Cerebral phaeohyphomycosis at a tertiary healthcare center in Saudi Arabia.

OBJECTIVES: To report cases of cerebral phaeohyphomycosis at a tertiary hospital in Riyadh, Saudi Arabia. Phaeohyphomycetes are a widely distributed group of fungi whose cell walls contain 1,8 dihydroxynaphthalene-melanin. Cerebral infections caused by these fungi are uncommon and primarily associated with neurotrophic phaeohyphomycetes. METHODS: In January of 2020 we looked back to identify cases of culture-positive cerebral phaeohyphomycosis from our medical records at King Faisal Specialist Hospital and Research Center in Riyadh, Saudi Arabia. Data on demographics, potential risk factors, clinical presentation, treatment, and outcomes were analyzed. RESULTS: Twelve cases of cerebral phaeohyphomycosis were identified, of which 4 were caused by Rhinocladiella mackenziei and the other 8 were caused by various phaeohyphomycetes. There were 2 cases caused by Neoscytalidium dimidiatum, and one case each caused by the following: Acrophialophora fusispora, Chaetomium atrobrunneum, Exophiala dermatitidis, Exerohilum rostratum, Fonsecaea pedrosoi, and Cladophialophora bantiana. Most patients (10 of 12) had underlying immunosuppression. R. mackenziei caused a brain-only infection manifesting as abscess formation. Four patients survived for more than a year after therapy. Surgical evacuation and triazole therapy with posaconazole or itraconazole, alone or in combination with other antifungal agents, were associated with success. CONCLUSION: Cerebral phaeohyphomycosis is an uncommon fungal infection that primarily affects immunocompromised patients and is associated with poor prognosis. R. mackenziei is the most prevalent fungus in our facility and has been linked to a universal mortality.

Portable RT-PCR System: a Rapid and Scalable Diagnostic Tool for COVID-19 Testing.

Combating the ongoing coronavirus disease 2019 (COVID-19) pandemic demands accurate, rapid, and point-of-care testing with fast results to triage cases for isolation and treatment. The current testing relies on reverse transcriptase PCR (RT-PCR), which is routinely performed in well-equipped laboratories by trained professionals at specific locations. However, during busy periods, high numbers of samples queued for testing can delay the test results, impacting efforts to reduce the infection risk. Besides, the absence of well-established laboratories at remote sites and low-resourced environments can contribute to a silent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These reasons compel the need to accommodate point-of-care testing for COVID-19 that meets the ASSURED criteria (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable). This study assessed the agreement and accuracy of the portable Biomeme SARS-CoV-2 system against the gold standard tests. Nasopharyngeal and nasal swabs were used. Of the 192 samples tested using the Biomeme SARS-CoV-2 system, the results from 189 samples (98.4%) were in agreement with the reference standard-of-care RT-PCR testing for SARS-CoV-2. The portable system generated simultaneous results for nine samples in 80 min with high positive and negative percent agreements of 99.0% and 97.8%, respectively. We performed separate testing in a sealed glove box, offering complete biosafety containment. Thus, the Biomeme SARS-CoV-2 system can help decentralize COVID-19 testing and offer rapid test results for patients in remote and low-resourced settings.

Challenge infection model for MERS-CoV based on naturally infected camels.

BACKGROUND: Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging virus that infects humans and camels with no approved antiviral therapy or vaccine. Some vaccines are in development for camels as a one-health intervention where vaccinating camels is proposed to reduce human viral exposure. This intervention will require an understanding of the prior exposure of camels to the virus and appropriate vaccine efficacy studies in camels. METHODS: We conducted a cross sectional seroprevalence study in young dromedary camels to determine the rate of MERS-CoV seropositivity in young camels. Next, we utilised naturally infected camels as a natural challenge model that can be used by co-housing these camels with healthy naive camels in a ratio of 1 to 2. This model is aimed to support studies on natural virus transmission as well as evaluating drug and vaccine efficacy. RESULTS: We found that 90% of the screened camels have pre-existing antibodies for MERS-CoV. In addition, the challenge model resulted in MERS-CoV transmission within 48 h with infections that continued for 14 days post challenge. CONCLUSIONS: Our finding suggests that the majority of young dromedary camels in Saudi Arabia are seropositive and that naturally infected camels can serve as a challenge model to assess transmission, therapeutics, and vaccine efficacy.

