Does variation among provincial drug formulary antimicrobial listings in Canada influence prescribing rates?

BACKGROUND: The financial accessibility of antimicrobial drugs to the outpatient community in Canada is governed at the provincial level through formularies. Each province may choose to list particular drugs or impose restriction criteria on products in order to guide prescribing and/or curtail costs. Although changes to formularies have been shown to change patterns in the use of individual products and alter costs, no comparison has been made among the provincial antimicrobial formularies with regards to flexibility/stringency, or an assessment of how these formularies impact overall antimicrobial use in the provinces. OBJECTIVES: To summarize provincial antimicrobial formularies and assess whether their relative flexibility/stringency had a statistical impact upon provincial prescription volume during a one year period. METHODS: Provincial drug plan formularies were accessed and summarized for all prescribed antimicrobials in Canada during 2010. The number of general and restricted benefits for each plan was compiled by antimicrobial classification. Population-adjusted prescription rates for all individual antimicrobials and by antimicrobial class were obtained from the Canadian Integrated Program for Antimicrobial Resistance Surveillance. Correlations between the number of general benefits, restricted benefits, and total benefits with the prescription rate in the provinces were assessed by Spearman rank correlation coefficients. RESULTS: Formularies varied considerably among the Canadian provinces. Quebec had the most flexible formulary, offering the greatest number of general benefits and fewest restrictions. In contrast, Saskatchewan's formulary displayed the lowest number of general benefits and most restrictions. Correlation analyses detected a single significant result; macrolide prescription rates decreased as the number of general macrolide benefits increased. All other rates of provincial antimicrobial prescribing and measures of flexibility/stringency revealed no significant correlations. CONCLUSIONS: Although antimicrobial formulary listings are used to guide prescribing rates within a province, our analysis of one year's data of the impact of the antimicrobial formulary structure did not correlate with antimicrobial prescribing rates, and other factors are likely to be at play.

Variation in outpatient oral antimicrobial use patterns among Canadian provinces, 2000 to 2010.

BACKGROUND: The volume and patterns of antimicrobial drug use are key variables to consider when developing guidelines for prescribing, and programs to address stewardship and combat the increasing prevalence of antimicrobial resistant pathogens. Because drug programs are regulated at the provincial level, there is an expectation that antibiotic use may vary among provinces. OBJECTIVE: To assess these potential differences according to province and time. METHODS: Provincial antimicrobial prescribing data at the individual drug level were acquired from the Canadian Integrated Program for Antimicrobial Resistance Surveillance for 2000 to 2010. Data were used to calculate two yearly metrics: prescriptions per 1000 inhabitant-days and the average defined daily doses per prescription. The proportion of liquid oral prescriptions of total prescriptions was also calculated as a proxy measure for the proportion of prescriptions given to children versus adults. To assess the significance of provincial antimicrobial use, linear mixed models were developed for each metric, accounting for repeated measurements over time. RESULTS: Significant differences among provinces were found, as well as significant changes in use over time. Newfoundland and Labrador was found to have significantly higher prescribing rates than all other provinces (P<0.001) in 2010, as well as the mean of all other provinces (P<0.001). In contrast, Quebec exhibited significantly lower prescribing than all other provinces (P<0.001 for all provinces except British Columbia, where P=0.024) and the mean of all other provinces (P<0.001). DISCUSSION/CONCLUSION: Reports of reductions in antimicrobial use at the Canadian level are promising, especially prescribing to children; however, care must be taken to avoid the pitfall of the ecological fallacy. Reductions are not consistent among the provinces or among the classes of antimicrobial drugs dispensed in Canada.

