QTc prolongation during levofloxacin and triazole combination chemoprophylaxis: Prevalence and predisposing risk factors in a cohort of hematopoietic cell transplantation recipients.

BACKGROUND: QTc interval prolongation has been reported when combining fluoroquinolones and triazoles for chemoprophylaxis in cancer patients. Herein, we aimed to identify the prevalence and contributing factors to QTc prolongation in hematopoietic cell transplantation (HCT) recipients who received these agents during the neutropenic phase. METHODS: This is a retrospective medical chart review conducted at a university hospital in Lebanon from 2017 to 2020. It included all adult HCT inpatients on antimicrobial prophylaxis with fluoroquinolones and triazoles and whose baseline ECG monitoring done prior to chemoprophylaxis administration, then on day-3 and day-6 of therapy, were available. RESULTS: Overall, 68 HCT recipients met our inclusion criteria, of which 22% developed QTc prolongation. Based on bivariate analysis, female gender contributed to QTc prolongation (P = 0.001). There was a trend to QTc prolongation in patients with predisposing thyroid disease (P = 0.12), grade 2 vomiting and diarrhea (P = 0.16, P = 0.46, respectively), baseline hypokalemia (P = 0.18) and hypocalcemia (P = 0.3), hypomagnesemia on day-3 (P = 0.21) and day-6 hyponatremia (P = 0.36). Patients receiving two or more drugs with a known or probable risk of QTc prolongation (other than the fluoroquinolone/ triazole combination) were more prone to experience a prolonged QTc interval (P = 0.09). None of the patients that had QTc prolongation died or developed serious arrhythmias. CONCLUSION: The prevalence of QTc prolongation was 22% among HCT recipients on fluoroquinolone and triazole prophylaxis, yet we did not identify any independent risk factors for this issue. None of the patients that had QTc interval prolongation died or developed serious arrhythmias.

Pre-engraftment infectious complications and patient outcomes after allogeneic hematopoietic cell transplantation: a single-center experience from Lebanon.

BACKGROUND: Infectious complications are significant causes of morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HCT). They occur variably over different periods, with scant data reported from Lebanon and neighboring countries. In this study, we described the pre-engraftment neutropenic phase, febrile episodes, and peri-transplant medical complications in patients undergoing allo-HCT at a tertiary-care hospital. METHODS: This is a retrospective chart review of patients who underwent allo-HCT between 2007 and 2016 at Makassed General Hospital in Beirut, Lebanon. Data were extracted from medical records, the HCT registry, and medical laboratory logbooks. RESULTS: One hundred and six patients were included, 75% having hematologic malignancies and 13% aplastic anemia. None received antibacterial prophylaxis with fluoroquinolones. Yet from conditioning chemotherapy till the say before HCT, 32% of the patients received broad-spectrum antibiotics (BSA) due to fever or infection. At the day of cell infusion, 41.5% of the patients were on BSA. Neutrophil engraftment failure was recorded in 8% of the patients. The cumulative incidence of pre-engraftment bacteremia and Gram-negative bacteremia was 14.3 and 7.1%, respectively. Aplastic anemia was an independent risk factor for pre-engraftment bacteremia [hazard ratio (HR) = 3.86, 95% confidence interval (CI) (1.29-11.5), P = 0.02]. The cumulative incidence of pre-engraftment pneumonia was 11.2%. Patient age significantly increased the risk of pre-engraftment pneumonia [HR = 12.35, 95% CI (1.27-120.50), P = 0.03]. Six-month post-transplant mortality reached 17% in our cohort. Myelodysplastic syndrome was the only significant parameter increasing the risk of death [HR = 3.40, 95% CI (1.05-10.98), P = 0.04]. CONCLUSION: The cumulative incidence of pre-engraftment bacteremia and pneumonia was 14.3% and 11.2% respectively in this cohort. Aplastic anemia predicted for the occurrence of bacteremia, increasing patient age contributed to the occurrence of pneumonia, and myelodysplastic syndrome increased the risk of death.

The effect of an antibiotic stewardship program on tigecycline use in a Tertiary Care Hospital, an intervention study.

