The Rapidly Changing Patterns in Bacterial Co-Infections Reveal Peaks in Limited Gram Negatives during COVID-19 and Their Sharp Drop Post-Vaccination, Implying Potential Evolution of Co-Protection during Vaccine-Virus-Bacterial Interplay.

SARS-CoV-2 has caused the most devastating pandemic of all time in recent human history. However, there is a serious paucity of high-quality data on aggravating factors and mechanisms of co-infection. This study aimed to identify the trending patterns of bacterial co-infections and types and associated outcomes in three phases of the pandemic. Using quality hospital data, we have investigated the SARS-CoV-2 fatality rates, profiles, and types of bacterial co-infections before, during, and after COVID-19 vaccination. Out of 389 isolates used in different aspects, 298 were examined before and during the pandemic (n = 149 before, n = 149 during). In this group, death rates were 32% during compared to only 7.4% before the pandemic with significant association (p-value = 0.000000075). However, the death rate was 34% in co-infected (n = 170) compared to non-co-infected patients (n = 128), indicating a highly significant value (p-value = 0.00000000000088). However, analysis of patients without other serious respiratory problems (n = 28) indicated that among the remaining 270 patients, death occurred in 30% of co-infected patients (n = 150) and only 0.8% of non-co-infected (n = 120) with a high significant p-value = 0.00000000076. The trending patterns of co-infections before, during, and after vaccination showed a significant decline in Staphylococcus aureus with concomitant peaks in Gram negatives n = 149 before/n = 149 during, including Klebsiella pneumonian = 11/49 before/during, E. coli n = 10/24, A. baumannii n = 8/25, Ps. aeruginosa n = 5/16, and S. aureus 13/1. Nevertheless, in the post-vaccination phase (n = 91), gender-specific co-infections were examined for potential differences in susceptibility. Methicillin-resistant S. aureus dominated both genders followed by E. coli in males and females, with the latter gender showing higher rates of isolations in both species. Klebsiella pneumoniae declined to third place in male patients. The drastic decline in K. pneumoniae and Gram negatives post-vaccination strongly implied a potential co-protection in vaccines. Future analysis would gain more insights into molecular mimicry.

A Sequent of Gram-Negative Co-Infectome-Induced Acute Respiratory Distress Syndrome Are Potentially Subtle Aggravators Associated to the SARS-CoV-2 Evolution of Virulence.

Acute respiratory distress syndrome (ARDS) is one of the major problems in COVID-19 that is not well understood. ARDS is usually complicated by co-infections in hospitals. Although ARDS is inherited by Europeans and Africans, this is not clear for those from the Middle East. There are severe limitations in correlations made between COVID-19, ARDS, co-infectome, and patient demographics. We investigated 298 patients for associations of ARDS, coinfections, and patient demographics on COVID-19 patients' outcomes. Of the 149 patients examined for ARDS during COVID-19, 16 had an incidence with a higher case fatality rate (CFR) of 75.0% compared to those without ARDS (27.0%) (p value = 0.0001). The co-infectome association showed a CFR of 31.3% in co-infected patients; meanwhile, only 4.8% of those without co-infections (p value = 0.01) died. The major bacteria were Acinetobacter baumannii and Escherichia coli, either alone or in a mixed infection with Klebsiella pneumoniae. Kaplan-Meier survival analysis of COVID-19 patients with and without ARDS revealed a significant difference in the survival time of patients with ARDS (58.8 +/- 2.7 days) and without ARDS (41.9 +/- 1.8 days) (p value = 0.0002). These findings prove that increased hospital time was risky for co-infectome-induced SDRS later on. This also explained that while empiric therapy and lethal ventilations delayed the mortality in 75% of patients, they potentially did not help those without co-infection or ARDS who stayed for shorter times. In addition, the age of patients (n = 298) was significantly associated with ARDS (72.9 +/- 8.9) compared to those without it (56.2 +/- 15.1) and was irrespective of gender. However, there were no significant differences neither in the age of admitted patients before COVID-19 (58.5 +/- 15.3) and during COVID-19 (57.2 +/- 15.5) nor in the gender and COVID-19 fatality (p value 0.546). Thus, Gram-negative co-infectome potentially induced fatal ARDS, aggravating the COVID-19 outcome. These findings are important for the specific differential diagnosis of patients with and without ARDS and co-infections. Future vertical investigations on mechanisms of Gram-negative-induced ARDS are imperative since hypervirulent strains are rapidly circulating. This study was limited as it was a single-center study confined to Ha'il hospitals; a large-scale investigation in major national hospitals would gain more insights.

