Characterization of blaNDM-19-producing IncX3 plasmid isolated from carbapenem-resistant Escherichia coli and Klebsiellapneumoniae.

The increase in the prevalence of carbapenem-producing Enterobacterales (CPE) is a major threat, with the New Delhi metallo-ß-lactamase (NDM) enzyme-producing CPEs being one of the major causative agents of healthcare settings infections. In this study, we characterized an IncX3 plasmid harboring blaNDM-19 in Lebanon, recovered from three Escherichia coli belonging to ST167 and one Klebsiella pneumoniae belonging to ST16 isolated from a clinical setting. Plasmid analysis using PBRT, Plasmid Finder, and PlasmidSPAdes showed that all four isolates carried a conjugative 47-kb plasmid having blaNDM-19, and was designated as pLAU-NDM19. We constructed a sequence-based maximum likelihood phylogenetic tree and compared pLAU-NDM19 to other representative IncX3 plasmids carrying NDM-variants and showed that it was closely linked to NDM-19 positive IncX3 plasmid from K. pneumoniae reported in China. Our findings also revealed the route mediating resistance transmission, the IncX3 dissemination among Enterobacterales, and the NDM-19 genetic environment. We showed that mobile elements contributed to the variability of IncX3 genomic environment and highlighted that clonal dissemination in healthcare settings facilitated the spread of resistance determinants. Antimicrobial stewardship programs implemented in hospitals should be coupled with genomic surveillance to better understand the mechanisms mediating the mobilization of resistance determinants among nosocomial pathogens and their subsequent clonal dissemination.

Phenotypic and molecular characterization of multi-drug resistant Klebsiella spp. isolates recovered from clinical settings.

Klebsiella pneumoniae is a Gram-negative bacterium that colonizes the gastrointestinal tract and nasopharynx with many being linked to nosocomial infections. Extended-spectrum ß-lactamases (ESBL)-producing and carbapenem-resistant K. pneumoniae is recognized by the World Health Organization (WHO) as a critical public health concern. In this study, whole-genome sequencing (WGS) - based analysis was performed to understand the molecular epidemiology of multi-drug resistant Klebsiella spp. clinical isolates. Genome comparison, multi-locus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and whole-genome-SNP-based phylogenetic analysis (wg-SNP) were used for in-depth molecular characterization. in silico typing was used to determine the resistance genes, virulence factors, Inc. groups, and capsular types. All except one isolate were non-susceptible to meropenem and 89% were non-susceptible to ertapenem and imipenem. blaNDM, blaOXA-48, and blaKPC were the detected carbapenemases with blaNDM-1 found in half of the sequenced genomes. Resistance to colistin was detected in one isolate and was linked to several genetic alterations in crrB, pmrB, and pmrC genes. The most common plasmid type was IncFIB followed by IncR, and the Type 3 fimbriae, encoded by the mrkABCDF operon, was conserved among all isolates. The most common sequence- (ST) and K-type detected were ST147 and K64. The prevelance and the genomic relatedness of ST147 isolates, as shown by the data from SNP-based phylogenetic analysis, PFGE, and genomic clustering, may be an outbreak marker. However, this can only be validated through a more comprehensive study encompassing a wider sampling scheme and over an extended timeframe.

Enhancing enteric pathogen detection: implementation and impact of multiplex PCR for improved diagnosis and surveillance.