BACKGROUND: A drug-oriented antibiotic stewardship intervention targeting tigecycline utilization was launched at Makassed General Hospital, Beirut, Lebanon, in 2016 as a part of a comprehensive Antibiotic Stewardship Program (ASP). In this study, we evaluated the effect of this intervention on changing tigecycline prescription behavior in different types of infections, patient outcome and mortality, along with tigecycline drug use density, when compared to an earlier period before the initiation of ASP. METHODS: This is a retrospective chart review of all adult inpatients who received tigecycline for more than 72 h between Jan-2012 and Dec-2013 [period (P) 1 before ASP] and between Oct-2016 and Dec-2018 [period (P) 2 during ASP]. RESULTS: Tigecycline was administered to 153 patients during P1 and 116 patients during P2. The proportion of patients suffering from cancer, those requiring mechanical ventilation, and those with hemodynamic failure was significantly reduced between P1 and P2. The proportion of patients who received tigecycline for FDA-approved indications increased from 19% during P1 to 78% during P2 (P < 0.001). On the other hand, its use in off-label indications was restricted, including ventilator-associated pneumonia (26.1% in P1, 3.4% in P2, P < 0.001), hospital-acquired pneumonia (19.6% in P1, 5.2% in P2, P = 0.001), sepsis (9.2% in P1, 3% in P2, P = 0.028), and febrile neutropenia (15.7% in P1, 0.9% in P2, P < 0.001). The clinical success rate of tigecycline therapy showed an overall significant increase from 48.4% during P1 to 65.5% during P2 (P = 0.005) in the entire patient population. All-cause mortality in the tigecycline-treated patients decreased from 45.1% during P1 to 20.7% during P2 (P < 0.0001). In general, mean tigecycline consumption decreased by 55% between P1 and P2 (P < 0.0001). CONCLUSION: The drug-oriented ASP intervention targeting tigecycline prescriptions improved its use and patient outcomes, where it helped curb the over-optimistic use of this drug in off-label indications where it is not a suitable treatment option.

The 2018 Lebanese Society of Infectious Diseases and Clinical Microbiology Guidelines for the use of antimicrobial therapy in complicated intra-abdominal infections in the era of antimicrobial resistance.

BACKGROUND: The Lebanese Society of Infectious Diseases and Clinical Microbiology (LSIDCM) is involved in antimicrobial stewardship. In an attempt at guiding clinicians across Lebanon in regards to the proper use of antimicrobial agents, members of this society are in the process of preparing national guidelines for common infectious diseases, among which are the guidelines for empiric and targeted antimicrobial therapy of complicated intra-abdominal infections (cIAI). The aims of these guidelines are optimizing patient care based on evidence-based literature and local antimicrobial susceptibility data, together with limiting the inappropriate use of antimicrobials thus decreasing the emergence of antimicrobial resistance (AMR) and curtailing on other adverse outcomes. METHODS: Recommendations in these guidelines are adapted from other international guidelines but modeled based on locally derived susceptibility data and on the availability of pharmaceutical and other resources. RESULTS: These guidelines propose antimicrobial therapy of cIAI in adults based on risk factors, site of acquisition of infection, and clinical severity of illness. We recommend using antibiotic therapy targeting third-generation cephalosporin (3GC)-resistant gram negative organisms, with carbapenem sparing as much as possible, for community-acquired infections when the following risk factors exist: prior (within 90 days) exposure to antibiotics, immunocompromised state, recent history of hospitalization or of surgery and invasive procedure all within the preceding 90 days. We also recommend antimicrobial de-escalation strategy after culture results. Prompt and adequate antimicrobial therapy for cIAI reduces morbidity and mortality; however, the duration of therapy should be limited to no more than 4 days when adequate source control is achieved and the patient is clinically stable. The management of acute pancreatitis is conservative, with a role for antibiotic therapy only in specific situations and after microbiological diagnosis. The use of broad-spectrum antimicrobial agents including systemic antifungals and newly approved antibiotics is preferably restricted to infectious diseases specialists. CONCLUSION: These guidelines represent a major step towards initiating a Lebanese national antimicrobial stewardship program. The LSIDCM emphasizes on development of a national AMR surveillance network, in addition to a national antibiogram for cIAI stratified based on the setting (community, hospital, unit-based) that should be frequently updated.

Bacteraemia post-autologous haematopoietic stem cell transplantation in the absence of antibacterial prophylaxis: a decade's experience from Lebanon.