Synthesis and Photophysical, Electrochemical, and DFT Studies of Piperidyl and Pyrrolidinyl Chalcones.

Small organic molecules with interesting optical and electrochemical properties find applications as organic luminescent materials. In this work, we report the synthesis of novel chalcones with D-A-D and D-A-D-A architecture, followed by their optical, electrochemical, and computational studies. The absorption band of these compounds occurs at 360-480 nm with emission maxima appearing around 513-552 nm. The large Stokes shifts (Δλ) for all compounds (90-132 nm) suggest intramolecular charge transfer (ICT) in the excited states. The molar absorptivity and fluorescence quantum yields were found to be in the range of 1.7-4.26 × 104 M-1 cm-1 and 0.29-0.39, respectively. The electrochemical parameters were determined by using cyclic voltammetry (CV). Density functional theory (DFT) calculations of all compounds were made by using B3LYP/G (d,p) functionals in chloroform and were found to have a good correlation with experimental results. Preliminary studies of absorption, photoluminescence, CV, and their theoretical correlation suggest that these compounds may be optimized for their applications in optoelectronics, sensing, and bioimaging.

Genome-Wide Mining of Selaginella moellendorffii for Hevein-like Lectins and Their Potential Molecular Mimicry with SARS-CoV-2 Spike Glycoprotein.

Multidisciplinary research efforts on potential COVID-19 vaccine and therapeutic candidates have increased since the pandemic outbreak of SARS-CoV-2 in 2019. This search has become imperative due to the increasing emergences and limited widely available medicines. The presence of bioactive anti-SARS-CoV-2 molecules was examined from various plant sources. Among them is a group of proteins called lectins that can bind carbohydrate moieties. In this article, we present ten novel, chitin-specific Hevein-like lectins that were derived from Selaginella moellendorffii v1.0's genome. The capacity of these lectin homologs to bind with the spike protein of SARS-CoV-2 was examined. Using the HDOCK server, 3D-modeled Hevein-domains were docked to the spike protein's receptor binding domain (RBD). The Smo446851, Smo125663, and Smo99732 interacted with Asn343-located complex N-glycan and RBD residues, respectively, with binding free energies of -17.5, -13.0, and -26.5 Kcal/mol. The molecular dynamics simulation using Desmond and the normal-state analyses via torsional coordinate association for the Smo99732-RBD complex using iMODS is characterized by overall higher stability and minimum deformity than the other lectin complexes. The three lectins interacting with carbohydrates were docked against five individual mutations that frequently occur in major SARS-CoV-2 variants. These were in the spike protein's receptor-binding motif (RBM), while Smo125663 and Smo99732 only interacted with the spike glycoprotein in a protein-protein manner. The precursors for the Hevein-like homologs underwent additional characterization, and their expressional profile in different tissues was studied. These in silico findings offered potential lectin candidates targeting key N-glycan sites crucial to the virus's virulence and infection.

Community-Acquired Methicillin-Resistant Staphylococcus aureus in Hospitals: Age-Specificity and Potential Zoonotic-Zooanthroponotic Transmission Dynamics.

Methicillin-resistant Staphylococcus aureus (MRSA) lineages are a devastating clinical and public health issue. Data on local lineage profiles are limited. We report on the frequency of community-acquired and hospital-acquired cases (CA-MRSA, HA-MRSA). We studied 147 isolates from King Khalid tertiary care hospitals (KKH), each from a case in a patient and including 33 patients at the Maternity and Children's Hospital (MCH). Of the 147 isolates, 87 males (59%) and 60 females (41%) were in KKH. The overwhelming majority (80%; n = 119/147) were CA-MRSA in KKH. Intriguingly, despite significant differences between males (70%) and females (53%), lineage-acquisition remained age-specific around 58-60 years in both genders. However, while CA-MRSA dominated early in life (0-20, 70% MCH), it increased with age in KKH adults; 21-50 (28%), >50 (59%) until the overall 80% (n = 144/180). Major specimens included skin-wounds, surgeries (70.3%), blood (13.5%), sputum (8.8%), very rarely urine (4.1%), and nasal (3.4%), albeit most patients showed severe enteritis and necrotizing pneumonia. Antibiograms showed high beta lactam resistances, including amoxicillin-clavulanate (83%), oxacillin (84%), cefoxitin FOX (100%), penicillin and ampicillin (~100%), as well as high resistance (82%) to carbapenem. Fortunately, high susceptibility was seen to non-beta lactams and, to a lesser extent, gentamicin, erythromycin, and fusidic acid; 33%, 34%, and 38%, respectively, in KKH. A similar pattern was seen in MCH except for a low resistance pattern to gentamicin CN, clindamycin CD, erythromycin E, and tobramycin TOB; 34%, 31%, 39%, and 41%, respectively, except for fusidic acid. These findings have significant clinical implications for MRSA patient management strategies. Clinical- and lineage-profiles imply host-selection and zoonotic-zooanthroponotic transmission dynamics. Future molecular typing, sequencing, and characterization of dominant clone(s) is imperative.

