion in frequent-use hospital settings present the highest risks and exceed US EPA and WHO acceptable infection risk thresholds.

The findings of this study necessitate a review of current toilet designs, public health policies and facility management practices to mitigate the overlooked risks of CDI transmission through toilet plume bioaerosols in healthcare settings. Additionally, this study lays a foundation for developing evidence-based interventions aimed at achieving substantial behavioural and infrastructural changes in infection control practices.

Appendicitis is the most common acute abdominal condition affecting general surgical practice. Recently, conservative treatment with antibiotics has been considered as an alternative. Therefore, this study was conducted to evaluate if antibiotics could be cost-effective compared to laparoscopic appendectomy or open appendectomy. A prospective study was undertaken to estimate health-related quality of life for antibiotic and operative treatment, and to ascertain costs in a cohort. A societal perspective incremental cost-effectiveness ratio (ICER) at 1 year after surgery was estimated. A probabilistic sensitivity analyses was performed. ICERs were estimated comparisons between individual antibiotics, laparoscopic appendectomy, and open appendectomy in uncomplicated acute appendicitis. Antibiotics showed improved cost savings compared to operative treatments with an ICER of -113,973.09 USD per quality adjusted life year at 1 year. Based on one year findings, antibiotics represent a lower cost treatment option with better cost-utility compared to operative treatment options in uncomplicated acute appendicitis patients. As such, antibiotic treatment can be initially considered as an alternative option where resources are limited to minimize complication rates associated with operative treatments.

Infective spondylitis is a rare but potentially devastating spinal infection that requires timely diagnosis and appropriate treatment to prevent severe complications, including neurological deficits and spinal deformity. Despite advancements in diagnostic imaging, microbiological techniques, and antimicrobial therapies, clinical challenges persist because of the disease's insidious onset, varied etiologies, and increasing antimicrobial resistance. This review article provides a comprehensive analysis of the current literature on the epidemiology, pathophysiology, diagnostic approaches, and treatment strategies for infective spondylitis.

Clostridioides difficile infections (CDIs) remain a prevalent and costly healthcare challenge, particularly affecting elderly, comorbid patients. Evidence on the health economic burden of CDI in Germany, particularly in refractory and recurrent patients is limited.

The IBIS study was a non-interventional retrospective and prospective study conducted from August 2017 to September 2020 in 10 German hospitals to assess the health economic burden of inpatient CDI treatment. It categorized CDI episodes into initial, refractory and recurrent, following the current ESCMID guidelines. A micro-costing approach from the societal perspective was applied, considering personnel, material, and infrastructure costs for treatment on different types of hospital wards, targeted antibiotic CDI therapies, and productivity losses due to illness-related disability.

Mean total costs per patient were €13,607 (95% CI: €12,124-€15,171) for the initial, €19,953 (95% CI: €16,839-€23,377) refractory and €22,671 (95% CI: €16,088-€30,474; P<0.001) for the recurrence group. Treatment on a general ward was the most important cost driver. Mean hospital length of stay in the initial, refractory group and recurrence group was 30 (95% CI: 27-33) vs 41 (95% CI: 35-46) vs 47 days (95% CI: 37-57; P<0.001), respectively. Patients with initial, refractory and recurrent CDI required 11 (95% CI: 10-1), 15 (95% CI: 13-16) and 24 days (95% CI: 22-27; P<0.001) of targeted antibiotic therapy for CDI.

The IBIS study contributes valuable insights to the health economic burden of refractory and recurrent CDI in the German inpatient setting and underlines the importance of effective first-line treatment to improve treatment outcomes and reduce overall costs related to CDI.

Clostridioides difficile infection (CDI) is a well-recognized complication of inflammatory bowel disease (IBD) that has been associated with poor clinical outcomes. The objective of this study is to characterize the global incidence, risk factors and outcomes of CDI in patients with IBD.

A search of MEDLINE/PubMed, Scopus, and Cochrane Database of Systematic Reviews was conducted for studies published between January 1960, and March 2024. Random-effect models were employed to estimate the incidence of CDI in the IBD population. Risk factors and outcomes were estimated using random effects meta-regression and subgroup analysis.

Twenty-eight articles from 11 countries on 3 continents, comprising 796, 244 patients with IBD were included. The overall CDI rate was 8.84% (95% CI, 5.91%-13.03%). The rate of CDI was slightly higher in Asia at 11% (95% CI, 6.7%-18.44%) compared to the North America (USA and Canada) at 7.85% (95% CI, 3.80%-15.51%) and Europe, where the incidence, was 7.92% (95% CI, 3.87%-15.51%). A univariable random-effects meta-regression model demonstrated that male gender (odds ratio [OR], 1.18; 95% CI, 1.00-1.40) and older age (OR, 1.06; 95% CI, 0.99-1.15, per one-year increase in age) were factors associated with higher CDI incidence in the IBD population. CDI testing by PCR compared to enzyme immunoassay was associated with higher rates of CDI (OR, 4.70; 95% CI, 01.39-15.90). No association was observed between length of hospital stay and CDI.

One in 10 patients with IBD were positive for CDI. Increasing age and male population were associated with higher risk of CDI.

Background/Objectives: Data about the relationship between COVID-19 and healthcare-associated Clostridioides difficile infection (HA-CDI) occurrence are still controversial. This study examines antibiotics associated with CDI in patients with and without COVID-19 infection. Methods: A prospective cohort study was conducted at the University Clinical Center Belgrade, Serbia, from January 2019 to December 2021. Patients with the first episode of HA-CDI without and with COVID-19 were included. Results of bacteriology analyses, demographic and clinical data, and data on antibiotic usage and daily defined doses (DDD) were collected by the hospital Infection Control Team. Results: Out of 547 HA-CDI cases, 341 (62.3%) had COVID-19 infection. HA-CDI patients with COVID-19 were significantly younger (p = 0.017) with fewer comorbidities (<0.001). Two or more antibiotics in therapy were more frequently used by those patients (p = 0.03). COVID-19 patients were treated significantly more by third- and fourth-generation cephalosporins, fluoroquinolones (p < 0.001) and macrolides (p = 0.01). Ceftriaxone had a higher median DDD in COVID-19 patients (6.00, range 1.00-20.00) compared to non-COVID-19 patients (4.00, range 1.00-14.00), (p = 0.007). Conversely, meropenem showed a lower median DDD in COVID-19 patients. Multivariate analysis identified the use of fourth-generation cephalosporins and fluoroquinolones as independent risk factors for HA-CDI in COVID-19 patients. Conclusions: Patients with HA-CDI and COVID-19 more frequently received two or more antibiotics before the onset of HAI-CDI. The third and fourth generations of cephalosporins, fluoroquinolones and macrolides were administered significantly more often in these patients. More frequent administration of ceftriaxone was observed, but the lower DDD associated with meropenem needed additional analysis.