Middle East Respiratory Syndrome Coronavirus Infection Dynamics and Antibody Responses among Clinically Diverse Patients, Saudi Arabia.

Middle East respiratory syndrome coronavirus (MERS-CoV) shedding and antibody responses are not fully understood, particularly in relation to underlying medical conditions, clinical manifestations, and mortality. We enrolled MERS-CoV-positive patients at a hospital in Saudi Arabia and periodically collected specimens from multiple sites for real-time reverse transcription PCR and serologic testing. We conducted interviews and chart abstractions to collect clinical, epidemiologic, and laboratory information. We found that diabetes mellitus among survivors was associated with prolonged MERS-CoV RNA detection in the respiratory tract. Among case-patients who died, development of robust neutralizing serum antibody responses during the second and third week of illness was not sufficient for patient recovery or virus clearance. Fever and cough among mildly ill patients typically aligned with RNA detection in the upper respiratory tract; RNA levels peaked during the first week of illness. These findings should be considered in the development of infection control policies, vaccines, and antibody therapeutics.

Epidemiology of a Novel Recombinant Middle East Respiratory Syndrome Coronavirus in Humans in Saudi Arabia.

BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans. Fundamental questions about circulating viruses and transmission routes remain. METHODS: We assessed routinely collected epidemiologic data for MERS-CoV cases reported in Saudi Arabia during 1 January-30 June 2015 and conducted a more detailed investigation of cases reported during February 2015. Available respiratory specimens were obtained for sequencing. RESULTS: During the study period, 216 MERS-CoV cases were reported. Full genome (n = 17) or spike gene sequences (n = 82) were obtained from 99 individuals. Most sequences (72 of 99 [73%]) formed a discrete, novel recombinant subclade (NRC-2015), which was detected in 6 regions and became predominant by June 2015. No clinical differences were noted between clades. Among 87 cases reported during February 2015, 13 had no recognized risks for secondary acquisition; 12 of these 13 also denied camel contact. Most viruses (8 of 9) from these 13 individuals belonged to NRC-2015. DISCUSSIONS: Our findings document the spread and eventual predominance of NRC-2015 in humans in Saudi Arabia during the first half of 2015. Our identification of cases without recognized risk factors but with similar virus sequences indicates the need for better understanding of risk factors for MERS-CoV transmission.

Antibody Response and Disease Severity in Healthcare Worker MERS Survivors.

We studied antibody response in 9 healthcare workers in Jeddah, Saudi Arabia, who survived Middle East respiratory syndrome, by using serial ELISA and indirect immunofluorescence assay testing. Among patients who had experienced severe pneumonia, antibody was detected for >18 months after infection. Antibody longevity was more variable in patients who had experienced milder disease.

Notes from the Field: Nosocomial Outbreak of Middle East Respiratory Syndrome in a Large Tertiary Care Hospital--Riyadh, Saudi Arabia, 2015.

Since the first diagnosis of Middle East respiratory syndrome (MERS) caused by the MERS coronavirus (MERS-CoV) in the Kingdom of Saudi Arabia in 2012, sporadic cases and clusters have occurred throughout the country (1). During June-August, 2015, a large MERS outbreak occurred at King Abulaziz Medical City, a 1,200-bed tertiary-care hospital that includes a 150-bed emergency department that registers 250,000 visits per year.

Invasive fungal infection due to Triadelphia pulvinata in a patient with acute myeloid leukemia.

