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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). Mortality rate in the overall ICU population during the pandemic was 76.6%, much higher than the previously reported mortality of candidemia from previous studies at our center. 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 hours following the candidemia (P = 0.008) and identifying the Candida spp. (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 like C. auris.

Objectives The Burkholderia cepacia complex (Bcc), which was originally thought to be a single species, represents a group of 24 distinct species that are often resistant to multiple antibiotics, and usually known to cause life-threatening pulmonary infections in cystic fibrosis patients. Herein we describe a series of non-respiratory Bcc infections, the risk factors and epidemiologic factors, in addition to the clinical course. Patients and methods This is a retrospective chart review of 44 patients with documented B. cepacia infections isolated from sites other than the respiratory tract admitted between June 2005 and February 2020 to the American University of Beirut Medical Center (AUBMC), a tertiary referral hospital for Lebanon and the Middle East region. The epidemiological background of these patients, their underlying risk factors, the used antibiotic regimens, and the sensitivities of the B. cepacia specimens were collected. Results The majority of the Bcc infections (26/44, 59.1%) were hospital-acquired infections. The most common nationality of the patients was Iraqi (18/44, 40.9%), and the most common site of infection was bacteremia (17/44, 38.6%), followed by skin and soft tissues infections (16/44, 36.4%) and vertebral osteomyelitis (8/44, 18.2%). Most of the isolated B. cepacia were susceptible to ceftazidime, carbapenems, followed by TMP-SMX. Patients responded well to therapy with good overall outcome. Conclusions Bcc can cause infections outside the respiratory tract, mostly as hospital-acquired infections and in immunocompromised patients. Most patients were referred from countries inflicted by wars raising the possibility of a potential role of conflicts which need to be investigated in future studies. Directed therapy according to susceptibility results proved effective in most patients.

BackgroundThe 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.MethodologyFrom 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-β-naphthylamide (PAβN)] was done.ResultsAntimicrobial 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 PAβN had a significant effect when combined with levofloxacin, and the latter regained its activity against two P. aeruginosa isolates.ConclusionThe 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.

Summary Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global threat. We therefore analysed the bacterial characteristics of CRKP infections and the clinical outcomes of patients with CRKP infections across different countries. Methods In this prospective, multicentre, cohort study (CRACKLE-2), hospitalised patients with cultures positive for CRKP were recruited from 71 hospitals in Argentina, Australia, Chile, China, Colombia, Lebanon, Singapore, and the USA. The first culture positive for CRKP was included for each unique patient. Clinical data on post-hospitalisation death and readmission were collected from health records, and whole genome sequencing was done on all isolates. The primary outcome was a desirability of outcome ranking at 30 days after the index culture, and, along with bacterial characteristics and 30-day all-cause mortality (a key secondary outcome), was compared between patients from China, South America, and the USA. The desirability of outcome ranking was adjusted for location before admission, Charlson comorbidity index, age at culture, Pitt bacteremia score, and anatomical culture source through inverse probability weighting; mortality was adjusted for the same confounders, plus region where relevant, through multivariable logistic regression. This study is registered at ClinicalTrials.gov , NCT03646227 , and is complete. Findings Between June 13, 2017, and Nov 30, 2018, 991 patients were enrolled, of whom 502 (51%) met the criteria for CRKP infection and 489 (49%) had positive cultures that were considered colonisation. We observed little intra-country genetic variation in CRKP. Infected patients from the USA were more acutely ill than were patients from China or South America (median Pitt bacteremia score 3 [IQR 2–6] vs 2 [0–4] vs 2 [0–4]) and had more comorbidities (median Charlson comorbidity index 3 [IQR 2–5] vs 1 [0–3] vs 1 [0–2]). Adjusted desirability of outcome ranking outcomes were similar in infected patients from China (n=246), South America (n=109), and the USA (n=130); the estimates were 53% (95% CI 42–65) for China versus South America, 50% (41–61) for the USA versus China, and 53% (41–66) for the USA versus South America. In patients with CRKP infections, unadjusted 30-day mortality was lower in China (12%, 95% CI 8–16; 29 of 246) than in the USA (23%, 16–30; 30 of 130) and South America (28%, 20–37; 31 of 109). Adjusted 30-day all-cause mortality was higher in South America than in China (adjusted odds ratio [aOR] 4·82, 95% CI 2·22–10·50) and the USA (aOR 3·34, 1·50–7·47), with the mortality difference between the USA and China no longer being significant (aOR 1·44, 0·70–2·96). Interpretation Global CRKP epidemics have important regional differences in patients’ baseline characteristics and clinical outcomes, and in bacterial characteristics. Research findings from one region might not be generalisable to other regions. Funding The National Institutes of Health.