Profiles of Independent-Comorbidity Groups in Senior COVID-19 Patients Reveal Low Fatality Associated with Standard Care and Low-Dose Hydroxychloroquine over Antivirals.

Introduction: The lack of feasible therapies and comorbidities aggravate the COVID-19 case-fatality rate (CFR). However, reports examining CFR associations with diabetes, concomitant cardiovascular diseases, chronic kidney disease, and chronic liver disease (CLD) are limited. More studies assessing hydroxychloroquine (Hcq) and antivirals are needed. Purpose: To examine associations of COVID-19 CFR in comorbid patient groups each with single comorbidities and after treatment with Hcq, favipiravir, and dexamethasone (Dex), either alone or in combination versus standard care. Methods: Using statistical analysis, we descriptively determined these associations among 750 COVID-19 patient groups during the last quarter of 2021. Results: A diabetes comorbidity (40%, n=299) showed twice the fatality (CFR 14%) of the others (CFR 7%; P=0.001). Hypertension (Htn) was the second-commonest comorbidity (29.5%, n=221), with similar CFR to diabetes (15% and 7% for Htn and non-Htn, respectively), but with higher significance (P=0.0006167). Although only 4% (n=30) heart failure (HF) was reported, the CFR (40%) was much higher than in those without it (8%). A similar rate (4%) for chronic kidney disease was reported, with CFRs of 33% and 9% among those with and without it, respectively (P=0.00048). Ischemic heart disease was 11% (n=74), followed by chronic liver disease (0.4%) and history of smoking (1%); however, these were not significant due to the sample sizes. Treatment indicated standard care and Hcq alone or in combination were superior (CFR of 4% and 0.5%, respectively) compared to favipiravir (25%) or Dex (38.5%) independently or in combination (35.4%). Furthermore, Hcq performed well (CFR 9%) when combined with Dex (9%; P=4.28-26). Conclusion: The dominance of diabetes and other comorbidities with significant association with CFR implied existence of a common virulence mechanism. The superiority of low-dose Hcq and standard care over antivirals warrants further studies.

A Sequalae of Lineage Divergence in Staphylococcus aureus from Community-Acquired Patterns in Youth to Hospital-Associated Profiles in Seniors Implied Age-Specific Host-Selection from a Common Ancestor.

The rapidly changing epidemiology of Staphylococcus aureus and evolution of strains with enhanced virulence is a significant issue in global healthcare. Hospital-associated methicillin-resistant S. aureus (HA-MRSA) lineages are being completely replaced by community-associated S. aureus (CA-MRSA) in many regions. Surveillance programs tracing the reservoirs and sources of infections are needed. Using molecular diagnostics, antibiograms, and patient demographics, we have examined the distributions of S. aureus in Ha'il hospitals. Out of 274 S. aureus isolates recovered from clinical specimens, 181 (66%, n = 181) were MRSA, some with HA-MRSA patterns across 26 antimicrobials with almost full resistances to all beta-lactams, while the majority were highly susceptible to all non-beta-lactams, indicating the CA-MRSA type. The rest of isolates (34%, n = 93) were methicillin-susceptible, penicillin-resistant MSSA lineages (90%). The MRSA in men was over 56% among total MRSA (n = 181) isolates and 37% of overall isolates (n = 102 of 274) compared to MSSA in total isolates (17.5%, n = 48), respectively. However, these were 28.4% (n = 78) and 12.4% (n = 34) for MRSA and MSSA infections in women, respectively. MRSA rates per age groups of 0-20, 21-50, and >50 years of age were 15% (n = 42), 17% (n = 48), and 32% (n = 89), respectively. However, MSSA in the same age groups were 13% (n = 35), 9% (n = 25), and 8% (n = 22). Interestingly, MRSA increased proportional to age, while MSSA concomitantly decreased, implying dominance of the latter ancestors early in life and then gradual replacement by MRSA. The dominance and seriousness of MRSA despite enormous efforts in place is potentially for the increased use of beta-lactams known to enhance virulence. The Intriguing prevalence of the CA-MRSA patterns in young otherwise healthy individuals replaced by MRSA later in seniors and the dominance of penicillin-resistant MSSA phenotypes imply three types of host- and age-specific evolutionary lineages. Thus, the decreasing MSSA trend by age with concomitant increase and sub-clonal differentiation into HA-MRSA in seniors and CA-MRSA in young and otherwise healthy patients strongly support the notion of subclinal emergences from a resident penicillin-resistant MSSA ancestor. Future vertical studies should focus on the surveillance of invasive CA-MRSA rates and phenotypes.