BACKGROUND: Syndromic surveillance of acute gastroenteritis plays a significant role in the diagnosis and management of gastrointestinal infections that are responsible for a substantial number of deaths globally, especially in developing countries. In Lebanon, there is a lack of national surveillance for acute gastroenteritis, and limited data exists regarding the prevalence of pathogens causing diarrhea. The one-year study aims to investigate the epidemiology of common gastrointestinal pathogens and compare our findings with causative agents of diarrhea reported by our study collaborative centers. METHODS: A multicenter, cross-sectional study was conducted over a one-year period. A total of 271 samples were obtained from outpatients and inpatients presenting with symptoms of acute gastroenteritis at various healthcare facilities. The samples were then analyzed using Allplex gastrointestinal assay that identifies a panel of enteric pathogens. RESULTS: Overall, enteropathogens were detected in 71% of the enrolled cases, 46% of those were identified in patients as single and 54% as mixed infections. Bacteria were observed in 48%, parasites in 12% and viruses in 11%. Bacterial infections were the most prevalent in all age groups. Enteroaggregative E. coli (26.5%), Enterotoxigenic E. coli (23.2%) and Enteropathogenic E. coli (20.3%) were the most frequently identified followed by Blastocystis hominis (15.5%) and Rotavirus (7.7%). Highest hospitalization rate occurred with rotavirus (63%), Enterotoxigenic E. coli (50%), Blastocystis hominis (45%) and Enteropathogenic E. coli (43%). Enteric pathogens were prevalent during summer, fall and winter seasons. CONCLUSIONS: The adoption of multiplex real-time PCR assays in the diagnosis of gastrointestinal infections has identified gaps and improved the rates of detection for multiple pathogens. Our findings highlight the importance of conducting comprehensive surveillance to monitor enteric infections. The implementation of a syndromic testing panel can therefore provide healthcare professionals with timely and accurate information for more effective treatment and public health interventions.

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.

Carbapenem resistance determinants and their transmissibility among clinically isolated Enterobacterales in Lebanon.

BACKGROUND: The occurrence of carbapenem-resistant bacterial infections has increased significantly over the years with Gram-negative bacteria exhibiting the broadest resistance range. In this study we aimed to investigate the genomic characteristics of clinical carbapenem-resistant Enterobacterales (CRE). METHODS: Seventeen representative multi-drug resistant (MDR) isolates from a hospital setting showing high level of resistance to carbapenems (ertapenem, meropenem and imipenem) were chosen for further characterization through whole-genome sequencing. Resistance mechanisms and transferability of plasmids carrying carbapenemase-encoding genes were also determined in silico and through conjugative mating assays. RESULTS: We detected 18 different ß-lactamases, including four carbapenemases (blaNDM-1, blaNDM-5, blaNDM-7, blaOXA-48) on plasmids with different Inc groups. The combined results from PBRT and in silico replicon typing revealed 20 different replicons linked to plasmids ranging in size between 80 and 200 kb. The most prevalent Inc groups were IncFIB(K) and IncM. OXA-48, detected on 76-kb IncM1 conjugable plasmid, was the most common carbapenemase. We also detected other conjugative plasmids with different carbapenemases confirming the role of horizontal gene transfer in the dissemination of antimicrobial resistance genes. CONCLUSION: Our findings verified the continuing spread of carbapenemases in Enterobacterales and revealed the types of mobile elements circulating in a hospital setting and contributing to the spread of resistance determinants. The occurrence and transmission of plasmids carrying carbapenemase-encoding genes call for strengthening active surveillance and prevention efforts to control antimicrobial resistance dissemination in healthcare settings.

Whole-genome sequence analysis of carbapenem-resistant Enterobacteriaceae recovered from hospitalized patients.

OBJECTIVES: Carbapenems are among the few effective antibiotics against multidrug-resistant Enterobacteriaceae. This study aimed at characterizing the plasmid content and resistome of clinical carbapenem-resistant Enterobacteriaceae (CRE) recovered from 2016 to 2019 from hospitalized patients in Lebanon. METHODS: Plasmid typing and whole-genome sequencing were used to study the genomic characteristics of 65 clinical CREs including 27 Escherichia coli, 24 Klebsiella pneumoniae, one Klebsiella quasipneumoniae, three Morganella morganii, three Citrobacter freundii, five Enterobacter hormaechei, and two Serratia marcescens. RESULTS: blaOXA-48 (33.8%; n = 22) and blaOXA-48-like genes were among the detected resistance determinants, with two isolates co-harbouring blaNDM-5. Various blaNDM variants, blaNDM-1 (16.9%; n = 11), blaNDM-5 (9.2%; n = 6), blaNDM-7 (9.2%; n = 6), and blaNDM-19 (4.6%; n = 3), different ESBLs, and AmpC ß-lactamases were detected. Carbapenem resistance determinants were linked to a variety of incompatibility groups with IncFIB(K) (43.1%; n = 28) being the most prevalent, followed by IncFIA (40.0%), IncL (35.4%), IncX3 (32.3%), IncI1 (32.3%), and IncFIIK (29.2%). CONCLUSIONS: We analysed the clonality and resistance determinants of 65 multidrug-resistant (MDR) Enterobacteriaceae recovered in the period from 2016 to 2019 from a large tertiary hospital in Lebanon. NDM variants, OXA-48, and OXA-181 were the most prevalent detected carbapenemases and were mostly linked to the dissemination of IncL, IncX3, and IncF. This study reinforces the need to track the spread and dominance of clinically relevant carbapenemase-encoding plasmids in healthcare settings.

