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Background The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. Methods In this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2-2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8–1.2 g/kg/day). The primary outcome is 90-day all-cause mortality, and other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30–25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data. Conclusion Ethics approval was obtained from the King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R ). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings Trial registration: ClinicalTrials.gov Identifier: NCT04475666. Registered on July 17, 2020 https://clinicaltrials.gov/ct2/show/NCT04475666

BackgroundThe rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU).MethodsThe SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations.ResultsThe SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations. ConclusionThe SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available.

Background Acinetobacter is an increasingly-problematic organism, especially in intensive care units (ICUs). In this study, we compared its incidence, outcomes, and predictors spanning eight ICUs in five geographically and climatologically-diverse cities in Saudi Arabia. Methods Geographic, climatologic, hospital-related, and patient-related factors were collected prospectively on 3179 patients admitted to eight Saudi ICUs from June 2018 through June 2019. These data then underwent both bivariable and multivariable analysis, the latter vis hierarchical logistic regression to identify predictors of clinically-manifest Acinetobacter infection. Results Overall incidence of Acinetobacter infection was 3.9% (n = 124). Of these 124 infections, 122 (98.4%) were cultured as A. baumannii. Incidence ranged from 1.0 to 7.9% across the eight ICUs. On bivariable analysis, incident Acinetobacter infection was more common in university and military hospitals, in hospitals with more total beds and ICU isolation rooms, and in 2018 versus 2019, incidence steadily declining over the 13 study months. Mechanically-ventilated patients had ten-fold increased odds of infection. Adjusted (multivariable) analysis revealed the risk of clinically-manifest Acinetobacter infection to increase the longer patients were on mechanical ventilation. Increased risk also existed at certain hospitals over others, especially in university-affiliated and military hospitals, larger hospitals with more isolation rooms, and hospitals with fewer ICU beds. Conclusion In our study of eight ICUs across Saudi Arabia, inter-hospital differences did appear to account for inter-hospital differences in Acinetobacter incidence rates. Patients requiring mechanical ventilation for longer periods of time were particularly at risk.

Summary Background and aims The optimal amount of protein intake in critically ill patients is unclear. The objective of this pilot trial is to assess the feasibility of a large randomized controlled trial testing higher versus lower protein intake in critically ill patients. Methods In this pilot randomized controlled trial (REPLacing Protein via Enteral Nutrition in a Stepwise ApproacH in critically ill patients: A pilot randomized controlled trial (REPLENISH pilot trial), critically ill patients underwent 2-step screening for eligibility on ICU day 1 and 5. Patients with renal disease were excluded. Eligible patients were randomized into REPLENISH group (target protein 1.8–2.2 g kg/day) and Standard group (target protein 0.8–1.0 g/kg/day) from day 6–14 after ICU admission. Dietitians adjusted caloric and protein intake throughout the study period (Day 1–14) to maintain similar caloric targets of permissive underfeeding (40–60% of estimated energy expenditure) in both study groups. Results Of 704 patients screened at 3 centers in Saudi Arabia from May 2018 to May 2019, only 63 (8.9%) were eligible and 40 (5.7% of screened) were randomized with an average of 2 patients enrolled in the trial per month. Among eligible patients, the consenting rate was high at 89%. During the intervention period, patients in the REPLENISH group (N = 21) had a modestly higher protein intake (median of 1.30 g/kg/day (Q1 Q3: 1.11, 1.57)) than those in the standard group (median of 0.77 g/kg/day (Q1 Q3: 0.57, 1.00); P = 0.0004). Only 31.4% of patients in the whole cohort had >80% of prescribed protein. The duration of daily interruption of feeding was almost 4 h in both groups. The 90-day mortality for the patient study cohort was 20.5%. Anthropometric and muscle strength measurements were performed in less than 50% of patients. Conclusions This pilot trial highlighted several areas for improvement in the study protocol before launching a large randomized controlled trial. The restrictive eligibility criteria, the complex adjustments of protein and energy and some of the outcome measurements were identified as targets for modifications, to improve enrollment and generalizability and to enhance adherence to study interventions and measurements. Trial registration: clinicaltrials.gov identifier NCT03480555.