Triadelphia pulvinata is a rare dematiaceous fungus found in soil. We report the first case of invasive disease in a patient with acute myeloid leukemia who had a bloodstream infection with possibly both lung and brain involvement. Identification was by combined phenotypic features and fungal ribosomal DNA sequence analysis.

Survival Outcome of Empirical Antifungal Therapy and the Value of Early Initiation: A Review of the Last Decade.

AIM: This rapid systematic review aimed to collect the evidence published over the last decade on the effect of empirical antifungal therapy and its early initiation on survival rates. METHODS: A systematic search was conducted in PubMed, Cochrane, Medline, Scopus, and Embase, in addition to a hand search and experts' suggestions. RESULTS: Fourteen cohort studies and two randomized clinical trials reporting the survival outcome of empirical antifungal therapy were included in this review. Two studies reported the association between early empirical antifungal therapy (EAFT) and survival rates in a hematological cancer setting, and fourteen studies reported the outcome in patients in intensive care units (ICU). Six studies reported that appropriate EAFT decreases hospital mortality significantly; ten studies could not demonstrate a statistically significant association with mortality rates. DISCUSSION: The inconsistency of the results in the literature can be attributed to the studies' small sample size and their heterogeneity. Many patients who may potentially benefit from such strategies were excluded from these studies. CONCLUSION: While EAFT is practiced in many settings, current evidence is conflicting, and high-quality studies are needed to demonstrate the true value of this approach. Meanwhile, insights from experts in the field can help guide clinicians to initiate EAFT when indicated.

Antimicrobial resistance trends of non-fermenter Gram negative bacteria in Saudi Arabia: A six-year national study.

BACKGROUND: Antimicrobial resistance (AMR) of non-fermenting Gram-negative bacteria (NFGNB) is increasingly recognized as urgent healthcare threat. Trend data on AMR of NFGNB in Saudi Arabia are either old or limited. The objective was to estimate the prevalence and resistance trends of isolated NFGNB in Saudi Arabia. METHODS: A retrospective multicenter study involving seven tertiary care hospitals in Saudi Arabia was conducted between 2011 and 2016. Susceptibility testing for non-duplicate isolates was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines in College of American Pathologists accredited diagnostic microbiology laboratories in the participating hospitals. RESULTS: Out of 461,274 isolates, 100,132 (21.7%) were NFGNB which represented 30% of gram-negative pathogens. Pseudomonas aeruginosa was the most common (73.6%), followed by Acinetobacter baumannii (21.0%) and Stenotrophomonas maltophilia (5.3%). Resistance trends of P. aeruginosa were increasing for aztreonam (absolute increase during the study was 17.3%), imipenem (12.3%), and meropenem (11.6%). A. baumannii was fully resistant to several beta lactam drugs, and resistance trends were increasing for potential treatments such as tigecycline (25.1%) and tobramycin (15.5%). S. maltophilia was >90% resistant to trimethoprim/ sulfamethoxazole and ciprofloxacin by the end of the study. CONCLUSION: We are reporting high and/or increasing resistance of NFGNB to common treatment options. The current findings call for urgent actions to combat the increasing resistance of NFGNB. Large scale sharing of AMR data collected at different hospitals with the Saudi AMR committee would be critical to set priorities and monitor progress.

Molecular characterization of carbapenem-resistant Enterobacterales in thirteen tertiary care hospitals in Saudi Arabia.

