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

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

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

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

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

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

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.

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.