Recent Patents on Anti-Infective Drug Discovery (v.10, #2)

Meet Our Editorial Board Member by Leonard Amaral (69-69).

Meet Our Associate Editor by Atli Thorarensen (70-70).

A Novel Advanced Laboratory Diagnosis to Guide Tuberculosis Drug Therapy. by Leonard Amaral, Dick van Soolingen (71-73).

Anti-Viral Agents in Neurodegenerative Disorders: New Paradigm for Targeting Alzheimer's Disease by Khushboo G. Faldu, Jigna S. Shah, Snehal S. Patel (76-83).
Alzheimer's disease (AD) is a neurodegenerative disease affecting geriatric populations for which several causes have been proposed. These include a relationship with known pathogens although the exact nature of such a relationship remains uncertain. Herpes simplex virus-1 has been proposed as potential cause of AD because of its ability to form ß amyloid(Aß) and neurofibrillary tangles due to tau hyperphosphorylation and action of beta & gamma secretase on amyloid precursor protein(APP) together with genetic association with apolipoprotein-E4(ApoE-?4), which points out to latent Herpes Simplex virus-1 as an agent causing AD. There are numerous studies that linked HSV-1 with AD like anti-HSV-1 IgM antibodies, nectin-2, heme oxygenase-1, phosphorylated eukaryotic initiation factor-2A, caspase-8 and nucleus-specific alteration of raphe neurons. Various possible mechanisms by which HSV-1 might lead to development of AD such as ApoE, ß-amyloid, tau phosphorylation, inflammation and oxidative stress are also discussed. Thus, this review discusses patent information and a strong relationship between latent HSV-1 and AD and also proposes antiviral therapy for AD.

Most of the defensive functions of the human skin are localized to the stratum corneum (SC), the outermost layer of the epidermis consisting of several layers of cornified keratinocytes embedded in a lipid matrix. Included in the armamentarium of the epidermal barrier against microbial invasion are surface pH, SC lipids, specialized antimicrobial peptides such as defensins and cathelicidins, enzymes and enzyme inhibitors, chemokines, and epidermal Toll-like receptors. Multiple epidermal defensive mechanisms are co-localized, coregulated, and intertwined. The purpose of this review is to discuss patents and to describe the current knowledge that concerns the role of the epidermis as an antimicrobial barrier, outlining potential clinical and therapeutic implications.

In vitro Antimicrobial Study for Biological Evaluation of Clerodendrum infortunatum Linn by Talukdar M. Waliullah, Akter M. Yeasmin, Ashraful Alam, Wahedul Islam, Parvez Hassan (98-104).
Objective: To explore a scientific idea, this study was examined for evaluation of antimicrobial potency using root, leaf and stem of ethyl acetate and chloroform extracts of C. infortunatum (Verbenaceae) due to randomly use in traditional medicine to cure common ailments such as intestinal disorder, diarrhea, tuberculosis and respiratory problems etc. Methods: The in vitro application was carried out by using disc diffusion, micro broth dilution and serial dilution techniques against clinically important life threatening organisms. Results: All the extracts showed significant inhibitory activity over the bacteria and fungus comparable to the standard drug tetracycline and fluconazole. The maximum average diameter zone of inhibition was recorded to bacterial strains against B. megaterium, S. typhi, K. pneumoniae and to fungi against A. niger and C. albicans. The MIC values of ethyl acetate and chloroform root extract were determined 64µg/ml to B. subtilis, and K. pneumoniae to S.-β-haemolyticus and S. typhi for ethyl acetate extracts, 128µg/ml to S. aureus, and E. coli for both ethyl acetate and chloroform root extracts but only S. typhi and S.-β-haemolyticus for chloroform extrtact. Conclusion: The findings evidently appear promising antibacterial and antifungal properties of C. infortunatum against antagonistic pathogens. Leaf possess quite potent activity than root and stem specially root extract > leaf extract > stem extract. One of the more significant achievements of this study to follows and covers the most recent and important patents WO2009075290 (2009) which deals on yeast having immunopotentiating effect and food or feed. This study serves as basis for further research to lead compounds to be isolated so that may be as a template for the implications of these results for bioactivity and drug discovery potential of herbal products are discussed.

Antiseptic Resistance in Methicillin Sensitive and Methicillin Resistant Staphylococcus aureus Isolates from Some Major Hospitals, Iran by Azar Hasanvand, Sobhan Ghafourian, Morovat Taherikalani, Farid A. Jalilian, Nourkhoda Sadeghifard, Iraj Pakzad (105-112).
Background: Extensive use of antibiotics and biocide in treatment of patients and cleaning of surfaces and medical equipment has led to the emergence of resistant microorganisms. The current research goals to determine the antiseptics Minimum Inhibitory Concentration value in Staphylococcus aureus (methicillin -resistant Staphylococcus aureus and methicillin sensitive Staphylococcus aureus) isolates from some major hospitals in Iran and to detect qacA/B, norA , smr and blaZ genes. Methods: Two hundred isolates of S. aureus including 100 MRSA and 100 MSSA clinical isolates were collected from 4 hospitals in the west of Iran during period 2012 to 2013. Detection of disinfectant resistant genes (qac A/B, smr and norA), antimicrobial resistance genes (mecA and blaZ) and SCCmec typing of MRSA isolates was performed by PCR. Results: MIC of chlorhexidine digluconate (CHX) in 70% of MRSA and 30% of MSSA strains was 8-16 µg/ml. High level of MIC of citrimide (>2 µg/ml) in MRSA and MSSA isolates was 20% and 5% ,respectively. MIC of benzalkonium chloride (BC) in 80% of MRSA and 83% of MSSA isolates was less than 2µg/ml; only 9% of MRSA had MIC higher than 2µg/ml. Frequency of antiseptic and antibiotic resistance genes norA, blaZ and qacA/B in MRSA isolates were 83%, 98% and 9%, respectively; while this value for MSSA isolates were 62%, 8% and 0%, respectively. The smr gene was not detected in both MRSA and MSSA isolates. In all biocides high MIC were observed in SCCmec type III and IVc. High frequency of qacA/B gene was found in SCCmec type III,Vc and IVb, which were 66.6% ,22% and 11.1% respectively. Conclusion: We found SCCmec types III, Vc was related to high MIC of biocide in MRSA isolates.

