Genomic surveillance as a scalable framework for precision phage therapy against antibiotic-resistant pathogens.

Phage therapy is gaining increasing interest in the fight against critically antibiotic-resistant nosocomial pathogens. However, the narrow host range of bacteriophages hampers the development of broadly effective phage therapeutics and demands precision approaches. Here, we combine large-scale phylogeographic analysis with high-throughput phage typing to guide the development of precision phage cocktails targeting carbapenem-resistant Acinetobacter baumannii, a top-priority pathogen. Our analysis reveals that a few strain types dominate infections in each world region, with their geographical distribution remaining stable within 6 years. As we demonstrate in Eastern Europe, this spatiotemporal distribution enables preemptive preparation of region-specific phage collections that target most local infections. Finally, we showcase the efficacy of phage cocktails against prevalent strain types using in vitro and animal infection models. Ultimately, genomic surveillance identifies patients benefiting from the same phages across geographical scales, thus providing a scalable framework for precision phage therapy.

COVID-19 Biomarkers Comparison: Children, Adults and Elders.

Background and Objectives: this study aimed to research links between C-reactive protein (CRP), lactate dehydrogenase (LDH), creatinekinase (CK), 25-OH vitamin D (25-OHD), ferritin (FER), high-density lipoprotein cholesterol (HDL)cholesterol and clinical severity in patients from the western part of Romania, and compare their potential use as biomarkers for intensive care units (ICU) admission and death in children, adults and elders. Materials and Methods: this study is a retrospective cohort study, performed on patients positively diagnosed with COVID-19. Available CRP, LDH, CK 25-OH vitamin D, ferritin, HDL cholesterol and clinical severity were recorded. The following were assessed: median group differences, association, correlation and receiver operating characteristic. Results: 381 children, 614 adults and 381 elders were studied between 1 March 2021 and 1 March 2022. Most children and adults presented mild symptomatology (53.28%, 35.02%, respectively), while most elders presented severe symptomatology (30.04%). ICU admission was 3.67% for children, 13.19% for adults and 46.09% for elders, while mortality was 0.79% for children, 8.63% for adults and 25.1% for elders. With the exception of CK, all other biomarkers showed some significant associations with clinical severity, ICU admission and death. Conclusions: CRP, LDH, 25-OH vitamin D, ferritin and HDL are important biomarkers for COVID-19 positive patients, especially in the pediatric population, while CK was mostly within normal ranges.

The Successful Recovery of a Critically Ill COVID-19 Patient, Following the Combination of Therapeutic Plasma Exchange and Convalescent Plasma Transfusion: A Case Report.

With an intricate symptom pattern involving a dysregulated host response to infection, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause severe inflammation and cytokine storms, acute respiratory distress syndrome, coagulopathy, multi-organ failure, and finally death. The uniqueness of this case report lies in the nature of the therapeutic intervention performed. While numerous studies are available on both the use of therapeutic plasma exchange in coronavirus disease 2019 (COVID-19) patients and convalescent plasma transfusion as separate treatment methods, there is very little information regarding the combination of these procedures. We present the case of a 52-year-old male, unvaccinated for COVID-19, who tested positive on reverse transcriptase polymerase chain reaction for SARS-CoV-2 for the first time and presented in the emergency room with fever, chills, severe cough, tachypnea, tachycardia, and dyspnea that started two days before presentation. Upon rapid assessment, the patient showed signs of acute respiratory failure, so it was decided to transfer the patient to the intensive care unit, COVID-19 ward, after preliminary radiological examination. For the next 24 days, the patient was stationed in the intensive care unit, where he was closely monitored and treated. Invasive mechanical ventilation was required following the initial worsening of his respiratory status. We performed therapeutic plasma exchange on the first day of his stay in the intensive care unit, and immediately after the procedure, the patient was transfused with 500 mL of convalescent plasma from healthy donors. The patient's condition improved over the next few days, which led to the cessation of mechanical ventilation and, after treating the superinfection, the patient was discharged home, making a full recovery. The early initiation of therapeutic plasma exchange followed by transfusion of convalescent plasma in severe and critical forms of COVID-19 may reduce the risk of the progression of the disease and ultimately reduce the risk of negative outcomes in a selected group of patients.

