Triazole antifungal drug interactions-practical considerations for excellent prescribing.

Systemic antifungal therapy is critical for reducing the mortality from many invasive and chronic fungal infections. Triazole antifungals are the most frequently prescribed antifungals but require attention to dosing and drug interactions. Nearly 600 severe drug-drug interactions and over 1100 moderate interactions requiring dose modifications are described or anticipated with systemic antifungal agents (see https://www.aspergillus.org.uk/antifungal-drug-interactions/). In this article, we address the common and less common, but serious, drug interactions observed in clinical practice with triazole antifungals, including a group of drugs that cannot be prescribed with all or most triazole antifungals (ivabradine, ranolazine, eplerenone, fentanyl, apomorphine, quetiapine, bedaquiline, rifampicin, rifabutin, sirolimus, phenytoin and carbamazepine). We highlight interactions with drugs used in children and new agents introduced for the treatment of haematological malignancies or graft versus host disease (midostaurin, ibrutinib, ruxolitinib and venetoclax). We also summarize the multiple interactions between oral and inhaled corticosteroids and triazole antifungals, and the strategies needed to optimize the therapeutic benefits of triazole antifungal therapy while minimizing potential harm to patients.

Pseudomonas aeruginosa Bloodstream Infections Presenting with Septic Shock in Neutropenic Cancer Patients: Impact of Empirical Antibiotic Therapy.

This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.

Invasive candidiasis.

Invasive candidiasis is an important fungal disease caused by Candida albicans and, increasingly, non-albicans Candida pathogens. Invasive Candida infections originate most frequently from endogenous human reservoirs and are triggered by impaired host defences. Signs and symptoms of invasive candidiasis are non-specific; candidaemia is the most diagnosed manifestation, with disseminated candidiasis affecting single or multiple organs. Diagnosis poses many challenges, and conventional culture techniques are frequently supplemented by non-culture-based assays. The attributable mortality from candidaemia and disseminated infections is ~30%. Fluconazole resistance is a concern for Nakaseomyces glabratus, Candida parapsilosis, and Candida auris and less so in Candida tropicalis infection; acquired echinocandin resistance remains uncommon. The epidemiology of invasive candidiasis varies in different geographical areas and within various patient populations. Risk factors include intensive care unit stay, central venous catheter use, broad-spectrum antibiotics use, abdominal surgery and immune suppression. Early antifungal treatment and central venous catheter removal form the cornerstones to decrease mortality. The landscape of novel therapeutics is growing; however, the application of new drugs requires careful selection of eligible patients as the spectrum of activity is limited to a few fungal species. Unanswered questions and knowledge gaps define future research priorities and a personalized approach to diagnosis and treatment of invasive candidiasis is of paramount importance.

Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU): 2024 consensus definitions from ESGCIP, EFISG, ESICM, ECMM, MSGERC, ISAC, and ISHAM.

PURPOSE: The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs). METHODS: After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method. RESULTS: Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies.

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.

Accelerating antibiotic access and stewardship: a new model to safeguard public health.

This Personal View discusses the challenges faced, especially by low-income and middle-income countries (LMICs), in responding to the growing burden of bacterial antimicrobial resistance. Many patients in LMICs lack access to effective and affordable treatments needed to successfully treat patients. Meanwhile, traditional antimicrobial stewardship models face implementation challenges due to financial, health system, and human resource constraints. These constraints call for a paradigm shift from traditional high-income country-style antimicrobial stewardship, which is often resource intensive and aimed at cost containment, to a broader concept of sustainable access. We suggest a model of context-adapted stewardship that continues to emphasise providing the right antibiotic, at the right time, for the right duration, and at an affordable price. Taking lessons from other disease areas, including tuberculosis, we identify interventions such as task shifting to various health-care workers and the implementation of a hub-and-spoke model to support appropriate use of antibiotics, to enable optimal access and maximisation of scarce resources.

Molecular Characteristics of Colistin Resistance in Acinetobacter baumannii and the Activity of Antimicrobial Combination Therapy in a Tertiary Care Medical Center in Lebanon.

