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Targeting Hepatitis B Virus and Human Papillomavirus Induced Carcinogenesis: Novel Patented Therapeutics
Rupinder K. Kanwar, Neha Singh, Sneha Gurudevan and Jagat R. Kanwar
[Abstract] [FULL-TEXT INQUIRY] [PMID: 21517743 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00001]


Targeting the Human Macrophage with Combinations of Drugs and Inhibitors of Ca²⁺ and K⁺ Transport to Enhance the Killing of Intracellular Multi-Drug Resistant M. tuberculosis (MDR-TB) - a Novel, Patentable Approach to Limit the Emergence of XDR-TB
Marta Martins
[Abstract] [FULL-TEXT INQUIRY] [PMID: 21517742 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00002]


New Patentable Use of an Old Neuroleptic Compound Thioridazine to Combat Tuberculosis: A Gene Regulation Perspective
Noton K. Dutta, Kaushiki Mazumdar, Sujata G. Dastidar, Petros C. Karakousis, and Leonard Amaral
[Abstract] [FULL-TEXT INQUIRY] [PMID: 21517741 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00003]


The Broad-spectrum Antimycobacterial Activities of Phenothiazines, InVitro: Somewhere in All of this there May be Patentable Potentials
Jakko van Ingen
[Abstract] [FULL-TEXT INQUIRY] [PMID: 21517740 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00004]


Inhibition of Drug Efflux in Mycobacteria with Phenothiazines and OtherPutative Efflux Inhibitors
Liliana Rodrigues, José A. Aínsa, Leonard Amaral, and Miguel Viveiros
[Abstract] [FULL-TEXT INQUIRY] [PMID: 21517739 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00005]


Direct Modification of Bioactive Phenothiazines by Exposure to Laser Radiation
Mihail-Lucian Pascu, Viorel Nastasa, Adriana Smarandache, Andra Militaru, Ana Martins, Miguel Viveiros, Mihai Boni, Ionut Relu Andrei, Alexandru Pascu, Angela Staicu, Joseph Molnar, Seamus Fanning and Leonard Amaral
[Abstract] [FULL-TEXT INQUIRY] [BSP/PRI/E-Pub/00006]


Commercial Development and Application of Type A Lantibiotics
Shawanda Wilson-Stanford and Leif Smith
[Abstract] [FULL-TEXT INQUIRY] [PMID: 21517737 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00007]


Global Clinical trials for the Treatment of TB with Thioridazine
Martin J. Boeree
[Abstract] [FULL-TEXT INQUIRY] [PMID: 21548879 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00008]


Latent Tuberculosis: Is There a Role for Thioridazine?
Charles Sohaskey
[Abstract] [FULL-TEXT INQUIRY] [PMID: 21548878 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00009]


Thioridazine: The Good and the Bad
H K Ruben Thanacoody
[Abstract] [FULL-TEXT INQUIRY] [PMID: 21548877 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00010]


Effective Therapy with the Neuroleptic Thioridazine as an Adjunct to Second Line of Defence Drugs, and the Potential that Thioridazine Offers for New Patents that Cover a Variety of “New Uses”
Leonard Amaral, Miguel Viveiros, Joseph Molnar, and Jette E Kristiansen
[Abstract] [FULL-TEXT INQUIRY] [PMID: 21548876 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00011]


The Role of Micafungin and Anidulafungin in the Treatment of Systemic Fungal Infections: Applications and Patents for Two Novel Echinocandins
Ludwig Christian G. Hinske, Florian Weis, Jens Heyn, Patricia Hinske and Andres Beiras-Fernandez
[Abstract] [FULL-TEXT INQUIRY] [BSP/PRI/E-Pub/00012]


Antimicrobial Activity of Carvacrol: Current Progress and Future Prospectives
Antonia Nostro and Teresa Papalia
[Abstract] [FULL-TEXT INQUIRY] [BSP/PRI/E-Pub/00013]


Current and Emerging Antivirals for the Treatment of Cytomegalovirus (CMV) Retinitis: an Update on Recent Patents
Aswani D. Vadlapudi, Ramya K. Vadlapatla and Ashim K. Mitra
[Abstract] [FULL-TEXT INQUIRY] [BSP/PRI/E-Pub/00014]