PURPOSE: In this study, we assessed the incidence, contributing factors and outcome of prolonged neutropenia above 7 days and of bacteraemia in patients with lymphoma and multiple myeloma who underwent autologous haematopoietic stem cell transplantation (AHSCT) without antibacterial prophylaxis. METHODS: This is a retrospective chart review of 190 adult patients who underwent AHSCT between 2005 and 2015 at a Lebanese hospital. RESULTS: Neutropenia of 7 days duration and longer was documented in 66% of the patient population. Through univariate analysis, patients with lymphoma were significantly more likely to have prolonged neutropenia (≥ 7 days) compared to those with myeloma. Mucositis above grade 3, diarrhoea and fever were more likely to occur in patients with prolonged neutropenia. Bacteraemia was documented in 12.6% of the patients. Total mortality rate was 3.7%, and that attributed to bacteraemia was 12.5% in the bacteraemia subgroup. Among bacterial isolates recovered from clinical specimens (89 isolates), 70% were Gram-negative, of which 57% were fluoroquinolone susceptible. Ninety-five percent of the Gram-negative bacteria causing bacteraemia were susceptible to fluoroquinolones. CONCLUSION: Bacterial pathogens causing bacteraemia were still highly susceptible to fluoroquinolones, despite the high prevalence of fluoroquinolone-resistant strains in the general bacterial ecology. Accordingly, the pertinence of fluoroquinolone prophylaxis in the AHSCT setting warrants further investigation. Moreover, continuous surveillance of local antibiograms in this patient population has become a must in an era of preponderant antibiotic resistance.

Correlation between antifungal consumption and the distribution of Candida species in different hospital departments of a Lebanese medical Centre.

BACKGROUND: In recent years, there has been a significant increase in the incidence of fungal infections attributed to Candida species worldwide, with a major shift toward non-albicans Candida (NAC). In this study, we have described the distribution of Candida species among different hospital departments and calculated the antifungal consumption in our facility. We also correlated the consumption of certain antifungals and the prevalence of specific Candida species. METHODS: This was a retrospective review of all the Candida isolates recovered from the computerised microbiology laboratory database of Makassed General Hospital, a tertiary care centre in Beirut, Lebanon, between January 2010 and December 2015. Data on antifungal consumption between January 2008 and December 2015 were extracted from the hospital pharmacy electronic database. We used Spearman's coefficient to find a correlation between Candida species distribution and antifungal consumption. RESULTS: Between 2008 and 2015, we observed that the highest antifungal consumption was in the haematology/oncology department (days of therapy/1000 patient days = 348.12 ± 85.41), and the lowest was in the obstetrics/gynaecology department (1.36 ± 0.47). In general, the difference in antifungal consumption among various departments was statistically significant (P < 0.0001). Overall, azoles were the most common first-line antifungals in our hospital. Echinocandins and amphotericin B were mostly prescribed in the haematology/oncology department. As for Candida species distribution, a total of 1377 non-duplicate isolates were identified between 2010 and 2015. A non-homologous distribution of albicans vs. non-albicans was noted among the different departments (P = 0.02). The most commonly isolated NAC was Candida glabrata, representing 14% of total Candida species and 59% of NAC. Candida famata (9% of NAC), Candida parapsilosis (3.6% of NAC) and Candida krusei (3% of NAC) were recovered unequally from the different departments. The total antifungal consumption correlated positively with the emergence of NAC. The use of azoles correlated positively with Candida glabrata, while amphotericin B formulations correlated negatively with it. None of these correlations reached statistical significance. CONCLUSION: Different Candida species were unequally distributed among different hospital departments, and this correlated with consumption of antifungals in respective departments, highlighting the need for antifungal stewardship.

E. coli, K. pneumoniae and K. oxytoca community-acquired infections susceptibility to cephalosporins and other antimicrobials in Lebanon.

OBJECTIVES: Cephalosporin resistance in Enterobacteriaceae has become an international concern. This article studies the distribution and trends of resistance of E. coli and Klebsiella species isolated from clinical specimens representing community-acquired infections. METHODS: E. coli, K. pneumoniae and K. oxytoca specimen strains were collected from patients presenting to three acute care hospitals in Lebanon. The study period extended from January 2010 to January 2011 and included patients presenting with community-acquired infections only. Automated microbiological system (VITEK 2) was used for identification and antimicrobial susceptibilities. RESULTS: Data from consecutive non-duplicate 589 E. coli, 54 K. pneumoniae and 40 K. oxytoca strains were collected of which 69.5%, 74.0% and 67.5% were susceptible to 3rd generation cephalosporins (3GC), respectively. Out of the 3GC-resistant E. coli strains, around 90% were susceptible to nitrofurantoin, 46% were susceptible to trimethoprim/sulfamethoxazole (TMP/SMX) and 53% to ciprofloxacin. The patterns of antimicrobial susceptibility in the two Klebsiella species did not parallel those in the E. coli strains. Yet, the number of Klebsiella strains was much lower than that of E. coli. Of note is that the 3GC-resistant strains of both Klebsiella species were less susceptible to nitrofurantoin compared to the overall groups reaching a maximum of 30%. However, susceptibility to TMP/SMX was much higher reaching 79% and that of ciprofloxacin reaching 86%. CONCLUSION: Clinical specimens of E. coli, Klebsiella pneumoniae and Klebsiella oxytoca, causing community-acquired infections in Lebanon showed that these organisms are significantly resistant to many antibiotics. These patterns of resistance were mainly to internationally recommended drugs for empiric treatment of community-acquired infections like community-acquired urinary tract infections (UTIs) and intra-abdominal infections. Therefore, continuous antimicrobial susceptibility surveillance is advisable to track emerging resistance in Enterobacteriaceae and national guidelines would be tailored accordingly.