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.

The impact of vaccination on the burden of invasive pneumococcal disease from a nationwide surveillance program in Lebanon: an unexpected increase in mortality driven by non-vaccine serotypes.

BACKGROUND: The impact of pneumococcal conjugate vaccines (PCVs) on the burden of invasive pneumococcal disease (IPD) and serotype distribution was examined across age groups from data collected by the Lebanese Inter-Hospital Pneumococcal Surveillance Program. METHODS: Between 2005 and 2020, 593 invasive Streptococcus pneumoniae isolates were collected from 79 hospitals throughout Lebanon. Serotypes and antimicrobial resistance (AMR) profiles were identified, and trends compared over 3 eras: PCV7, post-PCV7/ pre-PCV13, and PCV13 eras. RESULTS: The prevalence of PCV7 serotypes decreased significantly from 43.6% in the PCV7 era to 17.8% during the PCV13 era (p<0.001). PCV13-only serotypes remained stable in the PCV13 compared to the post-PCV7 eras, especially serotypes 1 and 3, whereas non-vaccine types (NVT) increased throughout the study period, especially 24 and 16F. The mortality rate increased substantially from 12.5% (PCV7 era) to 24.8% (PCV13 era). A significant decrease in AMR was observed across the three study eras. CONCLUSION: PCVs substantially impacted IPD and AMR in vaccinated and unvaccinated populations despite an increase in mortality driven by NVT. Broadening the recommendation of vaccination to include older age-groups, using higher valency vaccines, and implementing stringent antimicrobial stewardship are likely to further impact the burden of IPD.

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.

Epidemiology, risk factors, and prediction score of carbapenem resistance among inpatients colonized or infected with 3rd generation cephalosporin resistant Enterobacterales.

In this study, we determined the incidence and risk factors of Carbapenem-resistant Enterobacterales (CRE) acquisition in inpatients with 3rd generation cephalosporin-resistant (3GCR) Enterobacterales at a tertiary-care hospital in Lebanon, and suggested a risk prediction score for it. This is a retrospective matched case-control study of inpatients with 3GCR Enterobacterales that are carbapenem resistant (cases) versus those with carbapenem-sensitive isolates (controls). Data analysis was performed on IBM SPSS program, version 23.0 (Armonk, NY, USA: IBM Corp.). Categorical variables were compared between cases and controls through bivariate analysis and those with statistical significance (P < 0.05) were included in the forward stepwise multiple logistic regression analysis. To develop the CRE acquisition risk score, variables that maintained statistical significance in the multivariate model were assigned a point value corresponding to the odds ratio (OR) divided by the smallest OR identified in the regression model, and the resulting quotient was multiplied by two and rounded to the nearest whole number. Summation of the points generated by the calculated risk factors resulted in a quantitative score that was assigned to each patient in the database. Predictive performance was determined by assessing discrimination and calibration. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for different cutoffs of the score. The incidence of CRE acquisition significantly increased with time from 0.21 cases/1000 patient-days (PD) in 2015 to 1.89 cases/1000PD in 2019 (r2 = 0.789, P = 0.041). Multivariate analysis of matched data revealed that the history of cerebrovascular disease (OR 1.96; 95% CI 1.04-3.70; P = 0.039), hematopoietic cells transplantation (OR 7.75; 95% CI 1.52-39.36; P = 0.014), presence of a chronic wound (OR 3.38; 95% CI 1.73-6.50; P < 0.001), endoscopy done during the 3 months preceding the index hospitalization (OR 2.96; 95% CI 1.51-4.73; P = 0.01), nosocomial site of acquisition of the organism in question (OR 2.68; 95% CI 1.51-4.73; P = 0.001), and the prior use of meropenem within 3 months of CRE acquisition (OR 5.70; 95% CI 2.61-12.43; P < 0.001) were independent risk factors for CRE acquisition. A risk score ranging from 0 to 25 was developed based on these independent variables. At a cut-off of ≥ 5 points, the model exhibited a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 64.5%, 85.8%, 82%, 70.7% and 75%, respectively. We also showed that only meropenem consumption intensity and CRE acquisition incidence density showed a strong positive correlation(r = 0.798, P = 0.106), unlike imipenem (r = - 0.868, P = 0.056) and ertapenem (r = 0.385, P = 0.522). Patients with a score of ≥ 5 points in our model were likely to acquire CRE. Only meropenem was associated with CRE carriage. Our proposed risk prediction score would help target surveillance screening for CRE amongst inpatients at the time of hospital admission and properly guide clinicians on using anti-CRE therapy.

