Treatment Strategies of Colistin Resistance Acinetobacter baumannii Infections.

Acinetobacter baumannii has emerged as a pressing challenge in clinical practice, mainly due to the development of resistance to multiple antibiotics, including colistin, one of the last-resort treatments. This review highlights all the possible mechanisms of colistin resistance and the genetic basis contributing to this resistance, such as modifications to lipopolysaccharide or lipid A structures, alterations in outer membrane permeability via porins and heteroresistance. In light of this escalating threat, the review also evaluates available treatment options. The development of new antibiotics (cefiderocol, sulbactam/durlobactam) although not available everywhere, and the use of various combinations and synergistic drug combinations (including two or more of the following: a polymyxin, ampicillin/sulbactam, carbapenems, fosfomycin, tigecycline/minocycline, a rifamycin, and aminoglycosides) are discussed in the context of overcoming colistin resistance of A. baumannii infections. Although most studied combinations are polymyxin-based combinations, non-polymyxin-based combinations have been emerging as promising options. However, clinical data remain limited and continued investigation is essential to determine optimal therapeutic strategies against colistin-resistant A. baumannii.

Monitoring anti-Xa levels in elderly medical patients undergoing thromboprophylaxis: A prospective cohort study.

INTRODUCTION: Given the rising incidence of venous thromboembolism (VTE) and insufficient thromboprophylaxis dosing evidence in certain patients, the precise monitoring of anti-Xa (aFXa) levels is crucial. The aim of this study is to investigate the achievement of prophylactic aFXa levels in medical inpatients who were receiving parenteral anticoagulant and to evaluate the impact of various factors on aFXa levels. METHODS: This is a single-center observational cohort study conducted on patients admitted to the Department of Internal Medicine at the University Hospital of Heraklion, Greece, from March to August 2023. These individuals received low-molecular-weight heparins thromboprophylaxis owing to an increased risk of VTE. Data regarding demographics, past medical history, and somatometric and laboratory findings were recorded. The established range for peak prophylactic aFXa levels was defined as 0.2-0.5 IU/mL. RESULTS: In this study, we enrolled 150 individuals [91 (60.7%) women] with a mean age of 80.0 ± 14.1 years. Sixty-two (41.4%) patients exhibited non-prophylactic peak aFXa levels. Supratherapeutic levels were observed in all underweight patients and subtherapeutic levels in 12 of 13 obese patients in class II and III. A multivariate linear regression analysis revealed that body weight, cancer, and the Charlson Comorbidity Index (CCI) were independent factors influencing aFXa levels. CONCLUSIONS: Our study reveals a substantial portion of medical elderly inpatients on thromboprophylaxis with non-prophylactic aFXa levels, with a notable prevalence among underweight and severely obese patients. Body weight, cancer, and CCI were identified as independent factors influencing aFXa levels, advocating for tailored thromboprophylaxis strategies. Further research is warranted to validate personalized dosing approaches and to enhance clinical decision-making. Geriatr Gerontol Int 2024; 24: 587-594.

Fungemia by Wickerhamomyces anomalus-A Narrative Review.