HISTORIQUE: Le volume et les modes d'utilisation d'antimicrobiens sont des variables importantes à envisager lorsqu'on élabore des lignes directrices de prescription et des programmes pour aborder la question de la gouvernance et pour lutter contre la prévalence croissante des pathogènes résistants aux antimicrobiens. Puisque les programmes de médicaments sont réglementés sur la scène provinciale, on s'attend que l'utilisation d'antibiotiques varie entre les provinces. OBJECTIF: Évaluer ces différences potentielles selon la province et dans le temps. MÉTHODOLOGIE: Les chercheurs ont extrait les données sur la prescription de chaque médicament antimicrobien sur la scène provinciale du Programme intégré canadien de surveillance de la résistance aux antimicrobiens entre 2000 et 2010. À l'aide de ces données, ils ont calculé deux mesures annuelles : les prescriptions par 1 000 habitants-jours et les doses thérapeutiques quotidiennes moyennes dispensées par prescription. Ils ont également calculé la proportion de prescriptions orales liquides par rapport aux prescriptions totales pour établir approximativement la proportion de prescriptions administrées aux enfants par rapport aux adultes. Pour évaluer l'importance de l'utilisation d'antimicrobiens sur la scène provinciale, les chercheurs ont élaboré des modèles linéaires mixtes pour chaque mesure, tenant compte de mesures répétées dans le temps. RÉSULTATS: Les chercheurs ont constaté des différences significatives entre les provinces, ainsi que des changements importants d'utilisation dans le temps. Ils ont déterminé que Terre-Neuve-et-Labrador présentait des taux de prescription considérablement plus élevés que toutes les autres provinces (P<0,001) en 2010, ainsi que de la moyenne de toutes les autres provinces (P<0,001). Par contre, le Québec présentait des taux de prescription considérablement plus faibles que toutes les autres provinces (P<0,001 pour toutes les provinces sauf la Colombie-Britannique, où P=0,024) ainsi que de la moyenne de toutes les autres provinces (P<0,001). EXPOSÉ ET CONCLUSION: Les rapports sur la diminution de l'utilisation d'antimicrobiens sur la scène canadienne sont prometteurs, notamment les prescriptions aux enfants. Cependant, il faut s'assurer d'éviter l'écueil des erreurs écologiques. Les réductions ne sont pas uniformes entre les provinces ou entre les classes d'antimicrobiens administrées au Canada.

Longitudinal surveillance of outpatient quinolone antimicrobial use in Canada.

INTRODUCTION: Because antimicrobial use is commonly associated with the development of antimicrobial resistance, monitoring the volume and patterns of use of these agents is important. OBJECTIVE: To assess the use of quinolone antimicrobials within Canadian provinces over time. METHODS: ANTIMICROBIAL PRESCRIBING DATA COLLECTED BY IMS HEALTH CANADA WERE ACQUIRED FROM THE CANADIAN INTEGRATED PROGRAM FOR ANTIMICROBIAL RESISTANCE SURVEILLANCE AND THE CANADIAN COMMITTEE FOR ANTIMICROBIAL RESISTANCE, AND WERE USED TO CALCULATE TWO YEARLY METRICS: prescriptions per 1000 inhabitant-days and the mean defined daily doses (DDDs) per prescription. These measures were used to produce linear mixed models to assess differences among provinces and over time, while accounting for repeated measurements. RESULTS: The quinolone class of antimicrobials is used similarly among Canadian provinces. Year-to-year increases in quinolone prescribing occurred from 1995 to 2010, with a levelling off in the latter years. Year-to-year decreases in the DDDs per prescription were found to be significant from 2000 to 2010. DISCUSSION: Although the overall use of antimicrobials differs significantly among Canadian provinces, the use of the quinolone class does not vary at the provincial level. Results suggest that prescribing of ciprofloxacin may be a potential target for antimicrobial stewardship programs; however, decreases in the average DDDs per prescription suggest continued uptake of appropriate treatment guidelines.

INTRODUCTION: Puisque l'utilisation d'antimicrobiens s'associe souvent à l'apparition d'une résistance antimicrobienne, il est important d'en surveiller le volume et le mode d'utilisation. OBJECTIF: Évaluer l'utilisation d'antimicrobiens de la classe des quinolones au sein des provinces canadiennes au fil du temps. MÉTHODOLOGIE: Les chercheurs ont acquis les données de prescription d'antimicrobiens colligées par IMS Health Canada auprès du Programme intégré canadien de surveillance de la résistance aux antimicrobiens et du Comité canadien sur la résistance aux antibiotiques et les ont utilisées pour calculer deux mesures annuelles : les prescriptions par 1 000 habitants-jours et les doses quotidiennes définies (DTD) moyennes par prescription. Ils les ont utilisées pour produire des modèles linéaires mixtes afin d'évaluer les différences entre les provinces et au fil du temps, tout en tenant compte des mesures répétées. RÉSULTATS: Les antimicrobiens de la classe des quinolones sont utilisés de manière similaire dans les provinces canadiennes. Les prescriptions annuelles de quinolone ont augmenté de 1995 à 2010, mais ont plafonné au cours des dernières années. Les DTD par prescription ont diminué annuellement de manière significative entre 2000 et 2010. EXPOSÉ: Même si l'utilisation globale d'antimicrobiens diffère de manière significative entre les provinces canadiennes, l'utilisation de la classe des quinolones ne varie pas sur la scène provinciale. D'après les résultats, la prescription de ciprofloxacine peut être une cible potentielle des programmes de gestion des antimicrobiens. Cependant, les diminutions des DTD moyennes par prescription sont indicatrices d'une assimilation continue des directives thérapeutiques pertinentes.

