Interferon Beta-1b and Lopinavir-Ritonavir for Middle East Respiratory Syndrome.

BACKGROUND: Whether combined treatment with recombinant interferon beta-1b and lopinavir-ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear. METHODS: We conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir-ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results. RESULTS: A total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of -19 percentage points (upper boundary of the 97.5% confidence interval [CI], -3; one-sided P = 0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group. CONCLUSIONS: A combination of recombinant interferon beta-1b and lopinavir-ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset. (Funded by the King Abdullah International Medical Research Center; MIRACLE ClinicalTrials.gov number, NCT02845843.).

Identified Transmission Dynamics of Middle East Respiratory Syndrome Coronavirus Infection During an Outbreak: Implications of an Overcrowded Emergency Department.

A total 130 cases of Middle East respiratory syndrome coronavirus were identified during a large hospital outbreak in Saudi Arabia; 87 patients and 43 healthcare workers. The majority (80%) of transmission was healthcare-acquired (HAI) infection, with 4 generations of HAI transmission. The emergency department was the main location of exposure.

Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection.

BACKGROUND: Since September 2012, 170 confirmed infections with Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization, including 72 deaths. Data on critically ill patients with MERS-CoV infection are limited. OBJECTIVE: To describe the critical illness associated with MERS-CoV. DESIGN: Case series. SETTING: 3 intensive care units (ICUs) at 2 tertiary care hospitals in Saudi Arabia. PATIENTS: 12 patients with confirmed or probable MERS-CoV infection. MEASUREMENTS: Presenting symptoms, comorbid conditions, pulmonary and extrapulmonary manifestations, measures of severity of illness and organ failure, ICU course, and outcome are described, as are the results of surveillance of health care workers (HCWs) and patients with potential exposure. RESULTS: Between December 2012 and August 2013, 114 patients were tested for suspected MERS-CoV; of these, 11 ICU patients (10%) met the definition of confirmed or probable cases. Three of these patients were part of a health care-associated cluster that also included 3 HCWs. One HCW became critically ill and was the 12th patient in this case series. Median Acute Physiology and Chronic Health Evaluation II score was 28 (range, 16 to 36). All 12 patients had underlying comorbid conditions and presented with acute severe hypoxemic respiratory failure. Most patients (92%) had extrapulmonary manifestations, including shock, acute kidney injury, and thrombocytopenia. Five (42%) were alive at day 90. Of the 520 exposed HCWs, only 4 (1%) were positive. LIMITATION: The sample size was small. CONCLUSION: MERS-CoV causes severe acute hypoxemic respiratory failure and considerable extrapulmonary organ dysfunction and is associated with high mortality. Community-acquired and health care-associated MERS-CoV infection occurs in patients with chronic comorbid conditions. The health care-associated cluster suggests that human-to-human transmission does occur with unprotected exposure. PRIMARY FUNDING SOURCE: None.

Granulomatous myositis associated with brucellosis: a case report and literature review.

Brucellosis, a multisystem infectious disorder, continues to be a serious public health problem in some parts of the world. Neurobrucellosis constitutes about 4% of all brucellosis cases. Brucellosis-associated myositis is extremely rare, and there is only 1 reported case in the English literature. We report a 16-year-old boy with subacute, fluctuating, progressive muscle pain, with tenderness, swelling, and diffuse, asymmetric weakness. He also had significantly elevated serum Brucella titers and a muscle biopsy showed inflammatory granulomatous myositis. We review the literature on myositis associated with brucellosis.

Clinical Characteristics and Outcome of Candidemia: Experience from a Tertiary Referral Center in Saudi Arabia.