Insights into Airway Infections by Enterococci: A Review
Vincenzo Savini, Giovanni Gherardi, Chiara Catavitello, Daniela Astolfi, Ennio Polilli, Giordano Dicuonzo, Claudio D’Amario, Paolo Fazii and Domenico D’Antonio
[Abstract] [FULL-TEXT INQUIRY] [BSP/PRI/E-Pub/00015]


Carbapenem-Hydrolyzing Gram-Negative Bacteria: Current Options for Treatment and Review of Drugs in Development
Foad I. Abandeh, Mark E. Drew and Madhuri M. Sopirala
[Abstract] [FULL-TEXT INQUIRY] [BSP/PRI/E-Pub/00016]



Abstracts

Targeting Hepatitis B Virus and Human Papillomavirus Induced Carcinogenesis: Novel Patented Therapeutics
Rupinder K. Kanwar, Neha Singh, Sneha Gurudevan and Jagat R. Kanwar
[FULL-TEXT INQUIRY] [PMID: 21517743 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00001]

Viral infections leading to carcinogenesis tops the risk factors list for the development of human cancer. The decades of research has provided ample scientific evidence that directly links 10-15% of the worldwide incidence of human cancers to the infections with seven human viruses. Moreover, the insights gained into the molecular pathogenetic and immune mechanisms of hepatitis B virus (HBV) and human papillomavirus (HPV) viral transmission to tumour progression, and the identification of their viral surface antigens as well as oncoproteins have provided the scientific community with opportunities to target these virus infections through the development of prophylactic vaccines and antiviral therapeutics. The preventive vaccination programmes targeting HBV and high risk HPV infections, linked to hepatocellular carcinoma (HCC) and cervical cancer respectively have been recently reported to alter age-old cancer patterns on an international scale. In this review, with an emphasis on HBV and HPV mediated carcinogenesis because of the similarities and differences in their global incidence patterns, viral transmission, mortality, molecular pathogenesis and prevention, we focus on the development of recently identified HBV and HPV targeting innovative strategies resulting in several patents and patent applications.
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Targeting the Human Macrophage with Combinations of Drugs and Inhibitors of Ca²⁺ and K⁺ Transport to Enhance the Killing of Intracellular Multi-Drug Resistant M. tuberculosis (MDR-TB) - a Novel, Patentable Approach to Limit the Emergence of XDR-TB
Marta Martins
[FULL-TEXT INQUIRY] [PMID: 21517742 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00002]

The emergence of resistance in Tuberculosis has become a serious problem for the control of this disease. For that reason, new therapeutic strategies that can be implemented in the clinical setting are urgently needed. The design of new compounds active against mycobacteria must take into account that Tuberculosis is mainly an intracellular infection of the alveolar macrophage and therefore must maintain activity within the host cells. An alternative therapeutic approach will be described in this review, focusing on the activation of the phagocytic cell and the subsequent killing of the internalized bacteria. This approach explores the combined use of antibiotics and phenothiazines, or Ca2+ and K+ flux inhibitors, in the infected macrophage. Targeting the infected macrophage and not the internalized bacteria could overcome the problem of bacterial multi-drug resistance. This will potentially eliminate the appearance of new multi-drug resistant tuberculosis (MDR-TB) cases and subsequently prevent the emergence of extensively-drug resistant tuberculosis (XDR-TB). Patents resulting from this novel and innovative approach could be extremely valuable if they can be implemented in the clinical setting. Other patents will also be discussed such as the treatment of TB using immunomodulator compounds (for example: betaglycans).
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New Patentable Use of an Old Neuroleptic Compound Thioridazine to Combat Tuberculosis: A Gene Regulation Perspective
Noton K. Dutta, Kaushiki Mazumdar, Sujata G. Dastidar, Petros C. Karakousis, and Leonard Amaral
[FULL-TEXT INQUIRY] [PMID: 21517741 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00003]

