BACKGROUND:Ciprofloxacin is one of the few orally available antibiotics with activity against Pseudomonas aeruginosa. This study developed a population pharmacokinetic (popPK) model for oral ciprofloxacin in older adults and evaluated whether standard regimens achieve the pharmacokinetic/pharmacodynamic (PK/PD) target of 24 h area under the concentration-time curve over minimal inhibitory concentration (AUC0-24/MIC) ≥ 125. METHODS:This was a prospective pilot study in patients ≥75 years taking oral ciprofloxacin at the McGill University Health Centre, Canada. Plasma samples were collected at steady state (peak, mid-interval, trough) and data fitting was performed using NONMEM with stochastic approximation expectation-maximization. Monte Carlo simulations (n = 1000) assessed the probability of target attainment (PTA) for standard dosing regimens of 250-750 mg q12h across MICs of 0.125-2 mg/L. RESULTS:Fifteen patients (median age 82 years, weight 75 kg, creatinine clearance 46 mL/min) contributed 42 plasma concentrations to the analysis. A one-compartment model with first-order absorption and elimination best described the data. Population mean apparent clearance and volume of distribution were 14.3 L/h and 247 L, respectively (resulting in a 12 h half-life), with high interindividual variability (IIV: 75.2% and 36.0%). The absorption rate constant was fixed to 2.5 h-1. No covariate effects were retained in the final model. At the P. aeruginosa clinical MIC breakpoint of 0.5 mg/L, standard regimens achieved PTAs of 18.7% (250 mg q12h), 56.6% (500 mg q12h), and 76.5% (750 mg q12h). CONCLUSIONS:This first popPK model for oral ciprofloxacin specifically in older adults demonstrates that simulated standard dosing regimens fail to achieve PK/PD targets for P. aeruginosa. The large IIV, increased drug exposure and low target attainment support implementation of therapeutic drug monitoring in this population.

The Canadian Nosocomial Infection Surveillance Program piloted a study assessing inter-rater agreement among a point prevalence survey (PPS) of healthcare-associated infections and antimicrobial use in acute care hospitals across Canada. Results of this study revealed areas for improvement to be considered in future PPS methodology.

This study explores antimicrobial use (AMU) in a voluntary sample of Canadian adult hematology/oncology wards between 2018 and 2023. Although use of third- and fourth-generation cephalosporins significantly increased, overall AMU decreased by 25%. As trends change over time, ongoing surveillance is needed to guide AMU optimization in this high-risk setting.

Objective: Immunocompromised patients are at increased risk of bacterial and viral respiratory infections and related complications. Available vaccines against these infections are the most effective tools in preventing complications. Community pharmacist vaccination service is evolving in many countries, and they could present an opportunity to improve vaccination coverage in this population. This study aims to describe how community pharmacists are involved in vaccinating high-risk (immunocompromised) populations. Methods: This retrospective study included vaccination information of patients who received chronic immunosuppressive therapy among those who were taking selected chronic medications from community pharmacies in Montreal, Canada, from January 2020 to September 2023. Immunosuppressive therapy was categorized as either corticosteroids or immunosuppressive drugs or the combination of corticosteroids with one or two immunosuppressive drugs. Data were available from all private pharmacies through the Quebec Association of Pharmacists Owners database. Descriptive statistics are used for data analysis. Findings: Of the total number of 4,114,528 patients who were taking selected chronic medications from community pharmacies, 611,789 (14.8%) were taking immunosuppressives. Prednisone/prednisolone was the most commonly administered drug in this population (345,744 [8.4%]). Most of these patients are aged over 50 years (484,827 [79.2%]). A total of 409,171 (66.8%) co-administered at least one other drug. The vaccination rate was highest for influenza (142,877 [23.3%]) and lowest (23,532 [3.8%]) with the pneumococcus vaccine. Patients younger than 25 had the lowest vaccination rate with three respiratory vaccines. Vaccination rate decreased after the pandemic with all three vaccines in our study population. Conclusion: Vaccination rates of patients taking chronic immunosuppressive drugs in community pharmacies are low. These rates are worse than rates for other high-risk groups from the same database. This represents a missed opportunity for pharmacists to encourage this high-risk population to vaccinate proactively.