Contains fulltext : 293869.pdf (Publisher’s version ) (Open Access) Antimicrobial resistance (AMR) has been exacerbated by the inappropriate use of diagnostics, leading to excessive prescription of antimicrobials, and is an imminent threat to global health. Diagnostic stewardship (DS) is an auxiliary to antimicrobial stewardship (AMS) and comprises ordering the right tests, for the right patient, at the right time. It also promotes the judicious use of rapid and novel molecular diagnostic tools to enable the initiation of proper antibiotic therapy, while avoiding excessive use of broad-spectrum antibiotics. Proper interpretation of test results is crucial to avoid overdiagnosis and excessive healthcare costs. Although many rapid diagnostic tools have been developed with a high diagnostic yield, they are often limited by accessibility, cost, and lack of knowledge regarding their use. Careful consideration of clinical signs and symptoms with knowledge of the local epidemiology are essential for DS. This enables appropriate interpretation of microbiological results. Multidisciplinary teams that include well trained professionals should cooperate to promote DS. Challenges and barriers to the implementation of DS are mostly caused by scarcity of resources and lack of trained personnel and, most importantly, lack of knowledge. The lack of resources is often due to absence of awareness of the impact that good medical microbiology diagnostic facilities and expertise can have on the proper use of antibiotics. 01 juli 2023

Objective: Rates of ventilator-associated pneumonia (VAP) in low- and middle-income countries (LMIC) are several times above those of high-income countries. The objective of this study was to identify risk factors (RFs) for VAP cases in ICUs of LMICs. Design: Prospective cohort study. Setting: This study was conducted across 743 ICUs of 282 hospitals in 144 cities in 42 Asian, African, European, Latin American, and Middle Eastern countries. Participants: The study included patients admitted to ICUs across 24 years. Results: In total, 289,643 patients were followed during 1,951,405 patient days and acquired 8,236 VAPs. We analyzed 10 independent variables. Multiple logistic regression identified the following independent VAP RFs: male sex (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.16–1.28; P < .0001); longer length of stay (LOS), which increased the risk 7% per day (aOR, 1.07; 95% CI, 1.07–1.08; P < .0001); mechanical ventilation (MV) utilization ratio (aOR, 1.27; 95% CI, 1.23–1.31; P < .0001); continuous positive airway pressure (CPAP), which was associated with the highest risk (aOR, 13.38; 95% CI, 11.57–15.48; P < .0001); tracheostomy connected to a MV, which was associated with the next-highest risk (aOR, 8.31; 95% CI, 7.21–9.58; P < .0001); endotracheal tube connected to a MV (aOR, 6.76; 95% CI, 6.34–7.21; P < .0001); surgical hospitalization (aOR, 1.23; 95% CI, 1.17–1.29; P < .0001); admission to a public hospital (aOR, 1.59; 95% CI, 1.35-1.86; P < .0001); middle-income country (aOR, 1.22; 95% CI, 15–1.29; P < .0001); admission to an adult-oncology ICU, which was associated with the highest risk (aOR, 4.05; 95% CI, 3.22–5.09; P < .0001), admission to a neurologic ICU, which was associated with the next-highest risk (aOR, 2.48; 95% CI, 1.78–3.45; P < .0001); and admission to a respiratory ICU (aOR, 2.35; 95% CI, 1.79–3.07; P < .0001). Admission to a coronary ICU showed the lowest risk (aOR, 0.63; 95% CI, 0.51–0.77; P < .0001). Conclusions: Some identified VAP RFs are unlikely to change: sex, hospitalization type, ICU type, facility ownership, and country income level. Based on our results, we recommend focusing on strategies to reduce LOS, to reduce the MV utilization ratio, to limit CPAP use and implementing a set of evidence-based VAP prevention recommendations.

Purpose of review Staphylococcus aureus is a pathogen incriminated in skin and soft tissue infections (SSTIs), with methicillin-resistant S. aureus (MRSA) becoming the predominant cause and representing a significant burden to the healthcare system. The last updated Infectious Diseases Society of America (IDSA) guidelines concerning MRSA infections and SSTIs management were published in 2011 and 2014, respectively. The UK updated guidelines for MRSA infection treatment were published in 2021. Older treatment options may be associated with toxicity and require frequent dosing. There is a paucity of recent reviews on the armamentarium of new agents for MRSA SSTIs treatment. Recent findings Since 2005, several new antibiotics received a fast-track approval by the Food and Drug Administration (FDA) for SSTI treatment. These drugs include delafloxacin, omadacycline, tedizolid, ceftaroline, dalbavancin, oritavancin and telavancin. In this manuscript, we will review the data that led to these new drugs approval and discuss their advantages and disadvantages in MRSA SSTIs management. Summary MRSA is a major cause of SSTIs. Several novel therapies covering MRSA were FDA-approved for SSTIs. However, the current IDSA guidelines for MRSA infection and SSTIs as well as the recently published UK guidelines on MRSA treatment only consider these drugs as alternative choices or do not mention them at all.

