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Yosra M Alkabab,1 Mushira A Enani,2 Nouf Y Indarkiri,3 Scott K Heysell1 1Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA; 2Department of Infectious Diseases, King Fahad Medical City, 3Department of Family Medicine, Prince Sultan Military Medical City, Riyadh, Saudi Arabia Background: Prior research suggests that diabetes mellitus (DM) is associated with increasing risk for developing cavitary lung disease in patients with pulmonary tuberculosis (TB). Additionally, chest computed tomography (CT) scan may be more sensitive than chest X-ray in detecting cavitary disease in such patients. The aim of this study was to compare the performance of chest CT to chest X-ray in detecting cavitary lung disease and to compare the frequency of cavities between TB patients with DM and without DM.Patients and methods: We conducted a retrospective cohort study at King Fahad Medical City, Riyadh, Saudi Arabia, from January 2004 to December 2015. We included patients aged 18 years and older with a positive sputum culture for Mycobacterium tuberculosis, and their medical charts were reviewed from admission to discharge.Results: Of the 133 patients who met the inclusion criteria, 38 (28.6%) patients were known to have DM and were compared with 95 (71.4%) patients without DM. DM patients with glycated hemoglobin (HbA1c) >6.5% had significantly more cavitary lesions when compared to all patients (with or without DM) with HbA1c

Background: Several observational studies have inconsistently demonstrated that vitamin D deficiency is a risk factor for coronavirus disease-19 (COVID-19) infection and severity. Discrepancies in results may partially be explained by the individuals’ immune profiles, which are modulated, in varying degrees, by vitamin D status and sex hormones. Methods: In this study we evaluated the differences and associations of serum levels of 25(OH)D with 34 cytokines in 220 adults (82 controls (41 males; 41 females) and 138 SARS-CoV-2 patients (79 males and 59 females)) with and without COVID-19. Results: Serum 25(OH)D levels were significantly lower in the SARS-CoV-2 group than in the controls. Serum IP-10, MCP-1, CRP, IFNγ, IL-10, IL-13, IL-17α, IL-23, and IL-6 were significantly higher in COVID-19 patients compared to controls. Serum levels of VEGF, IFNγ, IL-13, and IL-5 were significantly higher in male patients than in females. 25(OH)D was significantly correlated with EFG (R = 0.39, p < 0.05) and IL-15 (R = 0.39, p < 0.05) in male patients, while it was inversely correlated with CRP (R = −0.51, p < 0.05) in female patients. Conclusions: Altered levels of cytokines, chemokines, and vitamin D were observed in SARS-CoV-2 adult patients. These expressions were sexually dimorphic and thus highlight the sex-specific nature of the active immune response following SARS-CoV-2 infection.

Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in hospitals worldwide. The cornerstones of effective treatment of IAIs include early recognition, adequate source control, appropriate antimicrobial therapy, and prompt physiologic stabilization using a critical care environment, combined with an optimal surgical approach. Together, the World Society of Emergency Surgery (WSES), the Global Alliance for Infections in Surgery (GAIS), the Surgical Infection Society-Europe (SIS-E), the World Surgical Infection Society (WSIS), and the American Association for the Surgery of Trauma (AAST) have jointly completed an international multi-society document in order to facilitate clinical management of patients with IAIs worldwide building evidence-based clinical pathways for the most common IAIs. An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting information was shared by an international task force from 46 countries with different clinical backgrounds. The aim of the document is to promote global standards of care in IAIs providing guidance to clinicians by describing reasonable approaches to the management of IAIs., (© 2021. The Author(s).)