BackgroundDiabetes is a risk factor for infection with coronaviruses. This study describes the demographic, clinical data, and outcomes of critically ill patients with diabetes and Middle East Respiratory Syndrome (MERS).MethodsThis retrospective cohort study was conducted at 14 hospitals in Saudi Arabia (September 2012–January 2018). We compared the demographic characteristics, underlying medical conditions, presenting symptoms and signs, management and clinical course, and outcomes of critically ill patients with MERS who had diabetes compared to those with no diabetes. Multivariable logistic regression analysis was performed to determine if diabetes was an independent predictor of 90-day mortality.ResultsOf the 350 critically ill patients with MERS, 171 (48.9%) had diabetes. Patients with diabetes were more likely to be older, and have comorbid conditions, compared to patients with no diabetes. They were more likely to present with respiratory failure requiring intubation, vasopressors, and corticosteroids. The median time to clearance of MERS-CoV RNA was similar (23 days (Q1, Q3: 17, 36) in patients with diabetes and 21.0 days (Q1, Q3: 10, 33) in patients with no diabetes). Mortality at 90 days was higher in patients with diabetes (78.9% versus 54.7%,p ConclusionsHalf of the critically ill patients with MERS have diabetes; which is associated with more severe disease. Diabetes is an independent predictor of mortality among critically patients with MERS.

IMPORTANCE: The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19. OBJECTIVE: To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021. INTERVENTION: Patients were randomized to awake prone positioning (n = 205) or usual care without prone positioning (control; n = 195). MAIN OUTCOMES AND MEASURES: The primary outcome was endotracheal intubation within 30 days of randomization. The secondary outcomes included mortality at 60 days, days free from invasive mechanical ventilation or noninvasive ventilation at 30 days, days free from the intensive care unit or hospital at 60 days, adverse events, and serious adverse events. RESULTS: Among the 400 patients who were randomized (mean age, 57.6 years [SD, 12.83 years]; 117 [29.3%] were women), all (100%) completed the trial. In the first 4 days after randomization, the median duration of prone positioning was 4.8 h/d (IQR, 1.8 to 8.0 h/d) in the awake prone positioning group vs 0 h/d (IQR, 0 to 0 h/d) in the control group. By day 30, 70 of 205 patients (34.1%) in the prone positioning group were intubated vs 79 of 195 patients (40.5%) in the control group (hazard ratio, 0.81 [95% CI, 0.59 to 1.12], P = .20; absolute difference, −6.37% [95% CI, −15.83% to 3.10%]). Prone positioning did not significantly reduce mortality at 60 days (hazard ratio, 0.93 [95% CI, 0.62 to 1.40], P = .54; absolute difference, −1.15% [95% CI, −9.40% to 7.10%]) and had no significant effect on days free from invasive mechanical ventilation or noninvasive ventilation at 30 days or on days free from the intensive care unit or hospital at 60 days. There were no serious adverse events in either group. In the awake prone positioning group, 21 patients (10%) experienced adverse events and the most frequently reported were musculoskeletal pain or discomfort from prone positioning (13 of 205 patients [6.34%]) and desaturation (2 of 205 patients [0.98%]). There were no reported adverse events in the control group. CONCLUSIONS AND RELEVANCE: In patients with acute hypoxemic respiratory failure from COVID-19, prone positioning, compared with usual care without prone positioning, did not significantly reduce endotracheal intubation at 30 days. However, the effect size for the primary study outcome was imprecise and does not exclude a clinically important benefit. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04350723

