The Open Microbiology Journal




ISSN: 1874-2858 ― Volume 13, 2019
RESEARCH ARTICLE

Detection of OXA Beta Lactamases Among Clinical Isolates of Acinetobacter baumannii Isolated from Tehran Hospitals, Iran



Reza Ranjbar1, *, Shahin Zayeri1, Davoud Afshar2, Shohreh Farshad3
1 Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
2 Department of Microbiology and Virology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
3 Alborzi Clinical Microbiology Research Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, IR Iran

Abstract

Background and Objective:

Acinetobacter baumannii is a non-motile Gram-negative bacterial pathogen with the history of vast resistant to antibiotics. The aim of this study was to determine the possibility of existence of OXAs genes among clinical isolates of A. baumannii obtained from Tehran hospitals.

Materials and Methods:

A total of 101 isolates were identified as A. baumannii by common biochemical and molecular tests. The susceptibility to different antibiotics was assessed with Kirby-Bauer disk diffusion method. Phenotypic Detection of MBLs was performed with CDT test and PCR assay was also performed for detection of blaOXA-23-like, blaOXA-24-like, blaOXA-40-like,blaOXA-51-like,blaOXA-58-like and blaOXA-143-like genes

Results:

All isolates of A. baumannii showed high-level of resistance to all antibiotics except for Polymyxin B. The blaOXA-51 like genes was found in all of the isolates and the prevalence of blaOXA-143like, blaOXA-23like,blaOXA-40like and blaOXA-24like were 56%, 45.45%, 33% and 11.8%, respectively.

Conclusion:

The blaOXA-51-like was the predominant mechanism of resistance to imipenem in A. baumannii and therefore, early recognition of carbapenem-resistant A. baumannii isolates is a useful tools to prevent their spreading within the hospital environment.

Keywords: Acinetobacter baumannii, Carbapenemase, PCR, Gram-negative, Phenotypic detection, Polymyxin B.


Article Information


Identifiers and Pagination:

Year: 2019
Volume: 13
First Page: 68
Last Page: 72
Publisher Id: TOMICROJ-13-68
DOI: 10.2174/1874285801913010068

Article History:

Received Date: 04/11/2018
Revision Received Date: 28/02/2019
Acceptance Date: 10/3/2019
Electronic publication date: 26/03/2019
Collection year: 2019

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© 2019 Ranjbar et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at the Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran; Tel: +98-21-88039883; Fax: +98-21-88039883; E-mail: ranjbarre@gmail.com




1. INTRODUCTION

Acinetobacter baumannii as a facultative, non-motile gram-negative coccobacillus, can spread from one patient to ‎others, easily [1Dong X, Chen F, Zhang Y, Liu H, Liu Y, Ma L. In vitro activities of rifampin, colistin, sulbactam and tigecycline tested alone and in combination against extensively drug-resistant Acinetobacter baumannii. J Antibiot (Tokyo) 2014; 67(9): 677-80.[http://dx.doi.org/10.1038/ja.2014.99] [PMID: 25095805] ]. The organism is the third common pathogenic ‎organism that isolates from hospitalized patients with pneumonia, urinary tract infections, bacteremia, surgical-site infection and Ventilator-Associated Pneumonia (VAP), significantly in intensive-care-unit (ICU) [2Gagliotti C, Morsillo F, Moro ML, et al. Infections in liver and lung transplant recipients: a national prospective cohort. Eur J Clin Microbiol Infect Dis 2018; 37(3): 399-407.[http://dx.doi.org/10.1007/s10096-018-3183-0] [PMID: 29380226] -6Ranjbar R, Sadeghifard N, Ahmadi A, et al. Antimicrobial susceptibility and AP-PCR typing of acine¬ tobac-ter Spp. strains. Iran J Public Health 2007; 36(4): 50-6.]. The low rates of the organism recovery from natural environments and its incidence in the community is opposed to the high rate of carriage among hospitalized patients in the hospital setting [7Perez F, Bonomo RA. Acinetobacter baumannii and Acinetobacter spp.Antimicrobial Drug Resistance 2017; 923-35.[http://dx.doi.org/10.1007/978-3-319-47266-9_10] ]. Its conditions for growth are simple and can survive in severe conditions even in the absence of humid. The persistence of A. baumannii in the hospital environment represents its main reservoirs, which might contribute to its long-term persistence [8Ferri M, Ranucci E, Romagnoli P, Giaccone V. Antimicrobial resistance: A global emerging threat to public health systems. Crit Rev Food Sci Nutr 2017; 57(13): 2857-76.[http://dx.doi.org/10.1080/10408398.2015.1077192] [PMID: 26464 037] ].

