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.

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.

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.

Epidemiology of common resistant bacterial pathogens in the countries of the Arab League.

No uniformly organised collection of data regarding antimicrobial resistance has occurred in the countries of the Arab League. 19 countries of the Arab League have published data for antimicrobial susceptibility for the WHO priority organisms, and seven of 14 of these organisms are included in this Review (Escherichia coli, Klebsiella spp, Pseudomonas aeruginosa, Acinetobacter baumannii, Salmonella spp, Staphylococcus aureus, and Streptococcus pneumoniae). Although E coli and Klebsiella spp resistance to third-generation cephalosporins is common in all countries, with prevalence reaching more than 50% in Egypt and Syria, carbapenem resistance is emerging, albeit with a prevalence of less than 10%. Conversely, a large amount of carbapenem resistance has been reported for P aeruginosa and A baumannii across the Arab League, reaching 50% and 88% of isolates in some countries. As for Salmonella spp, the prevalence of fluoroquinolone resistance has exceeded 30% in several areas. With regards to the Gram-positive pathogens, the prevalence of meticillin resistance in S aureus is reported to be between 20% and 30% in most countries, but exceeds 60% in Egypt and Iraq. The prevalence of penicillin non-susceptibility among pneumococci has reached more than 20% in Algeria, Egypt, Morocco, Saudi Arabia, and Tunisia. These findings highlight the need for structured national plans in the region to target infection prevention and antimicrobial stewardship.

Low rate of human papillomavirus vaccination among schoolgirls in Lebanon: barriers to vaccination with a focus on mothers' knowledge about available vaccines.

BACKGROUND: Human papillomavirus (HPV) infection is an established predisposing factor of cervical cancer. In this study, we assessed the awareness about genital warts, cervical cancer, and HPV vaccine among mothers having girls who are at the age of primary HPV vaccination attending a group of schools in Lebanon. We also assessed the rate of HPV vaccination among these girls and the barriers to vaccination in this community. SUBJECTS AND METHODS: This is a cross-sectional, school-based survey. A 23-item, self-administered, anonymous, pretested, structured questionnaire with closed-ended questions was used to obtain data. The questionnaire was sent to the mothers through their student girls, and they were asked to return it within a week. Data were analyzed using the Statistical Package for Social Sciences version 21.0. Bivariate analysis was performed using the chi-square test to compare categorical variables, whereas continuous variables were compared using the Student's t-test. Fisher's exact test was used when chi-square test could not be employed. RESULTS: The response rate in our survey was 39.4%. Among the responders, the rate of awareness about HPV infection was 34%, where 72% of the mothers had heard about cervical cancer, and 34% knew that a vaccine is available to prevent cervical cancer. HPV vaccination uptake rate was 2.5%. This lack of vaccination was primarily attributed to the low rate of mothers' awareness about the vaccine (34%). Factors significantly affecting awareness about the vaccine were the mothers' marital age, nationality, level of education, employment, and family income. Barriers to HPV vaccination, other than awareness, were uncertainty about safety or efficacy of the vaccine, conservative ideas of mothers regarding their girls' future sexual life, and relatively high price of the vaccine. CONCLUSION: Vaccine uptake is low among eligible girls attending this group of schools. The barriers to vaccination are multiple; the most important one is the mothers' lack of knowledge about HPV, cervical cancer, and the modes of prevention. Awareness campaigns along with a multimodal strategy that targets the identified barriers would be recommended to achieve higher rates of HPV vaccination.

An antibiotic stewardship exercise in the ICU: building a treatment algorithm for the management of ventilator-associated pneumonia based on local epidemiology and the 2016 Infectious Diseases Society of America/American Thoracic Society guidelines.

INTRODUCTION: Management of ventilator-associated pneumonia (VAP), the most common infection in patients on mechanical ventilation, should be tailored to local microbiological data. The aim of this study was to determine susceptibility patterns of organisms causing VAP to develop a treatment algorithm based on these findings and evidence from the literature. MATERIALS AND METHODS: This is a retrospective analysis of the microbiological etiology of VAP in the intensive care unit (ICU) of a Lebanese tertiary care hospital from July 2015 to July 2016. We reviewed the latest clinical practice guidelines on VAP and tried to adapt these recommendations to our setting. RESULTS: In all, 43 patients with 61 VAP episodes were identified, and 75 bacterial isolates caused VAP. Extensively drug-resistant (XDR) Acinetobacter baumannii was the most common organism (37%), and it had occurred endemically throughout the year. Pseudomonas aeruginosa was the next most common organism (31%), and 13% were XDR. Enterobacteriaceae (15%) and Stenotrophomonas maltophilia (12%) shared similar incidences. Our algorithm was based on guidelines, in addition to trials, systematic reviews, and meta-analyses that studied the effectiveness of available antibiotics in treating VAP. CONCLUSION: Knowing that resistance can rapidly develop within a practice environment, more research is needed to identify the best strategy for the management of VAP.

Prescription Patterns for Tigecycline in Severely Ill Patients for Non-FDA Approved Indications in a Developing Country: A Compromised Outcome.

Introduction: With the rise in antibiotic resistance, tigecycline has been used frequently in off-label indications, based on its in-vitro activity against multidrug-resistant organisms. In this study, our aim was to assess its use in approved and unapproved indications. Materials and Methods: This is a retrospective chart review evaluating a 2-year experience of tigecycline use for > 72 h in 153 adult patients inside and outside critical care unit from January 2012 to December 2013 in a Lebanese tertiary-care hospital. Results: Tigecycline was mostly used in off-label indications (81%) and prescribed inside the critical care area, where the number of tigecycline cycles was 16/1,000 patient days. Clinical success was achieved in 43.4% of the patients. In the critically ill group, it was significantly higher in patients with a SOFA score <7 using multivariate analysis (Odds Ratio (OR) = 12.51 [4.29-36.51], P < 0.0001). Microbiological success was achieved in 43.3% of patients. Yet, the univariate and adjusted multivariate models failed to show a significant difference in this outcome between patients inside vs. outside critical care area, those with SOFA score <7 vs. ≥ 7, and in FDA-approved vs. off-label indications. Total mortality reached ~45%. It was significantly higher in critically ill patients with SOFA score ≥7 (OR = 5.17 [2.43-11.01], P < 0.0001) and in off-label indications (OR = 4.00 [1.30-12.31], P = 0.01) using an adjusted multivariate model. Gram-negative bacteria represented the majority of the clinical isolates (81%) and Acinetobacter baumannii predominated (28%). Carbapenem resistance was present in 85% of the recovered Acinetobacter, yet, more than two third of the carbapenem-resistant Acinetobacter species were still susceptible to tigecycline. Conclusion: In our series, tigecycline has been mostly used in off-label indications, specifically in severely ill patients. The outcome of such infections was not inferior to that of FDA-approved indications, especially inside critical care area. The use of this last resort antibiotic in complicated clinical scenarios with baseline microbiological epidemiology predominated by extensively-drug resistant pathogens ought to be organized.

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.