Ceftazidime-avibactam use for the treatment of OXA-48- and/or New Delhi metallo-ß-lactamase-producing Enterobacterales in cancer patients: a retrospective observational study.

BACKGROUND: Infection is the second-leading cause of death among cancer patients, but there have been few studies on the effectiveness of novel antimicrobial agents to treat carbapenem-resistant Enterobacterales in cancer patients. OBJECTIVE: Evaluate the mortality and clinical outcomes of ceftazi-dime-avibactam for OXA-48- and/or New Delhi metallo-ß-lactamase (NDM)-producing Enterobacterales infection in cancer patients. DESIGN: Retrospective observational cohort study. SETTING: Tertiary academic medical center in Riyadh, Saudi Arabia. SUBJECTS AND METHODS: This study included patients who had cancer and received ceftazidime-avibactam for at least 72 hours for infections caused by OXA-48- and/or NDM-producing Enterobacterales. We excluded patients who died within 72 hours of treatment, patients with polymicrobial infections, and patients who did not receive appropriate antimicrobial therapy. MAIN OUTCOMES AND MEASURES: Primary outcomes were 30-day mortality and hospital mortality. Secondary outcomes included clinical cure, relapse, and reinfection. SAMPLE SIZE: 32 cancer patients. RESULTS: The 30-day mortality among all patients was 15/32 (47%), clinical cure was achieved in 19/32 (59%) of the patients, and the relapse and reinfection rates were 2/19 (10.5%) and 4/17 (23.5%), respectively. CONCLUSION: This is the largest study to evaluate clinical outcomes associated with infections caused by OXA-48- and/or NDM-producing Enterobacterales in cancer patients. The mortality rate remains high; however, ceftazidime-avibactam is an encouraging alternative for treating severe infections in cancer patients. LIMITATIONS: Small sample size and single center.

Successful utilization of nirmatrelvir/ritonavir and dexamethasone in a patient with total artificial heart and COVID-19: A case report.

RATIONALE: Management of coronavirus disease 2019 (COVID-19) has been the subject of extensive research and study, leading to the development of strategies and treatments. Nonetheless, there remains a dearth of information concerning patients who require mechanical circulatory system support. This case report presents one of the first documented cases of successful utilization of nirmatrelvir/ritonavir (Paxlovid) and dexamethasone in the treatment of a patient with a total artificial heart. PATIENT CONCERNS: The patient in this case study was a 28-year-old male who had been experiencing severe heart failure. In need of a heart transplant, he underwent a procedure for implantation of a total artificial heart as a bridge to transplantation. DIAGNOSES: Unfortunately, after the surgical intervention, the patient contracted COVID-19, as confirmed by polymerase chain reaction. INTERVENTIONS: The therapeutic approach involved a 5-day regimen of nirmatrelvir/ritonavir at a dosage of 300/100 mg administered twice daily, along with a daily dosage of 6 mg of dexamethasone. OUTCOMES: Remarkably, the patient oxygenation level improved on the second day of therapy. Consequently, he was transferred from the intensive care unit to the general floor. After 71 days with the total artificial heart, the patient successfully underwent heart transplantation. LESSONS: This case report provides a compelling example of the successful application of nirmatrelvir/ritonavir and dexamethasone in the treatment of a COVID-19 patient with a total artificial heart. The positive outcome observed in this case underscores the potential use of these therapeutic agents in this specific patient population. However, it is imperative to conduct further research to corroborate and validate these initial findings. This study lays the foundation for further exploration of the efficacy of these drugs in patients with mechanical circulatory support systems.

Brucellar, Pyogenic, and Tuberculous Spondylodiscitis at Tertiary Hospitals in Saudi Arabia: A Comparative Retrospective Cohort Study.