Association of Proteus mirabilis and Providencia stuartii Infections with Diabetes.

Background and Objectives: Proteus and Providencia are related genera of opportunistic pathogens belonging to the Morganellaceae family, often a cause of infections in the immunocompromised hosts, such as diabetic patients. Their clinical significance has increased due to their intrinsic resistance to polymyxins, which is often associated with acquired resistance mechanisms. In this study we evaluated the infections caused by Proteus mirabilis and Providencia stuartii in two groups of patients, with diabetes (group 1) and without diabetes (group 2) admitted to the intensive care unit and surgical wards. The infections were investigated in terms of infection type, risk factors, clinical course, predictive factors for unfavourable outcomes and antibiotic resistance profile. Materials and Methods: An observational, retrospective, cross-sectional study was conducted, comprising all patients infected with these pathogens. Bacterial identification and antibiotic sensitivity testing were performed using the Vitek2C automated system. Results: Comparison of the two groups showed that the statistically significant common infectious risk factors were found less frequently among diabetic patients when compared with non-diabetic patients, and that antimicrobial resistance was significantly lower in the diabetic patient group. However, survival rates did not differ between the two groups, drawing attention to the implications of diabetes as comorbidity. Additionally, with regard to the antibiotic resistance profile, 38.89% of P. stuartii strains isolated from diabetic patients belonged to the difficult-to-treat (DTR) phenotype, contributing to the severity of these infections compared with those caused by P. mirabilis, of which 32% were wild type strains and 0% were DTR phenotype. The DTR/extended spectrum beta-lactamase producing P. stuartii isolates more than doubled the risk of mortality, while the presence of nasogastric nutrition tripled the risk. Conclusions: P. stuartii infections that occurred in diabetic patients proved to be more difficult to treat, the majority of them being healthcare-associated bacteremias.

Profiles of multidrug-resistant organisms among patients with bacteremia in intensive care units: an international ID-IRI survey.

Evaluating trends in antibiotic resistance is a requisite. The study aimed to analyze the profile of multidrug-resistant organisms (MDROs) among hospitalized patients with bacteremia in intensive care units (ICUs) in a large geographical area. This is a 1-month cross-sectional survey for blood-borne pathogens in 57 ICUs from 24 countries with different income levels: lower-middle-income (LMI), upper-middle-income (UMI), and high-income (HI) countries. Multidrug-resistant (MDR), extensively drug-resistant (XDR), or pan-drug-resistant isolates were searched. Logistic regression analysis determined resistance predictors among MDROs. Community-acquired infections were comparable to hospital-acquired infections particularly in LMI (94/202; 46.5% vs 108/202; 53.5%). Although MDR (65.1%; 502/771) and XDR (4.9%; 38/771) were common, no pan-drug-resistant isolate was recovered. In total, 32.1% of MDR were Klebsiella pneumoniae, and 55.3% of XDR were Acinetobacter baumannii. The highest MDR and XDR rates were in UMI and LMI, respectively, with no XDR revealed from HI. Predictors of MDR acquisition were male gender (OR, 12.11; 95% CI, 3.025-15.585) and the hospital-acquired origin of bacteremia (OR, 2.643; 95%CI, 1.462-3.894), and XDR acquisition was due to bacteremia in UMI (OR, 3.344; 95%CI, 1.189-5.626) and admission to medical-surgical ICUs (OR, 1.481; 95% CI, 1.076-2.037). We confirm the urgent need to expand stewardship activities to community settings especially in LMI, with more paid attention to the drugs with a higher potential for resistance. Empowering microbiology laboratories and reports to direct prescribing decisions should be prioritized. Supporting stewardship in ICUs, the mixed medical-surgical ones in particular, is warranted.

Clostridium Difficile and COVID-19: General Data, Ribotype, Clinical Form, Treatment-Our Experience from the Largest Infectious Diseases Hospital in Western Romania.

