Class of 2011 Abstract / OBJECTIVES: To determine the appropriateness of antimicrobial therapy in patients initiated on empiric meropenem therapy. METHODS: Adult patients prescribed empiric meropenem therapy between January 1, 2010 and March 31, 2010 at a tertiary care, academic medical center were included. Data collected included site of infection, culture and susceptibility data, risk factors for multi-drug resistant organisms, and changes in antimicrobial therapy during the first seven days after meropenem therapy was initiated. Demographic variables included age, sex, weight, and race. RESULTS: RESULTS: A total of 89 patients were included in the study analysis. Initial culture(s) was obtained before administration of antibiotics in only 58% of patients. During the first 24 hours of admission, four or more different antibiotics were prescribed in 26% of patients often with overlapping spectrums of activity. The majority of patients received meropenem for either less than 1 day or greater than 4 days. CONCLUSION: The primary issues identified with appropriate antibiotic prescribing involved the timing of cultures, and multiple changes in antibiotic therapy without culture-driven reasoning.

No description available.

Work was undertaken towards the synthesis of the promising antibiotic lactonamycin (iii). Following the work of Parsons et al. it was proposed that cyclisation of the ene-diyne (i) would give access to advanced pentacyclic intermediate (ii) and that from this a total synthesis of lactonamycin would be achieved (scheme I). Scheme I : Proposed Parsons, Board, Waters cyclisation to form the pentacycle (iii)(For image refer to pdf). A synthesis towards the cyclisation precursor (i) was carried out and a route to the key tetrasubstituted phthalide (v) established. Further chemistry was proposed to complete the synthesis of lactonamycin (scheme II). Scheme II : Formation of a fully substituted benzolactone.(For image refer to pdf). During attempts to introduce the β-bromoallyl group of key intermediate (v) using a high temperature Claisen rearrangement it was established that the benzodioxin (vii) underwent thermolysis to generate the reactive quinone methide intermediate (viii) and that in the presence of a nucleophilic solvent the adduct (ix) was formed (scheme III). Model studies showed the reaction to be both general and high-yielding. Scheme III : Novel quinone methide methodology. (For image refer to pdf).

The purpose of this research was to investigate home intravenous antibiotic therapy (HIVAT) in a multicenter, retrospective study in 1986 and 1987. The stability of reconstituted ceftizoxime and cefonicid in normal saline were evaluated by HPLC to investigate their usability for HIVAT. Using the three HHCPs' records, 457 patients were screened, and 30 patients were randomly selected/HHCP/year using the study's inclusion criteria (n = 180). Outcomes of HIVAT for osteomyelitis patients (n = 90) were compared with that for osteomyelitis inpatients (n = 13) discharged to HHCP1 from the referral hospital. Outcomes were classified as "success", "complication", and "failure". Types and frequency of problems were categorized as problems with antibiotics, and problems with administration procedures. Demographic data were analyzed to test the homogeneity of each group of patients. Data were analyzed using ANOVA, chi-square test, Kruskal-Wallis test, and multiple comparisons among proportions. (Abstract shortened with permission of author.)