We examined the association between surveillance for deep vein thrombosis (DVT) among medical-surgical critically ill patients by twice-weekly ultrasonography and 90-day all-cause mortality. This was a pre-planned sub-study of the Pneumatic Compression for Preventing Venous Thromboembolism (PREVENT) trial (Clinicaltrials.gov: NCT02040103) that compared addition of intermittent pneumatic compression (IPC) to pharmacologic prophylaxis versus pharmacologic prophylaxis alone. The surveillance group included enrolled patients in the trial, while the non-surveillance group included eligible non-enrolled patients. Using logistic regression and Cox proportional hazards models, we examined the association of surveillance with the primary outcome of 90-day mortality. Secondary outcomes were DVT and pulmonary embolism (PE). The surveillance group consisted of 1682 patients and the non-surveillance group included 383 patients. Using Cox proportional hazards model with bootstrapping, surveillance was associated with a decrease in 90-day mortality (adjusted HR 0.75; 95% CI 0.57, 0.98). Surveillance was associated with earlier diagnosis of DVT [(median 4 days (IQR 2, 10) vs. 20 days (IQR 16, 22)] and PE [median 4 days (IQR 2.5, 5) vs. 7.5 days (IQR 6.1, 28.9)]. There was an increase in diagnosis of DVT (adjusted HR 5.49; 95% CI 2.92, 13.02) with no change in frequency in diagnosis of PE (adjusted HR 0.56; 95% CI 0.19, 1.91). Twice-weekly surveillance ultrasonography was associated with an increase in DVT detection, reduction in diagnostic testing for non-lower limb DVT and PE, earlier diagnosis of DVT and PE, and lower 90-day mortality. The PREVENT trial is registered at ClinicalTrials.gov, ID: NCT02040103. Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506. Registered on 30 October 2013.

IntroductionNoninvasive ventilation delivered by helmet is has been used for respiratory support of patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. The aim of this study is to compare helmet noninvasive ventilation with usual care versus usual care alone to reduce the mortality.Methods and analysisThis is a multicenter, pragmatic, parallel, randomized controlled trial that compares helmet noninvasive ventilation with usual care to usual care alone in 1:1 ratio. A total of 320 patients will be enrolled in this study. The primary outcome is 28-day all-cause mortality. The primary outcome will be compared between the two study groups in the intention-to-treat and per-protocol cohorts. An interim analysis will be conducted for both safety and effectiveness.Ethics and disseminationApprovals are obtained from the Institutional Review Boards (IRBs) of each participating institution. Our findings will be published in peer-review journals and presented at relevant conferences and meetings.Trial registration numberNCT04477668 registered on July 20, 2020Article SummaryStrengths and limitations of this studyThis trial compares helmet NIV to usual care for respiratory support of patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia.The trial is a multi-center, pragmatic, parallel randomized controlled trial.The main limitation is the unblinded design due to the nature of the intervention.

IntroductionNon-invasive ventilation (NIV) delivered by helmet has been used for respiratory support of patients with acute hypoxaemic respiratory failure due to COVID-19 pneumonia. The aim of this study was to compare helmet NIV with usual care versus usual care alone to reduce mortality.Methods and analysisThis is a multicentre, pragmatic, parallel randomised controlled trial that compares helmet NIV with usual care to usual care alone in a 1:1 ratio. A total of 320 patients will be enrolled in this study. The primary outcome is 28-day all-cause mortality. The primary outcome will be compared between the two study groups in the intention-to-treat and per-protocol cohorts. An interim analysis will be conducted for both safety and effectiveness.Ethics and disseminationApprovals are obtained from the institutional review boards of each participating institution. Our findings will be published in peer-reviewed journals and presented at relevant conferences and meetings.Trial registration numberNCT04477668.