Molecular evolutionary model based on phylogenetic and mutation analysis of SARS-CoV-2 spike protein sequences from Asian countries: A phylogenomic approach.

The lethal pathogenic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has caused the COVID-19 pandemic, posing serious risks to people. The clove-like spike (S) protein that distinguishes coronaviruses from other viruses is important for viral pathogenicity, evolution, and transmission. The investigation of the unique structural mutations of the SARS-CoV-2 spike protein among 34 Asian countries, as well as the resulting phylogenetic relationship, provided critical information in understanding the pathogenesis. This can be utilized for the discovery of possible treatments and vaccine development. The current study analyzed and depicted phylogenetic and evolutionary models useful for understanding SARS-CoV-2 human-human transmission dynamics in Asian regions with shared land borders. Further, integrated bioinformatics analysis was performed to predict the pathogenic potential and stability of 53 mutational positions among 34 coronavirus strains. Mutations at positions N969K, D614G and S884F have deleterious effects on protein function. These findings are crucial because the Asian mutations could potentially provide a vaccine candidate with co-protection against all SARS-CoV-2 strains. This region is vulnerable because of the high population density and the volume of domestic and international travel for business and tourism. These discoveries would also aid in the development of plans for governments and the general populace to implement all required biocontainment protocols common to all countries.

Pathogen Burden Among ICU Patients in a Tertiary Care Hospital in Hail Saudi Arabia with Particular Reference to ß-Lactamases Profile.

Purpose: Ventilator-associated pneumonia (VAP) is associated with a higher mortality risk for critical patients in the intensive care unit (ICU). Several strategies, including using ß-lactam antibiotics, have been employed to prevent VAP in the ICU. However, the lack of a gold-standard method for VAP diagnosis and a rise in antibiotic-resistant microorganisms have posed challenges in managing VAP. The present study is designed to identify, characterize, and perform antimicrobial susceptibility of the microorganisms from different clinical types of infections in ICU patients with emphasis on VAP patients to understand the frequency of the latter, among others. Patients and Methods: A 1-year prospective study was carried out on patients in the ICU unit at a tertiary care hospital, Hail, Saudi Arabia. Results: A total of 591 clinically suspected hospital-acquired infections (HAI) were investigated, and a total of 163 bacterial isolates were obtained from different clinical specimens with a high proportion of bacteria found associated with VAP (70, 43%), followed by CAUTI (39, 24%), CLABSI (25, 15%), and SSI (14, 8.6%). Klebsiella pneumoniae was the most common isolate 39 (24%), followed by Acinetobacter baumannii 35 (21.5%), Pseudomonas aeruginosa 25 (15.3%), and Proteus spp 23 (14%). Among the highly prevalent bacterial isolates, extended-spectrum beta-lactamase was predominant 42 (42.4%). Conclusion: Proper use of antibiotics, continuous monitoring of drug sensitivity patterns, and taking all precautionary measures to prevent beta-lactamase-producing organisms in clinical settings are crucial and significant factors in fending off life-threatening infections for a better outcome.

Molecular and Source-Specific Profiling of Hospital Staphylococcus aureus Reveal Dominance of Skin Infection and Age-Specific Selections in Pediatrics and Geriatrics.

