Narrative Review of the Epidemiology of Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia in Gulf Cooperation Council Countries.

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are the most common healthcare-associated infections, with rates varying between countries. Antimicrobial resistance (AMR) among common HAP/VAP pathogens has been reported, and multidrug resistance (MDR) is of further concern across Middle Eastern countries. This narrative review summarizes the incidence and pathogens associated with HAP/VAP in hospitals across Gulf Cooperation Council (GCC) countries. A PubMed literature search was limited to available data on HAP or VAP in patients of any age published within the past 10 years. Reviews, non-English language articles, and studies not reporting HAP/VAP data specific to a GCC country were excluded. Overall, 41 articles, a majority of which focused on VAP, were selected for inclusion after full-text screening. Studies conducted over multiple years showed a general reduction in VAP rates over time, with Gram-negative bacteria the most commonly reported pathogens. Gram-negative isolates reported across GCC countries included Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Rates of AMR varied widely among studies, and MDR among A. baumannii, K. pneumoniae, Escherichia coli, P. aeruginosa, and Staphylococcus aureus isolates was commonly reported. In Saudi Arabia, between 2015 and 2019, rates of carbapenem resistance among Gram-negative bacteria were 19-25%; another study (2004-2009) reported antimicrobial resistance rates in Acinetobacter species (60-89%), P. aeruginosa (13-31%), and Klebsiella species (100% ampicillin, 0-13% other antimicrobials). Although limited genotype data were reported, OXA-48 was found in ≥ 68% of patients in Saudi Arabia with carbapenem-resistant Enterobacteriaceae infections. Ventilator utilization ratios varied across studies, with rates up to 0.9 reported in patients admitted to adult medical/surgical intensive care units in both Kuwait and Saudi Arabia. VAP remains a burden across GCC countries albeit with decreases in rates over time. Evaluation of prevention and treatment measures and implementation of a surveillance program could be useful for the management of HAP and VAP.

Outcome of Transplant Recipients Infected with Omicron BA.1 and BA.2: A Single-Center Retrospective Study in Saudi Arabia.

The outcome of transplant recipients is variable depending on the study population, vaccination status and COVID-19 variants. Our aim was to study the impact of Omicron subvariants on the mortality of transplant recipients. We reviewed the results of SARS-CoV-2 whole genome sequence of random isolates collected from 29 December 2021 until 17 May 2022 in King Faisal Specialist Hospital and Research center, Jeddah (KFSHRC-J), Saudi Arabia performed as hospital genomic surveillance program for COVID-19 variants. We included 25 transplant patients infected with confirmed Omicron variants.17 (68%) and 8 (32%) patients had Omicron BA.1 and BA.2, respectively. 12 (68%) patients had renal transplants. Only 36% of patients received three doses of COVID-19 vaccines. 23 (92%) patients required hospitalization. 20 (80%) patients survived and 6 (25%) required intensive care unit (ICU) admission. Among ICU patients, 66.7% were more than 50 years, 50% had two to three comorbidities and 5 out of 6 (83%) died. The mortality of transplant patients infected with Omicron variants in our cohort was higher than other centers as a limited number of patients received booster vaccines. Optimizing booster vaccination is the most efficient method to improve the mortality of COVID-19 in transplant recipients recognizing the inefficacy of monoclonal antibodies in the presence of SARS-CoV-2 emerging variants. We did not show a difference in mortality in transplant patients infected with Omicron BA.1 and BA.2 knowing the limitation of our sample size.

Modeling the Potential Impact of Remdesivir Treatment for Hospitalized Patients with COVID-19 in Saudi Arabia on Healthcare Resource Use and Direct Hospital Costs: A Hypothetical Study.

BACKGROUND AND OBJECTIVES: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide. Saudi Arabia was significantly impacted by COVID-19. In March 2021, 381,000 cases were reported with 6539 deaths. This study attempts to quantify the impact of remdesivir on healthcare costs in Saudi Arabia, in terms of intensive care unit admissions, mechanical ventilation, and death prevention. METHODS: A forecasting model was designed to estimate the impact of remdesivir on the capacity of intensive care units and healthcare costs with patients requiring low flow oxygen therapy. The forecasting model was applied in the Saudi context with a 20-week projection between 1 February and 14 June, 2021. Model inputs were collected from published global and Saudi literature, available forecasting resources, and expert opinions. Three scenarios were assumed: the effective pandemic infection rate (Rt) remains at 1, the Rt increases up to 1.2, and the Rt declines from 1 to 0.8 over the study period. RESULTS: The model estimated that the use of remdesivir in hospitalized patients, in the optimistic and pessimistic scenarios, could prevent between 1520 and 3549 patient transfers to intensive care units and mechanical ventilation, prevent between 815 and 1582 deaths, and make potential cost savings between $US154 million and $US377 million owing to the reduction in intensive care unit capacity, respectively. CONCLUSIONS: The treatment with remdesivir may improve patient outcomes and reduce the burden on healthcare resources during this pandemic.