Este estudo teve o objetivo de avaliar a eficiência do probiótico em manter o equilíbrio da microbiota intestinal de aves submetidas à antibioticoterapia e as associações com o desempenho. Os tratamentos dietéticos consistiram de uma dieta basal única, à base de milho e farelo de soja, à qual foi acrescido ou não o probiótico Bacillus subtillis (100 g/ton de ração), na concentração de 10? UFC/g. Por 3 dias consecutivos a partir de 21 dias de idade, as aves foram submetidas à antibioticoterapia via água de bebida consistindo de 200 ppm de bacitracina metileno dissacilato (efeito em bactérias Gram-positivas ) e 1000 ppm de sulfato de neomicina (efeito em bactérias Gram-negativas). O experimento foi conduzido com frangos de corte no período de 1 a 42 dias, sendo que de 1 a 21 dias as aves receberam somente o tratamento dietético, e, a partir de 21 dias, as aves receberam os tratamentos dietético e terapêutico. Aos 2, 4 e 6 dias após a antibioticoterapia, 3 aves de cada unidade experimental foram sacrificadas para coleta do conteúdo do intestino delgado e do ceco e obtidos \"pools\" dos conteúdos intestinais em cada unidade experimental para constituir uma repetição. O experimento foi realizado com 4 tratamentos, obedecendo a esquema fatorial 2×2 para as variáveis de desempenho (com e sem probiótico × com e sem antibioticoterapia) com 9 repetições e 2×2×3 para as análises da microbiota intestinal (com e sem probiótico na dieta × com e sem antibioticoterapia × 2, 4 e 6 dias após a antibioticoterapia) com 3 repetições. O DNA total foi extraído dos conteúdos do intestino delgado e ceco para o isolamento da região 16S rRNA e análise das comunidades bacterianas. As técnicas moleculares utilizadas foram a de fingerprinting Terminal Restriction Length Polymorphism (T-RFLP), PCR em tempo real (qPCR) e o sequenciamento, sendo que, para todas as técnicas, a região alvo foi o gene 16S rRNA. Os fatores dietético e terapêutico modularam a microbiota intestinal de forma independente. Houve efeito dos fatores probiótico e antibioticoterapia nos grupos predominantes do conteúdo do intestino, desde a classificação taxonômica filo até a classificação gênero. Alguns grupos filogenéticos foram igualmente afetados pelos 2 fatores em estudo, enquanto que outros grupos foram alterados de forma específica em função do probiótico ou antibioticoterapia. A antibioticoterapia, assim como o probiótico dietético, reduziu o número de unidades taxonômicas operacionais (OTUs) no conteúdo do ceco. O melhor desempenho observado nas aves alimentadas com dietas com probiótico provavelmente está relacionado às alterações observadas na estrutura das comunidades intestinais e grupos filogenéticos, como o acréscimo de Lactobacillus e redução de Clostridiales. A antibioticoterapia modificou a estrutura da comunidade bacteriana, entretanto não provocou queda no desempenho das aves. A comunidade bacteriana do intestino das aves medicadas e suplementadas com probiótico apresentou alta similaridade com a comunidade das aves que receberam apenas probiótico dietético, indicando a possível recuperação da microbiota intestinal aos 6 dias após a antibioticoterapia. / The purpose of this study was to verify the ability of a probiotic in the feed to maintain the stability of gut microbiota in chickens after antibiotic therapy and associations with the performance. The dietary treatments consisted of a cornsoybean meal basal diet that was supplemented or not with a probiotic (Bacillus subtilis) in the concentration of 3×109 cfu/kg of feed. Starting on day 21, the birds were submitted to the antibiotic therapy consisting of 200 ppm of bacitracin methylene disalicylate (for Gram-positive bacteria) and 1,000 ppm of neomycin sulfate (for Gram-negative bacteria) in the drinking water, during 3 days. The trial was conducted with broiler chickens from 1 to 42 days of age, however, from 1 to 21 days, the chickens received only the dietary treatment, and after of the 21 days, the birds received the dietary and therapeutic treatments. At 2, 4 and 6 days after the antibiotic therapy, three chickens from each experimental unit were euthanized and the contents of the small intestine and ceca were collected and pooled by pen. The trial was conducted in a completely randomized design with 4 treatments and 9 replicates in a 2×2 factorial arrangement for performance characteristics (with and without probiotic × with and without antibiotic therapy), and in a 2×2×3 factorial arrangement for gut microbiota (with and without probiotic × with and without antibiotic therapy × 2, 4 and 6 days after of the antibiotic therapy) with 3 replicates per treatment. The DNA was extracted from the contents of the small intestine and ceca to isolate the 16S r RNA and study of the bacterial communities. The molecular techniques used were the terminal restriction fragment length polymorphism (TRFLP), quantitative PCR (qPCR) and sequencing, considering the 16S rRNA -genetargeted. The dietary and therapeutic factors modulated the gut microbiota independently. The probiotic and antibiotic therapy affected the main groups within of the gut content from the phylogenetic classification at the phylum level until the phylogenetic classification at the genera level. Some phylogenetic groups were equally affected by the two factors while other groups were changed in a distinct form depending on of the probiotic or antibiotic therapy. The antibiotic therapy and dietary probiotic decreased the number of taxonomic operational unit (OTUs) in cecal content. The improved performance observed in birds supplemented with probiotic was probably related to changes in the structure of intestinal bacterial communities and phylogenetic groups such as higher Lactobacillus and decreased Clostridiales. Antibiotic therapy modified the bacterial community structure; however it did not cause loss of broiler performance. The gut bacterial community in birds medicated and supplemented with probiotic had high similarity with the gut community of birds that received dietary probiotic only, indicating the possible recovery of the gut bacterial community 6 days after the antibiotic therapy.