BACKGROUND: Carbapenems are the antibiotics of last-resort for the treatment of bacterial infections caused by multidrug-resistant organisms. The emergence of resistance is a critical and worrisome problem for clinicians and patients. Carbapenem-resistant Enterobacterales (CRE) are spreading globally, are associated with an increased frequency of reported outbreaks in many regions, and are becoming endemic in many others. OBJECTIVES: Determine the molecular epidemiology of CRE isolates from various regions of Saudi Arabia to identify the genes encoding resistance and their clones for a better understanding of the epidemio-logical origin and national spread. DESIGN: Multicenter, cross-sectional, laboratory-based study. SETTING: Samples were collected from 13 Ministry of Health tertiary-care hospitals from five different regions of Saudi Arabia. METHODS: Isolates were tested using the GeneXpert molecular platform to classify CRE. MAIN OUTCOME MEASURES: Prevalence of various types of CRE in Saudi Arabia. SAMPLE SIZE: 519 carbapenem-resistant isolates. RESULT: Of 519 isolates, 440 (84.7%) were positive for CRE, with Klebsiella pneumoniae (410/456, 90%) being the most commonly isolated pathogen. The distribution of the CRE-positive K pneumoniae resistance genes was as follows: OXA-48 (n=292, 71.2%), NDM-1 (n=85, 20.7%), and NDM+OXA-48 (n=33, 8%). The highest percentage of a single blaOXA-48 gene was detected in the central and eastern regions (77%), while the blaNDM-gene was the predominant type in the northern region (27%). The southern regions showed the lowest percentages for harboring both blaOXA-48 and blaNDM genes (4%), while the western region isolates showed the highest percentage of harboring both genes (14%). CONCLUSION: The results illustrate the importance of molecular characterization of CRE isolates for patient care and infection prevention and control. Larger multicenter studies are needed to critically evaluate the risk factors and trends over time to understand the dynamics of spread and effective methods of control. LIMITATIONS: Lack of phenotypic susceptibility and clinical data. CONFLICT OF INTEREST: None.

Vertebral osteomyelitis due to Aspergillus fumigatus in a patient with chronic granulomatous disease successfully treated with antifungal agents and interferon-gamma.

We report a case of invasive aspergillosis due to Aspergillus fumigatus involving the cervical and thoracic vertebrae and upper mediastinum of a 17 year-old Saudi male with chronic granulomatous disease (CGD). The patient did not respond to a long course of liposomal amphotericin B but did to surgical drainage and a combination of caspofungin and itraconazole with subsequent suppression with oral voriconazole. Fourteen months after the start of therapy, the patient had anterior dislocation of T2 thoracic vertebra with cord transection and quadriplegia. He was then treated intravenously with liquid itraconazole and interferon-gamma. The patient made a remarkable recovery over a 2-year period and was eventually able to walk independently. Thus, a combination of antifungals and interferon-gamma may have resulted in the positive outcome in this case.

Six-year multicenter study on short-term peripheral venous catheters-related bloodstream infection rates in 246 intensive units of 83 hospitals in 52 cities of 14 countries of Middle East: Bahrain, Egypt, Iran, Jordan, Kingdom of Saudi Arabia, Kuwait, Lebanon, Morocco, Pakistan, Palestine, Sudan, Tunisia, Turkey, and United Arab Emirates-International Nosocomial Infection Control Consortium (INICC) findings.

BACKGROUND: Short-term peripheral venous catheters-related bloodstream infections (PVCR-BSIs) rates have not been systematically studied, and data on their incidence by number of device-days is not available. METHODS: Prospective, surveillance study on PVCR-BSI conducted from September 1st, 2013 to 31st Mays, 2019 in 246 intensive care units (ICUs), members of the International Nosocomial Infection Control Consortium (INICC), from 83 hospitals in 52 cities of 14 countries in the Middle East (Bahrain, Egypt, Iran, Jordan, Kingdom of Saudi Arabia, Kuwait, Lebanon, Morocco, Pakistan, Palestine, Sudan, Tunisia, Turkey, and United Arab Emirates). We applied U.S. RESULTS: We followed 31,083 ICU patients for 189,834 bed-days and 202,375 short term peripheral venous catheter (PVC)-days. We identified 470 PVCR-BSIs, amounting to a rate of 2.32/1000 PVC-days. Mortality in patients with PVC but without PVCR-BSI was 10.38%, and 29.36% in patients with PVC and PVCR-BSI. The mean length of stay in patients with PVC but without PVCR-BSI was 5.94 days, and 16.84 days in patients with PVC and PVCR-BSI. The microorganism profile showed 55.2 % of gram-positive bacteria, with Coagulase-negative Staphylococci (31%) and Staphylococcus aureus (14%) being the predominant ones. Gram-negative bacteria accounted for 39% of cases, and included: Escherichia coli (7%), Klebsiella pneumoniae (8%), Pseudomonas aeruginosa (5%), Enterobacter spp. (3%), and others (29.9%), such as Serratia marcescens. CONCLUSIONS: PVCR-BSI rates found in our ICUs were much higher than rates published from USA, Australia, and Italy. Infection prevention programs must be implemented to reduce the incidence of PVCR-BSIs.

