Antibiotics for Superbacteria

New antibiotics discovered that could beat back superbacteria

Researchers hope to stop virulent form of staph

By LEE BOWMANSCRIPPS HOWARD NEWS SERVICE

Researchers reported Friday they have found four promising antibiotics in chemical families never used before against germs through a novel testing tool that can screen dozens of compounds at once.

The four compounds appear to kill bacteria, at least in a lab dish. Because they probably attack bacteria in different ways, germs should take some time to develop resistant strains.
"These represent whole new classes of antibiotic agents," said Helen Blackwell, lead author of a University of Wisconsin-Madison report on the discoveries published in the journal Chemistry and Biology.

Also, while the most potent compounds were able to kill several dangerous strains of bacteria, the strongest activity was against a highly drug-resistant strain of staph infection (Staphylococcus aureus) that has been plaguing hospitals for years and has recently become common in community settings.

"Strains are emerging that are drug-resistant to all known antibiotics," Blackwell said. "This is not a problem that is going to go away, and actually it's going to get worse. There's a sense of urgency."

The best approach is to be able to hit bacteria with drugs they have not seen before. But finding a potentially useful drug against a broad spectrum of germs is not much different from finding a needle in a haystack.

Blackwell's team designed a way to sift through a lot of hay at once with a device it calls a small-molecule macroarray. The scientists synthesize molecules on a flexible, paperlike sheet, building a compound from the bottom up by adding ingredients to the sheet one at a time.

Each array has dozens of compounds arranged in grids of dots that are about the size of a pencil eraser.

They put each array up against a battery of germs, testing the potency of each compound against various bacterial strains.

The whole process of building and testing a batch of 50 to 300 compounds takes about two days.
Only about 2 percent of the compounds tested using the arrays show any potential against bacteria. And that's just a first step on a long path to drug development.

The next stage is to understand how the compounds work to kill bacteria. "What features of compounds are necessary for activity, and can we improve them?" Blackwell said.

Once the active elements and mechanism are understood, researchers can begin testing doses and evaluating the compounds for safety in animals and eventually humans, if trials go well.

The key is that with the new macroarray, Blackwell said it's possible to see which molecules are active fairly quickly, and "we can gather information on how to improve them fairly quickly."

Seattlepi

Hydrates and solid-state reactivity: A survey of beta-lactam antibiotics.

Hydrates and solid-state reactivity: A survey of beta-lactam antibiotics.

J Pharm Sci. 2007 Apr 23

Hickey MB,
Peterson ML,
Manas ES,
Alvarez J,
Haeffner F,
Almarsson O.

TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, Lexington, Massachusetts 02421.

Crystalline hydrates of hydrolytically susceptible pharmaceuticals are commonly encountered, and are particularly prevalent in the beta-lactam class of antibiotics. In order to rationalize how the apparent chemical incompatibility between water and beta-lactams is reduced through crystallization, a review of the published literature and available structural information on the solid state stability was undertaken. A search in the CSD yielded a total of 32 crystal structures of water-containing beta-lactams which were examined and classified in terms of hydrogen-bonded networks.

In most cases the waters of hydration in the single crystal structures were found to fulfill structural roles and were not sufficiently close in proximity to react with the beta-lactam ring. Published data for the solid-state of several hydrates were also considered. In general, the stability data indicate high thermal stability for the crystalline hydrates. Moreover, even when water molecules are in appropriate proximity and orientation with respect to the beta-lactam moiety for a reaction to occur, the crystalline solids remain stable.

The use of the crystal structure information along with computational modeling suggests that a combination of proximal relationships, steric and mechanistic arguments can explain the observed solid-state stability of crystalline beta-lactam hydrates.

(c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 1090-1099, 2007.

PMID: 17455335 [PubMed - as supplied by publisher]

Sequential Therapy Beats Standard Therapy For Helicobacter Pylori

Sequential Therapy Beats Standard Therapy For Helicobacter Pylori

Four antibiotics versus three

Main Category: GastroIntestinal / Gastroentorology News

Article Date: 19 Apr 2007 - 21:00 PDT

In a clinical trial testing two different ways to treat Helicobacter pylori infection (a common cause of stomach ulcers), researchers found that four antibiotics given sequentially cured the infection more often than standard treatment with three antibiotics taken together for 10 days (Article, p. 556). The cure rate for the sequential treatment was 91 percent compared to 71 percent for the standard treatment. The sequential regimen was also more effective than conventional therapy for patients with certain antibiotic-resistant H. pylori bacteria. (The article and editorial are published online. They will be available in the May 1, 2007, print edition of Annals of Internal Medicine.) Note: Annals of Internal Medicine is published by the American College of Physicians.