A. baumannii strains are generally Multidrug Resistance ‎‎(MDR), which leads in health worrying for their protection from the antibiotics like cephalosporins, aminoglycosides ‎and fluoroquinolones [9Argudín MA, Deplano A, Meghraoui A, et al. Bacteria from animals as a pool of antimicrobial resistance genes. Antibiotics (Basel) 2017; 6(2): 12.[http://dx.doi.org/10.3390/antibiotics6020012] [PMID: 28587316] ]. Surveillance studies highlighted the gradual decrease of carbapenem-resistant isolates over the last ten years in Europe, North America, and Latin America [10Hoban DJ, Reinert RR, Bouchillon SK, Dowzicky MJ. Global in vitro activity of tigecycline and comparator agents: Tigecycline evaluation and surveillance trial 2004-2013. Ann Clin Microbiol Antimicrob 2015; 14(1): 27.[http://dx.doi.org/10.1186/s12941-015-0085-1] [PMID: 25958201] , 11Giamarellou H. Epidemiology of infections caused by polymyxin-resistant pathogens. Int J Antimicrob Agents 2016; 48(6): 614-21.[http://dx.doi.org/10.1016/j.ijantimicag.2016.09.025] [PMID: 27865 627] ]. The high rate of carbapenem resistance among isolates has been considered recently so that carbapenem resistant A. baumannii has become to a challenge worldwide [12Doi Y, Murray GL, Peleg AY. Acinetobacter baumannii: Evolution of antimicrobial resistance-treatment options.Seminars in respiratory and critical care medicine 2015., 13Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. P&T 2015; 40(4): 277-83.[PMID: 25859123] ]. On the other hand, the resistance of A. baumannii to carbapenems can be mediated by one of the known resistance mechanisms occur in bacteria, including enzymatic inactivation, active efflux of drugs, and modification of target sites. However, among the reportedly imipenem resistance mechanisms, the most common mechanism might contain the association between carbapenem-hydrolyzing-β-lactamases belonging to the metallo-β-lactamases (Ambler class B) and oxacillinases (Ambler class D). It should be noted that A. baumannii has the ability to hydrolyze oxacillin more efficiently than benzyl penicillin [14Sartelli M, Weber DG, Ruppé E, et al. Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA). World J Emerg Surg 2016; 11(1): 33.[http://dx.doi.org/10.1186/s13017-016-0089-y] [PMID: 27429642] , 15Mitchell JM, Clasman JR, June CM, et al. Structural basis of activity against aztreonam and extended spectrum cephalosporins for two carbapenem-hydrolyzing class D β-lactamases from Acinetobacter baumannii. Biochemistry 2015; 54(10): 1976-87.[http://dx.doi.org/10.1021/bi501547k] [PMID: 25710192] ]. Class B carbapenemase, such as IMP and VIM enzymes are metallo beta lactamases [16Pitout JD, Nordmann P, Poirel L. Carbapenemase -producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance. Antimicrob Agents Chemother 2015; 59(10): 5873-84.[http://dx.doi.org/10.1128/AAC.01019-15] [PMID: 26169401] , 17Rotondo CM, Wright GD. Inhibitors of metallo-β-lactamases. Curr Opin Microbiol 2017; 39: 96-105.[http://dx.doi.org/10.1016/j.mib.2017.10.026] [PMID: 29154026] ]. Antimicrobial chemotherapy, particularly carbapenems, has contributed to the appearance of carbapenem-hydrolyzing class D β-lactamases (CHDLs). The application of this chemotherapy initiated from the first discovery of a CHDL-encoding gene in 1995 [18Meletis G. Carbapenem resistance: Overview of the problem and future perspectives. Ther Adv Infect Dis 2016; 3(1): 15-21.[http://dx.doi.org/10.1177/2049936115621709] [PMID: 26862399] -20Ideker T, Galitski T, Hood L. A new approach to decoding life: systems biology. Annu Rev Genomics Hum Genet 2001; 2(1): 343-72.[http://dx.doi.org/10.1146/annurev.genom.2.1.343] [PMID: 11701654] ]. There are four major subgroups of acquired CHDLs in A. baumannii strains, including OXA-23, OXA-40, OXA-58, and OXA-143 β-lactamase groups in addition to the naturally-occurring OXA -51 β-lactamase [21Higgins PG, Poirel L, Lehmann M, Nordmann P, Seifert H. OXA-143, a novel carbapenem-hydrolyzing class D β-lactamase in Acinetobacter baumannii. Antimicrob Agents Chemother 2009; 53(12): 5035-8.[http://dx.doi.org/10.1128/AAC.00856-09] [PMID: 19770279] ]. The blaOXA-58 like has been identified worldwide, but frequently from France, England, Argentina, Spain, Turkey, Romania, Austria, Greece, Scotland, and Kuwait [22Poirel L, Nordmann P. Carbapenem resistance in Acinetobacter baumannii: mechanisms and epidemiology. Clin Microbiol Infect 2006; 12(9): 826-36.[http://dx.doi.org/10.1111/j.1469-0691.2006.01456.x] [PMID: 16882 287] ].

