Synergy of meropenem and ciproxin against clinical isolates of acinetobacter baumannii and detection of antibiotic resistant genes for Quinolones and carbapenems

Other Title(s)

التعاون بين السيبروكسين و الميروبينيم ضد السينيتوباكتر بوماني المعزولة سريريا في التجربة المخبرية و تحديد النماط الجينية المقاومة للكوينولونز و الكاربابينيمز

Dissertant

Idkeidek, Suzan Khamis

Thesis advisor

Farraj, Muhammad A.

University

Birzeit University

Faculty

Faculty of Science

Department

Department Nutrition and Dietetics

University Country

Palestine (West Bank)

Degree

Master

Degree Date

2009

English Abstract

Acinetobacter baumannii has emerged as a major nosocomial pathogen.

Meropenem and imipenem are the most commonly used antimicrobials to treat infections inflicted by this pathogen.

Recently, resistance mechanisms have evolved causing this microorganism to become resistant to these antibiotics.

Eighty five clinical isolates of A.

baumannii were collected from inpatients at Makassed Islamic Hospital in Jerusalem, Palestine.

Antimicrobial susceptibility testing was performed against several antibiotics including meropenem, ciproxin and colistin.

Minimal Inhibitory Concentration was performed on these three antibiotics individually and on meropenem and ciproxin in combination.

Polymerase chain reaction was performed to detect mutations in the Quinolone Resistant Determining Region for selection gyrA and parC genes.

In addition, PCR was performed to detect the acquisition of beta lactam class D oxacillinase genes, specifically oxa24, oxa23, oxa51 and oxa58.

Representative samples were sequenced to confirm the presence of mutations responsible for quinolone resistance and the presence of beta lactam oxacillinase genes responsible for carbamepenem-resistance.

The results obtained revealed that A.

baumannii was resistant to ciproxin (86%), meropenem (74%) and none was resistant to colistin.

Combination results revealed the existence of synergy between ciproxin and imipenem where the MICs were elevated in both (9.5%).

Partial synergy was seen in situations when the organism was resistant to both drugs with the MIC elevated for one of the two drugs tested (52%).

Our results indicated the presence of correlation between resistance to ciproxin and mutations on gyrA at codon 83 for all isolates with MIC ≥2 μg/ml.

Sequencing revealed the presence of substitution of serine to leucine.

Mutations in the parC gene were detected on codon 80 only when the MICs were > 32 ug/ml.

Among the A.

baumannii resistant isolates to meropenem, our results revealed that all isolates carried oxa51, 86.7% carried oxa24 while only 3.3% carried by each of oxa23 and oxa58 genes.

Regarding gyrA and parC, our results agree with published literature as in many other countries.

Regarding beta lactamase genes, the rate of oxa24 carriage seems to be similar to results obtained by other Mediterranean and European countries such Spain and Portugal.

A small number of isolates carried the other clusters of beta lactamases pointing to the potential of further spread of these genes.

The aim of this project was to investigate the antimicrobial susceptibility pattern of A.

baumannii and to determine the presence of synergistic effects between meropenem and ciproxin.

In addition, we investigate the presence of mutations on the gyrA and parC genes, responsible for quinolone resistance, and the acquisition of beta lactamase genes oxa51, oxa24, oxa23 and oxa51 responsible for carbapenem resistance.

Main Subjects

Biology

Topics

• Drugs

No. of Pages

62

Table of Contents

• APA
• MLA
• AMA

Language

English

Data Type

Arab Theses

Record ID

BIM-303664