Introduction: Spondylodiscitis is rare yet the most common form of spinal infection. It is characterized by inflammation of the intervertebral disk space and adjacent vertebral body. In Western countries, the incidence of spondylodiscitis is increasing. Clinical outcomes most commonly reported in the literature are the 1-year mortality rate (range, 6%-12%) and neurologic deficits. Methods: This multicenter retrospective cohort study assessed patients diagnosed with infectious spondylodiscitis who received treatment at King Abdulaziz Medical City in Riyadh and Jeddah, Saudi Arabia. All enrolled patients were ≥18 years old and were diagnosed per radiologic and microbiological findings and clinical manifestations between January 2017 and November 2021. Results: This study enrolled 76 patients with infectious spondylodiscitis, with a median age of 61 years. All patients presented with back pain for a median 30 days. Patients were stratified into 3 groups based on the causative pathogen: brucellar spondylodiscitis (n = 52), tuberculous spondylodiscitis (n = 13), and pyogenic spondylodiscitis (n = 11). All laboratory data and biochemical markers were not significantly different. However, C-reactive protein, erythrocyte sedimentation rate, and white blood cells were significantly different in the pyogenic spondylodiscitis group, with medians of 121 mg/dL (P = .03), 82 mmol/h (P = .04), and 11.2 × 109/L (P = .014), respectively. Conclusions: Back pain is a common clinical feature associated with infectious spondylodiscitis. The immense value of microbiological investigations accompanied with histologic studies in determining the causative pathogen cannot be emphasized enough. Treatment with prolonged intravenous antimicrobial therapy with surgical intervention in some cases produced a cure rate exceeding 60%.

Prevalence of Breech Presentation and Other Gestational/Delivery Characteristics Among Patients Born With Developmental Dysplasia of the Hip.

Introduction Developmental dysplasia of the hip (DDH) is the most common congenital disability in newborns. The condition can range from a slight laxity in the hip joint to secondary femoral head injury, early osteoarthritis (OA), and mobility issues. There are several risk factors for DDH, including positive family history, female sex, breech presentation, and the presence of clubfoot. Early detection and treatment are crucial to avoid long-term hip dysplasia and arthritis, which can cause difficulty in walking and discomfort. Breech presentation, in particular, is a significant risk factor for DDH, with spontaneous vaginal birth increasing the risk of hip pathology and instability compared to elective Caesarean section. However, whether breech presentation continues to be a risk factor for DDH in preterm children is unknown. Objective and methods This study aimed to investigate the prevalence of breech presentation and other gestational/delivery characteristics among newborns diagnosed with DDH. This retrospective study was conducted at Abha Maternity and Children Hospital, Abha, Saudi Arabia, over a period of six months. Data were collected from medical records of DDH cases diagnosed between 2016 and 2023. Data analysis was performed using Microsoft Excel (Microsoft Corporation, Redmond, Washington, United States) and IBM SPSS Statistics for Windows, Version 22 (Released 2013; IBM Corp., Armonk, New York, United States). Descriptive statistics and statistical tests were used to analyze the data. Results Most of the diagnosed children were female (86.7%), and bilateral hip dislocation (40%) was the most common presentation. X-ray was the most common diagnostic tool (48.3%), and operative management was the most common management strategy (73.3%). A positive family history of DDH was reported in more than one-third of cases. The study also analyzed the association between complications during pregnancy and various factors such as mode of delivery, presentation at delivery, gestational age at delivery, and associated maternal diseases. The difference in complication rates between women who delivered via C-section and those who delivered vaginally was insignificant (p = 0.14). Similarly, the difference in complication rates between women with breech and cephalic presentation was not statistically significant (p = 0.094). The difference in complication rates between women who delivered preterm, at term, or post-term was also not statistically significant (p = 0.578). Furthermore, the association between complications during pregnancy and pregnancy-associated maternal diseases was not statistically significant (p = 1.00). Conclusion DDH is a significant health issue in newborns, leading to long-term mobility problems and discomfort. Positive family history of DDH is a significant risk factor. Breech presentation was not significantly associated with DDH in preterm children, and no significant associations were found between complications during pregnancy and various factors. Early detection and treatment of DDH are crucial for preventing long-term complications. Family history should be considered an important risk factor, emphasizing the need for screening programs in families with a history of DDH.

Evaluation of the Clinical Outcome and Cost Analysis of Antibiotics in the Treatment of Acute Respiratory Tract Infections in the Emergency Department in Saudi Arabia.

