Recent advances in the treatment of Ebola disease: A brief overview.

Ebola disease (EBOD) remains a significant and ongoing threat to African countries, characterized by a mortality rate of 25% to 90% in patients with high viral load and significant transmissibility. The most recent outbreak, reported in Uganda in September 2022, was declared officially over in January 2023. However, it was caused by the Sudan Ebola virus (SUDV), a culprit species not previously reported for a decade. Since its discovery in 1976, the management of EBOD has primarily relied on supportive care. Following the devastating outbreak in West Africa from 2014 to 2016 secondary to the Zaire Ebola virus (EBOV), where over 28,000 lives were lost, dedicated efforts to find effective therapeutic agents have resulted in considerable progress in treating and preventing disease secondary to EBOV. Notably, 2 monoclonal antibodies-Ebanga and a cocktail of monoclonal antibodies, called Inmazeb-received Food and Drug Administration (FDA) approval in 2020. Additionally, multiple vaccines have been approved for EBOD prevention by various regulatory bodies, with Ervebo, a recombinant vesicular stomatitis virus-vectored vaccine against EBOV being the first vaccine to receive approval by the FDA in 2019. This review covers the key signs and symptoms of EBOD, its modes of transmission, and the principles guiding supportive care. Furthermore, it explores recent advancements in treating and preventing EBOD, highlighting the unique properties of each therapeutic agent and the ongoing progress in discovering new treatments.

Epidemiology and microbiology of catheter-associated urinary tract infections: A 14-year surveillance study at a tertiary care center in Lebanon.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are the most common device-associated healthcare-acquired infections and pose a significant burden on patients and healthcare systems worldwide. However, there is a paucity of data on CAUTI epidemiology and microbiology in the Middle East and North Africa (MENA) region, including Lebanon. METHODS: This 14-year retrospective cohort study was conducted at a tertiary care center in Lebanon. It analyzed data on all adult patients diagnosed with CAUTI between January 2009 and December 2022 in intensive care units (ICUs) and between June 2011 and December 2022 in regular units. Incidence rates, urinary catheter utilization ratios, and microbiological profiles were collected and analyzed. RESULTS: A total of 620 CAUTI cases were identified during the study period. The overall CAUTI rate was 2.4 per 1000 catheter-days, with higher rates in ICUs (3.2 per 1000 catheter-days) compared to regular units (1.4 per 1000 catheter-days). No significant changes in the rates were noted despite implementing many interventions. The most common pathogens were Gram-negative bacteria, with Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae being predominant. Multidrug-resistant organisms represented 48% of all isolates. Enterobacterales were largely extended-spectrum ß-lactamase (ESBL) producing, and most Acinetobacter baumannii isolates showed multidrug resistance. CONCLUSIONS: This study provides important insights into CAUTI epidemiology and microbiology in a tertiary care center in Lebanon, addressing the knowledge gap in this area in the MENA region. Despite implementing prevention measures, CAUTI rates remained stable over the 14-year period. The findings highlight the need for continuous improvement in infection prevention practices, diagnostic stewardship, and antimicrobial stewardship, especially given the rising threat of antimicrobial resistance. These results can serve as a guide for the development of targeted preventive strategies to reduce the burden of CAUTIs, particularly in low- and middle-income countries where antimicrobial resistance is a major issue.

Metallo-beta-lactamases: mechanisms, treatment challenges, and future prospects.