Provincial and temporal variation in macrolide and lincosamide antimicrobial use by outpatients in Canada, 1995 to 2010.

INTRODUCTION: Because antimicrobial use is commonly associated with the development of antimicrobial resistance, monitoring the volume and patterns of use of these agents is very important. OBJECTIVE: To assess the use of macrolide and lincosamide (ML) antimicrobials within Canadian provinces over time, and to compare use rates with those reported by European countries. METHODS: ANTIMICROBIAL PRESCRIBING DATA WERE USED TO DEVELOP TWO YEARLY METRICS: prescriptions per 1000 inhabitant-days (PrIDs) and the mean defined daily doses (DDDs) per prescription, which were then used to build linear mixed models to assess differences among provinces over time. RESULTS: After accounting for repeated measures over time, prescribing rates (PrIDs) varied significantly according to province and year (P<0.001). However, little change occurred within each province over the time frame studied; from 1995 to 2010, each province had a PrID change <0.01. Quebec and British Columbia had significantly lower prescribing rates than all other provinces. No overall secular trend was apparent. In contrast, the DDDs per prescription did not vary significantly according to province, but showed a significant year-to-year increase. DISCUSSION: ML prescribing varied among provinces in Canada between 1995 and 2010, but remained relatively stable within each province. The average DDDs per ML prescription did not vary according to province, but increased linearly over time. These increases are likely to indicate that fewer prescriptions are being written for children over time, a practice supported by good antimicrobial stewardship principles.

INTRODUCTION: Puisque l'utilisation d'antimicrobiens s'associe souvent à l'apparition d'une résistance aux antimicrobiens, il est très important d'en surveiller le volume et les profils d'utilisation. OBJECTIF: Évaluer l'utilisation des antimicrobiens marcolides et lincasomides (ML) dans les provinces canadiennes au fil du temps et comparer les taux d'utilisation par rapport à ceux des pays européens. MÉTHODOLOGIE: Les données de prescription d'antimicrobiens ont permis d'établir deux mesures annuelles : les prescriptions par 1 000 habitants-jours (PrID) et les doses quotidiennes définies (DQD) moyennes par prescription, qui ont ensuite été utilisées pour créer des modèles linéaires mixtes d'évaluation des différences entre les provinces au fil du temps. RÉSULTATS: Après avoir tenu compte des mesures répétées au fil du temps, les taux de prescription (PrID) variaient de manière significative selon la province et l'année (P<0,001). Cependant, on a observé peu de changements dans chaque province pendant la période de l'étude. En effet, de 1995 à 2010, chaque province présentait un changement des PrID de moins de 0,01. Le Québec et la Colombie-Britannique présentaient un taux de prescription considérablement plus faible que toutes les autres provinces. Aucune tendance lourde globale n'était apparente. Par contre, les DQD par prescription ne variaient pas de manière significative selon la province, mais augmentait de manière significative d'une année à l'autre. EXPOSÉ: Les prescriptions de ML étaient variables entre les provinces du Canada de 1995 à 2010, mais demeuraient relativement stables dans chaque province. Les DQD moyennes par prescription de ML ne variaient pas selon la province, mais présentaient une augmentation linéaire au fil du temps. Ces augmentations sont susceptibles d'indiquer que moins de prescriptions sont rédigées pour les enfants au fil du temps, une pratique soutenue par de bons principes de gouvernance antimicrobienne.

Longitudinal surveillance of outpatient ß-lactam antimicrobial use in Canada, 1995 to 2010.

INTRODUCTION: ß-lactam antimicrobials are the most commonly prescribed group of antimicrobials in Canada, and are categorized by the WHO as critically and highly important antimicrobials for human medicine. Because antimicrobial use is commonly associated with the development of antimicrobial resistance, monitoring the volume and patterns of use of these agents is highly important. OBJECTIVE: To assess the use of penicillin and cephalosporin antimicrobials within Canadian provinces over the 1995 to 2010 time frame according to two metrics: prescriptions per 1000 inhabitant-days and the average defined daily doses dispensed per prescription. METHODS: Antimicrobial prescribing data were acquired from the Canadian Integrated Program for Antimicrobial Resistance Surveillance and the Canadian Committee for Antimicrobial Resistance, and population data were obtained from Statistics Canada. The two measures developed were used to produce linear mixed models to assess differences among provinces and over time for the broad-spectrum penicillin and cephalosporin groups, while accounting for repeated measurements at the provincial level. RESULTS: Significant differences among provinces were found, as well as significant changes in use over time. A >28% reduction in broad-spectrum penicillin prescribing occurred in each province from 1995 to 2010, and a >18% reduction in cephalosporin prescribing occurred in all provinces from 1995 to 2010, with the exception of Manitoba, where cephalosporin prescribing increased by 18%. DISCUSSION: Significant reductions in the use of these important drugs were observed across Canada from 1995 to 2010. Newfoundland and Labrador and Quebec emerged as divergent from the remaining provinces, with high and low use, respectively.