Objective: Vitamin D deficiency has been associated with an increased risk of COVID-19 severity. This multi-center randomized clinical trial aims to determine the effects of 5000 IU versus 1000 IU daily oral vitamin D3 supplementation in the recovery of symptoms and other clinical parameters among mild to moderate COVID-19 patients with sub-optimal vitamin D status., Study Design and Setting: A total of 69 reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 positive adults who were hospitalized for mild to moderate COVID-19 disease were allocated to receive once daily for 2 weeks either 5000 IU oral vitamin D3 ( n = 36, 21 males; 15 females) or 1000 IU oral vitamin D3 (standard control) ( n = 33, 13 males; 20 females). Anthropometrics were measured and blood samples were taken pre- and post-supplementation. Fasting blood glucose, lipids, serum 25(OH)D, and inflammatory markers were measured. COVID-19 symptoms were noted on admission and monitored until full recovery., Results: Vitamin D supplementation for 2 weeks caused a significant increase in serum 25(OH)D levels in the 5000 IU group only (adjusted p = 0.003). Within-group comparisons also showed a significant decrease in BMI and IL-6 levels overtime in both groups ( p -values < 0.05) but was not clinically significant in between-group comparisons. Kaplan-Meier survival analysis revealed that the 5000 IU group had a significantly shorter time to recovery (days) than the 1000 IU group in resolving cough, even after adjusting for age, sex, baseline BMI, and D-dimer (6.2 ± 0.8 versus 9.1 ± 0.8; p = 0.039), and ageusia (loss of taste) (11.4 ± 1.0 versus 16.9 ± 1.7; p = 0.035)., Conclusion: A 5000 IU daily oral vitamin D3 supplementation for 2 weeks reduces the time to recovery for cough and gustatory sensory loss among patients with sub-optimal vitamin D status and mild to moderate COVID-19 symptoms. The use of 5000 IU vitamin D3 as an adjuvant therapy for COVID-19 patients with suboptimal vitamin D status, even for a short duration, is recommended.

Understanding the immune response to Middle East respiratory syndrome coronavirus (MERS-CoV) is crucial for disease prevention and vaccine development. We studied the antibody responses in 48 human MERS-CoV infection survivors who had variable disease severity in Saudi Arabia. MERS-CoV-specific neutralizing antibodies were detected for 6 years postinfection.

Objectives: Vitamin D status in patients with COVID-19 is an on-going controversial issue. This study aims to determine differences in the serum 25(OH)D concentrations of Arab Gulf adult residents screened for SARS-CoV-2 and its association with risk of COVID-19 infection together with other comorbidities., Methods: In this multi-center, case-control study, a total of 220 male and female adults presenting with none to mild symptoms were screened for COVID-19 (n = 138 RT-PCR-confirmed SARS-CoV-2 positive and 82 negative controls). Medical history was noted. Anthropometrics were measured and non-fasting blood samples were collected for the assessment of glucose, lipids, inflammatory markers and serum 25(OH)D concentrations., Results: Serum 25(OH)D levels were significantly lower in the SARS-CoV-2 positive group compared to the negative group after adjustment for age and BMI (52.8 nmol/l ± 11.0 versus 64.5 nmol/l ± 11.1; p = 0.009). Being elderly (> 60 years) [Odds ratio 6 (95% Confidence Interval, CI 2-18; p = 0.001) as well as having type 2 diabetes (T2D) [OR 6 (95% CI 3-14); p < 0.001)] and low HDL cholesterol (HDL-c) [OR 6 (95% CI 3-14); p < 0.001)] were significant risk factors for COVID-19 infection independent of age, sex and obesity., Conclusions: Among Arab Gulf residents screened for SARS-CoV-2, serum 25(OH) D levels were observed to be lower in those who tested positive than negative individuals, but it was the presence of old age, diabetes mellitus and low-HDL-c that were significantly associated with risk of COVID-19 infection. Large population-based randomized controlled trials should be conducted to assess the protective effects of vitamin D supplementation against COVID-19.

Public health endorsements during the present COVID-19 pandemic has led the governments of largely affected countries to imply policies that restrict social mobility to slow COVID-19 spread. The study aimed to explore the effects of COVID-19 home quarantine on lifestyle and health behavior of Saudi residents. An online survey in Saudi Arabia was launched from May 11 to June 6, 2020. The survey was designed by multidisciplinary scientists and academics uploaded and shared through the Google platform in Arabic and English languages. Questions presented related to responses "before" and "during" COVID-19 home quarantine. A total of 1965 respondents participated and were included in the analysis [921 (47.0%) males and 1044 (53.0%) females]. Non-Saudis were more likely to increase their physical activity during quarantine [odds ratio (95% confidence interval 1.41 (1.11-1.79); p < 0.005]. Prevalence of participants walking daily for more than 4 times per week significantly decreased during pandemic (before vs during, 30.5% vs 29.1%) which was in parallel to the significant increase in the prevalence of participants who did not perform daily walking during the quarantine (21% vs 22.9%; p < 0.001). The prevalence of participants who often consume snacks between meals increased during quarantine (27.4% vs 29.4%, p < 0.001), while the prevalence of participants who never consumed fresh fruits and vegetables significantly increased during home quarantine (2.4% vs 3.7%; p = 0.019). The lockdown imposed in Saudi Arabia modestly but significantly impacted physical activity and dietary behaviors of several citizens and residents in an unhealthy way. Interventions to alleviate these acute adverse lifestyle behaviors during pandemic should be formulated.