INTRODUCTION: Metallo-beta-lactamases (MBLs) are responsible for resistance to almost all beta-lactam antibiotics. Found predominantly in Gram-negative bacteria, they severely limit treatment options. Understanding the epidemiology, risk factors, treatment, and prevention of infections caused by MBL-producing organisms is essential to reduce their burden. AREAS COVERED: The origins and structure of MBLs are discussed. We describe the mechanisms of action that differentiate MBLs from other beta-lactamases. We discuss the global epidemiology of MBL-producing organisms and their impact on patients' outcomes. By exposing the mechanisms of transmission of MBLs among bacterial populations, we emphasize the importance of infection prevention and control. EXPERT OPINION: MBLs are spreading globally and challenging the majority of available antibacterial agents. Genotypic tests play an important role in the identification of MBL production. Phenotypic tests are less specific but may be used in low-resource settings, where MBLs are more predominant. Infection prevention and control are critical to reduce the spread of organisms producing MBL in healthcare systems. New combinations such as avibactam-aztreonam and new agents such as cefiderocol have shown promising results for the treatment of infections caused by MBL-producing organisms. New antibiotic and non-antibiotic agents are being developed and may improve the management of infections caused by MBL-producing organisms.

Blood Stream Infections in COVID-19 Patients From a Tertiary Care Center in Lebanon: Causative Pathogens and Rates of Multi-Drug Resistant Organisms.

Objective: To report the microbiological profile of the pathogens implicated in blood stream infections (BSI) in hospitalized coronavirus disease 2019 (COVID-19) patients and to examine the risk factors associated with multidrug-resistant organisms (MDROs) causing BSI. Patients and Methods: Between March 2020 and September 2021, 1647 patients were hospitalized with COVID-19 at the American University of Beirut. From 85 patients, 299 positive blood cultures were reported to the Infection Control and Prevention Program. The BSI was defined as 1 positive blood culture for bacterial or fungal pathogens. The following organisms were considered MDROs: methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp, carbapenem-resistant Enterobacterales spp., carbapenem-resistant Pseudomonas aeruginosa, MDR Acinetobacter baumannii only susceptible to colistin or tigecycline, and Candida auris. Results: We identified 99 true positive BSI events. Gram-negative bacteria accounted for 38.4 %, followed by Gram-positive bacteria (37.4%), and fungi (24.2%). The most isolated species were Candida spp. (23%), 3 of which were C. auris, followed by Enterobacterales spp. (13%), Enterococcus spp. (12%), S. aureus (9%), P. aeruginosa (9%), and A. baumannii (3%). The MDROs represented 26% of the events. The overall mortality rate was 78%. The time to acquisition of BSI in patients with MDROs was significantly longer compared with that of non-MDROs (20.2 days vs 11.2 days). And there was a significantly shorter time from acquisition of BSI to mortality between MDROs and non-MDROs (1.5 vs 8.3 days). Conclusion: Rigorous infection prevention and control measures and antimicrobial stewardship are important to prevent antimicrobial resistance progression, especially in low-resource settings.

Bacterial respiratory infections in patients with COVID-19: A retrospective study from a tertiary care center in Lebanon.

BACKGROUND: Despite multiple reports of increased incidence of bacterial respiratory tract infections following COVID-19 globally, the microbiology is not yet fully elucidated. In this study, we describe the microbiology of bacterial infections and the prevalence of multidrug resistant organisms (MDROs) in hospitalized COVID-19 patients with community-acquired pneumonia (CAP), and hospital-acquired pneumonia (HAP) which includes both non-ventilated hospital acquired pneumonia (NVHAP) and ventilator-associated pneumonia (VAP). To our knowledge, this is the first study that compares the microbiology of VAP and NVHAP in COVID-19 patients. METHODS: This is a longitudinal retrospective cohort study conducted at the American University of Beirut Medical Center (AUBMC), a tertiary-care centre in Lebanon. Adult patients with confirmed COVID-19 and concurrent bacterial respiratory infections with an identifiable causative organism who were hospitalized between March 2020 and September 2021 were included. Bacterial isolates identified in hospital-acquired pneumonia (HAP) were divided into 3 groups based on the time of acquisition of pneumonia after admission: hospital day 3-14, 15-28 and 29-42. RESULTS: Out of 1674 patients admitted with COVID-19, 159 (9.5%) developed one or more respiratory infections with an identifiable causative organism. Overall, Gram-negative bacteria were predominant (84%) and Stenotrophomonas maltophilia was the most common pathogen, particularly in HAP. Among 231 obtained isolates, 59 (26%) were MDROs, seen in higher proportion in HAP, especially among patients with prolonged hospital stay (> 4 weeks). Non-fermenter Gram-negative bacilli (NFGNB) (OR = 3.52, p-value<0.001), particularly S. maltophilia (OR = 3.24, p-value = 0.02), were significantly more implicated in VAP compared to NVHAP. CONCLUSIONS: NFGNB particularly S. maltophilia were significantly associated with COVID-19 VAP. A high rate of bacterial resistance (25%), especially among Gram-negative bacteria, was found which may compromise patients' outcomes and has important implications in guiding therapeutic decisions in COVID-19 patients who acquire bacterial respiratory infections.