Introduction Data are lacking on impact of Middle East Respiratory Syndrome (MERS) on health-related quality of life (HRQoL) among survivors. Methods We conducted a cross-sectional survey of MERS survivors who required hospitalization in Saudi Arabia during 2016–2017, approximately 1 year after diagnosis. The Short-Form General Health Survey 36 (SF-36) was administered by telephone interview to assess 8 quality of life domains for MERS survivors and a sample of survivors of severe acute respiratory infection (SARI) without MERS. We compared mean SF-36 scores of MERS and non-MERS SARI survivors using independent t-test, and compared categorical variables using chi-square test. Adjusted analyses were performed using multiple linear regression. Results Of 355 MERS survivors, 83 were eligible and 78 agreed to participate. MERS survivors were younger than non-MERS SARI survivors (mean ± SD): (44.9 years ±12.9) vs (50.0 years ±13.6), p = 0.031. Intensive care unit (ICU) admissions were similar for MERS and non-MERS SARI survivors (46.2% vs. 57.1%), p = 0.20. After adjusting for potential confounders, there were no significant differences between MERS and non-MERS SARI survivors in physical component or mental component summary scores. MERS ICU survivors scored lower than MERS survivors not admitted to an ICU for physical function (p = 0.05), general health (p = 0.01), vitality (p = 0.03), emotional role (p = 0.03) and physical component summary (p

CONTEXT: Asthma control is suboptimal in the Middle East and North Africa (MENA). AIMS: The aim of this study is to assess the level of asthma control in Saudi patients as per the Global Initiative for Asthma 2012 classification and explore its potential predictive factors. SETTINGS AND DESIGN: Epidemiological Study on the Management of Asthma in Asthmatic Middle East Adult Population (ESMAA) is a multicentric, descriptive, epidemiological study assessing asthma management in the MENA region. In this article, we report the results of patients from Saudi Arabia included in the ESMAA study. METHODS: Adult patients diagnosed with asthma at least 1 year before study entry were considered for inclusion. Asthma control level and its predictive factors were explored. Treatment adherence and quality of life (QoL) were assessed by MMAS-4© and Short Form 8 Health Survey QoL questionnaires, respectively. STATISTICAL ANALYSIS USED: Descriptive statistics were done considering two-sided 95% confidence intervals. Logistic regression was used to explore the potential predictive factors of asthma control. All statistical tests were two-sided, and P < 0.05 was considered statistically significant. RESULTS: Data of 1009 patients from Saudi Arabia were analyzed. Less than one-third of patients (30.1%) were found to have controlled asthma with significantly higher QoL. High level of asthma control was reported among male patients and those with high educational level, while age, body mass index, and adherence to treatment were found to have no effect on asthma control. CONCLUSIONS: Asthma control remains suboptimal among Saudi population. This needs huge efforts to achieve acceptable levels of control and better QoL for asthma patients. Further studies are still needed in Saudi Arabia and the Middle East region.

Background To evaluate the effect of screening for sepsis using an electronic sepsis alert vs. no alert in hospitalized ward patients on 90-day in-hospital mortality. Methods The SCREEN trial is designed as a stepped-wedge cluster randomized controlled trial. Hospital wards (total of 45 wards, constituting clusters in this design) are randomized to have active alert vs. masked alert, 5 wards at a time, with each 5 wards constituting a sequence. The study consists of ten 2-month periods with a phased introduction of the intervention. In the first period, all wards have a masked alert for 2 months. Afterwards the intervention (alert system) is implemented in a new sequence every 2-month period until the intervention is implemented in all sequences. The intervention includes the implementation of an electronic alert system developed in the hospital electronic medical records based on the quick sequential organ failure assessment (qSOFA). The alert system sends notifications of “possible sepsis alert” to the bedside nurse, charge nurse, and primary medical team and requires an acknowledgment in the health information system from the bedside nurse and physician. The calculated sample size is 65,250. The primary endpoint is in-hospital mortality by 90 days. Discussion The trial started on October 1, 2019, and is expected to complete patient follow-up by the end of October 2021. Trial registration ClinicalTrials.gov NCT04078594. Registered on September 6, 2019

