Open Access Research Article
Pharmaceutica
Analytica Acta
Mahmoud et al., Pharmaceut Anal Acta 2012, S15
http://dx.doi.org/10.4172/2153-2435.S15-007
Special Issue 15 • 2012
Pharmaceut Anal Acta
ISSN: 2153-2435 PAA, an open access journal
Keywords: Biofilm formation of P. aeruginosa; Tetracycline;
Antimicrobial susceptibility; Microtiter plate method; Drug-loaded
chitosan microsphere
Introduction
P. aeruginosa is one of the most important opportunistic human
pathogens. It has emerged as a dominant pulmonary pathogen with
biofilm-forming capability, resulting in progressive chronic pulmonary
infections, cystic fibrosis [1]. here is also an increasing awareness of
the important role of P. aeruginosa biofilms in the contamination
of medical biomaterials such as catheters and prostheses. Biofilm
infections are diicult to eradicate with antimicrobial treatment, and
in vitro susceptibility tests show considerable resistance of biofilm cells
to killing [2].
Biofilms are deined as microbial-derived sessile communities
attached to a surface and embedded in a self-produced polymeric
matrix. hey play a central role in the pathogenesis of serious
infections caused by P. aeruginosa. Bacteria grown in biofilms are more
resistant to antimicrobial agents than their planktonic counterparts
[3]. Susceptibility testing of planktonic bacteria may fail to predict in
vivo resistance of device-related infections to antimicrobial agents.
Standardized laboratory models to test antimicrobial agents in biofilms
are still lacking, although a broad range of models for quantifying
treated vs. untreated biofilms have been described. In most of these
models, the quantiication of biofilm is done by conventional plating
ater disruption of the biofilm. hese methods are labour-intensive and
slow, and the process of disrupting the biofilm can be incomplete or
kill cells so that, the number of colonies does not necessarily relect the
number of viable bacteria in the biofilm. Indirect methods are based on
quantiication of biomass (both living and dead cells), viability assays
(living cells) and matrix quantiication [4].
Many studies have now demonstrated that biofilm-producer
microorganisms have an inherent lack of susceptibility to antibiotics,
whereas planktonic cultures of this same organism do not. his
resistance is lost once the biofilm is reverted to conditions that permit
planktonic growth [5]. he innate resistance of microbial biofilms to
antibiotic therapy has led to problems in their eradication and in the
management of patients with device related infections. Biofilms may
also interfere with the immune clearance of infectious agents. his
diference in antibiotic susceptibility between planktonic and biofilm
populations of the same organism may result from diferences in the
difusion of antibiotics or much more complex changes in the microbial
physiology of the biofilm. he concentrations of antibiotics needed to
inhibit bacterial growth in the sessile phase are oten much higher than
those required for bacteria in the planktonic phase [6].
*Corresponding author: Dr. Nahla A Melake, Department of Pharmaceutics,
Faculty of Pharmacy, King Saud University, Saudi Arabia, Tel: +966-1-2913735;
E-mail: nmelake@ksu.edu.sa
Received March 13, 2012; Accepted June 21, 2012; Published June 23, 2012
Citation: Mahmoud HA, Melake NA, El-Semary MT (2012) Bactericidal Activity
of Various Antibiotics versus Tetracycline-loaded Chitosan Microspheres against
Pseudomonas aeruginosa Bioilms. Pharmaceut Anal Acta S15. doi:10.4172/2153-
2435.S15-007
Copyright: © 2012 Mahmoud HA, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.
Abstract
The discovery of bioilms in 1980’s has brought much interest to the study of the contribution of bacterial bioilms
with many recurrent and chronic infectious diseases. In this study, we evaluated the utility of chitosan microspheres
in delivering antibiotic in dosage form that could be effective against Pseudomonas aeruginosa (P. aeruginosa)
bioilms. P. aeruginosa isolates were collected and identiied using standard methods. A modiied microtiter plate
test was used to determine the bioilm-forming capacity of the isolates. Moreover, bactericidal activity of various
antibiotics vs. tetracycline-loaded chitosan microspheres against P. aeruginosa sessile and planktonic cells was
tested. Results showed that, most P. aeruginosa strains (92.9%) were eficient bioilm producer-strains. There were
differences in the antibiotic susceptibility of planktonic and sessile cell populations. Fluoroquinolones, aminoglycoside
and tetracycline showed more potent activity (MIC
50
was 0.8, 4.88 and 34.19 μg/ml, respectively) than penicillin,
cephalosporin, clarithromycin and macrolides. Bioilm growth was inhibited after 3 h treatment with 2x and 4x MICs
and after 24 h treatment with MIC of tetracycline-loaded chitosan microspheres prepared by coacervation method
than that prepared by water in oil emulsion method. This was correlated to the cumulative amount of tetracycline
that was released from tetracycline-loaded chitosan microspheres prepared by coacervation method which released
about 60% of tetracycline in the irst 6 h and continued for 24 h. This in the clinical ield may be translated into
maintaining constant drug concentration for a prolonged period and maximize the therapeutic effect of antibiotics
while minimizing antibiotic resistance and improved patient compliance. So, the use of tetracycline-chitosan
microspheres may be a new strategy for the development of a speciic drug delivery system to increase the eficacy
of tetracycline against bioilm-associated P. aeruginosa infections. However, it would be appropriate to conduct
clinical studies to conirm this.
Bactericidal Activity of Various Antibiotics versus Tetracycline-loaded
Chitosan Microspheres against Pseudomonas aeruginosa Biofilms
Hanaa A Mahmoud
1
, Nahla A Melake
1,2
* and Mona T El-Semary
1
1
Department of Pharmaceutics, Faculty of Pharmacy, King Saud University, Saudi Arabia
2
Department of Medical Microbiology and Immunology, Faculty of Medicine, Menuiya University, Egypt