Use of the old antipsychotic phenothiazine thioridazine (THZ) for therapy of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) infection is now being seriously considered. It is reported that THZ primarily acts on enzymes involved in fatty acid metabolism and membrane proteins, particularly efflux pumps, as well as oxidoreductases and proteins involved in aerobic respiration that overlap with a number of conventional antituberculous drugs. It targets the products of the Rv3160c-Rv3161c operon, which are perhaps required for the detoxification of THZ, members of the sigma factor SigB regulon that play a crucial role in protecting the pathogen against cell envelope damage, and Rv2745c, a transcription factor that regulates ATP-dependent proteolysis. Some of these genes have been shown to be essential for the survival or persistence of Mycobacterium tuberculosis in the infected host. Since THZ targets multiple pathways, including those involved in cell wall processes and respiratory chain components, it may serve as a model for multi-target drug development, as well as constitute a highly potent addition to a combination of antituberculous drug regimens. The discussion of some of the patents relevant to thioridazine to combat tuberculosis is also included in the present manuscript.
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The Broad-spectrum Antimycobacterial Activities of Phenothiazines, InVitro: Somewhere in All of this there May be Patentable Potentials
Jakko van Ingen
[FULL-TEXT INQUIRY] [PMID: 21517740 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00004]

The phenothiazines are neuroleptic drugs that have long been known to have antimycobacterial activity, in vitro. Of the various commercially available phenothiazines, thioridazine, chlorpromazine and trifluoperazine are mostactive against mycobacteria, in vitro. Their MICs for Mycobacterium tuberculosis are in the 8-16 g/ml range and MICsfor Mycobacterium avium in the 10-32 g/ml range, depending on methods and media. These concentrations cannot besafely attained in humans, where maximum serum concentrations are 0.5 g/ml (thioridazine) to 1  g/ml (chlorpromazine)or 4 g/ml (trifluoperazine). Phenothiazines still have potential as antimycobacterial drugs because they accumulate inmacrophages; concentrations inside macrophages are at least 10 fold higher than in serum. When applied to mycobacteriainside macrophages, concentrations as low as 0.1 g/ml (thioridazine) or 0.1-3.6 g/ml (chlorpromazine) kill phagocytized M. tuberculosis and M. avium in 3-7 days. Owing to their multiple and novel drug targets, phenothiazine resistance hasnot been observed. The drug targets and less toxic phenothiazine derivatives (patents include WO2005105145A andWO2010122012A) provide excellent patentable potentials. Thioridazine itself may be patented as “new use”. New drugsfor treatment of mycobacterial disease, most notable multidrug- and extensively drug-resistant tuberculosis, are urgentlyneeded; phenothiazines and their targets should be exploited for this use.
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Inhibition of Drug Efflux in Mycobacteria with Phenothiazines and OtherPutative Efflux Inhibitors
Liliana Rodrigues, José A. Aínsa, Leonard Amaral, and Miguel Viveiros
[FULL-TEXT INQUIRY] [PMID: 21517739 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00005]

Mycobacteria are responsible for some of the oldest diseases known to Man, usually associated with high morbility and mortality rates. An example is tuberculosis (TB), a major public health problem that accounts for eight million new cases each year. Furthermore, the increase of multidrug and extremely-drug resistance seriously threatens the success of the TB control programmes. Resistance to anti-mycobacterial drugs is often due to spontaneous mutations in target genes, followed by selection of resistant mutants during treatment. However, this does not explain all cases of drug resistance and other mechanism(s) may be involved, namely efflux pumps that extrude the drug to the exterior of the cell.

Efflux pumps are becoming attractive drug targets for the development of new anti-mycobacterial compounds and several efflux inhibitors have been developed and published in patent applications (i.e., WO2004062674, US2004204378, US2003118541, WO2008141012, WO2009110002, WO2010054102). However, none of these inhibitors is used in clinical practice. This review will focus on the potential use of efflux inhibitors as adjuvants of the anti-mycobacterial therapy, an approach that may restore the activity of antibiotics that are subject to efflux and render the mycobacteria more susceptible to drugs transported by these pumps.
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Direct Modification of Bioactive Phenothiazines by Exposure to Laser Radiation
Mihail-Lucian Pascu, Viorel Nastasa, Adriana Smarandache, Andra Militaru, Ana Martins, Miguel Viveiros, Mihai Boni, Ionut Relu Andrei, Alexandru Pascu, Angela Staicu, Joseph Molnar, Seamus Fanning and Leonard Amaral
[FULL-TEXT INQUIRY] [BSP/PRI/E-Pub/00006]