INTRODUCTION: Les ß-lactamines représentent le groupe d'antimicrobiens le plus prescrit au Canada et, d'après l'OMS, elles revêtent une importance capitale en médecine humaine. Puisque l'utilisation d'antimicrobiens s'associe souvent au développement d'une résistance antimicrobienne, il est essentiel de surveiller le volume et les modes d'utilisation de ces agents. OBJECTIF: Évaluer l'utilisation de pénicilline et de céphalosporines au sein des provinces canadiennes entre 1995 et 2010 selon deux mesures : les prescriptions par 1 000 habitants-jours et les doses théra-peutiques quotidiennes moyennes dispensées par prescription. MÉTHODOLOGIE: Les chercheurs ont extrait les données sur la prescription d'antimicrobiens du Programme intégré canadien de surveillance de la résistance aux antimicrobiens et du Comité canadien sur la résistance aux antibiotiques, et les données en population de Statistique Canada. À l'aide des deux mesures élaborées, ils ont produit des modèles linéaires mixtes pour évaluer les différences entre les provinces et dans le temps dans les groupes de pénicilline à large spectre et de céphalosporines, tout en tenant compte des mesures répétées sur la scène provinciale. RÉSULTATS: Les chercheurs ont constaté des différences significatives entre les provinces, ainsi que des changements importants d'utilisation dans le temps. Les prescriptions de pénicilline à large spectre ont diminué de plus de 28 % dans chaque province entre 1995 et 2010, et celles de céphalosporines ont reculé de plus de 18 % dans toutes les provinces entre 1995 et 2010, à l'exception du Manitoba, où les prescriptions de céphalosporines ont augmenté de 18 %. EXPOSÉ: Les chercheurs ont observé d'importantes réductions dans l'utilisation de ces médicaments au Canada entre 1995 et 2010. Terre-Neuve-et-Labrador et le Québec divergeaient des autres provinces, avec un usage élevé et faible, respectivement.

Longitudinal surveillance of outpatient tetracycline, sulfonamide-trimethoprim and 'other' antimicrobial use in Canada, 1995 to 2010.

INTRODUCTION: Monitoring the volume and patterns of use of antimicrobial agents is important in light of antimicrobial resistance. OBJECTIVE: To assess the use of three antimicrobial groups - tetracycline, sulfonamide-trimethoprim and 'other' antimicrobials - within Canadian provinces over time. METHODS: Prescription counts from 1995 to 2010 were acquired for the tetracycline and sulfonamide-trimethoprim groups of antimicrobials, and from 2001 to 2010 for the 'other' antimicrobial group. Linear mixed models were produced to assess differences among provinces and over time while accounting for repeated measurements. Prescription rate, defined daily dose per 1000 inhabitant-days and defined daily doses per prescription measures for the year 2009 were also compared with those reported by participating European Union countries to determine where Canadian provinces rank in terms of antimicrobial use among these countries. RESULTS: Prescribing of all three groups varied according to province and over time. Tetracycline and sulfonamide-trimethoprim group prescribing were significantly reduced over the study period, by 36% and 61%, respectively. Prescribing of the 'other' antimicrobial group increased in all provinces from 2001 to 2010 with the exception of Prince Edward Island, although by varying amounts (10% to 61% increases). DISCUSSION: The overall use of antimicrobials in Canada has dropped from 1995 to 2010, and the tetracycline and sulfonamide-trimethoprim groups have contributed to this decline. The use of the 'other' antimicrobials has increased, however. These results may suggest that switches are being made among these groups, particularly among the antimicrobials used to treat urinary tract infections.