International Nosocomial Infection Control Consortium (INICC) report, data summary of 45 countries for 2012-2017: Device-associated module.

BACKGROUND: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2012 to December 2017 in 523 intensive care units (ICUs) in 45 countries from Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific. METHODS: During the 6-year study period, prospective data from 532,483 ICU patients hospitalized in 242 hospitals, for an aggregate of 2,197,304 patient days, were collected through the INICC Surveillance Online System (ISOS). The Centers for Disease Control and Prevention-National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI) were applied. RESULTS: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the medical-surgical ICUs, the pooled central line-associated bloodstream infection rate was higher (5.05 vs 0.8 per 1,000 central line-days); the ventilator-associated pneumonia rate was also higher (14.1 vs 0.9 per 1,000 ventilator-days,), as well as the rate of catheter-associated urinary tract infection (5.1 vs 1.7 per 1,000 catheter-days). From blood cultures samples, frequencies of resistance, such as of Pseudomonas aeruginosa to piperacillin-tazobactam (33.0% vs 18.3%), were also higher. CONCLUSIONS: Despite a significant trend toward the reduction in INICC ICUs, DA-HAI rates are still much higher compared with CDC-NHSN's ICUs representing the developed world. It is INICC's main goal to provide basic and cost-effective resources, through the INICC Surveillance Online System to tackle the burden of DA-HAIs effectively.

Six-year multicenter study on short-term peripheral venous catheters-related bloodstream infection rates in 727 intensive care units of 268 hospitals in 141 cities of 42 countries of Africa, the Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific Regions: International Nosocomial Infection Control Consortium (INICC) findings.

BACKGROUND: Short-term peripheral venous catheter-related bloodstream infection (PVCR-BSI) rates have not been systematically studied in resource-limited countries, and data on their incidence by number of device days are not available. METHODS: Prospective, surveillance study on PVCR-BSI conducted from September 1, 2013, to May 31, 2019, in 727 intensive care units (ICUs), by members of the International Nosocomial Infection Control Consortium (INICC), from 268 hospitals in 141 cities of 42 countries of Africa, the Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific regions. For this research, we applied definition and criteria of the CDC NHSN, methodology of the INICC, and software named INICC Surveillance Online System. RESULTS: We followed 149,609 ICU patients for 731,135 bed days and 743,508 short-term peripheral venous catheter (PVC) days. We identified 1,789 PVCR-BSIs for an overall rate of 2.41 per 1,000 PVC days. Mortality in patients with PVC but without PVCR-BSI was 6.67%, and mortality was 18% in patients with PVC and PVCR-BSI. The length of stay of patients with PVC but without PVCR-BSI was 4.83 days, and the length of stay was 9.85 days in patients with PVC and PVCR-BSI. Among these infections, the microorganism profile showed 58% gram-negative bacteria: Escherichia coli (16%), Klebsiella spp (11%), Pseudomonas aeruginosa (6%), Enterobacter spp (4%), and others (20%) including Serratia marcescens. Staphylococcus aureus were the predominant gram-positive bacteria (12%). CONCLUSIONS: PVCR-BSI rates in INICC ICUs were much higher than rates published from industrialized countries. Infection prevention programs must be implemented to reduce the incidence of PVCR-BSIs in resource-limited countries.