Toxoplasma gondii causes widespread chronic infections that are not cured by current treatments due to the inability to affect semidormant bradyzoite stages within tissue cysts. To identify compounds to eliminate chronic infection, we developed an HTS using a recently characterized strain of T. gondii that undergoes efficient conversion to bradyzoites in vitro. Stage-specific expression of luciferase was used to selectively monitor the growth inhibition of bradyzoites by the Library of Pharmacological Active Compounds, consisting of 1280 drug-like compounds. We identified 44 compounds with >50% inhibitory effects against bradyzoites, including new highly potent compounds, several of which have precedent for antimicrobial activity. Subsequent characterization of the compound sanguinarine sulfate revealed potent and rapid killing against in vitro-produced bradyzoites and bradyzoites harvested from chronically infected mice, including potent activity against intact cysts. These findings provide a platform for expanded screening and identify promising compounds for further preclinical development against T. gondii bradyzoites that are responsible for chronic infection.

Data are limited regarding use of narrow-spectrum agents for the treatment of complicated urinary tract infections (cUTIs). We sought to evaluate cefazolin compared with ceftriaxone for the empiric treatment of patients with cUTIs in an inpatient setting.

We conducted a retrospective, single-center, cohort study involving patients with cUTI treated with cefazolin or ceftriaxone at a Veterans Affairs (VA) medical center between November 1, 2019 and September 30, 2022. The primary outcome was 30-day clinical success, defined as resolution of signs and symptoms of infection without re-initiation of antibiotics during hospitalization or relapse within 30 days after cUTI diagnosis. Secondary outcomes included hospital length of stay and Clostridioides difficile infection (CDI) within 30 days of the end of antibiotic therapy.

We identified 113 patients with cUTI treated with cefazolin (n = 52) or ceftriaxone (n = 61) meeting study criteria. The study arms had similar demographics, although patients treated with ceftriaxone more frequently had subjective fever on admission or nephrolithiasis while cefazolin-treated patients had more altered mental status as the only UTI symptom reported, urinary catheter, and had a single dose of another antibiotic prior to starting the study medication. Clinical success was achieved in 47/52 (90%) and 53/61 (87%) in the cefazolin and ceftriaxone groups, respectively (P = 0.56). Additionally, there were no statistically significant differences in length of stay and development of CDI.

In this retrospective cohort study of patients with cUTI at a VA medical center, empiric therapy with cefazolin appears to be a safe and effective treatment option.

Drug allergies, specifically antibiotic allergies, are frequently encountered in obstetrics and gynecology, with 10% of the US population reporting a penicillin allergy. This poses a particular challenge to the obstetrician-gynecologist, as beta-lactam antibiotics are indicated as first-line therapy for the treatment and prevention of most specialty-specific infections. Alternative antibiotic use in the setting of a reported allergy is not benign and has been associated with increased cesarean delivery, endometritis, wound complication, length of hospital stay in pregnant patients, Group B Streptococcus sepsis, neonatal length of stay, neonatal laboratory draw in neonates born to patients with allergies, and surgical site infection in gynecologic patients. Furthermore, alternative antibiotic use leads to increased antibiotic resistance, toxicity, and healthcare cost. In addition, the administration of antibiotics in a patient with a history of type I immediate hypersensitivity reaction poses a risk of anaphylaxis with repeat exposure. Fortunately, >90% of patients who report a penicillin allergy are not truly allergic and would tolerate penicillins if administered. This can be due to either mislabeling of the index reaction as an allergy (when it was due to a drug intolerance or a viral exanthem) or waning immunoglobulin E-mediated immunity over time. Given this, allergy evaluation is widely recommended, even in pregnancy. Allergy evaluation involves detailed patient history and allergy testing with skin testing and/or oral challenge, as appropriate. These tools have been found to be safe and effective in gravid and nongravid individuals and to result in increased use of first-line antibiotics when used appropriately. Furthermore, even in the setting of a true penicillin allergy, cross-reactivity with cephalosporins is extremely low and estimated at 2% to 3% among patients with a verified penicillin allergy and considerably lower than this among patients with an unverified penicillin allergy. Guidelines support the routine use of cephalosporins without testing or additional precautions in patients with an unverified nonanaphylactic penicillin allergy and the routine use of structurally dissimilar cephalosporins (specifically Ancef) even in patients with an anaphylactic penicillin allergy. In cases in which there is no appropriate alternative antibiotic than that for which the patient is allergic, such as syphilis in a pregnant patient with penicillin allergy, desensitization can be performed. This process involves temporary induction of drug tolerance through exposure to small amounts of the allergen until a therapeutic dose is achieved and has been safely performed in pregnancy. Desensitization requires expert supervision and is most often performed in the intensive care setting with a multidisciplinary team. The other 2 most common antibiotic allergies encountered in the field of obstetrics and gynecology are cephalosporin and metronidazole allergies. Cephalosporin allergies are managed similarly to penicillin allergies with readily available skin testing and oral challenge. Skin testing for metronidazole allergy lacks sensitivity and specificity, and thus, oral challenge or desensitization procedure is the preferred approach for low-risk and high-risk patients, respectively. When it comes to drug allergies, specifically antibiotic allergies, the role of the obstetrician-gynecologist is to identify patients with reported allergies and to refer patients to a specialist for further evaluation as soon as possible. Allergy evaluation using a detailed patient history and allergy testing (skin testing and/or oral challenge) when indicated has been shown to be safe and effective and is an important part of antibiotic stewardship.

Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea. The infection is associated with a high mortality rate and risk of recurrence. We assessed risk factors for death or recurrent CDI (CDI) in patients with diabetes mellitus (DM).

This retrospective cohort study was conducted at a single institution from 2019 to 2020. CDI was defined as a positive toxin assay for C. difficile. CDI was defined as a repeat positive toxin assay within ≤ 60 days of stopping CDI treatment. Logistic regression models were used to identify risk factors for CDI-related mortality, recurrence, and the combined outcome of mortality and recurrence.