Background: Nephrotoxicity is a known adverse effect of polymyxin antibiotics, including colistin. Although previous meta-analyses have aimed to characterize colistin-associated nephrotoxicity risk relative to other antibiotics, included studies were observational in nature with high risk of confounding and heterogeneity. We conducted this systematic review and meta-analysis of exclusively randomized controlled trials (RCTs) to evaluate the incidence of nephrotoxicity associated with colistin versus minimally nephrotoxic antibiotics., Methods: We searched PubMed, EMBASE, Cochrane Library, and 3 trial registries for RCTs comparing the nephrotoxicity of colistin to nonpolymyxin antibiotics. Randomized controlled trials that used aminoglycosides were excluded. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. The study outcome was the rate of nephrotoxicity., Results: Five RCTs with a total of 377 patients were included. Most patients received colistin for pneumonia in the intensive care unit, and the comparators were β-lactam-based regimens. Colistimethate sodium was dosed at 9 million units/day (300 mg/day of colistin base activity), with administration of a loading dose in 4 studies. The nephrotoxicity incidence in patients who received colistin was 36.2% (95% CI, 23.3% to 51.3%). The nephrotoxicity rate was significantly higher in the colistin arm than comparators (RR, 2.40; 95% CI, 1.47 to 3.91; P ≤ .001; I 2 = 0%), and the number needed to harm was 5. Findings persisted upon one-study-removed-analysis., Conclusions: This meta-analysis of RCTs found a colistin-associated nephrotoxicity rate of 36.2% and an increase in this risk compared with β-lactam-based regimens by 140%. Colistin should be regarded as a last-line agent and safer alternatives should be considered when possible., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: To systematically review the literature about the association between systemic corticosteroid therapy (CST) and outcomes of COVID-19 patients., Methods: We searched Medline, Embase, EBM Reviews, Scopus, Web of Science, and preprints up to July 20, 2020. We included observational studies and randomized controlled trials (RCT) that assessed COVID-19 patients treated with CST. We pooled adjusted effect estimates of mortality and other outcomes using a random effect model, among studies at low or moderate risk for bias. We assessed the certainty of evidence for each outcome using the GRADE approach., Results: Out of 1067 citations screened for eligibility, one RCT and 19 cohort studies were included (16,977 hospitalized patients). Ten studies (1 RCT and 9 cohorts) with 10,278 patients examined the effect of CST on short term mortality. The pooled adjusted RR was 0.92 (95% CI 0.69-1.22, I 2 = 81.94%). This effect was observed across all stages of disease severity. Four cohort studies examined the effect of CST on composite outcome of death, ICU admission and mechanical ventilation need. The pooled adjusted RR was 0.41(0.23-0.73, I 2 = 78.69%). Six cohort studies examined the effect of CST on delayed viral clearance. The pooled adjusted RR was 1.47(95% CI 1.11-1.93, I 2 = 43.38%)., Conclusion: In this systematic review, as of July 2020, heterogeneous and low certainty cumulative evidence based on observational studies and one RCT suggests that CST was not associated with reduction in short-term mortality but possibly with a delay in viral clearance in patients hospitalized with COVID-19 of different severities. However, the discordant results between the single RCT and observational studies as well as the heterogeneity observed across observational studies, call for caution in using observational data and suggests the need for more RCTs to identify the clinical and biochemical characteristics of patients' population that could benefit from CST., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a lethal zoonotic pathogen circulating in the Arabian Peninsula since 2012. There is no vaccine for MERS and anti-viral treatment is generally not applicable. We investigated the evolution of the MERS-CoV spike gene sequences and changes in viral loads over time from patients in Saudi Arabia from 2105-2017. All the MERS-CoV strains belonged to lineage 5, and showed high sequence homology (99.9%) to 2017 strains. Recombination analysis showed a potential recombination event in study strains from patients in Saudi Arabia. The spike gene showed eight amino acid substitutions, especially between the A1 and B5 lineage, and contained positively selected codon 1020. We also determined that the viral loads were significantly ( p < 0.001) higher in fatal cases, and virus shedding was prolonged in some fatal cases beyond 21 days. The viral concentration peaked during the first week of illness, and the lower respiratory specimens had higher levels of MERS-CoV RNA. The presence of the diversifying selection and the topologies with the structural mapping of residues under purifying selection suggested that codon 1020 might have a role in the evolution of spike gene during the divergence of different lineages. This study will im-prove our understanding of the evolution of MERS-CoV, and also highlights the need for enhanced surveillance in humans and dromedaries. The presence of amino acid changes at the N-terminal domain and structural mapping of residues under positive selection at heptad repeat 1 provides better insight into the adaptive evolution of the spike gene and might have a potential role in virus-host tropism and pathogenesis.

