Synthesis and structure-activity relationship of a novel class of 15-membered macrolide antibiotics known as '11a-azalides'

August 2012

Sugimoto T, Tanikawa T, Suzuki K, Yamasaki Y.

Source

Medicinal Research Laboratories, Taisho Pharmaceutical Co. Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan.

Abstract

Macrolide antibiotics are widely prescribed for the treatment of respiratory tract infections; however, the increasing prevalence of macrolide-resistant pathogens is a public health concern. Therefore, the development of new macrolide scaffolds with activities against resistant pathogens is urgently needed. An efficient method for reconstructing the erythromycin A macrolactone skeleton has been established. Based on this methodology, novel 15-membered macrolides, known as '11a-azalides', with substituents at the C12, C13, or C4″ positions were synthesized and their antibacterial activities were evaluated. These derivatives showed promising antibacterial activities against erythromycin-resistant Streptococcus pneumoniae. Among them, the C4″ substituted derivatives had the most potent activity against erythromycin-resistant S. pneumoniae.

Science Direct

Antibiotic susceptibility profile of Aeromonas species isolated from wastewater treatment plant.

2012

Igbinosa IH, Okoh AI.

Source

Applied and Environmental Microbiology Research Group (AEMREG), Department of Biochemistry and Microbiology, University of Fort Hare, Private Bag X1314, Alice 5700, South Africa.

Abstract

This study assessed the prevalence of antibiotic-resistant Aeromonas species isolated from Alice and Fort Beaufort wastewater treatment plant in the Eastern Cape Province of South Africa. Antibiotic susceptibility was determined using the disc diffusion method, and polymerase chain reaction (PCR) assay was employed for the detection of antibioticsresistance genes. Variable susceptibilities were observed against ciprofloxacin, chloramphenicol, nalidixic acid, gentamicin, minocycline, among others. Aeromonas isolates from both locations were 100% resistant to penicillin, oxacillin, ampicillin, and vancomycin. Higher phenotypic resistance was observed in isolates from Fort Beaufort compared to isolates from Alice. Class A pse1 β-lactamase was detected in 20.8% of the isolates with a lower detection rate of 8.3% for bla(TEM) gene. Class 1 integron was present in 20.8% of Aeromonas isolates while class 2 integron and TetC gene were not detected in any isolate. The antibiotic resistance phenotypes observed in the isolates and the presence of β-lactamases genes detected in some isolates are of clinical and public health concern as this has consequences for antimicrobial chemotherapy of infections associated with Aeromonas species. This study further supports wastewater as potential reservoirs of antibiotic resistance determinants in the environment.

Scientific World Journal

Residual antibiotics disrupt meat fermentation and increase risk of infection.

August 2012

Kjeldgaard J, Cohn MT, Casey PG, Hill C, Ingmer H.

Source

Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark.

Abstract

ABSTRACT Fermented sausages, although presumed safe for consumption, sometimes cause serious bacterial infections in humans that may be deadly. Not much is known about why and when this is the case. We tested the hypothesis that residual veterinary antibiotics in meat can disrupt the fermentation process, giving pathogenic bacteria a chance to survive and multiply. We found that six commercially available starter cultures were susceptible to commonly used antibiotics, namely, oxytetracycline, penicillin, and erythromycin. In meat, statutorily tolerable levels of oxytetracycline and erythromycin inhibited fermentation performance of three and five of the six starter cultures, respectively. In model sausages, the disruption of meat fermentation enhanced survival of the pathogens Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium compared to successful fermentations. Our work reveals an overlooked risk associated with the presence of veterinary drugs in meat. 

IMPORTANCE Antibiotics have for a long time been used as growth promoters in farm animals, and while they are banned as such in Europe, their clinical use in farm animals still accounts for the majority of consumption. Here, we examined how acceptable levels of antibiotics in meat influence fermentation. Our results show that commonly used bacterial starter cultures are sensitive to residual antibiotics at or near statutorily tolerable levels, and as a result, processed sausages may indeed contain high levels of pathogens. Our findings provide a possible explanation for outbreaks and disease cases associated with consumption of fermented sausages and offer yet another argument for limiting the use of antimicrobials in farm animals.

PubMed

Prompt treatment of acne improves quality of life.

June 2012

Tidman MJ.

Source

Department of Dermatology, Royal Infirmary of Edinburgh, Edinburgh, UK.