Wickerhamomyces anomalus has been previously classified as Hansenula anomala, Pichia anomala, and Candida pelliculosa and was recently reclassified in the genus Wickerhamomyces after phylogenetic analysis of its genetic sequence. An increasing number of reports of human infections by W. anomalus have emerged, suggesting that this microorganism is an emerging pathogen. The present review aimed to provide data on the epidemiology, antifungal resistance, clinical characteristics, treatment, and outcomes of fungemia by W. anomalus by extracting all the available information from published original reports in the literature. PubMed/Medline, Cochrane Library, and Scopus databases were searched for eligible articles reporting data on patients with this disease. In total, 36 studies involving 170 patients were included. The age of patients with fungemia by W. anomalus ranged from 0 to 89 years; the mean age was 22.8 years, the median age was 2.2 years, with more than 37 patients being less than one month old, and 54% (88 out of 163 patients) were male. Regarding patients' history, 70.4% had a central venous catheter use (CVC), 28.7% were on total parenteral nutrition (TPN), 97% of neonates were hospitalized in the neonatal ICU (NICU), and 39.4% of the rest of the patients were hospitalized in the intensive care unit (ICU). Previous antimicrobial use was noted in 65.9% of patients. The most common identification method was the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in 34.1%, VITEK and VITEK 2 in 20.6%, and ID32 C in 15.3%. W. anomalus had minimal antifungal resistance to fluconazole, echinocandins, and amphotericin B, the most commonly used antifungals for treatment. Fever and sepsis were the most common clinical presentation noted in 95.8% and 86%, respectively. Overall mortality was 20% and was slightly higher in patients older than one year. Due to the rarity of this disease, future multicenter studies should be performed to adequately characterize patients' characteristics, treatment, and outcomes, which will increase our understanding and allow drawing safer conclusions regarding optimal management.

Infective Endocarditis by Capnocytophaga Species-A Narrative Review.

Bacteria belonging to the genus Capnocytophaga are thin, capnophilic, Gram-negative bacilli with tapered ends that include nine species that are isolated from the mouth of humans and animals and, from a phylogenetical perspective, they belong to the family Flavobacteriaceae. Two more species, namely C. endodontalis and C. stomatis have been recovered from a periapical abscess and human and animal infections, respectively. Capnocytophaga spp. can cause serious and potentially life-threatening infections in humans, such as bacteremia and meningitis, most commonly in the context of penetrating trauma as a result of contact with animals, especially after animal bites. Other invasive diseases such as osteomyelitis, septic arthritis, and infective endocarditis (IE) may also occur more rarely. The aim of this study was to review all previously described cases of IE by Capnocytophaga spp. and provide information about the epidemiology, microbiology, antimicrobial susceptibility, clinical characteristics, treatment, and outcomes of this infection. A narrative review based on a search in PubMed, the Cochrane Library, and Scopus was performed. Studies published until 11 September 2023 providing relevant data for IE caused by Capnocytophaga spp. in humans were included. A total of 31 studies containing data from 31 patients were included. A history of dog bites was present in 10 out of 26 patients (38.5%). A prosthetic valve was present in 3 patients (9.7%). The most commonly infected valve was the aortic valve, followed by the tricuspid valve. Fever, embolic phenomena, paravalvular abscess, and sepsis were the most common clinical presentations. Beta-lactams and aminoglycosides were the antimicrobials most commonly used. Surgery was performed in 20 patients (64.5%). Overall mortality reached 16.1%.

Role of source control in critically ill candidemic patients: a multicenter retrospective study.

PURPOSE: Candidemia is associated with high mortality especially in critically ill patients. Our aim was to identify predictors of mortality among critically ill patients with candidemia with a focus on early interventions that can improve prognosis. METHODS: Multicenter retrospective study. SETTING: This retrospective study was conducted in Intensive Care Units from three European university hospitals from 2015 to 2021. Adult patients with at least one positive blood culture for Candida spp. were included. Patients who did not require source control were excluded. Primary outcome was 14-day mortality. RESULTS: A total of 409 episodes of candidemia were included. Most candidemias were catheter related (173; 41%), followed by unknown origin (170; 40%). Septic shock developed in 43% episodes. Overall, 14-day mortality rate was 29%. In Cox proportional hazards regression model, septic shock (P 0.001; HR 2.20, CI 1.38-3.50), SOFA score ≥ 10 points (P 0.008; HR 1.83, CI 1.18-2.86), and prior SARS-CoV-2 infection (P 0.003; HR 1.87, CI 1.23-2.85) were associated with 14-day mortality, while combined early appropriate antifungal treatment and source control (P < 0.001; HR 0.15, CI 0.08-0.28), and early source control without appropriate antifungal treatment (P < 0.001; HR 0.23, CI 0.12-0.47) were associated with better survival compared to those without neither early appropriate antifungal treatment nor source control. CONCLUSION: Early source control was associated with better outcome among candidemic critically ill patients.