Environmental monitoring for filamentous fungal pathogens in hematopoietic cell transplant units.

The incidence of invasive fungal disease (IFD) is on the rise due to increasing numbers of highly immunocompromized patients. Nosocomial IFD remains common despite our better understanding of its risk factors and pathophysiology. High-efficiency particulate air filtration with or without laminar air flow, frequent air exchanges, a positive pressure care environment, and environmental hygiene, amongst other measures, have been shown to reduce the mould burden in the patient environment. Environmental monitoring for moulds in areas where high-risk patients are cared for, such as hematopoietic cell transplant units, has been considered an adjunct to other routine environmental precautions. As a collaborative effort between authors affiliated to the Infection Prevention and Control Working Group and the Fungal Infection Working Group of the International Society of Antimicrobial Chemotherapy (ISAC), we reviewed the English language literature and international guidance to describe the evidence behind the need for environmental monitoring for filamentous fungi as a quality assurance approach with an emphasis on required additional precautions during periods of construction. Many different clinical sampling approaches have been described for air, water, and surface sampling with significant variation in laboratory methodologies between reports. Importantly, there are no agreed-upon thresholds that correlate with an increase in the clinical risk of mould infections. We highlight important areas for future research to assure a safe environment for highly immunocompromized patients.

Mould infections have a high mortality in high-risk patients. Ventilation engineering significantly reduces the risk of acquiring such infections. Environmental sampling for moulds is carried out in many centers in addition to standard precautions. We review the literature on this subject.

Mucormycosis: A 14-Year Retrospective Study from a Tertiary Care Center in Lebanon.

Mucormycosis (MCM) is a serious invasive fungal disease (IFD) that is associated with high mortality, particularly in immunocompromised patients. A global surge in MCM cases was reported with the COVID-19 pandemic. We analyzed all recorded cases of MCM at the American University of Beirut Medical Center (AUBMC), a tertiary care center in Lebanon, over 14 years. We aimed to identify the incidence, seasonal variation, clinical characteristics of the patients, and predictors of mortality. We conducted a retrospective chart review between 1 January 2008 and 1 January 2023. All patients with proven or probable MCM were included in the study. Proven or probable MCM was defined by positive histopathology and/or positive cultures. A total of 43 patients were identified as having MCM. Their median age was 53 years, and the majority were males (58.1%). Most of the cases were diagnosed in the autumn season. In total, 67.4% of the patients had hematological malignancies (HMs), and 34.9% had uncontrolled diabetes mellitus (DM). The most common site of involvement was rhino-orbital-cerebral MCM (ROCM) (74%). The annual cases of MCM per 100,000 patient days increased markedly during the years of the COVID-19 pandemic (from 0 to 4.4 cases/100,000 patient days to 7.5 cases/100,000 during 2020 and 2021). Liposomal amphotericin (Ampho) B was used as a first-line agent in most of the patients (86%). The median duration of total in-hospital antifungal therapy was 21 days and 51.2% of the patients received step-down therapy with azoles. Surgical debridement and isolated ROCM were significantly associated with survival (p-value: 0.02 and <0.001, respectively). All-cause mortality was 46.7%, with chronic renal disease being significantly associated with mortality (p-value < 0.05). The incidence of MCM has been increasing at our institution, particularly since the COVID-19 pandemic. Early diagnosis, treatment, and surgical debridement improve patient outcomes and overall survival.