The Lebanese Society for Infectious Diseases and Clinical Microbiology (LSIDCM) guidelines for adult community-acquired pneumonia (Cap) in Lebanon.

Adult community-acquired pneumonia (CAP) is a common cause of morbidity and mortality which is managed by different disciplines in a heterogeneous fashion. Development of consensus guidelines to standardize these wide variations in care has become a prime objective. The Lebanese Society of Infectious Diseases and Clinical Microbiology (LSIDCM) convened to set Lebanese national guidelines for the management of CAP since it is a major and a prevalent disease affecting the Lebanese population. These guidelines, besides being helpful in direct clinical practice, play a major role in establishing stewardship programs in hospitals in an effort to contain antimicrobial resistance on the national level. These guidelines are intended for primary care practitioners and emergency medicine physicians. They constitute an appropriate starting point for specialists' consultation being based on the available local epidemiological and resistance data. This document includes the following: 1/ Rationale and scope of the guidelines; 2/ Microbiology of CAP based on Lebanese data; 3/ Clinical presentation and diagnostic workup of CAP; 4/ Management and prevention strategies based on the IDSA/ATS Consensus Guidelines, 2007, and the ESCMID Guidelines, 2011, and tailored to the microbiological data in Lebanon; 5/ Comparison to regional guidelines. The recommendations made in this document were graded based on the strength of the evidence as in the 2007 IDSA/ATS Consensus Guidelines. Hopefully, these guidelines will be an important step towards standardization of CAP care in Lebanon and set the agenda for further research in this area.

Longitudinal genomic surveillance of multidrug-resistant Escherichia coli carriage in critical care patients.

Colonization with multidrug-resistant Escherichia coli strains causes a substantial health burden in hospitalized patients. We performed a longitudinal genomics study to investigate the colonization of resistant E. coli strains in critically ill patients and to identify evolutionary changes and strain replacement events within patients. Patients were admitted to the intensive care unit and hematology wards at a major hospital in Lebanon. Perianal swabs were collected from participants on admission and during hospitalization, which were screened for extended-spectrum beta-lactamases and carbapenem-resistant Enterobacterales. We performed whole-genome sequencing and analysis on E. coli strains isolated from patients at multiple time points. The E. coli isolates were genetically diverse, with 11 sequence types (STs) identified among 22 isolates sequenced. Five patients were colonized by E. coli sequence type 131 (ST131)-encoding CTX-M-27, an emerging clone not previously observed in clinical samples from Lebanon. Among the eight patients whose resident E. coli strains were tracked over time, five harbored the same E. coli strain with relatively few mutations over the 5 to 10 days of hospitalization. The other three patients were colonized by different E. coli strains over time. Our study provides evidence of strain diversity within patients during their hospitalization. While strains varied in their antimicrobial resistance profiles, the number of resistance genes did not increase over time. We also show that ST131-encoding CTX-M-27, which appears to be emerging as a globally important multidrug-resistant E. coli strain, is also prevalent among critical care patients and deserves further monitoring.IMPORTANCEUnderstanding the evolution of bacteria over time in hospitalized patients is of utmost significance in the field of infectious diseases. While numerous studies have surveyed genetic diversity and resistance mechanisms in nosocomial infections, time series of within-patient dynamics are rare, and high-income countries are over-represented, leaving low- and middle-income countries understudied. Our study aims to bridge these research gaps by conducting a longitudinal survey of critically ill patients in Lebanon. This allowed us to track Escherichia coli evolution and strain replacements within individual patients over extended periods. Through whole-genome sequencing, we found extensive strain diversity, including the first evidence of the emerging E. coli sequence type 131 clone encoding the CTX-M-27 beta-lactamase in a clinical sample from Lebanon, as well as likely strain replacement events during hospitalization.

The Prevalence and Risk Factors of Acute Kidney Injury during Colistin Therapy: A Retrospective Cohort Study from Lebanon.