Molecular epidemiology and outcome of carbapenem-resistant Enterobacterales in Saudi Arabia.

BACKGROUND: The burden of carbapenem resistance is not well studied in the Middle East. We aimed to describe the molecular epidemiology and outcome of carbapenem-resistant Enterobacterales (CRE) infections from several Saudi Arabian Centers. METHODS: This is a multicenter prospective cohort study conducted over a 28-month period. Patients older than 14 years of age with a positive CRE Escherichia coli or Klebsiella pneumoniae culture and a clinically established infection were included in this study. Univariate and multivariable logistic models were constructed to assess the relationship between the outcome of 30-day all-cause mortality and possible continuous and categorical predictor variables. RESULTS: A total of 189 patients were included. The median patient age was 62.8 years and 54.0% were male. The most common CRE infections were nosocomial pneumonia (23.8%) and complicated urinary tract infection (23.8%) and 77 patients (40.7%) had CRE bacteremia. OXA-48 was the most prevalent gene (69.3%). While 100 patients (52.9%) had a clinical cure, 57 patients (30.2%) had died within 30 days and 23 patients (12.2%) relapsed. Univariate analysis to predict 30-day mortality revealed that the following variables are associated with mortality: older age, high Charlson comorbidity index, increased Pitt bacteremia score, nosocomial pneumonia, CRE bacteremia and diabetes mellitus. In multivariable analysis, CRE bacteremia remained as an independent predictor of 30 day all-cause mortality [AOR and 95% CI = 2.81(1.26-6.24), p = 0.01]. CONCLUSIONS: These data highlight the molecular epidemiology and outcomes of CRE infection in Saudi Arabia and will inform future studies to address preventive and management interventions.

Epidemiology and Clinical Characteristics of People with Confirmed SARS-CoV-2 Infection during the Early COVID-19 Pandemic in Saudi Arabia.

This study provides epidemiologic and clinical characteristics of 492 consecutive patients diagnosed with SARS-CoV-2 infection at King Faisal Specialist Hospital and Research Centre in Saudi Arabia between March and September 2020. Data were collected from electronic case reports. The cohort was 54% male, with 20.4% aged >60 years, 19.9% aged 31−40 years, and 17% aged 41−50 years. The median incubation period was 16 days, with upper and lower 95% quartiles of 27 and 10 days, respectively. Most patients (79.2%) were symptomatic. Variables significantly different between symptomatic and asymptomatic patients were age, blood oxygen saturation percentage, hemoglobin level, lymphocyte count, neutrophil to lymphocyte (NTL) ratio, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level. Asymptomatic patients were mostly younger, with lower body mass index and ALT and AST levels but higher lymphocyte counts, NTL ratio, and CD4, CD8, natural killer cell, IgG, and IgM levels. Factors associated with increased risk of mortality were age (>42 years) and comorbidities, particularly diabetes mellitus and hypertension. Patients who were not given an antiviral regimen were associated with better prognosis than patients who received an antiviral regimen (HR, 0.07; 95% CI, 0.011−0.25). These findings will help clinicians and policymakers adopt best management and treatment options for SARS-CoV-2 infection.

SARS-COV-2 Triggers the Development of Class I and Class II HLA Antibodies in Recovered Convalescent Plasma Donors.

