ORIGINAL ARTICLE |
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Year : 2004 | Volume
: 22
| Issue : 4 | Page : 222-225 |
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In vitro activity of gatifloxacin against gram negative clinical isolates in a tertiary care hospital
VV Shailaja , V Himabindu , K Anuradha , T Anand , V Lakshmi
Department of Microbiology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad - 500 082, India
Correspondence Address: Department of Microbiology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad - 500 082, India
PURPOSE: The study was carried out to test the in vitro activity of gatifloxacin (GT) against the commonly isolated gram negative pathogens from clinical specimens and compare the same with that of two other fluoroquinolones-ciprofloxacin (CIP) and levofloxacin (LVX) and four non-quinolone agents- cefotaxime (CF), ceftriaxone (CTX), ceftazidime (CAZ) and amoxyclav (AMC). The study included 77 gram negative isolates. METHODS: The in vitro activity of gatifloxacin was evaluated by the Kirby-Bauer disc diffusion method and the MIC was determined by the agar dilution method as per the NCCLS guidelines. RESULTS: Of the organisms tested, 62.8% of the isolates belonging to the family Enterobacteriaceae were sensitive to GT, compared to 36.1 to LVX, 27.8 to CIP, 41.61 to AMC and 32.2% to the cephalosporins tested. For P.aeruginosa, the figures were 41.2, 41.2, 23.5 and 35.3% for GT, CIP, LVX, and the III generation cephalosporins, respectively. CONCLUSION: Gatifloxacin was more effective than the other two fluoroquinolones and the non-quinolone antibiotics against the members of Enterobacteriaceae. However, GT and CIP were found to be equally effective against P.aeruginosa.
How to cite this article: Shailaja V V, Himabindu V, Anuradha K, Anand T, Lakshmi V. In vitro activity of gatifloxacin against gram negative clinical isolates in a tertiary care hospital. Indian J Med Microbiol 2004;22:222-5 |
How to cite this URL: Shailaja V V, Himabindu V, Anuradha K, Anand T, Lakshmi V. In vitro activity of gatifloxacin against gram negative clinical isolates in a tertiary care hospital. Indian J Med Microbiol [serial online] 2004 [cited 2021 Jan 19];22:222-5. Available from: https://www.ijmm.org/text.asp?2004/22/4/222/12811 |
The quinolone class of drugs has been in existence since 1962. However, the class has been considered a major antibacterial group only since the fluorination of the molecule in 1983.[1] This class of antimicrobial agents has a wide antibacterial spectrum though differences exist between compounds in their potency against gram positive bacteria, non fermentative bacteria and anaerobic organisms.[2] The pharmacokinetic/pharmacodynamic properties of fluoroquinolones have a significant impact on their clinical efficacy and safety. All new fluoroquinolones have a bactericidal activity and a post-antibiotic effect. Gatifloxacin (GT) is a fluoroquinolone with a methoxy side chain at the C-8 position that not only seems to increase the bactericidal action and enhance the ability of the drug to inhibit the growth of mutants but also reduces the quinolone associated phototoxicity.[2] The mechanism of action is the inhibition of essential bacterial type II topoisomerases and topoisomerase IV.[1] In this study we determined the activity of GT against 77 gram negative clinical isolates and compared it with those of ciplofloxacin (CIP), levofloxacin (LVX), third generation cephalosporins and amoxyclav.
~ Materials and Methods | |  |
Antibacterial agents All the antibiotic discs used in the study were obtained from M/S Becton, Dickinson and company, Sparks, MD21152, USA. Pure lyophilized antibiotic powders were obtained courtesy Dr. Reddy's Research Foundation, Hyderabad. Media used for propagation and testing the isolates were purchased from Hi Media Pvt. Ltd., Mumbai, India. Bacterial isolates A total of 77 clinical isolates comprising members of family Enterobacteriaceae and P.aeruginosa were included in the study.The isolates were identified by conventional techniques[3] and also by the Mini API (Bio Merieux, France). Isolates were maintained by subculturing on semisolid nutrient agar at 4-8°C. Antibiotic susceptibility testing Kirby Bauer disc diffusion method was used to determine the antibiotic susceptibility of the isolates.[4],[5] MIC values were determined by an agar dilution method in accordance with the procedures out lined by the NCCLS.[4] Stock solutions of the antibiotics were prepared from pure powders by the two-fold dilution scheme. These were added to sterile molten agar to obtain the required final concentration of the drug in the Mueller Hinton agar.[6] Inocula were adjusted to yield approximately 10[4] cfu/spot. Inoculated plates were incubated at 37°C for 18-24 hours. The lowest concentration of the drug that prevented visible growth was recorded as the MIC90 in P.aeruginosa g/mL. Escherichia More Details coli ATCC 25922 and P.aeruginosa ATCC 27853 were used as quality controls to evaluate the accuracy of test methods. The concentrations of the antibiotics used in the study and the interpretative criteria are depicted in [Table - 1] and [Table - 2].
