Sofosbuvir and daclatasvir compared with standard of care in the treatment of patients admitted to hospital with moderate or severe coronavirus infection (COVID-19): a randomized controlled trial.

BACKGROUND: Currently no effective antiviral therapy has been found to treat COVID-19. The aim of this trial was to assess if the addition of sofosbuvir and daclatasvir improved clinical outcomes in patients with moderate or severe COVID-19. METHODS: This was an open-label, multicentre, randomized controlled clinical trial in adults with moderate or severe COVID-19 admitted to four university hospitals in Iran. Patients were randomized into a treatment arm receiving sofosbuvir and daclatasvir plus standard care, or a control arm receiving standard care alone. The primary endpoint was clinical recovery within 14 days of treatment. The study is registered with IRCT.ir under registration number IRCT20200128046294N2. RESULTS: Between 26 March and 26 April 2020, 66 patients were recruited and allocated to either the treatment arm (n = 33) or the control arm (n = 33). Clinical recovery within 14 days was achieved by 29/33 (88%) in the treatment arm and 22/33 (67%) in the control arm (P = 0.076). The treatment arm had a significantly shorter median duration of hospitalization [6 days (IQR 4-8)] than the control group [8 days (IQR 5-13)]; P = 0.029. Cumulative incidence of hospital discharge was significantly higher in the treatment arm versus the control (Gray's P = 0.041). Three patients died in the treatment arm and five in the control arm. No serious adverse events were reported. CONCLUSIONS: The addition of sofosbuvir and daclatasvir to standard care significantly reduced the duration of hospital stay compared with standard care alone. Although fewer deaths were observed in the treatment arm, this was not statistically significant. Conducting larger scale trials seems prudent.

Relationship Between Preoperative 25-Hydroxy Vitamin D and Surgical Site Infection.

BACKGROUND: Surgical site infection (SSI) is one of the most important and costly complications of surgical operations. Vitamin D antimicrobial and wound healing effects have been recently shown in animal models and in laboratory settings. Furthermore, potential effects of vitamin D in mitigating nosocomial infections and SSIs have been examined at a limited scale. To our knowledge, no comprehensive study has been performed to show the relationship between preoperative level of vitamin D and incidence of SSI. The present study was designed and implemented to investigate this relationship. MATERIALS AND METHODS: We performed a prospective cross-sectional study involving 300 adult patients who were admitted to undergo surgery in our tertiary care unit from January 2016 to January 2018. Cutoff point was considered at a level of 30 (ng/mL) in defining vitamin D deficiency. The presence of any SSI was investigated and recorded at the time of discharge and at postoperative visits up to 30 d after the surgery. Cross-tabulation and bivariate and multivariate logistic regression with unadjusted and adjusted odd ratio were used to determine the association between dependent and independent variables and to identify factors associated with SSIs. RESULTS: Overall, of 300 patients who were investigated, 39% had preoperative vitamin D deficiency and 11% developed SSI. In univariate logistic regressions, 20 predictors were selected to be included in the multivariate analysis. Finally preoperative level of 25-hydroxy vitamin D, history of recent infection, preoperative and postoperative hospital length of stay, and postoperative blood transfusions were confirmed as statistically significant independent predictors of SSI. CONCLUSIONS: Preoperative 25-hydroxy vitamin D level has a strong effect on postoperative SSI. Prospective double-blinded randomized clinical trials are required to confirm such strong relationship and to settle preoperative vitamin D measurement as a standard approach to reduce postoperative complications including SSI. Preoperative patient optimization, limiting hospital length of stay, and blood transfusion are other strategies to reduce SSI.

Characterization of Clostridioides difficile isolates recovered from hospitalized patients and the hospitals environment and air: A multicenter study.