A significant contribution of these enzymes in the carbapenem resistance phenotypes has been emphasized, particularly when they are accompanied by ISAba1 and ISAba3 in the naturally occurring plasmid [23Poirel L, Pitout JD, Nordmann P. Carbapenemases: Molecular diversity and clinical consequences 2007; 2(5): 502-12.[http://dx.doi.org/10.2217/17460913.2.5.501] ]. Therefore, the present study was aimed to determine the drug susceptibility patterns, MBLs detection with imipenem-EDTA Combined Disk Method (CDT) test and molecular epidemiology of blaOXA-23-like, blaOXA-24-like, blaOXA-40-like,blaOXA-51-like,blaOXA-58-like and blaOXA-143-like genes of A. baumannii isolates collected from Hospitals of Tehran, Iran.

2. MATERIALS AND METHODS

2.1. Bacterial Isolation and Identification

A total of 101 Acinetobacter baumannii. was obtained from patients with urinary tract infection from different hospitals of Tehran (Iran) during 2016–2017. The strains were identified as A. baumannii by conventional phenotypic tests (growth in 44˚C, motility, oxidative-fermentative, catalase and oxidase test) and their confirmation was completed by rpoB gene [24Rafei R, et al. Extra-human epidemiology of Acinetobacter baumannii in Lebanon. Applied and environmental microbiology 2015; 9(AEM): 03824-14.].

2.2. Antimicrobial Susceptibility Testing

All isolates were tested by the Kirby-Bauer disk diffusion method according to the Clinical and Laboratory Standards Institute (CLSI) guidelines (CLSI 2018) to assess their susceptibilities to Ciprofloxacin (5 μg), Trimethoprim-sulfamethoxazole (1.25-23.75 µg), Chloramphenicol (10 μg), Gentamicin (10 μg), Imipenem (10 μg), Meropenem (10 μg), Polymyxin B (300 unit), Clindamycin (5 μg), Nalidixic acid (75 μg), Tetracycline (30 μg) (Mast Co., Merseyside, UK). The Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 strains were used as quality control of antibiotics disc.

2.3. Phenotypic Detection of MBLs with CDT Test

A. baumannii isolates resistant to imipenem and meropenem were taken for confirmation of the MBLs enzymes CDT test. Each of isolates was subcultured on Mueller-Hinton agar plate and two 10 μg imipenem discs with and without of 0.5 M EDTA were placed on the culture plate. Isolates have shown ≥7 mm increase in inhibition zone imipenem-EDTA disc in comparison to the imipenem disc which is considered as MBLs producers [25Galani I, Rekatsina PD, Hatzaki D, Plachouras D, Souli M, Giamarellou H. Evaluation of different laboratory tests for the detection of metallo-β-lactamase production in Enterobacteriaceae. J Antimicrob Chemother 2008; 61(3): 548-53.[http://dx.doi.org/10.1093/jac/dkm535] [PMID: 18222954] ].

2.4. Molecular Analysis of OXA Genes

DNA extraction of A. baumanni strains was performed by Alkaline lysis method from single colonies from purity plates [26Kheyrodin H, Ghazvinian K. DNA purification and isolation of genomic DNA from bacterial species by plasmid purification system. Afr J Agric Res 2012; 7(3): 433-42.]. Polymerase Chain Reaction (PCR) was done in 20 µl for detection of the carbapenemase-encoding genes (blaOXA-23-like, blaOXA-24-like, blaOXA-40-like,blaOXA-51-like,blaOXA-58-like and blaOXA-143-like). The primers and PCR reaction condition of OXA genes used in amplification reactions were previously described by Kuo et al. [27Lee M-H, Chen TL, Lee YT, et al. Dissemination of multidrug-resistant Acinetobacter baumannii carrying BlaOxA-23 from hospitals in central Taiwan. J Microbiol Immunol Infect 2013; 46(6): 419-24.[http://dx.doi.org/10.1016/j.jmii.2012.08.006] [PMID: 23010539] ].

