Multi-drug Resistant Acinetobacter baumannii: Phenotypic and Genotypic Resistance Profiles and the Associated Risk Factors in Teaching Hospital in Jordan.

BACKGROUND: This study aimed to determine the prevalence of Antimicrobial Resistance Genes (ARGs), with a focus on colistin resistance in clinical A. baumannii, as well as the risk factors associated with A. baumannii infection in Jordanian patients. METHODS: In total, 150 A. baumannii isolates were obtained from patients at a teaching hospital. The isolates were tested for antimicrobial susceptibility using disc diffusion and microdilution methods. PCR amplification was used to detect ARGs, and statistical analysis was conducted to evaluate the influence of identified risk factors on the ARGs acquisition. RESULTS: More than 90% of A. baumannii isolates were resistant to monobactam, carbapenem, cephalosporins, Fluoroquinolones, penicillin, and ß-lactam agents. Moreover, 20.6% of the isolates (n = 31) were colistin-resistant. Several ARGs were also detected in A. baumannii isolates. Univariate analysis indicated that risk factors and the carriage of ARGs were significantly associated P ≤ (0.05) with gender, invasive devices, immunodeficiency, systemic diseases, tumors, and covid-19. Logistic regression analysis indicated seven risk factors, and three protective factors were associated with the ARGs (armA, strA, and strB) P ≤ (0.05). In contrast, tetB and TEM were associated with 2 risk factors each P ≤ (0.05). CONCLUSION: Our study indicates a high prevalence of MDR A. baumannii infections in ICU patients, as well as describing the case of colistin-resistant A. baumannii for the first time in Jordan. Additionally, the risk factors associated with ARGs-producing A. baumannii infections among ICU patients suggest a rapid emergence and spread of MDR A. baumannii without adequate surveillance and control measures.

Methicillin-resistant Staphylococcus aureus contamination of high-touched surfaces in a university campus.

AIM: Methicillin-resistant Staphylococcus (MRSA) is a public and occupational health concern, both in community and healthcare settings. In recent years, community-acquired MRSA (CA-MRSA) has emerged as a major causative agent of infections in individuals with no health care exposure or any of the classical risk factors associated with infections. Environmental surfaces frequently touched by hands play a role in the transmission of CA-MRSA, where inanimate objects are considered potential reservoirs and the source of MRSA infections. The purpose of this study was to examine the prevalence of MRSA on environmental surfaces inside a university campus. METHODS AND RESULTS: A total of 1078 high-touch surface samples were collected from door handles, light switches, desks, keyboards and restroom surfaces. MRSA isolates were identified and confirmed by PCR, utilizing the Staph. aureus nuc and mecA genes. Antibiotic resistance profiles were determined using disc diffusion and minimum inhibitory concertation methods. In addition, the ability to form biofilms was investigated by the 96-well plate microdilution technique. PCR assays were performed to detect enterotoxin and antibiotic-resistant genes. The genetic diversity of MRSA was determined through multi-locus sequence typing (MLST), spa and agr typing methods. The overall contamination of Staph. aureus and MRSA was 14.6% (157/1078) and 2.8% (30/1078), respectively. The highest rate of MRSA contamination was detected in restroom sinks and door handles. All MRSA isolates were MDR, with the highest resistance observed was against trimethoprim-sulfamethoxazole. Most MRSA isolates (29/30, 97%) carried at least one gene encoding for staphylococcal enterotoxins (SE), with 10 different SE genotypes were observed. A total of 16 different spa types were detected among the 30 MRSA isolates. Multi-locus sequence typing revealed that 21 MRSA isolates belonged to eight known sequence types (ST), while nine isolates were novel strains. The most detected ST and spa types were ST22 and t223, respectively. Agr types I and III were represented in 28 out of the 30 isolates. The majority of the isolates carried SCCmec type IV, but only one isolate was positive for PVL. CONCLUSIONS: Our findings signify the potential of the high-touch surfaces in harbouring and transmitting MRSA to campus staff and students. Thus, the implementation of effective prevention measures outside the healthcare setting is needed to reduce the risk of acquiring CA-MRSA infections. SIGNIFICANCE AND IMPACT: MRSA infections impose a profound economic burden due to illness and productivity loss. The results of this study not only help us to better understand the environmental reservoirs of this pathogen, but also provide information about its transmission pathways and healthcare settings entry routs.

Discovery of new heat shock protein 90 inhibitors using virtual co-crystallized pharmacophore generation.

The pharmacophoric features of the virtual cocrystallized protein of 178 Hsp90 proteins were obtained from the protein data bank and explored to generate 1260 pharmacophores evaluated using the decoy list composed of 1022 compounds. Accordingly, 51 pharmacophores were selected with high receiver operating characteristic (ROC) value for further processing. Subsequently, genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of pharmacophoric models and 2D physicochemical descriptors capable of accessing a self-consistent quantitative structure-activity relationship (QSAR) of optimal predictive potential (R672 = 0.819, F = 43.0, R2LOO = 0.782, R2PRESS against 16 external test inhibitors equal 0.735). Two orthogonal pharmacophores emerged in the QSAR equation suggesting the existence of at least two binding modes accessible to ligands within the Hsp90 binding pocket. The fifth generated pharmacophoric model from Hsp90 protein 2XJX (2XJX_2_05), and the forth generated cocrystallized pharmacophoric model from Hsp90 protein 4LWF (4LWF_2_04) with area under the curve AUC-ROC values 0.812 and 0.876, respectively were selected to be used as a searching tool sequentially of the National Cancer Institute (NCI) database. The captured hits were mapped based on successful hypotheses and the best predicted hits were selected. Twenty-four hits showed Hsp90 inhibition, 15 hits were measured with low micromolar IC50 ranged from 5.0 µM to 77.1 µM.