Neracionalus antimikrobinių vaistų (AMV) vartojimas didina mikroorganizmų atsparumą, gydymo kaštus ir hospitalizacijos trukmę. Didėjantis atsparumas AMV yra svarbi visuomenės sveikatos problema. Magistro darbo tikslas - kokybiškai ir kiekybiškai įvertinti AMV skyrimo KMU klinikose paplitimą bei jo pokyčius ir atitikimo racionalaus AMV vartojimo rekomendacijoms ypatumus ir dėsningumus. Tyrimas atliktas naudojant „skersinio pjūvio“ metodiką. 2007 m. kovo mėnesį vienmomentinio apžvalginio tyrimo metu (2 savaičių laikotarpyje) atrinktos ir išanalizuotos pacientų, kurie gauna AMV, ligos istorijos ir paskyrimai 32-iuose KMU klinikų skyriuose. AMV vartojimas yra racionalus, jei jų skyrimas atitinka racionalaus AMV vartojimo rekomendacijoms. Peržiūrėta 1213 paskyrimų, AMV buvo skirti 265 pacientams. Rekomendacijų neatitiko pusė (54 proc.) visų AMV paskyrimų. Daugiau kaip pusė (58 proc.) gydymo tikslu skirtų empirinių AMV paskyrimų vertinti kaip neatitinkantys racionalaus AMV rekomendacijų. Vertinant AMV skyrimo atitikimą rekomendacijoms atskiruose skirtingo profilio skyriuose daugiausia neatitikusių paskyrimų nustatyta chirurginio (74 proc.) ir terapinio (55 proc.) profilio skyriuose, atitikusių – pediatrinio (71proc.) ir intensyvios terapijos (60 proc.) profilių skyriuose. Ryšio tarp skyriaus profilio ir atitikimo rekomendacijoms nenustatyta. (r = 0,5387 , p = 0,4613, Spearmano koreliacija). Didžiąją dalį neatitinkančių rekomendacijų paskyrimų atvejų (56,86 proc.) sudarė... [toliau žr. visą tekstą] / Irrational and excessive use of antibiotics increases resistance to these preparations. Antimicrobial resistance is a serious public health problem worldwide. The main goal of our study was to evaluate and to compare the non-adherence (NA) to guidelines (NfG) on rational antibiotic therapy and prophylaxis (ABT/P) in tertiary hospital setting among two years (2006 and 2007). A cross-sectional study was performed in order to collect the data for patients receiving prescriptions for antimicrobial agents in March, 2007. Descriptive and comparative data were processed and evaluated using Graph Pad Prism 4 statistics program. Rationality of antibiotic therapy was evaluated according for adherence to published guidelines. A total of 265 (21%) patients recieved antibiotic therapy. 54% of all events were considered as non-adherent.The majority of NA cases was determined in the departments of therapeutic profile (55%) and in surgical profile (74%). The adherent events - in paediatric profile(71%) and in the intensive therapy profile (60%). No dependence between the type of profile and adherence to guidelines was determined (r = 0,5387, p = 0,4613, Spearman correlation). The main reasons of NA were inapropriate dosage (57%) and choice of drug (43% ). NA case analysis revealed too high dose prescribed in 40/87 (46%) cases, too low dose 47/87 (54%)cases; too broad spectrum in 28/61 (46%) cases, too narrow - in 9/61(15%), 2/61 ( 3 %) case as unsafe and 22/61 (36%) cases... [to full text]