Whereas exposure of combinations of a phenothiazine and bacterium to incoherent UV increases the activity of the phenothiazine, exposure of the phenothiazine alone does not yield an increase of its activity. Because the laser beam energy is greater than that produced by the incoherent UV sources, exposure of phenothiazines to specific lasers may yield molecules with altered activities over that of the unexposed parent. Chlorpromazine, thioridazine and promethazine active against bacteria were exposed to two distinct lasers for varying periods of time. Absorption and fluorescence spectra were conducted prior to and post-exposure and the products of laser exposure evaluated for activity against a Staphylococcus aureus ATCC strain via a disk susceptibility assay. Exposure to lasers alters the absorption/fluorescence spectra of the phenothiazines; reduces the activity of thioridazine against the test bacterium; produces a highly active chlorpromazine compound against the test organism. Exposure of phenothiazines to lasers alters their structure that results in altered activity against a bacterium. This is the first report that lasers can alter the physico-chemico characteristics to the extent that altered bioactivity results. Exposure to lasers is expected to yield compounds that are difficult to make via chemical manipulation methods. A survey of selected patents of interest, even co-lateral for the subject of this article is shortly made.
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Commercial Development and Application of Type A Lantibiotics
Shawanda Wilson-Stanford and Leif Smith
[FULL-TEXT INQUIRY] [PMID: 21517737 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00007]

Lantibiotics are an interesting group of antimicrobial peptides. There are a number of reviews that describe the potential application of lantibiotics for controlling foodborne illnesses and their potential to treat Gram positive infections caused by organisms like Staphylococcus aureus. In this review, commercial potential for the producing organism for promoting health and their potential for protein chemistry applications are discussed. Lantibiotics are ribozomally synthesized as a prepropeptide, comprised of a leader sequence that directs the propeptide to the enzymes that perform a number of post-translational modifications. This system affords several possibilities for the synthesis of a library of peptides that may have therapeutic use. We also take a look at a couple of lantibiotic producing organisms that have potential applications in the field of probiotics, given their ability to displace pathogenic microorganisms. The use of lantibiotics and the application along with the discussion of recent patents are discussed in this review article.
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Global Clinical trials for the Treatment of TB with Thioridazine
Martin J. Boeree
[FULL-TEXT INQUIRY] [PMID: 21548879 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00008]

Current evidence shows that thioridazine (THZ) is ready for global clinical evaluation, while some of its derivatives and other efflux pump inhibitors reach the end stage of preclinical evaluation. In this paper, a clinical trial plan is described that investigates the antituberculosis potency, the safety profile and the role of THZ and/or its derivatives in the treatment of TB in humans, both in patients infected with drug sensitive strains as in patients infected with multi or extensive drug resistant strains of Mycobacterium tuberculosis and some of the patents related to thioridazine are also discussed.
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Latent Tuberculosis: Is There a Role for Thioridazine?
Charles Sohaskey
[FULL-TEXT INQUIRY] [PMID: 21548878 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00009]

Approximately 1/3 of the world’s population is infected with Mycobacterium tuberculosis. In the vast majority of cases this results in latent not active disease. Latent disease is defined as a positive reaction to tuberculin antigens but without any further clinical symptoms. Models have been developed to study latent tuberculosis with the two most prominent being the in vivo murine model and the in vitro Wayne model. In both cases M. tuberculosis undergoes a change in its respiratory profile as it shifts down to a nonreplicating state. However in both the mouse and the Wayne model, dormant M. tuberculosis is sensitive to the phenothiazine thioridazine. This antibiotic has several targets, and the main one is respiration. There is a growing burden of multidrug resistant and extensively drug resistant tuberculosis. Treatment of these cases is expensive with high mortality. We propose that thioridazine alone, or with other antibiotics, be used to treat drug resistant latent tuberculosis. The advantages are that thioridazine is inexpensive, effective against drug resistant tuberculosis, well characterized and unlikely to induce drug resistance. The disadvantages include possible side effects, although these should be rare at the doses and length of time of treatment. Recent patents involving analogs of thioridazine suggest this class of drugs may hold great promise for the future treatment of the most drug resistant strains.
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Thioridazine: The Good and the Bad
H K Ruben Thanacoody
[FULL-TEXT INQUIRY] [PMID: 21548877 PubMed - indexed for MEDLINE] [BSP/PRI/E-Pub/00010]