Background and Objectives: In Coronavirus Disease 2019 (COVID-19), which is caused by the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the clinical manifestations are primarily related to the pulmonary system. Under 10% of cases also develop gastrointestinal events such as diarrhea, nausea, vomiting and abdominal pain. Materials and Methods: We conducted an observational, retrospective study in the Infectious Diseases Clinic of "Victor Babes" Hospital, Timis County, in order to assess the incidence, outcome and risk factors for clostridium difficile infection (CDI) in COVID-19 patients. Results: Out of 2065 COVID-19 cases, hospitalized between 1st September 2020 and 30th April 2021, 40 cases of CDI were identified with 32 cases of hospital-onset of CDI and eight cases of community-onset and healthcare-associated CDI. By randomization, polymerase chain reaction ribotyping of Clostridium Difficile was performed in six cases. All the randomized cases tested positive for ribotype 027. The percentage of cases recovered with complications at discharge was higher among COVID-19 patients and CDI (p = 0.001). The in-hospital stay, 36 days versus 28 days, was longer among COVID-19 patients and CDI (p = 0.01). The presence of previous hospitalization (p = 0.004) and administration of antibiotics during the hospital stay, increased the risk of CDI among COVID-19 patients. The mean adjusted CCI at admission was lower among controls (p = 0.01). In two cases, exitus was strictly CDI-related, with one case positive for 027 ribotype. Conclusions: CDI has complicated the outcome of COVID-19 patients, especially for those with comorbidities or previously exposed to the healthcare system. In the face of the COVID-19 pandemic and the widespread, extensive use of antibiotics, clinicians should remain vigilant for possible CDI and SARS-CoV-2 co-infection.

Multidrug-Resistant Gram-Negative Bacilli: A Retrospective Study of Trends in a Tertiary Healthcare Unit.

Background and objective: Bacterial multidrug resistance is particularly common in Gram-negative bacilli (GNB), with important clinical consequences regarding their spread and treatment options. The aim of this study was to investigate the trend of multidrug-resistant GNB (MDR-GNB) in high-risk hospital departments, between 2000⁻2015, in intervals of five years, with the intention of improving antibiotic therapy policies and optimising preventive and control practices. Materials and methods: This is an observational, retrospective study performed in three departments of the most important tertiary healthcare unit in the southwestern part of Romania: the Intensive Care Unit (ICU), the General Surgery Department (GSD), and the Nutrition and Metabolic Diseases Department (NMDD). MDR was defined as acquired resistance to at least one agent in three or more antimicrobial categories. Trends over time were determined by the Cochran⁻Armitage trend test and linear regression. Results: During the study period, a total of 2531 strains of MDR-GNB were isolated in 1999 patients: 9.20% in 2000, 18.61% in 2005, 37.02% in 2010, and 35.17% in 2015. The most significant increasing trend was recorded in the ICU (gradient = 7.63, R² = 0.842, p < 0.001). The most common MDR-GNB in the ICU was isolated from bronchoalveolar aspiration samples. Concerning the proportion of different species, most of the changes were recorded in the ICU, where a statistically significant increasing trend was observed for Proteus mirabilis (gradient = 2.62, R² = 0.558, p < 0.001) and Acinetobacter baumannii (gradient = 2.25, R² = 0.491, p < 0.001). Analysis of the incidence of the main resistance phenotypes proportion identified a statistically significant increase in carbapenem resistance in the ICU (Gradient = 8.27, R² = 0.866, p < 0.001), and an increased proportion of aminoglycoside-resistant strains in all three departments, but more importantly in the ICU and GSD. Conclusion: A statistically significant increasing trend was observed in all three departments; the most significant one was recorded in the ICU, where after 2010, carbapenem-resistant strains were isolated.

Antimicrobial consumption, costs and resistance patterns: a two year prospective study in a Romanian intensive care unit.

