(Klett Manufacturing Company, New York). In a separate .... On the other hand the drug possesses good anti- fungal activity against ... To the best of .... New Delhi, India, 1998. [2] ..... Kaatz, G.W.; Moudgal, V.V.; Seo, S.M.; Kristiansen, J.E. Phe-.
Anti-Infective Agents, 2012, 10, 000-000
1
Evaluation of In Vivo and In Vitro Antimicrobial Activities of a Selective Serotonin Reuptake Inhibitor Sertraline Hydrochloride Amalesh Samantaa, Debprasad Chattopadhyayb,*,+, Chandrima Sinhaa,+, Ananda Dulal Janaa,+, Soma Ghosha, Anurup Mandala Ananya Banerjeea, Oliver Hendricksc, Jørn B. Christensend and Jette Elisabeth Kristiansene,+ a
Division of Microbiology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, India; ICMR Virus Unit, ID and BG Hospital, GB-4, First Floor, 57 Dr Suresh C Banerjee Road, Beliaghata, Kolkata 700 010, India; cDepartment of Research, Sygehus Sønderjylland, Denmark and King Christian X Hospital for Rheumatic Diseases, Gråsten, Denmark; dDepartment of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen, Denmark; eMember of MEMPHYS Center for Biomembrane Physics, Department of Physics and Chemistry Campusvej 55, DK-5230 Odense M, Denmark b
Abstract: We investigated the in vitro and in vivo antimicrobial potential of a selective serotonin reuptake inhibitor sertraline hydrochloride, against clinical isolates of bacteria and Candida species. Minimum Inhibitory Concentration of sertraline against 161 human isolates of 12 Gram negative and 5 Gram positive genera, Candida albicans ATCC10231 and Candida tropicalis ATCC13803 was determined by spot inoculation, broth and agar dilution methods along with its postantibiotic effect following a short drug exposure. The toxicity and protective efficacy was tested in vivo with a mousevirulent strain of Salmonella typhimurium NCTC74.The MIC was 20-200μg/ml for bacteria, and 200μg/ml for Candida. The growth inhibitory study with Bacillus subtilis UC564 and Shigella dysenteriae NCTC599/52 revealed that the drug is bacteriostatic at its MIC and cidal at higher concentrations. Study on its post-antibiotic effect following a short drug exposure revealed that Sertraline has a time- and dose-dependent effect. Treatment for 4h at concentrations below and equipotent to the minimal static concentration resulted in a lag of regrowth at 8-24h for Candida isolates. The in vivo study with Salmonella typhimurium in Swiss mice showed that the median lethal dose was 1.9 x 107 cfu and 50 LD50 was 0.95x109. Interestingly, the drug at a non-toxic single dose provides significant protection (P200
Staphylococcus spp.
45
15
23
2
4
1
-
Streptococcus faecalis
1
-
1
-
-
-
-
Micrococcus luteus
2
1
1
-
-
-
-
Bacillus subtilis
6
1
4
-
-
-
1
Shigella spp.
33
6
5
8
13
-
1
Salmonella spp.
11
-
3
1
1
5
1
Vibrio cholerae
13
6
2
-
2
3
-
Vibrio parahaemolyticus
6
-
-
2
3
-
1
Escherichia coli
21
3
1
5
5
7
-
Klebsiella pneumoniae
7
-
1
1
2
3
-
Pseudomonas aeruginosa
9
2
1
-
1
1
4
Proteus vulgaris
3
-
-
-
-
1
2
Citrobacter fruendii
1
-
1
-
-
-
-
Providencia spp.
1
-
-
-
-
1
-
Enterobacter cloacae
1
-
-
-
-
1
-
Lactobacillus sporogenes
1
-
-
-
-
-
1
S. aureus ATCC 25923
1
-
1
-
-
-
-
E. coli ATCC 25922
1
-
1
-
-
-
-
P. aeruginosa ATCC 27853
1
-
-
-
1
-
-
Total
164
34
45
19
32
23
11
Table 2.
Inhibitory Effect of Sertraline Hydrochloride on Candida spp.
Name of Fungal Strains
*
nificant inhibitory action on Staphylococcus spp., Bacillus spp. Shigella dysenteriae, E. coli, Micrococcus spp. and V. cholerae. Moderate inhibitory activity was noted with Salmonella spp and Klebsiella pneumoniae; while V. parahaemolyticus, Pseudomonas spp. and Proteus sp. are resistant up to the highest concentration tested.
Growth in SDA Containing different Concentration of Sertraline Hydrochloride(μg/ml) 0*
100
200
500
1000
Candida albicans ATCC10231
+
+
-
-
-
Candida tropicalis ATCC13803
+
+
-
-
-
Control without drug; +, growth; - , no growth.
Evaluation of In Vivo and In Vitro Antimicrobial Activities of a Selective Serotonin
3.3. Bacteriostatic Action of Sertraline Hydrochloride The MIC of sertraline hydrochloride against Bacillus subtilis UC564 and Shigella dysenteriae NCTC 599/52 was 25μg/ml and 10μg/ml respectively. For Bacillus subtilis UC564 the initial colony count was 4.5x109 CFU/ml before the addition of the drug. Subsequently the viable counts at 2h intervals was 5x104, at 4h it was 6x103, 0.6x103 after 6h and 4x102 at the end of 18h (Fig. 2) Similar experiments with Shigella dysenteriae NCTC 599/52 using 4x108 CFU/ml showed that after 2h of drug treatment the viable count was reduced to 8x106, while after 4h it was 7x106, 7x105 after 6h and 6.4x105 at the end of 18h respectively (Fig. 2). Thus, the data indicated that Sertraline hydrochloride is bacteriostatic against both the Gram positive and Gram negative bacterial isolates tested. 3.4. In Vivo Tests The results of animal study depicted in Table 3 show that Sertraline hydrochloride can protect the mice challenged with S. typhimurium NCTC 74 for which the MIC value for Sertraline was 50g/ml. In the saline control group, 25 (83.3%) of the 30 animals died within 100h of the lethal challenge. The difference between the drug-treated (1300μg/ mouse) and control was significant according to the Chisquare test (P