Staphylococcus aureus is a major human-associated pathogen that causes a wide range of clinical infections. However, the increased human dynamics and the changing epidemiology of the species have made it imperative to understand the population structure of local ecotypes, their transmission dynamics, and the emergence of new strains. Since the previous methicillin-resistant S. aureus (MRSA) pandemic, there has been a steady increase in global healthcare-associated infections involving cutaneous and soft tissue and resulting in high morbidities and mortalities. Limited data and paucity of high-quality evidence exist for many key clinical questions about the pattern of S. aureus infections. Using clinical, molecular, and epidemiological characterizations of isolates, hospital data on age and infection sites, as well as antibiograms, we have investigated profiles of circulating S. aureus types and infection patterns. We showed that age-specific profiling in both intensive care unit (ICU) and non-ICU revealed highest infection rates (94.7%) in senior-patients > 50 years; most of which were MRSA (81.99%). However, specific distributions of geriatric MRSA and MSSA rates were 46.5% and 4.6% in ICU and 35.48% and 8.065% in non-ICU, respectively. Intriguingly, the age groups 0−20 years showed uniquely similar MRSA patterns in ICU and non-ICU patients (13.9% and 9.7%, respectively) and MSSA in ICU (11.6%). The similar frequencies of both lineages in youth at both settings is consistent with their increased socializations and gathering strongly implying carriage and potential evolutionary replacement of MSSA by MRSA. However, in age groups 20−50 years, MRSA was two-fold higher in non-ICU (35%) than ICU (18.6%). Interestingly, a highly significant association was found between infection-site and age-groups (p-value 0.000). Skin infections remained higher in all ages; pediatrics 32.14%, adults 56%, and seniors 25% while respiratory infections were lower in pediatrics (14.3%) and adults (17%) while it was highest in seniors (38%). Blood and "other" sites in pediatrics were recorded (28.6%; 25%, respectively), and were slightly lower in adults (18.6%; 8.6%) and seniors (14%; 22.8%), respectively. Furthermore, a significant association existed between infection-site and MRSA (Chi-Square Test, p-value 0.002). Thus, the common cutaneous infections across all age-groups imply that skin is a significant reservoir for endogenous infections; particularly, for geriatrics MRSA. These findings have important clinical implications and in understanding S. aureus profiles and transmission dynamics across different age groups that is necessary for strategic planning in patient management and infection control.

Molecular Characterization and Antibiogram of Acinetobacter baumannii Clinical Isolates Recovered from the Patients with Ventilator-Associated Pneumonia.

A 2-year prospective study carried out on ventilator-associated pneumonia (VAP) patients in the intensive care unit at a tertiary care hospital, Hail, Kingdom of Saudi Arabia (KSA), revealed a high prevalence of extremely drug-resistant (XDR) Acinetobacter baumannii. About a 9% increase in the incidence rate of A. baumannii occurred in the VAP patients between 2019 and 2020 (21.4% to 30.7%). In 2019, the isolates were positive for IMP-1 and VIM-2 (31.1% and 25.7%, respectively) as detected by PCR. In comparison, a higher proportion of isolates produced NDM-1 in 2020. Here, we observed a high proportion of resistant ICU isolates towards the most common antibiotics in use. Colistin sensitivity dropped to 91.4% in the year 2020 as compared to 2019 (100%). Thus, the finding of this study has a highly significant clinical implementation in the clinical management strategies for VAP patients. Furthermore, strict implementation of antibiotic stewardship policies, regular surveillance programs for antimicrobial resistance monitoring, and screening for genes encoding drug resistance phenotypes have become imperative.

Catheter-Associated Urinary Tract Infection in Intensive Care Unit Patients at a Tertiary Care Hospital, Hail, Kingdom of Saudi Arabia.

Catheter-associated urinary tract infections (CAUTIs) are some of the most common hospital-acquired infections (HAIs). Prolonged hospitalization, invasive devices such as catheters, and irrational use of antimicrobial agents are believed to be the major causes of high rates of HAIs. Infections such as pyelonephritis, urethritis, cystitis, and prostatitis are the main concerns in catheterized ICU patients. In these cases, Gram-negative bacteria are the most common bacteria. The present study was undertaken to determine the frequency, antibiograms, disease pattern, and risk factors involved in providing an advocacy recommendation to prevent CAUTI. A total of 1078 patients were admitted to the hospital ICU, out of which healthcare-associated infection was reported in 316 patients. CAUTI was reported only in 70 patients. Klebsiella pneumoniae (20%) was the predominant isolate, with Serratia (3%) and Providencia (3%) species being the least common isolates in this study. The present study provides CAUTI incidence rates in a tertiary care hospital in Hail, Saudi Arabia. Furthermore, information on the risk factors of common associated CAUTI causative organisms and their antibiogram patterns are also presented. This study provides vital information that can be used to formulate an effective antibiotic stewardship program that can be implemented throughout the kingdom.