MERS-CoV, a highly pathogenic virus in humans, is associated with high morbidity and case fatality. Inflammatory responses have a significant impact on MERS-CoV pathogenesis and disease outcome. However, CD4 + T-cell induced immune responses during acute MERS-CoV infection are barely detectable, with potent inhibition of effector T cells and downregulation of antigen presentation. The local pulmonary immune response, particularly the Th1 and Th2-related immune response during acute severe MERS-CoV infection is not fully understood. In this study, we offer the first insights into the pulmonary gene expression profile of Th1 and Th2-related cytokines/chemokines (Th1 & Th2 responses) during acute MERS-CoV infection using RT 2 Profiler PCR Arrays. We also quantified the expression level of primary inflammatory cytokines/chemokines. Our results showed a downregulation of Th2, inadequate (partial) Th1 immune response and high expression levels of inflammatory cytokines IL-1α and IL-1β and the neutrophil chemoattractant chemokine IL-8 (CXCL8) in the lower respiratory tract of MERS-CoV infected patients. Moreover, we identified a high viral load in all included patients. We also observed a correlation between inflammatory cytokines, Th1, and Th2 downregulation and the case fatality rate. Th1 and Th2 response downregulation, high expression of inflammatory cytokines, and high viral load may contribute to lung inflammation, severe infection, the evolution of pneumonia and ARDS, and a higher case fatality rate. Further study of the molecular mechanisms underlying the Th1 and Th2 regulatory pathways will be vital for active vaccine development and the identification of novel therapeutic strategies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The World Health Organization Essential Medicines List (WHO-EML) includes 'access' antibiotics, judged essential to treat common infections. The European Society of Clinical Microbiology and Infectious Diseases Study Group for Antimicrobial Stewardship defined a list of 'forgotten' antibiotics, some old and often off-patent antibiotics, which have particular value for specific indications., Objective: To investigate which WHO-EML 'access' and 'forgotten' antibiotics are approved at national level in a sample of low- to middle-income countries (LMICs)., Methods: The Scientific Committee used a consensus procedure to select 26 WHO-EML 'access' and 15 'forgotten' antibiotics. Paediatric formulations were explored for 14 antibiotics. An internet-based questionnaire was circulated to 40 LMIC representatives. Antibiotics were defined as approved if an official drug regulatory agency and/or the national ministry of health licensed their use, making them, at least theoretically, available on the market., Results: Twenty-eight LMICs (11 in Africa, 11 in Asia and six in America) were surveyed. Nine WHO-EML 'access' antibiotics (amoxicillin, ampicillin, benzylpenicillin, ceftriaxone, clarithromycin, ciprofloxacin, doxycycline, gentamicin and metronidazole) were approved in all countries, and all 26 'access' antibiotics were approved in more than two-thirds of countries. Among the 15 'forgotten' antibiotics, only one was approved in more than two-thirds of countries. The median number of approved antibiotics per country was 30 (interquartile range 23-35). Six of 14 paediatric formulations (amoxicillin, amoxicillin-clavulanic acid, oral antistaphylococcal penicillin, cotrimoxazole, erythromycin and metronidazole) were approved in more than two-thirds of countries., Conclusions: WHO-EML 'access' antibiotics and the most frequently used formulations for paediatrics were approved in the vast majority of the 28 surveyed LMICs. This was not the case for many of the 'forgotten' antibiotics, despite their important role, particularly in areas with high prevalence of multi-drug-resistant bacteria., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Insulin and lysozyme share the common features of being prone to aggregate and having biomedical importance. Encapsulating lysozyme and insulin in micellar nanoparticles probably would prevent aggregation and facilitate oral drug delivery. Despite the vivid structural knowledge of lysozyme and insulin, the environment-dependent oligomerization (dimer, trimer, and multimer) and associated structural dynamics remain elusive. The knowledge of the intra- and intermolecular interaction profiles has cardinal importance for the design of encapsulation protocols. We have employed various biophysical methods such as NMR spectroscopy, X-ray crystallography, Thioflavin T fluorescence, and atomic force microscopy in conjugation with molecular modeling to improve the understanding of interaction dynamics during homo-oligomerization of lysozyme (human and hen egg) and insulin (porcine, human, and glargine). The results obtained depict the atomistic intra- and intermolecular interaction details of the homo-oligomerization and confirm the propensity to form fibrils. Taken together, the data accumulated and knowledge gained will further facilitate nanoparticle design and production with insulin or lysozyme-related protein encapsulation., Competing Interests: The authors declare no competing financial interest.