Detection and genomic characterization of mcr-9 in Enterobacter hormaechei recovered from a pediatric patient in Lebanon.

BACKGROUND: The emergence and spread of mobilized colistin resistance (mcr) genes are a global health concern. OBJECTIVES: In this study, we report the detection and genomic characterization of mcr-9 in a colistin-susceptible Enterobacter hormaechei (EH23) recovered from a pediatric patient in Lebanon. RESULTS: EH23 was susceptible to colistin with a minimal inhibitory concentration (MIC) of 0.25 mg/L. Studying the mcr-9 genetic environment revealed that it was chromosomal and was bracketed by IS903 and IS26. QseCB, a two-component regulatory system, mediating the inducible expression of mcr-9 gene was not detected within the mcr-9 cassette but elsewhere on the genome. EH23 was 99.96% similar based on average nucleotide identity (ANI) to another mcr-negative E. hormaechei OIPH-N069 isolate recovered from Japan. wgSNP-based phylogenetic analysis divided all mcr-9 positive E. hormaechei isolates into five clades (I to V), with isolates from the same ST being clustered together. CONCLUSION: The silent spread of mcr-9, particularly in the globally successful ST-78 Enterobacter lineage, is worrisome and requires close monitoring in humans and animals.

The Emergence of Invasive Streptococcus pneumoniae Serotype 24F in Lebanon: Complete Genome Sequencing Reveals High Virulence and Antimicrobial Resistance Characteristics.

BACKGROUND: Invasive pneumococcal disease (IPD) remains a global health problem. IPD incidence has significantly decreased by the use of pneumococcal conjugate vaccines (PCV). Nevertheless, non-PCV serotypes remain a matter of concern. Eight Streptococcus pneumoniae serotype 24F isolates, belonging to a non-PCV serotype, were detected through the Lebanese Inter-Hospital Pneumococcal Surveillance Program. The aim of the study is to characterize phenotypic and genomic features of the 24F isolates in Lebanon. METHODS: WGS using long reads sequencing (PacBio) was performed to produce complete circular genomes and to determine clonality, antimicrobial resistance and virulence determinants. RESULTS: The sequencing results yielded eight closed circular genomes. Three multilocus sequence typing (MLST) types were identified (ST11618, ST14184, ST15253). Both MLST and WGS analyses revealed that these isolates from Lebanon were genetically homogenous belonging to clonal complex CC230 and clustered closely with isolates originating from Canada, United States of America, United Kingdom and Iceland. Their penicillin binding protein profiles correlated with both ß-lactam susceptibility patterns and MLST types. Moreover, the isolates harbored the macrolide and tetracycline resistance genes and showed a similar virulence gene profile. To our knowledge, this study represents the first report of complete phenotypic and genomic characterization of the emerging Streptococcus pneumoniae, serotype 24F, in the Middle East and North Africa region.

