The battle against fungi: lessons in antifungal stewardship from COVID 19 times

The COVID-19 pandemic has highlighted the detrimental effect of secondary pathogens in patients with a primary viral insult. In addition to superinfections with bacterial pathogens, invasive fungal infections were increasingly reported. The diagnosis of pulmonary fungal infections has always been challenging; however, it became even more problematic in the setting of COVID-19, particularly regarding the interpretation of radiological findings and mycology test results in patients with these infections. Moreover, prolonged hospitalization in ICU, coupled with underlying host factors. such as preexisting immunosuppression, use of immunomodulatory agents, and pulmonary compromise, caused additional vulnerability to fungal infections in this patient population. In addition, the heavy workload, redeployment of untrained staff, and inconsistent supply of gloves, gowns, and masks during the COVID-19 outbreak made it harder for healthcare workers to strictly adhere to preventive measures for infection control. Taken together, these factors favored patient-to-patient spread of fungal infections, such as those caused by Candida auris, or environment-to-patient transmission, including nosocomial aspergillosis. As fungal infections were associated with increased morbidity and mortality, empirical treatment was overly used and abused in COVID-19-infected patients, potentially contributing to increased resistance in fungal pathogens. The aim of this paper was to focus on essential elements of antifungal stewardship in COVID-19 for three fungal infections, COVID-19-associated candidemia (CAC), -pulmonary aspergillosis (CAPA), and -mucormycosis (CAM).

COVID-19 Infections and Predictors of Sickness Related Absences Among Healthcare Workers: The Experience of a Tertiary Care Center With the COVID-19 Pandemic.

BACKGROUND: Little has been published on predictors of prolonged sick leaves during the COVID-19 pandemic. This study aims to determine the rate of COVID-19 infections among healthcare workers (HCWs) and to identify the predictors of longer sick leave days. METHODS: We identified predictors of longer sick leave using linear regression analysis in a cross-sectional study design. RESULTS: Thirty-three percent of the total workforce contracted COVID-19. On average, HCWs took 12.5 sick leave days after COVID-19 infection. The regression analysis revealed that older employees, nurses, and those who caught COVID-19 earlier in the pandemic were more likely to take longer sick leave. CONCLUSIONS: Age, job position, and month of infection predicted sick leave duration among HCWs in our sample. Results imply that transmission was most likely community-based. Public health interventions should consider these factors when planning for future pandemics.

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.

The under investigated facet of the COVID-19 pandemic: Molecular analysis of secondary bacterial infections at a COVID dedicated intensive care unit within a tertiary care center in Lebanon.

Background: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Secondary bacterial infections are associated with unfavorable outcomes in respiratory viral infections. This study aimed at determining the prevalence of secondary bacterial infections in COVID-19 patients admitted at a tertiary medical center in Lebanon. Methodology: From May till November, 2020, a total of 26 Gram-negative isolates were recovered from 16 patients during the course of their COVID-19 infection with Escherichia coli being the most prevalent. The isolates were assessed for their antimicrobial susceptibility by broth microdilution against 19 antimicrobial agents from different classes. Whole genome sequencing of 13 isolates allowed the mining of antimicrobial resistance (AMR) determinants as well as mobile genetic elements and sequence types (ST). Finally, broth microdilution with three different efflux pump inhibitors [theobromine, conessine and PheArg-ß-naphthylamide (PAßN)] was done. Results: Antimicrobial susceptibility testing showed that out of the 26 Gram-negative isolates, 1 (4%) was extensively drug resistant and 14 (54%) were multi-drug resistant (MDR). Whole genome sequencing results revealed a plethora of AMR determinants among the 13 sequenced isolates. Moreover, the 9 Enterobacterales and 4 Pseudomonas aeruginosa sequenced isolates belonged to 9 and 2 different ST, respectively. Using a variety of efflux pump inhibitors we demonstrated that only PAßN had a significant effect when combined with levofloxacin, and the latter regained its activity against two P. aeruginosa isolates. Conclusion: The identification of carbapenem and colistin resistant Gram-negative bacilli causing secondary bacterial infections in critical patients diagnosed with COVID-19 should be of high concern. Additionally, it is crucial to monitor and track AMR, post-COVID pandemic, in order to better understand the effect of this disease on AMR exacerbation.