BACKGROUND: Due to the vulnerable nature of its patients, the wide use of invasive devices and broad-spectrum antimicrobials used, the intensive care unit (ICU) is often called the epicentre of infections. In the present study, we quantified the burden of hospital acquired pathology in a Romanian university hospital ICU, represented by antimicrobial agents consumption, costs and local resistance patterns, in order to identify multimodal interventional strategies. METHODS: Between 1st January 2012 and 31st December 2013, a prospective study was conducted in the largest ICU of Western Romania. The study group was divided into four sub-samples: patients who only received prophylactic antibiotherapy, those with community-acquired infections, patients who developed hospital acquired infections and patients with community acquired infections complicated by hospital-acquired infections. The statistical analysis was performed using the EpiInfo version 3.5.4 and SPSS version 20. RESULTS: A total of 1596 subjects were enrolled in the study and the recorded consumption of antimicrobial agents was 1172.40 DDD/ 1000 patient-days. The presence of hospital acquired infections doubled the length of stay (6.70 days for patients with community-acquired infections versus 16.06/14.08 days for those with hospital-acquired infections), the number of antimicrobial treatment days (5.47 in sub-sample II versus 11.18/12.13 in sub-samples III/IV) and they increased by 4 times compared to uninfected patients. The perioperative prophylactic antibiotic treatment had an average length duration of 2.78 while the empirical antimicrobial therapy was 3.96 days in sample II and 4.75/4.85 days for the patients with hospital-acquired infections. The incidence density of resistant strains was 8.27/1000 patient-days for methicilin resistant Staphylococcus aureus, 7.88 for extended spectrum ß-lactamase producing Klebsiella pneumoniae and 4.68/1000 patient-days for multidrug resistant Acinetobacter baumannii. CONCLUSIONS: Some of the most important circumstances collectively contributing to increasing the consumption of antimicrobials and high incidence densities of multidrug-resistant bacteria in the studied ICU, are represented by prolonged chemoprophylaxis and empirical treatment and also by not applying the definitive antimicrobial therapy, especially in patients with favourable evolution under empirical antibiotic treatment. The present data should represent convincing evidence for policy changes in the antibiotic therapy.

Intensive care antibiotic consumption and resistance patterns: a cross-correlation analysis.

BACKGROUND: Over recent decades, a dramatic increase in infections caused by multidrug-resistant pathogens has been observed worldwide. The aim of the present study was to investigate the relationship between local resistance bacterial patterns and antibiotic consumption in an intensive care unit in a Romanian university hospital. METHODS: A prospective study was conducted between 1st January 2012 and 31st December 2013. Data covering the consumption of antibacterial drugs and the incidence density for the main resistance phenotypes was collected on a monthly basis, and this data was aggregated quarterly. The relationship between the antibiotic consumption and resistance was investigated using cross-correlation, and four regression models were constructed, using the SPSS version 20.0 (IBM, Chicago, IL) and the R version 3.2.3 packages. RESULTS: During the period studied, the incidence of combined-resistant and carbapenem-resistant P. aeruginosa strains increased significantly [(gradient = 0.78, R2 = 0.707, p = 0.009) (gradient = 0.74, R2 = 0.666, p = 0.013) respectively], mirroring the increase in consumption of ß-lactam antibiotics with ß-lactamase inhibitors (piperacillin/tazobactam) and carbapenems (meropenem) [(gradient = 10.91, R2 = 0.698, p = 0.010) and (gradient = 14.63, R2 = 0.753, p = 0.005) respectively]. The highest cross-correlation coefficients for zero time lags were found between combined-resistant vs. penicillins consumption and carbapenem-resistant P. aeruginosa strains vs. carbapenems consumption (0.876 and 0.928, respectively). The best model describing the relation between combined-resistant P. aeruginosa strains and penicillins consumption during a given quarter incorporates both the consumption and the incidence of combined-resistant strains in the hospital department during the previous quarter (multiple R2 = 0.953, p = 0.017). The best model for explaining the carbapenem resistance of P. aeruginosa strains based on meropenem consumption during a given quarter proved to be the adjusted model which takes into consideration both previous consumption and incidence density of strains during the previous quarter (Multiple R2 = 0.921, p = 0.037). CONCLUSIONS: The cross-correlation coefficients and the fitted regression models provide additional evidence that resistance during the a given quarter depends not only on the consumption of antibacterial chemotherapeutic drugs in both that quarter and the previous one, but also on the incidence of resistant strains circulating during the previous quarter.

Early Prediction of Sepsis Incidence in Critically Ill Patients Using Specific Genetic Polymorphisms.