In a recent simulation-based study, we found that sample size had minimal influence on the external evaluation of population pharmacokinetic (PK) models. However, the applicability of these findings to clinical data remains unexplored. This study aims to validate our previous simulation-based results using real-world clinical data. Data from a prospective clinical study in the > 75-year-old population admitted to the McGill University Health Center (MUHC) receiving piperacillin/tazobactam were collected. A virtual population of 1000 patients representative of the characteristics of MUHC patients was also simulated. A population PK model was externally evaluated both using the small clinical dataset and a larger simulated dataset. The predictive performance of the model was assessed using bias, imprecision, goodness-of-fit plots (GOF), and prediction-corrected visual predictive checks (pcVPC). The distribution of prediction errors between the clinical and simulated datasets was compared using the Wilcoxon rank-sum test. Data from 13 patients undergoing piperacillin/tazobactam therapy were collected. The Ishihara et al. model showed low bias (2.4

Background:The impact of the COVID-19 pandemic on antimicrobial use in Canadian hospitals is not well characterized. We explored the relationship between the COVID-19 pandemic and Canadian hospital antimicrobial purchasing (AMP)-a proxy for consumption. Methods:Hospital-level AMP data were obtained from IQVIA, a health analytics company, and matched with inpatient patient-day denominator data from 28 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Monthly AMP was measured using defined daily doses (DDDs) per 1,000 patient-days. Segmented linear regression with hospital-level clustering assessed for step and slope changes in AMP between pre-pandemic (January 1, 2018 - February 29, 2020) and pandemic (March 1, 2020 - December 31, 2021) periods. Results:Although we found an initial increase in AMP with the onset of the pandemic (+42 DDDs/1,000 patient-days [pd]) followed by a decreasing trend in AMP during the pandemic (-5 DDDs/1,000 pd per month), neither was statistically significant. Changes in trends varied across antimicrobial classes/subclasses, with decreases in broad-spectrum penicillins (-2 DDDs/1,000 pd per month, p < .001) and macrolides/lincosamides (-2 DDDs/1,000 pd per month, p < .001) and an increase in carbapenems (1 DDD/1,000 pd per month, p < .001). These results coincided with decreases in piperacillin/tazobactam (p = .003) and azithromycin (p = .001) and an increase in meropenem (p < .001). Conclusions:We observed a transient increase in overall AMP with the onset of the pandemic (March 2020) in this exploratory analysis of a sample of 28 hospitals. Changes in trends varied by antimicrobial class/subclass and individual agent. Further work is needed to discern contributors to these trends, such as changes in inpatient characteristics and treatment guidelines.

Background:Antimicrobial use data from inpatients in northern Canada suitable to inform stewardship programs are limited. Objective:As a special project of the Canadian Nosocomial Infection Surveillance Program, to describe antimicrobial use for inpatients in northern Canadian acute care hospitals. Methods:Participating acute care hospitals serving adult or mixed adult and pediatric populations in northern Canada submitted annual data on the use of all systemic antimicrobials from 2019 to 2021. Patient-day denominators were also submitted. Northern Canada was defined as the territories and Statistics Canada's provincial north. Data were analyzed in terms of defined daily doses per 1000 patient days (DDD/1000pd), as per the Anatomical Therapeutic Chemical classification system. Antimicrobials were categorized using the World Health Organization's AWaRe (Access/ Watch/Reserve) classification system. Results:Each year, 42-47 hospitals participated. More than 90% of participating hospitals were in Alberta or British Columbia. There was large variation in overall antimicrobial use between hospitals (e.g., interquartile range 429 to 779 DDD/1000pd in 2021). From 2019 to 2021, there was a 49% relative increase in antimicrobial use, from 401 to 596 DDD/1000pd (p = 0.11). Over the same period, the use of third- and first-generation cephalosporins increased by 80% and 64%, respectively; antimicrobials in the "Reserve" category increased from 0.4% to 2% of overall use. Conclusions:This study represents the largest collection of antimicrobial use data for inpatients in northern Canada to date. From 2019 to 2021, there was an increase in antimicrobial use of 195 DDD/1000pd, largely driven by increases in the use of third- and first-generation cephalosporins. The findings should be interpreted with caution, as results may not be generalizable to all northern hospitals.