INTRODUCTION: The current study aimed to determine the prevalence, risk factors, and stages of severity of acute kidney injury (AKI) caused by colistimethate sodium (CMS) treatment in patients diagnosed with systemic antibiotic-resistant Gram-negative bacterial infections. The predictors of all-cause mortality in this patient population were also examined. METHODS: This retrospective cohort study included patients who were admitted to a university-affiliated hospital and acute tertiary care referral center in Beirut, Lebanon between January 2015 and December 2018 and underwent CMS treatment for a period of 48 h or more. RESULTS: The study sample included 298 adult patients, of which 46.3% (n = 138/298) developed AKI (assessed using the Kidney Disease Improving Global Outcomes (KDIGO) criteria). Of these, 37.7% (n = 51/138) were diagnosed with stage 1 AKI, 23.9% with stage 2 (n = 33/138), and 38.4% with stage 3 (n = 53/138). Nephrotoxicity was reversed in 87.5% of AKI patients who survived until hospital discharge. Independent risk factors for AKI included patient age ≥ 75 years (aOR = 1.854; 95% CI: 1.060-3.241; p-value = 0.03); underlying chronic kidney disease (aOR = 4.849; 95% CI: 2.618-9.264; p-value < 0.0001); and concomitant use of vasopressors (aOR = 4.305; 95% CI: 2.517-7.456; p-value < 0.0001). Multivariate analysis showed that the predictors of severe AKI (stage 2 or 3) included baseline hypoalbuminemia (aOR = 2.542; 95% CI: 1.000-6.564; p-value = 0.05); concomitant use of vasopressors (aOR = 6.396; 95% CI: 2.741-15.87; p-value < 0.0001); and CMS days of therapy (DOT) prior to development of AKI ≥ 7 days (aOR = 4.728; 95% CI: 2.069-11.60; p-value < 0.0001). All-cause mortality was recorded in 51.3% of patients (n = 153/298), and this was significantly higher in patients with AKI (76.8%; n = 106/138) compared to those without (29.4%; n = 47/160; OR = 7.964; 95% CI: 4.727-13.417; p-value < 0.0001). Independent predictors of all-cause mortality included a baseline Charlson comorbidity index score ≥5 (aOR = 4.514; 95% CI: 2.443-8.530; p-value < 0.0001); concomitant use of vasopressors (aOR = 7.76; 95% CI: 4.238-14.56; p-value < 0.0001); and CMS-induced AKI (aOR = 4.117; 95% CI: 2.231-7.695; p-value < 0.0001). CONCLUSIONS: The findings of this study suggest that old age, history of chronic kidney disease, and concomitant vasopressor treatment are all independent predictors of CMS-induced AKI. The risk of developing severe AKI significantly increases with CMS DOT. Understanding the risk factors of nephrotoxicity is essential for improving prognosis and treatment outcomes.

Characterization and susceptibility of non-albicans Candida isolated from various clinical specimens in Lebanese hospitals.

Background: Invasive fungal infections have presented a challenge in treatment. In the past, it was known that the frontrunner in such infections is Candida albicans with little emphasis placed on non-albicans Candida species (NAC). Studies worldwide have shown a rise in fungal infections attributed to non-albicans Candida species. The aim of this study is to describe the epidemiology of NAC infections along with an overview of resistance in Lebanese hospitals. Methods: This is a two-year observational multi-central descriptive study. Between September 2016 and May of 2018, a total of 1000 isolates were collected from 10 different hospitals distributed all over the country. For the culture, Sabouraud Dextrose Agar was used. Antifungal Susceptibility was evaluated by determining the Minimum Inhibitory Concentration (MIC) in broth (microdilution) of the different antifungal treatments. Results: Out of the 1000 collected isolates, Candida glabrata, being the most isolated species (40.8%), followed by Candida tropicalis: 231(23.1%), Candida parapsilosis: 103(10.3%), and other NAC species at lower percentage. Most of these isolates (88.67%) were susceptible to posaconazole, 98.22% were susceptible to micafungin, and 10% were susceptible to caspofungin. Conclusion: The change of etiology of fungal infections involving a significant increase in NAC cases is alarming due to the different antifungal susceptibility patterns and the lack of local guidelines to guide the treatment. In this context, proper identification of such organisms is of utmost importance. The data presented here can help in establishing guidelines for the treatment of candida infections to decrease morbidity and mortality. Future surveillance data are needed.

Mapping of infection prevention and control education and training in some countries of the World Health Organization's Eastern Mediterranean Region: current situation and future needs.