Background: Candida bloodstream infections cause significant excess morbidity and mortality in the health-care setting. There is limited evidence regarding Candida species causing invasive infections in Saudi Arabia. Objective: To identify Candida species causing bloodstream infection and determine the clinical outcome and factors associated with mortality in a tertiary center in Saudi Arabia. Materials and Methods: This retrospective study included all cases of positive blood culture for Candida in patients admitted to King Abdulaziz Medical City, a tertiary care center in Riyadh, Saudi Arabia, between January 1, 2013 and June 30, 2019. Results: A total of 532 patients with candidemia were identified (male: 55.4%; mean age: 54 ± 26.2 years). The most common Candida species isolated was Candida albicans (26.7%), followed by Candida glabrata (22.7%), Candida parapsilosis (22.2%), and Candida tropicalis (18.4%). Non-albicans candidemia was more common in patients with diabetes (76.7%; P = 0.0560), neutropenia (89.8%; P = 0.0062), recent exposure to fluconazole (85.7%; P = 0.0394), and active chemotherapy (83.1%; P = 0.0128). In non-albicans, susceptibility to fluconazole varied from 95.9% with C. tropicalis to 41.5% with C. parapsilosis; nonetheless, all species were highly susceptible to echinocandins. The overall 30- and 90-day mortality rates were 39.9% and 56.4%, respectively. The mortality rate was nonsignificantly higher with non-albicans species at 30 days (41.2% vs. 35.9%; P = 0.2634) and 90 days (58.2% vs. 51.4%; P = 0.1620). Conclusion: This study found a changing pattern in the Candida species causing bloodstream infections and an epidemiological shift toward more non-albicans Candida species in Saudi Arabia.

Safety and immunogenicity of ChAdOx1 MERS vaccine candidate in healthy Middle Eastern adults (MERS002): an open-label, non-randomised, dose-escalation, phase 1b trial.

BACKGROUND: ChAdOx1-vectored vaccine candidates against several pathogens have been developed and tested in clinical trials and ChAdOx1 nCoV-19 has now been licensed for emergency use for COVID-19. We assessed the safety and immunogenicity of the ChAdOx1 MERS vaccine in a phase 1b trial in healthy Middle Eastern adults. METHOD: MERS002 is an open-label, non-randomised, dose-escalation, phase 1b trial. Healthy Middle Eastern adults aged 18-50 years were included in the study. ChAdOx1 MERS was administered as a single intramuscular injection into the deltoid muscle of the non-dominant arm at three different dose groups: 5·0 × 109 viral particles in a low-dose group, 2·5 × 1010 viral particles in an intermediate-dose group, and 5·0 × 1010 viral particles in a high-dose group. The primary objective was to assess the safety and tolerability of ChAdOx1 MERS, measured by the occurrence of solicited and unsolicited adverse events after vaccination for up to 28 days and occurrence of serious adverse events up to 6 months. The study is registered with ClinicalTrials.gov, NCT04170829. FINDINGS: Between Dec 17, 2019, and June 1, 2020, 24 participants were enrolled (six to the low-dose, nine to the intermediate-dose, and nine to the high-dose group) and received a dose; 23 were available for follow-up at 6 months. The one dose of ChAdOx1 MERS vaccine was well tolerated with no serious adverse event reported during the 6 months of follow-up. Most adverse events were mild (67, 74%) and moderate (17, 19%). Six (7%) severe adverse events were reported by two participants in the intermediate-dose group (two feverish, two headache, one joint pain, and one muscle pain). Pain at the injection site was the most common local and overall adverse event, reported by 15 (63%) of the 24 participants. The most common systemic adverse event was headache, reported by 14 (58%), followed by muscle pain reported by 13 (54%). The vaccine induced both antibody and T cell immune responses in all volunteers; antibodies peaked at day 28 and T cell responses peaked at day 14; and continued until the end of follow-up at 6 months. INTERPRETATION: The acceptable safety and immunogenicity data from this phase 1b trial of ChAdOx1 MERS vaccine candidate in Healthy Middle Eastern adults, combined with previous safety and immunogenicity data from a trial in the UK, support selecting the ChAdOx1 MERS vaccine for advancement into phase 2 clinical evaluation. FUNDING: UK Department of Health and Social Care, using UK Aid funding, managed by the UK National Institute for Health Research; and King Abdullah International Medical Research Center.

Methicillin-Resistant Staphylococcus Aureus Bacteremia: Epidemiology, Clinical Characteristics, Risk Factors, and Outcomes in a Tertiary Care Center in Riyadh, Saudi Arabia.

