Middle East Respiratory Syndrome Coronavirus Transmission in Extended Family, Saudi Arabia, 2014.

Risk factors for human-to-human transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) are largely unknown. After MERS-CoV infections occurred in an extended family in Saudi Arabia in 2014, relatives were tested by using real-time reverse transcription PCR (rRT-PCR) and serologic methods. Among 79 relatives, 19 (24%) were MERS-CoV positive; 11 were hospitalized, and 2 died. Eleven (58%) tested positive by rRT-PCR; 8 (42%) tested negative by rRT-PCR but positive by serology. Compared with MERS-CoV-negative adult relatives, MERS-CoV-positive adult relatives were older and more likely to be male and to have chronic medical conditions. Risk factors for household transmission included sleeping in an index patient's room and touching respiratory secretions from an index patient. Casual contact and simple proximity were not associated with transmission. Serology was more sensitive than standard rRT-PCR for identifying infected relatives, highlighting the value of including serology in future investigations.

The emergence of highly resistant and hypervirulent Klebsiella pneumoniae CC14 clone in a tertiary hospital over 8 years.

BACKGROUND: Klebsiella pneumoniae is a major bacterial and opportunistic human pathogen, increasingly recognized as a healthcare burden globally. The convergence of resistance and virulence in K. pneumoniae strains has led to the formation of hypervirulent and multidrug-resistant strains with dual risk, limiting treatment options. K. pneumoniae clones are known to emerge locally and spread globally. Therefore, an understanding of the dynamics and evolution of the emerging strains in hospitals is warranted to prevent future outbreaks. METHODS: In this study, we conducted an in-depth genomic analysis on a large-scale collection of 328 multidrug-resistant (MDR) K. pneumoniae strains recovered from 239 patients from a single major hospital in the western coastal city of Jeddah in Saudi Arabia from 2014 through 2022. We employed a broad range of phylogenetic and phylodynamic methods to understand the evolution of the predominant clones on epidemiological time scales, virulence and resistance determinants, and their dynamics. We also integrated the genomic data with detailed electronic health record (EHR) data for the patients to understand the clinical implications of the resistance and virulence of different strains. RESULTS: We discovered a diverse population underlying the infections, with most strains belonging to Clonal Complex 14 (CC14) exhibiting dominance. Specifically, we observed the emergence and continuous expansion of strains belonging to the dominant ST2096 in the CC14 clade across hospital wards in recent years. These strains acquired resistance mutations against colistin and extended spectrum ß-lactamase (ESBL) and carbapenemase genes, namely blaOXA-48 and blaOXA-232, located on three distinct plasmids, on epidemiological time scales. Strains of ST2096 exhibited a high virulence level with the presence of the siderophore aerobactin (iuc) locus situated on the same mosaic plasmid as the ESBL gene. Integration of ST2096 with EHR data confirmed the significant link between colonization by ST2096 and the diagnosis of sepsis and elevated in-hospital mortality (p-value < 0.05). CONCLUSIONS: Overall, these results demonstrate the clinical significance of ST2096 clones and illustrate the rapid evolution of an emerging hypervirulent and MDR K. pneumoniae in a clinical setting.

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).

The economic burden of dengue fever in the Kingdom of Saudi Arabia.

Rapid urbanization, global trade, and the exceptionally great numbers of worldwide visitors during Hajj and Umrah have all placed the Kingdom of Saudi Arabia at a significant risk of introducing several vector-borne tropical diseases, such as dengue fever virus (DENV) infection. In this study we estimated DENV infection cost of illness (COI) in Saudi Arabia in the period 2013-2017, by processing national data including all declared cases recorded in referral centers in the western region, being the endemic region of the country. Using a statistically validated predictive model that was built on a representative sample of 717 laboratory-confirmed cases of DENV infection, direct costs, due to care-related expenditures, were estimated by applying the predictive equation to national data. However, indirect costs, which are due to productivity loss, were estimated using the human capital model based on gross domestic product adjusted for invalidity duration. Further, under-reporting was adjusted by using an expansion factor EF = 3. We observed highest estimated costs in 2016 with over US$168.5 Million total costs, including direct (US$29.0 Million) and indirect (US$139.5 Million) costs, for a total 4415 confirmed cases. The total DENV COI for the five years was estimated as US$551.0 Million for a total 15,369 patients (59.7%) out of 25,745 declared cases, resulting in an average cost of US$11 947.6 by patient. Depending on the year, productivity years loss costs accounted for 63.3% to 83.8% of the estimated total costs. Dengue has a substantial local economic burden that costs US$110.2 Million per year, stressing the urgent need for an effective national prevention strategy to perform considerable cost-savings besides reducing morbidity.

First report of Klebsiella quasipneumoniae harboring blaKPC-2 in Saudi Arabia.