Of the 252 enrolled patients with CDI, 19% had DM. Only 49% of patients with DM fully recovered after the first CDI occurrence, whereas 69% of patients without diabetes fully recovered (p = 0.021); 23% of patients with DM vs. 17% of patients without DM had recurrences (p = 0.200); and 23% of patients with DM vs. 15% of patients without DM died (p = 0.169). DM was associated with mortality (OR 2.75, 95% CI 0.94-8.06) and the combined outcome (OR 2.10, 95% CI 1.05-4.18). Nosocomial transmission, immunosuppression, CKD, and age were associated with mortality.

Diabetes is associated with a worse prognosis in patients with CDI. Prevention efforts should be optimized in patients with diabetes by reducing CDI transmission and avoiding nonessential medications, such as PPIs or antibiotics when they are not necessary. [Figure: see text].

Clostridioides difficile is a major cause of antimicrobial-associated colitis. While antimicrobial stewardship has reduced the incidence of C. difficile infection (CDI), managing CDI is challenging because knowledge about preventing it is limited among healthcare professionals. To address this, we examined associations between antimicrobial use and CDI development.

This observational, nested case-controlled study was conducted using the Shizuoka Kokuho Database (SKDB). Individuals with no record of CDI or antimicrobial-associated enterocolitis within 1 year after SKDB enrolment, but who subsequently developed CDI, were included as the Case group. The Control group comprised individuals selected via 1:4 matching sampling without replacement for sex, age, and month of CDI onset. Conditional logistic regression analysis was performed to assess associations between antimicrobial use (number and combination) and CDI development, controlling for matched variables, background factors, and underlying conditions.

Of the 2,398,393 individuals, 4917 were assigned to the Case group and 19,668 to the Control group. The adjusted odds ratios (ORs) for CDI were 3.65 for one antimicrobial and 8.58, 17.3, and 38.9 for combinations of two, three, or four or more agents (all p < 0.001). Penicillins, fourth-generation cephems, and carbapenems exhibited high ORs. Similar results were observed in certain demographic and comorbidity-free subgroups. Several combinations (penicillins + carbapenems, penicillins + cephems + carbapenems, cephems + fluoroquinolones, and penicillins + cephems + carbapenems) were notably associated with CDI development.

CDI prevalence increased with the number of antimicrobial classes used in combination. Certain types or combinations of antimicrobials may increase the OR for CDI.

Clostridioides difficile infection (CDI) is the most common nosocomial infection in the US. CDI has become a growing concern due to C. difficile's resistance to several antibiotics, including cephalosporins. Furthermore, patients administered cephalosporins are at higher risk of contracting CDI. Cephalosporins are β-lactam antibiotics, which prevent bacterial cell wall synthesis by inhibiting penicillin-binding proteins (PBPs). β-lactam-resistant bacteria evade these antibiotics by producing β-lactamases or by harboring low-affinity PBPs. A genomic analysis of C. difficile strain 630 identified 31 putative β-lactam resistance genes. Upon cefoxitin exposure, few C. difficile strain 630 putative antibiotic-resistant genes were overexpressed. Most notably, the β-lactamase blaCDD gene was upregulated approximately 600-fold, as previously reported. Deletion of the blaCDD locus did not change in cephalosporin susceptibility. Deletion of the second most upregulated gene, the PBP vanY, was also ineffective at decreasing cephalosporin resistance. Cefoxitin exposure of the C. difficile strain 630ΔblaCDD mutant did not increase upregulation of other putative antibiotic resistance genes compared to wildtype C. difficile strain 630. Transcriptomic analyses of wildtype C. difficile strain 630 exposed to cephradine, cefoxitin, ceftazidime, or cefepime revealed the shared upregulation of a putative heterodimeric ABC transporter encoded by loci CD630_04590 (ABC transporter ATP-binding protein) and CD630_04600 (ABC transporter permease). These genes are genomically located directly downstream of blaCDD (CD630_04580). The deletion mutant CD630_04600 remained resistant to a number of antibiotics. Thus, even though blaCDD, CD630_04590, and CD630_04600 are all upregulated when exposed to cephalosporins, they do not seem to be involved in antibiotic resistance in C. difficile strain 630.

Clostridium difficile infection (CDI) has become a significant healthcare issue with increasing morbidity and mortality in the US and Europe. Frailty, characterized by reduced physical reserves and resistance to stressors, is linked to poor outcomes but its impact on CDI patients remains underexplored. This study seeks to address this gap through a nationwide analysis.

Using the National Readmission Database from 2016 to 2020, we employed the International Classification of Diseases, 10th revision, Clinical Modifications codes to identify adult patients admitted with CDI. We further stratified CDI hospitalizations based on frailty. Utilizing a regression model, we assessed the impact of frailty on CDI outcomes.

We included 144,611 CDI patients of whom 98,167 (67.88 %) were frail. Multivariate analysis showed that frail CDI patients had significantly higher mortality (adjusted odds ratio (aOR) 4.87), acute kidney injury requiring dialysis (aOR 9.50), septic shock (aOR 14.23), and intensive care unit admission (aOR 6.80). CDI-specific complications were more likely in frail patients, including toxic megacolon (aOR 10.22), intestinal perforation (aOR 2.30), need for colectomy (aOR 3.90) and CDI recurrence (aOR 3.65). Resource utilization, indicated by hospitalization charges, length of stay, and 30-day readmission rates, was greater among frail patients.

Our study underscores the significant association between frailty and various critical endpoints of CDI, including its incidence, mortality, and recurrence. Additionally, frailty independently predicts higher resource utilization and elevated 30-day readmission. Recognizing frailty as a determinant of CDI outcomes can aid clinicians in risk stratification and guide tailored interventions for this population.