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.

Difficulties in achieving a sustainable blood supply: report from the first national seminar on blood donation in Lebanon.

BACKGROUND: Lebanon has a decentralized/fragmented transfusion system. The current blood supply does not meet the World Health Organization target of achieving 100% voluntary non-remunerated blood donation (VNRD). There are currently 3 types of donors/donations in Lebanon: replacement/family donations (70-75%), VNRD (20-25%), and compensated donations (5-10%). Remunerated donations are illegal. AIMS: This report summarizes the content of presentations given during the first World Blood Donor Day seminar in Lebanon in June 2017. The aim is to describe the current Lebanese blood supply system and the major road blocks and to suggest practical recommendations that may assist in achieving 100% VNRD. METHODS: The content of presentations given during the first World Blood Donor Day seminar in Lebanon in June 2017 were summarized. RESULTS: The seminar was attended by all major stakeholders involved in transfusion medicine (Lebanese National Committee of Blood Transfusion, Hospital Blood Banks directors, Lebanese Army Blood Bank, Lebanese Red Cross and Donner Sang Compter). CONCLUSIONS: The Ministry of Public Health should focus on performing regular audits regarding the implementation of national guidelines. There is a need for a national blood supply committee, unifying all stakeholders in the transfusion and donation fields. Transfusion medicine should be declared by law as a public health issue and considered a priority for patient safety.

The effect of temporary closure and enhanced terminal disinfection using aerosolized hydrogen peroxide of an open-bay intensive care unit on the acquisition of extensively drug-resistant Acinetobacter baumannii.

BACKGROUND: At Makassed Hospital's open-bay intensive care unit (ICU), enhanced terminal disinfection (ETD) using hydrogen peroxide (H2O2) was performed without a predefined schedule in extensively-drug-resistant Acinetobacter baumannii (XDR-AB) outbreaks. In this study, we aimed to check for the value of the temporary closure of the ICU and the use of ETD with aerosolized H2O2 and Ag+ on minimizing the rate of XDR-AB acquisition in patients admitted to the ICU of our facility, which might consequently help us determine the optimal schedule for such procedure in this unit. METHODS: This is a retrospective medical file review of patients admitted to the ICU between January 2016 and May 2018. We divided this period into numerical weeks (NW) after each closure and ETD episode. Risk factors of acquisition (RFA) were determined by comparing the characteristics of patients who acquired XDR-AB to those who didn't. The proportion of patients residing in each NW was included in the RFA analysis. RESULTS: Out of 335 patients, 13% acquired XDR-AB. The overall incidence of XDR-AB acquisition was 14.6 cases/1000 patient days. RFA were XDR-AB contact pressure ≥ 3 days [Odds Ratio (OR) = 9.86, 95% Confidence Interval (CI) (3.65-26.64), P < 0.0001)], mechanical ventilation [OR = 4.99, 95%CI (1.76-14.15), P = 0.002)], and having a wound [OR = 3.72, 95%CI (0.99-13.96), P = 0.05)]. Patients who stayed during NW 7,11 and 14 were at risk of acquisition where the odds significantly increased by 6.5, 9.7 and 14.4 folds respectively (P = 0.03,0.01, and 0.01, respectively). We considered NW 7 as the most suitable time for temporary closure of the ICU and ETD with aerosolized H2O2. CONCLUSION: Contact pressure, mechanical ventilation, and presence of a wound were RFA of XDR-AB. Temporary closure of the ICU with ETD using aerosolized H2O2 decreased the rate of XDR-AB acquisition, yet this effect fades away with time. The ETD was shown to be most efficiently done when repeated every 7 calendar weeks in our open-bay ICU as part of a prevention bundle.

Effect of a "handshake" stewardship program versus a formulary restriction policy on High-End antibiotic use, expenditure, antibiotic resistance, and patient outcome.