INTRODUCTION: Il est important de surveiller le volume et le mode d'utilisation des antimicrobiens compte tenu de la résistance antimicrobienne. OBJECTIF: Évaluer l'utilisation de trois groupes d'antimicrobiens, soit la tétracycline, la sulfonamide-triméthoprime et d'« autres ¼ antimicrobiens dans les provinces canadiennes au fil du temps. MÉTHODOLOGIE: Les chercheurs ont obtenu le nombre de prescriptions des groupes de tétracycline et de sulfonamide-triméthoprime entre 1995 et 2010 et du groupe d'« autres ¼ antimicrobiens entre 2001 et 2010. Ils ont produit des modèles linéaires mixtes pour évaluer les différences entre les provinces et dans le temps tout en tenant compte des mesures répétées. Ils ont également comparé le taux de prescriptions, les doses quotidiennes définies par 1 000 habitants-jours et les doses quotidiennes définies par mesures de prescription à ceux des pays participants de l'Union européenne en 2009 pour déterminer le classement des provinces canadiennes en matière d'utilisation d'antimicrobiens au sein de ces pays. RÉSULTATS: Les prescriptions des trois groupes de médicaments variaient selon la province et dans le temps. La prescription des groupes de tétracycline et de sulfonamide-triméthoprime a diminué considérablement pendant la période de l'étude, soit de 36 % et de 61 %, respectivement. La prescription du groupe d'« autres ¼ antimicrobiens a augmenté dans toutes les provinces entre 2001 et 2010, à l'exception de l'Île-du-Prince-Édouard, mais selon des taux différents (augmentations de 10 % à 61 %). EXPOSÉ: L'utilisation globale d'antimicrobiens a diminué au Canada entre 1995 et 2010, et les groupes de tétracycline et de sulfonamide-triméthoprime y ont contribué. L'utilisation d'« autres ¼ antimicrobiens a toutefois augmenté. Ces résultats laissent peut-être supposer des substitutions entre ces groupes, notamment entre les antimicrobiens utilisés pour soigner les infections urinaires.

MDRO Beijing Consensus Meeting Report: Global burden of multidrug-resistant organisms' current antimicrobial resistance problems in Asia-Pacific.

The International Society of Chemotherapy's Working Groups on Antibiotic Resistance and Antibiotic Stewardship convened a half-day workshop on the burden of multidrug-resistant organisms in the Asia-Pacific. This short review is a summary of their discussion and conclusions.

Administration of low dose methamphetamine 12 h after a severe traumatic brain injury prevents neurological dysfunction and cognitive impairment in rats.

We recently published data that showed low dose of methamphetamine is neuroprotective when delivered 3 h after a severe traumatic brain injury (TBI). In the current study, we further characterized the neuroprotective potential of methamphetamine by determining the lowest effective dose, maximum therapeutic window, pharmacokinetic profile and gene expression changes associated with treatment. Graded doses of methamphetamine were administered to rats beginning 8 h after severe TBI. We assessed neuroprotection based on neurological severity scores, foot fault assessments, cognitive performance in the Morris water maze, and histopathology. We defined 0.250 mg/kg/h as the lowest effective dose and treatment at 12 h as the therapeutic window following severe TBI. We examined gene expression changes following TBI and methamphetamine treatment to further define the potential molecular mechanisms of neuroprotection and determined that methamphetamine significantly reduced the expression of key pro-inflammatory signals. Pharmacokinetic analysis revealed that a 24-hour intravenous infusion of methamphetamine at a dose of 0.500 mg/kg/h produced a plasma Cmax value of 25.9 ng/ml and a total exposure of 544 ng/ml over a 32 hour time frame. This represents almost half the 24-hour total exposure predicted for a daily oral dose of 25mg in a 70 kg adult human. Thus, we have demonstrated that methamphetamine is neuroprotective when delivered up to 12 h after injury at doses that are compatible with current FDA approved levels.

Declines in outpatient antimicrobial use in Canada (1995-2010).

BACKGROUND: With rising reports of antimicrobial resistance in outpatient communities, surveillance of antimicrobial use is imperative for supporting stewardship programs. The primary objective of this article is to assess the levels of antimicrobial use in Canada over time. METHODS: Canadian antimicrobial use data from 1995 to 2010 were acquired and assessed by four metrics: population-adjusted prescriptions, Defined Daily Doses, spending on antimicrobials (inflation-adjusted), and average Defined Daily Doses per prescription. Linear mixed models were built to assess significant differences among years and antimicrobial groups, and to account for repeated measurements over time. Measures were also compared to published reports from European countries. RESULTS: Temporal trends in antimicrobial use in Canada vary by metric and antimicrobial grouping. Overall reductions were seen for inflation-adjusted spending, population-adjusted prescription rates and Defined Daily Doses, and increases were observed for the average number of Defined Daily Doses per prescription. The population-adjusted prescription and Defined Daily Doses values for 2009 were comparable to those reported by many European countries, while the average Defined Daily Dose per prescription for Canada ranked high. A significant reduction in the use of broad spectrum penicillins occurred between 1995 and 2004, coupled with increases in macrolide and quinolone use, suggesting that replacement of antimicrobial drugs may occur as new products arrive on the market. CONCLUSIONS: There have been modest decreases of antimicrobial use in Canada over the past 15 years. However, continued surveillance of antimicrobial use coupled with data detailing antimicrobial resistance within bacterial pathogens affecting human populations is critical for targeting interventions and maintaining the effectiveness of these products for future generations.