Nanotechnology in the Diagnosis and Treatment of Antibiotic-Resistant Infections.

The development of antimicrobial resistance (AMR), along with the relative reduction in the production of new antimicrobials, significantly limits the therapeutic options in infectious diseases. Thus, novel treatments, especially in the current era, where AMR is increasing, are urgently needed. There are several ongoing studies on non-classical therapies for infectious diseases, such as bacteriophages, antimicrobial peptides, and nanotechnology, among others. Nanomaterials involve materials on the nanoscale that could be used in the diagnosis, treatment, and prevention of infectious diseases. This review provides an overview of the applications of nanotechnology in the diagnosis and treatment of infectious diseases from a clinician's perspective, with a focus on pathogens with AMR. Applications of nanomaterials in diagnosis, by taking advantage of their electrochemical, optic, magnetic, and fluorescent properties, are described. Moreover, the potential of metallic or organic nanoparticles (NPs) in the treatment of infections is also addressed. Finally, the potential use of NPs in the development of safe and efficient vaccines is also reviewed. Further studies are needed to prove the safety and efficacy of NPs that would facilitate their approval by regulatory authorities for clinical use.

Infective Endocarditis by Lactobacillus Species-A Narrative Review.

Bacteria of the genus Lactobacillus are microaerophilic or aerotolerant anaerobic Gram-positive non-spore-forming rods. They are considered essential members of the human gut microbiome; however, recent studies have revealed that these microorganisms are less predominant in the gut microbiome than initially thought. Lactobacillus spp. is mainly known for its use as a probiotic in foods and supplements to prevent and treat specific issues such as infectious diseases, irritable bowel syndrome, and diabetes mellitus. However, Lactobacillus spp. may occasionally cause infections such as bacteremia or infective endocarditis (IE). The present study aimed to review all cases of IE by Lactobacillus spp. and describe the epidemiology, microbiology, clinical characteristics, treatment, and outcomes of this infection by collecting relevant data from studies existing in Pubmed and Scopus until 28 September 2023. A total of 77 studies containing data for 82 patients were included. The median age was 56 years, and 69.6% were male. A prosthetic valve was present in 16% of patients, and 17.3% had previously been on probiotics. The aortic valve was the most commonly involved intracardiac site, followed by the mitral valve. Fever, embolic phenomena, sepsis, and heart failure were the most common clinical presentations. Aminoglycosides and penicillin were the most commonly used antimicrobials for definitive treatment. Surgery was performed in 53.7% of patients. Overall mortality was 17.1%. IE in prosthetic valves and presentation with shock were independently associated with overall mortality.

A narrative review of management of wounds in palliative care setting.

BACKGROUND AND OBJECTIVE: A chronic wound is one that is physiologically compromised as a result of a disturbance of the wound-healing cycle brought on by, among other parameters, poor angiogenesis, innervation, or cellular migration. Given the high frequency and incidence rates of different wound categories in clinical practice in the setting of chronically ill patients, wound management is becoming an increasingly important component and pillar of the overall care of patients with terminal illnesses. The purpose of this narrative review is to provide an overview and evaluation of the assessment methods and management of chronic wounds in the clinical practice of palliative care. METHODS: Papers on the management of wounds in palliative care have been retrieved using PubMed to July 2023. The search terms used included "wounds", "ulcers", "palliative care", "palliative management", and "end of life". KEY CONTENT AND FINDINGS: The review highlights the importance of early palliative care referral and total pain management in the management of wounds. Patients with wounds often report multiple symptoms, and pain is one of the most common and distressing among them. Despite the availability of multiple guidelines about treatment to relieve pain, almost half of all cancer patients still receive inappropriate care for pain. The review also discusses the etiology of pain and provides strategies for managing the painful wound once it has been identified. The greatest need today in the treatment of chronic wounds is consensus-based knowledge vetted by practical experience and backed up by scientific evidence, which is easily communicated and available to all wound care practitioners. CONCLUSIONS: High-quality research together with wound care practice that leads to the best outcomes might include pain reduction, exudate management, odor management, and/or other quality-of-life benefits to wound care. There is a need for specialized palliative care teams to manage expectations throughout the process while maintaining hope.