This study aims to assess the prevalence and antibiotic-treatment patterns of respiratory tract infections (RTIs), prevalence and types of antibiotic-prescribing errors, and the cost of inappropriate antibiotic use among emergency department (ED) patients. A cross-sectional study was conducted at the ED in King Abdulaziz Medical City, Riyadh, Saudi Arabia. Patient characteristics (age, sex, weight, allergies, diagnostic tests (CX-Ray), cultures, microorganism types, and prescription characteristics) were studied. During the study, 3185 cases were diagnosed with RTIs: adults (>15 years) 55% and pediatrics (<15 years) 44%. The overall prevalence of RTIs was 21%, differentiated by upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI) (URTI 13.4%; LRTI 8.4%), of total visits. Three main antibiotics (ATB) categories were prescribed in both age groups: penicillin (pediatrics 43%; adults 26%), cephalosporin (pediatrics 29%; adults 19%), and macrolide (pediatrics 26%; adults 38%). The prevalence of inappropriate ATB prescriptions was 53% (pediatrics 35%; adults 67%). Errors in ATB included selection (3.3%), dosage (22%), frequency (3%), and duration (32%). There is a compelling need to create antimicrobial stewardship (AMS) programs to improve antibiotic use due to the high number of prescriptions in the ED deemed as inappropriate. This will help to prevent unwanted consequences on the patients and the community associated with antibiotic use.

Evaluation of ceftazidime/avibactam for treatment of carbapenemase-producing carbapenem-resistant Enterobacterales with OXA-48 and/or NDM genes with or without combination therapy.

Background: Carbapenem-resistant Enterobacterales (CRE) is an urgent public health threat of significant global concern. Few observational studies have evaluated the clinical outcomes for treatment of CRE harbouring OXA-48 or NDM genes with ceftazidime/avibactam. Previous findings showed lower 30 day mortality with ceftazidime/avibactam ranges between 8.3% and 22%. Method: This single-centre retrospective cohort study included adult patients aged ≥18 years admitted to King Abdulaziz Medical City (KAMC) who had received ceftazidime/avibactam for at least 72 h for infections caused by CRE with genes encoding for carbapenemase production (CP-CRE). Results: A total of 211 patients, mostly male (57%), having CP-CRE infections treated with ceftazidime/avibactam were included, with an average age of 62 years. More than 50% of patients were critically ill, for which 46% received invasive ventilation and 36% were on inotropes. The most frequent infectious disease was hospital/ventilator-acquired pneumonia with Klebsiella pneumoniae being the most frequent causative pathogen. The majority of isolates harboured OXA-48 (81%), followed by NDM ±â€ŠOXA-48 (19%). The overall clinical cure and 30 day mortality was 78% and 21% respectively (stratified per gene: 79% and 21.6% for OXA-48 and 75% and 17.5% for NDM ±â€ŠOXA-48). Conclusions: This was the largest study that evaluated clinical outcomes associate with CP-CRE harbouring OXA-48 gene infections treated with ceftazidime/avibactam. Clinical cure and 30 day mortality were consistent with those of previous studies. Findings suggested that combination therapy with ceftazidime/avibactam had no direct impact on clinical outcomes for CP-CRE with OXA-48.

Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicentre, placebo-controlled clinical trial.

OBJECTIVE: To evaluate whether favipiravir reduces the time to viral clearance as documented by negative RT-PCR results for severe acute respiratory syndrome coronavirus 2 in mild cases of coronavirus disease 2019 (COVID-19) compared to placebo. METHODS: In this randomized, double-blinded, multicentre, and placebo-controlled trial, adults with PCR-confirmed mild COVID-19 were recruited in an outpatient setting at seven medical facilities across Saudi Arabia. Participants were randomized in a 1:1 ratio to receive either favipiravir 1800 mg by mouth twice daily on day 1 followed by 800 mg twice daily (n = 112) or a matching placebo (n = 119) for a total of 5 to 7 days. The primary outcome was the effect of favipiravir on reducing the time to viral clearance (by PCR test) within 15 days of starting the treatment compared to the placebo group. The trial included the following secondary outcomes: symptom resolution, hospitalization, intensive care unit admissions, adverse events, and 28-day mortality. RESULTS: Two hundred thirty-one patients were randomized and began the study (median age, 37 years; interquartile range (IQR): 32-44 years; 155 [67%] male), and 112 (48.5%) were assigned to the treatment group and 119 (51.5%) into the placebo group. The data and safety monitoring board recommended stopping enrolment because of futility at the interim analysis. The median time to viral clearance was 10 days (IQR: 6-12 days) in the favipiravir group and 8 days (IQR: 6-12 days) in the placebo group, with a hazard ratio of 0.87 for the favipiravir group (95% CI 0.571-1.326; p = 0.51). The median time to clinical recovery was 7 days (IQR: 4-11 days) in the favipiravir group and 7 days (IQR: 5-10 days) in the placebo group. There was no difference between the two groups in the secondary outcome of hospital admission. There were no drug-related severe adverse events. CONCLUSION: In this clinical trial, favipiravir therapy in mild COVID-19 patients did not reduce the time to viral clearance within 15 days of starting the treatment.