In healthcare settings, contamination of environment with toxigenic and hypervirulent Clostridioides difficile strains is a serious concern. Here, we assessed whether patients with C. difficile have a role to play in the dissemination of C. difficile in our settings or other sources are implicated in its circulation. A total of 700 fecal specimens and 1435 environmental samples from surfaces, equipment and air of rooms occupied by patients suspected of C. difficile infection were taken from 4 tertiary hospitals in Tehran, Iran between April 2016 and August 2017. Antibiotic susceptibility testing and detection of resistance genes were performed for the environmental isolates. The clinical and environmental isolates of C. difficile were subjected to Pulsed Field Gel Electrophoresis (PFGE) analysis. Forty three (6.14%) and 2 (0.13%) isolates of C. difficile were recovered from the clinical and environmental samples, respectively. In the clinical settings, 2 patients were suspected of recurrent C. difficile infection. Thirty distinct pulsotypes were found among the C. difficile isolates including 28 singletons and 2 common types. One of the two environmental isolates was isolated from floor in the Medical ward, of pulsotype/ribotype/toxinotype PT10/New ribotype/toxinotype V, harbored cdtA/B and tcdC-A, and resistant to ciprofloxacin. The other one was isolated from air of a room in ICU, assigned to PT11/RT001/toxinotype 0, belonged to tcdC-sc3 genotypes and resistant to metronidazole. The environmental isolates did not generate amplicons in PCR assays targeting vanA and nim genes. This study provided evidence for dissemination of genetically diverse strains of C. difficile in hospitalized patients, presence of C. difficile in hospital air, existence of binary toxin positive/antibiotic-resistant isolate on the floor and intra-hospital dissemination of this pathogen.

Genotyping of clinical and environmental Aspergillus flavus isolates from Iran using microsatellites.

Aspergillus flavus is the second most important Aspergillus species causing human infections in tropical countries. Despite an increasing number of infections of A. flavus in Iran, the molecular epidemiology of clinical and environmental strains has not been well studied. We used a panel of nine microsatellite markers to analyse the genetic relatedness of A. flavus. Microsatellite typing of 143 (n = 119 clinical and n = 24 environmental) isolates demonstrated 118 different genotypes. A possible outbreak at a pulmonary ward was discovered. The discriminatory power for the individual markers ranged from 0.4812 to 0.9457 and the panel of all nine markers combined yielded a diversity index of 0.9948. This high-resolution typing method assists in better understanding of the molecular epidemiology of A. flavus.

Rate, Risk Factors, and Outcomes of Invasive Fungal Infections in Patients with Hematologic Malignancies.

Background: Invasive fungal infections (IFIs) are a significant cause of mortality and morbidity in patients with hematological malignancies. Given the considerable prevalence and consequences of IFIs, hence revealing the exact cause of fungal infections, their rate, associated risk factors, and complications could contribute to reducing both financial and life costs, choosing targeted antifungal treatment, and avoiding unnecessary toxic treatments in individuals who are not suffering from mycoses. Materials and Methods: This prospective cross-sectional study was conducted in the first semester of 2019. All patients with hematologic malignancies (HM) admitted to Dr. Shariati Hospital were studied. Only those with probable/proven IFIs defined according to the last update of EORTC/MSG criteria were included in the study. The demographic and clinical data were recorded from the hospital information registration system using a questionnaire. Statistical analysis was performed using SPSS software version 24. Results: Out of 1109 HM patients hospitalized during the study period, 67 (6.04%) IFIs were diagnosed. Of these, 57 (85.04%) were aspergillosis, 7 (10.4%) were mucormycosis, and 3 patients developed other fungal infections. Males constituted 67.2% of the entire IFI population. The mean±SD age of the samples was 43.16 ± 13.8 years. The most common type of malignancy was AML. Lung imaging showed lesions associated with fungal infections in 52 cases (77.6%), with multiple nodules as the most prevalent pattern being observed in 64.2% of cases. Sinus involvement was evidenced in the PNS CT scan of 46 (68.6%) patients. The attributable mortality rate for IFIs was 62.7%. Both the types of IFI and malignancies had no significant relationship with the outcome of patients. Central venous catheter, mucositis, and antibiotic use were the most frequent risk factors. Conclusion:  IFI represents a frequent complication for HM patients with high mortality. Aspergillus species are the predominant etiology in these settings. Considering our results, in high-risk patients, manifestations of warning signs in the sinus and lungs, which would not be cleared despite receiving antibiotics, should raise the possibility of IFIs.

Population pharmacokinetics of vancomycin in patients with diabetic foot infection: a comparison of five models.