Telomere length as a predictive biomarker in osteoporosis (Review).

Telomeres are the ends of chromosomes that protect them from DNA damage. There is evidence to suggest that telomere shortening appears with advanced age. Since aging is a significant risk factor for developing age-related complications, it is plausible that telomere shortening may be involved in the development of osteoporosis. The present review summarizes the potential of telomere shortening as a biomarker for detecting the onset of osteoporosis. For the purposes of the present review, the following scientific databases were searched for relevant articles: PubMed/NCBI, Cochrane Library of Systematic Reviews, Scopus, Embase and Google Scholar. The present review includes randomized and non-randomized controlled studies and case series involving humans, irrespective of the time of their publication. In six out of the 11 included studies providing data on humans, there was at least a weak association between telomere length and osteoporosis, with the remaining studies exhibiting no such association. As a result, telomere shortening may be used as a biomarker or as part of a panel of biomarkers for tracking the onset and progression of osteoporosis.

High-Flow Nasal Oxygen for Severe COVID-19 Pneumonia in Greek Patients: A Prospective Observational Study.

INTRODUCTION: High-flow nasal oxygen (HFNO) and prone positioning may improve outcomes of coronavirus disease 2019 (COVID-19) patients treated in the intensive care unit (ICU). The aim of this study was to describe outcomes following the timely application of HFNO and prone positioning in COVID-19 patients treated in a ward setting. METHODS: The study included 89 prospectively recruited subjects at the COVID-19 ward unit of the University Hospital of Heraklion, Greece, between March and December 2020. RESULTS: Seventy-four (83%) of the 89 subjects in the study had severe COVID-19. Of those, 33 (45%) required HFNO treatment and prone positioning and 15 (45%) were transferred to the ICU, with 4 of them being intubated. Severe COVID-19 and HFNO needs were associated with an increased pneumonia severity index (PSI) score on admission and a worse PaO2/FiO2 ratio. In multivariate analysis, PSI was the only independent predictor of subsequent HFNO needs (OR=1.022). Overall intubation and mortality rates were 5.6% and 3.4%, respectively. CONCLUSION: This study shows that for patients with severe COVID-19 hospitalized in medical wards, standard COVID-19 treatment, along with the timely utilization of HFNO and prone positioning, resulted in excellent outcomes with fewer ICU admission rates.

Long COVID-19 Pathophysiology: What Do We Know So Far?

Long COVID-19 is a recognized entity that affects millions of people worldwide. Its broad clinical symptoms include thrombotic events, brain fog, myocarditis, shortness of breath, fatigue, muscle pains, and others. Due to the binding of the virus with ACE-2 receptors, expressed in many organs, it can potentially affect any system; however, it most often affects the cardiovascular, central nervous, respiratory, and immune systems. Age, high body mass index, female sex, previous hospitalization, and smoking are some of its risk factors. Despite great efforts to define its pathophysiology, gaps remain to be explained. The main mechanisms described in the literature involve viral persistence, hypercoagulopathy, immune dysregulation, autoimmunity, hyperinflammation, or a combination of these. The exact mechanisms may differ from system to system, but some share the same pathways. This review aims to describe the most prevalent pathophysiological pathways explaining this syndrome.

Evaluation of Febrile Neutropenia in Hospitalized Patients with Neoplasia Undergoing Chemotherapy.