Strategic and standardised approaches to analysis and reporting of surveillance data are essential to inform antimicrobial resistance (AMR) mitigation measures, including antibiotic policies. Targeted guidance on linking full-scale AMR and antimicrobial consumption (AMC)/antimicrobial residues (AR) surveillance data from the human, animal, and environmental sectors is currently needed. This paper describes the initiative whereby a multidisciplinary panel of experts (56 from 20 countries—52 high income, 4 upper middle or lower income), representing all three sectors, elaborated proposals for structuring and reporting full-scale AMR and AMC/AR surveillance data across the three sectors. An evidence-supported, modified Delphi approach was adopted to reach consensus among the experts for dissemination frequency, language, and overall structure of reporting; core elements and metrics for AMC/AR data; core elements and metrics for AMR data. The recommendations can support multisectoral national and regional plans on antimicrobials policy to reduce resistance rates applying a One Health approach. [This article was written with the contribution of the One Health EJP WP5 Science to Policy Translation]

Background Carbapenemase-producing (CP) Escherichia coli (CPEc) are a global public health threat. We describe the epidemiology and outcomes of patients with CPEc isolates obtained in CRACKLE 2, a prospective cohort study of hospitalized patients with positive cultures for CP Enterobacteriaceae. Methods In CRACKLE-2, patients with CPEc were enrolled from 26 hospitals in 6 countries (ClinicalTrials.gov NCT03646227). Clinical data were collected, and bacterial isolates underwent whole genome sequencing (WGS). Here, we included unique patients with CPEc by WGS (n=114). The primary outcome was desirability of outcome ranking (DOOR) at 30 days after index culture. Chi squared tests with alpha = 0.05 were used to evaluate differences in culture source and outcomes between metallo-beta-lactamase (MBL) and non-MBL isolates. Results Of 114 CPEc isolates, 57 (50%) represented infection (Table 1). Isolates primarily arose from urine (34%) and blood (21%). Compared to non-MBL isolates, isolates containing MBL were more often from urine (41% vs 29%) and less frequently from blood (6% vs 32%); p=0.02. We observed strong regional variations in CP (Figure 1) and MBL (p < 0.0001). Sequence type (ST) 167 was more common among MBL than non-MBL isolates (31% vs 2%, p< 0.0001); non-MBL isolates were more often ST410 and ST131 (17% and 20%). Extended-spectrum beta-lactamases (ESBL) were present in 52% of isolates; most commonly, CTX-M-15 in both MBL (33%) and non-MBL isolates (34%). Phylogenetic analysis of the isolates and corresponding region, bacterial characteristics, and DOOR outcomes are in Figure 1. Death at 30 days occurred in 18 (16%) of patients, more commonly among non-MBL than MBL CPEc (23% vs 6%; p=0.01). The probability of a better DOOR outcome for a randomly selected MBL was 58% [95% CI: 48.2, 67.4], indicating no significant difference between the groups. Figure 1:Phylogenetic population structures of Carbapenemase-producing Escherichia coli (CPEc) isolates Legend: Infection = categorization as infection or colonization. ST = sequence type. BlaCarb = Carbapenemase gene. BlaESBL = acquired ESBL enzymes. DOOR = desirability of outcome ranking. DOOR rankings: 1 = Alive without events; DOOR 2 = Alive with 1 event; DOOR 3 = Alive with 2 or 3 events; DOOR 4 = dead. Conclusion Emergence of carbapenem resistance with important geographic variations was observed in E coli including among high-risk clones such as ST131. Mortality was higher among non-MBL isolates, which were more frequently from blood, but these findings may be confounded by region. Disclosures Vance G. Fowler, Jr, MD, MHS, Affinergy: Grant/Research Support|Affinergy: Honoraria|Affinium: Honoraria|Amphliphi Biosciences: Honoraria|ArcBio: Stocks/Bonds|Basilea: Grant/Research Support|Basilea: Honoraria|Bayer: Honoraria|C3J: Honoraria|Cerexa/Forest/Actavis/Allergan: Grant/Research Support|Contrafect: Grant/Research Support|Contrafect: Honoraria|Cubist/Merck: Grant/Research Support|Debiopharm: Grant/Research Support|Deep Blue: Grant/Research Support|Destiny: Honoraria|Genentech: Grant/Research Support|Genentech: Honoraria|Integrated Biotherapeutics: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|Karius: Grant/Research Support|Medicines Co.: Honoraria|MedImmune: Grant/Research Support|MedImmune: Honoraria|NIH: Grant/Research Support|Novartis: Grant/Research Support|Novartis: Honoraria|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Regeneron: Honoraria|Sepsis diagnostics: Sepsis diagnostics patent pending|UpToDate: Royalties|Valanbio: Stocks/Bonds Cesar A. Arias, MD, PhD, Entasis Phramceuticals: Grant/Research Support|MeMed Diagnostics: Grant/Research Support|Merck: Grant/Research Support David Paterson, MBBS, Accelerate: Honoraria|bioMerieux: Honoraria|Entasis: Advisor/Consultant|Janssen-Cilag: Grant/Research Support|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria|PPD: Grant/Research Support|Shionogi: Grant/Research Support|VenatoRx: Advisor/Consultant Karen M. Ordonez, MD, AstraZeneca: Expert Testimony|Biomerieux: Expert Testimony|Farma de Colombia: Expert Testimony|MSD: Expert Testimony|Pfizer: Expert Testimony Souha S. Kanj, Pr, MSD, Pfizer, Gilead, Menarini, Astellas: Advisor/Consultant|MSD, Pfizer, Gilead, Menarini, Astellas: Honoraria Robert Bonomo, MD, Cystic Fibrosis Foundation: Grant/Research Support|Merck: Grant/Research Support|NIH: Grant/Research Support|VA: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt: Grant/Research Support David van Duin, MD, PhD, Achaogen: Advisor/Consultant|Allergan: Advisor/Consultant|Astellas: Advisor/Consultant|MedImmune: Advisor/Consultant|Melinta: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|NeuMedicine: Advisor/Consultant|Pfizer: Advisor/Consultant|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Sanofi-Pasteur: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|T2 Biosystems: Advisor/Consultant|Tetraphase: Advisor/Consultant.