Outcomes associated with tocilizumab with or without corticosteroid versus dexamethasone for treatment of patients with severe to critical COVID-19 pneumonia.

INTRODUCTION: Immunomodulators, including dexamethasone (DEX), have been recommended by the Infectious Disease Society of America (IDSA) to treat moderate, severe, and critical COVID-19. Tocilizumab (TCZ) was added to the treatment recommendations based on recent data from two large randomized controlled trials and its potential synergistic effect with DEX. METHOD: We included adult patients admitted from June until October 2020 with a PCR confirmed SARS-CoV-2 infection. 135 patients with severe to critical COVID-19 and received TCZ and/or corticosteroid or DEX were retrospectively evaluated and followed until hospital discharge or death. RESULTS: The cohort was divided into two different groups of patients; TCZ group received TCZ ± corticosteroid, N = 100 and DEX group received DEX, N = 35. Groups were analyzed for hospital mortality. The rate of hospital mortality was 36% in TCZ and 37% in the DEX group, p = 0.91. Age of 60 years and above was associated with higher mortality rate with OR = 1.030 and 95% CI = (1.004, 1.057). More than 50% of patients required MV in both groups. Development of bacterial or fungal infection post immunomodulator were similar in TCZ and DEX groups, 29% vs. 31.4%. CONCLUSION: Our study revealed that age of 60 years and above is the only factor associated with higher mortality rate regardless of the type of immunomodulator therapy. Findings of this study also revealed the lack of synergistic effect between TCZ and DEX on the hospital mortality.

Clinical characteristics and risk factors of patients with severe COVID-19 in Riyadh, Saudi Arabia: A retrospective study.

BACKGROUND: COVID-19 is newly emerging infectious disease that spread globally at unpredictable and unique pattern to the extent that the World Health Organization announced COVID-19 as a pandemic in the first couple months of 2020. This study aims to describe clinical and demographic features of COVID-19 patients and the influence of various risk factors on the severity of disease. METHODS: This research is a retrospective study based on Saudi Arabia's ministry of health's Covid-19 data. The analysis relies on data of all COVID-19 patients recorded in Riyadh between 1st, March 2020 and 30th, July 2020. Statistical analyses were performed to investigate the effect of demographic characteristic, clinical presentation, and comorbidities on infection severity. RESULTS: A total number of 1026 COVID-19 patients were identified based on the demographic data as follows: 709 cases (69% of cases) were males and 559 cases (54% of cases) were Saudi. Most of patients were diagnosed with mild signs and symptoms 697 (68% of cases), while 164 patient (16% of cases) demonstrated moderate signs and symptoms, and 103 cases (10%) were severe and 62 (6%) had critical febrile illness. Fever, cough, sore throat, and shortness of breath were the most common symptoms among patients with COVID-19. Among studied comorbidities in COVID-19 patients, diabetes mellitus and hypertension were the most prevalent. The results from the bivariate logistic regression analysis revealed that older age, diabetes mellitus, asthma, smoking, and fever are associated with severe or critically ill cases. CONCLUSION: The findings of this study show that old age, fever, and comorbidities involving diabetes mellitus, asthma, and smoking were significantly associated with infection severity.

Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID-19 (FACCT Trial): An Open-Label, Multicenter, Randomized, Controlled Trial.