Febrile neutropenia (FN) is a common but serious complication encountered in patients with cancer and is associated with significant morbidity and mortality. In this prospective study, 63 patients with solid tumors under chemotherapy or immunotherapy were admitted to the hospital due to febrile neutropenia, confirmed through clinical or microbiological documentation. The aim of this study was to provide a comprehensive overview of the epidemiological and microbiological characteristics of hospitalized neutropenic patients with solid tumors undergoing treatment. Additionally, we aimed to assess the duration of neutropenia and identify factors influencing patient outcomes. The median age of patients was 71 ± 10.2 years, most of which were males (66.7%), and the primitive tumor location was the lung (38.1%), with most patients (82.5%) being at disease stage IV. The median duration of neutropenia was three days (range 1-10), and, notably, mucositis was significantly associated with neutropenia lasting ≥3 days (p = 0.012). Patients with lung cancer (38.1%) and patients with stage IV disease (82.5%) presented a higher risk of FN, although these differences did not reach statistical significance. The site of infection was identifiable in 55.6% of patients, with positive cultures detected in 34.9% and positive blood cultures (BC) drawn in 17.5% of cases. Gram-positive bacteria were the predominant causative agents in BC (63.6%), with Staphylococci being the most prevalent among them (66.7%). The median duration of hospitalization was nine days (range, 3-43 days), and most patients showed improvement or cure of infection (16.9% and 74.6%, respectively). Among recorded risk factors, the Eastern Cooperative Oncology Group (ECOG) performance status (PS) appears to be statistically significant. Patients with an impaired PS score (2-4) experienced worse outcomes and higher likelihood of mortality (p = 0.004). Regarding the outcome, a longer duration of neutropenia was also statistically significant (p = 0.050). Of the patients, 12.7% ultimately succumbed to their conditions, with 37.5% attributed to infections. FN is a common yet serious complication in solid tumor patients. Adequate knowledge of the predictors of mortality and the microbiological causes are of utmost importance to allow accurate diagnosis and prompt treatment as they significantly influence patient outcomes.

Streptococcus pseudoporcinus bacteremia in a patient with skin and soft tissue infection. A case report and literature review.

Streptococcus pseudoporcinus is a beta-hemolytic Streptococcus species arranged in short chains, which was first described in 2006. In the last years, there have been several reports of human infections by this bacterium, with five skin and soft tissue infections identified. Herein, a case of S. pseudoporcinus skin and soft tissue infection in a patient, who also developed bacteremia and was successfully treated with intravenous antibiotics, is reported. A 67-year-old man with a history of diffuse large B-cell lymphoma presented to the emergency department because of fever, redness, swelling, and pain in the left lower limb. He was admitted to the medical ward, diagnosed with severe non-purulent skin and soft tissue infection, and treated empirically with intravenous piperacillin/tazobactam at 4.5 gr thrice daily and daptomycin at 10mg/kg once daily. Blood cultures were obtained before the initiation of the antibiotics and grew S. pseudoporcinus. Treatment was de-escalated to ceftriaxone at a dose of 2 gr once daily. He completed two weeks of intravenous antimicrobial treatment. S. pseudoporcinus is an emerging pathogen associated with skin and soft tissue infections, bacteremia, and other invasive, potentially life-threatening infections. Further investigation is warranted to clarify this microorganism's pathogenesis and biological significance.

Kocuria Species Infections in Humans-A Narrative Review.

Kocuria species are catalase-positive and coagulase-negative Gram-positive coccoid bacteria that belong to the family Micrococcaceae, order Actinomycetales, and class Actinobacteria. Even though they may be relatively rare, they have been increasingly reported as the causes of human infections lately. The present study aims to review all published cases of Kocuria spp. infections in humans reporting data on epidemiology, microbiology, antimicrobial susceptibility, antimicrobial treatment, and mortality. A narrative review was performed based on a search of Pubmed and Scopus databases in the literature. In total, 73 studies provided data on 102 patients with Kocuria spp. infections. The mean age of patients was 47 years, and 68.3% were male. The most common types of infection were bacteremia (36.3%), skin and soft tissue infection (18.6%), endophthalmitis (15.7%), infective endocarditis (13.7%), and peritonitis (11.8%), most commonly peritoneal-dialysis-associated. The most frequently isolated species was K. kristinae (46.1%), and antimicrobial resistance was lower for vancomycin (7%) and tetracyclines (6.7%). Vancomycin (47%), cephalosporins (39.6%), and quinolones (36.6%) were the most commonly used antimicrobials. The empirical antimicrobial treatment of Kocuria spp. infections should include vancomycin as long as antimicrobial susceptibility results are pending. The infection outcome mainly depends on the type of infection and is higher for infective endocarditis. Endophthalmitis is associated with increased rates of low visual acuity after treatment.

