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Mohammed S Almuhayawi,1 Mohammed H Alruhaili,1,2 Hattan S Gattan,2,3 Mohanned Talal Alharbi,4 Mohammed Nagshabandi,4 Soad Al Jaouni,5,6 Samy Selim,7 Awadh Alanazi,7 Yasir Alruwaili,7 Osama Ahmed Faried,8 Mohamed E Elnosary9 1Department of Clinical Microbiology and Immunology, Faculty of Medicine, King AbdulAziz University, Jeddah, Saudi Arabia; 2Special Infectious Agents Unit, King Fahad Medical Research Center, King AbdulAziz University, Jeddah, Saudi Arabia; 3Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Medical Microbiology and Parasitology, Faculty of Medicine, University of Jeddah, Jeddah, 23218, Saudi Arabia; 5Department of Hematology/Oncology, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 6Yousef Abdulatif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 7Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia; 8Medical Microbiology and Immunology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt; 9Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Cairo, EgyptCorrespondence: Mohammed S Almuhayawi; Samy Selim, Email msalmuhayawi@kau.edu.sa; sabdulsalam@ju.edu.saBackground: Wound infection is a prevalent concern in the medical field, being is a multi-step process involving several biological processes. Methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) infections often occur in areas of damaged skin, such as abrasions and open wounds.Methods: This research aims to light the incidence of MRSA and VRSA in wound swabs, the antimicrobial susceptibility configuration of isolated S. aureus patterns in pus/wound samples collected from Saudi Arabian tertiary hospital. The cross section study, β- lactamase detection, VRSA genotyping, MAR index, D-test and VRSA genotyping are methods, which used for completed this research.Results: Patients of several ages and genders delivered specimens from two hospitals in the Al jouf area, in the northern province of Saudi Arabia. S. aureus was found in 188 (34.7%) of the 542 wounds. The traumatized wounds provided 71 isolates (38.8%), surgical wound provided 49 isolates (26.8%) and abscess were represented 16 by isolates (8.7%). In the study, 123 (65.4%) out of 188 were MRSA, 60 (31.9%) were MSSA, and five (2.7%) were VRSA. Linezolid and rifampin were found to be the most effective antimicrobials with 100% in vitro antibacterial activity against S. aureus isolates. The Multiple antimicrobials resistance (MAR) index revealed 73 isolates (38.9%) with a MAR index greater than 0.2, and 115 (61.1%) less than 0.2. The D-test showed that of MLSb phenotypes among S. aureus, 22 (11.7%) strains were D-test positive (MLSbi phenotype), 53 (28.2%) strains were constitutive MLSc phenotypes, and 17 (9%) strains were shown to have MSb phenotypes. All VRSA isolates (n=5) were found to be positive for vanA, and no vanB positive isolates were detected in the study.Conclusion: Regular monitoring and an antimicrobials stewardship program should be in place to provide critical information that can be utilized for empirical therapy and future prevention strategies.Keywords: methicillin, vancomycin, resistant, Staphylococcus aureus, emergence, virulent, wound infection, MAR index, D-test, tertiary hospital, Saudi Arabia

Na Xie,1 Lifang Jiang,1 Mingtao Chen,1 Guijun Zhang,1 Yanyan Liu,2 Jiabin Li,2 Xiaohui Huang1 1Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Xiaohui HuangDepartment of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, Anhui Province, 230032, People’s Republic of ChinaTel +86 138 5518 3138Email math2088@163.comJiabin LiDepartment of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Jixi Road, 218#, Hefei, Anhui Province, 230032, People’s Republic of ChinaFax +86 551 62922713Email lijiabin@ahmu.edu.cnObjective: The purpose of this study is to assess the in vitro/vivo activities of linezolid plus fosfomycin against Staphylococcus aureus (S. aureus) isolates with varying susceptibility to the study drugs.Methods: The increasing concentration stepwise method was used to induce S. aureus resistant strains. The in vitro antibacterial activity of linezolid combined with fosfomycin against S. aureus in vitro was studied by time-kill curve and PAE. The transmission electron microscopy (TEM) was employed to observe the cell morphology of bacteria treated with drug, and the changes of cell wall thickness were recorded. The Galleria mellonella infection model was established to demonstrate the in vivo efficacy of linezolid and fosfomycin against S. aureus with varying susceptibility.Results: The antibiotic combination showed excellent synergistic or additive effects on the original and the linezolid-resistant strain, but showed indifferent effect for fosfomycin-resistant strain. TEM images showed that fosfomycin alone and in combined could reduce the cell wall thickness of the strains resistant to linezolid and cell lysis, while linezolid increases the cell wall thickness of the strains resistant to fosfomycin. In the Galleria mellonella infection model, the survival rate of the antibiotic combined was improved compared with that of the single drug. There was a good correlation between in vivo efficacy and in vitro susceptibility.Conclusion: The type of interaction expressed in the test combination was highly dependent on fosfomycin resistance.Keywords: linezolid, fosfomycin, interaction, resistant, Staphylococcus aureus, Galleria mellonella