Several diagnostic methods for the evaluation and monitoring were used to find out the pro-inflammatory status, as well as incidence of sepsis in critically ill patients. One such recent method is based on investigating the genetic polymorphisms and determining the molecular and genetic links between them, as well as other sepsis-associated pathophysiologies. Identification of genetic polymorphisms in critical patients with sepsis can become a revolutionary method for evaluating and monitoring these patients. Similarly, the complications, as well as the high costs associated with the management of patients with sepsis, can be significantly reduced by early initiation of intensive care.

Early Evaluation and Monitoring of Critical Patients with Acute Respiratory Distress Syndrome (ARDS) Using Specific Genetic Polymorphisms.

A high percentage of critical patients are found to develop acute respiratory distress syndrome (ARDS). Several studies have reported high mortality rates in these cases which are most frequently associated with multiple organ dysfunctions syndrome. Lately, many efforts have been made to evaluate and monitor ARDS in critical patients. In this regard, the assessment of genetic polymorphisms responsible for developing ARDS present as a challenge and are considered future biomarkers. Early detection of the specific polymorphic gene responsible for ARDS in critically ill patients can prove to be a useful tool in the future, able to help decrease the mortality rates in these cases. Moreover, identifying the genetic polymorphism in these patients can help in the implementation of a personalized intensive therapy scheme for every type of patient, based on its genotype.

The Use of Lipid Peroxidation Expression as a Biomarker for the Molecular Damage in the Critically Ill Polytrauma Patient.

BACKGROUND: The critically ill polytrauma patient, apart from the primary, traumatic injuries and the secondary, port-traumatic injuries, presents with a series of molecular disasters. Dysfunctions of the biochemical pathways and molecular damage add to the worsening of the clinical status of these patients, one of the most well-known molecular phenomena being oxidative stress (OS), responsible for an escalation of the inflammatory status, multiple infections, and multiple organ dysfunction syndrome (MODS). METHODS: For this study was analysed the literature available on PubMed and Scopus. The key words used in the search were "oxidative stress", "lipid peroxidation", "critically ill", "polytrauma patients", and "biomarkers oxidative stress". RESULTS: For the study we selected 47 science articles. The oxidative attack on lipids is responsible for the biosynthesis of an increased quantity of free radicals (FR), which further intensifies and aggravates the redox status in these patients. CONCLUSIONS: One of the most aggressive redox mechanisms related to lipid molecules is known as lipid peroxidation (LPOX).

Clostridium difficile in western Romania: unfavourable outcome predictors in a hospital for infectious diseases.

BACKGROUND: The recent emergence of Clostridium difficile infections has included this condition among top nosocomial infections, due to its incidence, complications and important fatality, as well as to significant economic costs. METHODS: A prospective surveillance study of Clostridium difficile enterocolitis cases was performed in "Victor Babes" Infectious Diseases Hospital in Timisoara (Romania) between 01.01.2013 - 30.06.2014, to estimate the incidence and to investigate the risk factors for unfavourable outcome and relapse. Dichotomous variables were compared by the chi-square test or Fisher exact test and the Mann-Whitney U test was used for continuous variables. Risk factors for unfavourable outcome/recurrence were investigated by logistic regression. RESULTS: 210 patients who experienced 219 episodes of infection with Clostridium difficile were identified, which gives an incidence per hospital of 20.57/15.70 to 1,000 discharged patients in 2013/2014 or 17.73/14.04 to 10,000 patient-days. In 162 patients (77.14%) the evolution was favourable while in 48 (22.86%) the outcome was unfavourable. In 42 patients (20.00%) recurrence of symptoms was identified. The multivariate analysis by logistic regression identified the ATLAS score (OR = 4.97, 95% CI = 2.12 to 11.66, p <0.001), age (OR = 1.12, 95% CI = 1.00 to 1.25, p = 0.046), and the number of antibiotics after episode onset (OR = 2.692, 95% CI = 1.01 to 7.17, p = 0.047) as predictors of an unfavourable evolution, while the number of hospitalization days (OR = 1.10, 95% CI = 1.03 to 1.16, p = 0.0015) was associated with recurrence of symptoms. CONCLUSIONS: The high incidence identified in our study is explained by the endemic character of these infections in some hospitals in Timisoara, released in late 2012, and the fact that "Victor Babes" Hospital is the only one in our area that provides treatment in all suspected or confirmed cases of this condition requiring hospitalization. The study identified the ATLAS score, age, and the number of antibiotics after episode onset as predictors of unfavourable evolution, while the number of days of hospitalization was associated with the recurrence of symptoms.