(1) Background: Infections with pan-drug-resistant (PDR) bacteria, such as A. baumannii, are becoming increasingly common, especially in healthcare facilities. In this study, we selected 15 colistin-resistant clinical A. baumannii isolates from a hospital in Beirut, Lebanon, to test combination therapies and determine their sequence types (STs) and the mechanism of colistin resistance using whole-genome sequencing (WGS). (2) Methods: Antimicrobial susceptibility testing via broth microdilution against 12 antimicrobials from different classes and growth rate assays were performed. A checkerboard assay was conducted on PDR isolates using six different antimicrobials, each in combination with colistin. Genomic DNA was extracted from all isolates and subjected to WGS. (3) Results: All isolates were resistant to all tested antimicrobials with the one exception that was susceptible to gentamicin. Combining colistin with either meropenem, ceftolozane-tazobactam, or teicoplanin showed synergistic activity. Sequencing data revealed that 67% of the isolates belonged to Pasteur ST2 and 33% to ST187. Furthermore, these isolates harbored a number of resistance genes, including blaOXA-23. Mutations in the pmrC gene were behind colistin resistance. (4) Conclusions: With the rise in antimicrobial resistance and the absence of novel antimicrobial production, alternative treatments must be found. The combination therapy results from this study suggest treatment options for PDR ST2 A. baumannii-infected patients.

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.

Necrotizing fasciitis: an update on epidemiology, diagnostic methods, and treatment.

PURPOSE OF REVIEW: The aim of this review is to discuss the latest evidence of epidemiology, diagnostic methods, and treatment of necrotizing soft tissue infections (NSTIs) with a particular focus on necrotizing fasciitis (NF). RECENT FINDINGS: NSTIs have been historically referred to as NF but encompass a broader range of infections, with variable rates ranging from 0.86 to 32.64 per 100 000 person-years, influenced by factors such as climate and seasonal variations. They have diverse microbiological profiles categorized into different types based on the involved pathogens, including polymicrobial or monomicrobial infections caused by organisms such as group A streptococcus (GAS), Staphylococcus aureus , some Gram-negative pathogens, and filamentous fungi following trauma and natural disasters. Diagnosis relies on clinical symptoms and signs, laboratory markers, and imaging. However, the gold standard for diagnosis remains intraoperative tissue culture. Treatment involves repeated surgical debridement of necrotic tissues in addition to intravenous antibiotics. Adjuvant therapies with intravenous immunoglobulin (IVIG) and hyperbaric oxygen therapy (HBOT) might have a role. Soft tissue reconstruction may be necessary following surgery. SUMMARY: Prompt diagnosis and proper medical and surgical management of NSTI will improve outcomes.

Clinical Outcomes and Bacterial Characteristics of Carbapenem-resistant Acinetobacter baumannii Among Patients From Different Global Regions.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. METHODS: In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis. RESULTS: Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases. CONCLUSIONS: CRAb infection types and clinical outcomes differed significantly across regions. Although CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. Clinical Trials Registration. NCT03646227.

The experience of an antimicrobial stewardship program and antibiotic consumption and resistance trends during the COVID-19 pandemic at a tertiary care center in Beirut.

BACKGROUND: Antimicrobial Resistance, a global concern, worsened with the COVID-19 pandemic that caused a surge of critically ill patients, increased antimicrobial consumption, and the spread of infections with multidrug-resistant organisms (MDROs). Antimicrobial Stewardship Programs (ASP) aim to optimize antimicrobial utilization to fight resistance. We aim to describe the ASP experience and to study antimicrobial consumption and MDRO rates among COVID-19 patients at a tertiary care center in Beirut. METHODS: We compiled the ASP interventions, defined as ASP team recommendations, from January 2019 until December 2021. Data on antimicrobial consumption, expressed as a defined daily dose (DDD) per 100 patient days, was collected per quarter for all antimicrobials and restricted antimicrobials per ASP guidance. Our primary objective was to report on the ASP experience, and the secondary objective was to reflect on the rates of MDROs among hospitalized COVID-19 patients with respiratory or bloodstream bacterial co-infections between March 2020 and September 2021. RESULTS: 9922 ASP interventions were documented during this study period, with a noticeable correlation between COVID-19 surges in Lebanon and the number of ASP interventions. Acceptance rates for these recommendations improved over time, with a noticeable decrease in the proportion of interventions related to de-escalation and discontinuation of broad-spectrum antimicrobials. We noted an increase in all antimicrobial consumption after the onset of the pandemic, peaking in Q4 2020 (142.8 DDD of anti-infectives/100 patient days) and Q1 2021 (79.1 DDD of restricted anti-infectives/100 patient days). As expected, MDROs, particularly ESKAPE organisms (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Carbapenem-resistant Enterobacteriaceae) accounted for 24% of isolates obtained from this cohort. CONCLUSION: This study highlights the experience of the ASP as we adapted to the COVID-19 pandemic. The ASP team maintained its operations and continued to monitor antibiotic consumption and provide recommendations to limit antibiotic misuse in an effort to mitigate the impact of the pandemic on antimicrobial resistance.