The Impact of COVID-19 on the Epidemiology and Outcomes of Candidemia: A Retrospective Study from a Tertiary Care Center in Lebanon.

Invasive fungal infections, notably candidemia, have been associated with COVID-19. The epidemiology of candidemia has significantly changed during the COVID-19 pandemic. We aim to identify the microbiological profile, resistance rates, and outcomes of COVID-19-associated candidemia (CAC) compared to patients with candidemia not associated with COVID-19. We retrospectively collected data on patients with candidemia admitted to the American University of Beirut Medical Center between 2004 and 2022. We compared the epidemiology of candidemia during and prior to the COVID-19 pandemic. Additionally, we compared the outcomes of critically ill patients with CAC to those with candidemia without COVID-19 from March 2020 till March 2022. Among 245 candidemia episodes, 156 occurred prior to the pandemic and 89 during the pandemic. Of the latter, 39 (43.8%) were CAC, most of which (82%) were reported from intensive care units (ICU). Non-albicans Candida (NAC) spp. were predominant throughout the study period (67.7%). Candida auris infection was the most common cause of NAC spp. in CAC. C. glabrata had decreased susceptibility rates to fluconazole and caspofungin during the pandemic period (46.1% and 38.4%, respectively). The mortality rate in the overall ICU population during the pandemic was 76.6%, much higher than the previously reported candidemia mortality rate observed in studies involving ICU patients. There was no significant difference in 30-day mortality between CAC and non-CAC (75.0% vs. 78.1%; p = 0.76). Performing ophthalmic examination (p = 0.002), CVC removal during the 48 h following the candidemia (p = 0.008) and speciation (p = 0.028) were significantly associated with a lower case-fatality rate. The epidemiology of candidemia has been significantly affected by the COVID-19 pandemic at our center. Rigorous infection control measures and proper antifungal stewardship are essential to combat highly resistant species such as C. auris.

Management of cytomegalovirus infection in allogeneic hematopoietic stem cell transplants.

Cytomegalovirus (CMV) is a common infection encountered in immunocompromised patients. It is associated with high morbidity and mortality, particularly in patients undergoing allogeneic (allo-) haematopoietic stem cell transplantation (HSCT). This review presents the most recent management strategies for CMV infection in allo-HSCT recipients. Pre-emptive treatment (PET) consists of frequent monitoring of CMV polymerase chain reaction (PCR) after HSCT; this has been the standard of care for prevention of CMV for many years, given the potential drug toxicity associated with the traditional drugs used as prophylaxis. However, letermovir, recently approved as a chemoprophylactic agent for prevention of CMV, has shown great efficacy in randomized clinical trials and real-world data. Treatment of CMV disease is becoming increasingly difficult, and must take into account the patient's risk profile and the potential for CMV drug resistance. Different treatment strategies exist for refractory and resistant CMV disease. Maribavir is a new drug that showed promising results in the treatment of refractory and resistant CMV disease. Other alternative treatments, such as cellular adoptive immunotherapy, artesunate and leflunomide, may play an adjunctive role in the treatment of challenging cases; however, further investigation is warranted.

Diagnostic stewardship in infectious diseases: a continuum of antimicrobial stewardship in the fight against antimicrobial resistance.