~ Results | |  |
The results obtained by both the test procedures were comparable with minor variations that are acceptable for manual techniques [Table - 3]. Among the members of the family Enterobacteriaceae, 41.2% of the isolates of Escherichia More Details coli were sensitive to GT while being resistant to the other quinolones and non-quinolone antibiotics. The isolates of Klebsiella pneumoniae were highly resistant to the non-quinolone antibiotics and CIP while 35.3% of the isolates were sensitive to GT and 23% to LVX. 87% of the isolates of Enterobacter cloacae were sensitive to GT with a high level of resistance to the other quinolones and non- quinolone antibiotics. The isolates of Proteus mirabilis were equally susceptible to both GT and the third generation cephalosporins. However, compared to the other two quinolones, GT was found to be more effective. All the isolates of Salmonella More Details typhi were sensitive to GT. While 75% of the isolates were sensitive to the non-quinolone antibiotics, only 50% were sensitive to the comparator quinolones. Pseudomonas aeruginosa isolates (41.2 %) were equally sensitive to both GT and CIP with a high level resistance to LVX and the cephalosporins. The MIC90 of the test isolates sensitive to GT was between 0.25 - 2 µg/mL [Table - 4]. The results are represented graphically from [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6].
~ Discussion | |  |
The efficacies of various antimicrobial agents are being threatened by a global increase in the numbers of resistant bacterial pathogens. Introduced in the 1960s, quinolones represented a significant therapeutic advancement in the treatment of patients with infectious diseases.[1],[7] Ever since the fluorination of the molecule in 1983, this class of drugs has been considered a major antibacterial group. The classic fluoroquinolones like ciprofloxacin, norfloxacin and ofloxacin exhibit strong activity against gram negative bacilli but the effectiveness of these compounds against the gram positive bacteria has been debated. The fluoroquinolones developed during 1990 notably levofloxacin, gatifloxacin and moxifloxacin have demonstrated enhanced activity against both the gram positive and gram negative bacteria.[1] GT and other newer quinolones also possess favourable pharmacokinetic properties when compared with the earlier fluoroquinolones. In one study from California wherein the activity of GT was compared with that of five other quinolones versus aerobic and anaerobic isolates, GT was documented to be more active than the other quinolones.[8] Fung- Tome et al documented that GT has a notably enhanced potency against both gram negative and gram positive aerobic and anaerobic bacteria.[2] CIP was found to be more potent than GT when tested against P. aeruginosa To summarize, in our study both GT and CIP were found to be equipotent against P.aeruginosa isolates while GT was found to be more active than other quinolones and the non-quinolone agents against the members of Enterobacteriaceae.
~ Acknowledgements | |  |
We thank Dr.Reddy's Research Foundation for the pure antibiotic powders provided for the study.
~ References | |  |
1. | Lode H, Allewelt M. Role of newer fluoroquinolones in lower respiratory tract infections. Antimicrob Chem 2002;49(5):709-712. |
2. | Fung-Tome J, Minassian B, et al. In vitro antimicrobial spectrum of a new broad-spectrum 8-methoxy fluoroquinolone, Gatifloxacin. Antimicrob Chem 2000;45:437-446. |
3. | Forbes BA, Sahm DF, Weissfeld AS. (Eds.) Overview of conventional methods for identification, Chapter 13. In: Bailey and Scott's Diagnostic Microbiology: 10th ed. (The CV Mosby Company, St. Louis) 1998:167-181. |
4. | NCCLS, Performance standards for Antimicrobial disc susceptibility tests; Approved Standard - Seventh Ed. Jan 2000;20(1). |
5. | Hindler J, Hochstein L, Howell A. Preparation of Routine Media and Reagents used in Antimicrobial Susceptibility Testing. In: Clinical Microbiology Practical Hand Book Antimicrobial Susceptibility Testing, Section-5. Hindler J (ed). |
6. | Woods GL, Washington J, Antibacterial Susceptibility Tests: Dilution and Disc Diffusion Methods, Chapter 113.In: Manual Of Clinical Microbiology, 6th ed. Murray PR, Baron ES, Pfaller MA, Tenover FC, Yolken RH, Eds. (ASM Press, Washington DC) 1995:1327-1341. |
7. | Lu T, Zhao X, et al. Gatifloxacin activity against Quinolone-resistant gyrase: Allele-specific enhancement of bacteriostatic and bactericidal activities by the C-8-methoxy Group. Antimicrobial Agents and Chemotherapy. 1999;43(12):2969-2974. |
8. | Goldstein EJC, Citron DM, et al. Activity of gatifloxacin compared to those of five other quinolones versus aerobic and anaerobic isolates from skin and soft tissue samples of human and animal bite wound infections. Antimicrobial Agents and Chemotherapy 1999;43(6):1475-1479. |
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