The Frequency and Patterns of Post-COVID-19 Vaccination Syndrome Reveal Initially Mild and Potentially Immunocytopenic Signs in Primarily Young Saudi Women.

Vaccination is the most promising approach for ending or containing the SARS-CoV-2 pandemic. However, serious post-COVID-19 vaccine reactions, including immunocytopenia (ITP) syndrome, have been increasingly reported. Several factors cause increased risks including multiple doses, age-dependent heterogeneity in immune-responses, platelet cross-reactions with microbial components, and Long-COVID syndrome. Thus, in the absence of widely available specific therapeutics, vigilance is important while more studies are needed. Using a structured questionnaire sent to different regions in Saudi Arabia, we conducted a comprehensive investigation on the frequency, rates, disease patterns, and patient demographics of post-COVID-19 vaccine side effects on febrile patients after administration three major vaccines. Results indicated that the majority of respondents administered Pfizer BioNtech vaccine (81%, n = 809); followed by AstraZeneca (16%, n = 155); and Moderna (3%, n = 34). Overall 998 participants, 74% (n = 737) showed no serious symptoms; however, 26.2% (n = 261) revealed typical syndromes. In a focused group of 722 participants, the following rates were identified: shortness of breath (20%), bruises or bleeding (18%), inattention (18%), GIT symptoms (17.6%), skin irritation (8.6%), and anosmia and ageusia (8%) were the most prominent among those who showed typical symptoms. The onset time was mostly between 1-3 days in 49% (n = 128), followed by 4-7 days in 21.8% (n = 57), 8-14 days in 16.5% (n = 43), and more than a month in 12.6% (n = 33). The onsets occurred mostly after the first, second, or both doses, 9%, 10%, and 7% of participants, respectively. The frequency of symptoms was significantly higher after Moderna® vaccine (p-value = 0.00006) and it was significantly lower in participants who received Pfizer (p-value = 0.00231). We did not find significant difference in symptoms related to differences in regions. Similarly, the region, age, sex, education, and nationality had no influence on the dose and onset timings. The findings of this study have significant clinical implications in disease management strategies, preventive measures, and vaccine development. Future vertical studies would reveal more insights into the mechanisms of post-COVID-19 vaccine syndrome.

COVID-19 Clinical Profiles and Fatality Rates in Hospitalized Patients Reveal Case Aggravation and Selective Co-Infection by Limited Gram-Negative Bacteria.

Bacterial co-infections may aggravate COVID-19 disease, and therefore being cognizant of other pathogens is imperative. We studied the types, frequency, antibiogram, case fatality rates (CFR), and clinical profiles of co-infecting-pathogens in 301 COVID-19 patients. Co-infection was 36% (n = 109), while CFR was 31.2% compared to 9.9% in non-co-infected patients (z-value = 3.1). Four bacterial species dominated, namely, multidrug-resistant Klebsiella pneumoniae (37%, n = 48), extremely drug-resistant Acinetobacter baumannii (26%, n = 34), multidrug-resistant Eschericia. coli (18.6%, n = 24), and extremely drug-resistant Pseudomonas aeruginosa (8.5%, n = 11), in addition to other bacterial species (9.3%, n = 12). Increased co-infection of K. pneumoniae and A. baumannii was associated with increased death rates of 29% (n = 14) and 32% (n = 11), respectively. Klebsiella pneumoniae was equally frequent in respiratory and urinary tract infections (UTI), while E. coli mostly caused UTI (67%), and A. baumannii and P. aeruginosa dominated respiratory infections (38% and 45%, respectively). Co-infections correlated with advance in age: seniors ≥ 50 years (71%), young adults 21-49 years (25.6%), and children 0-20 years (3%). These findings have significant clinical implications in the successful COVID-19 therapies, particularly in geriatric management. Future studies would reveal insights into the potential selective mechanism(s) of Gram-negative bacterial co-infection in COVID-19 patients.