Antimicrobial resistance (AMR) has been exacerbated by the inappropriate use of diagnostics, leading to excessive prescription of antimicrobials, and is an imminent threat to global health. Diagnostic stewardship (DS) is an auxiliary to antimicrobial stewardship (AMS) and comprises ordering the right tests, for the right patient, at the right time. It also promotes the judicious use of rapid and novel molecular diagnostic tools to enable the initiation of proper antibiotic therapy, while avoiding excessive use of broad-spectrum antibiotics. Proper interpretation of test results is crucial to avoid overdiagnosis and excessive healthcare costs. Although many rapid diagnostic tools have been developed with a high diagnostic yield, they are often limited by accessibility, cost, and lack of knowledge regarding their use. Careful consideration of clinical signs and symptoms with knowledge of the local epidemiology are essential for DS. This enables appropriate interpretation of microbiological results. Multidisciplinary teams that include well trained professionals should cooperate to promote DS. Challenges and barriers to the implementation of DS are mostly caused by scarcity of resources and lack of trained personnel and, most importantly, lack of knowledge. The lack of resources is often due to absence of awareness of the impact that good medical microbiology diagnostic facilities and expertise can have on the proper use of antibiotics.

COVID-19-associated mucormycosis: a systematic review and meta-analysis of 958 cases.

BACKGROUND: Mucormycosis, a rare fungal infection, has shown an increase in the number of reported cases during the COVID-19 pandemic. OBJECTIVES: To provide a comprehensive insight into the characteristics of COVID-19-associated mucormycosis, through a systematic review and meta-analysis. METHODS OF DATA SYNTHESIS: Demographic information and clinical features were documented for each patient. Logistic regression analysis was used to predict the risk of mortality. DATA SOURCES: PubMed, Scopus, Web of Science, Cochrane, CINAHL, Ovid MEDLINE, and FungiSCOPE. STUDY ELIGIBILITY CRITERIA: Studies reporting individual-level information in patients with adult COVID-19-associated mucormycosis (CAM) between 1 January 2020 and 28 December 2022. PARTICIPANTS: Adults who developed mucormycosis during or after COVID-19. INTERVENTIONS: Patients with and without individual clinical variables were compared. ASSESSMENT OF RISK OF BIAS: Quality assessment was performed based on the National Institutes of Health quality assessment tool for case series studies. RESULTS: Nine hundred fifty-eight individual cases reported from 45 countries were eligible. 88.1% (844/958) were reported from low- or middle-income countries. Corticosteroid use for COVID-19 (78.5%, 619/789) and diabetes (77.9%, 738/948) were common. Diabetic ketoacidosis (p < 0.001), history of malignancy (p < 0.001), underlying pulmonary (p 0.017), or renal disease (p < 0.001), obesity (p < 0.001), hypertension (p 0.040), age (>65 years) (p 0.001), Aspergillus coinfection (p 0.037), and tocilizumab use during COVID-19 (p 0.018) increased the mortality. CAM occurred on an average of 22 days after COVID-19 and 8 days after hospitalization. Diagnosis of mucormycosis in patients with Aspergillus coinfection and pulmonary mucormycosis was made on average 15.4 days (range, 0-35 days) and 14.0 days (range, 0-53 days) after hospitalization, respectively. Cutaneous mucormycosis accounted for <1% of the cases. The overall mortality rate was 38.9% (303/780). CONCLUSION: Mortality of CAM was high, and most reports were from low- or middle-income countries. We detected novel risk factors for CAM, such as older age, specific comorbidities, Aspergillus coinfection, and tocilizumab use, in addition to the previously identified factors.

Infective Endocarditis after Transcatheter Aortic Valve Replacement: Challenges in the Diagnosis and Management.