Background We report the results of INICC surveillance study from 2013 to 2018, in 664 intensive care units (ICUs) in 133 cities, of 45 countries, from Latin-America, Europe, Africa, Eastern-Mediterranean, Southeast-Asia, and Western-Pacific. Methods Prospective data from patients hospitalized in ICUs were collected through INICC Surveillance Online System. CDC-NHSN definitions for device-associated healthcare-associated infection (DA-HAI) were applied. Results We collected data from 428,847 patients, for an aggregate of 2,815,402 bed-days, 1,468,216 central line (CL)-days, 1,053,330 mechanical ventilator (MV)-days, 1,740,776 urinary catheter (UC)-days. We found 7,785 CL-associated bloodstream infections (CLAB), 12,085 ventilator-associated events (VAE), and 5,509 UC-associated urinary tract infections (CAUTI). Pooled DA-HAI rates were 5.91% and 9.01 DA-HAIs/1,000 bed-days. Pooled CLAB rate was 5.30/1,000 CL-days; VAE rate was 11.47/1,000 MV-days, and CAUTI rate was 3.16/1,000 UC-days. P aeruginosa was non-susceptible (NS) to imipenem in 52.72% of cases; to colistin in 10.38%; to ceftazidime in 50%; to ciprofloxacin in 40.28%; and to amikacin in 34.05%. Klebsiella spp was NS to imipenem in 49.16%; to ceftazidime in 78.01%; to ciprofloxacin in 66.26%; and to amikacin in 42.45%. coagulase-negative Staphylococci and S aureus were NS to oxacillin in 91.44% and 56.03%, respectively. Enterococcus spp was NS to vancomycin in 42.31% of the cases. Conclusions DA-HAI rates and bacterial resistance are high and continuous efforts are needed to reduce them.