Thioridazine is a phenothiazine drug which has previously been extensively used for its antipsychotic properties as it is associated with a low risk of extra-pyramidal side-effects. There is good evidence to suggest that, in common with other phenothiazine drugs, thioridazine has important anti-microbial activity and is a potential candidate for development as an anti-microbial drug against multi-resistant organisms, including drug-resistant strains of M. tuberculosis. The clinical pharmacology and toxicity profile of thioridazine are reviewed in this article and the implications for future drug development along with the patent are discussed.
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Effective Therapy with the Neuroleptic Thioridazine as an Adjunct to Second Line of Defence Drugs, and the Potential that Thioridazine Offers for New Patents that Cover a Variety of “New Uses”
Leonard Amaral, Miguel Viveiros, Joseph Molnar, and Jette E Kristiansen
[FULL-TEXT INQUIRY] [PMID: 21548876 PubMed - indexed for MEDLINE]
[BSP/PRI/E-Pub/00011]

New and active infections of tuberculosis continue to increase globally. Although antibiotic susceptible infections can be readily cured with isoniazide and rifampicin, infections resistant to these two antibiotics, named Multi-Drug Resistant TB (MDR TB), are problematic for therapy, extol high costs in terms of human suffering and finances, and when these MDR infections progress to Extensive Drug Resistant TB (XDR TB) status, they are not only difficult to treat, they produce high levels of mortality regardless of therapeutic modality employed. The neuroleptic thioridazine (TZ) has been shown to have wide spectrum in vitro and ex vivo activities against antibiotic susceptible, MDR and XDR strains, and has been successfully used for curing mice of active tuberculosis produced by antibiotic susceptible and MDR strains, and has cured 10 out of 12 XDR TB patients when used in combination with three antibiotics to which the XDR TB patients were non-responsive. Mycobacterium tuberculosis TZ has been recommended for “Compassionate Therapy” of MDR/XDR TB infections whose prognoses are significantly serious and anticipated to result in mortality. This review of TZ activity and its potential to cure MDR/XDR TB supports the contention that this neuroleptic offers patenting opportunities for “New Use”. The motivation for patents therefore is expected to rapidly bring TZ to the forefront for therapy of MDR/XDR TB and therefore, the striving for new patents is expected to contribute to the prevention of new infections of antibiotic resistant tuberculosis.
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The Role of Micafungin and Anidulafungin in the Treatment of Systemic Fungal Infections: Applications and Patents for Two Novel Echinocandins
Ludwig Christian G. Hinske, Florian Weis, Jens Heyn, Patricia Hinske and Andres Beiras-Fernandez
[FULL-TEXT INQUIRY] [BSP/PRI/E-Pub/00012]

Fungal infections are becoming an increasing menace in the hospital care setting. Among them, non-albicans Candida species have gained significant attention. Especially in the ICU setting, therapeutic options are limited in many cases by the side-effects of conventional antifungal therapy. Echinocandins are a relatively new class of antifungal agents that promise good effectiveness against Candida and Aspergillus species. Due to their underlying mechanisms of action, they yield good tolerability and few limitations of usage. In the current manuscript we describe the patents of two recently approved echinocandins, micafungin (US approved 2005) and anidulafungin (2006) and provide an overview of the mechanisms, clinical effectiveness and safety of antifungal therapy with these agents.
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Antimicrobial Activity of Carvacrol: Current Progress and Future Prospectives
Antonia Nostro and Teresa Papalia
[FULL-TEXT INQUIRY] [BSP/PRI/E-Pub/00013]

During the last few years the scientific community has shown a considerable interest in the study of plant materials as sources of new compounds to be processed into antimicrobial agents. In this context, carvacrol, a monoterpenic phenol, has emerged for its wide spectrum activity extended to food spoilage or pathogenic fungi, yeast and bacteria as well as human, animal and plant pathogenic microorganisms including drug-resistant and biofilm forming microorganisms. The antibacterial activity of carvacrol has been attributed to its considerable effects on the structural and functional properties of cytoplasmatic membrane. The data reported in this review provide an overview of the published literature regarding the antimicrobial properties of carvacrol and the recent patents claimed in order to highlight its future applications as a new antimicrobial agent. These could concern either the natural preservation in the cosmetic and food industries or an alternative which supports the conventional antimicrobial protocols. Interestingly, carvacrol alone or associated with one or more synergistic products could be incorporated in different formulations for biomedical and food packaging applications. However, more detailed safety investigations and in vivo studies should be carried out so that this molecule could be used in the future.
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Current and Emerging Antivirals for the Treatment of Cytomegalovirus (CMV) Retinitis: an Update on Recent Patents
Aswani D. Vadlapudi, Ramya K. Vadlapatla and Ashim K. Mitra
[FULL-TEXT INQUIRY] [BSP/PRI/E-Pub/00014]