Background: Undervaccination is a public health issue that disproportionately affects underserved populations. Pharmacists are accessible health care professionals who have the potential to better reach communities. The aim of this study is to understand how organizational obstacles influence the pharmacist's ability to meet underserved clients' vaccination needs in community pharmacy.Methods: We conducted semi-structured interviews with key stakeholders in Quebec. Results were codified according to domains of the Consolidated Framework for Implementation Research.Results: Fourteen interviews were carried out with representatives from pharmacy associations, pharmacy chains and banners, integrated health and social service centres, and local Quebec Public Health departments. Barriers to promoting vaccination were identified in four areas: 1) vaccine service logistics, 2) the pharmacy setting, 3) external influences and 4) pharmacist's knowledge and beliefs.Discussion: Technological tools accessible to pharmacists are sufficient but not user-friendly due to the lack of integration between the pharmacy software, the vaccine registry and the provincial appointment system. Technology limits access to vaccination for certain underserved populations. Moreover, the incentives linked to vaccination do not favour the vaccination of difficult-to-reach clients and they limit pharmacists' ability to be proactive with vaccine recommendations. Pharmacists are more inclined to participate in mass vaccination campaigns, and delegating vaccine administration to nurses and technicians allows pharmacies to financially break even. Certain services such as travel health vaccination require an extended set of knowledge, which creates resistance for some pharmacists to integrate the role.Conclusion: Pharmacists are well-placed to improve vaccination uptake, but several technological and organizational barriers limit their ability to provide vaccination services and reach underserved communities. A better alignment between incentives and proactive promotion should be put forward to encourage pharmacists to actively identify and reach underserved populations.

Objective:To describe the epidemiology of healthcare-associated Clostridioides difficile infection (HA-CDI) in two Québec hospitals in Canada following the 2003 epidemic and to evaluate the impact of antibiotic stewardship on the incidence of HA-CDI and the NAP1/027 strain.Design:Time-series analysis.Setting:Two Canadian tertiary care hospitals based in Montréal, Québec.Patients:Patients with a positive assay for toxigenic C. difficile were identified through infection control surveillance. All cases of HA-CDI, defined as symptoms occurring after 72 hours of hospital admission or within 4 weeks of hospitalization, were included.Methods:The incidence of HA-CDI and antibiotic utilization from 2003 to 2020 were analyzed with available C. difficile isolates. The impact of antibiotic utilization on HA-CDI incidence was estimated by a dynamic regression time-series model. Antibiotic utilization and the proportion of NAP1/027 strains were compared biannually for available isolates from 2010 to 2020.Results:The incidence of HA-CDI decreased between 2003 and 2020 at both hospitals from 26.5 cases per 10,000 patient-days in 2003 to 4.9 cases per 10,000 patient-days in 2020 respectively. Over the study period, there were an increase in the utilization of third-generation cephalosporins and a decrease in usage of fluoroquinolones and clindamycin. A decrease in fluoroquinolone utilization was associated with a significant decrease in HA-CDI incidence as well as decrease in the NAP1/027 strain by approximately 80% in both hospitals.Conclusions:Decreased utilization of fluoroquinolones in two Québec hospitals was associated with a decrease in the incidence of HA-CDI and a genotype shift from NAP1/027 to non-NAP1/027 strains.