Although initially conceived for high-risk patients who are ineligible for surgical aortic valve replacement (SAVR), transcatheter aortic valve replacement (TAVR) is now recommended in a wider spectrum of indications, including among young patients. However, similar to SAVR, TAVR is also associated with a risk of infectious complications, namely, prosthetic valve endocarditis (PVE). As the number of performed TAVR procedures increases, and despite the low incidence of PVE post-TAVR, clinicians should be familiar with its associated risk factors and clinical presentation. Whereas the diagnosis of native valve endocarditis can be achieved straightforwardly by applying the modified Duke criteria, the diagnosis of PVE is more challenging given its atypical symptoms, the lower sensitivity of the criteria involved, and the low diagnostic yield of conventional echocardiography. Delay in proper management can be associated with increased morbidity and mortality. Therefore, clinicians should have a high index of suspicion and initiate proper work-up according to the severity of the illness, the underlying host, and the local epidemiology of the causative organisms. The most common causative pathogens are Gram-positive bacteria such as Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus spp., and Streptococcus spp. (particularly the viridans group), while less-likely causative pathogens include Gram-negative and fungal pathogens. The high prevalence of antimicrobial resistance complicates the choice of therapy. There remain controversies regarding the optimal management strategies including indications for surgical interventions. Surgical assessment is recommended early in the course of illness and surgical intervention should be considered in selected patients. As in other PVE, the duration of therapy depends on the isolated pathogen, the host, and the clinical response. Since TAVR is a relatively new procedure, the outcome of TAVR-PVE is yet to be fully understood.

Community-acquired skin and soft-tissue infections in people who inject drugs.

PURPOSE OF REVIEW: The aim of this review is to discuss the latest evidence of the epidemiology, microbiology, risk factors, diagnosis and management of community-acquired skin and soft tissue infections (SSTIs) in people who inject drug (PWID). RECENT FINDINGS: SSTIs are common complications in PWID and a major cause of morbidity and mortality. Infections can range from uncomplicated cellulitis, to abscesses, deep tissue necrosis and necrotizing fasciitis. They are predominantly caused by Gram-positive pathogens in particular Staphylococcus aureus and Streptococcus species; however, toxin-producing organisms such as Clostridium botulism or Clostridium tetani should be considered. The pathogenesis of SSTI in the setting of intravenous drug use (IDU) is different from non-IDU related SSTI, and management often requires surgical interventions in addition to adjunctive antibiotics. Harm reduction strategies and education about safe practices should be implemented to prevent morbidity and mortality as well as healthcare burden of SSTI in PWID. SUMMARY: Prompt diagnosis and proper medical and surgical management of SSTI will improve outcomes in PWID.

The Ten Most Common Questions on Cytomegalovirus Infection in Hematopoietic Stem Cell Transplant Patients.

With the rising number of patients undergoing hematopoietic stem cell transplantation (HSCT), clinicians are more likely to encounter infectious complications in immunocompromised hosts, particularly cytomegalovirus (CMV) infection. Besides the high mortality of CMV end-organ disease, patients with detectable CMV viremia may have worse outcomes and decreased survival even in the absence of end-organ disease. In view of the implications on morbidity and mortality, clinicians should maintain a high index of suspicion and initiate antiviral drugs promptly when CMV infection is confirmed. High-risk patients should be identified in order to provide optimal management. Additionally, novel antiviral agents with a good safety profile and minor adverse events are now available for prophylaxis in high-risk patients and for treatment of resistant or refractory CMV infection. The following review provides concise, yet comprehensive, guidance on the burden and risk factors of CMV in this population, as well as an update on the latest evidence for the management of CMV infection.

Antimicrobial Treatment of Pseudomonas aeruginosa Severe Sepsis.

Pseudomonas aeruginosa is a pathogen often encountered in a healthcare setting. It has consistently ranked among the most frequent pathogens seen in nosocomial infections, particularly bloodstream and respiratory tract infections. Aside from having intrinsic resistance to many antibiotics, it rapidly acquires resistance to novel agents. Given the high mortality of pseudomonal infections generally, and pseudomonal sepsis particularly, and with the rise of resistant strains, treatment can be very challenging for the clinician. In this paper, we will review the latest evidence for the optimal treatment of P. aeruginosa sepsis caused by susceptible as well as multidrug-resistant strains including the difficult to treat pathogens. We will also discuss the mode of drug infusion, indications for combination therapy, along with the proper dosing and duration of treatment for various conditions with a brief discussion of the use of non-antimicrobial agents.