"Ten Commandments" for the Appropriate use of Antibiotics by the Practicing Physician in an Outpatient Setting.

A multi-national working group on antibiotic stewardship, from the International Society of Chemotherapy, put together ten recommendations to physicians prescribing antibiotics to outpatients. These recommendations are: (1) use antibiotics only when needed; teach the patient how to manage symptoms of non-bacterial infections; (2) select the adequate ATB; precise targeting is better than shotgun therapy; (3) consider pharmacokinetics and pharmacodynamics when selecting an ATB; use the shortest ATB course that has proven clinical efficacy; (4) encourage patients' compliance; (5) use antibiotic combinations only in specific situations; (6) avoid low quality and sub-standard drugs; prevent prescription changes at the drugstore; (7) discourage self-prescription; (8) follow only evidence-based guidelines; beware those sponsored by drug companies; (9) rely (rationally) upon the clinical microbiology lab; and (10) prescribe ATB empirically - but intelligently; know local susceptibility trends, and also surveillance limitations.

Cytomegalovirus colitis following azacitidine therapy.

The present report describes the first recognized case of cytomegalovirus (CMV) colitis following azacitidine therapy. A 66-year-old woman with myelodysplastic syndrome developed CMV colitis, which responded to treatment with ganciclovir. Currently, patients receiving azacitidine do not undergo CMV testing, or receive prophylaxis or CMV-free blood products; however, this policy needs to be revised.

Postdated versus usual delayed antibiotic prescriptions in primary care: Reduction in antibiotic use for acute respiratory infections?

OBJECTIVE: To determine whether postdating delayed antibiotic prescriptions results in a further decrease (over usual delayed prescriptions) in antibiotic use. DESIGN: Randomized controlled trial. SETTING: A small rural town in Newfoundland and Labrador. PARTICIPANTS: A total of 149 consecutive adult primary care patients who presented with acute upper respiratory tract infections. INTERVENTION: Delayed prescriptions for patients who might require antibiotics were randomly dated either the day of the office visit (ie, the usual group) or 2 days later (ie, the postdated group). MAIN OUTCOME MEASURES: Whether or not the prescriptions were filled and the time it took for the patients to fill the prescriptions were noted by the 4 local pharmacies and relayed to the investigators. RESULTS: In total, 149 delayed antibiotic prescriptions were written, 1 per patient. Of the 74 usual delayed prescriptions given out, 32 (43.2%) were filled; of the 75 postdated delayed prescriptions given out, 33 (44.0%) were filled. Sixteen patients from each group filled their delayed prescriptions earlier than the recommended 48 hours. Statistical analyses-χ² tests to compare the rates of antibiotic use between the 2 groups and t tests to compare the mean time to fill the prescription between the 2 groups-indicated that these results were not significant (P > .05). CONCLUSION: Although delayed prescriptions reduce the rate of antibiotic use, postdating the delayed prescription does not seem to lead to further reduction in use.

Molecular characterization of moxifloxacin resistance from Canadian Clostridium difficile clinical isolates.

Fluoroquinolone resistance in Clostridium difficile has been implicated in recent outbreaks of C. difficile infection. The purpose of this report was to characterize the molecular mechanism conferring resistance to moxifloxacin among C. difficile clinical isolates. Eighty-four C. difficile clinical isolates (collected as part of the Canadian Nosocomial Infection Surveillance Program) were evaluated in the current study. Pulsed-field gel electrophoresis was used to type the isolates. Susceptibility testing was performed using Clinical and Laboratory Standards Institute agar dilution methods. The quinolone resistance-determining region of both gyrA and gyrB was amplified using polymerase chain reaction and sequenced for each isolate. The proportion of isolates studied by the North American pulsed-field (NAP) type was as follows: NAP1 (47.6%), NAP2 (20.2%), NAP3 (5.9%), NAP4 (4.8%), NAP5 (2.4%), NAP6 (3.6%), and other patterns (15.5%). All isolates were resistant to ciprofloxacin. Among moxifloxacin-susceptible isolates (MIC < or =2 microg/mL), no amino acid substitutions were detected in either GyrA or GyrB. Three distinct amino acid substitutions were observed among the 3 isolates that had a moxifloxacin MIC of 8 microg/mL (GyrA Asp71 to Val, GyrB Asp426 to Asn, or Glu466 to Val). Isolates with a moxifloxacin MIC of 16 or 32 microg/mL (moderate-level resistance) all had a single identical amino acid substitution in GyrA (Thr82 to Ile). For isolates with a moxifloxacin MIC of > or =64 microg/mL (high-level resistance), this Thr82 to Ile substitution in GyrA was accompanied by at least 1 other amino acid substitution in either GyrA (Asp71 to Glu, Pro116 to Ala, or Ala118 to Ser) or GyrB (Ser366 to Ala, Asp426 to Asn, Asp426 to Val, or Leu444 to Phe) in all but 1 case. Moderate-level moxifloxacin resistance was associated with a single substitution in GyrA. High-level moxifloxacin resistance was associated with this GyrA substitution plus at least 1 other substitution in GyrA or GyrB.