Background: Diabetes is a risk factor for infection with coronaviruses. This study describes the demographic, clinical data and outcomes of critically ill patients with diabetes who developed Middle East Respiratory Syndrome (MERS).Methods: This retrospective cohort study was conducted at 14 hospitals in Saudi Arabia (September 2012-January 2018). We compared the demographic characteristics, underlying medical conditions, presenting symptoms and signs, management and clinical course and outcomes between critically ill MERS patients who had diabetes and those with no diabetes. Multivariable logistic regression analysis was performed to determine if diabetes was an independent predictor of 90-day mortality.Results: Of the 350 MERS patients, 171 (48.9%) had diabetes, were more likely to be older and have comorbid conditions. Patients with diabetes were more likely to present with respiratory failure requiring intubation, vasopressors and corticosteroids. The median time to clearance of MERS-CoV RNA was similar (23 days (Q1, Q3: 17, 36) in patients with diabetes and 21.0 days (Q1, Q3: 10, 33) in patients with no diabetes. Mortality at 90 days was higher in patients with diabetes (78.9% versus 54.7%, pConclusions: Critically ill patients with diabetes constitute half of critically ill patients with MERS, presenting with more severe disease requiring mechanical ventilation compared to those who do not have diabetes. Diabetes is an independent predictor of mortality.

Objectives Pulmonary embolism (PE) is seven times more common in cancer patients than non-cancer patients. Since the existing clinical prediction rules (CPRs) were validated predominantly in a non-cancer population, we decided to look at the utility of arterial blood gas (ABG) analysis and D-dimer in predicting PE in cancer patients. Methods Electronic medical records were reviewed between December 2005 and November 2010. A total of 177 computed tomography pulmonary angiograms (CTPAs) were performed. We selected 104 individuals based on completeness of laboratory and clinical data. Patients were divided into two groups, CTPA positive (patients with PE) and CTPA negative (PE excluded). Wells score, Geneva score, and modified Geneva score were calculated for each patient. Primary outcomes of interest were the sensitivities, specificities, positive, and negative predictive values for all three CPRs. Results Of the total of 104 individuals who had CTPAs, 33 (31.7%) were positive for PE and 71 (68.3%) were negative. There was no difference in basic demographics between the two groups. Laboratory parameters were compared and partial pressure of oxygen was significantly lower in patients with PE (68.1 mmHg vs. 71 mmHg, p = 0.030). Clinical prediction rules showed good sensitivities (88-100%) and negative predictive values (93-100%). An alveolar-arterial (A-a) gradient > 20 had 100% sensitivity and negative predictive values. Conclusions CPRs and a low A-a gradient were useful in excluding PE in cancer patients. There is a need for prospective trials to validate these results.

The Middle East respiratory syndrome corona virus (MERS-CoV) is a novel positive sense singlestranded ribonucleic acid virus of the genus Beta corona virus. This virus was first isolated from a patient who died from severe respiratory illness in June 2012 in Jeddah, Kingdom of Saudi Arabia. We describe an unusual case of a 42 year old healthcare worker who was admitted to our Intensive Care Unit (ICU) King Abdul-Aziz Medical City, with MERS-CoV and severe acute respiratory distress Syndrome and developed a sudden-onset diabetes insipidus and spontaneous massive intracranial hemorrhage with intra-ventricular extension and tonsillar herniation. Computed angiogram of the brain did not reveal any aneurysm or structural defects. She never had uncontrolled hypertension, or coagulopathy, nor she received antiplatelets. We are reporting a rare case of structural neurological damage associated with MERS-CoV infection.