3. RESULTS

A total of 101 clinical isolates of A. baumannii were collected from two hospitals in Tehran (Iran). The complete resistance to Tetracycline (100%), Clindamycin (100%) and Gentamicin (100%) as well as the high resistance to other antibiotics i.e. Meropenem (97%), Nalidixic ‎acid (95%), Ciprofloxacin (93%), Imipenem (94%) and Trimethoprim-sulfamethoxazole ‎(94%) are shown in Table (1). The resistance rates for polymyxin ‎B (86%) were relatively low. In the present study, 97 isolates were able to produce MBL IN CDT test that was significantly associated with imipenem and meropenem resistance resistance (χ2 p<0.05). Furthermore, all of the isolates were extensively drug-resistant phenotype (XDR), which have been defined for the strains showing resistance to some of the most effective anti-bacterial drugs.

Table 1
Antimicrobial-susceptibility for A. baumannii isolates.


Using PCR assay, all of A. baumannii isolates were positive blaOXA-51 like genes but about (33%) of the isolates were positive for blaOXA-40 like. While 56%, 11.8%, and 45.45% of isolates were positive for blaOXA-143 like,blaOXA-24 like and blaOXA-23 like, respectively but none gave any amplicon for the blaOXA-58 like (Fig. 1).

Co-existence of blaOXA-40 and blaOXA-51 like was observed among 33% of the isolates. The co-relations between carbapen-emase, blaOXA-51 like with blaOXA-143 like and blaOXA-51 like with blaOXA-23 like were statistically significant (χ2 p<0.05).

Fig. (1)
Frequency of OXA genes among A. baumannii isolates.


4. DISCUSSION

Carbapenem resistance has been emerged as a recent common challenge among A. baumannii isolates in Iran and it is difficult to treat of various infections caused by A. baumannii Clinical isolate. This study focused to evaluate the susceptibility rates of A. baumannii isolates toward most of the clinically available antimicrobial agents and molecular epidemiology of blaOXA-23-like, blaOXA-24-like, blaOXA-40-like,blaOXA-51-like,blaOXA-58-like and blaOXA-143-like genes in Tehran. Our results showed that there was a 100% resistance to Tetracycline, Clindamycin, Gentamicin antibiotics‎, whereas relatively low resistance to Polymyxin B. This antibiotic can be helpful in treating A. baumannii-related infections in hospitals. The global incidence of meropenem resistance in A. baumannii was approximately 6% in 1998 but it has dramatically increased to approximately 29% in 2005 [28Hsueh P-R, Chen W-H, Luh K-T. Relationships between antimicrobial use and antimicrobial resistance in Gram-negative bacteria causing nosocomial infections from 1991-2003 at a university hospital in Taiwan. Int J Antimicrob Agents 2005; 26(6): 463-72.[http://dx.doi.org/10.1016/j.ijantimicag.2005.08.016] [PMID: 16280 243] ].

This rapid increase has also been observed in the Tehran hospitals, where resistance rates to imipenem and meropenem were 94% and 97%, respectively. On the other hand, A. baumannii carbapenem resistance is a multiple drug resistance which is needed in combination therapy. In addition, A. baumannii isolates from other countries were also highly resistant to carbapenems [29Queenan AM, Bush K. Carbapenemases: the versatile β-lactamases. Clin Microbiol Rev 2007; 20(3): 440-58.[http://dx.doi.org/10.1128/CMR.00001-07] [PMID: 17630334] -31Sadeghifard N, et al. Antimicrobial susceptibility, plasmid profiles, and RAPD-PCR typing of Acinetobacter bacteria. Asian Biomed 2010; 4(6): 901-11.[http://dx.doi.org/10.2478/abm-2010-0118] ].

All the clinical A. baumannii isolates obtained in 2006–2007 from Malaysia, exhibited high resistance to all the examined antimicrobial agents except for polymyxin B (different mechanisms are involved in the A. baumannii resistance to imipenem. β-Lactamase enzymes is an important factor to carbapenem-resistance [32Loh LC, Yii CT, Lai KK, Seevaunnamtum SP, Pushparasah G, Tong JM. Acinetobacter baumannii respiratory isolates in ventilated patients are associated with prolonged hospital stay. Clin Microbiol Infect 2006; 12(6): 597-8.[http://dx.doi.org/10.1111/j.1469-0691.2006.01411.x] [PMID: 16700 715] ].

The acquisition of carbapenem resistance in A. baumannii is mainly because of the production of two types of β-lactamases; Metallo- β-lactamases (MBLs) and carbapenem-hydrolyzing class D β-lactamases (CHDLs).