Background Methicillin-resistant Staphylococcus aureus (MRSA) has become increasingly common in hospitals worldwide. In an era of pandemics, it is important to understand all types of infectious diseases in order to control its outcome and reduce mortality rates related to it. This study aims to identify the epidemiology of MRSA bloodstream infection, risk factors, and mortality in King Abdulaziz Medical City in Riyadh. Methods This is a retrospective chart review study from January 2013 to June 2017. All patients with positive blood culture for MRSA at King Abdulaziz Medical City (KAMC), which is a tertiary care center in Riyadh, Saudi Arabia, were included. Data were extracted from electronic and paper medical records for patients who had a positive blood culture for MRSA. Data collected included demographics, microbiological details, risk factors, and 30-day mortality. Results From 2013 through June 2017, 633 Staphylococcus aureus bacteremia were reported in KAMC, of which 184 (29.1%) were MRSA with a mean age of 60±19 years. Almost all of our isolates were susceptible to vancomycin, linezolid, and tigecycline. The most common infectious syndrome these patients presented with was an endovascular infection which accounts for 30.4% while 19.9% presented as a case of pneumonia. The mortality within 30 days of collection of the positive blood culture was 20.65%. Male gender (OR = 2.33; 95% CI = 1.34-4.05; P-value = 0.003) and patients with history of recent hospital (OR = 2.34; 95% CI = 1.27-4.34; P-value = 0.007) or ICU (OR = 1.66; 95% CI = 1.09-2.52; P-value = 0.018) admissions were more likely to acquire MRSA. Conclusions The incidence of MRSA bacteremia at King Abdulaziz Medical City is high and increasing in conjunction with incidence rate posing a significantly high rate of mortality. Recent history of hospital admission, ICU admission and males were found to be significantly associated with higher rates of MRSA infection. Some modifiable risk factors that could be used to facilitate the reduction of MRSA acquisition rates is to avoid unnecessary hospital and ICU admissions.

Multicentre randomised double-blinded placebo-controlled trial of favipiravir in adults with mild COVID-19.

INTRODUCTION: A novel coronavirus, designated SARS-CoV-2, caused an international outbreak of a respiratory illness, termed COVID-19 in December 2019. There is a lack of specific therapeutic agents based on evidence for this novel coronavirus infection; however, several medications have been evaluated as a potential therapy. Therapy is required to treat symptomatic patients and decrease the virus carriage duration to limit the communitytransmission. METHODS AND ANALYSIS: We hypothesise that patients with mild COVID-19 treated with favipiravir will have a shorter duration of time to virus clearance than the control group. The primary outcome is to evaluate the effect of favipiravir on the timing of the PCR test conversion from positive to negative within 15 days after starting the medicine.Adults (>18 years, men or nonpregnant women, diagnosed with mild COVID-19 within 5 days of disease onset) are being recruited by physicians participating from the Ministry of National Guard Health Affairs and the Ministry of Health ethics committee approved primary healthcare centres. This double-blind, randomised trial comprises three significant parts: screening, treatment and a follow-up period. The treating physician and patients are blinded. Eligible participants are randomised in a 1:1 ratio to either the therapy group (favipiravir) or a control group (placebo) with 1800 mg by mouth two times per day for the first day, followed by 800 mg two times per day for 4-7 days. Serial nasopharyngeal/oropharyngeal swab samples are obtained on day 1 (5 days before therapy). On day5±1 day, 10±1 day, 15±2 days, extra nasopharyngeal/oropharyngeal PCR COVID-19 samples are requested.The primary analysis population for evaluating both the efficacy and safety outcomes will be a modified intention to treat population. Anticipating a 10% dropout rate, we expect to recruit 288 subjects per arm. The results assume that the hazard ratio is constant throughout the study and that the Cox proportional hazard regression is used to analyse the data. ETHICS AND DISSEMINATION: The study was approved by the King Abdullah International Medical Research Centre Institutional Review Board (28 April 2020) and the Ministry of Health Institutional Review Board (1 July 2020). Protocol details and any amendments will be reported to https://clinicaltrials.gov/ct2/show/NCT04464408. The results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: National Clinical Trial Registry (NCT04464408).

Ceftobiprole for Treatment of MRSA Blood Stream Infection: A Case Series.

While methicillin-resistant Staphylococcus aureus (MRSA) bacteremia has poor outcomes, we describe our experience with Ceftobiprole mainly as a combination therapy for the treatment of MRSA bacteremia. All the cases of MRSA bacteremia in our center at the King Abdulaziz Medical City (KAMC), Riyadh, that had undergone Ceftobiprole treatment were included. We had six cases of MRSA bacteremia between 2018 and 2019, secondary to different infectious syndromes including endocarditis. There was a severe infection that required intensive care unit (ICU) admission in four cases. Ceftobiprole is used in combination with vancomycin in four cases. On day 14, all cases had a favorable outcome with microbiological and clinical improvement. However, three patients died after months of suffering from bacteremia from unrelated causes for the infection. The clinical outcome in our series of treatment of MRSA bacteremia using Ceftobiprole was favorable. Further studies for the evaluation of the use of Ceftobiprole in MRSA bacteremia should be encouraged.