Dental Work and Antibiotics

Guidelines: Only Some Need Dental Antibiotics

Risks May Outweigh Benefits

POSTED: 9:46 am EDT April 20, 2007

Taking antibiotics before visiting the dentist may do more harm than good, the American Heart Association says.

Some dentists prescribe antibiotics before routine cleanings or extractions to prevent infective endocarditis, an infection of the heart's inner lining or valves. But the AHA now says that is only needed for people at high risk, such as those with artificial valves, a history of endocarditis or serious heart problems.

The doctor who led the work, Walter Wilson, said there is no evidence that the antibiotics prevent infection, and they may increase resistance of bacteria when infections do occur.

A news release said that everyday tooth brushing causes 154,000 times the risk of exposure to bacteria that could cause problems than having a tooth pulled.

Original Post

Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus: Management Principles and Selection of Antibiotic Therapy.

Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus: Management Principles and Selection of Antibiotic Therapy.
Dermatol Clin. 2007 Apr

Elston DM.
Department of Dermatology, Geisinger Medical Center, 100 North Academy Ave., Danville, PA 17822, USA; Department of Pathology, Geisinger Medical Center, 100 North Academy Ave., Danville, PA 17822, USA.

Strains of community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) have emerged as an important group of pathogens. Most infections present as cutaneous abscess and most of these may respond to drainage alone. Sulfonamide and tetracycline antibiotics remain valuable agents for most CA-MRSA infections, but inducible resistance to clindamycin is problematic in some areas. Linezolid, and the newer parenteral antibiotics should be reserved for serious infections.

PMID: 17430753 [PubMed - as supplied by publisher]

Antibiotic-containing collagen for the treatment of bone defects

Antibiotic-containing collagen for the treatment of bone defects
J Biomed Mater Res B Appl Biomater. 2007 Apr 5

Rupprecht S,
Petrovic L,
Burchhardt B,
Wiltfang J,
Neukam FW,
Schlegel KA.
Oral and Maxillofacial Surgery, Friedrich Alexander University Erlangen-Nuremberg, Germany.

Recent studies have explored the use of biodegradable implants that incorporate antibiotics for the treatment of bone infections. In this study, a biodegradable composite containing bovine collagen and teicoplanin (Targobone(R)) was used for the treatment of mandibular nonunion defects. Patients with mandibular nonunion defects subsequent to osteosynthesis were treated with Targobone(R) (n = 9) or with autologous bone grafts (n = 12). Clinical and radiological evaluations were performed preoperatively, immediately postoperatively, and 4 and 24 weeks postoperatively. Bone regeneration was defined relative to the original defect area in the panoramic radiograph by using image analysis software. In the Targobone(R) group, the defect area decreased to 78% (SD +/- 21.8%) of the preoperative area within 4 weeks and to 21% (SD +/- 9.7%) of the preoperative area within 24 weeks. In the autologous bone graft group, the defect area decreased to 69% (SD +/- 32.4%) of the preoperative area within 4 weeks and to 4.7% (SD +/- 5.6%) of the preoperative area within 24 weeks. Thus, Targobone(R) is a promising option for the treatment of bone defects.

2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007.

PMID: 17415766 [PubMed - as supplied by publisher]

Parental knowledge about antibiotic use: results of a cluster-randomized, multicommunity intervention

Parental knowledge about antibiotic use: results of a cluster-randomized, multicommunity intervention
Pediatrics. 2007 Apr

Huang SS,
Rifas-Shiman SL,
Kleinman K,
Kotch J,
Schiff N,
Stille CJ,
Steingard R,
Finkelstein JA.
Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, 133 Brookline Ave, 6th Floor, Boston, MA 02215. sshuang@partners.org.

OBJECTIVE. The goal was to determine the impact of a community-wide educational intervention on parental misconceptions likely contributing to pediatric antibiotic overprescribing.

METHODS. We conducted a cluster-randomized trial of a 3-year, community-wide, educational intervention directed at parents of children <6>

RESULTS. There were 1106 (46%) and 2071 (40%) respondents to the 2000 and 2003 surveys, respectively. Between 2000 and 2003, the proportion of parents who answered >/=7 of 10 knowledge questions correctly increased significantly in both intervention (from 52% to 64%) and control (from 54% to 61%) communities. We did not detect a significant intervention impact on knowledge regarding appropriate antibiotic use in the population overall. In a subanalysis, we did observe a significant intervention effect among parents of Medicaid-insured children, who began with lower baseline knowledge scores.

CONCLUSIONS. Although knowledge regarding appropriate use of antibiotics is improving without additional targeted intervention among more socially advantaged populations, parents of Medicaid-insured children may benefit from educational interventions to promote judicious antibiotic use. These findings may have implications for other health education campaigns.

PMID: 17403840 [PubMed - in process]