INTRODUCTION: Antiviral drugs have shown limited effectiveness in treating patients with coronavirus disease 2019 (COVID-19). We aimed to assess the effects of a favipiravir and hydroxychloroquine combination on treating moderate-to-severe COVID-19 patients. METHODS: An investigator-initiated, multicenter, open-label, randomized trial at nine hospitals. Eligible patients were adults with moderate-to-severe COVID-19 defined as oxygen saturation (SaO2) of ≤ 94% while breathing ambient air or significant clinical symptoms with chest x-ray changes requiring hospital admission. Randomization was in a 1:1 ratio to receive standard care (control group) or standard care plus favipiravir and hydroxychloroquine. The primary outcome was time to clinical improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital within 14 days. Analyses were done in an intention-to-treat population. RESULTS: From May 2020 to Jan 2021, 254 patients were enrolled; 129 were assigned to standard of care and 125 to the treatment. The mean age was 52 (± 13) years, and 103 (41%) were women. At randomization, six patients were on invasive mechanical ventilation, 229 (90.15%) were requiring supplemental oxygen only (with or without non-invasive ventilation), and 19 (7.48%) were receiving neither. The time to clinical improvement was not significantly different between the groups: median of 9 days in the treatment group and 7 days in the control group (HR: 0.845; 95% CI 0.617-1.157; p-value = 0.29). The 28-day mortality was not significantly different between the groups (7.63% treatment) vs. (10.32% control); p-value = 0.45. The most prevalent adverse events were headache, elevation in ALT, and the prolonged QTc interval in the treatment group. CONCLUSION: The combination of favipiravir and hydroxychloroquine did not result in a statistically significant clinical benefit in patients with moderate-to-severe COVID-19. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04392973).

Infections and patterns of antibiotic utilization in support and comfort care patients: A tertiary care center experience.

PURPOSE: Little is known regarding the burden of infections and clinical practice towards hospitalized patients with limits on life-sustaining measures. We aim to describe the infectious syndromes, clinical care, the emergence of multi-drug resistant organisms and outcomes in this population. PATIENTS AND METHODS: Retrospective cohort of patients labeled as support or comfort care in a tertiary care center between 2016-2019. RESULTS: A total of 347 patients were included with a mean age of 68.5 years, who were predominantly males (59.94%), bedbound (69.74%), on tube feeding (66.86%), and required indwelling urinary catheters (61.96%). The total number of admissions during the first year was 498, with the mean length of stay being 30 days. The number of infectious syndromes identified during that period was 821episodes, with a mean of 2 infectious syndromes per admission. The most common infection identified was pneumonia (41.66%) followed by urinary tract infections (27.16%). A total of 3891 microbiological cultures were taken with a mean of 5 cultures per infectious syndrome. The most commonly identified pathogens were Gram-negative bacteria (61.03%), with a high rate of multidrug-resistant organisms (MDROs) (48.53%). The one-year mortality was 86.4%. Using carbapenem antibiotic and pneumonia were the independent predictors used for the MDROs. CONCLUSION: Our study reflects the high burden of infections, antimicrobial resistance, and hospital admissions among a population with limited life expectancy. A consensus regarding investigating and managing of infectious syndromes, and antimicrobial prescription is needed to reduce the harms associated with overuse of antimicrobials.

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).

Impact of Rapid Identification of Staphylococcus Species in Positive Blood Culture Using GeneXpert Methicillin-Resistant Staphylococcus aureus/ Staphylococcus aureus Blood Culture Assay Combined with Antibiotic Stewardship.

Staphylococcus aureus bacteremia is a life-threatening condition associated with a substantial financial burden on the health care system. The use of the GeneXpert® methicillin-resistant S. aureus (MRSA)/S. aureus blood culture (BC) test for the identification of S. aureus may influence antibiotic stewardship and clinical outcomes. This study assessed the clinical and financial impact of utilizing GeneXpert MRSA/SA in combination with criterion-based testing. The outcomes between October 1, 2018, and June 30, 2019, were evaluated in 65 adult patients who had positive BCs with Gram-positive cocci in clusters. GeneXpert MRSA/SA significantly shortened the time to optimal antimicrobial therapy by 1.7 days (2.5 vs. 44 hr, p < 0.0001). The cost saved because of interventions based on GeneXpert testing results was $4,121. GeneXpert testing has shortened the time to optimal therapy and positively impacted cost, although it had no significant effect on length of hospital stay and mortality rate.