INTRODUCTION: Venous thromboembolism (VTE) during hospitalization is a serious and potentially fatal condition. Despite its effectiveness, evidence-based thromboprophylaxis is still underutilized in many countries including Saudi Arabia. OBJECTIVE OF THE STUDY: Our objectives were to determine how often hospital-acquired VTE patients received appropriate thromboprophylaxis, VTE-associated mortality, and the percentage of patients given anticoagulant therapy and adherence to it after discharged. METHODS: This study was conducted in seven major hospitals in Saudi Arabia. From July 1, 2009, till June 30, 2010, all recorded deep vein thrombosis (DVT) and pulmonary embolism (PE) cases were noted. Only patients with confirmed VTE diagnosis were included in the analysis. RESULTS: A total of 1241 confirmed VTE cases occurred during the 12-month period. Most (58.3%) of them were DVT only, 21.7% were PE, and 20% were both DVT and PE. 21.4% and 78.6% of confirmed VTE occurred in surgical and medical patients, respectively. Only 40.9% of VTE cases received appropriate prophylaxis (63.2% for surgical patients and 34.8% for medical patients; P < 0.001). The mortality rate was 14.3% which represented 1.6% of total hospital deaths. Mortality was 13.5% for surgical patients and 14.5% for medical patients (P > 0.05). Appropriate thromboprophylaxis was associated with 4.11% absolute risk reduction in mortality (95% confidence interval: 0.24%–7.97%). Most (89.4%) of the survived patients received anticoagulation therapy at discharge and 71.7% of them were adherent to it on follow-up. CONCLUSION: Thromboprophylaxis was underutilized in major Saudi hospitals denoting a gap between guideline and practice. This gap was more marked in medical than surgical patients. Hospital-acquired VTE was associated with significant mortality. Efforts to improve thromboprophylaxis utilization are warranted.

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a preventable disease. Long distant travelers are prone to variable degree to develop VTE. However, the low risk of developing VTE among long-distance travelers and which travelers should receive VTE prophylaxis, and what prophylactic measures should be used led us to develop these guidelines. These clinical practice guidelines are the result of an initiative of the Ministry of Health of the Kingdom of Saudi Arabia involving an expert panel led by the Saudi Association for Venous Thrombo Embolism (a subsidiary of the Saudi Thoracic Society). The McMaster University Guideline working group provided the methodological support. The expert panel identified 5 common questions related to the thromboprophylaxis in long-distance travelers. The corresponding recommendations were made following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.

Background: Assessing the effectiveness of antibiotics and communicating the problem of resistance is essential when devising antimicrobial stewardship programs in hospital settings. The drug resistance index (DRI) is a useful tool that combines antibiotic consumption and bacterial resistance into a single measure. In this study, we used the DRI to assess the impact of introducing a new antibiotic restriction form on antibiotic effectiveness for the treatment of gram-negative infections in the intensive care unit (ICU). Methods: We conducted a before-and-after intervention study from 2015 to 2017 at King Abdulaziz Medical City, a tertiary-care facility in Jeddah, Saudi Arabia. The antibiotic susceptibility of gram-negative bacteria and antibiotic prescribing rates for antibiotics indicated for gram-negative bacteria were assessed to evaluate the impact of a new antibiotic restriction form introduced in the ICU in July 2016. Changes in antibiotic effectiveness before and after the intervention were evaluated by calculating the DRI for 4 of the most common gram-negative pathogens and 8 commonly used antibiotic classes. Results: The overall DRI for the adult ICU (59.45) was higher than the hospital-wide DRI (47.96). A higher DRI was evident for carbapenems and antipseudomonal penicillins + β-lactamase inhibitors. A. baumannii had the highest DRI, followed by K. pneumoniae in both the adult ICU and hospital-wide. After implementation of antibiotic restriction in the adult ICU, the DRI for carbapenems was significantly lower in the postintervention phase, from 31.61 to 26.05 (P = 0.031). Conclusions: DRI is a useful tool for tracking the effectiveness of antibiotics over time. The results highlight the importance of having effective antibiotic stewardship program in healthcare settings as well as regular feedback of antibiotic consumption data to the stakeholders to keep the antibiotic prescriptions in check, thereby ensuring their sustained effectiveness.Funding: NoneDisclosures: None

Background The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders. Methods This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders. Results Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73–1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30–1.44]; P = .29). Conclusions In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance., In this observational study accounting for baseline and time-varying confounders, ribavirin and recombinant interferon (rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.