Imipenem and meropenem are the recommended antipseudomonal carbapenems for nosocomial pneumonia per clinical practice guidelines. However, these agents have a relatively broader spectrum of activity than other antibiotics and need to be reserved. Carbapenems might cause higher rate of superinfection. The aim of this study was to compare the rate of superinfection between patients who received imipenem or meropenem versus those who received non-carbapenem treatment. PubMed, EMBASE, Cochrane Library databases and two trial registries were searched for relevant randomized controlled trials of hospitalized adults with pneumonia through February 24, 2017 without date or language restrictions. Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using random-effects models. The primary outcome was based on the intention-to-treat analysis while clinically evaluable patients were analyzed as secondary outcome. Eight RCTs were included in this meta-analysis. A statistically higher risk of superinfection with low heterogeneity (RR = 1.690, 95% CI 1.247-2.291, p = 0.001, I 2  = 0%) was associated with the two carbapenems compared to non-carbapenems. However, in comparison with non-carbapenems, superinfection with imipenem was significantly higher (RR = 1.694, 95% CI 1.234-2.325, p = 0.001, I 2  = 0%), while it was non-significant with meropenem (RR = 1.647, 95% CI 0.552-4.919, p = 0.371, I 2  = 0%). Superinfection was statistically higher in both double-blind and open-label studies and when carbapenems were compared to other antipseudomonal beta-lactams. This meta-analysis identified significantly higher superinfection with imipenem compared to non-carbapenems. The findings confirm the theory of higher superinfections with broader spectrum agents and provide additional support for reserving carbapenems for the treatment of infections caused by multidrug-resistant organisms., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The Global Alliance for Infections in Surgery appreciates the great effort of the task force who derived and validated the Sepsis-3 definitions and considers the new definitions an important step forward in the evolution of our understanding of sepsis. Nevertheless, more than a year after their publication, we have a few concerns regarding the use of the Sepsis-3 definitions., Competing Interests: Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objectives: To identify clinical presentation, predisposing factors, and the outcome in patients with Group A Streptococcal bacteremia. Methods: This is a retrospective study of 33 pediatric and adult patients with Streptococcus pyogenes bacteremia, admitted at King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia from 2007 to 2015. Results: Thirty-three patient records, documenting bacteremia with group A beta-hemolytic streptococcus, were reviewed. Approximately 51.5% were pediatric and 48.5% were adult patients, with a male to female ratio of 2:1. The most frequently reported complications were renal impairment (45.5%) and acute respiratory distress (21.2%), followed by localized infection (15.2%), pleural effusion (6.1%), abscess (9.1%), necrotizing fasciitis (9.1%), septic arthritis, and osteomyelitis (3%). There were 10 episodes of shock: 6 were in pediatric and 4 were in adult patients. At the end of the study period, 12.1% patients died from the illness, 81.1% recovered from illness with no sequelae, while 6.1% recovered with sequelae. Mortality was observed in 4 patients; of them, 3 were pediatric patients and one was an adult with co-morbidities. Conclusions: We have noted a minimal change in the disease pattern over the 28 years in Saudi Arabia. The management of invasive GAS infection depends on an accurate and timely diagnosis with an appropriate use of antimicrobial therapy. The highest risks appear to be related to chronic illness. Invasive Group A Streptococcal infection is known to have a high mortality rate.

We explored in detail the nationwide existence of Mycobacterium riyadhense in Saudi Arabia. In 18 months, 12 new cases of M. riyadhense infection were observed, predominantly among Saudi nationals, as a cause of pulmonary disease. M. riyadhense may be emerging as a more common pathogen in Saudi Arabia.

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].