Various studies have shown that SARS-CoV-2 is a highly immunogenic virus. It is known that different types of immunogenic viral pathogens could trigger the formation of HLA antibodies. Therefore, there is a concern that the SARS-CoV-2 could also induce the development of HLA antibodies in volunteers, who donate convalescent plasma after their recovery from COVID-19. HLA antibodies have been identified as the main cause for transfusion-related acute lung injury (TRALI), a well-documented life-threatening complication of transfusions. The TRALI risk could be high in COVID-19 patients who need convalescent plasma, as such patients usually have already an impaired respiratory system affected by the SARS-CoV-2 infection. In this study, we screened 34 convalescent plasma donors on the presence of antibodies against HLA class I and II antigens. All included donors have no any history of sensitization events such as blood transfusions, pregnancy, or previous transplants. We found a high rate of HLA antibody formation in convalescent plasma donors. The frequency of positivity for HLA antibodies for class I, class II, class I and II, and the overall reactivity was 23%, 31%, 46%, and 76%, respectively. The presented data suggest a closed correlation between SARS-CoV-2 virus infection and the development of HLA antibodies in recovered convalescent plasma donors. This finding might have the potential to reduce the risk of TRALI and mortality rate in COVID-19 patients by implementing HLA diagnostic strategies before the administration of convalescent plasma.

Ceftolozane-tazobactam vs. colistin for the treatment of infections due to multidrug-resistant Pseudomonas aeruginosa: a multicentre cohort study.

OBJECTIVES: The aim of this study was to compare the safety and effectiveness of ceftolozane-tazobactam (C-T) to colistin-based regimen for treating infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa. METHODS: This was a retrospective, multicentre, observational cohort study of inpatients who received either C-T or intravenous colistin for treating infections caused by MDR P. aeruginosa. The study was conducted in five tertiary care hospitals in Saudi Arabia. The main study outcomes included clinical cure at end of treatment, in-hospital mortality, and acute kidney injury (AKI). Univariate analysis and multivariate logistic regression model were conducted to evaluate the independent effect of C-T on the clinical outcome. RESULTS: A total of 184 patients were included in the study: 82 patients received C-T, and 102 patients received colistin-based regimen. Clinical cure (77% vs. 57%; P = 0.005; OR, 2.52; 95% CI, 1.32-4.79) was significantly more common in patients who received C-T. After adjusting the difference between the two groups, treatment with C-T is independently associated with clinical cure (adjusted OR, 2.47; 95% CI, 1.16-5.27). In-hospital mortality (39% vs. 49%; P = 0.175; OR, 0.67; 95% CI, 0.37-1.20) was lower in patients who received C-T, but the difference was not significant. AKI (15% vs. 41%; P < 0.001; OR, 0.25; 95% CI, 0.12-0.51) was significantly less common in patients who received C-T. CONCLUSION: C-T is associated with a higher rate of clinical cure and lower rate of AKI compared to colistin. Our findings support the preferential use of C-T over colistin-based regimen for treating these infections.

Early use of tocilizumab in solid organ transplant recipients with COVID-19: A retrospective cohort study in Saudi Arabia.

BACKGROUND: Tocilizumab was studied to reduce cytokine syndrome in patients with severe COVID-19 pneumonia in solid organ transplant (SOT) recipients with conflicting results. We aim to study the early use of tocilizumab in SOT with COVID-19 pneumonia on low flow oxygen. METHODS: This is a retrospective cohort study that was conducted in two transplant centers in Saudi Arabia among 46 SOT with COVID-19 comparing 21 patients who received tocilizumab to 25 patients who received standard of care. Their clinical characteristics and outcomes were described. RESULTS: Compared to patients who received standard of care, patients in the tocilizumab group were older (60.2 ± 12.8 vs. 48.6 ± 12.3, p = .003), had higher ferritin (862.1 ± 919.1 vs. 414 ± 447.3, p = .025) and C-reactive protein (CRP) (85 ± 83.1 vs. 42.9 ± 57.3, p = .012). More patients in the tocilizumab group required high flow oxygen (38.1% vs. 8.0%, p = .028) compared to patients on standard of care. There were no differences in mortality or mechanical ventilation requirement. Hospital stay was significantly shorter in the tocilizumab group than the standard of care group (9.6 ± 7.4 vs. 20.7 ± 11.7, p < .001). CONCLUSIONS: Early use of tocilizumab in SOT was associated with a shorter hospital stay. There was no difference in mortality rate and the requirement for mechanical ventilation in both groups.

Promoting cross-regional collaboration in antimicrobial stewardship: Findings of an infectious diseases working group survey in Arab countries of the Middle East.