Purpose: This study aimed to compare individual pharmacokinetic (PK) parameters of vancomycin with predicted values from five population PK models in patients with diabetic foot infections (DFIs). Methods: Patients with a diagnosis of DFI and an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min were included in the study. Individual PK data was carried on by collecting three vancomycin serum concentrations in a steady-state condition. Five published population-based nomograms were assumed to predict PK parameters. Optimal vancomycin exposure was considered as a trough level of 15-20 mg/L or the area under the curve over 24 h/minimum inhibitory concentration (AUC24/MIC) ≥ 400. Results: A total of 48 samples from 16 patients were analyzed. There was a statistically significant difference between the volume of distribution (Vd) obtained from population methods and the individual estimations (P ≤ 0.001 in Ambrose and Burton, P = 0.010 and 0.006 in Bauer and Burton revised models, respectively). AUC/MIC ≥ 400 was achieved in 68.7% of patients while 50% had a trough level of less than 15 mg/L. Conclusions: Vancomycin PK parameters, particularly individualized Vd, may not be predictable by population nomograms in patients with DFI and stable renal function. Moreover, the weak correlation between AUC24 values and trough concentrations underlines the starting practice of vancomycin AUC24-based monitoring and dosing in the clinical setting.

Intraventricular CNS aspergillosis in a patient with prior history of COVID-19: Case report and review of literature.

Introduction and importance: Although some immunocompetent patients have developed invasive aspergillosis, the vast majority of cases are seen in immunocompromised patients. COVID-19 infection has been proposed to cause immune dysfunction or suppression, which predisposes patients to fungal co-infections such as mucormycosis and aspergillosis. Case presentation: A 58-year-old woman was admitted to the hospital with confusion, dysarthria, and loss of consciousness. The patient had a 1-month prior history of severe COVID-19 infection. A computerized tomography (CT) scan and a magnetic resonance imaging (MRI) revealed an intraventricular lesion with perilesional edema and a significant midline shift, which was initially thought to be an intraventricular tumor. Following a posterior parietal craniotomy, the lesion was resected via a transcortical approach from the posterior parietal region to the right lateral ventricle. Histopathological findings confirmed intraventricular aspergillosis (IVA). The patient was treated with intravenous amphotericin B for two months and discharged with oral variconazole for 4 months. Discussion: Covid-19 infections can result in- dissemination of fungal diseases such as aspergillosis. As a minor component of cerebral aspergillosis with a poor prognosis, intraventricular aspergillosis necessitates prompt treatment, which includes surgical resection and the administration of anti-fungal medications. Conclusion: Infection with COVID-19 causes immune dysfunction, which leads to fungal co-infection, including CNS aspergillosis. As a result, all COVID-19 patients who present with acute neurologic symptoms should have CNS aspergillosis considered in their differential diagnosis.

Health care-associated infections, including device-associated infections, and antimicrobial resistance in Iran: The national update for 2018.

Introduction: Surveillance of health care-associated infections (HAIs) is an essential part of an efficient healthcare system. This study is an update on incidence and mortality rates of HAIs in Iran in 2018. Methods: Almost all hospitals across the country (940 hospitals) entered the data of HAIs and denominators to the Iranian Nosocomial Infections Surveillance (INIS) software. Statistics were derived from INIS. Results: From 9,607,213 hospitalized patients, 127,953 suffered from HAI, 15.65% of whom died. The incidence rate of HAI was calculated as 4.2 per 1000 patient-days. Considering relative frequencies among HAIs, Pneumonia (29.1%) and UTIs (25.6%) were the most common types of infection. Ventilator-associated pneumonia (VAP) was the most frequent device-associated infection (DAI) 25.66 per 1000 ventilator-days, and had the highest mortality rate (43.08%). Incidence density of other DAIs was 5.43 for catheter-associated UTI and 2.86 for catheter-associated BSI per 1000 device-days. Medical ICUs had the highest incidence and percentage of deaths (15.35% and 37.63%, respectively). The most causative organisms were Escherichia coli, Acinetobacter baumannii, and Klebsiella pneumonia. The rate of methicillin-resistance Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria was about 49%, 57%, and 58% respectively. Conclusion: This study provided an overview of HAIs in Iran and indicated that HAIs required special attention both in detection/reporting and in infection control measures. Future studies could be done on adherence rate of DAIs' preventive bundles, interventions via multimodal strategies, evaluating the effect of training, and effect of antibiotic stewardship programs.