Bacterial Resistances and Sensibilities in a Tertiary Care Hospital in Romania-A Retrospective Analysis.

The increase in bacterial resistance is currently a global burden for the health care system. In order to evaluate the resistance rates of several bacteria from the most encountered cultures in clinical practice, we performed a retrospective analysis of all of the positive cultures from the year 2021 in a tertiary care hospital in Romania. Our analysis captured 3299 positive cultures. The median age of the patients was 62 years (IQR: 41-71 years old) with a slight predominance among females (53.1%). Overall, the most common cultures were urocultures, wound secretion cultures and blood cultures, and the most common identified bacteria were Escherichia coli, Staphylococcus aureus and Klebsiella spp. Positive cultures with the highest resistance rates were found in the bronchial aspirate cultures, catheter tip cultures, urocultures and blood cultures. Escherichia coli (n = 996) had the highest resistance to ampicillin (19.8%) and trimetoprim-sulfametoxazole (16.4%), while Staphylococcus aureus (n = 698) presented the highest resistance rates to clindamycin (27.4%) and oxaciline (19.7%). Klebsiella (n = 481) presented the highest resistance rates to piperaciline-tazobactam (25.2%) and ampicillin (20.4%), whereas Acinetobacter baumanii (n = 123) presented a resistance rate of more than 50% to carbapenems, gentamicin, ciprofloxacin and ceftazidime. The aim of our study was to identify bacterial resistance rates in order to provide updated clinical data to guide physicians in choosing the best empirical antibiotic treatment, especially in the west part of Romania.

A Comprehensive Review of Microbial Biofilms on Contact Lenses: Challenges and Solutions.

Contact lenses (CL) have become an immensely popular means of vision correction, offering comfort to millions worldwide. However, the persistent issue of biofilm formation on lenses raises significant problems, leading to various ocular complications and discomfort. The aim of this review is to develop safer and more effective strategies for preventing and managing microbial biofilms on CL, improving the eye health and comfort of wearers. Taking these into consideration, the present study investigates the intricate mechanisms of biofilm formation, by exploring the interplay between microbial adhesion, the production of extracellular polymeric substances, and the properties of the lens material itself. Moreover, it emphasizes the diverse range of microorganisms involved, encompassing bacteria, fungi, and other opportunistic pathogens, elucidating their implications within lenses and other medical device-related infections and inflammatory responses. Going beyond the challenges posed by biofilms on CL, this work explores the advancements in biofilm detection techniques and their clinical relevance. It discusses diagnostic tools like confocal microscopy, genetic assays, and emerging technologies, assessing their capacity to identify and quantify biofilm-related infections. Finally, the paper delves into contemporary strategies and innovative approaches for managing and preventing biofilms development on CL. In Conclusion, this review provides insights for eye care practitioners, lens manufacturers, and microbiology researchers. It highlights the intricate interactions between biofilms and CL, serving as a foundation for the development of effective preventive measures and innovative solutions to enhance CL safety, comfort, and overall ocular health. Research into microbial biofilms on CL is continuously evolving, with several future directions being explored to address challenges and improve eye health outcomes as far as CL wearers are concerned.

The Profile of Bacterial Infections in a Burn Unit during and after the COVID-19 Pandemic Period.