Abstract

Acne vulgaris is an inflammatory disorder of the pilosebaceous (hair follicle) units. It may be exacerbated by stress, topical greasy preparations that encourage blockage of the pores, trauma and humid climates. Certain medications may induce or exacerbate acne, including some oral and implanted contraceptives, and anabolic steroids. Occasionally, 'normal' acne can dramatically deteriorate: this may be due to a Gram-negative folliculitis superimposed on acne being treated with long-termantibiotics, or the development of one of the much more severe, destructive and aggressively scarring forms. Disfigurement from inflammation, pigmentation changes and scarring often causes embarrassment, and not infrequently undermines confidence and lowers self-esteem. Acne can also potentially induce much more serious psychological distress. It may take up to four to six months before the full benefit of treatment is apparent. Patients should be referred to a dermatologist if they: have a very severe variant; severe social or psychological problems; are at risk of scarring; have failed to respond to treatment or are suspected of having an underlying endocrinological cause.

PubMed

Newer Approaches to the Treatment of Acne Vulgaris.

Aug 2012

Simonart T.

Source

Private Practice, Brussels, Belgium.

Abstract

The multifactorial etiology of acne vulgaris makes it challenging to treat. Current treatments include topical retinoids, benzoyl peroxide, topical and systemic antibiotics, azelaic acid, and systemic isotretinoin. Adjunctive and/or emerging approaches include topical dapsone, taurine bromamine, resveratrol, chemical peels, optical treatments, as well as complementary and alternative medications. The purpose of this paper is to discuss the therapies available for acne and their latest developments, including new treatment strategies (i.e. re-evaluation of the use of oral antibiotics and avoidance of topical antibiotic monotherapy, use of subantimicrobial antibiotic dosing, use of low-dose isotretinoin, optical treatments), new formulations (microsponges, liposomes, nanoemulsions, aerosol foams), new combinations (fixed-combination products of topical retinoids and topical antibiotics [essentially clindamycin] or benzoyl peroxide), new agents (topical dapsone, taurine bromamine, resveratrol) and their rationale and likely place in treatment. Acne vaccines, topical natural antimicrobial peptides, and lauric acid represent other promising therapies.

PubMed

Different patterns in use of antibiotics for lower urinary tract infection in institutionalized and home-dwelling elderly: a register-based study.

Aug 2012

Haasum Y, Fastbom J, Johnell K.

Source

Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet and Stockholm University, Gävlegatan 16, 113 30, Stockholm, Sweden, Ylva.Haasum@ki.se.

Abstract

PURPOSE:

We compared the quality and pattern of use of antibiotics to treat urinary tract infection (UTI) between institutionalized and home-dwelling elderly.

METHODS:

We analyzed the quality of use of UTI antibiotics in Swedish people aged ≥65 years at 30 September 2008 (1,260,843 home-dwelling and 86,721 institutionalized elderly). Data regarding drug use, age and sex were retrieved from the Swedish Prescribed Drug Register and information about type of housing from the Social Services Register. In women, we assessed: (1) the proportion who use quinolones (should be as low as possible); (2) the proportion treated with the recommended drugs (pivmecillinam, nitrofurantoin, or trimethoprim) (proportions should be about 40 %, 40 % and 15-20 %, respectively); In men, we assessed: (1) the proportion who used quinolones or trimethoprim (should be as high as possible).

RESULTS:

The 1-day point prevalence for antibiotic use for UTI was 1.6 % among institutionalized and 0.9 % among home-dwelling elderly. Of these, about 15 % of institutionalized and 19 % of home-dwelling women used quinolones. The proportion of women treated with the recommended drugs pivmecillinam, nitrofurantoin or trimethoprim was 29 %, 27 % and 45 % in institutions and 40 %, 28 % and 34 % for home-dwellers. In men treated with antibiotics for UTI, quinolones or trimethoprim were used by about 76 % in institutions and 85 % in home-dwellers.

CONCLUSIONS:

Our results indicate that recommendations for UTI treatment with antibiotics are not adequately followed. The high use of trimethoprim amongst institutionalized women and the low use of quinolones or trimethoprim among institutionalized men need further investigation.

PubMed

Medicine utilization review at a university teaching hospital in New Delhi.

July 2012

Aqil M, Bhadana V, Alam MS, Pillai KK, Kapur P.

Source

Department of Pharmaceutics, Faculty of Pharmacy, Majeedia Hospital, Jamia Hamdard, New Delhi, India.

Abstract

OBJECTIVE:

A prospective medicine usage evaluation based on prescription monitoring was conducted in the medicine OPD of our university teaching hospital to know prescribing trends of different categories of medicines.

MATERIALS AND METHODS:

A total of 600 patients were included in the study comprising of 339 (56.5%) males and 261 (43.5%) females. The data were recorded within the OPD by a registered pharmacist on a medicine usage evaluation form, approved by The University Institutional Review Board (IRB).