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.

Molecular characterization and differential effects of levofloxacin and ciprofloxacin on the potential for developing quinolone resistance among clinical Pseudomonas aeruginosa isolates.

Background: Fluoroquinolones are some of the most used antimicrobial agents for the treatment of Pseudomonas aeruginosa. This study aimed at exploring the differential activity of ciprofloxacin and levofloxacin on the selection of resistance among P. aeruginosa isolates at our medical center. Methods: 233 P. aeruginosa clinical isolates were included in this study. Antimicrobial susceptibility testing (AST) was done using disk diffusion and broth microdilution assays. Random Amplification of Polymorphic DNA (RAPD) was done to determine the genetic relatedness between the isolates. Induction of resistance against ciprofloxacin and levofloxacin was done on 19 isolates. Fitness cost assay was done on the 38 induced mutants and their parental isolates. Finally, whole genome sequencing was done on 16 induced mutants and their 8 parental isolates. Results: AST results showed that aztreonam had the highest non-susceptibility. RAPD results identified 18 clusters. The 19 P. aeruginosa isolates that were induced against ciprofloxacin and levofloxacin yielded MICs ranging between 16 and 256 µg/mL. Levofloxacin required fewer passages in 10 isolates and the same number of passages in 9 isolates as compared to ciprofloxacin to reach their breakpoints. Fitness cost results showed that 12 and 10 induced mutants against ciprofloxacin and levofloxacin, respectively, had higher fitness cost when compared to their parental isolates. Whole genome sequencing results showed that resistance to ciprofloxacin and levofloxacin in sequenced mutants were mainly associated with alterations in gyrA, gyrB and parC genes. Conclusion: Understanding resistance patterns and risk factors associated with infections is crucial to decrease the emerging threat of antimicrobial resistance.

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.

International Epidemiology of Carbapenemase-Producing Escherichia coli.

BACKGROUND: Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of patients from several countries with CP-Ec isolates obtained from a prospective cohort. METHODS: Patients with CP-Ec were enrolled from 26 hospitals in 6 countries. Clinical data were collected, and isolates underwent whole-genome sequencing. Clinical and molecular features and outcomes associated with isolates with or without metallo-ß-lactamases (MBLs) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after the index culture. RESULTS: Of the 114 CP-Ec isolates in Consortium on resistance against carbapenems in Klebsiella and other Enterobacterales-2 (CRACKLE-2), 49 harbored an MBL, most commonly blaNDM-5 (38/49, 78%). Strong regional variations were noted with MBL-Ec predominantly found among patients in China (23/49). Clinically, MBL-Ec were more often from urine sources (49% vs 29%), less often met criteria for infection (39% vs 58%, P = .04), and had lower acuity of illness when compared with non-MBL-Ec. Among patients with infection, the probability of a better DOOR outcome for a randomly selected patient with MBL-Ec as compared with non-MBL-Ec was 62% (95% CI: 48.2-74.3%). Among infected patients, non-MBL-Ec had increased 30-day (26% vs 0%; P = .02) and 90-day (39% vs 0%; P = .001) mortality compared with MBL-Ec. CONCLUSIONS: Emergence of CP-Ec was observed with important geographic variations. Bacterial characteristics, clinical presentations, and outcomes differed between MBL-Ec and non-MBL-Ec. Mortality was higher among non-MBL isolates, which were more frequently isolated from blood, but these findings may be confounded by regional variations.