Evaluating the effect of antibiotics sub-inhibitory dose on Pseudomonas aeruginosa quorum sensing dependent virulence and its phenotypes.

The opportunistic Pseudomonas aeruginosa virulence controlled by quorum sensing (QS) also identified as, cell-cell communication. QS system is organized by the LasI-LasR and the RhlI-RhlR components. Provided that QS tends to perform a key role in virulence gene expression and host defence function, QS inhibitors have been proposed as potential antipseudomonal therapies. Sub-inhibitory concentrations (sub-MIC) of antibiotics, although having biostatic effect on bacteria, but can interfere with bacterial QS system and virulence. This research aimed to examine the impact of sub-MIC of azithromycin, imipenem, cefepime and piperacillin/tazobactam on the QS-dependent virulence including pyocyanin and biofilm production, haemolysin, protease and DNase in P. aeruginosa wildtype and mutant strains; transcriptional-regulator (ΔLasR), autoinducer synthesis protein (ΔLasI), transcriptional-regulator (ΔRhlR), protease precursor (ΔLasA) and double regulators mutants (ΔLasR/RhlR). The growth of all strains showed similar pattern, however, in presence of antibiotics significant growth variation was observed among mutant strains when compared to wild type strain. Antimicrobial activity tested by agar diffusion method of all antibiotics on all strains were used to compare the zones of therapeutic and sub-MIC doses showing a significant difference in the inhibition zone. QS-dependant virulence as biofilm, pyocyanin, protease, haemolysin and DNase production showed significant variation on all strains compared to wild type in response to antibiotics used at sub-MIC doses. In conclusion well known antibiotics can be used in sub-MIC doses to decrease the virulence of P. aeruginosa in addition to overcoming the major side effect of the high doses and the occurrence of resistance.

Influence of the minimum inhibitory concentration of daptomycin on the outcomes of Staphylococcus aureus bacteraemia.

OBJECTIVES: Recent studies have shown that methicillin-resistantStaphylococcus aureus (MRSA) bacteraemia with vancomycin minimum inhibitory concentration (MIC) >1 µg/mL is associated with a higher rate of treatment failure and a higher mortality rate. Daptomycin is an alternative to vancomycin but has not been as well studied. The aim of this literature review was to evaluate the effect of daptomycin MIC on the outcomes of S. aureus bacteraemia. METHODS: We conducted a literature search for the period January 2010 to January 2019 using the MEDLINE and Embase databases. RESULTS: Four studies were included in the review. The outcomes were clinical cure and 30- or 60-day mortality. In two retrospective studies, 60-70% ofS. aureus isolates had a low daptomycin MIC (≤0.5 µg/mL) and patients with MRSA bacteraemia who were treated with daptomycin had a lower mortality rate. In another study, patients with methicillin-susceptible S. aureus bacteraemia with low daptomycin MICs had a lower risk of developing septic thrombophlebitis. One study showed that patients with MRSA bacteraemia had a higher mortality rate if the daptomycin MIC was >0.5 µg/mL. CONCLUSION: The included studies in this review suggest a possible association between high daptomycin MIC and unfavourable clinical outcomes ofS. aureus bacteraemia. Further prospective studies are required to evaluate the impact of the daptomycin MIC on the clinical outcomes of S. aureus bacteraemia.

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.

Antibacterial Activity of Chitosan Nanoparticles Against Pathogenic N. gonorrhoea.