Pei Li, Yang Yang, Li Ding, Xiaogang Xu, Dongfang Lin Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Dongfang Lin Tel/ Fax +86-21-52888193Email lindongfang@fudan.edu.cnPurpose: The OptrA protein is a member of ATP-binding cassette (ABC) transporters, a transporter family which can confer resistance to oxazolidinone antibiotics by transferring plasmid. We aim to describe the distribution of optrA-harbored Enterococcus in Huashan hospital in 2017 and to address the effects of optrA mutations on the susceptibility of linezolid antibiotic drug.Methods: Linezolid-resistance-related genes were tested for Enterococcus by polymerase chain reaction (PCR) and then sequenced for amino acid substitution site analysis. Broth microdilution and agar dilution test were applied to determine the minimal inhibitory concentration (MIC) of linezolid for Enterococcus containing optrA. Pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used to evaluate the genotypes of optrA-positive isolates. To verify the functions of two main optrA variants, optrA over-expressing strains were constructed.Results: Among 20 optrA-positive strains, only two were resistant to linezolid. No amino acid substitution existed in 23S rRNA V domain among Enterococcus faecalis. None had cfr, cfr(B) or cfr(C) genes. F101L and G4D/K/R or T150A were the main substitutions of ribosomal protein L4, L3, respectively. We found one Enterococcus faecium isolate co-contained optrA and poxtA and another E. faecalis isolate co-contained optrA and cfr(D), but they were not resistant to linezolid. Among 20 optrA-positive strains, ST-16 was the main type. Two main optrA variants KD (T112K, Y176D) and RDK (I104R, Y176D, E256K) slightly raised enterococci’s MIC of linezolid.Conclusion: OptrA exists in linezolid non-resistant enterococci with diverse amino acid substitutions. The variants play different roles in changing the MIC of linezolid.Keywords: linezolid, resistant, enterococci, optrA

Effat Davoudi-Monfared, Hossein Khalili Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Abstract: Data on the status of carbapenem-resistant microorganisms in the Middle East countries are scarce. The aim of this review was to collect available data regarding resistance to carbapenems in a Middle East region. Available data regarding carbapenem-resistant isolates were considered for evaluation in this review. Biomedical electronic databases were systematically searched to find related articles. The key terms used were “carbapenem-resistant, resistant gram-negative bacilli, Enterobacteriaceae, fermenting and non-fermenting gram-negative bacilli, Pseudomonas, Acinetobacter, Klebsiella and Iran”. After primary screening, 275 relevant articles were selected to be assessed thoroughly. Resistance rate to carbapenems was reported between 1% and 86% during years 2006–2018. Most of the carbapenem-resistant microorganisms were isolated from burn patients. Modified Hodge test was a commonly used phenotypic test. Only in few studies, genotypic assays were considered. Pattern of antibiotic use can affect emergence of resistant microorganisms. Rational use of drugs, and specifically, antibiotics is a challenging issue in developing countries. Mean number of drugs per prescription in these countries was higher than the World Health Organization standards. Overuse of antibiotics, especially injectable ones, and easy access to antibiotics without prescription is a warning alarm for future antibiotic resistance in developing countries. Establishing antimicrobial stewardship’s programs is new in the hospitals. Unfortunately, rules and regulatory issues to restrict antibiotic access in community pharmacies and prescription by general physicians are limited. Keywords: carbapenem, resistant, gram-negative bacteria, antibiotics

Background: Across Europe, methicillin-resistant Staphylococcus aureus (MRSA) is considered to be the primary cause of nosocomial pneumonia (NP). In Germany alone, approximately 14,000 cases of MRSA-associated NP occur annually, which may have a significant impact on health care resource use and associated economic costs. The objective of this study was to investigate the economic impact of linezolid compared with that of vancomycin in the treatment of hospitalized patients with MRSA-confirmed NP in the German health care system., Methods: A 4-week decision tree model incorporated published data and expert opinion on clinical parameters, resource use, and costs (2012 euros) was constructed. The base case first-line treatment duration for patients with MRSA-confirmed NP was 10 days. Treatment success (survival), failure due to lack of efficacy, serious adverse events, and mortality were possible outcomes that could impact costs. Alternate scenarios were analyzed, such as varying treatment duration (7 or 14 days) or treatment switch due to a serious adverse event/treatment failure (at day 5 or 10)., Results: The model calculated total base case inpatient costs of €15,116 for linezolid and €15,239 for vancomycin. The incremental cost-effectiveness ratio favored linezolid (versus vancomycin), with marginally lower costs (by €123) and greater efficacy (+2.7% absolute difference in the proportion of patients successfully treated for MRSA NP). Approximately 85%-87% of the total treatment costs were attributed to hospital stay (primarily in the intensive care unit). Sensitivity analysis yielded similar results., Conclusion: The model results show that linezolid is a cost-effective alternative to vancomycin for MRSA-confirmed NP, largely attributable to the higher clinical response rate of patients treated with linezolid.