Cytomegalovirus (CMV) retinitis is the most common ocular opportunistic complication and a serious cause of vision loss in immunocompromised patients. Even though, a rise in human immunodeficiency virus (HIV) infected individuals seems to be a major factor responsible for the prevalence of CMV retinitis, the introduction of highly active antiretroviral therapy (HAART) significantly reduced the incidence and severity of CMV retinitis. Thorough evaluation of the patient’s immune status and an exact classification of the retinal lesions may provide better understanding of the disease etiology, which would be necessary for optimizing the treatment conditions. Current drugs such as ganciclovir, valganciclovir, cidofovir and foscarnet have been highly active against CMV, but prolonged therapy with these approved drugs is associated with dose-limiting toxicities thus limiting their utility. Moreover development of drug-resistant mutants has been observed particularly in patients with acquired immunodeficiency syndrome (AIDS). Continuous efforts by researchers in the industry and academia have led to the development of newer candidates with enhanced antiviral efficacy and apparently minimal side effects. These novel compounds can suppress viral replication and prevent reactivation in the target population. Though some of the novel therapeutics possess potent viral inhibitory activity, these compounds are still in stages of clinical development and yet to be approved. This review provides an overview of disease etiology, existing anti-CMV drugs, advances in emerging therapeutics in clinical development and related recent patents for the treatment of CMV retinitis.
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Insights into Airway Infections by Enterococci: A Review
Vincenzo Savini, Giovanni Gherardi, Chiara Catavitello, Daniela Astolfi, Ennio Polilli, Giordano Dicuonzo, Claudio D’Amario, Paolo Fazii and Domenico D’Antonio
[FULL-TEXT INQUIRY] [BSP/PRI/E-Pub/00015]

Enterococcus is an uncommon but emerging agent of upper and lower airway diseases, including sinuses, trachea, bronchi, lung and pleural infections. In particular, pneumonia and thoracic empyema may jeopardize the clinical outcome of compromised, hospitalized hosts, as well as affect outpatients. Treatment may highlight the effects of inherent and acquired resistances such organisms show to commonly used drugs, with the spread of glycopeptide/vancomycin resistant enterococci (GRE/VRE, respectively) being of serious concern. With this work, we want to unearth the impact of members of the genus in the ambit of respiratory infections, aiming to increase the consciousness of their role as resourceful pathogens for human airways. Also, we are revising patents of interest aiming to timely screen GRE and soon provide clinicians with speciation and glycopeptide resistances.
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Carbapenem-Hydrolyzing Gram-Negative Bacteria: Current Options for Treatment and Review of Drugs in Development
Foad I. Abandeh, Mark E. Drew and Madhuri M. Sopirala
[FULL-TEXT INQUIRY] [BSP/PRI/E-Pub/00016]

Multidrug resistant gram-negative bacteria are an increasing therapeutic challenge. The beta-lactamases are a group of enzymes that confer resistance to the beta-lactam antibiotics. The carbapenems have been in wide use to treat beta-lactamase producing, multi-drug resistant gram-negative bacterial infections. However, the emergence of carbapenemases, enzymes capable of hydrolyzing the carbapenems, has limited our therapeutic options. In the recent years, there has been some development in the discovery of new agents such as boronic acid derivatives, ME1071 and Ca-EDTA that may enhance the activity of existing antibiotics, CTC-96 which reverses antibiotic resistance and polymyxin derivatives with decreased renal toxicity. While global efforts towards new drug development should continue, appropriate use of currently available antibiotics is equally important. In this review, we will discuss the general characteristics of carbapenemases, recent patents with drugs under development and current treatment options.
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