BACKGROUND: A strong understanding of infection prevention and control (IPC) procedures and comprehensive training among healthcare workers is essential for effective IPC programs. These elements play a crucial role in breaking the chain of nosocomial infections by preventing the transmission of resistant organisms to patients and staff members. This study mapped the components of IPC education and training across various member states of the World Health Organization (WHO) in the Eastern Mediterranean Region (EMR) at national, academic, and healthcare institutional levels. METHODS: A self-administered structured online questionnaire based on the WHO "Core Component 3" of IPC programs at the national and acute healthcare facility levels (IPC education and training) was given to national IPC focal persons in each of the WHO's EMR countries between February and March 2023. RESULTS: From 14 of the 22 countries,15 IPC persons participated in the survey. Most countries have scattered nonhomogeneous IPC education programs in human health undergraduate majors without considering it a standalone module. Academic institutions are rarely involved, and elaborate and predefined undergraduate IPC education programs provided by universities are present in 21.4% of the countries. In 71.4% of these countries, postgraduate training targeting IPC professionals is provided by national IPC teams, primarily based on national IPC guidelines developed with the aid of the WHO. Generally, healthcare worker training relies heavily on healthcare facilities in 92.9% of the countries, rather than on a national training program. In 42.9% of the countries, practicing IPC physicians are not necessarily specialists of infectious disease or medical microbiologists and IPC nurses are not required to specialize in IPC. However, nonspecialized IPC professionals are expected to undergo training upon employment and before beginning practice. Nongovernmental organizations such as the WHO play a significant role in IPC education and in supporting national IPC authorities in establishing national IPC guidelines, as it is the case in 78.6% of these countries. CONCLUSION: Clear disparities exist in IPC education and training across different countries in the WHO's EMR. Establishing a regional scientific network specializing in IPC would help bridge the existing gaps and standardize this education within individual countries and across countries in the region. This region needs to establish IPC certification standards and standardized education curricula.

COVID-19: Second Wave or Multiple Peaks, Natural Herd Immunity or Vaccine - We Should be Prepared.

Between December 31, 2019, and August 30, 2020 (date of this article), the novel coronavirus and its corresponding infection, coronavirus disease (COVID-19), increased to more than 25 million cases, and 843 158 deaths have been registered. Countries around the world have been affected, albeit in different levels and intensities.Despite implementations of preventive public health measures, most countries are seriously preparing for 1 or more waves. The threat of this surge is likely to persist until herd immunity is acquired either by natural infection or through vaccination. However, given the time frame needed for herd immunity to occur and the low probability that a vaccine will be available on a global scale by the coming fall and winter seasons, contingency preparedness plans should be established and put in place for the coming days or months. These plans should help mitigate new peaks of the pandemic while relaxing the social isolation rules, patient, public health, and hospital levels.In this article, we discuss recommendations that practicing physicians and public health agencies should provide to individuals, especially those at risk of infection, to take and implement pre-emptive measures in anticipation of the potential next peak of the pandemic.

Immunogenicity and Effectiveness of Primary and Booster Vaccine Combination Strategies during Periods of SARS-CoV-2 Delta and Omicron Variants.

In this study involving a cohort of employees of the National Airline company in Lebanon, we assessed humoral immunity levels and the effectiveness of two COVID-19 vaccines, Gam-COVID-Vac versus BNT162b2, after two doses and after a homologous and heterologous BNT162b2 booster, in addition to the impact of hybrid immunity. Vaccine effectiveness (VE) was retrospectively determined against laboratory-confirmed SARS-CoV-2 infection during the periods of Delta and Omicron variants' predominance, separately, and was calculated based on a case-control study design. The humoral immune response, measured by a SARS-CoV-2 anti-spike receptor-binding domain (RBD) IgG titer, was prospectively assessed after the aforementioned vaccination schemes at different time points. This study showed higher effectiveness of BNT162b2 after two doses (81%) compared to two doses of Gam-COVID-Vac (41.8%) against the Delta variant of SARS-CoV-2, which correlated with anti-spike antibody levels. Regarding the Omicron variant, protection against infection and antibody levels were severely compromised and the correlation between an anti-spike IgG titer and effectiveness was lost, unlike the situation during the Delta wave. Considering the booster vaccination schemes, a homologous BNT162b2 booster after a BNT162b2 primary vaccination induced a higher humoral immune response when compared to that induced by a heterologous BNT162b2 booster after a Gam-COVID-Vac primary vaccination. However, the VE of both booster regimens against the Omicron variant was almost equal (64% in the homologous regimen and 57% in heterologous regimen). Hybrid immunity evidenced a better humoral response and a greater and longer protection against Delta and Omicron infections compared to vaccination-induced immunity in COVID-19-naïve individuals. Finally, the findings show that VE waned with time during the same wave, highlighting the importance of reinforcing primary and booster COVID-19 vaccination mainly at the beginning of each wave during the surge of a new variant of concern.

Pneumococcal Disease in High-Risk Adults in Lebanon: Expert Opinion.