Infections represent a major complication for burn-injured patients. The aim of this study was to highlight the changes in the incidence and antimicrobial resistance of bacterial strains isolated from burn patients, at the end of the COVID-19 pandemic, in relation to the antibiotics used during the pandemic. A comparative analysis of the demographic data and the microorganisms identified in the clinical samples of two groups of burn patients admitted to a university hospital in Romania was carried out. The first group consisted of 48 patients and the second of 69 patients, hospitalized in January-August 2020 and 2023, respectively. The bacterial species with the highest incidence were S. aureus, A. baumannii, Pseudomonas spp. The significant changes between 2023 and 2020 are reflected in the increase in the frequency of non-fermentative Gram-negative bacteria, especially S. maltophilia, and the increase in antimicrobial resistance of Pseudomonas and Klebsiella spp. Klebsiella spp. did not change in frequency (7%), but there was a significant increase in the incidence of K. pneumoniae strains with pan-drug resistant behaviour to antibiotics (40%), including colistin. The phenomenon can be explained by the selection of specimens carrying multiple resistance genes, as a result of antibiotic treatment during the COVID-19 period. The post-pandemic antimicrobial resistance detected in burn patients indicates the need for permanent surveillance of the resistance trends, primarily due to the limited therapeutic options available for these patients.

Enterobacterales carrying chromosomal AmpC ß-lactamases in Europe (EuESCPM): Epidemiology and antimicrobial resistance burden from a cohort of 27 hospitals, 2020-2022.

INTRODUCTION: The ESCPM group (Enterobacter species including Klebsiella aerogenes - formerly Enterobacter aerogenes, Serratia species, Citrobacter freundii complex, Providencia species and Morganella morganii) has not yet been incorporated into systematic surveillance programs. METHODS: We conducted a multicentre retrospective observational study analysing all ESCPM strains isolated from blood cultures in 27 European hospitals over a 3-year period (2020-2022). Diagnostic approach, epidemiology, and antimicrobial susceptibility were investigated. RESULTS: Our study comprised 6,774 ESCPM isolates. MALDI-TOF coupled to mass spectrometry was the predominant technique for bacterial identification. Susceptibility to new ß-lactam/ß-lactamase inhibitor combinations and confirmation of AmpC overproduction were routinely tested in 33.3% and 29.6% of the centres, respectively. The most prevalent species were E. cloacae complex (44.8%) and S. marcescens (22.7%). Overall, third-generation cephalosporins (3GC), combined third- and fourth-generation cephalosporins (3GC + 4GC) and carbapenems resistance phenotypes were observed in 15.7%, 4.6%, and 9.5% of the isolates, respectively. AmpC overproduction was the most prevalent resistance mechanism detected (15.8%). Among carbapenemase-producers, carbapenemase type was provided in 44.4% of the isolates, VIM- (22.9%) and OXA-48-enzyme (16%) being the most frequently detected. E. cloacae complex, K. aerogenes and Providencia species exhibited the most notable cumulative antimicrobial resistance profiles, with the former displaying 3GC, combined 3GC + 4GC and carbapenems resistance phenotypes in 15.2%, 7.4%, and 12.8% of the isolates, respectively. K. aerogenes showed the highest rate of both 3GC resistant phenotype (29.8%) and AmpC overproduction (32.1%), while Providencia species those of both carbapenems resistance phenotype (42.7%) and carbapenemase production (29.4%). ESCPM isolates exhibiting both 3GC and combined 3GC + 4GC resistance phenotypes displayed high susceptibility to ceftazidime/avibactam (98.2% and 95.7%, respectively) and colistin (90.3% and 90.7%, respectively). Colistin emerged as the most active drug against ESCPM species (except those intrinsically resistant) displaying both carbapenems resistance phenotype (85.8%) and carbapenemase production (97.8%). CONCLUSIONS: This study presented a current analysis of ESCPM species epidemiology in Europe, providing insights to inform current antibiotic treatments and guide strategies for antimicrobial stewardship and diagnostics.

The Challenges of The Diagnostic and Therapeutic Approach of Patients with Infectious Pathology in Emergency Medicine.