Background: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world., Methods: A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery., Results: The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4-6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p  < 0.05) compared to community teaching (83.3%) and community hospitals (66.7%). Protocols for pre-operative prophylaxis and for antimicrobial treatment of surgical infections were respectively implemented in 96.2 and 82.3% of the hospitals. The majority of the surgical departments implemented both persuasive and restrictive interventions (72.8%). The most common types of interventions in surgical departments were dissemination of educational materials (62.5%), expert approval (61.0%), audit and feedback (55.1%), educational outreach (53.7%), and compulsory order forms (51.5%)., Conclusion: The survey showed a heterogeneous organization of ASPs worldwide, demonstrating the necessity of a multidisciplinary and collaborative approach in the battle against antimicrobial resistance in surgical infections, and the importance of educational efforts towards this goal.

Purpose: To evaluate the follow-up chest radiographic findings in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) who were discharged from the hospital following improved clinical symptoms., Materials and Methods: Thirty-six consecutive patients (9 men, 27 women; age range 21-73 years, mean ± SD 42.5 ± 14.5 years) with confirmed MERS-CoV underwent follow-up chest radiographs after recovery from MERS-CoV. The 36 chest radiographs were obtained at 32 to 230 days with a median follow-up of 43 days. The reviewers systemically evaluated the follow-up chest radiographs from 36 patients for lung parenchymal, airway, pleural, hilar and mediastinal abnormalities. Lung parenchyma and airways were assessed for consolidation, ground-glass opacity (GGO), nodular opacity and reticular opacity (i.e., fibrosis). Follow-up chest radiographs were also evaluated for pleural thickening, pleural effusion, pneumothorax and lymphadenopathy. Patients were categorized into two groups: group 1 (no evidence of lung fibrosis) and group 2 (chest radiographic evidence of lung fibrosis) for comparative analysis. Patient demographics, length of ventilations days, number of intensive care unit (ICU) admission days, chest radiographic score, chest radiographic deterioration pattern (Types 1-4) and peak lactate dehydrogenase level were compared between the two groups using the student t -test, Mann-Whitney U test and Fisher's exact test., Results: Follow-up chest radiographs were normal in 23 out of 36 (64%) patients. Among the patients with abnormal chest radiographs (13/36, 36%), the following were found: lung fibrosis in 12 (33%) patients GGO in 2 (5.5%) patients, and pleural thickening in 2 (5.5%) patients. Patients with lung fibrosis had significantly greater number of ICU admission days (19 ± 8.7 days; P value = 0.001), older age (50.6 ± 12.6 years; P value = 0.02), higher chest radiographic scores [10 (0-15.3); P value = 0.04] and higher peak lactate dehydrogenase levels (315-370 U/L; P value = 0.001) when compared to patients without lung fibrosis., Conclusion: Lung fibrosis may develop in a substantial number of patients who have recovered from Middle East respiratory syndrome coronavirus (MERS-CoV). Significantly greater number of ICU admission days, older age, higher chest radiographic scores, chest radiographic deterioration patterns and peak lactate dehydrogenase levels were noted in the patients with lung fibrosis on follow-up chest radiographs after recovery from MERS-CoV., Competing Interests: There are no conflicts of interest.

Interactions between human lysozyme (HL) and the lipopolysaccharide (LPS) of Klebsiella pneumoniae O1, a causative agent of lung infection, were identified by surface plasmon resonance. To characterize the molecular mechanism of this interaction, HL binding to synthetic disaccharides and tetrasaccharides representing one and two repeating units, respectively, of the O-chain of this LPS were studied. pH-dependent structural rearrangements of HL after interaction with the disaccharide were observed through nuclear magnetic resonance. The crystal structure of the HL-tetrasaccharide complex revealed carbohydrate chain packing into the A, B, C, and D binding sites of HL, which primarily occurred through residue-specific, direct or water-mediated hydrogen bonds and hydrophobic contacts. Overall, these results support a crucial role of the Glu35/Asp53/Trp63/Asp102 residues in HL binding to the tetrasaccharide. These observations suggest an unknown glycan-guided mechanism that underlies recognition of the bacterial cell wall by lysozyme and may complement the HL immune defense function.

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.