BACKGROUND: Antimicrobial resistance is a significant global issue that presents an increasing threat to patients' wellbeing. Although a global concern, the emergence of multi-drug resistant organisms is of particular significance in the Middle East. In recent years, this region has seen an alarming increase in antimicrobial resistance presenting a major challenge to physicians managing various infectious diseases. METHODS: A Working Group comprising experts in infectious diseases from Arab countries of Middle East assembled to review similarities and differences in antimicrobial practices and management of multi-drug resistant organisms across the region and assess the barriers to achieving cross-regional collaboration. The Working Group conducted an anonymous online survey to evaluate current practice and understanding of management of multi-drug resistant organisms across the region. RESULTS: A total of 122 physicians from Arab countries of the Middle East responded to the survey. Their responses demonstrated heterogeneity between countries in awareness of local epidemiology, management of multi-drug resistant organisms and antimicrobial stewardship practices. The Working Group recognized similarities and differences in the management of multi-drug resistant organisms across the region, and these were validated by the data collected in the survey. Overall, the similarities across the region reflect several key issues that can have an impact on the management of multi-drug resistant organisms and the prevention of antimicrobial resistance. CONCLUSIONS: This paper highlights the urgency of addressing antimicrobial resistance in Arab countries of the Middle East. The Working Group identified key barriers to effective management which may guide the development of future coherent strategies to promote effective antimicrobial stewardship in the region. Here, we outline a call to action for the region, with a need to focus on training and education, capacity building, infrastructure, regional research, and regional surveillance.

Critically ill patients with diabetes and Middle East respiratory syndrome: a multi-center observational study.

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 and 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 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. RESULTS: Of 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 < 0.0001). Multivariable regression analysis showed that diabetes was an independent risk factor for 90-day mortality (odds ratio, 2.09; 95% confidence interval, 1.18-3.72). CONCLUSIONS: Half 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.

Outcome of COVID19 in Patients With Osteogenesis Imperfecta: A Retrospective Multicenter Study in Saudi Arabia.

Background: Although genetic diseases are rare, children with such conditions who get infected with COVID-19 tend to have a severe illness requiring hospitalization. Osteogenesis imperfecta (OI) is a rare genetic disorder of collagen resulting in fractures and skeletal deformities. Kyphoscoliosis, restrictive lung disease, and pneumonia worsen the prognosis of patients with OI. The use of bisphosphonate improves bone mineral density (BMD) and reduces fractures in OI. There is no literature describing the impact of COVID-19 in patients with OI. Methodology: A retrospective multi-center study was performed in three hospitals in Jeddah and Riyadh, Saudi Arabia, from March 1st, 2020, until August 31st, 2021, aiming to evaluate the outcome of COVID-19 in patients with OI. Demographics, vaccination status, underlying kyphoscoliosis, functional status, use of bisphosphonate, BMD, and COVID-19 severity, and course were recorded for all patients. Results: Twelve cases of confirmed COVID-19 were identified among 146 patients with OI. 9 (75%) of patients were less than 18 years, 6 (50%) were male, 5 (41%) had kyphoscoliosis, and 5 (41%) were wheelchair-bound. 6 (50%) received bisphosphonate, and 7(58%) had normal BMD. All patients had mild disease and did not require hospitalization. None of OI the patients with COVID-19 were fully vaccinated before the infection, and some were ineligible for vaccination. Conclusion: Patients with OI and COVID-19 in our study recovered without complications, unlike patients with other genetic diseases. Young age and mild illness contributed to the favorable outcome. Half of the patients received bisphosphonate and had normal BMD.

Management of infections caused by WHO critical priority Gram-negative pathogens in Arab countries of the Middle East: a consensus paper.

Antimicrobial resistance is an important global issue that impacts the efficacy of established antimicrobial therapy. This is true globally and within the Arab countries of the Middle East, where a range of key Gram-negative pathogens pose challenges to effective therapy. There is a need to establish effective treatment recommendations for this region given specific challenges to antimicrobial therapy, including variations in the availability of antimicrobials, infrastructure and specialist expertise. This consensus provides regional recommendations for the first-line treatment of hospitalized patients with serious infections caused by World Health Organization critical priority Gram-negative pathogens Acinetobacter baumannii and Pseudomonas aeruginosa resistant to carbapenems, and Enterobacteriaceae resistant to carbapenems and third-generation cephalosporins. A working group comprising experts in infectious disease across the region was assembled to review contemporary literature and provide additional consensus on the treatment of key pathogens. Detailed therapeutic recommendations are formulated for these pathogens with a focus on bacteraemia, nosocomial pneumonia, urinary tract infections, skin and soft tissue infections, and intra-abdominal infections. First-line treatment options are provided, along with alternative agents that may be used where variations in antimicrobial availability exist or where local preferences and resistance patterns should be considered. These recommendations take into consideration the diverse social and healthcare structures of the Arab countries of the Middle East, meeting a need that is not filled by international guidelines. There is a need for these recommendations to be updated continually to reflect changes in antimicrobial resistance in the region, as well as drug availability and emerging data from clinical trials.

Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study.

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-ß1a; none received rIFN-ß1b). 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-ß1a) 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.

Antifungal resistance in patients with Candidaemia: a retrospective cohort study.

BACKGROUND: Candidaemia is the most common form of invasive candidiasis. Resistant Candida blood stream infection (BSI) is rising, with limitations on the development of broader-spectrum antifungal agents worldwide. Our study aimed to identify the occurrence of antifungal-resistant candidaemia and the distribution of these species, determine the risk factors associated with antifungal resistance and evaluate the association of antifungal-resistant candidaemia with the length of intensive care unit (ICU) and hospital stay and with 30-day mortality. METHODS: A retrospective cohort study was conducted at King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia. Adult patients diagnosed with candidaemia from January 2006 to December 2017 were included. RESULTS: A total of 196 BSIs were identified in 94 males (49.74%) and 95 females (50.26%). C. glabrata was the most commonly isolated Candida species, with 59 (30%), followed by C. albicans with 46 (23%). Susceptibility data were available for 122/189 patients, of whom 26/122 (21%) were resistant to one or more antifungals. C. parapsilosis with available sensitivity data were found in 30/122 isolates, of which 10/30 (33%) were resistant to fluconazole. Risk factors significantly associated with antifungal-resistant candidaemia included previous echinocandin exposure (odds ratio (OR) =1.38; 95% confidence interval (CI) (1.02-1.85); P = 0.006) and invasive ventilation (OR = 1.3; 95% CI (1.08-1.57); P = 0.005). The median length of ICU stay was 29 days [range 12-49 days] in the antifungal-resistant group and 18 days [range 6.7-37.5 days] in the antifungal-sensitive group (P = 0.28). The median length of hospital stay was 51 days [range 21-138 days] in the antifungal-resistant group and 35 days [range 17-77 days] in the antifungal-sensitive group (P = 0.09). Thirty-day mortality was 15 (57.7%) and 54 (56.25%) among the antifungal-resistant and antifungal-sensitive groups, respectively (OR = 1.01; 95% CI (0.84-1.21); P = 0.89). CONCLUSIONS: Our results indicate a high frequancy of non- C. albicans candidaemia. The rise in C. parapsilosis resistance to fluconazole is alarming. Further studies are required to confirm this finding.

Family cluster of multi-drug resistant tuberculosis in Kingdom of Saudi Arabia.

We describe the clinical and genetic characteristics of multi-drug resistant tuberculosis (MDR-TB) in a family cluster in the western region of Kingdom of Saudi Arabia diagnosed between 2012 and 2016. All cases had risk factors for tuberculosis acquisition and they were not household contacts of the index case. Genetic analysis detected both MDR-TB and pre-extensively drug-resistant tuberculosis (pre-XDR TB) strains in the index case and confirmed tuberculosis transmission between two cases. Lack of early diagnosis of MDR-TB by molecular testing and lack of extended contact tracing contributed to the transmission of MDR-TB among this family cluster over four years.

Systematic review and meta-analysis of the safety of erythromycin compared to clarithromycin in adults and adolescents with pneumonia.