Introduction: Fosfomycin has re-emerged as a possible therapeutic alternative for the treatment of resistant bacterial pathogens. Its main mechanism of action is the inhibition of the initial step of cell wall synthesis and is active against both Gram-positive and Gram-negative bacteria. However, its clinical effectiveness against multidrug resistant bacteria remains largely unknown. Therefore, we aim to evaluate the clinical and microbiological effectiveness of intravenous fosfomycin as well as its safety in a tertiary care teaching hospital in Lebanon. Methodology: This is a retrospective chart review of adult patients who had presented to the hospital and were treated with intravenous fosfomycin for at least 24 hours for any type of infection between 2014 and 2019. Results: Among 31 episodes treated with intravenous fosfomycin, 68% had an overall favorable clinical response. In 84% of the episodes, fosfomycin was administered in combination with other antibiotics, commonly tigecycline. Of those with available cultures at end of therapy, 73% achieved microbiological success. No relapse was documented within 30 days of completion of therapy. In the episodes secondary to resistant pathogens, the rates of favorable clinical outcome and microbiological success at the end of therapy were 71% and 73%, respectively. Fosfomycin resistance developed in two cases and mild adverse events occurred in 65% of the episodes during the course of treatment. Conclusions: Fosfomycin is a safe and effective option in the treatment of multi-drug resistant infections. Nevertheless, careful stewardship is important to maintain its efficacy and to reduce the risk of selection of antimicrobial resistance.

Campylobacter fetus is a rare pathogen in humans. It mainly causes invasive infections in immunosuppressed patients. Herein, we report the first case of cervical vertebral osteomyelitis in a previously healthy man with a history of daily alcohol consumption. Treatment was given for six weeks with excellent clinical recovery and normalization of laboratory markers.

Aim: This rapid systematic review aimed to collect the evidence published over the last decade on the effect of empirical antifungal therapy and its early initiation on survival rates. Methods: A systematic search was conducted in PubMed, Cochrane, Medline, Scopus, and Embase, in addition to a hand search and experts’ suggestions. Results: Fourteen cohort studies and two randomized clinical trials reporting the survival outcome of empirical antifungal therapy were included in this review. Two studies reported the association between early empirical antifungal therapy (EAFT) and survival rates in a hematological cancer setting, and fourteen studies reported the outcome in patients in intensive care units (ICU). Six studies reported that appropriate EAFT decreases hospital mortality significantly; ten studies could not demonstrate a statistically significant association with mortality rates. Discussion: The inconsistency of the results in the literature can be attributed to the studies’ small sample size and their heterogeneity. Many patients who may potentially benefit from such strategies were excluded from these studies. Conclusion: While EAFT is practiced in many settings, current evidence is conflicting, and high-quality studies are needed to demonstrate the true value of this approach. Meanwhile, insights from experts in the field can help guide clinicians to initiate EAFT when indicated.

Background: Despite multiple reports of increased incidence of bacterial respiratory tract infections following COVID-19 globally, the microbiology is not fully elucidated. In this study, we describe the incidence and microbiology of bacterial infections and the burden of multidrug resistant organisms (MDROs) in hospitalized COVID-19 patients with community-acquired pneumonia (CAP), non-ventilated hospital acquired pneumonia (NVHAP) or 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 center in Lebanon. Adult patients with confirmed COVID-19 who were hospitalized between March 2020 and September 2021 were included. Only pathogens isolated within 42 days of positive SARS-CoV-2 tests were included. Bacterial isolates identified in hospital-acquired pneumonia (HAP) were divided into 3 groups based on the time of acquiring 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. Overall, Gram-negative bacteria were predominant (83.5%) andS. maltophiliawas the most common pathogen (14.3%).S. aureusandHaemophilusspp. were implicated in most CAPs, whileK. pneumonia,S. maltophilia and E. coliwere the top culprits in HAP during hospital days 3-14, 15-28 and 29-42 respectively. Among 231 isolates obtained, 59 (25.5%) were MDROs, seen in higher proportion in HAP, especially among patients with prolonged hospital stay (> 4 weeks). Non-fermenter Gram-negative bacilli (NFGNB) (OR = 3.521, p-value = 0.000), particularlyS. maltophilia(OR = 3.236, p-value = 0.022), were significantly more implicated in VAP compared to NVHAP.Conclusions:COVID-19 patients hospitalized at AUBMC are at a slightly lower risk for bacterial respiratory infections compared to other studies. The pathogens varied according to the time since hospitalization. The burden of NFGNB and S.maltophiliais particularly high in COVID-19 VAP, indicating the need for further studies targeting these pathogens. A high rate of bacterial resistance was found which has important implications in guiding therapeutic decisions in COVID-19 patients who acquire bacterial infections.