Influenza vaccination coverage and obstacles in healthcare workers (HCWs) and the follow up of side effects: a multicenter investigation in Iran.

INTRODUCTION: Seasonal influenza is an annual common occurrence in cold seasons; but the COVID-19 pandemic is also currently ongoing. These two diseases can't be distinguished from their symptoms alone; therefore, the importance of preventing influenza by vaccination is more than ever. Due to the high exposure of hospital personnel, widespread influenza vaccination of these high-risk groups seems to be a necessity. This Study conducted to determine vaccination coverage in the personnel of four tertiary referral collegiate hospitals in 2019 and to further investigate individual obstacles for Influenza vaccination. METHODS: In this cross-sectional descriptive study, 637 personnel were selected randomly from distinctive hospitals in a list-wised. Ones vaccinated filled the side effects questionnaire and who not vaccinated filled the vaccination obstacles questionnaire. The study was approved by the ethics committee of Tehran University of Medical Sciences with this reference number: IR.TUMS.IKHC.REC.1398.218. RESULTS: The mean vaccination coverage was 29.4% and the coverage difference among centers was not statistically significant (p = 0.192). The following items had the most impact on personnel decision: confidence about one's immune system (p < 0.05), the experience of side effects from previous vaccinations (p = 0.011), attitude about vaccination in colleagues (p = 0.021) and work experience (p < 0.05). About 23% of vaccinated individuals reported side effects following vaccination and the most common side effect was mild cold symptoms with 12.3% prevalence. CONCLUSION: The results of the current study revealed that influenza vaccination coverage among HCWs is not satisfactory in Iran. Hospital authorities and infection control units should plan to remove the obstacles of influenza vaccination.

Assessment of device-associated infection rates in teaching hospitals in Islamic Republic of Iran.

BACKGROUND: Surveillance of health care-associated infections (HCAIs) is an integral part of infection control programmes, especially in intensive care units (ICUs). Device-associated infections (DAIs) are a major threat to patient safety. AIM: To measure DAI rates in ICUs. METHODS: Central line-associated bloodstream infection (CLABSI), ventilator-associated pneumonia (VAP), and catheter- associated urinary tract infection (CAUTI) were assessed in the ICUs of 4 tertiary-care teaching hospitals in Tehran, Islamic Republic of Iran. RESULTS: The incidence rate of CLABSI, VAP and CAUTI was 10.20, 21.08 and 7.42 per 1000 device-days, respectively. The utilization ratio for central lines, ventilators and urinary catheters was 0.62, 0.47, and 0.84, respectively. The most common organisms were Acinetobacter (33.5 %) and Klebsiella (19.0 %). Sixty to eighty percent of Enterobacteriaceae were extended- spectrum beta-lactamase producing. About half of Pseudomonas aeruginosa isolates were resistant to piperacillin/ tazobactam and carbapenem. Acinetobacter resistance rate to ampicillin/sulbactam and carbapenem was 70-80 %. The prevalence of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus was 84.6 % and 83.3 %, respectively. CONCLUSIONS: This study showed high incidence rates of DAIs and resistant organisms, and appropriate interventions are necessary to reduce these rates.

Health care-associated infections in Iran: A national update for the year 2015.

BACKGROUND: A national surveillance system for health care-associated infections (HAIs) in Iran is relatively new, and an update on incidence and mortality rates can aid clinicians and stakeholders in development of new guidelines and imperative modifications to be made. METHODS: Data were extracted from the national HAIs surveillance software for more than 7 million hospitalizations during 2015. Data regarding age, gender, deaths, ward of admission, and microbiologic findings were collected and analyzed. RESULTS: From 491 hospitals, 7,018,393 hospitalizations were reported during 2015; 82,950 patients had been diagnosed with at least 1 HAI, 6,355 of whom died (crude fatality rate, 7.7). Men comprised 51.4% of the patients. The incidence rate was calculated to be 1.18. Urinary tract infections and pneumonia were the most commonly reported infections (27.9% and 23.8%) and 33% of patients were older than age 65 years. Intensive care units had the highest incidence rates, followed by burn units with incidence rates close to 9. Highest percentages of deaths were reported among patients with an HAI in the intensive care unit (20.6%) and those with pneumonia (39.6%). CONCLUSION: Although the underreporting of HAIs hinders accurate calculation of incidence, the present study provides a general update. The results can help in modification of national guidelines and appropriate choice of antimicrobial agents in the management of HAIs.

