Colistin in the 21st century

Colistin in the 21st century

Curr Opin Infect Dis. 2009 Sep 30

Nation RL, Li J.

Facility for Anti-infective Drug Development and Innovation, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.

PURPOSE OF REVIEW: Colistin is a 50-year-old antibiotic that is being used increasingly as a 'last-line' therapy to treat infections caused by multidrug-resistant Gram-negative bacteria, when essentially no other options are available. Despite its age, or because of its age, there has been a dearth of knowledge on its pharmacological and microbiological properties. This review focuses on recent studies aimed at optimizing the clinical use of this old antibiotic.

RECENT FINDINGS: A number of factors, including the diversity in the pharmaceutical products available, have hindered the optimal use of colistin. Recent advances in understanding of the pharmacokinetics and pharmacodynamics of colistin, and the emerging knowledge on the relationship between the pharmacokinetics and pharmacodynamics, provide a solid base for optimization of dosage regimens. The potential for nephrotoxicity has been a lingering concern, but recent studies provide useful new information on the incidence, severity and reversibility of this adverse effect. Recent approaches to the use of other antibiotics in combination with colistin hold promise for increased antibacterial efficacy with less potential for emergence of resistance.

SUMMARY:Because few, if any, new antibiotics with activity against multidrug-resistant Gram-negative bacteria will be available within the next several years, it is essential that colistin is used in ways that maximize its antibacterial efficacy and minimize toxicity and development of resistance. Recent developments have improved use of colistin in the 21st century.

Infectious Diseases

Retapamulin: a review of its use in the management of impetigo and other uncomplicated superficial skin infections.

Retapamulin: a review of its use in the management

of impetigo

and other uncomplicated superficial skin infections

Drug Ther Bull. 2008 Oct

Last year, we concluded that topical fusidic acid should be first-line treatment for impetigo. Since then, retapamulin ointment (Altargo - GlaxoSmithKline), a new antibacterial, has been licensed in the European Union as a short-term treatment for impetigo and infected small lacerations, abrasions or sutured wounds in people aged 9 months or above. Advertisements claim that the product "treats localised impetigo in just 5 days"; by comparison, the British National Formulary (BNF) advises a 7-day course of fusidic acid. Here we consider the place of retapamulin in impetigo and its other licensed indications.

PubMed/BMJ

Antibacterial activity and cytotoxicity of PEGylated poly(amidoamine) dendrimers

Antibacterial activity and cytotoxicity of PEGylated poly(amidoamine) dendrimers

Mol Biosyst. 2009 Oct;
Lopez AI, Reins RY, McDermott AM, Trautner BW, Cai C.
Department of Chemistry, University of Houston, Houston, TX, USA. cai@uh.edu.

We have investigated the antibacterial activity and cytotoxicity of a series of amino-terminated poly(amidoamine) (PAMAM) dendrimers modified with poly(ethylene glycol) (PEG) groups. The antibacterial activity of the PAMAM dendrimers and their derivatives against the common ocular pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, was evaluated by their minimum inhibitory concentrations (MICs). For the unmodified third and fifth generation (G3 and G5) amino-terminated dendrimers, the MICs against both P. aeruginosa and S. aureus were in the range of 6.3-12.5 mug mL(-1), comparable to that of the antimicrobial peptide LL-37 (1.3-12.5 mug mL(-1)) and within the wide range of 0.047-128 mug mL(-1) for the fluoroquinolone antibiotics. PEGylation of the dendrimers decreased their antibacterial activities, especially for the Gram-positive bacteria (S. aureus). The reduction in potency is likely due to the decrease in the number of protonated amino groups and shielding of the positive charges by the PEG chains, thus decreasing the electrostatic interactions of the dendrimers with the negatively-charged bacterial surface. Interestingly, localization of a greater number of amino groups on G5 vs. G3 dendrimers did not improve the potency. Significantly, even a low degree of PEGylation, e.g. 6% with EG(11) on G3 dendrimer, greatly reduced the cytotoxicity towards human corneal epithelial cells while maintaining a high potency against P. aeruginosa. The cytotoxicity of the PEGylated dendrimers to host cells is much lower than that reported for antimicrobial peptides. Furthermore, the MICs of these dendrimers against P. aeruginosa are more than two orders of magnitude lower than other antimicrobial polymers reported to date. These results motivate further exploration of the potential of cationic dendrimers as a new class of antimicrobial agents that may be less likely to induce bacterial resistance than standard antibiotics.

PubMed

Goniothalamus species: a source of drugs for the treatment of cancers and bacterial infections?

Goniothalamus species: a source of drugs for the treatment of cancers and bacterial infections?
Evid Based Complement Alternat Med. 2007 Sep

Wiart C.
School of Pharmacy, The University of Nottingham (Malaysia Campus), Jalan Broga, 43500 Semenyih, Selangor, Malaysia.

Keywords: acetogenins, antibacterial, antifungal, apoptosis, cytotoxic, foodborn bacteria, Goniothalamus, Goniothalamus scortechinii, nosocomial, styryl-lactones.

Irrespective of the presence of cytotoxic acetogenins and styryl-lactones in the genus Goniothalamus, only 22 species in the genus Goniothalamus, out of 160 species (13.7%) have so far been investigated. In an effort to promote further research on the genus Goniothalamus which could represent a source of drugs for the treatment of cancers and bacterial infections, this work offers a broad analysis of current knowledge on Goniothalamus species. Therefore, it includes (i) taxonomy (ii) botanical description (iii) traditional medicinal uses and (iv) phytochemical and pharmacological studies. We discuss the molecular mechanisms of actions of acetogenins and styryl-lactones, with some emphasis on the possible involvement of protein kinase, Bax and TRAIL receptors in the cytotoxic effects of styryl-lactones. We also report (v) the growth inhibition of several nosocomial bacteria by Goniothalamus. scortechinii. The crude methanol extract of G. scortechinii showed a good and broad spectrum of antibacterial activity against both Gram-negative and Gram-positive bacteria.

Full Text Article

Evidence-based Complementary and Alternative Medicine