Pneumococcal disease affects people across all ages but is more prevalent in young children and the elderly. Despite the availability of the pneumococcal vaccine for adults, the disease burden and mortality associated with it remains a challenge. A few studies conducted in Lebanon have reported epidemiology of pneumococcal disease, concurring the high burden among adults and older adults in the region. The pneumococcal vaccine is a part of the routine immunization schedule for children, but there are no recommendations for adult vaccination. A medical advisory board was hence conducted in September 2020 to discuss the burden of pneumococcal disease (PD) among adults in Lebanon. The participants were experts from the fields of internal medicine, family medicine, hematology, cardiology, oncology, endocrinology, pulmonology, and infectious diseases. The experts reached a consensus that there is a need to take steps to increase the rate of adult vaccination uptake and create awareness among physicians, pharmacists, caregivers, and patients. The physicians should be trained on adult immunization and should actively discuss the importance of the pneumococcal vaccine, especially with high-risk adult patients. Implementing adult vaccination as a routine practice and involving various stakeholders to address the gaps can help in reducing the burden of pneumococcal disease in adults.

A randomized clinical trial of lipid metabolism modulation with fenofibrate for acute coronavirus disease 2019.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cytotoxicity may involve inhibition of peroxisome proliferator-activated receptor alpha. Fenofibrate activates peroxisome proliferator-activated receptor alpha and inhibits SARS-CoV-2 replication in vitro. Whether fenofibrate can be used to treat coronavirus disease 2019 (COVID-19) infection in humans remains unknown. Here, we randomly assigned inpatients and outpatients with COVID-19 within 14 d of symptom onset to 145 mg of oral fenofibrate nanocrystal formulation versus placebo for 10 d, in a double-blinded fashion. The primary endpoint was a severity score whereby participants were ranked across hierarchical tiers incorporating time to death, mechanical ventilation duration, oxygenation, hospitalization and symptom severity and duration. In total, 701 participants were randomized to fenofibrate (n = 351) or placebo (n = 350). The mean age of participants was 49 ± 16 years, 330 (47%) were female, mean body mass index was 28 ± 6 kg/m2 and 102 (15%) had diabetes. Death occurred in 41 participants. Compared with placebo, fenofibrate had no effect on the primary endpoint. The median (interquartile range) rank in the placebo arm was 347 (172, 453) versus 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in secondary and exploratory endpoints, including all-cause death, across arms. There were 61 (17%) adverse events in the placebo arm compared with 46 (13%) in the fenofibrate arm, with slightly higher incidence of gastrointestinal side effects in the fenofibrate group. Overall, among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes ( NCT04517396 ).

A Randomized Trial of Lipid Metabolism Modulation with Fenofibrate for Acute Coronavirus Disease 2019.

Background Abnormal cellular lipid metabolism appears to underlie SARS-CoV-2 cytotoxicity and may involve inhibition of peroxisome proliferator activated receptor alpha (PPARα). Fenofibrate, a PPAR-α activator, modulates cellular lipid metabolism. Fenofibric acid has also been shown to affect the dimerization of angiotensin-converting enzyme 2, the cellular receptor for SARS-CoV-2. Fenofibrate and fenofibric acid have been shown to inhibit SARS-CoV-2 replication in cell culture systems in vitro . Methods We randomly assigned 701 participants with COVID-19 within 14 days of symptom onset to 145 mg of fenofibrate (nanocrystal formulation with dose adjustment for renal function or dose-equivalent preparations of micronized fenofibrate or fenofibric acid) vs. placebo for 10 days, in a double-blinded fashion. The primary endpoint was a ranked severity score in which participants were ranked across hierarchical tiers incorporating time to death, duration of mechanical ventilation, oxygenation parameters, subsequent hospitalizations and symptom severity and duration. ClinicalTrials.gov registration: NCT04517396. Findings: Mean age of participants was 49 ± 16 years, 330 (47%) were female, mean BMI was 28 ± 6 kg/m 2 , and 102 (15%) had diabetes mellitus. A total of 41 deaths occurred. Compared with placebo, fenofibrate administration had no effect on the primary endpoint. The median (interquartile range [IQR]) rank in the placebo arm was 347 (172, 453) vs. 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in various secondary and exploratory endpoints, including all-cause death, across randomization arms. These results were highly consistent across pre-specified sensitivity and subgroup analyses. Conclusion Among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes.

Phenotypic and genotypic characterisation of cephalosporin-, carbapenem- and colistin-resistant Gram-negative bacterial pathogens in Lebanon, Jordan and Iraq.