Renal disorders in HIV-infected patients.

BACKGROUND: HIV infection affects all body organs including kidney. Since the frequency of HIV-related renal disorders is unknown in Iran and the number of HIV-infected patients is increasing, this study was conducted for the first time in Iran to assess the frequency of electrolyte imbalance, renal failure, and proteinuria among HIV-infected patients. METHODS: Between April and December 2005, 65 HIV-infected patients who were receiving care at an outpatient counseling center in Tehran, participated in this study. Blood samples were collected to measure serum levels of sodium, potassium, calcium, phosphorus, blood urea nitrogen, and creatinine. Urine samples were analyzed to detect protein, red blood cells, white blood cells, and cast. RESULTS: Of the 65 HIV-infected patients, 86.2% were males. The mean age of the patients was 37+/-8.7 years, and 58.5% of the patients had a history of injecting illicit drugs. Urinalysis was normal in all patients, and serum levels of electrolytes, blood urea nitrogen, and creatinine were all in normal range. CONCLUSION: We found no electrolyte imbalance, proteinuria, or renal failure in HIV-infected patients. It seems that renal disorder is infrequent in Iranian HIV-infected patients.

Jolt accentuation of headache: can this maneuver rule out acute meningitis?

OBJECTIVE: Acute meningitis is a medical emergency and its accurate diagnosis could help physicians to accelerate treatment and reduce the mortality and morbidity of patients. Jolt accentuation of headache (Jolt) is an easy clinical maneuver that can be used to diagnose meningitis, but its diagnostic accuracy is controversial. We aimed to assess the "Jolt maneuver" in diagnosis of suspected acute meningitis patients admitted to the emergency ward of Imam-Khomeini Hospital Complex in Tehran, Iran. RESULTS: Out of 250 patients, 227 were included and 64 (28.2%) had cerebrospinal fluid (CSF) changes compatible with meningitis. Jolt was positive in 40 of 64 (62.5%) meningitis patients. Sensitivity, specificity, positive and negative likelihood ratio (+ LR and - LR) of Jolt were 62.5, 88.3%, 5.36 and 0.42, respectively. These indices were also compared to nuchal rigidity, Kernig's and Brudzinski's signs. The highest + LR was for Kernig's sign (6.79) and the lowest - LR was for nuchal rigidity (0.39). CSF culture was positive in two patients (Streptococcus pneumoniae and Aspergillus sp.). We found that in adult patients with fever and acute headache, a positive Jolt maneuver has a good diagnostic accuracy for diagnosis of meningitis and indicates a need for CSF assessment, but negative results cannot exclude it.

Fungal air quality in hospital rooms: a case study in Tehran, Iran.

Fungi are usually presented in indoor environments and cause of many diseases. The aim of this descriptive study was to investigate the level of fungal contamination in hospital rooms. Sampling was conducted with an Andersen one-stage viable impactor (Quick Take-30) and counting plates containing a fungus-selective medium. A total of 120 air samples from ten hospital environments were performed. Airborne fungi concentrations were determined 72-120 hours after sampling. Total mean concentration of detected fungi in the hospital rooms was 55 ± 56 (mean ± SD) cfu/m3. The findings of the fungal concentration in the various hospital rooms revealed different levels of contamination: the lowest mean counts (37 ± 17 cfu/m3) were observed in NS 1 (Nursing Stations 1), and the highest (97 ± 217 cfu/m3) were reported in Orthopedics Operating Room (OOR). The most common fungal genus isolated were Penicillium (70%), Aspergillus (14%), Cladosporium (12%), Alternaria (2%) and others (2%). The obtained results showed that fungal concentrations in the present study were nearly high and these conditions should be considered as a risk factor for patients and other persons in the hospital.