Ciprofloxacin-Resistant Neisseria meningitidis, Delhi, India

Decreased susceptibility of Neisseria meningitidis isolates to ciprofloxacin emerged from an outbreak in Delhi, India. Results of antimicrobial susceptibility testing of the meningococcal isolates to ciprofloxacin and further sequencing of DNA gyrase A quinolone-resistance–determining region confirmed the emergence of ciprofloxacin resistance in the outbreak

Efficacy of linezolid against Staphylococcus aureus in different rodent skin and soft tissue infections models

Linezolid is approved for complicated and uncomplicated skin and soft tissue infections. We have evaluated the efficacy of this drug in murine as well as in rat skin and soft tissue infection models using Staphylococcus aureus ATCC and clinical strains. In thigh infection model the dose of linezolid required for more than 1 log10 kill from baseline inoculum in neutropenic mice and rats was 100 mg/kg and 50 mg/Kg BW bid /day, respectively, which was 5 and 4 folds more than that in immunocompetent animals, respectively. Dose required to achieve 1 log10 killing was similar against different strains of S. aureus in immunocompetent mouse thigh infection model. However, in murine groin abscess infection model, a dose of 100 mg/kg, b.i.d/day of linezolid produce static effect in 2 days, but revealed to be superior in 4 days treatment and showed approximately 1 log10 killing from base line inoculums. Based upon pharmacokinetic profile, a 24-h AUC/MIC required for linezolid efficacy in murine groin abscess model was 91.5 for the strain used in this study. As linezolid is taken as a gold standard drug in the evaluation of new chemical entity, this data could be useful for comparing the preclinical efficacy of new anti-MRSA agents.</p

<i>Cissampelos pareira</i> Linn: Natural Source of Potent Antiviral Activity against All Four Dengue Virus Serotypes

<div><p>Background</p><p>Dengue, a mosquito-borne viral disease, poses a significant global public health risk. In tropical countries such as India where periodic dengue outbreaks can be correlated to the high prevalence of the mosquito vector, circulation of all four dengue viruses (DENVs) and the high population density, a drug for dengue is being increasingly recognized as an unmet public health need.</p><p>Methodology/Principal findings</p><p>Using the knowledge of traditional Indian medicine, Ayurveda, we developed a systematic bioassay-guided screening approach to explore the indigenous herbal bio-resource to identify plants with pan-DENV inhibitory activity. Our results show that the alcoholic extract of <i>Cissampelos pariera</i> Linn (<i>Cipa</i> extract) was a potent inhibitor of all four DENVs in cell-based assays, assessed in terms of viral NS1 antigen secretion using ELISA, as well as viral replication, based on plaque assays. Virus yield reduction assays showed that <i>Cipa</i> extract could decrease viral titers by an order of magnitude. The extract conferred statistically significant protection against DENV infection using the AG129 mouse model. A preliminary evaluation of the clinical relevance of <i>Cipa</i> extract showed that it had no adverse effects on platelet counts and RBC viability. In addition to inherent antipyretic activity in Wistar rats, it possessed the ability to down-regulate the production of TNF-α, a cytokine implicated in severe dengue disease. Importantly, it showed no evidence of toxicity in Wistar rats, when administered at doses as high as 2g/Kg body weight for up to 1 week.</p><p>Conclusions/Significance</p><p>Our findings above, taken in the context of the human safety of <i>Cipa</i>, based on its use in Indian traditional medicine, warrant further work to explore <i>Cipa</i> as a source for the development of an inexpensive herbal formulation for dengue therapy. This may be of practical relevance to a dengue-endemic resource-poor country such as India.</p></div

Effect of <i>Cipa</i> extract on platelets.

<p>(A) Freshly collected human blood was incubated with saline (white bars) or <i>Cipa</i> extract (at 2 μg/ml: blue bars; or 10 μg/ml: red bars) for up to 4 hours. Aliquots were drawn at the indicated times for determination of platelet counts. (B) Wistar rats were orally administered 0.25% methyl cellulose containing <i>Cipa</i> extract ranging from 0–1000 mg/Kg body weight. Fresh blood collected from these rats at 0 (white bars), 1 (blue bars) and 4 (red bars) hours post-administration, were analysed for platelet counts. For both panels, data shown are mean values (<i>n</i> = 5); the vertical bars represent standard deviation, SD.</p

Evaluation of protective efficacy of <i>Cipa</i> extract <i>in vivo</i>.

<p>AG129 mice (9–12 weeks old) were injected i.p. with 10⁶ PFU brain-passaged DENV-2. Infected mice were treated orally with 0.25% methyl cellulose (solid red squares) or <i>Cipa</i> extract at 125 mg (empty blue circles) and 250 mg/kg body weight (solid blue circles). Treatment was twice daily for the first 5 days. A sham control group that was not virus-infected, but which received the higher dose of <i>Cipa</i> extract orally (solid green squares), was tested in parallel. The mice were monitored daily for mortality and the resultant data plotted as Kaplan-Meier survival curves. The <i>p</i> values to assess the statistical significance in the survival rates on day 35 between the <i>Cipa</i> extract-treated and placebo-treated (0.25% methyl cellulose) groups were determined using the Log-rank test.</p

Schematic representation of the antiviral screening assays.

<p>An outline of the three types of screening assays (indicated by Arabic numbers 1, 2 and 3) is shown. The multi-coloured sphere represents DENV and the Eppendorf tube with green liquid represents the herbal extract. These two were pre-incubated (1) before addition to the monolayer or added sequentially (2, 3) to the monolayer. In assays 1 and 2, the treated-monolayers were overlaid with methyl cellulose-containing growth medium. Shown at the bottom are the possible outcomes of the type 1 and 2 assays. The ‘x’ mark denotes failure of entry into cells. In assay 3, liquid growth medium was added instead of the methyl cellulose overlay, and followed by analysis of NS1 and virus released into the culture supernatant.</p