In the face of rising antimicrobial resistance, bacteriophage therapy, also known as phage therapy, is seeing a resurgence as a potential treatment for bacterial infections including urinary tract infection (UTI). Primarily caused by uropathogenic Escherichia coli, the 400 million UTI cases annually are major global healthcare burdens and a primary cause of antibiotic prescriptions in the outpatient setting. Phage therapy has several potential advantages over antibiotics including the ability to disrupt bacterial biofilms and synergize with antimicrobial treatments with minimal side effects or impacts on the microbiota. Phage therapy for UTI treatment has shown generally favorable results in recent animal models and human case reports. Ongoing clinical trials seek to understand the efficacy of phage therapy in individuals with asymptomatic bacteriuria and uncomplicated cystitis. A possible challenge for phage therapy is the development of phage resistance in bacteria during treatment. While resistance frequently develops in vitro and in vivo, resistance can come with negative consequences for the bacteria, leaving them susceptible to antibiotics and other environmental conditions and reducing their overall virulence. "Steering" bacteria toward phage resistance outcomes that leave them less fit or virulent is especially useful in the context of UTI where poorly adherent or slow-growing bacteria are likely to be flushed from the system. In this article, we describe the history of phage therapy in treating UTI and its current resurgence, the state of its clinical use, and an outlook on how well-designed phage therapy could be used to "steer" bacteria toward less virulent and antimicrobial-susceptible states.

Recurrent C. difficile infection (CDI) is a major health threat with significant mortality and financial costs. Fecal Microbiota Transplantation (FMT) is an effective therapy, however the mechanisms by which it acts, particularly on the host, are poorly understood. Here we enrolled a prospective cohort of human patients with recurrent CDI (n=16) undergoing FMT therapy. Colonic biopsies were collected and bulk RNA sequencing was performed to compare changes in host gene expression pre- and two months post-FMT. Transcriptional profiles were significantly altered after FMT therapy, with many differentially expressed genes (~15% of annotated genes detected). Enrichment analysis determined that these changes were reflective of increased protein production post-FMT, with enrichment of pathways such as Ribosome Biogenesis, Protein Processing, and signaling pathways (Myc, mTORc1, E2F) associated with cell proliferation and protein biosynthesis. Histology of H&E-stained biopsies identified a significant increase in colonic crypt length post-FMT, suggesting that this treatment promotes cell proliferation. Crypt length was significantly correlated with enriched Myc and mTOR signaling pathways as well as genes associated with polyamine biosynthesis, providing a potential mechanism through which this may occur. Finally, signaling pathways upstream of Myc and mTOR, notably IL-33 Signaling and EGFR ligands, were significantly upregulated, suggesting that FMT may utilize these signals to promote cell proliferation and restoration of the intestine.

Antibiotic treatment is a well-known risk factor for Clostridioides difficile infection (CDI). The time from start of antibiotic exposure to onset of CDI for different antibiotics is sparsely studied. CDI with onset in the community is often treatable without in-hospital care while CDI patients treated in hospital need isolation, resulting in higher costs and infection control measures.

To determine the time from start of antibiotic exposure to onset of healthcare facility-associated CDI for different antibiotics.

Time between antibiotic exposure and disease onset was evaluated retrospectively with chart reading in a two-centre Swedish setting. A case was attributed to an antibiotic group if this represented more than 2/3 of total antibiotic exposure 30 days before onset of CDI.

Cephalosporins caused CDI faster (mean 7.6 days), and more often during ongoing antibiotic therapy (81% of the cases) than any other antibiotic group. All other common agents had between 2-3 times longer period between start of exposure to onset of CDI (quinolones more than 3 times).

The time gap between antibiotic exposure and onset of CDI is markedly different between different antibiotics. Decreased cephalosporin use could delay onset of healthcare facility-associated CDI and limit infections with onset within the hospital. This might decrease costs for inpatient care, need of infection control measures and shortage of beds in the hospital.

Health care-associated infections (HAIs) can affect patient safety and recovery. Musical instruments used by music therapy services may carry pathogens, particularly in ICUs. The aim of this study was to determine the efficacy of the cleaning and disinfection protocol by the music therapy service of the University Hospital Fundación Santa Fe de Bogotá.

This prospective cohort study included all ICU music therapy patients from July to August 2023. Adenosine triphosphate (ATP) bioluminescence tests and microbiological cultures were taken before and after cleaning the musical instruments for nine patients in the adult and pediatric ICUs. ATPs were taken before starting music therapy, after finishing music therapy, and after cleaning the instruments. Cultures were taken if an ATP test was above the established cutoff of ≤ 200 relative light units (RLUs). If no ATP value was above the cutoff, cultures were taken randomly.

A total of 63 ATPs and 10 random microbiological cultures were taken. After applying the cleaning and disinfection protocol, all ATP values were ≤ 200 RLUs. Of the 10 microbiological cultures, 1 screened positive for Streptococcus sp., yeast, and Micrococcus. One hundred ICU music therapy patients were followed up, and positive associations with HAIs were found for age (p = 0.01), type of unit (p = 0.001), tracheostomy (p < 0.001), arterial line (p = 0.005), hemodialysis catheter (p = 0.05), bladder catheter (p = 0.02), number of invasive devices (p = 0.02), duration use of invasive devices (p = 0.01), and days of hospitalization (p = 0.01). Number of music therapy sessions/patient was not associated with HAIs (p = 0.86).

The results indicate that the current cleaning and disinfection protocol can be considered safe and effective. To the authors' knowledge, this is one of the first studies investigating biosafety of musical instruments in a hospital-based music therapy service. Patient safety is of the utmost importance in hospital settings, and awareness about proper cleaning of their work tools among music therapists is paramount.

Clostridioides difficile is a major causative pathogen for antibiotic-associated diarrhea and C. difficile infections (CDIs) may lead to life-threatening diseases in clinical settings. Most of the risk factors for the incidence of CDIs, i.e., antibiotic use, treatment by proton pump inhibitors, old age, and hospitalization, are associated with dysbiosis of gut microbiota and associated metabolites and, consequently, treatment options for CDIs include normalizing the composition of the intestinal microbiome. In this review, with an introduction to the CDI and its global epidemiology, CDI-associated traits of the gut microbiome and its metabolites were reviewed, and microbiome-targeting treatment options were introduced, which was approved recently as a new drug by the United States Food and Drug Administration (U.S. FDA), rather than a medical practice.

Clostridium difficile (C. difficile) infection (CDI) is a rare clinical disease caused by changes in the intestinal microenvironment, which has a variety of causes and a poor prognosis, and for which there is no standardized clinical treatment.

A patient experienced recurrent difficulty in bowel movements over the past decade. Recently, symptoms worsened within the last ten days, leading to a clinic visit due to constipation. The patient was subsequently referred to our department. Preoperatively, the patient was diagnosed with obstructed colon accompanied by gallstones. Empirical antibiotics were administered both before and after surgery to prevent infection. On the fourth day post-surgery, symptoms of CDI emerged. Stool cultures confirmed the presence of C. difficile DNA. Treatment involved a combination of vancomycin and linezolid, resulting in the patient's successful recovery upon discharge. However, the patient failed to adhere to the prescribed medication after discharge and was discovered deceased during a follow-up two months later.