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

The term difficult-to-treat resistance has been recently coined to identify Gram-negative bacteria exhibiting resistance to all fluoroquinolones and all β-lactam categories, including carbapenems. Such bacteria are posing serious challenges to clinicians trying to identify the best therapeutic option for any given patient. Delayed appropriate therapy has been associated with worse outcomes including increase in length of stay, increase in total in-hospital costs and ∼20% increase in the risk of in-hospital mortality. In addition, time to appropriate antibiotic therapy has been shown to be an independent predictor of 30 day mortality in patients with resistant organisms. Improving and anticipating aetiological diagnosis through optimizing not only the identification of phenotypic resistance to antibiotic classes/agents, but also the identification of specific resistance mechanisms, would have a major impact on reducing the frequency and duration of inappropriate early antibiotic therapy. In light of these considerations, the present paper reviews the increasing need for rapid diagnosis of bacterial infections and efficient laboratory workflows to confirm diagnoses and facilitate prompt de-escalation to targeted therapy, in line with antimicrobial stewardship principles. Rapid diagnostic tests currently available and future perspectives for their use are discussed. Early appropriate diagnostics and treatment of MDR Gram-negative infections require a multidisciplinary approach that includes multiple different diagnostic methods and further consensus of algorithms, protocols and guidelines to select the optimal antibiotic therapy.

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.

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.

International audience; Background - Infective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD). Objectives - This study sought to investigate whether there are significant differences in complications, cardiac surgery, relapses, and mortality between IE cases in HD and non-HD patients. Methods - Prospective cohort study (International Collaboration on Endocarditis databases, encompassing 7,715 IE episodes from 2000 to 2006 and from 2008 to 2012). Descriptive analysis of baseline characteristics, epidemiological and etiological features, complications and outcomes, and their comparison between HD and non-HD patients was performed. Risk factors for major embolic events, cardiac surgery, relapses, and in-hospital and 6-month mortality were investigated in HD-patients using multivariable logistic regression. Results - A total of 6,691 patients were included and 553 (8.3%) received HD. North America had a higher HD-IE proportion than the other regions. The predominant microorganism was Staphylococcus aureus (47.8%), followed by enterococci (15.4%). Both in-hospital and 6-month mortality were significantly higher in HD versus non-HD-IE patients (30.4% vs. 17% and 39.8% vs. 20.7%, respectively; p

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

BackgroundAntimicrobial surveillance and antimicrobial stewardship (AMS) are essential pillars in the fight against antimicrobial resistance (AMR), but practical guidance on how surveillance data should be linked to AMS activities is lacking. This issue is particularly complex in the hospital setting due to structural heterogeneity of hospital facilities and services. The JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks have joined efforts to formulate a set of target actions for linking surveillance data with AMS activities.MethodsA scoping review of the literature was carried out addressing research questions on three areas: (i) AMS leadership and accountability; (ii) antimicrobial usage and AMS; (iii) AMR and AMS. Consensus on the target actions was reached through a RAND-modified Delphi process involving over 40 experts in different fields from 18 countries.ResultsEvidence was retrieved from 51 documents. Initially 38 targets were proposed, differentiated as essential or desirable according to clinical relevance, feasibility and applicability to settings and resources. In the first consultation round, preliminary agreement was reached for 32 targets. Following a second consultation, 27 targets were approved, 11 were deleted and 4 were suggested for rephrasing, leading to a final approved list of 34 target actions in the form of a practical checklist.ConclusionsThis White Paper provides a pragmatic and flexible tool to guide the development of calibrated hospital-surveillance-based AMS interventions. The strength of this tool is that it is a comprehensive perspective that takes into account the hospital patient case-mix and the related epidemiology, which ultimately drives antimicrobial usage, and the feasibility in low-resource settings.

Background The outpatient setting is a key scenario for the implementation of antimicrobial stewardship (AMS) activities, considering that overconsumption of antibiotics occurs mainly outside hospitals. This publication is the result of a joint initiative by the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks, which is aimed at formulating a set of target actions for linking surveillance data with AMS activities in the outpatient setting. Methods A scoping review of the literature was carried out in three research areas: AMS leadership and accountability; antimicrobial usage and AMS; antimicrobial resistance and AMS. Consensus on the actions was reached through a RAND-modified Delphi process involving over 40 experts in infectious diseases, clinical microbiology, AMS, veterinary medicine or public health, from 18 low-, middle- and high-income countries. Results Evidence was retrieved from 38 documents, and an initial 25 target actions were proposed, differentiating between essential or desirable targets according to clinical relevance, feasibility and applicability to settings and resources. In the first consultation round, preliminary agreement was reached for all targets. Further to a second review, 6 statements were re-considered and 3 were deleted, leading to a final list of 22 target actions in the form of a practical checklist. Conclusions This White Paper is a pragmatic and flexible tool to guide the development of calibrated surveillance-based AMS interventions specific to the outpatient setting, which is characterized by substantial inter- and intra-country variability in the organization of healthcare structures, maintaining a global perspective and taking into account the feasibility of the target actions in low-resource settings.