Macrolides are recommended for the treatment of community-acquired pneumonia (CAP). It is debatable whether erythromycin is associated with more adverse drug reactions (ADRs) compared to clarithromycin, and both are recommended in clinical practice guidelines. This meta-analysis aim is to compare ADRs in CAP patients treated with erythromycin versus clarithromycin. Two investigators independently searched PubMed, EMBASE and Cochrane Library databases through Feb 07, 2019. Randomized-controlled trials (RCTs) comparing ADRs of monotherapy with erythromycin versus with clarithromycin in adults or adolescents with CAP were included. We estimated risk ratios (RRs) with 95% confidence intervals (CIs) using random-effects models and evaluated heterogeneity (I2). Bias risk was assessed using the Cochrane risk of bias tool for RCTs. Five RCTs (total of 693 patients) were included. A significantly higher discontinuation rate due to ADRs was found with erythromycin compared with clarithromycin (RR, 4.347; 95% CI, 2.506-7.539; p < 0.001; I2=0%). Overall, ADRs occurred more significantly with erythromycin compared with clarithromycin (RR, 1.773; 95% CI, 1.423-2.209; p < 0.001; I2=0%). Gastrointestinal (GI) ADRs were higher with erythromycin (RR, 2.678; 95% CI, 1.791-4.006; p < 0.001; I2=5.835%). Restriction of analyses to double-blind RCTs did not change our findings. Based on meta-analysis of RCTs in adults and adolescents with CAP, erythromycin results in more overall ADRs and GI ADRs, as well as a higher rate of discontinuation due to ADRs. Therefore, given that erythromycin is not more effective than clarithromycin, erythromycin should not be selected unless other macrolides cannot be used.

Efficacy of ceftazidime-avibactam in the treatment of infections due to Carbapenem-resistant Enterobacteriaceae.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) represent an important global threat. The aim of this study is to describe the clinical course and outcomes of patients with CRE infections treated with ceftazidime-avibactam (CAZ-AVI) compared to patients treated with other agents. METHODS: A retrospective cohort study of patients with established CRE infections from January 2017 until August 2018 was conducted. All patients who received CAZ-AVI and all cultures with carbapenem-resistant isolates were screened. We compared patients who received CAZ-AVI for CRE infections with patients who received other agents. RESULTS: A total of 38 consecutive patients with CRE infections were identified. Age and baseline comorbidities were similar between the two groups. The median time from admission to isolation of CRE culture was 22.5 days in the CAZ-AVI group and 17 days in the comparative group (P = 0.7). The incidence of CRE bacteremia was similar between the two groups: 7 patients (70%) in the CAZ-AVI group and 15 patients (53.6%) in the comparative group (P = 0.47). The most common type of CRE infections in both groups was hospital acquired pneumonia (HAP). Klebsiella pneumoniae was the predominant pathogen in both groups. A carbapenemase gene was detected in 35 (92%) patients; the OXA-48 gene was the predominant gene identified in 28 (74%) isolates. Eight out of ten patients in the CAZ-AVI group and fifteen out of twenty-eight in the comparative group achieved clinical remission (P = 0.14). After thirty days, all-cause mortality was observed in five patients in the CAZ-AVI group and 16 patients in the comparative group, accounting for 50 and 57% respectively. CONCLUSIONS: In patients with established OXA-48-type CRE infection, CAZ-AVI is a reasonable alternative to standard therapy. These findings need to be confirmed in prospective studies.

Quality of life reported by survivors after hospitalization for Middle East respiratory syndrome (MERS).

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 < 0.02). CONCLUSIONS: Functional scores were similar for MERS and non-MERS SARI survivors. However, MERS survivors of critical illness reported lower quality of life than survivors of less severe illness. Efforts are needed to address the long-term medical and psychological needs of MERS survivors.

Noninvasive ventilation in critically ill patients with the Middle East respiratory syndrome.

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.

Management and outcome of latent tuberculosis in living renal transplant donors.

In regions where tuberculosis (TB) is endemic, up to 15% of kidney transplant recipients develop Mycobacterium tuberculosis infections (TBI), typically with an increased risk of disseminated disease and allograft loss. To reduce these risks, donors and recipients with latent TB usually receive isoniazid (INH) prophylaxis. However, it is unclear whether latent TB in donors justifies routine prophylaxis of recipients. At our institution, donors and recipients with latent infection receive INH prophylaxis, and those who do not have latent infections are not routinely treated. We retrospectively analyzed the records of 269 living donor kidney transplant recipient and donor pairs in order to determine the risk of posttransplant TB in those whose kidneys were obtained from living donors with latent TB. Three recipients (1.1%) developed active TB, three, 11, and 12 months after transplantation. Neither donors nor recipients in these pairs had evidence of latent TB before transplantation. Of the 224 pairs with complete data, 24 transplant recipients with negative tuberculin skin test received organs from living donors with evidence of latent TB. None developed active TB, and kidney function one and three years later was preserved. Our findings suggest that routine use of prophylaxis in recipients without latent TB who receive organs from positive donors might not add additional benefit.