High Burden of Resistant Gram Negative Pathogens Causing Device-associated Healthcare Infections in a Tertiary Care Setting in Saudi Arabia, 2008-2016.

OBJECTIVES: There is local and regional deficiency in the data examining the contribution of resistant pathogens to device-associated healthcare-associated infections (DA-HAIs). The objective was to examine such data in a multi-hospital system in Saudi Arabia in comparison with the US National Health Surveillance Network (NHSN). METHODS: Surveillance of DA-HAIs was prospectively conducted between 2008 and 2016 in four hospitals of Ministry of National Guard Health Affairs. Consecutive NHSN reports were used for comparisons. Definitions and methodology of DA-HAIs and bacterial resistance were based on NHSN. RESULTS: A total 1260 pathogens causing 1141 DA-HAI events were included. Gram negative pathogens (GNPs) were responsible for 62.5% of DA-HAIs, with a significantly higher Klebsiella, Pseudomonas, Acinetobacter, and Enterobacter than NHSN hospitals. Approximately 28.3% of GNPs and 23.5% of gram positive pathogens (GPPs) had some type of resistance. Nearly 34.3% of Klebsiella were resistant to third/fourth generation cephalosporins, 4.8% of Enterobacteriaceae were carbapenem-resistant (CRE), 24.4% of Staphylococcus aureus were methicillin-resistant (MRSA), and 21.9% of Enterococci were vancomycin-resistant (VRE). Multidrug resistance (MDR) was 65.0% in Acinetobacter, 26.4% in Escherichia coli, 23.0% in Klebsiella, and 14.9% in Pseudomonas. Resistant GNPs including cephalosporin-resistant Klebsiella, MDR Klebsiella, and MDR Escherichia coli were significantly more frequent while resistant GPPs including MRSA and VRE were significantly less frequent than NHSN hospitals. CONCLUSION: The current findings showed heavier and more resistant contribution of GNPs to DA-HAIs in Saudi hospitals compared with American hospitals. The higher resistance rates in Klebsiella and Escherichia coli are alarming and call for effective antimicrobial stewardship programs.