The Impact of Antimicrobial Stewardship and Infection Control Interventions on Acinetobacter baumannii Resistance Rates in the ICU of a Tertiary Care Center in Lebanon.

Antimicrobial resistance is a serious threat to global health, causing increased mortality and morbidity especially among critically ill patients. This toll is expected to rise following the COVID-19 pandemic. Carbapenem-resistant Acinetobacter baumannii (CRAb) is among the Gram-negative pathogens leading antimicrobial resistance globally; it is listed as a critical priority pathogen by the WHO and is implicated in hospital-acquired infections and outbreaks, particularly in critically ill patients. Recent reports from Lebanon describe increasing rates of infection with CRAb, hence the need to develop concerted interventions to control its spread. We set to describe the impact of combining antimicrobial stewardship and infection control measures on resistance rates and colonization pressure of CRAb in the intensive care units of a tertiary care center in Lebanon before the COVID-19 pandemic. The antimicrobial stewardship program introduced a carbapenem-sparing initiative in April 2019. During the same period, infection control interventions involved focused screening, monitoring, and tracking of CRAb, as well as compliance with specific measures. From January 2018 to January 2020, we report a statistically significant decrease in carbapenem consumption and a decrease in resistance rates of isolated A. baumannii. The colonization pressure of CRAb also decreased significantly, reaching record low levels at the end of the intervention period. The results indicate that a multidisciplinary approach and combined interventions between the stewardship and infection control teams can lead to a sustained reduction in resistance rates and CRAb spread in ICUs.

Challenges of coronavirus disease 2019 (COVID-19) in Lebanon in the midst of the economic collapse.

Lebanon, one of the smallest countries in the Middle East, has held for decades a reputation for being the premier medical hub for patients from the Arab world as well as neighboring countries and for offering world-class treatment and advanced medical services. However, this once world-renowned healthcare sector is now facing a risk of imminent collapse as overlapping crises have struck the country since October 2019. In this article, we describe the concomitant political, economic, and financial challenges that Lebanon is facing, which have strained the national healthcare system and have undermined its ability to respond to the coronavirus disease 2019 (COVID-19) pandemic. We present an overview of the political instability, the Lebanese revolution with countrywide protests, as well as the devaluation of the Lebanese currency representing one of the worst economic meltdowns since the 19th century. We describe the unprecedented energy crisis the country is facing and the disastrous consequences of the Beirut port explosion of August 2020. We review the efforts and measures taken by different stakeholders to contain the COVID-19 pandemic amid the multifaceted challenges and the large exodus of healthcare personnel.

COVID-19 and C. auris: A Case-Control Study from a Tertiary Care Center in Lebanon.

Many healthcare centers around the world have reported the surge of Candida auris (C. auris) outbreaks during the COVID-19 pandemic, especially among intensive care unit (ICU) patients. This is a retrospective study conducted at the American University of Beirut Medical Center (AUBMC) between 1 October 2020 and 15 June 2021, to identify risk factors for acquiring C. auris in patients with severe COVID-19 infection and to evaluate the impact of C. auris on mortality in patients admitted to the ICU during that period. Twenty-four non-COVID-19 (COV-) patients were admitted to ICUs at AUBMC during that period and acquired C. auris (C. auris+/COV-). Thirty-two patients admitted with severe COVID-19 (COV+) acquired C. auris (C. auris+/COV+), and 130 patients had severe COVID-19 without C. auris (C. auris-/COV+). Bivariable analysis between the groups of (C. auris+/COV+) and (C. auris-/COV+) showed that higher quick sequential organ failure assessment (qSOFA) score (p < 0.001), prolonged length of stay (LOS) (p = 0.02), and the presence of a urinary catheter (p = 0.015) or of a central venous catheter (CVC) (p = 0.01) were associated with positive culture for C. auris in patients with severe COVID-19. The multivariable analysis showed that prolonged LOS (p = 0.008) and a high qSOFA score (p < 0.001) were the only risk factors independently associated with positive culture for C. auris. Increased LOS (p = 0.02), high "Candida score" (p = 0.01), and septic shock (p < 0.001) were associated with increased mortality within 30 days of positive culture for C. auris. Antifungal therapy for at least 7 days (p = 0.03) appeared to decrease mortality within 30 days of positive culture for C. auris. Only septic shock was associated with increased mortality in patients with C. auris (p = 0.006) in the multivariable analysis. C. auris is an emerging pathogen that constitutes a threat to the healthcare sector.