Este estudo teve o objetivo de avaliar a eficiência do probiótico em manter o equilíbrio da microbiota intestinal de aves submetidas à antibioticoterapia e as associações com o desempenho. Os tratamentos dietéticos consistiram de uma dieta basal única, à base de milho e farelo de soja, à qual foi acrescido ou não o probiótico Bacillus subtillis (100 g/ton de ração), na concentração de 10? UFC/g. Por 3 dias consecutivos a partir de 21 dias de idade, as aves foram submetidas à antibioticoterapia via água de bebida consistindo de 200 ppm de bacitracina metileno dissacilato (efeito em bactérias Gram-positivas ) e 1000 ppm de sulfato de neomicina (efeito em bactérias Gram-negativas). O experimento foi conduzido com frangos de corte no período de 1 a 42 dias, sendo que de 1 a 21 dias as aves receberam somente o tratamento dietético, e, a partir de 21 dias, as aves receberam os tratamentos dietético e terapêutico. Aos 2, 4 e 6 dias após a antibioticoterapia, 3 aves de cada unidade experimental foram sacrificadas para coleta do conteúdo do intestino delgado e do ceco e obtidos \"pools\" dos conteúdos intestinais em cada unidade experimental para constituir uma repetição. O experimento foi realizado com 4 tratamentos, obedecendo a esquema fatorial 2×2 para as variáveis de desempenho (com e sem probiótico × com e sem antibioticoterapia) com 9 repetições e 2×2×3 para as análises da microbiota intestinal (com e sem probiótico na dieta × com e sem antibioticoterapia × 2, 4 e 6 dias após a antibioticoterapia) com 3 repetições. O DNA total foi extraído dos conteúdos do intestino delgado e ceco para o isolamento da região 16S rRNA e análise das comunidades bacterianas. As técnicas moleculares utilizadas foram a de fingerprinting Terminal Restriction Length Polymorphism (T-RFLP), PCR em tempo real (qPCR) e o sequenciamento, sendo que, para todas as técnicas, a região alvo foi o gene 16S rRNA. Os fatores dietético e terapêutico modularam a microbiota intestinal de forma independente. Houve efeito dos fatores probiótico e antibioticoterapia nos grupos predominantes do conteúdo do intestino, desde a classificação taxonômica filo até a classificação gênero. Alguns grupos filogenéticos foram igualmente afetados pelos 2 fatores em estudo, enquanto que outros grupos foram alterados de forma específica em função do probiótico ou antibioticoterapia. A antibioticoterapia, assim como o probiótico dietético, reduziu o número de unidades taxonômicas operacionais (OTUs) no conteúdo do ceco. O melhor desempenho observado nas aves alimentadas com dietas com probiótico provavelmente está relacionado às alterações observadas na estrutura das comunidades intestinais e grupos filogenéticos, como o acréscimo de Lactobacillus e redução de Clostridiales. A antibioticoterapia modificou a estrutura da comunidade bacteriana, entretanto não provocou queda no desempenho das aves. A comunidade bacteriana do intestino das aves medicadas e suplementadas com probiótico apresentou alta similaridade com a comunidade das aves que receberam apenas probiótico dietético, indicando a possível recuperação da microbiota intestinal aos 6 dias após a antibioticoterapia. / The purpose of this study was to verify the ability of a probiotic in the feed to maintain the stability of gut microbiota in chickens after antibiotic therapy and associations with the performance. The dietary treatments consisted of a cornsoybean meal basal diet that was supplemented or not with a probiotic (Bacillus subtilis) in the concentration of 3×109 cfu/kg of feed. Starting on day 21, the birds were submitted to the antibiotic therapy consisting of 200 ppm of bacitracin methylene disalicylate (for Gram-positive bacteria) and 1,000 ppm of neomycin sulfate (for Gram-negative bacteria) in the drinking water, during 3 days. The trial was conducted with broiler chickens from 1 to 42 days of age, however, from 1 to 21 days, the chickens received only the dietary treatment, and after of the 21 days, the birds received the dietary and therapeutic treatments. At 2, 4 and 6 days after the antibiotic therapy, three chickens from each experimental unit were euthanized and the contents of the small intestine and ceca were collected and pooled by pen. The trial was conducted in a completely randomized design with 4 treatments and 9 replicates in a 2×2 factorial arrangement for performance characteristics (with and without probiotic × with and without antibiotic therapy), and in a 2×2×3 factorial arrangement for gut microbiota (with and without probiotic × with and without antibiotic therapy × 2, 4 and 6 days after of the antibiotic therapy) with 3 replicates per treatment. The DNA was extracted from the contents of the small intestine and ceca to isolate the 16S r RNA and study of the bacterial communities. The molecular techniques used were the terminal restriction fragment length polymorphism (TRFLP), quantitative PCR (qPCR) and sequencing, considering the 16S rRNA -genetargeted. The dietary and therapeutic factors modulated the gut microbiota independently. The probiotic and antibiotic therapy affected the main groups within of the gut content from the phylogenetic classification at the phylum level until the phylogenetic classification at the genera level. Some phylogenetic groups were equally affected by the two factors while other groups were changed in a distinct form depending on of the probiotic or antibiotic therapy. The antibiotic therapy and dietary probiotic decreased the number of taxonomic operational unit (OTUs) in cecal content. The improved performance observed in birds supplemented with probiotic was probably related to changes in the structure of intestinal bacterial communities and phylogenetic groups such as higher Lactobacillus and decreased Clostridiales. Antibiotic therapy modified the bacterial community structure; however it did not cause loss of broiler performance. The gut bacterial community in birds medicated and supplemented with probiotic had high similarity with the gut community of birds that received dietary probiotic only, indicating the possible recovery of the gut bacterial community 6 days after the antibiotic therapy.