Selective COVID-19 Coinfections in Diabetic Patients with Concomitant Cardiovascular Comorbidities Are Associated with Increased Mortality.

Coinfections and comorbidities add additional layers of difficulties into the challenges of COVID-19 patient management strategies. However, studies examining these clinical conditions are limited. We have independently investigated the significance of associations of specific bacterial species and different comorbidities in the outcome and case fatality rates among 129 hospitalized comorbid COVID-19 patients. For the first time, to best of our knowledge, we report on the predominance of Klebsiella pneumoniae and Acinetobacter baumannii in COVID-19 non-survival diabetic patients The two species were significantly associated to COVID-19 case fatality rates (p-value = 0.02186). Coinfection rates of Klebsiella pneumoniae and Acinetobacter baumannii in non-survivors were 93% and 73%, respectively. Based on standard definitions for antimicrobial resistance, Klebsiella pneumoniae and Acinetobacter baumannii were classified as multidrug resistant and extremely drug resistant, respectively. All patients died at ICU with similar clinical characterisitics. Of the 28 major coinfections, 24 (85.7%) were in non-survivor diabetic patients, implying aggravating and worsening the course of COVID-19. The rates of other comorbidities varied: asthma (47%), hypertension (79.4%), ischemic heart disease (71%), chronic kidney disease (35%), and chronic liver disease (32%); however, the rates were higher in K. pneumoniae and were all concomitantly associated to diabetes. Other bacterial species and comorbidities did not have significant correlation to the outcomes. These findings have highly significant clinical implications in the treatment strategies of COVID-19 patients. Future vertical genomic studies would reveal more insights into the molecular and immunological mechanisms of these frequent bacterial species. Future large cohort multicenter studies would reveal more insights into the mechanisms of infection in COVID-19.

Iridium-Catalyzed C-H Borylation of CF3-Substituted Pyridines.

Iridium-catalyzed C-H borylation of CF3-substituted pyridines is described in this paper. The boronic ester group can be installed on the α, ß, or γ position of pyridine by an appropriate substitution pattern. Sterically governed regioselectivity provides convenient access to a variety of CF3-substituted pyridylboronic esters. These catalytic C-H borylation reactions were carried out neatly without the use of any solvent. Several functional groups, such as halo, ester, alkoxy, amino, etc., are compatible with this methodology. These pyridylboronic esters are amenable to column chromatography and the products were isolated in good to excellent yields. α-Borylated pyridines, although isolated in good yields, do not have a long shelf life. The boronic ester derivatives of these CF3-substituted pyridines can serve as useful precursors in the synthesis regime.

A Multi-Point Surveillance for Antimicrobial Resistance Profiles among Clinical Isolates of Gram-Negative Bacteria Recovered from Major Ha'il Hospitals, Saudi Arabia.

The devastating nosocomial resistance is an on-going global concern. Surveillance of resistance is crucial for efficient patient care. This study was aimed to conduct a surveillance in four major Ha'il Hospitals from September to December 2020. Using a multipoint program, records of 621 non-duplicate Gram-negative cultures were tested across 21 drugs belonging to different categories. Major species were Klebsiella pneumoniae (n = 187, 30%), E. coli (n = 151, 24.5%), Pseudomonas aeruginosa, (n = 84, 13.6%), Acinetobacter baumannii (n = 82, 13.3%), and Proteus mirabilis (n = 46, 7%). Based on recent resistance classifications, A. baumanni, P. aeruginosa, and enteric bacteria were defined as pan-resistant, extremely resistant, and multi-drug resistant, respectively. A. baumannii (35%) and K. pneumoniae (23%) dominated among coinfections in SARS-CoV2 patients. The "other Gram-negative bacteria" (n = 77, 12.5%) from diverse sources showed unique species-specific resistance patterns, while sharing a common Gram-negative resistance profile. Among these, Providencia stuartii was reported for the first time in Ha'il. In addition, specimen source, age, and gender differences played significant roles in susceptibility. Overall infection rates were 30% in ICU, 17.5% in medical wards, and 13.5% in COVID-19 zones, mostly in male (59%) senior (54%) patients. In ICU, infections were caused by P. mirabilis (52%), A. baumannii (49%), P. aeruginosa (41%), K. pneumoniae (24%), and E. coli (21%), and most of the respiratory infections were caused by carbapenem-resistant A. baumannii and K. pneumoniae and UTI by K. pneumoniae and E. coli. While impressive IC, hospital performances, and alternative treatment options still exist, the spread of resistant Gram-negative bacteria is concerning especially in geriatric patients. The high selective SARS-CoV2 coinfection by A. baumannii and K. pneumoniae, unlike the low global rates, warrants further vertical studies. Attributes of resistances are multifactorial in Saudi Arabia because of its global partnership as the largest economic and pilgrimage hub with close social and cultural ties in the region, especially during conflicts and political unrests. However, introduction of advanced inter-laboratory networks for genome-based surveillances is expected to reduce nosocomial resistances.