This study reports the effect of implementing an antibiotic stewardship program (ASP) based on the "handshake" strategy for 2 years on multiple endpoints compared with that in a preceding period when an antimicrobial restriction policy was only applied in the absence of a complete program in a tertiary-care Lebanese hospital. The studied endpoints were broad-spectrum antibiotic consumption, antibiotic expenditure, nosocomial bacteremia incidence rate, and patient outcome.An interrupted time series analysis was undertaken to assess the changes in the trend (ΔT) and level (ΔL) of the aforementioned endpoints among adult inpatients before (October 2013 to September 2015) and after the introduction of the ASP (October 2016 to September 2018).After the implementation of the "handshake" ASP, marked changes were observed in the consumption of broad-spectrum antibiotics. The mean use density levels for imipenem and meropenem decreased by 13.72% (P = 0.017), coupled with a decreasing rate of prescription (ΔT = -24.83 defined daily dose [DDD]/1,000 patient days [PD]/month; P = 0.02). Tigecycline use significantly decreased in level by 69.19% (P < 0.0001) and in trend (ΔT = -25.63 DDD/1,000 PD/month; P < 0.0001). A reduction in the use of colistin was also documented but did not reach statistical significance (ΔL = -8.71%, P = 0.56; ΔT = -5.51 DDD/1,000 PD/month = -5.5; P = 0.67). Antibiotic costs decreased by 24.6% after ASP implementation (P < 0.0001), and there was a distinct change from an increasing rate to a decreasing rate of expenditure (ΔT = -12.19 US dollars/PD/month; P = 0.002). The incidence rate of nosocomial bacteremia caused by carbapenem-resistant gram-negative bacteria (CRGNB) decreased by 34.84% (P = 0.13) coupled with a decreasing trend (ΔT = -0.23 cases/1,000 PD/month, P = 0.08). Specifically, a noticeable reduction in the incidence rate of bacteremia due to carbapenem-resistant Acinetobacter baumannii was documented (ΔL = -54.34%, P = 0.01; ΔT = -0.24 cases/1000 PD/month, P = 0.01). Regarding patient outcome, all-cause mortality rates did not increase in level or in rate (ΔL = -3.55%, P = 0.59; ΔT = -0.29 deaths/1000 PD/month, P = 0.6). The length of stay and 7-day readmission rate remained stable between the two periods.In conclusion, the "handshake" ASP succeeded in controlling the prescription rates of antibiotics and in decreasing the nosocomial bacteremia rates caused by CRGNB without compromising patient outcome in our facility. It also had an economic effect in reducing antibiotic costs compared with the previous restriction policy on antimicrobial dispensing.

Molecular epidemiology and socio-demographic risk factors of sexually transmitted infections among women in Lebanon.

BACKGROUND: Sexually transmitted infections (STIs) cause a major public health problem that affect both men and women in developing and developed countries. The aim of the study was to estimate the prevalence of 11 STIs among women who voluntarily participated in the study, while seeking gynecological checkup. The existence of an association between the presence of pathogens and symptoms and various sociodemographic risk factors was assessed. METHODS: A total of 505 vaginal and cervical specimens were collected from women above 18 years of age, with or without symptoms related to gynecological infections. Nucleic acid was extracted and samples were tested by real-time PCR for the following pathogens: Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Ureaplasma urealyticum, Urealplasma parvum, Trichomonas vaginalis, Mycoplasma hominis, Mycoplasma girerdii, Gardnerella vaginalis, Candida albicans and Human Papillomavirus (HPV). Positive HPV samples underwent genotyping using a microarray system. RESULTS: Of the 505 samples, 312 (62%) were screened positive for at least one pathogen. Of these, 36% were positive for Gardnerella vaginalis, 35% for Ureaplasma parvum, 8% for Candida albicans, 6.7% for HPV, 4.6% for Ureaplasma urealyticum, 3.6% for Mycoplasma hominis, 2% for Trichomonas vaginalis, 0.8% for Chlamydia trachomatis, 0.4% for Mycoplasma girerdii, 0.2% for Mycoplasma genitalium and 0.2% for Neisseria gonorrhoeae. Lack of symptoms was reported in 187 women (37%), among whom 61% were infected. Thirty-four samples were HPV positive, with 17 high risk HPV genotypes (HR-HPV); the highest rates being recorded for types 16 (38%), 18 (21%) and 51 (18%). Out of the 34 HPV positives, 29 participants had HR-HPV. Association with various risk factors were reported. CONCLUSIONS: This is the first study that presents data about the presence of STIs among women in Lebanon and the MENA region by simultaneous detection of 11 pathogens. In the absence of systematic STI surveillance in Lebanon, concurrent screening for HPV and PAP smear is warranted.