RESULTS:

A total of 2365 medicines were prescribed to 600 patients during the 3 months study period. The mean number of medicines per prescription were found to be 3.94. Medicines were most frequently prescribed as solid dosage forms (85.62%), especially tablets (70.82%), and liquid formulations (14.12%). Oral route (96.17%) was the most preferred mode of administration, followed by topical (2.11%) and parenteral (1.60%) routes. Combination therapy (94.33%) was more prevalent than monotherapy (5.66%). An overwhelming tendency for prescribing medicines by brand names (99%) was observed by the physicians. The most frequently prescribed class of medicines were antimicrobials > analgesics > cardiovascular > gastrointestinal agents. The most prescribed individual medicines among various therapeutic classes included isoniazid (antimicrobial), amlodipine (cardiovascular), metformin (hypoglycemic), cetirizine (antiallergic), rabeprazole (GI medicine), atorvastatin (hypolipidemic), dextromethorphan (respiratory medicine), alprazolam (sedative-hypnotic), paracetamol (analgesic).

CONCLUSIONS:

There is a considerable scope of improvement in the existing prescribing practice, especially prescribing by generic names, needs to be encouraged and a hospital formulary has to be developed for the purpose. The number of medicines to be included per prescription should be judged rationally and polypharmacy ought to be curbed. Use of antimicrobial also needs to be rationalized as over usage of antibiotics may lead to the problems such as medicine resistance and noncompliance.

PubMed

A situational analysis of antimicrobial drug resistance in Africa: are we losing the battle?

July 2012

Kimang'a AN.

Source

Sub-department of Medical Microbiology, Faculty of Science, Jomo Kenyatta University of Agriculture and Technology. P.O. Box 62000-00100, Nairobi-Kenya. Email: kinyerere@yahoo.com.

Abstract

BACKGROUND:

The first arrival of a sizable shipment of penicillin at the North African Theatre of Operations for USA military use in 1943 was a landmark that turned a new chapter of antibiotic use in Africa. Over the past decade the expansion of resources and the technological advances have meant that much larger quantities of drugs are available in developing countries than ever before. As a result, many more individuals are receiving necessary treatment or therapy than just ten years ago. This very welcome event is accompanied by the terrible irony that increases in drug availability and use can promote drug resistance and render the same life-saving drugs ineffective.

METHODS: 

The study focused on bacterial pathogens. One hundred and three relevant literatures were identified from the PubMed online database. The coverage included research articles concerning antimicrobial resistance involving subjects of an African country.

RESULTS:

Resistant bacteria are on a war path and evidently have acquired an edge over us. Our actions are evidently fuelling the resistance. The indiscriminate use of antibiotics in humans and livestock, wrong and substandard prescriptions by unqualified 'medical personnel' together with poor diagnosis or lack of it are all adding fuel to the already fired train of resistant microbes.

CONCLUSION:

To win the war and turn tables as we did with the discovery of penicillin and other antimicrobials in the 1940s, then we must all act now. Antimicrobial stewardship programs-Education, training of laboratory personnel and investment in laboratory infrastructure development are desirable in these situations.

PubMed

Selection of resistance at lethal and non-lethal antibiotic concentrations.

Selection of resistance at lethal and non-lethal antibiotic concentrations.

Aug 2012
Hughes D, Andersson DI.

Source

Abstract

Department of Medical Biochemistry and Microbiology, Box 582, SE-75123 Uppsala, Sweden.

Much of what we currently know about the genetics and evolution of antibiotic-resistance is based on selections with lethal drug concentrations that allow the detection of rare mutants with strong phenotypes. These data may be misleading with regard to the evolution of antibiotic resistance in natural environments, because bacteria are frequently exposed to concentration gradients of antibiotics. A significant part of antibiotic-resistance evolution may occur when bacteria are exposed to non-lethal concentrations of drug. High-resolution competition assays show that resistance mutations are rapidly enriched, and selected de novo, at very low antibiotic concentrations. Genomic analysis is providing a better understanding of how frequent and small-effect mutations selected at very low antibiotic concentrations contribute to the step-wise development of antibiotic resistance.

PubMed

15th Annual State of GA Lymphedema Education Program

Winship Cancer Institute of Emory University

and The Lighthouse Lymphedema Network

Cordially invite you to the

15th State of Georgia Lymphedema Education & Awareness Conference

Saturday, October 27, 2012

Emory University Hospital Midtown, 550 Peachtree Street, Atlanta, GA 30308

7:30am-4:30pm

Speakers include: Jane Armer, PhD, Richard Mistretta, DPM,

Joseph Feldman, MD, and David W. Chang, MD

The Conference Brochure may be viewed by clicking here:

http://lighthouselymphedema.org/announcements/15th-annual-state-of-georgia-lymph\
edema-education-and-awareness-program

You may register online by clicking here:

http://lighthouselymphedema.org/get-involved/secureregistration.htm

INFO PAGE:

http://lighthouselymphedema.org/announcements/15th-annual-state-of-georgia-lymph\
edema-education-and-awareness-program