The Antimicrobial peptides (e.g. defensins, hevein-like molecules and food-protecting peptides like nisin) are able to interact specifically with contact structures on pathogen surfaces. Besides protein receptors, important recognition points for such contacts are provided by pathogen glycan chains or surface lipids. Therefore, structural data concerning surface exposed glycans and lipids are of the highest clinical interest since these recognition functions play a key role when optimising anti-infection therapies. Approaches in nanomedicine and nanopharmacology in which various biophysical techniques such as NMR (Nuclear Magnetic Resonance), AFM (Atomic Force Microscopy), SPR (Surface Plasmon Resonance) and X-ray crystallography can be combined with biochemical and cell-biological methods will lead to improved antimicrobial peptides by this rational drug design approach. Such a strategy is extremely well suited to support clinical studies focussing on an effective fight against multiresistant pathogens. The data sets which are described here can be considered as universal for the design of various antimicrobial drugs against certain pathogens (bacteria, viruses and fungi) which cause severe diseases in humans and animals. Furthermore, these insights are also helpful for progressing developments in the field of food conservation and food preservation. A detailed analysis of the structure-function relationships between antimicrobial peptides and contact molecules on pathogen surfaces at the sub-molecular level will lead to a higher degree of specificity of antimicrobial peptides.

Objectives: The purpose of the current study is to describe the prevalence and characteristics of antimicrobial stewardship programs (ASP) in Gulf Cooperation Council (GCC) states to explore opportunities and overcome barriers to effective ASP implementation., Methods: A cross-sectional questionnaire survey was used to evaluate the current status of ASP: major stewardship components, barriers of implementation and program impact in acute care hospitals of GCC states., Results: Forty-seven healthcare professionals responded from four GCC states, the majority from Saudi Arabia (81%). Twenty-nine (62%) participating hospitals had ASP in place. Of these established programs, 35 (75%) reported lack of funding and personnel as major barriers to program implementation. The top three objectives cited for the hospital ASP were to reduce resistance (72.3%), improve clinical outcomes (70.2%) and reduce costs (44.7%). The reported impact of existing ASP was reduction of inappropriate prescribing (68%), reduction of broad spectrum antibiotic use (63.8%), reduction of healthcare-associated infections (61.7%), reduction of length of stay or mortality metrics (59.6%), reduction in direct antibiotic cost (57.4%) and reduction of reported antibiotic resistance (55.3%)., Conclusion: Survey participants from GCC states who have implemented ASP report significant impacts in the reduction of broad spectrum antibiotic use, hospital-acquired infection, inappropriate prescribing and antimicrobial resistance. These findings suggest a promising opportunity to enhance existing ASP through sharing of best practices and support the development of regional guidelines across GCC states., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: To validate a new practical Sepsis Severity Score for patients with complicated intra-abdominal infections (cIAIs) including the clinical conditions at the admission (severe sepsis/septic shock), the origin of the cIAIs, the delay in source control, the setting of acquisition and any risk factors such as age and immunosuppression., Methods: The WISS study (WSES cIAIs Score Study) is a multicenter observational study underwent in 132 medical institutions worldwide during a four-month study period (October 2014-February 2015). Four thousand five hundred thirty-three patients with a mean age of 51.2 years (range 18-99) were enrolled in the WISS study., Results: Univariate analysis has shown that all factors that were previously included in the WSES Sepsis Severity Score were highly statistically significant between those who died and those who survived (p < 0.0001). The multivariate logistic regression model was highly significant (p < 0.0001, R2 = 0.54) and showed that all these factors were independent in predicting mortality of sepsis. Receiver Operator Curve has shown that the WSES Severity Sepsis Score had an excellent prediction for mortality. A score above 5.5 was the best predictor of mortality having a sensitivity of 89.2 %, a specificity of 83.5 % and a positive likelihood ratio of 5.4., Conclusions: WSES Sepsis Severity Score for patients with complicated Intra-abdominal infections can be used on global level. It has shown high sensitivity, specificity, and likelihood ratio that may help us in making clinical decisions.