No presenta resumen. / Revisión por pares

Treatment of enterococcal endocarditis requires up to 6 weeks of intravenous (IV) antimicrobial therapy. When susceptible, an ampicillin-based regimen is preferred. Studies evaluating ampicillin stability utilizing high-pressure liquid chromatography have indicated enhanced stability (greater than 24 hours at room temperature), supporting outpatient administration. Thus, we report the successful treatment of a 30-year-old male with tricuspid valve enterococcal endocarditis in an outpatient setting using continuous infusion ampicillin via an ambulatory infusion pump. The patient received daily gentamicin at an outpatient infusion center with the ampicillin dose to be infused over the next 24 hours. Outpatient ambulatory infusion pumps allow for delivery of ampicillin via continuous infusion or pump-programmed pulse dosing. Preparation and administration in an outpatient infusion center may be a viable option to circumvent stability and delivery issues. Furthermore, 81% (34/42) of treatment days were completed outpatient, supporting that this approach may increase access to treatment and help reduce the economic burden to health care.

Le traitement antibiotique local de l'infection osseuse par le polyméthacrylate de méthyle (PMMA), chargé de gentamicine ou de tobramycine, montre actuellement des limites. Ses inconvénients sont liés à la non résorbabilité du PMMA et à la rétention d'une grande partie de l'antibiotique intégré au PMMA. L’association fréquente à l’infection de pertes de substance osseuse a favorisé la recherche de vecteurs d’antibiothérapie locale, alternative au PMMA, parmi les substituts de comblement osseux résorbables et ostéoconducteurs. Les ciments phosphocalciques (CPC) pourraient devenir parmi les plus performants dans cette utilisation. Ils sont biocompatibles et offrent avec le Dicalcium Phosphate-ß-Tricalcium Phosphate (DCPD-ß-TCP), un CPC, la possibilité d'obtention d'un mélange DCPD-ß-TCP-gentamicine à une température de 43°C n'altérant pas l'antibiotique, contrairement aux céramiques phosphocalciques qui sont fabriquées par frittage à très haute température. Le but de notre travail était de tester in vitro (élution d’antibiotique) et in vivo (essai de traitement d'ostéite expérimentale) le DCPD-ß-TCP-gentamicine comme alternative possible au PMMA-gentamicine. [...] / Local antibiotic treatment of osteomyelitis is based on the use of gentamicin- (or tobramycin-) loaded polymethylmethacrylate (PMMA). These two aminoglycosides are effective against most cultured orthopedic microorganisms, including Staphylococcus aureus, the most frequent cause of infection. The extensive use of PMMA as a Local Antibiotic Delivery System (LADS) has various disadvantages. Firstly, only a small proportion (about 5 to 17%) of the antibiotic is released by the cement (trapping effect). Secondly, the most significant problem is that PMMA is not resorbable and presents a physical obstacle to osteogenesis. A second surgical operation is therefore always required to remove the PMMA and to fill the cavity caused by bone loss with a bone graft or a synthetic substitute. Several absorbable synthetic substitutes, such as calcium phosphate ceramics, calcium sulfate, and polymers of polylactic-polyglycolic acids, have been investigated as antibiotic carriers. These synthetic substitutes are largely underused as LADS in clinical practice. Polymers are not perfectly biocompatible, and ceramics provide a burst release of antibiotics as a consequence of their manufacturing techniques (Antibiotic adsorption onto the carrier, after sintering of the carrier at high temperature, 1000-1200°C). We have developed a possible alternative to gentamicin loaded-PMMA for local treatment of osteomyelitis in the form of novel calcium phosphate cement (CPC): dicalcium phosphate dihydrate-β-tricalcium phosphate (DCPD-β-TCP). The biocompatibility of such a cement has been demonstrated experimentally and has been clinically confirmed for the treatment of burst fractures and for filling bone cavities in osteoporotic fractures. DCPD-ß-TCP is made in granules from 2 to 3 mm in diameter to avoid the superficial ―creeping substitution‖ observed when DCPD-β-TCP is used as a cement block. [...]