Background: Nosocomial infections caused by multi-drug resistant Enterobacteriaceae are a global public health threat that ought to be promptly identified, reported, and addressed accurately. Many carbapenem-resistant Enterobacteriaceae-associated genes have been identified in Saudi Arabia but not the endemic Klebsiella pneumoniae carbapenemases (KPCs), which are encoded by blaKPC-type genes. KPCs are known for their exceptional spreading potential. Methods: We collected n = 286 multi-drug resistant (MDR) Klebsiella spp. isolates as part of screening for resistant patterns from a tertiary hospital in Saudi Arabia between 2014 and 2018. Antimicrobial susceptibility testing was carried out using both VITEK II and the broth microdilution of all collected isolates. Detection of resistance-conferring genes was carried out using Illumina whole-genome shotgun sequencing and PacBio SMRT sequencing protocols. Results: A Carbapenem-resistant Enterobacteriaceae (CRE) Klebsiella quasipneumoniae subsp. similipneumoniae strain was identified as a novel ST-3510 carrying a blaKPC-2 carbapenemase encoding gene. The isolate, designated as NGKPC-421, was obtained from shotgun Whole Genome Sequencing (WGS) surveillance of 286 MDR Klebsiella spp. clinical isolates. The NGKPC-421 isolate was collected from a septic patient in late 2017 and was initially misidentified as K. pneumoniae. The sequencing and assembly of the NGKPC-421 genome resulted in the identification of a putative ~ 39.4 kb IncX6 plasmid harboring a blaKPC-2 gene, flanked by transposable elements (ISKpn6-blaKPC-2-ISKpn27). Conclusion: This is the first identification of a KPC-2-producing CRE in the Gulf region. The impact on this finding is of major concern to the public health in Saudi Arabia, considering that it is the religious epicenter with a continuous mass influx of pilgrims from across the world. Our study strongly highlights the importance of implementing rapid sequencing-based technologies in clinical microbiology for precise taxonomic classification and monitoring of antimicrobial resistance patterns.

Burden and treatment patterns of invasive fungal infections in hospitalized patients in the Middle East: real-world data from Saudi Arabia and Lebanon.

OBJECTIVES: The objective of this study was to document the burden and treatment patterns associated with invasive fungal infections (IFIs) due to Candida and Aspergillus species in Saudi Arabia and Lebanon. METHODS: A retrospective chart review study was conducted using data recorded from 2011 to 2012 from hospitals in Saudi Arabia and Lebanon. Patients were included if they had been discharged with a diagnosis of IFI due to Candida or Aspergillus, which was culture proven or suspected based on clinical criteria. Hospital data were abstracted for a random sample of patients to capture demographics, treatment patterns, hospital resource utilization, and clinical outcomes. Descriptive results were reported. RESULTS: Five hospitals participated and provided data on 102 patients with IFI (51 from Lebanon and 51 from Saudi Arabia). The mean age of the patients was 55 years, and 55% were males. Comorbidities included diabetes (41%), coronary artery disease (24%), leukemia (19%), moderate-to-severe renal disease (16%), congestive heart failure (15%), and chronic obstructive pulmonary disease (15%). Twenty percent of patients received corticosteroids prior to admission and 26% had received chemotherapy in the past 90 days. Inpatient mortality was 42%, and the mean hospital length of stay was 32.4±28.6 days. Fifty-five percent of patients required intensive care unit admission (17.2±14.1 days), 37% required mechanical ventilation (13.7±13.2 days), and 11% required dialysis (14.6±14.2 days). The most commonly used first-line antifungal was fluconazole. CONCLUSION: Patients with IFI in Saudi Arabia and Lebanon frequently have multiple medical comorbidities and may not have traditionally observed IFI risk factors. Efforts to increase use of rapid diagnostic tests and appropriate antifungal treatments may impact the substantial mortality and high length of stay observed in these patients.

Burden of methicillin-resistant Staphylococcus aureus pneumonia among hospitalized patients in Lebanon and Saudi Arabia.

OBJECTIVES: The objective of this study is to describe the real-world treatment patterns and burden of suspected or confirmed methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in Saudi Arabia and Lebanon. METHODS: A retrospective chart review study evaluated 2011-2012 data from hospitals in Saudi Arabia and Lebanon. Patients were included if they had been discharged with a diagnosis of MRSA pneumonia, which was culture proven or suspected based on clinical criteria. Hospital data were abstracted for a random sample of patients to capture demographics (eg, age and comorbidities), treatment patterns (eg, timing and use of antimicrobials), hospital resource utilization (eg, length of stay), and clinical outcomes (eg, clinical status at discharge and mortality). Descriptive results were reported using frequencies or proportions for categorical variables and mean and standard deviation for continuous variables. RESULTS: Chart-level data were collected for 93 patients with MRSA pneumonia, 50 in Saudi Arabia and 43 in Lebanon. The average age of the patients was 56 years, and 60% were male. The most common comorbidities were diabetes (39%), congestive heart failure (30%), coronary artery disease (29%), and chronic obstructive pulmonary disease (28%). Patients most frequently had positive cultures from pulmonary (87%) and blood (27%) samples. All isolates were sensitive to vancomycin, teicoplanin, and linezolid, and only one-third of the isolates tested were sensitive to ciprofloxacin. Beta-lactams (inactive therapy for MRSA) were prescribed 21% of the time across all lines of therapy, with 42% of patients receiving first-line beta-lactams. Fifteen percent of patients did not receive any antibiotics that were considered to be MRSA active. The mean hospital length of stay was 32 days, and in-hospital mortality was 30%. CONCLUSION: The treatment for MRSA pneumonia in Saudi Arabia and Lebanon may be suboptimal with inactive therapy prescribed a substantial proportion of the time. The information gathered from this Middle East sample provides important perspectives on the current treatment patterns.