Amongst carbapenemase enzymes, MBLs show the most important role in creating resistance to carbapenems but CHDLs are the most prevalence carbapenemases detected in A. baumannii. The CHDLs such as blaOXA-23, blaOXA-24, blaOXA-51 appear to be more prevalent and important to carbapenem resistance in this bacterium in some countries, including Bahrain, UAE and Kuwait. In our study, the most detected genes were OXA-51, OXA-143, OXA-23 and OXA-40 which weresimilar to another study from Iran and Bahrain, UAE and Kuwait [33Zowawi HM, et al. Molecular epidemiology of carbapenem resistant Acinetobacter baumannii in the Gulf Cooperation Council States. Dominance of OXA-23-type producers. J Clin Microbiol 2015; p(JCM): 02784-14.-35Sohrabi N, Farajnia S, Akhi MT, et al. Prevalence of OXA-type β-lactamases among Acinetobacter baumannii isolates from Northwest of Iran. Microb Drug Resist 2012; 18(4): 385-9.[http://dx.doi.org/10.1089/mdr.2011.0077] [PMID: 22352411] ]

Despite the weak capability blaOXA-51 and blaOXA-23 to hydrolyze carbapenem antibiotics but, sometimes because of the insertion of ISAba1 element upstream of the blaOXA-51/23-like gene, it may be the decreased level of susceptibility to carbapenems in A. baumannii isolates.

CONCLUSION

In conclusion, blaOXA-51-like has the predominant mechanisms of resistance to imipenem in A. baumannii. However, for a global epidemiologic analysis, further studies on large scale and at different places should be conducted.

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

The study was approved by Ethical committe in Baqiyatallah University of Medical Sciences, Tehran, Iran.

HUMAN AND ANIMAL RIGHTS

No animals/humans were used for studies that are the basis of this research.

CONSENT FOR PUBLICATION

Informed consent was obtained from all the participants.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

We would like to thank from the “Clinical Research Development Center of Baqiyatallah hospital” for their kindly cooperation. This study was supported in part by a grant from “Clinical Research Development Center of Baqiyatallah hospital”.

REFERENCES

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[21] Higgins PG, Poirel L, Lehmann M, Nordmann P, Seifert H. OXA-143, a novel carbapenem-hydrolyzing class D β-lactamase in Acinetobacter baumannii. Antimicrob Agents Chemother 2009; 53(12): 5035-8.[http://dx.doi.org/10.1128/AAC.00856-09] [PMID: 19770279]
[22] Poirel L, Nordmann P. Carbapenem resistance in Acinetobacter baumannii: mechanisms and epidemiology. Clin Microbiol Infect 2006; 12(9): 826-36.[http://dx.doi.org/10.1111/j.1469-0691.2006.01456.x] [PMID: 16882 287]
[23] Poirel L, Pitout JD, Nordmann P. Carbapenemases: Molecular diversity and clinical consequences 2007; 2(5): 502-12.[http://dx.doi.org/10.2217/17460913.2.5.501]
[24] Rafei R, et al. Extra-human epidemiology of Acinetobacter baumannii in Lebanon. Applied and environmental microbiology 2015; 9(AEM): 03824-14.
[25] Galani I, Rekatsina PD, Hatzaki D, Plachouras D, Souli M, Giamarellou H. Evaluation of different laboratory tests for the detection of metallo-β-lactamase production in Enterobacteriaceae. J Antimicrob Chemother 2008; 61(3): 548-53.[http://dx.doi.org/10.1093/jac/dkm535] [PMID: 18222954]
[26] Kheyrodin H, Ghazvinian K. DNA purification and isolation of genomic DNA from bacterial species by plasmid purification system. Afr J Agric Res 2012; 7(3): 433-42.
[27] Lee M-H, Chen TL, Lee YT, et al. Dissemination of multidrug-resistant Acinetobacter baumannii carrying BlaOxA-23 from hospitals in central Taiwan. J Microbiol Immunol Infect 2013; 46(6): 419-24.[http://dx.doi.org/10.1016/j.jmii.2012.08.006] [PMID: 23010539]
[28] Hsueh P-R, Chen W-H, Luh K-T. Relationships between antimicrobial use and antimicrobial resistance in Gram-negative bacteria causing nosocomial infections from 1991-2003 at a university hospital in Taiwan. Int J Antimicrob Agents 2005; 26(6): 463-72.[http://dx.doi.org/10.1016/j.ijantimicag.2005.08.016] [PMID: 16280 243]
[29] Queenan AM, Bush K. Carbapenemases: the versatile β-lactamases. Clin Microbiol Rev 2007; 20(3): 440-58.[http://dx.doi.org/10.1128/CMR.00001-07] [PMID: 17630334]
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Endorsements



"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."


Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."


Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


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