Hypervirulent Clostridium difficile strains in hospitalized patients, Canada.

To determine the incidence rate of infections with North American pulsed-field types 7 and 8 (NAP7/NAP8) strains of Clostrodium difficile, ribotype 078, and toxinotype V strains, we examined data collected for the Canadian Nosocomial Infections Surveillance Program (CNISP) CDI surveillance project during 2004-2008. Incidence of human infections increased from 0.5% in 2004/2005 to 1.6% in 2008.

Burkholderia cepacia infection of the prostate caused by inoculation of contaminated ultrasound gel during transrectal biopsy of the prostate.

Burkholderia cepacia infection of the prostate is very rare. We report 6 cases of prostatic infection secondary to inoculation of contaminated ultrasound gel during transrectal biopsy of the prostate. All of these patients required hospitalization and were treated with intravenous antibiotics. One of these cases is the first description of chronic prostatitis with B. cepacia.

Glycemic control prevents microvascular remodeling and increased tone in type 2 diabetes: link to endothelin-1.

Medial thickening and vascular hypertrophy of resistance arteries can lead to cardiovascular complications associated with diabetes. While previous studies have established a role of type 1 diabetes in vascular remodeling, we recently extended these observations to type 2 diabetes and reported increased collagen deposition due to alterations in matrix metalloproteinase expression and activity in mesenteric resistance arteries. These studies also showed that remodeling response was mediated by endothelin-1 (ET-1) via activation of ET(A) receptors, whereas blockade of ET(B) receptors exacerbated the remodeling. However, the effectiveness of glycemic control strategies in preventing these vascular changes, including activation of the ET system still remained unclear. Also, very little is known about whether and to what extent reorganization of the extracellular matrix (ECM) affects vascular compliance and vasomotor tone. Accordingly, this study assessed structural remodeling of mesenteric microvessels, vascular compliance, and myogenic tone, as well as the role of matrix metalloproteinases (MMP) in mediating these processes. Spontaneously diabetic, non-obese Goto-Kakizaki (GK) rats, a model for type 2 diabetes, and normoglycemic Wistar rats were used for the studies. A subset of GK rats were administered metformin to achieve euglycemia. Glycemic control normalized the increased media-to-lumen ratios (M/L) and myogenic tone seen in diabetes, as well as normalizing plasma ET-1 levels and mesenteric ET(A) receptor expression. There was increased collagen synthesis in diabetes paralleled by decreased collagenase MMP-13 activity, while glycemic control attenuated the process. These findings and our previous study taken together suggest that hyperglycemia-mediated activation of ET-1 and ET(A) receptors alter vascular structure and mechanics in type 2 diabetes.

Differential effects of diet-induced dyslipidemia and hyperglycemia on mesenteric resistance artery structure and function in type 2 diabetes.

Type 2 diabetes and dyslipidemia oftentimes present in combination. However, the relative roles of diabetes and diet-induced dyslipidemia in mediating changes in vascular structure, mechanics, and function are poorly understood. Our hypothesis was that addition of a high-fat diet would exacerbate small artery remodeling, compliance, and vascular dysfunction in type 2 diabetes. Vascular remodeling indices [media/lumen (M/L) ratio, collagen abundance and turnover, and matrix metalloproteinase dynamics], mechanical properties (vessel stiffness), and reactivity to pressure and vasoactive factors were measured in third-order mesenteric arteries in control Wistar and type 2 diabetic Goto-Kakizaki (GK) rats fed either a regular or high-fat diet. M/L ratios, total collagen, and myogenic tone were increased in diabetes. Addition of the high-fat diet altered collagen patterns (mature versus new collagen) in favor of matrix accumulation. Addition of a high-fat diet caused increased constriction to endothelin-1 (0.1-100 nM), showed impaired vasorelaxation to both acetylcholine (0.1 nM-1 microM) and sodium nitroprusside (0.1 nM-1 microM), and increased cardiovascular risk factors in diabetes. These results suggest that moderate elevations in blood glucose, as seen in our lean GK model of type 2 diabetes, promote resistance artery remodeling resulting in increased medial thickness, whereas addition of a high-fat diet contributes to diabetic vascular disease predominantly by impairing vascular reactivity in the time frame used for this study. Although differential in their vascular effects, both hyperglycemia and diet-induced dyslipidemia need to be targeted for effective prevention and treatment of diabetic vascular disease.