Antimicrobial resistance (AMR) is a worldwide health concern that continues to escalate. A PubMed literature search identified articles from January 2015-August 2020 reviewing cephalosporin-, carbapenem- and colistin-resistant Gram-negative bacteria (GNB) in Lebanon, Jordan and Iraq, specifically focused on three main pathogens, namely Acinetobacter spp., Enterobacteriaceae (i.e. Escherichia coli and Klebsiella spp.) and Pseudomonas aeruginosa. Sixty-seven relevant articles published within the past 5 years highlighting trends in AMR in Lebanon, Jordan and Iraq were included. Increased resistance to carbapenems in Acinetobacter spp. isolates was observed in Lebanon, Jordan and Iraq; colistin resistance remained relatively low. Studies on Enterobacteriaceae isolates were more varied, with high rates of carbapenem and cephalosporin resistance and lower levels of colistin resistance in Lebanon. Studies from Iraq found high cephalosporin and colistin resistance along with increased susceptibility to carbapenems. In Jordan, most studies recorded high resistance to cephalosporins along with high susceptibility to carbapenems and colistin. Studies on P. aeruginosa isolates were limited: most isolates in Lebanon were carbapenem-resistant and colistin-susceptible; studies in Iraq showed varying levels of resistance to carbapenems and cephalosporins with high susceptibility to colistin; and studies in Jordan found varying levels of susceptibility to carbapenems, cephalosporins and colistin. The most commonly observed resistance mechanisms in GNB were genetic modifications causing increased expression of antimicrobial-inactivating enzymes and decreased permeability. Overall, this review highlights the concerning rise in AMR and the need for improved understanding of the resistance mechanisms to better inform healthcare providers when recommending treatment for patients in this region.

Outcome of Neglected Versus Treated Tuberculous Dactylitis in the Same Patient - A case report.

INTRODUCTION: Skeletal tuberculosis is a rare form of extrapulmonary Mycobacterium tuberculosis infection. When tubular bones are affected, it is called tuberculous dactylitis (TD). This rare entity can be seen in the hand or foot and has been mentioned in a handful of case reports. CASE REPORT: A 56-year-old female patient presented to our clinic for left hand middle finger swelling and pain of 1-year duration. Her medical history was relevant for 15 years history of progressive 4th and 5th fingers malformations that were attributed to "sarcoidosis," and for which she was treated with anti-inflammatory and low dose steroids therapy. At our clinic, physical examination was consistent with a swelling of the base of the middle finger associated with tenderness and decreased range of motion. Radiographs of the hand showed a lytic lesion involving the distal half of the first phalanx, along with blurred limits of the bone surfaces involved. An magnetic resonance imaging was ordered and showed hyper-intense signal of the first phalanx, along with subcutaneous enclosed collections on both sides of the phalanx. Surgical debridement with open biopsy and culture was done. Pathology results showed caseating granulomas, and cultures confirmed the diagnosis of TD. A computed tomography scan of the chest was done postoperatively; where few calcified nodules were noted. She also received a 9-months course of anti-tuberculous drugs and had complete cure by 9 months postoperatively. CONCLUSION: TD of the hand is a very rare entity of the spectrum of extrapulmonary M. tuberculosis infection. Clinicians should have a high index of suspicion concerning this pathology not to delay the diagnosis, which could lead to permanent deformity. Early diagnosis and treatment can significantly improve outcomes.

Immunogenicity and reactogenicity of BNT162b2 booster in BBIBP-CorV-vaccinated individuals compared with homologous BNT162b2 vaccination: Results of a pilot prospective cohort study from Lebanon.

Facing new COVID-19 waves, the effectiveness of BBIBP-CorV has been noted to be low in countries whose populations were already administered two doses of the vaccine. Heterologous vaccination using ChAdOx1-S/BNT162b2 elicited higher immunogenicity compared with homologous immunization. BBIBP-CorV/BNT162b2 combination is worth testing. In this pilot prospective cohort study conducted at Makassed General Hospital, Beirut, Lebanon, from February 17, 2021, to June 30, 2021, we tested the safety and immunogenicity of a BNT162b2 booster dose in COVID-19-naïve individuals who had received two doses of the BBIBP-CorV vaccine. Heterologous booster vaccination was found to be safe and well tolerated. It was significantly associated with higher anti-spike IgG geometric mean titers compared to that after homologous BNT162b2 immunization in COVID-19-naïve individuals [(8040BAU/mL, 95%confidence interval (CI), 4612-14016) vs (1384BAU/mL, 95%CI, 1063-1801), respectively, (P < 0.0001)]. In countries with limited access to mRNA vaccines and where populations have already received BBIBP-CorV, mixing BBIBP-CorV/BNT162b2 is seen to overcome the low immunogenicity induced by BBIBP-CorV alone, thus potentially providing protection against emerging variants.