CDI is the leading cause of nosocomial post-operative care, with limited clinical cases and poor patient prognosis, and comprehensive clinical treatment guidelines are still lacking. This infection can be triggered by a variety of factors, including intestinal hypoxia, inappropriate antibiotic use, and bile acid circulation disorders. In patients with chronic bowel disease and related etiologies, prompt preoperative attention to possible CDI and preoperative bowel preparation is critical. Adequate and prolonged medication should be maintained in the treatment of CDI to prevent recurrence of the disease.

Clostridioides difficile is a bacterium that causes life-threatening intestinal infections. Infection symptoms are mediated by a toxin secreted by the bacterium. Toxin pathogenesis is modulated by the intracellular molecule, inositol-hexakisphosphate (IP6). IP6 binds to a cysteine protease domain (CPD) on the toxin, inducing autoproteolysis, which liberates a virulence factor in the cell cytosol. We developed second-generation IP6 analogs designed to induce autoproteolysis in the gut lumen, prior to toxin uptake, circumventing pathogenesis. We synthesized a panel of thiophosphate-/sulfate-containing IP6 analogs and characterized their toxin binding affinity, autoproteolysis induction, and cation interactions. Our top candidate was soluble in extracellular cation concentrations, unlike IP6. The IP6 analogs were more negatively charged than IP6, which improved affinity and stabilization of the CPD, enhancing toxin autoproteolysis. Our data illustrate the optimization of IP6 with thiophosphate biomimetic which are more capable of inducing toxin autoproteolysis than the native ligand, warranting further studies in vivo.

Clostridioides difficile infection (CDI) is a health crisis comprising a majority of healthcare-associated infections and is now being seen in the community. Persistent dysbiosis despite treatment with standard-of-care antibiotics increases risk of recurrent infections. Fecal microbiota transplantation has been an effective way of addressing dysbiosis, but the studies have lacked standardization, which makes outcome and safety data difficult to interpret. Standardized microbiome therapies have demonstrated efficacy and safety for recurrent CDI and have been approved to prevent recurrent infection. In this review, we discuss the data behind and the practice use of fecal microbiota spores, live-brpk (VOWST™ / VOS), a US FDA approved live biotherapeutic for the prevention of recurrent CDI.

Biofilm formation and toxin production are some of the virulence factors of Clostridioides difficile (C. difficile), which causes hospital-acquired C. difficile infection (HA-CDI). This work investigated the prevalence and distribution of different strains recovered from HA-CDI patients hospitalized in 4 medical centres across Israel, and characterized strains' virulence factors and antibiotic susceptibility. One-hundred and eighty-eight faecal samples were collected. C. difficile 's toxins were detected by the CerTest Clostridium difficile GDH + Toxin A + B combo card test kit. Toxin loci PaLoc and PaCdt were detected by whole-genome sequencing (WGS). Multi-locus sequence typing (MLST) was performed to classify strains. Biofilm production was assessed by crystal violet. Antibiotic susceptibility was determined using Etest. Fidaxomicin susceptibility was tested via agar dilution. Sequence type (ST) 42 was the most (13.8%) common strain. All strains harboured the 2 toxins genes; 6.9% had the binary toxin. Most isolates were susceptible to metronidazole (98.9%) and vancomycin (99.5%). Eleven (5.85%) isolates were fidaxomicin-resistant. Biofilm production capacity was associated with ST (p < 0.001). In conclusion, a broad variety of C. difficile strains circulate in Israel's medical centres. Further studies are needed to explore the differences and their contribution to HA-CDI epidemiology.

Toxoplasma gondii causes widespread chronic infections that are not cured by current treatments due to inability to affect semi-dormant bradyzoite stages within tissue cysts. To identify compounds to eliminate chronic infection, we developed a HTS using a recently characterized strain of T. gondii that undergoes efficient conversion to bradyzoites in intro. Stage-specific expression of luciferase was used to selectively monitor growth inhibition of bradyzoites by the Library of Pharmacological Active Compounds, consisting of 1,280 drug-like compounds. We identified 44 compounds with >50% inhibitory effects against bradyzoites, including new highly potent compounds, several of which have precedent for antimicrobial activity. Subsequent characterization of the compound Sanguinarine sulfate revealed potent and rapid killing against in vitro produced bradyzoites and bradyzoites harvested from chronically infected mice. These findings provide a platform for expanded screening and identify promising compounds for further preclinical development against T. gondii bradyzoites responsible for chronic infection.

How to cite this article: Khilnani GC, Tiwari P, Mittal S, Kulkarni AP, Chaudhry D, Zirpe KG, et al. Guidelines for Antibiotics Prescription in Critically Ill Patients. Indian J Crit Care Med 2024;28(S2):S104-S216.

There is an unmet need for effective treatments of Clostridioides difficile infection, an emerging health crisis in the United States. The management of C. difficile infection should include treatment of active infection and a strategy to prevent recurrence. Current gold standard therapy includes oral antibiotics which predispose patients to gut dysbiosis and increase the risk of recurrent infection. Addressing dysbiosis via fecal microbiota transplantation is an active and promising area of research, but studies have lacked standardization which makes outcome and safety data difficult to interpret. Rebyota™, formerly known as RBX2660, is a live biotherapeutic product designed using a standardized protocol and manufacturing process that has been shown to be effective for preventing recurrent C. difficile infection.

Antibiotic use is a major risk factor for recurrent Clostridioides difficile infection (CDI) due to the associated disruption in gut microbiota. Fecal microbiota, live-jslm (REBYOTA®; RBL, previously RBX2660), is the first microbiota-based live biotherapeutic approved by the US Food and Drug Administration to prevent recurrent CDI in adults following standard-of-care antibiotic treatment. To investigate the impact of non-CDI antibiotics on the durability of RBL, a subgroup analysis was conducted on PUNCH™ Open-Label study participants who received non-CDI antibiotics during the period between RBL administration and up to 2 years after.

Participants in PUNCH™ Open-Label who received non-CDI antibiotics after RBL administration were included in this subgroup analysis. Treatment response was defined as the absence of CDI diarrhea needing retreatment at the last evaluable time point (8 weeks, 6 months, 1 year, or 2 years) after RBL administration.