A Trial of Favipiravir and Hydroxychloroquine combination in Adults Hospitalized with moderate and severe Covid-19: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The selected combination was based on limited evidence clinically and in vitro on the efficacy of the Favipiravir and Hydroxychloroquine in SARS-CoV-2. The two medications were listed in many guidelines as treatment options and ongoing trials assessing their efficacy and safety. Thus, we want to prove the clinical effectiveness of the combination as therapy. TRIAL DESIGN: This is an Open label, multicenter, randomized controlled clinical trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. It is a multicenter trial that will compare Favipiravir plus Hydroxychloroquine combination (experimental arm) to a control arm. PARTICIPANTS: All study procedures will be conducted in eight centres in Saudia Arabia: King Abdulaziz Medical City National Guard Health Affairs in Riyadh. King Abdulaziz Hospital - Al Ahsa, Saudi Arabia AlMadina General Hospital, Madnia, Saudi Arabia Al-Qatif Central Hospital, Saudi Arabia Imam Abdulrahman Al Faisal Hospital, Dammam, Saudi Arabia King Abdulaziz Medical City, Jeddah, Saudi Arabia King Abdulaziz Hospital, Makkah, Saudi Arabia Imam Abdulrahman Alfaisal Hospital, Riyadh, Saudi Arabia Inclusion Criteria • Should be at least 18 years of age, • Male or nonpregnant female, • Diagnosed with COVID-19 by PCR confirmed SARS-coV-2 viral infection. • Able to sign the consent form and agree to clinical samples collection (or their legal surrogates if subjects are or become unable to make informed decisions).. • Moderate or Severe COVID-19, defined as oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or significant clinical symptoms that require hospital admission. • patients had to be enrolled within 10 days of disease onset. Exclusion Criteria • Patients who are pregnant or breastfeeding. • Will be transferred to a non-study site hospital or discharged from hospital within 72 hours. • Known sensitivity/allergy to hydroxychloroquine or Favipiravir • Current use of hydroxychloroquine for another indication • Prior diagnosis of retinopathy • Prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency • Major comorbidities increasing the risk of study drug including: i. Hematologic malignancy, ii. Advanced (stage 4-5) chronic kidney disease or dialysis therapy, iii. Known history of ventricular arrhythmias, iv. Current use of drugs that prolong the QT interval, Severe liver damage (Child-Pugh score ≥ C, AST> 5 times the upper limit), HIV. • The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues). • Clinical prognostic non-survival, palliative care, or in deep coma and no have response to supportive treatment within three hours of admission • Patient with irregular rhythm • Patient with a history of heart attack (myocardial infarction) • Patient with a family history of sudden death from heart attack before the age of 50 • Take other drugs that can cause prolonged QT interval • Patient who is receiving immunosuppressive therapy (cyclosporin) which cannot be switched to another agent or adjusted while using the investigational drug • Gout/history of Gout or hyperuricemia (above the ULN), hereditary xanthinuria or xanthine calculi of the urinary tract. INTERVENTION AND COMPARATOR: The treatment intervention would be for a maximum of 10 days from randomization and it would be as follows: Favipiravir for 10 days: Administer 1800 mg (9 tablets) by mouth twice daily for one day, followed by 800mg (4 tablets) twice daily (total days of therapy is 10 days) Hydroxychloroquine for 5 days: (400mg) twice daily on day 1; for days 2-5 (200mg) twice daily. Reference Comparator Therapy: Standard of care is defined as: Treatment that is accepted by medical experts as a proper treatment for Covid-19 disease. Standard care comprised of, as necessary, supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, extracorporeal membrane oxygenation (ECMO), and antiviral therapy except Favipiravir. Also, it may include intravenous fluids and medications for symptoms relief . MAIN OUTCOMES: The primary endpoint is the time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first (14 days from Randomization). RANDOMISATION: Eligible participants will be randomized in a 1:1 ratio to either the combination group (Favipiravir and Hydroxychloroquine) or a control group. The patients will be randomized utilizing Web based data entry System with a stratification based on the centre and the ICU admission. BLINDING (MASKING): This is an Open label study and only the analyst will be blinded during the study conduct. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Under the classical two arm parallel design the total effective sample sizes needed is 472 subjects (236 subjects per group). TRIAL STATUS: Protocol version 3.1 (dated 11 Aug 2020), and currently recruitment is ongoing. The date recruitment started was May 21, 2020 and the investigators anticipate the trial will finish recruiting by the end of December 2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04392973 , 19 May 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Prevalence of infections and antimicrobial use in the acute-care hospital setting in the Middle East: Results from the first point-prevalence survey in the region.

OBJECTIVES: Community-acquired (CAIs) and healthcare-associated (HAIs) infections are associated with significant morbidity and mortality. Data related to the epidemiology of these infections in the Middle East is scarce. The aim of this study is to estimate the prevalence of infections and antimicrobial use in the acute hospital setting in this region. METHODS: A multicentre Point-Prevalence Survey was conducted in seven Middle Eastern countries: Egypt, Kingdom of Saudi Arabia, United Arab Emirates, Lebanon, Oman, Kuwait and Bahrain. Data were collected by the infection control and infectious diseases teams of the respective hospitals. Study surveys were completed in one day (03 April 2018). RESULTS: The overall point prevalence of infection was 28.3%; HAI and CAI point prevalence was 11.2% and 16.8%, respectively. The majority of patients with an infection (98.2%) were receiving antimicrobial therapy. There were high levels of resistance to antimicrobials among Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae and other Klebsiella sp. CONCLUSIONS: Our findings indicate that the point prevalence of both HAI and CAI is high in a sample of Middle Eastern countries. These findings along with the increased use of antimicrobials represent a significant public health problem in the region; particularly in light of the growing regional antimicrobial resistance.

Ten-year resistance trends in pathogens causing healthcare-associated infections; reflection of infection control interventions at a multi-hospital healthcare system in Saudi Arabia, 2007-2016.