PURPOSE: The emergence of Neisseria gonorrhoeae strains that are resistant to the most commonly used antibiotics represents a great concern for global public health. This challenges the effectiveness of clinical treatment regimens and demands the development of alternative antigonococcal agent. In this regard, chitosan nanoparticles (CNPs) are known to have antimicrobial activity against a wide range of pathogens. Thus, they have become a potential candidate for combatting this era of multi-drug resistance. This study aims to formulate CNPs, characterize their physicochemical properties, and examine their antimicrobial activity against gonococcus. MATERIALS AND METHODS: The ionic gelation method was used to prepare CNPs of different concentrations. Characterization for their particle size (PZ), polydispersity index (PDI), and zeta potential (ZP) was performed. The anti-microbial activity of CNPs was investigated against 13 WHO N. gonorrhoeae reference strains, using the broth dilution method. Cytotoxicity of CNPs and their effect on bacterial adhesion to HeLa cells were investigated. RESULTS: The average PZ and ZP of the prepared NPs were increased when the concentration of chitosan was increased from 1 to 5 mg/mL and found to be in the range of 193 nm ± 1.9 to 530 nm ± 13.3, and 14 mV ± 0.5 to 20 mV ± 1, respectively. Transmission electron microscopes (TEM) images revealed spherical NPs, and the NPs had a low PDI value of ≤0.27. The formed CNPs produced antibacterial activity against all tested strains, including those resistant to multiple antibiotics, with a minimum inhibitory concentration (MIC90) of 0.16 to 0.31 mg/mL and a minimum bactericidal concentration (MBC) of 0.31 to 0.61 mg/mL. Of note, at all MIC90 and MBC, the CNPs had no significant cytotoxic effect on HeLa cells and reduced bacterial adhesion to these cells at MBC doses. CONCLUSION: The present work findings suggest the potential of the CNPs for the treatment of gonorrhoea.

Treatment of Recurrent Clostridium difficile Infection in an Immunocompromised Patient with Severe Neutropenia Not Responding to Standard Therapy.

One of the most effective strategies in reducing the risk of Clostridium difficile infection (CDI) recurrence is fecal microbiota transplantation (FMT). However, several adverse events have been reported post FMT, and data on the efficacy and safety of FMT in immunocompromised patients with hematological malignancies are rare. This report presents FMT treatment for refractory CDI in a severely immunocompromised patient. A 69-year-old female presented to the emergency department complaining of foul smelling, intractable, watery diarrhea and generalized abdominal pain. She was recently diagnosed with high-risk myelodysplastic Syndrome (MDS) requiring daily blood transfusions and reported multiple CDI episodes in the past treated successfully with metronidazole and vancomycin as mono- or combotherapy. During this admission, treatment with oral vancomycin (high dose) and intravenous metronidazole was unsuccessful, so FMT was administered. The patient recovered well despite an absolute neutrophil count (ANC) < 0.25 × 109/L, and chemotherapy was initiated soon after. FMT was successful and safe in this patient, with no relapse and adverse events seen in 8 weeks of follow-up via phone calls and office visits.

IgA Nephropathy Flare-Up Mimicking Staphylococcus Post-Infection Glomerulonephritis in Patient with Staphylococcus Aureus Infection Treated with Cefazolin: A Case Report and Brief Review of the Literature.

BACKGROUND Glomerulonephritis (GN) associated with post staphylococcus infection (PSIGN) and high serum immunoglobulin A (IgA) has been reported recently. Patients with GN after infection with underlying IgA nephropathy create a challenge to determine the etiology of GN. Therefore, treatment should be accordingly, with steroids used if the IgA nephropathy flare-up is determined to be the etiology. The aim of this case report was to shed light on the difference between PSIGN and IgA nephropathy flare-ups in patients with a history of IgA nephropathy, and how to treat patient cases accordingly. CASE REPORT An 81-year-old male presented to our Emergency Department complaining of increasing pain, swelling, and redness of his left knee since 2 days ago. He had a history of recent methicillin sensitive Staphylococcus aureus (MSSA) left knee arthroplasty infection that was treated with cefazolin, and he had a history of IgA nephropathy diagnosed 1 year ago. CONCLUSIONS In our patient case, renal biopsy studies were not enough to differentiate between PSIGN and IgA nephropathy flare-ups, thus, clinical presentation was important. PSIGN was found to have a delayed onset compared to IgA nephropathy. Lower serum complement 3 (C3) level, heavier proteinuria, and acute renal failure are common with PSIGN compared to IgA nephropathy. Identifying the etiology and treating our patient accordingly with immunosuppressive therapy had a positive impact on the patient, restoring renal function without further damage.