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From July 2002 to September 2003, 10 patients were identified as having CA-MRSA skin and soft tissue infections at an indigent health care clinic in San Antonio, Texas. These infections were classified as community-acquired MRSA based on several factors: 1 ; none of the patients had risk factors for nosocomially acquired MRSA ie, recent hospitalization or surgery1 ; or those risk factors previously associated with acquisition of MRSA outside a short-term care setting: residence in a long-term care facility, current intravenous drug abuse, or underlying illnesses such as cardiovascular or pulmonary disease, diabetes mellitus, malignancy, or chronic skin disease such as eczema, 14 and 2 ; antimicrobial resistance patterns were consistent with CA-MRSA--ie, they showed susceptibility to several classes of antimicrobial agents other than -lactams. Patients were identified through a positive wound culture using an aerobic anaerobic Culturette. Many had been diagnosed and treated for other causes of their infection, including spider bites, impetigo, and varicella zoster. Four of the patients had been incarcerated and reported they had been treated for recurring skin infections several times while in prison. One of these 4 patients had a positive nasal culture for CA-MRSA. The other 6 patients had contact with either a prison facility or someone recently released from prison. One patient also played on his high school football team. Several patients were treated by other providers for what were thought to be spider bites. All CA-MRSA infections treated at the community clinic responded well to clindamycin, mupirocin, and drainage of the abscess, if present. The sensitivity pattern was similar in the positive MRSA cultures in that all were sensitive to clindamycin, rifampin, trimethoprim sulfamethoxazole, and vancomycin Table 1 ; . All the isolates were resistant to amoxicillin clavulanic acid, cefazolin, erythromy. 22-392 Does amoxicillin improve outcomes in patients with purulent rhinorrhea? A pragmatic randomized double-blind controlled trial in family practice and amphetamine.

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Treatment failure was observed in three patients from the amoxxicillin clavulanate group, and relapse occurred in one patient from each group.
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2001 ; impact of helicobacter pylori resistance to clarithromycin on the efficacy of the omeprazole– amoxicillin– clarithromycin therapy and avandia.
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Fourth Quarter Start of pivotal Phase III program for our Amoxicilllin PULSYS products We selected an amoxicillin formulation targeting pharyngitis tonsillitis and initiated dosing in October 2004 for our adolescent and adult Phase III trial, and began enrollment of our pediatric Phase III trial in January 2005. Also, in December 2004, we announced that our amoxicillin collaboration with Par was revised to include the development of an amoxicillin clavulanate PULSYS product for the treatment of otitis media. Preclinical studies presented in scientific forums A number of preclinical studies were conducted in 2004, and two studies supporting the efficiency of our once-daily pulsatile dosing approach were published in November and December 2004 issues of anti-infective industry journals. Steps taken to reduce spending In November 2004, we reduced staff and delayed the development of some of our product candidates, as a result of the unexpected GlaxoSmithKline GSK ; collaboration termination and our decision to discontinue our generic Biaxin XL program. We expect the actions taken will result in our current funds, together with payments expected from existing collaborations and Keflex product sales, to be adequate to support our existing operations through at least early 2006. Termination of GSK Collaboration On October 15, 2004, GSK notified us of their decision to terminate our collaboration for amoxicillin clavulanate Augmentin ; , under which we had licensed patents and PULSYS technology to them for their own clinical development efforts. GSK's continued development efforts could have resulted in additional milestone and royalty revenue to us; however, we believe that pulsatile amoxicillin clavulanate remains technically and commercially viable. Discontinuance of generic clarithromycin XL program During 2004, we continued to develop our generic non-pulsatile formulation of Abbott Laboratories' Biaxin XL clarithromycin extended release tablets ; . However, two formulations developed missed the peak concentration in one condition required to achieve the bioequivalence standard required for regulatory approval. In October 2004, we decided to end further development of this product, due to the non-core nature of the product that did not use our PULSYS technology, an increased number of competitors with similar generic product candidates nearing release, and the potential for diversion of resources and attention away from our proprietary PULSYS product candidates. Third Quarter Acquisition of Keflex brand of cephalexin from Eli Lilly for $11.2 million We began selling Keflex during the third quarter of 2004, and began pre-clinical work on a once-daily version of Keflex PULSYS along with the development of additional non-PULSYS Keflex products for potential sale in 2005. Cephalexin had retail sales of $545 million in 2004, on a prescription base of 25 million. Second Quarter Amoxixillin PULSYS product collaboration with Par In May 2004, we entered into a collaborative agreement with Par Pharmaceutical Companies, Inc. Par ; to develop and commercialize a pulsatile amoxicillin product for pharyngitis tonsillitis and, subsequently, an amoxicillin clavulanate combination PULSYS product for acute otitis media. Under this agreement, we received an upfront payment of $5 million and a commitment from Par to fund future product development expenses. First Quarter New patents issued In January 2004, we had two additional U.S. patents issue covering the formulation and use of two additional antibiotic products. This brings the total patent estate of our issued and allowed patents to 16, further protecting our novel biological finding related to the pulsatile dosing of antibiotics and other anti-infective therapies. Management team strengthened In 2004, we continued to build our senior management and hired a number of key personnel. Beginning in the first quarter of 2004, we added Barry Hafkin, M.D. as Chief Scientific Officer, Joseph Rogus as Senior Vice President, Technical Operations and Donald Anderson, M.D. as Vice President, Discovery. During the year, we also elevated Edward Rudnic, Ph.D. to the role of Chairman, President and Chief Executive Officer, Kevin Sly to Chief Business Officer, and Susan Clausen, Ph.D. to Vice President, Clinical Research. Parameters were also amelio Table 1 ; . Mean systolic blood and bactroban. Year published yr ; : 200 audience code ac ; : health professionals 100.
Nevertheless, all the above-mentioned PK parameters are totally interdependent. -Lactam antibiotics follow linear PKs and because of the principle of superposition, all these parameters are always directly proportional to the dose. They are also complex functions of the multicompartmental characteristics of the drug and of the dosing interval. However, the dose remains the first determinant of kinetics. In an attempt to better understand the interaction of amoxicillin with S. pneumoniae in the lung, and to tentatively determine the parameters of therapeutic efficacy of the antimicrobial agent amoxicillin, we used a PK-PD model to describe the overall dose-effect relationship of amoxicillin against 12 strains of S. pneumoniae with penicillin MICs ranging from 0.01 to 16 g neutropenic murine pneumonia model.

Tax expense constituted 16.5% 1.5% ; of pre-tax profit loss. The next table explains the difference between recognised tax expense and the parent company's profit loss before tax calculated using the local tax rate for Sweden 28% ; . 2005 Reconciliation of effective tax Pre-tax profit loss, SEK million Tax as per the applicable tax rate for the parent company, % Non-profit loss-related deductible items, % Other non-deductible expenses, % Non-taxable income, % Tax attributable to previous years, % Recognised effective tax, % Temporary differences resulted in these deferred tax assets: Deferred tax assets Inventories On 1 January 2004 Recognised in the income statement On 31 December 2004 Recognised in the income statement On 31 December 2005 0.0 1.0 0.0 2004, for example, amoxicillin strep throat.

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