Background: Noninvasive ventilation (NIV) has been used in patients with the Middle East respiratory syndrome (MERS) with acute hypoxemic respiratory failure, but the effectiveness of this approach has not been studied.Methods: Patients with MERS from 14 Saudi Arabian centers were included in this analysis. Patients who were initially managed with NIV were compared to patients who were managed only with invasive mechanical ventilation (invasive MV).Results: Of 302 MERS critically ill patients, NIV was used initially in 105 (35%) patients, whereas 197 (65%) patients were only managed with invasive MV. Patients who were managed with NIV initially had lower baseline SOFA score and less extensive infiltrates on chest radiograph compared with patients managed with invasive MV. The vast majority (92.4%) of patients who were managed initially with NIV required intubation and invasive mechanical ventilation, and were more likely to require inhaled nitric oxide compared to those who were managed initially with invasive MV. ICU and hospital length of stay were similar between NIV patients and invasive MV patients. The use of NIV was not independently associated with 90‐day mortality (propensity score‐adjusted odds ratio 0.61, 95% CI [0.23, 1.60] P = 0.27).Conclusions: In patients with MERS and acute hypoxemic respiratory failure, NIV failure was very high. The use of NIV was not associated with improved outcomes.

Highlights • More than one-third of critically ill patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) received empiric therapy with macrolides. • Macrolide therapy is not significantly associated with a reduction in 90-day mortality of critically ill patients with MERS-CoV. • Macrolide therapy is not significantly associated with improvement in MERS-CoV RNA clearance of critically ill patients with MERS-CoV., Objectives Macrolides have been reported to be associated with improved outcomes in patients with viral pneumonia related to influenza and other viruses, possibly because of their immune-modulatory effects. Macrolides have frequently been used in patients with Middle East Respiratory Syndrome (MERS). This study investigated the association of macrolides with 90-day mortality and MERS coronavirus (CoV) RNA clearance in critically ill patients with MERS. Methods This retrospective analysis of a multicenter cohort database included 14 tertiary-care hospitals in five cities in Saudi Arabia. Multivariate logistic-regression analysis was used to determine the association of macrolide therapy with 90-day mortality, and the Cox-proportional hazard model to determine the association of macrolide therapy with MERS-CoV RNA clearance. Results Of 349 critically ill MERS patients, 136 (39%) received macrolide therapy. Azithromycin was most commonly used (97/136; 71.3%). Macrolide therapy was commonly started before the patient arrived in the intensive care unit (ICU) (51/136; 37.5%), or on day1 in ICU (53/136; 39%). On admission to ICU, the baseline characteristics of patients who received and did not receive macrolides were similar, including demographic data and sequential organ failure assessment score. However, patients who received macrolides were more likely to be admitted with community-acquired MERS (P = 0.02). Macrolide therapy was not independently associated with a significant difference in 90-day mortality (adjusted odds ratio [OR]: 0.84; 95% confidence interval [CI] :0.47–1.51; P = 0.56) or MERS-CoV RNA clearance (adjusted HR: 0.88; 95% CI:0.47–1.64; P = 0.68). Conclusions These findings indicate that macrolide therapy is not associated with a reduction in 90-day mortality or improvement in MERS-CoV RNA clearance.