Many healthcare centers around the world have reported the surge of

PurposeThe use of carbapenem before and after implementation of an antimicrobial stewardship-led carbapenem-sparing strategy at a tertiary care center in Lebanon was evaluated.MethodsA retrospective, observational chart review was performed on all hospitalized pediatric and adult patients who received carbapenem therapy during January 2019 and January 2020. Patients who started their regimen before January or received carbapenems for less than 24 hours were excluded. Primary outcomes included the appropriateness of physician prescribing patterns and pharmacists’ interventions, as well as appropriateness and response rates of the latter. Secondary outcomes included the carbapenem defined daily dose (DDD) and days of therapy (DOT). Descriptive statistics were used in the analysis and a p-value < 0.05 was considered to be statistically significant.ResultsA total of 157 and 150 patients charts were reviewed in January 2019 and January 2020, respectively. There was no difference in baseline characteristics except for inpatient services and rates of isolated multidrug-resistant organisms. When comparing the two timelines, the appropriateness of physicians’ prescribing patterns increased in terms of empirical therapy, targeted therapy, and duration of therapy but the results were not statistically significant. Pharmacists’ interventions significantly increased with regards to the duration of therapy (p= ConclusionThe carbapenem-sparing strategy adopted by the antimicrobial stewardship program contributed to an increase in the number of interventions made by pharmacists on carbapenem therapy, including their appropriateness, and response rate. Despite an improvement in the physician-prescribing patterns, more awareness and education may be needed to achieve a better impact.

To assess the effect of combination antibiotic empirical therapy on 30-day case-fatality rate in neutropenic cancer patients with

Invasive candidiasis (IC) has become a serious problem in the intensive care unit patients with an attributable mortality rate that can reach up to 51%. Multiple global surveillance studies have shown an increasing incidence of candidemia. Despite their limited sensitivity (21–71%), cultures remain the gold standard for the diagnosis of IC associated with candidemia. Many adjunct laboratory tests exist to support or rule out the diagnosis, each with its indications and limitations, including procalcitonin, 1,3-β-D-glucan, mannan and anti-mannan antibodies, and Candida albicans germ tube antibody. In addition, polymerase chain reaction-based methods could expedite species identification in positive blood cultures, helping in guiding early empirical antifungal therapy. The management of IC in critically ill patients can be classified into prophylactic, preemptive, empiric, and directed/targeted therapy of a documented infection. There is no consensus concerning the benefit of prophylactic therapy in critically ill patients. While early initiation of appropriate therapy in confirmed IC is an important determinant of survival, the selection of candidates and drug of choice for empirical systemic antifungal therapy is more controversial. The choice of antifungal agents is determined by many factors, including the host, the site of infection, the species of the isolated Candida, and its susceptibility profile. Echinocandins are considered initial first-line therapy agents. Due to the conflicting results of the various studies on the benefit of preemptive therapy for critically ill patients and the lack of robust evidence, the Infectious Diseases Society of America (IDSA) omitted this category from its updated guidelines and the European Society of Intensive Care Medicine (ESICM) and the Critically Ill Patients Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) do not recommend it.

Purpose of review Pseudomonas aeruginosa is one of the most feared nosocomial pathogens. Treatment of P. aeruginosa infections is challenging because of the limited choices of antibiotics and the emergent resistance of the pathogen. The present review aims at addressing the management of P. aeruginosa infections and highlighting the novel antibiotics that show a future promising role. Recent findings Novel fluoroquinolones have been recently introduced and show favorable activity. New combinations of β-lactams/β-lactamase inhibitors have been studied in various indications of infections because of P. aeruginosa. Cefiderocol, a new cephalosporin, shows very promising results against P. aeruginosa. Currently, combination therapy is only recommended in limited scenarios. Extended-infusion of β-lactams exhibit clinical benefit. Bacteriophage therapy is a growing field of interest and may have an impactful effect on the treatment of resistant P. aeruginosa. Summary Factors that guide clinical decisions for empiric and directed P. aeruginosa therapy include the epidemiology, the patient's risk factors, the site of infection, and the available treatment options. Conventional antipseudomonal antibiotics have been used successfully for a long time, but the increase in worldwide resistance necessitates the need for newer agents. Antimicrobial stewardship is essential to preserve the new drugs and prevent future development of resistance.