Epidemiology and outcome of invasive fungal infections and methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and complicated skin and soft tissue infections (cSSTI) in Lebanon and Saudi Arabia.

The objectives of this retrospective medical chart review study were to document the inpatient incidence, treatment, and clinical outcomes associated with invasive fungal infections (IFI) due to Candida and Aspergillus species, Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and MRSA complicated skin and soft tissue infections (cSSTI) in the Middle East. This study evaluated 2011-2012 data from 5 hospitals in Saudi Arabia and Lebanon with a combined total of 207,498 discharges. Hospital medical chart data were abstracted for a random sample of patients with each infection type (102 patients - IFI, 93 patients - MRSA pneumonia, and 87 patients-MRSA cSSTI). Descriptive analysis found that incidence of IFI (per 1000 hospital discharges) was higher than MRSA cSSTI and MRSA pneumonia (IFI: 1.95 and 2.57; MRSA cSSTI: 2.01 and 0.48; and MRSA pneumonia 0.59 and 0.55 for Saudi Arabia and Lebanon, respectively). Median time from hospital admission to diagnosis and from admission to initiation of active therapy were 6 and 7 days, respectively, in IFI patients; median time from admission to diagnosis was 2days for both MRSA pneumonia and cSSTI, with a median of 4 and 2days from admission to MRSA-active antibiotic start, respectively. The mean hospital LOS was 32.4days for IFI, 32.4days for MRSA pneumonia and 26.3days for MRSA cSSTI. Inpatient mortality was higher for IFI (42%) and MRSA pneumonia (30%) than for MRSA cSSTI (8%). At discharge, 33% of patients with IFI and 27% and 9% of patients with MRSA pneumonia and cSSTI, respectively, were considered to have failed therapy. In conclusion, there is a significant burden of these serious infections in the Middle East, as well as opportunity for hospitals to improve the delivery of patient care for difficult-to-treat infections by promoting expedited diagnosis and initiation of appropriate antimicrobial therapy.

Treatment patterns, resource utilization, and outcomes among hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections in Lebanon and Saudi Arabia.

OBJECTIVES: To describe treatment patterns and medical resource use for methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft tissue infections (cSSTI) in Saudi Arabia and Lebanon in terms of drug selection against the infecting pathogen as well as hospital resource utilization and clinical outcomes among patients with these infections. METHODS: This retrospective chart review study evaluated 2011-2012 data from five hospitals in Saudi Arabia and Lebanon. Patients were included if they had been discharged with a diagnosis of MRSA cSSTI, which was culture-proven or suspected based on clinical criteria. Hospital data were abstracted for a random sample of patients with each infection type to capture demographics, treatment patterns, hospital resource utilization, and clinical outcomes. Statistical analysis was descriptive. RESULTS: Data were abstracted from medical records of 87 patients with MRSA cSSTI; mean age 52.4±25.9 years and 61% male. Only 64% of patients received an MRSA active initial therapy, with 56% of first-line regimens containing older beta-lactams. The mean total length of stay was 26.3 days, with the majority (19.1 days) spent in general wards. Surgical procedures included incision and drainage (22% of patients), debridement (14%), and amputation (5%). Mechanical ventilation was required by 9% of patients, with a mean duration of 18 days per patient. Hemodialysis was required by four patients (5%), two of whom were reported to have moderate to severe renal disease on admission, for a mean of 5.5 days. Inpatient mortality was 8%. Thirty-nine percent were prescribed at least one antibiotic at discharge, with the most commonly prescribed discharge antibiotics being clindamycin (44%), ciprofloxacin (18%), trimethoprim/sulfamethoxazole (12%), and linezolid (9%). CONCLUSION: This Middle Eastern real-world study of resource use and treatment patterns in MRSA cSSTI indicates that management of this condition could be further optimized in terms of drug selection and resource utilization.

Rhizopus-associated soft tissue infection in an immunocompetent air-conditioning technician after a road traffic accident: a case report and review of the literature.

Rhinocerebral or sinopulmonary mucromycosis is a well-recognized human fungal infection found among immunocompromised and diabetic patients. However, the infection is rare among immunocompetent hosts. We are reporting the case of an adult immunocompetent male patient working as an air-conditioning technician. The patient was a victim of a road traffic accident (RTA) and sustained multiple fractures in the proximal part of the left tibia, distal femur, and scapula. Two weeks postoperatively, Rhizopus microspores were isolated from an infected traumatic wound over the distal femur. Surgical debridement was performed, and the patient was started on amphotericin B. Occupational exposure history and workplace environmental sanitation are crucial for the prevention of this potentially fatal yet preventable infection.