Molecular characterization and susceptibility screening for methicillin-resistant Staphylococcus aureus reveals the dominant clones in a tertiary care hospital in Al Qassim, Saudi Arabia.

OBJECTIVE: Staphylococcus aureus has become an important pathogen in hospitals worldwide. Despite its differentiation into human and animal lineages, common methods are used for genotyping. While these methods are useful, they are based on the stable genome, and hence, are insensitive to host-specific subtyping. The objectives of this study were to investigate the repeat-domain of the Clumping-Factor A gene (clfA- R) as an objective and adaptation-sensitive approach. METHODOLOGY: We have used 113 isolates for susceptibility testing and genotyping by polymerase chain reaction amplification of the clfA- R regions. Of these, 105 were from King Fahad Specialist Hospital, Buraidah and eight were published sequences used as references. Isolates were further confirmed as S. aureus by the commercial Kits. Amplicon sizes were measured and the number of the 18-bp-repeating-units in each isolate was determined against that of methicillin-resistant S. aureus COL (MRSA) sequence. RESULTS: Results showed that all 42 nasal screening isolates (100%) and all but six isolates from clinical specimens were MRSA with 37% of the former and 50% of the latter isolates showing community-acquired-MRSA susceptibility patterns. clfA-R analysis grouped 113 isolates into 14 repeat-genotypes. The two dominant types, D and X, represented the long- and short clfA-R types found in humans and animals, respectively. Linezolid, rifampicin, and vancomycin were the drugs of choice. CONCLUSIONS: clfA-R was useful in rapid genotyping and implied host-specific phenotypic properties of the ClfA. It has been recommended that the approach used in regional laboratories for uniform strain-profiling. Future work will show more insights into the gene content and origins of clones .

Surveillance of antimicrobial resistance among clinical isolates recovered from a tertiary care hospital in Al Qassim, Saudi Arabia.

BACKGROUND: The emergences of antimicrobial-resistances have become an important issue in global healthcares. Limitations in surveying hinder the actual estimates of resistance in many countries. THE AIM: the present study was designed to retrospectically survey antimicrobial susceptibility for resistance profiling of dominant pathogens in a tertiary-care center in Buraidah, Saudi Arabia from January-2011 to December-2011. MATERIALS AND METHODS: the design was cross-sectional and spanned records of a 1000 bacterial non-related isolates. Antibiograms were based on the 2012 Clinical and Laboratory Standards Institute guidelines. RESULTS: showed that Staphylococcus aureus, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Escherichia coli, were the most resistant. All isolates of S. aureus, S. epidermidis, and Staphylococcus haemolyticus, were resistant to penicillin (100%), and oxacillin with 52%, 75%, and 82%, respectively. Interestingly, an increasing trend of resistance-pattern was seen for the three species against gentamicin 26%, 50%, 68% ciprofloxacin 22%, 50%, 68%, tetracycline 30%, 44%, 27%, erythromycin 26%, 64%, 73%, and clindamycin 20%, 47%, 50% suggesting potential between-species transfer of resistances. Acinetobacter baumannii was resistances to all antibiotics tested including ciprofloxacin (90%), ceftazidime (89%), cefepime (67%), Trimethoprim/sulfamethoxazole (66%), amikacin (63%), gentamicin (51%), tetracycline (43%), piperacillin-tazobactam (42%), and imipenem (9%). A similar pattern was seen by P. aeruginosa. Furthermore, a typical pattern of resistance in K. pneumoniae carbapenemase-producing organisms was observed. CONCLUSION: we have shown staphylococci, Acinetobacter baumannii, Pseudomonas aeruginosa, and enteric bacteria were the most resistant species in this region.