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العنوان
Microbial resistance of polymyxin and its potential underlying mechanism(s) among Gram-negative bacteria recovered from nosocomial infections in Egypt /
المؤلف
Quraishi,Amani Thaer Abdulzahra.
هيئة الاعداد
باحث / Amani Thaer Abdulzahra Quraishi
مشرف / Walid Faisal Ahmed Elkhatib
مشرف / Mahmoud Abdel-Ati Fouad Khalil
تاريخ النشر
2019
عدد الصفحات
158p.:
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الصيدلة ، علم السموم والصيدلانيات
تاريخ الإجازة
1/1/2019
مكان الإجازة
جامعة عين شمس - كلية الصيدلة - Microbiology and Immunology
الفهرس
Only 14 pages are availabe for public view

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from 158

Abstract

Recently, the rise in infections caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB), especially the resistance to carbapenems most importantly observed in Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli, has led to the resuscitation of Polymyxins (polymyxin B and colistin) worldwide as a last-resort treatment option.
group consists of polymyxins A–E, of which only polymyxin B and polymyxin E (colistin) are currently on the market. Colistin is available in two forms: colistin sulfate (tablets or syrup for bowel decontamination and powder for topical use) and colistin methanesulfonate (International Nonproprietary Name: colistimethate sodium) for parenteral use. In the USA and Brazil, polymyxin B sulfate is also used parenterally.
Colistin is active in vitro against Enterobacteriaceae (including carbapenemase-producing strains), Haemophilus influenzae, Legionella pneumophila, MDR P. aeruginosa and Acinetobacter spp., and Stenotrophomonas maltophilia, including most of the pan-drug resistant (PDR) strains.
Resistance to polymyxins by bacteria that are normally susceptible to these drugs has been reported. There are also reports of increases in infections caused by naturally polymyxin-resistant bacteria, such as Proteus, Providencia, Morganella, and Serratia.
Bacteria employ several means to protect itselfe from adverse environmental stimuli, including exposure to cationic antimicrobial peptides, such as polymyxin B and colistin. These strategies include alterations of their lipopolysaccharides (LPSs), which have overall negative charges and are the initial targets of polymyxins. Such alterations can be achieved by covalent modifications of the lipid A moiety of LPS through the addition of phosphoethanolamine (PEtN) and 4-amino-4-deoxy-L-arabinose (L-Ara4N), deacylation and hydroxylation.
Other strategies include the utilization of an efflux pump and capsule formation. The most common LPS modification is the cationic substitution of the phosphate groups by L-Ara4N, which decreases the net negative charge of lipid A to 0, and the second most common is the PEtN modification, which decreases the net charge from −1.5 to −1. The resultant net positive charge of the modified LPS reduces its binding to polymyxins, leading to resistance.
Throughout this study period, 40 carbapenem-resistant A. baumannii isolates (CRAB) were recovered from male (n = 28; 70%) and female (n = 12; 30%) patients in EL-Kasr El-Aini hospital (Cairo, Egypt). Almost half of A. baumannii isolates were recovered from sputum
samples (n = 19; 47.5%) followed by urine (n = 13; 32.5%), and pus (n = 8; 20%). All isolates (n = 40; 100%) were resistant to amoxicillin-clavulanic acid, cefotaxime, imipenem, meropenem, gentamicin, and amikacin. Most isolates 19 revealed resistance to ciprofloxacin (95%; n = 38) and co-trimoxazole (92.5%; n = 37). Resistance to tobramycin and doxycycline represented 80% (n = 32) and 62.5% (n = 25) of the tested clinical isolates, respectively. Only two A. baumannii isolates (A119, and A140) demonstrated colistin-resistance and they were selected for further study.
Emergence of colistin-resistant/carbapenem-resistant A. baumannii in our healthcare setting is an alarming issue. Colistin-resistance was associated with mutations in pmrABC genes and OXA-23-like carbapenem-hydrolyzing class was the most predominant carbapenemase. Also, armA was the main methyltransferase gene among the clinical isolates of A. baumannii. Our findings revealed that colistin-resistance was associated with high resistance level to other antimicrobials and it was attributed to the current findings represent a serious healthcare problem capable of restraining future therapeutic options. Strict regulations of antibiotic usage are crucially needed in Egyptian hospitals to prohibit spread of CRAB and colistin-resistant A. baumannii in clinical settings.