The emerging pathogen Candida auris: A focus on the Middle-Eastern countries.

Recent emergence of Candida auris as a multidrug resistant fungal pathogen, associated with difficult-to-control nosocomial transmission and high mortality, raises serious concerns for public health. Since it was first reported from Japan in 2009, C. auris infections have been diagnosed in several countries from all over the world. However, there is a paucity of reported cases from the Middle East. Literature search resulted in finding only six countries (Kuwait, Israel, Oman, KSA, UAE and Iran) reporting C. auris infections in the past three years. All patients were adults with several underlying comorbidities. Majority of the cases presented with bloodstream infection with crude mortality rate of 60%. All isolates were misidentified as C. haemulonii by commercial systems requiring specialized methods for identification. In vitro antifungal susceptibility testing showed 100% strains to be resistant to fluconazole (MIC 32 ≥ 256 mg/L) while variable resistance against other antifungal agents.

Point prevalence survey of antibiotic use in 26 Saudi hospitals in 2016.

OBJECTIVE: To evaluate the antibiotic prescribing trends, qualitatively and quantitatively, among Saudi Ministry of Health (MOH) hospitals. METHOD AND MATERIALS: In May 2016, information about the hospitals and patients was collected for all inpatients from 26 MOH hospitals in Saudi Arabia. Additional information about antibiotic treatment and infections was gathered. Data collection was done using Global Point Prevalence Survey (PPS) tool designed by University of Antwerp, Belgium. RESULTS: A total of 3240 antibiotic doses were administrated to 2182 patients who represented 46.9% of the total eligible admitted patients. Of those patients on antibiotics, 510 (24%) patients were in the Intensive Care Unit (ICU), 646 (30.4%) patients were medically treated, and 972 (45.7%) patients were in surgical departments. The most commonly prescribed antibiotic group was third-generation cephalosporin (17.2%) and the most frequent indication was respiratory ract infectiont (n=597; 18.2%). Antibiotics for surgical prophylaxis represented 23.4% of the total antibiotic doses. Of those, 78% were administrated for more than 24hs. The rate of adherence to antibiotic guidelines was 48.1%. The indications for antibiotics were not documented in the patients' notes for 51.1% of the prescriptions. CONCLUSION: This national PPS provided a useful tool to identify targets for quality improvement in order to enhance the prudent use of antibiotics in hospital settings. This survey can provide a background to assess the quality of antibiotic utilisation after any intervention by administering it regularly.

Middle East respiratory coronavirus (MERS-CoV) spike (S) protein vesicular stomatitis virus pseudoparticle neutralization assays offer a reliable alternative to the conventional neutralization assay in human seroepidemiological studies.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel zoonotic coronavirus that was identified in 2012. MERS-CoV infection in humans can result in an acute, severe respiratory disease and in some cases multi-organ failure; the global mortality rate is approximately 35 %. The MERS-CoV spike (S) protein is a major target for neutralizing antibodies in infected patients. The MERS-CoV microneutralization test (MNt) is the gold standard method for demonstrating prior infection. However, this method requires the use of live MERS-CoV in biosafety level 3 (BSL-3) containment. The present work describes the generation and validation of S protein-bearing vesicular stomatitis virus (VSV) pseudotype particles (VSV-MERS-CoV-S) in which the VSV glycoprotein G gene has been replaced by the luciferase reporter gene, followed by the establishment of a pseudoparticle-based neutralization test to detect MERS-CoV neutralizing antibodies under BSL-2 conditions. Using a panel of human sera from confirmed MERS-CoV patients, the VSV-MERS-CoV particle neutralization assay produced results that were highly comparable to those of the microneutralization test using live MERS-CoV. The results suggest that the VSV-MERS-CoV-S pseudotype neutralization assay offers a highly specific, sensitive and safer alternative method to detect MERS-CoV neutralizing antibodies in human sera.