Among participants from PUNCH™ Open-Label, 43 received non-CDI antibiotics after RBL administration but before CDI recurrence as evaluated over a 2-year period. Across all evaluable time points, 86% (37/43) of participants had a treatment response regardless of when non-CDI antibiotic exposure occurred. Treatment response was sustained for a median 470 days (IQR, 212-648) from the first day of non-CDI antibiotic use. Most participants (5/6) with CDI recurrences received a high-risk antibiotic.

RBL remained efficacious in participants with a history of recurrent CDI after subsequent non-CDI antibiotic exposure.

NCT02589847 (https://clinicaltrials.gov/study/NCT02589847).

Urinary tract infection (UTI) is the second most common indication for antibiotic therapy among inpatients in the United States. Ceftriaxone, a third-generation cephalosporin, is habitually chosen to treat inpatient UTIs due to familiarity, cost, and perceived safety. However, third-generation cephalosporins increase the risk of health care facility-onset Clostridioides difficile infection (HOCDI) more than any other antibiotic group, while no statistical risk exists for first-generation cephalosporins. Recent evidence comparing Enterobacterales susceptibility for first- and third-generation cephalosporins in urinary specimens in the United States is limited. This analysis assessed the comparative activity of cefazolin and ceftriaxone for Enterobacterales urinary isolates and incidence of HOCDI to determine the usefulness of cefazolin as an empirical agent to manage inpatient UTI and limit ceftriaxone collateral damage.

This was a retrospective single-center observational study. Microbiologic susceptibility data were analyzed for Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis urinary specimens taken from adult inpatients admitted from January 1, 2022, to December 31, 2022. Primary outcome was incidence of E coli, K pneumoniae, and P mirabilis susceptibility to cefazolin in uncomplicated UTI (MIC <16 µg/mL). Secondary outcomes include susceptibility for complicated UTI and HOCDI risk associated with cefazolin and ceftriaxone.

A total of 1150 urine samples were identified as E coli, K pneumoniae, and P mirabilis in 2022. Susceptibility to cefazolin was observed in 1064 (92.5%) of 1150 isolates using the MIC breakpoint for uncomplicated UTI and to ceftriaxone in 1115 (97.0%) of 1150 isolates (P < 0.001). From 2016 to 2022, either cefazolin or ceftriaxone was administered in 26,462 inpatient admissions, with HOCDI diagnoses occurring in 89 admissions. HOCDI developed in 78 admissions (0.40%) with ceftriaxone exposure, and 11 cases (0.15%) developed in cefazolin-exposed admissions (adjusted odds ratio, 2.44; 95% CI, 1.25-4.76; P < 0.001).

Cefazolin exhibits high susceptibility for uropathogens commonly implicated in cases of uncomplicated UTI, the most common UTI diagnosis among inpatients. Although ceftriaxone shows a higher susceptibility rate against these common uropathogens, it more than doubles the risk for HOCDI compared with cefazolin. For institutions evaluating opportunities to reduce ceftriaxone use to limit associated collateral damage such as HOCDI, use of cefazolin for uncomplicated UTI may be evaluated by using local susceptibility data.

Current guidelines recommend broad-spectrum antibiotics for high-severity community-acquired pneumonia (CAP), potentially contributing to antimicrobial resistance (AMR). We aim to compare outcomes in CAP patients treated with amoxicillin (narrow-spectrum) versus co-amoxiclav (broad-spectrum), to understand if narrow-spectrum antibiotics could be used more widely.

We analysed electronic health records from adults (≥16 y) admitted to hospital with a primary diagnosis of pneumonia between 01-January-2016 and 30-September-2023 in Oxfordshire, United Kingdom. Patients receiving baseline ([-12 h,+24 h] from admission) amoxicillin or co-amoxiclav were included. The association between 30-day all-cause mortality and baseline antibiotic was examined using propensity score (PS) matching and inverse probability treatment weighting (IPTW) to address confounding by baseline characteristics and disease severity. Subgroup analyses by disease severity and sensitivity analyses with missing covariates imputed were also conducted.

Among 16,072 admissions with a primary diagnosis of pneumonia, 9685 received either baseline amoxicillin or co-amoxiclav. There was no evidence of a difference in 30-day mortality between patients receiving initial co-amoxiclav vs. amoxicillin (PS matching: marginal odds ratio 0.97 [0.76-1.27], p = 0.61; IPTW: 1.02 [0.78-1.33], p = 0.87). Results remained similar across stratified analyses of mild, moderate, and severe pneumonia. Results were also similar with missing data imputed. There was also no evidence of an association between 30-day mortality and use of additional macrolides or additional doxycycline.

There was no evidence of co-amoxiclav being advantageous over amoxicillin for treatment of CAP in 30-day mortality at a population-level, regardless of disease severity. Wider use of narrow-spectrum empirical treatment of moderate/severe CAP should be considered to curb potential for AMR.

Microbiota restoration therapy has become a standard treatment for recurrent Clostridioides difficile infection (rCDI). In this article, we review the studies supporting the licensure of two live biotherapeutic products (LBPs) designed to prevent rCDI and to provide clinicians with a perspective on their differences. PubMed was reviewed on 1 October 2023, for all papers published concerning the current Food and Drug Administration allowance of the use of fecal microbiota transplantation (FMT) and the studies that led to the licensure of RBX2660 (REBYOTA™), generic name, fecal microbiota, live-jslm, and SER-109 (VOWST™), generic name, fecal microbiota spores, live-brpk. OpenBiome continues to produce fecal products for patients with rCDI at their treatment sites, and the American Gastroenterology Association has a National Registry focused on long-term safety of administering fecal microbiota products. The science behind the licensing of fecal microbiota, live-jslm, a consortium of fecal anaerobes found in stool augmented with strains of Bacteroidetes and fecal microbiota spores, live-brpk, a mixture of 50 species of purified Firmicutes spores is reviewed. Both products appear to be safe in clinical trials and effective in reducing rCDI episodes by mechanisms established for FMT, including normalization of α- and β-diversity of the microbiome and by increasing fecal secondary bile acids. The different makeup of the two LBPs suggests that rCDI responds to a variety of engrafting microbiota which explains why nearly all donors in FMT of rCDI are generally effective. Fecal microbiota, live-jslm has also been shown to successfully treat rCDI in elderly patients with advanced comorbidities. With the licensure of two novel LBPs, we are entering a new phase of microbiota replacement therapy. Having standardized manufacturing and proper monitoring of products, harnessing the microbiome to control and prevent disease has a new beginning.