BACKGROUND: Studying temporal changes in resistant pathogens causing healthcare-associated infections (HAIs) is crucial in improving local antimicrobial and infection control practices. The objective was to describe ten-year trends of resistance in pathogens causing HAIs in a tertiary care setting in Saudi Arabia and to compare such trends with those of US National Health Surveillance Network (NHSN). METHODS: Pooled analysis of surveillance data that were prospectively collected between 2007 and 2016 in four hospitals of Ministry of National Guard Health Affairs. Definitions and methodology of HAIs and antimicrobial resistance were based on NHSN. Consecutive NHSN reports were used for comparisons. RESULTS: A total 1544 pathogens causing 1531 HAI events were included. Gram negative pathogens (GNP) were responsible for 63% of HAIs, with a significant increasing trend in Klebsiella spp. and a decreasing trend in Acinetobacter. Methicillin-resistant Staphylococcus aureus (27.0%) was consistently less frequent than NHSN. Vancomycin-resistant Enterococci (VRE, 20.3%) were more than doubled during the study, closing the gap with NHSN. Carbapenem resistance was highest with Acinetobacter (68.3%) and Pseudomonas (36.8%). Increasing trends of carbapenem resistance were highest in Pseudomonas and Enterobacteriaceae, closing initial gaps with NHSN. With the exception of Klebsiella and Enterobacter, multidrug-resistant (MDR) GNPs were generally decreasing, mainly due to the decreasing resistance towards cephalosporins, fluoroquinolones, and aminoglycosides. CONCLUSION: The findings showed increasing trends of carbapenem resistance and VRE, which may reflect heavy use of carbapenems and vancomycin. These findings may highlight the need for effective antimicrobial stewardship programs, including monitoring and feedback on antimicrobial use and resistance.

Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-ß1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial.

The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-ß1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-ß1b 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.

Can identification badges be vectors of infection: Experience from a tertiary care center in Riyadh, Saudi Arabia.

BACKGROUND: Wearing identification badges is mandatory in many hospitals. Identification badges worn by healthcare workers may be contaminated with pathogens. OBJECTIVE: The objective of this study is to determine the levels and types of contamination on identification badges of healthcare workers at King Abdulaziz Medical City in Riyadh, Saudi Arabia. MATERIALS AND METHODS: This is a cross-sectional study of 200 healthcare workers at King Abdulaziz Medical City in Riyadh, Saudi Arabia. A data collection form was handed to all the participants and swab cultures of their identification badges were taken. RESULTS: A total of 200 identification badges were sampled in this study. 37% were contaminated with pathogens. Coagulase-negative Staphylococcus was isolated from 70 badges (35%), and methicillin-sensitive Staphylococcus aureus from four badges (2%). Contamination was highest in physicians (45% compared to 14-32% in other healthcare workers). Males and females had similar contamination rates (39 and 36%, respectively). CONCLUSION: Identification badges worn by healthcare workers may be vectors of significant infection. We suggest more compliance of infection control measures in regards to disinfecting badges or personal belongings of healthcare workers.

Experience with ceftazidime-avibactam treatment in a tertiary care center in Saudi Arabia.

INTRODUCTION: Carbapenem-resistant organisms have become major healthcare-associated pathogens and are responsible for significant morbidity and mortality worldwide. CASES AND MANAGEMENTS: This case-series describes our experience with ceftazidime-avibactam in the treatment of six cases with carbapenem-resistant organisms in King Abdulaziz Medical City in Riyadh, Saudi Arabia. After trying various combinations of antibiotic therapies without improvement, cases were treated with ceftazidime-avibactam. OUTCOMES: Five of the six achieved complete cure, both clinically and microbiologically.

Antimicrobial consumption in five adult intensive care units: a 33-month surveillance study.