Challenges to Antimicrobial Stewardship in the Countries of the Arab League: Concerns of Worsening Resistance during the COVID-19 Pandemic and Proposed Solutions.

The COVID-19 pandemic is expected to worsen the global problem of antimicrobial resistance (AMR). There is a heightened interest in understanding this effect and to develop antimicrobial stewardship (AMS) interventions accordingly to curb this threat. Our paper aims to evaluate the potential magnitude of COVID-19 on AMR and AMS with a focus on the countries of the Arab league, given the social, political, and economic environments. We also evaluate obstacles in applying the rational use of antibiotics, monitoring resistance trends in the midst of the pandemic, and evaluating the impact of the economic crisis in some countries. We aim to raise awareness about the potential effects of antibiotic overuse during the pandemic and to propose practical approaches to tackle this issue.

A pandemic recap: lessons we have learned.

On January 2020, the WHO Director General declared that the outbreak constitutes a Public Health Emergency of International Concern. The world has faced a worldwide spread crisis and is still dealing with it. The present paper represents a white paper concerning the tough lessons we have learned from the COVID-19 pandemic. Thus, an international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making. With the present paper, international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making.

Antimicrobial stewardship in the ICU in COVID-19 times: the known unknowns.

Since the start of the COVID-19 pandemic, there has been concern about the concomitant rise of antimicrobial resistance. While bacterial co-infections seem rare in COVID-19 patients admitted to hospital wards and intensive care units (ICUs), an increase in empirical antibiotic use has been described. In the ICU setting, where antibiotics are already abundantly-and often inappropriately-prescribed, the need for an ICU-specific antimicrobial stewardship programme is widely advocated. Apart from essentially warning against the use of antibacterial drugs for the treatment of a viral infection, other aspects of ICU antimicrobial stewardship need to be considered in view of the clinical course and characteristics of COVID-19. First, the distinction between infectious and non-infectious (inflammatory) causes of respiratory deterioration during an ICU stay is difficult, and the much-debated relevance of fungal and viral co-infections adds to the complexity of empirical antimicrobial prescribing. Biomarkers such as procalcitonin for the decision to start antibacterial therapy for ICU nosocomial infections seem to be more promising in COVID-19 than non-COVID-19 patients. In COVID-19 patients, cytomegalovirus reactivation is an important factor to consider when assessing patients infected with SARS-CoV-2 as it may have a role in modulating the patient immune response. The diagnosis of COVID-19-associated invasive aspergillosis is challenging because of the lack of sensitivity and specificity of the available tests. Furthermore, altered pharmacokinetic/pharmacodynamic properties need to be taken into account when prescribing antimicrobial therapy. Future research should now further explore the 'known unknowns', ideally with robust prospective study designs.

First Candida auris Outbreak during a COVID-19 Pandemic in a Tertiary-Care Center in Lebanon.

Candida auris is an emerging fungal pathogen considered as a global health threat. Recently there has been growing concern regarding drug resistance, difficulty in identification, as well as problems with eradication. Although outbreaks have been reported throughout the globe including from several Arab countries, there were no previous reports from Lebanon. We herein report the first cases of C. auris infection from the American University of Beirut Medical Center, a tertiary care center in Lebanon describing the clinical features of the affected patients in addition to the infection control investigation and applied interventions to control the outbreak. Fourteen patients with C. auris infection/colonization identified using MALDI-TOF and VITEK 2- Compact system were reported over a period of 13 weeks. Patients were admitted to four separate critical care units. All of them came through the emergency room and had comorbid conditions. Half of the patients were infected with COVID-19 prior to isolation of the C. auris. C. auris was isolated from blood (two isolates), urine (three isolates), respiratory tract (10 isolates) and skin (one isolate). All the patients had received broad spectrum antibiotics prior to isolation of C. auris. Six patients received antifungal treatment, while the remaining eight patients were considered colonized. Environmental cultures were taken from all four units and failed to isolate the organism from any cultured surfaces. A series of interventions were initiated by the Infection Prevention and Control team to contain the outbreak. Rapid detection and reporting of cases are essential to prevent further hospital transmission. A national standardized infection control registry needs to be established to identify widespread colonization.