Clostridioides difficile is a causative agent of antibiotic-associated diarrhea as well as pseudomembranous colitis. So far, all known bacteriophages infecting these bacteria are temperate, which means that instead of prompt lysis of host cells, they can integrate into the host genome or replicate episomally. While C. difficile phages are capable of spontaneous induction and entering the lytic pathway, very little is known about the regulation of their maintenance in the state of lysogeny. In this study, we investigated the properties of a putative major repressor of the recently characterized C. difficile phiCDKH01 bacteriophage. A candidate protein belongs to the XRE family and controls the transcription of genes encoding putative phage antirepressors, known to be involved in the regulation of lytic development. Hence, the putative major phage repressor is likely to be responsible for maintenance of the lysogeny.

Antimicrobial stewardship programs (ASPs) can lower antibiotic use, decrease medical expenses, prevent the emergence of resistant bacteria, and enhance treatment for infectious diseases. This study summarizes the stepwise implementation and effects of ASPs in a single university-affiliated tertiary care hospital in Korea; it also presents future directions and challenges in resource-limited settings. At the study hospital, the core elements of the ASP such as leadership commitment, accountability, and operating system were established in 2000, then strengthened by the formation of the Antimicrobial Stewardship (AMS) Team in 2018. The actions of ASPs entail key components including a computerized restrictive antibiotic prescription system, prospective audit, post-prescription review through quantitative and qualitative intervention, and pharmacy-based interventions to optimize antibiotic usage. The AMS Team regularly tracked antibiotic use, the effects of interventions, and the resistance patterns of pathogens in the hospital. The reporting system was enhanced and standardized by participation in the Korea National Antimicrobial Use Analysis System, and educational efforts are ongoing. Stepwise implementation of the ASP and the efforts of the AMS Team have led to a substantial reduction in the overall consumption of antibiotics, particularly regarding injectables, and optimization of antibiotic use. Our experience highlights the importance of leadership, accountability, institution-specific interventions, and the AMS Team.

Introduction: Breast reduction mammoplasty (BRM) is a common procedure performed by plastic surgeons treating patients with hypermastia. It is customary to give preoperative prophylactic intravenous antibiotics for BRM, followed by several days of postoperative prophylactic oral antibiotics, despite the lack of evidence of their effectiveness in preventing surgical site infections (SSIs). The purpose of this study is to determine if the addition of prophylactic postoperative antibiotics is more effective in preventing SSIs in comparison to a single dose of preoperative prophylactic antibiotics in BRM. Methods: A retrospective analysis of 124 elective BRM cases by a single senior plastic surgeon was completed. Two study groups were formed based on the location of surgery and each group was assigned a different antibiotic regimen. The first antibiotic regimen consisted of a single preoperative intravenous dose of antibiotics (group 1), while the second regimen consisted of a preoperative intravenous dose followed by a 5-day course of oral antibiotics (group 2). Results: Overall SSI rate was 5.6%. Infection rate in group 1 was 8.1% in comparison to 3.2% for group 2 (P value .44). Overall, the incidence of complications was 29.0%; 38.7% in group 1 and 19.4% in group 2 (P value .03). Complications consisted of 35 cases of delayed wound healing, 7 SSIs and 2 hematomas requiring evacuation. Conclusion: Study results demonstrated that the use of postoperative prophylactic antibiotics for BRM had no significant effect on the rate of SSIs.

Many factors have been associated with the risk of toxigenic C. difficile diarrhea (TCdD). This study derived and internally validated a multivariate model for estimating the risk of TCdD in patients with diarrhea using readily available clinical factors.

A random sample of 3,050 symptomatic emergency department or hospitalized patients undergoing testing for toxigenic C. difficile at a single teaching hospital between 2014 and 2018 was created. Unformed stool samples positive for both glutamate dehydrogenase antigen by enzyme immunoassay and tcdB gene by polymerase chain reaction were classified as TCdD positive. The TCdD Model was created using logistic regression and was modified to the TCdD Risk Score to facilitate its use.

8.1% of patients were TCdD positive. TCdD risk increased with abdominal pain (adjusted odds ratio 1.3; 95% CI, 1.0-1.8), previous C. difficile diarrhea (2.5, 1.1-6.1), and prior antibiotic exposure, especially when sampled in the emergency department (4.2, 2.5-7.0) versus the hospital (1.7, 1.3-2.3). TCdD risk also increased when testing occurred earlier during the hospitalization encounter, when age and white cell count increased concurrently, and with decreased eosinophil count. In internal validation, the TCdD Model had moderate discrimination (optimism-corrected C-statistic 0.65, 0.62-0.68) and good calibration (optimism-corrected Integrated Calibration Index [ICI] 0.017, 0.001-0.022). Performance decreased slightly for the TCdD Risk Score (C-statistic 0.63, 0.62-0.63; ICI 0.038, 0.004-0.038).

TCdD risk can be predicted using readily available clinical risk factors with modest accuracy.

Clostridioides difficile infection (CDI) is the leading hospital-acquired infection in North America. While previous work on fecal microbiota transplantation (FMT), a highly effective treatment for CDI, has focused on colonization resistance mounted against C. difficile by FMT-delivered commensals, the effects of FMT on host gene expression are relatively unexplored. This study aims to identify transcriptional changes associated with FMT, particularly changes associated with protective immune responses.

Gene expression was assessed on day 2 and day 7 after FMT in mice after antibiotic-induced dysbiosis. Flow cytometry was also performed on colon and mesenteric lymph nodes at day 7 to investigate changes in immune cell populations.

FMT administration after antibiotic-induced dysbiosis successfully restored microbial alpha diversity to levels of donor mice by day 7 post-FMT. Bulk RNA sequencing of cecal tissue at day 2 identified immune genes, including both pro-inflammatory and Type 2 immune pathways as upregulated after FMT. RNA sequencing was repeated on day 7 post-FMT, and expression of these immune genes was decreased along with upregulation of genes associated with restoration of intestinal homeostasis. Immunoprofiling on day 7 identified increased colonic CD45+ immune cells that exhibited dampened Type 1 and heightened regulatory and Type 2 responses. These include an increased abundance of eosinophils, alternatively activated macrophages, Th2, and T regulatory cell populations.