Objective: The objective of our study was to describe lung changes on serial chest radiographs from patients infected with the acute Middle East respiratory syndrome corona-virus (MERS-CoV) and to compare the chest radiographic findings and final outcomes with those of health care workers (HCWs) infected with the same virus. Chest radiographic scores and comorbidities were also examined as indicators of a fatal outcome to determine their potential prognostic value., Materials and Methods: Chest radiographs of 33 patients and 22 HCWs infected with MERS-CoV were examined for radiologic features indicative of disease and for evidence of radiographic deterioration and progression. Chest radiographic scores were estimated after dividing each lung into three zones. The scores (1 [mild] to 4 [severe]) for all six zones per chest radiographic examination were summed to provide a cumulative chest radiographic score (range, 0-24). Serial radiographs were also examined to assess for radiographic deterioration and progression from type 1 (mild) to type 4 (severe) disease. Multivariate logistic regression analysis, Kaplan-Meier survival curve analysis, and the Mann-Whitney U test were used to compare data of deceased patients with those of individuals who recovered to identify prognostic radiographic features., Results: Ground-glass opacity was the most common abnormality (66%) followed by consolidation (18%). Overall mortality was 35% (19/55). Mortality was higher in the patient group (55%, 18/33) than in the HCW group (5%, 1/22). The mean chest radiographic score for deceased patients was significantly higher than that for those who recovered (13 ± 2.6 [SD] vs 5.8 ± 5.6, respectively; p = 0.001); in addition, higher rates of pneumothorax (deceased patients vs patients who recovered, 47% vs 0%; p = 0.001), pleural effusion (63% vs 14%; p = 0.001), and type 4 radiographic progression (63% vs 6%; p = 0.001) were seen in the deceased patients compared with those who recovered. Univariate and logistic regression analyses identified the chest radiographic score as an independent predictor of mortality (odds ratio [OR], 1.38; 95% CI, 1.07-1.77; p = 0.01). The number of comorbidities in the patient group (n = 33) was significantly higher than that in the HCW group (n = 22) (mean number of comorbidities, 1.90 ± 1.27 vs 0.17 ± 0.65, respectively; p = 0.001). The Kaplan-Meier analysis revealed a median survival time of 15 days (95% CI, 4-26 days)., Conclusion: Ground-glass opacity in a peripheral location was the most common abnormality noted on chest radiographs. A higher chest radiographic score coupled with a high number of medical comorbidities was associated with a poor prognosis and higher mortality in those infected with MERS-CoV. Younger HCWs with few or no comorbidities had a higher survival rate.

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.

Objective: The purpose of this article is to retrospectively analyze chest CT findings for 15 patients with Middle East respiratory syndrome coronavirus and to identify features associated with survival., Materials and Methods: Patients were assigned to group 1 if they died (n=9) and to group 2 if they made a full recovery (n=6). Two reviewers scored chest radiographs and CT examinations for segmental involvement, ground-glass opacities, consolidation, and interstitial thickening., Results: Eight patients had ground-glass opacity (53%), five had ground-glass and consolidation in combination (33%), five had pleural effusion (33%), and four patients had interlobular thickening (27%). Of 281 CT findings, 151 (54%) were peripheral, 68 (24%) were central, and 62 (22%) had a mixed location. The number of involved lung segments was higher in group 1. The lower lobe was more commonly involved (mean, 12.2 segments) than in the upper and middle lobes combined (mean, 6.3 segments). The mean number of lung segments involved was 12.3 segments in group 1 and 3.4 segments in group 2. The CT lung score (mean±SD, 15.78±7.9 vs 7.3±5.7, p=0.003), chest radiographic score (20.8±1.7 vs 5.6±5.4; p=0.001), and mechanical ventilation duration (13.11±8.3 vs 0.5±1.2 days; p=0.002) were higher in group 1. All nine group 1 patients and three of six group 2 patients had pleural effusion (p=0.52)., Conclusion: CT of patients with Middle East respiratory syndrome coronavirus predominantly showed ground-glass opacities, with peripheral lower lobe preference. Pleural effusion and higher CT lung and chest radiographic scores correlate with poor prognosis and short-term mortality.

A community-acquired syndrome of cryptogenic invasive Klebsiella pneumoniae (K. pneumoniae) liver abscess (CIKPLA) has been emerging worldwide over the past 3 decades, particularly in Taiwan and Korea. It is caused by highly virulent hypermucoviscous, rmpA positive K. pneumoniae serotype K1. This condition occurs in predominantly diabetic persons with no underlying hepatobiliary disease. Metastatic infections of the brain, meninges, lungs, pleura, bones, soft tissues, and eyes are unique features of this syndrome. We report a laboratory-confirmed regulator of mucoid phenotype (rmp)A-positive, K1 serotype K. pneumoniae from Saudi Arabia in 2 diabetic native Saudis presenting with community acquired, invasive liver abscess complicated in one by endogenous endophthalmitis. Following medical and surgical treatment, both patients were cured from liver abscesses, however there was unilateral permanent visual loss in one patient.

An unusual case of granulocytic sarcoma developing at the site of a previous cerebral hemorrhage in a patient with acute myelogenous leukemia in complete hematological remission is presented. The pathogenesis of the tumor growth at this site and its relevance to the antecedent hemorrhage are discussed.