Background Clostridium difficile is a gram-positive, anerobic, toxin-producing bacillus that mainly causes diarrhea and colitis. A recent meta-analysis reported an overall rate of 3.54 per 10,000 patient-days per year for C difficile infection (CDI). The highest incidence was observed in intensive care units (ICUs). In the USA, C difficile caused an estimated half a million infections and 29,000 deaths in 2012. More than 80% of these deaths occurred in individuals aged 65 years or older. The approximate cost of CDI treatment in the USA was US$ 5.4–6.3 billion per year. For the countries in the Arabian Peninsula including Jordan, Kuwait, Qatar, Saudi Arabia, Egypt, and Lebanon, the prevalence rates range from 4.6% to 23.6% for CDI isolates. Saudi Arabia has the lowest rate (4.6%) among these countries. A remarkable increase in nosocomial CDI cases in the adult ICU at King Abdulaziz Medical City was observed between 18 January and 11 March 2018.The aim of our study was to decrease the incidence of CDI in adult ICUs by implementing evidence-based interventions. Methods Cluster investigations were done; a time, place, and person table created, brain storming to identify the possible risk factors was evoked by the investigative team, a root cause analysis/fishbone diagram was pulled, and corrective actions were formulated. Clinicians: hand hygiene (soap and water), use of gloves, barrier precautions, prompt identification and early treatment of CDI cases were applied. Environmental: proper cleaning, housekeeping protocol review, and types of disinfectants used were highlighted. Surveillance: outcome surveillance of CDI cases was added to the patient safety annual report plan. Administration: antibiotic stewardship program (ASP), managing staff shortage, and reinforcement of the guidelines were essential. Results In the first quarter, the rate of CDI was 2.1 per 1000 patient-days, which dropped to 0.9, 0.4, and 0.4 per 1000 patient-days, respectively, in the second, third, and fourth quarters of 2018. Conclusion There was a significant reduction in the number of CDI cases after timely and appropriate actions were taken. However, maintaining a zero rate was challenging. Continuous monitoring, ongoing data collection, and education were considered key to reducing CDI.

Efficacy testing will be challenging because of the small pool of donors with sufficiently high antibody titers., We explored the feasibility of collecting convalescent plasma for passive immunotherapy of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using ELISA to screen serum samples from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed MERS-CoV infection, 230 healthcare workers, and 17 household contacts exposed to MERS-CoV. ELISA-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. Of the 443 tested samples, 12 (2.7%) had a reactive ELISA result, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. Undertaking clinical trials of convalescent plasma for passive immunotherapy of MERS-CoV infection may be feasible, but such trials would be challenging because of the small pool of potential donors with sufficiently high antibody titers. Alternative strategies to identify convalescent plasma donors with adequate antibody titers should be explored, including the sampling of serum from patients with more severe disease and sampling at earlier points during illness.

Abstract The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-β1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-β1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment. Trial registration ClinicalTrials.gov, NCT02845843. Registered on 27 July 2016.

Objectives: To determine the impact of applying the best available clinical evidence on the preventive measures to reduce the rate of catheter-associated urinary tract infections (CAUTI) in adult intensive care units (ICU). Methods : Data were collected from adult ICUs (28 beds) from 2008 to 2016. The proper use of silicon catheter, aseptic insertion technique, emptying bag three-fourth via close circuit, the use of appropriate size catheter, securing the draining tube on the thigh to keep catheter bag below patient’s bladder level and removal of the catheter as early as possible were ensured in all patients. Results : Rate of UTI and urinary catheter utilization ratios were reviewed during the study period. There was a mean of 6,175 catheter days/year for ICU. Despite the overall rise in the urinary catheterization ratio over these years; we observed a significant reduction in the UTI rate per 1000 Urinary catheter days; from 2.3 in 2010 to 0.3 in 2011 and it was sustained through 2016. Conclusion : The monthly rates of CAUTI significantly declined after the enforcement of agreed strategies and interventions to prevent CAUTI rates in adult ICU. Saudi Med J 2018; Vol. 39 (1): 97-102 doi: 10.15537/smj.2018.1.20999 How to cite this article: Al-Hameed FM, Ahmed GR, AlSaedi AA, Bhutta MJ, Al-Hameed FF, AlShamrani MM. Applying preventive measures leading to significant reduction of catheter-associated urinary tract infections in adult intensive care unit. Saudi Med J . 2018 Jan;39(1):97-102. doi: 10.15537/smj.2018.1.20999.

Background It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. Methods The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. Discussion This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. Trial registration ClinicalTrials.gov, ID: NCT02845843. Registered on 27 July 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2427-0) contains supplementary material, which is available to authorized users.