Chronic kidney disease, (CKD) a gradual and inevitable deterioration in renal function, is the disease with the most associations in dentistry. Dosage adjustment is one amongst the vital elements to be familiar with during their oral care. CKD patients take extended duration to filter out medications, therefore dosage must always be tailored under the supervision of nephrologist. The relished benefits from antibiotic could transform as anti-microbial resistance on their abuse and nephrotoxic when contraindicated drugs are encouraged. New patented drug belonging to oxazoliodine group has driven the researchers to handle the emerging AMR. The present communication discusses the pharmacological factors influencing in prescribing the antibiotics for CKD patient from the dentist's point of view. The formulas destined for calculating the optimal dosage of antibiotics have been documented to aid oral physicians.

The colonization and infection with methicillin-resistant Staphylococcus aureus is a major health problem in hospitals and long-term care facilities. Although bacteriaemias with MRSA (methicillin-resistant Staphylococcus aureus) can be treated with vancomycin and other reserve antibiotics, 20% of patients cannot be successfully cured. Inpatients colonized with MRSA are isolated in hospitals according to the guidelines of the Robert-Koch-Institute, although in long-term care facilities these patients are not urgently isolated. Active decolonization measures are taken to eradicate colonization with MRSA. In order to reduce MRSA colonization, it could be possible to administer cultures of Staphylococcus epidermidis which have no antibiotic resistance, so that physiological genes could be conferred from Staphylococcus epidermidis to MRSA bacteria.

Antibiotic Susceptibility Patterns of Extended Spectrum beta-lactamase and non Extended Spectrum beta-lactamase Pseudomonas aeruginosa Clinical Isolates by Mostafa Akbariqomi, Sobhan Ghafourian, Morovat Taherikalani, Satar Mohammadi, Iraj Pakzad, Nourkhoda Sadeghifard (128-133).
Background: Pseudomonas aeruginosa is known as an opportunistic pathogen responsible for nosocomial infections. Multidrug (MDR) resistance bacteria are considered as a worldwide issue. The current research goal to investigate the antibiotic susceptibility pattern in Extended Spectrum beta-lactamase and non Extended Spectrum beta-lactamase producing P. aeruginosa clinical isolates. Methods: A total of 76 P.aeruginosa clinical isolates were collected from Milad hospital in Tehran, Iran, during 8 months period in 2012. P.aeruginosa clinical isolates were subjected for ESBL production by phenotypic methods. The antibiotic susceptibility patterns were identified in ESBL and non-ESBL P. aeruginosa by MIC. Results: our results demonstrated that 76.3% (n =58) isolates were resistant to more than three antibiotics and classified as MDR. The majority of MDR strains were found in ESBL producer P. aeruginosa. ceftazidim as 3rd generation of cephalosporins, ciprofloxacin, Ticarcillin and aztreonam were found as a base for definition of MDR in the current research. The effectiveness antibiotics against ESBL and non-ESBL were meropenem and amikacin, respectively. Conclusion: based on our knowledge obtained from results, both ESBL and non-ESBL P. aeruginosa were resistant to extended antibiotics and this is a major health care problem. On the other hand, MDR strains more identified in ESBL producer P .a eruginosa. Also, carabapenem resistance observed in non-ESBL producer strains. Hence, it is recommended that the MDR strains should be following up. the prescription of ceftazidim, ciprofloxacin, Ticarcillin and aztreonam should be limited.

Chloroquine: An Old Drug with New Perspective Against Giardiasis by Angel A. Escobedo, Pedro Almirall, Sérgio Cimerman, Marco Lalle, Frank Pacheco, Carlos Z. Acanda, Niurka Sánchez (134-141).
The occurrence of treatment failures to first-line treatment for giardiasis, one of the most widespread although neglected parasitic disease, has long been recognised. Nowadays, it starts to represent a great challenge to clinicians, especially in endemic countries. This requires the introduction of new drug interventions, but the development of novel drugs is a time and money consuming effort with most of the compounds never reaching the market. Consequently, alternative strategies are needed, especially for the treatment of giardiasis. Chloroquine (CQ), a synthetic drug developed as antimalarial agent, has been shown to also exert antigiardial activity. Here, we present a mini-research summarizing results on the treatment of human clinical cases with CQ, going through in vitro research, case report, and case series to human clinical trials, highlighting the benefits and mentioning possible adverse effects.

Patent Selections (142-145).