The emergency department (ED) represents an important setting for addressing inappropriate antimicrobial prescribing practices because of the time constraints and the duration of microbiological diagnosis. The purpose of this study is to evaluate the etiology and antimicrobial resistance (AMR) pattern of the community-acquired pathogens, as well as the epidemiological characteristics of patients admitted through the ED, in order to guide appropriate antibiotic therapy. METHODS: A retrospective observational study was performed on 657 patients, from whom clinical samples (urine, purulent secretions, blood cultures, etc.) were collected for microbiological diagnosis in the first 3 days after presentation in the ED. The identification of pathogens and the antimicrobial susceptibility testing with minimum inhibitory concentration determination were carried out according to the laboratory protocols. RESULTS: From the 767 biological samples analyzed, 903 microbial isolates were identified. E. coli was most frequently isolated (24.25%), followed by Klebsiella spp., S. aureus (SA), and non-fermentative Gram-negative bacilli. E. coli strains maintained their natural susceptibility to most antibiotics tested. In the case of Pseudomonas spp. and Acinetobacter spp., increased rates of AMR were identified. Also, 32.3% of SA strains were community-acquired MRSA. CONCLUSIONS: The introduction of rapid microbiological diagnostic methods in emergency medicine is imperative in order to timely identify AMR strains and improve therapeutic protocols.

Therapeutic plasma exchange followed by convalescent plasma transfusion in severe and critically ill COVID-19 patients: A single centre non-randomized controlled trial.

Therapeutic plasma exchange (TPE) has been proposed as a rescue therapy in critically ill COVID-19 patients. The aim of the present study was to determine whether combining TPE with convalescent plasma (CVP) transfusion early in the intensive care unit (ICU) stay improves survival among this heterogeneous population. The primary endpoint was survival at 30 days. Secondary endpoints included assessing the evolution of biomarkers, such as the partial pressure of arterial oxygen to fractional inspired oxygen ratio, and C reactive protein (CRP), lactate dehydrogenase (LDH) and ferritin levels at the 7-day follow-up. This single centre, prospective, non-randomized controlled trial was conducted in an 8-bed COVID-19 ICU and included patients with severe COVID-19 pneumonia requiring intensive care treatment. A total of 19 patients were treated by performing TPE followed by CVP transfusion, in addition to standard treatment, while for another 19 patients, only standard treatment according to hospital protocols was used. TPE was initiated during the first 24 h after ICU admission, followed immediately by transfusion of CVP. Survival at 30 days was 47.37% in the TPE CVP group and 26.32% in the control group (P=0.002). Patients in the TPE CVP group also showed better oxygenation and a reduction in inflammation, with decreased CRP, LDH and ferritin levels compared with those in the control group. Overall, the study indicated that early initiation of TPE followed by CVP transfusion may be a valid rescue therapy in severe and critically ill COVID-19 patients, with a statistically significant survival benefit, improved oxygenation and a reduction in inflammatory markers. The trial was registered in the ClinicalTrials.gov database (trial registration number: NCT04973488) on July 22, 2021 (retrospectively registered).

Association between ribotype and clinical form of enterocolitis with C. difficile in Western Romania: A 2-year study.

During the last decade, several changes in the epidemiology, clinical symptoms, and evolution of Clostridium difficile infection (CDI) have been reported. The number of diagnosed cases has increased, especially in individuals over 60 years of age. There has also been an increase in the share of severe forms of the disease, the number of patients with recurrent infections and the lethality caused by this condition. The aim of the present study was to determine the incidence of CDI over the past few years; to monitor the bacterial toxin by ribotyping; to observe the migration of circulating toxins; to correlate the ribotyping with the clinical form of the disease; and to correlate the treatment with the ribotyping and the clinical form. Therefore, we performed an observational retrospective study regarding the incidence of CDI at 'Victor Babeș' Hospital of Infectious Diseases and Pneumophtisiology of Timișoara, between January 2016 and December 2017. The results revealed that 210 patients were hospitalized with a diagnosis of acute enterocolitis with C. difficile. All patients tested showed C. difficile toxin A/B positivity. In 28 cases, the ribotyping was positive with binary toxin and hypervirulent strain 027. The tested patients were discharged or transferred from various medical/surgical clinics. In the study, we also ascertained the correlation between the clinical form of the disease and comorbidities and pre-hospital treatments as risk factors in the occurrence of the infection. In accordance with the rise of CDI during the last decade, it was possible to observe the increase in the number of infectious recurrences. From this point of view, highlighting of the ribotype in this pathology becomes a primary aspect both by increasing the success rate in curing the disease (with a reduction in the risk of recurrence) and by targeted and non-empirical administration of the antibiotic.