These results highlight the impact of FMT on host gene expression, providing evidence that FMT restores intestinal homeostasis after antibiotic treatment and facilitates tolerogenic and Type 2 immune responses.

Innate lymphoid cells (ILCs) play a critical role in maintaining intestinal health in homeostatic and diseased conditions. During Clostridium difficile infection (CDI), IL-33 activates ILC2 to protect from colonic damage and mortality. The function of IL-33 and ILC is tightly regulated by the intestinal microbiota. We set out to determine the impact of antibiotic-induced disruption of the microbiome on ILC function. Our goal was to understand antibiotic-induced changes in ILC function on susceptibility to C. difficile colitis in a mouse model. We utilized high-throughput single-cell RNAseq to investigate the phenotypic features of colonic ILC at baseline, after antibiotic administration with or without IL-33 treatment. We identified a heterogeneous landscape of colonic ILCs with gene signatures of inflammatory, anti-inflammatory, migratory, progenitor, plastic, and antigen-presenting ILCs. Antibiotic treatment decreased ILC2 while coordinately increasing ILC1 and ILC3 phenotypes. Notably, Ifng+, Ccl5+, and Il23r+ ILC increased after antibiotics. IL-33 treatment counteracted the antibiotic effect by downregulating ILC1 and ILC3 and activating ILC2. In addition, IL-33 treatment markedly induced the expression of type 2 genes, including Areg and Il5. Finally, we identified amphiregulin, produced by ILC2, as protective during C. difficile infection. Together, our data expand our understanding of how antibiotics induce susceptibility to C. difficile colitis through their impact on ILC subsets and function.IMPORTANCEClostridium difficile infection (CDI) accounts for around 500,000 symptomatic cases and over 20,000 deaths annually in the United States alone. A major risk factor of CDI is antibiotic-induced dysbiosis of the gut. Microbiota-regulated IL-33 and innate lymphoid cells (ILCs) are important in determining the outcomes of C. difficile infection. Understanding how antibiotic and IL-33 treatment alter the phenotype of colon ILCs is important to identify potential therapeutics. Here, we performed single-cell RNAseq of mouse colon ILCs collected at baseline, after antibiotic treatment, and after IL-33 treatment. We identified heterogeneous subpopulations of all three ILC subtypes in the mouse colon. Our analysis revealed several potential pathways of antibiotic-mediated increased susceptibility to intestinal infection. Our discovery that Areg is abundantly expressed by ILCs, and the protection of mice from CDI by amphiregulin treatment, suggests that the amphiregulin-epidermal growth factor receptor pathway is a potential therapeutic target for treating intestinal colitis.

Antibiotics and proton pump inhibitors (PPI) are recognized risk factors for acquisition and recurrence of Clostridioides difficile infection (CDI), yet combined effects remain unclear.

To assess the short- and long-term effects of antibiotics and PPIs on CDI risk and recurrence.

Population-based study including all 43 152 patients diagnosed with CDI in Sweden (2006-2019), and 355 172 matched population controls without CDI. The impact of antibiotics and PPIs on CDI risk and recurrence was explored for recent (0-30 days) and preceding (31-180 days) use prior to their first CDI diagnosis, using multivariable conditional logistic regression presented as odds ratios (ORs) and 95% confidence interval, adjusted for demographics, comorbidities and other drugs.

Compared to controls, the combined effect of recent PPIs and antibiotics [ORAB+PPI = 17.51 (17.48-17.53)] on CDI risk was stronger than the individual effects [ORAB = 15.37 (14.83-15.93); ORPPI = 2.65 (2.54-2.76)]. Results were less pronounced for exposure during the preceding months. Dose-response analyses showed increasing exposure correlated with CDI risk [recent use: ORAB = 6.32 (6.15-6.49); ORPPI = 1.65 (1.62-1.68) per prescription increase].Compared to individuals without recurrence (rCDI), recent [ORAB = 1.30 (1.23-1.38)] and preceding [ORAB = 1.23 (1.16-1.31); ORPPI = 1.12 (1.03-1.21)] use also affected the risk of recurrence yet without significant interaction between both. Recent macrolides/lincosamides/streptogramins; other antibacterials including nitroimidazole derivates; non-penicillin beta lactams and quinolones showed the strongest association with CDI risk and recurrence, particularly for recent use. PPI use, both recent and preceding, further increased the CDI risk associated with almost all antibiotic classes.

Recent and less recent use of PPIs and systemic antibiotics was associated with an increased risk of CDI, particularly in combination.

Plastic surgery trainees are often called to render care in the emergency department (eg, for established patients, trauma, burns). Broad-based knowledge in pharmacotherapeutics during these encounters is critical. This includes an understanding of pain medications, anxiolytics, local anesthetics, antibiotics, anticoagulants, antidotes, and more to ensure optimal patient care. The purpose of this report is to describe 25 frequently used and other important medications that plastic surgery trainees should know for an adult emergency department encounter.

Clostridioides difficile is a Gram-positive bacteria that causes nosocomial infections, significantly impacting public health. In the present study, we aimed to describe the clinical characteristics, outcomes, and relationship between antibiotic exposure and Clostridioides difficile infection (CDI) in patients based on reports from two databases. Thus, we conducted a retrospective study of patients diagnosed with CDI from Sibiu County Clinical Emergency Hospital (SCCEH), Romania, followed by a descriptive analysis based on spontaneous reports submitted to the EudraVigilance (EV) database. From 1 January to 31 December 2022, we included 111 hospitalized patients with CDI from SCCEH. Moreover, 249 individual case safety reports (ICSRs) from EVs were analyzed. According to the data collected from SCCEH, CDI was most frequently reported in patients aged 65-85 years (66.7%) and in females (55%). In total, 71.2% of all patients showed positive medical progress. Most cases were reported in the internal medicine (n = 30, 27%), general surgery (n = 26, 23.4%), and infectious disease (n = 22, 19.8%) departments. Patients were most frequently exposed to ceftriaxone (CFT) and meropenem (MER). Also, in the EV database, most CDI-related ADRs were reported for CFT, PIP/TAZ (piperacillin/tazobactam), MER, and CPX (ciprofloxacin). Understanding the association between previous antibiotic exposure and the risk of CDI may help update antibiotic stewardship protocols and reduce the incidence of CDI by lowering exposure to high-risk antibiotics.