γδ T lymphocytes contribute to immune defense against infection through the production of cytokines, chemokines, anti-bacterial compounds, and killing of infected cells. The major subpopulation of human peripheral blood γδ T cells expresses a Vγ9Vδ2 T cell receptor. Vγ9Vδ2 T cells recognize at picomolar concentrations pyrophosphate molecules generated by bacteria and parasites through the 2-C-methyl-D-erythritol 4-phosphate (also termed 1-deoxy-Dxylulose 5-phosphate) pathway. Pyrophosphates including isopentenyl pyrophosphate (IPP) generated in mammalian cells through the alternative mevalonate pathway also activate Vγ9Vδ2 T cells, but require 1,000- to 10,000-fold higher concentrations. Synthetic compounds have been patented which efficiently activate Vγ9Vδ2 T cells in vitro and in vivo. In addition, the mevalonate pathway of IPP synthesis in mammalian cells can be manipulated by aminobisphosphonates and alkylamines, giving rise to the development of additional strategies for the therapeutic activation of anti-infective γδ T cells. The recent developments in the discovery of new and selective γδ T cell-activating compounds open new avenues for cell-based therapies of infectious diseases.
First isolated in the 1960s methicillin-resistant Staphylococcus aureus (MRSA) has become a leading hospital acquired (HA) pathogen, although community acquired isolates (CA-MRSA) are on the rise, particularly in the USA. Treatment of serious MRSA infections has been based for many years upon the use of glycopeptides, i.e. vancomycin and teicoplanin. Other drugs indicated in particular clinical settings, such as prosthetic valve endocarditis or osteomyelitis, are rifampin, gentamycin, fusidic acid, minocycline, co-trimoxazole, clindamycin. Quinolones and doxycycline may be active on some MRSA isolates, and add some this important clinical setting. In the last few years new anti-MRSA drugs have been registered and patented, expanding therapeutic opportunities, i.e. linezolid, the first oxazolidinone, available both as oral and parenteral formulation in being the most widely used new anti-MRSA agent, quinupristin-dalfopristin, daptomycin, a novel lipopeptide, active on germs both in the replicating and in the resting phase, and tigecycline, the first approved glycylcycline. Other drugs from different classes are in the pipeline and will further enhance in the next few years our therapeutic armamentarium: three glycopeptides, i.e. dalbavancin, telavancin, and oritavancin, two broad spectrum cephalosporins, ceftobiprole and ceftaroline, iclaprim, a diaminopyrimidine, as well as a carbapenem, CS- 023/RO-4908463, and adjuvant therapies such as the monoclonal antibody tefibazumab.
Tuberculosis (TB) is a highly infectious disease caused by several species of mycobacteria. Multi drug resistant strains of mycobacteria leading to the increase of patient world wide. There is an urgent need for new effective antimicrobial agent to replace those currently in use because of highly toxic. Screening methods available for discovering new chemical entities active against the resistant strains are detailed. The plant origin antimicrobial agents are the valuable anti tubercular drugs. The present review of patent stated several findings from an extensive literature search of semi synthetic, synthetic and natural plants that have been assessed for the antimicrobial activity over 20 years. An attempt has been made to summarize the information in order to highlight those chemical entities and plant species which are of worthy for further investigation as leads to the drug developments. Over 150 chemical entities of semi synthetic and synthetic and over 350 plant species from wide range of families containing various chemical classes of compounds have been cited here which are worthy for the researchers and the industrialist concerned to tuberculosis. The present review includes some patents relevant to the treatment of tuberculosis.
As our aged population increases, infections among elderly residing in long term care facilities will challenge our ability to maintain an effective battery of antibiotics. In this setting, we can predict infection by antibiotic resistant organisms in elderly patients with a history of previous antibiotic treatment and exposure to resistant organisms from multiple hospitalizations. The elderly often acquire infections in tandem with common disease states such as diabetes and heart disease. Polypharmacy increases risk of synergistic and antagonist reactions between pharmaceuticals. Elderly patients may be deficient in their ability to clear drugs from the body due to declining lung, kidney/bladder, gastrointestinal and circulatory efficiency. Accumulation of standard antibiotic doses in the body leads to heightened risk of achieving toxic drug levels and increases the chances of unfavorable interactions with other medications. Optimized dosing strategies must be designed specifically for this population using pharmacodynamic principles that honor the unique circumstances of the elderly. Rational and effective dosing strategies based on pharmacodynamic breakpoints and detailed understanding of the pharmacokinetics of antibiotics in the elderly further the goal of achieving complete eradication of an infection in a timely manner, prevent selection of drug resistant bacteria and minimize toxic effects in elderly patients. The present article includes information of patents for antibiotic therapy in the elderly
This article reviews the current literature about the use of intraocular drugs for treatment of bacterial, fungal, viral and protozoal intraocular infection. This route of administration has the advantage of delivering antimicrobials directly into the eye achieving a high therapeutic concentration above the MIC90 of most pathogens and with minimal systemic side effects. It is usually well tolerated but carries a small risk of intraocular complications. Intraocular therapy is now the main therapeutic approach for treatment of bacterial endophthalmitis and has an important adjunctive role in the management of endogenous fungal endophthalmitis and viral retinitis. Intravitreal clindamycin therapy offers a recent additional strategy to treat ocular toxoplasmosis in patients who are intolerant or resistant to systemic treatment. Current researches is now focusing on new patents as well as on the use of intraocular lenses that incorporate antibiotics during cataract surgery and thus provide a sustained high antibiotic levels in the eye in the immediate postoperative period, not depending on patients compliance.
Chronic hepatitis B in children is mainly asymptomatic, but they are at life long risk for severe complications. Treatment is considered to suppress the virus and to prolong the survival by preventing the progression to cirrhosis and HCC. Therapeutic options for children are interferon-alpha (IFN-α) with antiviral, antiproliferative and immunomodulatory effects and lamivudine (LAM) which inhibits HBV replication and increases cellular immune response. IFN- α, 5 MU/m2, thrice weekly for 6 months is used in patients with high ALT levels which is associated with virologic response rate of 30-40%. Predictors of response are high ALT levels, low HBVDNA levels and high histological activity index. The response is sustained in 85%-90% of responders. Adverse events include flu-like syndrome, bone marrow suppression, hair loss, and psychiatric side effects, induction of autoimmunity and temporarily supression of weight gain and growth velocity. LAM, a nucleoside anolog, leads to a virologic response rate of 20-30% when used for 12 months. High ALT levels, low HBVDNA levels and high histological activity index predict better response. Maintenance of HBeAg seroconversion is 56-80%. Longer courses of treatment with LAM increases the seroconversion rate but with high mutation rate and viral resistance. Except for causing mutations, LAM doesn ’ t have serious adverse events. Different timing and durations of combination treatment with IFN and LAM were also evaluated without any significant superiority over monotherapy. In conclusion, the best approach for treatment of chronic HBV infection in children hasnt been determined yet. Future developments concerning new drugs and different treatment strategies are needed.