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.

Epidemiology of invasive and non-invasive pneumococcal infections in hospitalised adult patients in a Lebanese medical centre, 2006-2015.

This is a retrospective medical file review of adult inpatients with Streptococcus pneumoniae infections admitted to a Lebanese hospital between 2006 and 2015. We revisited the clinical scenarios of these infections in view of increasing antibiotic resistance in Lebanon. One hundred and three patients were included; 92% were eligible for pneumococcal vaccination, yet none were vaccinated. Non-invasive pneumococcal disease (non-IPD) represented 64% of these infections. Superinfections caused by antibiotic-resistant bacteria were documented in 17.5% of the patients, with the predominance of ventilator-associated pneumonia (12.6%). Kidney disease and septic shock were positive predictors for mortality [adjusted odds ratio (OR) = 14.96, 95% confidence interval (CI) 2.34-95.45, P = 0.004; OR = 5.09, 95% CI 1.33-19.51, P = 0.02, respectively]. Herein, the differences in clinical success, S. pneumoniae infection-related death, and total mortality were not statistically significant between invasive pneumococcal disease (IPD) and non-IPD subgroups (59.5% vs. 77.3%, P = 0.056; 21.6% vs. 9.1%, P = 0.08; and 35.1% vs. 22.7%, P = 0.174; respectively). Upon comparing antibiotic susceptibility of S. pneumoniae during the first two years of the study (2006-2007) (n = 32 isolates) and the last two (2014-2015) (n = 14 isolates), there was an increasing non-susceptibility to penicillin (34.4%-50.0%, P = 0.25), and a decreasing susceptibility to erythromycin and clindamycin (81.3%-78.6%, P = 0.67 and 90.6%-85.7%, P = 0.65; respectively).

A compilation of antimicrobial susceptibility data from a network of 13 Lebanese hospitals reflecting the national situation during 2015-2016.

Background: There is a lack of official national antimicrobial resistance (AMR) data in Lebanon. Individual hospitals generate their own antibiotic susceptibility data in the form of yearly pamphlets. Methods: In this study, antibiotic susceptibility data from 13 hospitals distributed across different governorates of Lebanon were collected to conduct a compilation-based surveillance of AMR in Lebanon for the years 2015-2016. The findings were compared with those of a previous nationwide study in this country conducted between 2011 and 2013 as well as with similar data obtained from the 2015 and 2016 European surveillance reports of AMR. To provide a clear presentation of the AMR situation, mean percent susceptibility of different antibiotic-microbe combinations was calculated. Results: During 2015-2016, the percent susceptibility of Enterobacteriaceae to third-generation cephalosporins and to carbapenems was 59 and 97%, respectively. Among Pseudomonas aeruginosa and Acinetobacter spp., carbapenem susceptibility reached 70 and 12%, respectively. Among Gram positive organisms, the percent susceptibility to methicillin in Staphylococcus aureus was 72%, that to vancomycin in Enterococcus spp. was 98% and that to penicillin in Streptococcus pneumoniae was 75%. Compared with results of 2011-2013, there was an overall trend of decreased susceptibility of bacteria to the tested antibiotics, with a variation of 5 to 10%. The antibiotic susceptibility data from Lebanon were found to be comparable with those from Eastern and South-eastern European countries. Conclusion: This study highlights the need to establish a robust national AMR surveillance system that enables data from Lebanon to be included in global AMR maps.