Background: Estimating the baseline antimicrobial consumption is extremely important to monitor the impact of antimicrobial stewardship activities that aim to reduce the burden and cost of antimicrobial consumption. Objectives: To quantify service-specific antimicrobial consumption using different metrics. Methods: A surveillance study was conducted at King Abdulaziz Medical City, Riyadh, Saudi Arabia, between October 2012 and June 2015 in five adult intensive care units (ICUs). Consumption data were collected manually on a daily basis by infection control practitioners. Data were presented as defined daily dose (DDD), days of therapy (DOT) per 1000 patient days, and frequency of daily consumption. Results: A total of 43,970 DDDs and 46,940 DOTs were monitored during 54,116 patient-days. For the most frequently consumed antimicrobials, the consumption of carbapenems, piperacillin/tazobactam, vancomycin, and colistin (respectively) in all ICUs combined were 255.9, 134.3, 98.2, and 13.6 DDDs per 1000 patient-days and 235.7, 145.9, 129.5, and 117.5 DOTs per 1000 patient-days. For the frequency of daily consumption, carbapenems were the most frequently consumed antimicrobial group in medical/surgical, burn, and step-down ICUs while piperacillin/tazobactam was the most frequently consumed antimicrobial in neuro-surgical and cardio-thoracic ICUs. Conclusion: High consumption of broad-spectrum antimicrobial agents such as meropenem and piperacillin/tazobactam is observed in multiple ICUs in a tertiary care hospital. Meropenem consumption is considerably higher than similar ICUs internationally. Future studies focusing on concurrent monitoring of antimicrobial resistance and identifying patient and physician characteristics associated with specific prescription patterns may help in improving judicious antimicrobial consumption.

Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-ß1b (MIRACLE trial): study protocol for a randomized controlled trial.

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-ß1b (IFN-ß1b) 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-ß1b 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.

Prevalence of Latent Mycobacterium Tuberculosis Infection (LTBI) in Saudi Arabia; Population based survey.

BACKGROUND: The annual risk of tuberculosis infection (ARTI) data in Saudi Arabia has not been updated since 1993. OBJECTIVES: To estimate the prevalence of latent TB infection (LTBI) and ARTI in a population-based sample in Saudi Arabia using Tuberculin skin test (TST) and QuantiFERON TB Gold in tube (QFT-GIT) test. METHODS: A population-based cross sectional study was conducted between July 2010 and March 2013. Participants were randomly selected from the population served by the primary healthcare centers of the Ministry of National Guard Health Affairs in Riyadh, Jeddah, Alhassa and Dammam, Saudi Arabia. RESULTS: A total of 1369 participants were included. The overall prevalence of LTBI was similar using TST and QFT-GIT (9.3% and 9.1% respectively, p=0.872) but stratified prevalence rates were variable in all sociodemographic groups except marital status. Additionally, the prevalence rates of LTBI using either test alone showed significant differences by several sociodemographic and behavioral characteristics. The overall ARTI was 0.36% using TST and 0.35% using QFT-GIT. CONCLUSIONS: We are reporting much lower estimates for the prevalence of LTBI and the ARTI in a population-based sample in Saudi Arabia relative to the data that have been used for more than two decades.

Epidemiology and outcome of invasive fungal infections and methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and complicated skin and soft tissue infections (cSSTI) in Lebanon and Saudi Arabia.

The objectives of this retrospective medical chart review study were to document the inpatient incidence, treatment, and clinical outcomes associated with invasive fungal infections (IFI) due to Candida and Aspergillus species, Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and MRSA complicated skin and soft tissue infections (cSSTI) in the Middle East. This study evaluated 2011-2012 data from 5 hospitals in Saudi Arabia and Lebanon with a combined total of 207,498 discharges. Hospital medical chart data were abstracted for a random sample of patients with each infection type (102 patients - IFI, 93 patients - MRSA pneumonia, and 87 patients-MRSA cSSTI). Descriptive analysis found that incidence of IFI (per 1000 hospital discharges) was higher than MRSA cSSTI and MRSA pneumonia (IFI: 1.95 and 2.57; MRSA cSSTI: 2.01 and 0.48; and MRSA pneumonia 0.59 and 0.55 for Saudi Arabia and Lebanon, respectively). Median time from hospital admission to diagnosis and from admission to initiation of active therapy were 6 and 7 days, respectively, in IFI patients; median time from admission to diagnosis was 2days for both MRSA pneumonia and cSSTI, with a median of 4 and 2days from admission to MRSA-active antibiotic start, respectively. The mean hospital LOS was 32.4days for IFI, 32.4days for MRSA pneumonia and 26.3days for MRSA cSSTI. Inpatient mortality was higher for IFI (42%) and MRSA pneumonia (30%) than for MRSA cSSTI (8%). At discharge, 33% of patients with IFI and 27% and 9% of patients with MRSA pneumonia and cSSTI, respectively, were considered to have failed therapy. In conclusion, there is a significant burden of these serious infections in the Middle East, as well as opportunity for hospitals to improve the delivery of patient care for difficult-to-treat infections by promoting expedited diagnosis and initiation of appropriate antimicrobial therapy.