Fluoroquinolone resistant mechanisms in methicillin-resistant Staphylococcus aureus clinical isolates in Cairo, Egypt

Abstract

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is a persistent problem in community and health care settings. Fluoroquinolones are among the drugs of choice used to treat MRSA infections. This study aims to identify different mechanisms of fluoroquinolne resistance in local MRSA random sampling isolates in Cairo, Egypt. Methodology: A total of 94 clinical isolates of S. aureus were collected from two major University hospitals in Cairo. Identification was confirmed by appropriate morphological, cultural, and biochemical tests. The antibiotic susceptibility pattern was determined for all isolates. The possible involvement of efflux pumps in mediating fluoroquinolone resistance as well as changes in the quinolone resistance determining region (QRDR) of gyrA and gyrB genes were investigated Results: A total of 45 isolates were found to be MRSA, among which 26 isolates were found to be fluoroquinolone-resistant. The MIC values of the tested fluoroquinolones in the presence of the efflux pump inhibitors omeprazole and piperine were reduced. Measuring the uptake of ciprofloxacin upon the addition of the efflux pump inhibitor omeprazole, an increased level of accumulation was observed. Non-synonymous and silent mutations were detected in the QRDR of gyrA and gyrB genes. Conclusions: These results shed light on some of the resistance patterns of MRSA strains isolated from local health care settings in Cairo, Egypt. The resistance of these MRSA towards fluoroquinolones does not depend only on mutation in target genes; other mechanisms of resistance such as the permeability effect, efflux pumps and decreased availability of quinolones at the target site can also be involved.

Molecular Characterization and Resistance Profile of Methicillin Resistant Staphylococcus aureus Strains Isolated from Hospitalized Patients in Intensive Care Unit, Tehran-Iran

“…They showed that the most commonly detected antibiotic resistance genes in the MRSA strains were tetK (89.18%), mecA (71.62%), msrA (56.75%), and tetM (54.05%). In accordance with the results of the studies in Italy (35), Croatia (21), and Hungary (20), a high resistance to ciprofloxacin was seen in the current study (63.2%), which could be due to the widespread use of ciprofloxacin in the treatment of MRSA infections, mutation in gyrase or topoisomerase IV enzymes, and efflux pumps (36).…”

Identification of DNA gyrase Subunit a Mutations Associated with Ciprofloxacin Resistance in Staphylococcus aureus Isolated from Nasal Infection in Kurdistan-Iran

“…In the study of Santos Costa reported that nearly all gyrA mutations related to fluoroquinolone resistance in Staphylococcus aures was Ser84->Leu and in 3 isolates Glu88->Lys was identified (Costa et al, 2013). In the study of Rasha Ser84->Leu, two silent mutations in Ile86 and Leu103, Glu88->Lys, Gly106->Asp, Ser112->Arg in GyrA was reported (Hashem et al, 2013). In our study we could find Ser 84->Leu only in one of the isolates.After indentification new common mutations to understading influence of these mutations on ciprofloxacin resistance, structure of ciprofloxacin and reference and mutated GyrA in pdb format were prepared and molecular docking were done.…”

Molecular epidemiology and mechanisms of antibiotic resistance inEnterococcusspp.,Staphylococcusspp., andStreptococcusspp. in Africa: a systematic review from a One Health perspective

“…MDR to drugs, such as GEN, AMP, amoxicillin, cefepime, TET, and chloramphenicol (CHL) in MRSA, is mediated by diverse resistance mechanisms, including impermeability effects and activity of efflux pumps. Unrestricted access to antibiotics and inappropriate prescriptions were responsible for the high rates of drug resistance in study described above . In a similar study, MRSA was isolated from patients suffering from surgical wound infections, diabetic foot, abscess, and burns.…”

“…Hashem et al . isolated 94 S. aureus strains from blood and wounds among which 45 were MRSA, while 25 were fluoroquinolone resistant . Mutations in gyrase enzymes, including C2402T, T2409C, T2460G, T1497C, and A1578G, which lead to fluoroquinolone target‐site alterations, were implicated in resistance to fluoroquinolones (CIP, levofloxacin, and ofloxacin).…”