Background Influenza is a major cause of morbidity and mortality worldwide. Following the 2009 pandemic, there was widened interest in studying influenza burden in all regions. However, since data from the World Health Organization (WHO) Middle East and North Africa (MENA) region remain limited, we aimed to contribute to the understanding of influenza burden in Lebanon. Methods A retrospective chart review extending over a period of 8 seasons from Jan 1st, 2008 till June 30th, 2016 at a tertiary care center in Beirut was performed. All cases confirmed to have influenza based on rapid antigen detection or/and polymerase chain reaction on a respiratory sample were included for analysis. Data on epidemiology, clinical presentation, complications, antiviral use and mortality were collected for analysis. Results A total of 1829 cases of laboratory-confirmed influenza were identified. Average annual positivity rate was 14% (positive tests over total requested). Both influenza A and B co-circulated in each season with predominance of influenza A. Influenza virus started circulating in December and peaked in January and February. The age group of 19–50 years accounted for the largest proportion of cases (22.5%) followed by the age group of 5–19 years (18%). Pneumonia was the most common complication reported in 33% of cases. Mortality reached 3.8%. The two extremes of age ( Conclusion Patients with laboratory-confirmed influenza at our center had a high rate of hospitalization and mortality. A population based prospective surveillance study is needed to better estimate the burden of Influenza in Lebanon that would help formulate a policy on influenza control.

Purpose of review The increase in skin and soft tissue infections (SSTI) because of multidrug-resistant (MDR) pathogens is a global concern. Although MDR Gram-negative bacteria (GNB) are often overlooked as a cause of SSTIs, their burden on the morbidity of many subgroups of patients is high. There is a paucity in the available treatment options and guidelines on how to treat these pathogens. This manuscript reviews the management of SSTIs caused by carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa (CRPA), Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia. We also highlight a few novel antibiotics that show promise in the future management of MDR-GNB SSTIs. Recent findings Studies on treatment options of MDR-GNB SSTIs are scarce. Most clinical trials investigating new antibiotics have addressed conditions such as complicated intraabdominal infections, complicated urinary infections, and respiratory infections. CREs are a heterogenous group of pathogens with various mechanisms of resistance dictating susceptibility to different antimicrobial agents. Ceftazidime--avibactam, and meropenem--vaborbactam have potent activity against some of the CREs, especially Klebsiella pneumoniae carbapenemase (KPC) producers. Several novel antibiotics have potent activity against CRPA SSTIs, such as ceftazidime--avibactam, ceftolozane--tazobactam, cefiderocol, delafloxacin, finafloxacin, and murepavadin. Cefiderocol may also play an important role in the management of CRAB SSTIs, along with plazomicin and eravacycline. Summary MDR-GNB play a major role in SSTIs in patients with underlying immunodeficiency, as well as burn or trauma-related injuries. With the alarming global rise in MDR-GNB resistance, antibiotic therapy for SSTIs is challenging and must be guided by in-vitro susceptibility results. Currently, data extrapolated from other indications and combination therapy can be used empirically pending microbiological data and susceptibilities. Novel antibiotics are currently under development. It is hoped that future clinical trials will be designed to address MDR-GNB SSTIs.

Multidrug-resistant (MDR) Gram-negative bacteria (GNB) pose a critical threat to global healthcare, worsening outcomes and increasing mortality among infected patients. Carbapenemase- and extended-spectrum β-lactamase-producing Enterobacterales, as well as carbapenemase-producing Pseudomonas and Acinetobacter spp., are common MDR pathogens. New antibiotics and combinations have been developed to address this threat. Clinical trial findings support several combinations, notably ceftazidime-avibactam (CZA, a cephalosporin-β-lactamase inhibitor combination), which is effective in treating complicated urinary tract infections (cUTI), complicated intra-abdominal infections and hospital-acquired and ventilator-associated pneumonia caused by GNBs. Other clinically effective combinations include meropenem-vaborbactam (MVB), ceftolozane-tazobactam (C/T) and imipenem-relebactam (I-R). Cefiderocol is a recent siderophore β-lactam antibiotic that is useful against cUTIs caused by carbapenem-resistant Enterobacterales (CRE) and is stable against many β-lactamases. Carbapenem-resistant Enterobacterales are a genetically heterogeneous group that vary in different world regions and are a substantial cause of infections, among which Klebsiella pneumoniae are the most common. Susceptible CRE infections can be treated with fluoroquinolones, aminoglycosides or fosfomycin, but alternatives include CZA, MVB, I-R, cefiderocol, tigecycline and eravacycline. Multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa are increasingly common pathogens producing a range of different carbapenemases, and infections are challenging to treat, often requiring novel antibiotics or combinations. Currently, no single agent can treat all MDR-GNB infections, but new β-lactam-β-lactamase inhibitor combinations are often effective for different infection sites and, when used appropriately, have the potential to improve outcomes. This article reviews clinical studies investigating novel β-lactam approaches for treatment of MDR-GNB infections.