Effect of chronic and selective endothelin receptor antagonism on microvascular function in type 2 diabetes.

Vascular dysfunction, which presents either as an increased response to vasoconstrictors or an impaired relaxation to dilator agents, results in worsened cardiovascular outcomes in diabetes. We have established that the mesenteric circulation in Type 2 diabetes is hyperreactive to the potent vasoconstrictor endothelin-1 (ET-1) and displays increased nitric oxide-dependent vasodilation. The current study examined the individual and/or the relative roles of the ET receptors governing vascular function in the Goto-Kakizaki rat, a mildly hyperglycemic, normotensive, and nonobese model of Type 2 diabetes. Diabetic and control rats received an antagonist to either the ET type A (ETA; atrasentan; 5 mg x kg(-1) x day(-1)) or type B (ET(B); A-192621; 15 or 30 mg x kg(-1) x day(-1)) receptors for 4 wk. Third-order mesenteric arteries were isolated, and vascular function was assessed with a wire myograph. Maximum response to ET-1 was increased in diabetes and attenuated by ETA antagonism. ETB blockade with 15 mg/kg A-192621 augmented vasoconstriction in controls, whereas it had no further effect on ET-1 hyperreactivity in diabetes. The higher dose of A-192621 showed an ETA-like effect and decreased vasoconstriction in diabetes. Maximum relaxation to acetylcholine (ACh) was similar across groups and treatments. ETB antagonism at either dose had no effect on vasorelaxation in control rats, whereas in diabetes the dose-response curve to ACh was shifted to the right, indicating a decreased relaxation at 15 mg/kg A-192621. These results suggest that ETA receptor blockade attenuates vascular dysfunction and that ETB receptor antagonism exhibits differential effects depending on the dose of the antagonists and the disease state.

Evidence for vasculoprotective effects of ETB receptors in resistance artery remodeling in diabetes.

OBJECTIVE: Vascular remodeling, characterized by extracellular matrix deposition and increased media-to-lumen (M/l) ratio, contributes to the development of microvascular complications in diabetes. Matrix metalloproteinases (MMPs) play an important role in the regulation of extracellular matrix (ECM) turnover and vascular remodeling. Vasoactive factor endothelin (ET)-1 not only causes potent vasoconstriction but also exerts profibrotic and proliferative effects that change vessel architecture, which makes it a likely candidate for a key role in vascular complications of diabetes. Thus, this study investigated the regulation of MMP activity of resistance arteries under mild-to-moderate diabetes conditions, as seen in type 2 diabetes, and the relative role of ET receptors in this process. RESEARCH DESIGN AND METHODS: Vessel structure, MMP activity, and ECM proteins were assessed in control Wistar and diabetic Goto-Kakizaki (GK) rats treated with vehicle, ET(A) receptor antagonist atrasentan (5 mg x kg(-1) x day(-1)), or ET(B) receptor antagonist A-192621 (15 mg x kg(-1) x day(-1)) for 4 weeks. RESULTS: M/l ratio was increased in diabetes. Atrasentan prevented this increase, whereas A-192621 caused further thickening of the medial layer. Increased MMP-2 activity in diabetes was prevented by atrasentan treatment. Collagenase activity was significantly decreased in diabetes, and while ET(A) antagonism improved enzyme activity, ET(B) blockade further reduced collagenase levels. Accordingly, collagen deposition was augmented in GK rats, which was reversed by atrasentan but exacerbated with A-192621. CONCLUSIONS: ET-1 contributes to the remodeling of mesenteric resistance arteries in diabetes via activation of ET(A) receptors, and ET(B) receptors provide vasculoprotective effects.

A fatal case of Staphylococcus aureus: associated toxic shock syndrome following nipple piercing.

We describe a case of a healthy adolescent with a fatal toxic shock syndrome due to Staphylococcus aureus. This infection developed 2 weeks after the patient underwent a nipple piercing by a friend. This case should serve as a strong reminder of the potentially fatal consequences of piercing that is becoming increasingly popular worldwide.