Daptomycin as an option for lock therapy: a systematic literature review.

Aim: To review preclinical and clinical data relevant to daptomycin lock therapy in catheter-related bloodstream infection (CRBSI). Methods: Systematic review in PubMed, Scopus and clinical trial registries. Results: Preclinical data demonstrate daptomycin lock solution stability and compatibility with heparin, good biofilm penetration, bactericidal activity against biofilm-embedded bacteria, and high efficacy in vitro and in animal catheter infection models. Clinical data remain limited (two case reports and five case series totaling n = 65 CRBSI episodes), albeit promising (successful catheter salvage in about 80% of cases). Conclusion: Despite theoretical advantages of daptomycin, clinical data remain scarce. Comparative studies versus alternative lock solutions are needed, as well as studies to define optimal daptomycin lock regimen (including optimal concentration, dwell time and lock duration).

Some patients, such as those needing cancer treatments, kidney dialysis or to be fed through a vein, need long-term access to central veins by a tube called a catheter. These central venous catheters can often become infected and will need to be removed and replaced. Sometimes, the catheter can be saved by 'locking' the tube with a solution to kill any germs. In this review, we discuss the potential to use an antibiotic called daptomycin as the solution in lock therapy. Available data are reviewed and advantages over alternative antimicrobial lock solutions are discussed. Finally, directions for future research are proposed.

Antibiotics and Lipid-Modifying Agents: Potential Drug-Drug Interactions and Their Clinical Implications.

Evidence-based prescribing requires taking into consideration the many aspects of optimal drug administration (e.g., dosage, comorbidities, co-administered drugs, etc.). A key issue is the administration of drugs for acute disorders that may potentially interfere with previously prescribed long-term medications. Initiating an antibiotic for an acute bacterial infection constitutes a common example. Hence, appropriate knowledge and awareness of the potential DDIs of antibiotics would lead to proper adjustments, thus preventing over- or under-treatment. For example, some statins, which are the most prescribed lipid-modifying agent (LMA), can lead to clinically important drug-drug interactions (DDIs) with the concurrent administration of antibiotics, e.g., macrolides. This review discusses the clinically significant DDIs of antibiotics associated with co-administrated lipid-lowering therapy and highlights common cases where regimen modifications may or may not be necessary.

Antimicrobial Peptides in Infectious Diseases and Beyond-A Narrative Review.

Despite recent medical research and clinical practice developments, the development of antimicrobial resistance (AMR) significantly limits therapeutics for infectious diseases. Thus, novel treatments for infectious diseases, especially in this era of increasing AMR, are urgently needed. There is ongoing research on non-classical therapies for infectious diseases utilizing alternative antimicrobial mechanisms to fight pathogens, such as bacteriophages or antimicrobial peptides (AMPs). AMPs are evolutionarily conserved molecules naturally produced by several organisms, such as plants, insects, marine organisms, and mammals, aiming to protect the host by fighting pathogenic microorganisms. There is ongoing research regarding developing AMPs for clinical use in infectious diseases. Moreover, AMPs have several other non-medical applications in the food industry, such as preservatives, animal husbandry, plant protection, and aquaculture. This review focuses on AMPs, their origins, biology, structure, mechanisms of action, non-medical applications, and clinical applications in infectious diseases.

Special Issue: "Current Trends and Outcomes of Infective Endocarditis".

Infective endocarditis (IE) is an infectious disease involving the endothelium of the heart and, more commonly, the cardiac valves and prosthetic material (such as pacemakers and implantable defibrillators), and carries high morbidity and mortality rates [...].