ABSTRACT:Tobramycin is widely used to treat pulmonary exacerbations of cystic fibrosis. Height has been previously found to be significantly more predictive of tobramycin pharmacokinetics than body weight. This study aimed to develop a height-based initial dosing nomogram and evaluate its performance in peak concentration (Cmax) precision relative to standard and fixed dosing. Monte Carlo simulations were performed to develop a nomogram representing the doses required to reach Cmax targets at different heights. Cmax data observed at 2 clinical centers [McGill University Health Centre (MUHC) and Institut universitaire de cardiologie et pneumologie de Québec (IUCPQ-UL)] were compared with population-predicted Cmax using the doses derived from the nomogram alongside a fixed dose. Height-based dosing resulted in significantly less variable-predicted Cmax values [coefficient of variation (CV) MUHC = 15.7% and IUCPQ-UL = 10.8%] than the Cmax values observed in clinical practice (CV MUHC = 30.0% and CV IUCPQ-UL = 26.9%) and predicted Cmax values obtained from a fixed dose (CV MUHC = 21.2% and CV IUCPQ-UL = 16.3%). An initial dosing nomogram was developed to help reduce pharmacokinetic variability in the observed Cmax. More precise dosing would allow for better clinical outcomes in adult patients with cystic fibrosis.

Context Social determinants of health are drivers of vaccine inequity and lead to higher risks of complications from infectious diseases in under vaccinated communities. In many countries, pharmacists have gained the rights to prescribe and administer vaccines, which contributes to improving vaccination rates. However, little is known on how they define and target vulnerable communities. Objective The purpose of this study is to describe how vulnerable communities are targeted in community pharmacies. Methods We performed a systematic search of the Embase and MEDLINE database in August 2021 inspired by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocols (PRISMA ScR). Articles in English, French or Spanish addressing any vaccine in a community pharmacy context and that target a population defined as vulnerable were screened for inclusion. Results A total of 1039 articles were identified through the initial search, and 63 articles met the inclusion criteria. Most of the literature originated from North America ( n = 54, 86%) and addressed influenza ( n = 29, 46%), pneumococcal ( n = 14, 22%), herpes zoster ( n = 14, 22%) or human papilloma virus vaccination ( n = 14, 22%). Lifecycle vulnerabilities ( n = 48, 76%) such as age and pregnancy were most often used to target vulnerable patients followed by clinical factors ( n = 18, 29%), socio-economical determinants ( n = 16, 25%) and geographical vulnerabilities ( n = 7, 11%). The most frequently listed strategy was providing a strong recommendation for vaccination, promotional posters in pharmacy, distributing leaflet/bag stuffers and providing staff training. A total of 24 barriers and 25 facilitators were identified. The main barriers associated to each vulnerable category were associated to effective promotional strategies to overcome them. Conclusion Pharmacists prioritize lifecycle and clinical vulnerability at the expense of narrowing down the definition of vulnerability. Some vulnerable groups are also under targeted in pharmacies. A wide variety of promotional strategies are available to pharmacies to overcome the specific barriers experienced by various groups.

BACKGROUND:Antimicrobial resistance threatens the ability to successfully prevent and treat infections. While hospital benchmarks regarding antimicrobial use (AMU) have been well documented among adult populations, there is less information from among paediatric inpatients. This study presents benchmark rates of antimicrobial use (AMU) for paediatric inpatients in nine Canadian acute-care hospitals.METHODS:Acute-care hospitals participating in the Canadian Nosocomial Infection Surveillance Program submitted annual AMU data from paediatric inpatients from 2017 and 2018. All systemic antimicrobials were included. Data were available for neonatal intensive care units (NICUs), pediatric ICUs (PICUs), and non-ICU wards. Data were analyzed using days of therapy (DOT) per 1000 patient days (DOT/1000pd).RESULTS:Nine hospitals provided paediatric AMU data. Data from seven NICU and PICU wards were included. Overall AMU was 481 (95% CI 409-554) DOT/1000pd. There was high variability in AMU between hospitals. AMU was higher on PICU wards (784 DOT/1000pd) than on non-ICU (494 DOT/1000pd) or NICU wards (333 DOT/1000pd). On non-ICU wards, the antimicrobials with the highest use were cefazolin (66 DOT/1000pd), ceftriaxone (59 DOT/1000pd) and piperacillin-tazobactam (48 DOT/1000pd). On PICU wards, the antimicrobials with the highest use were ceftriaxone (115 DOT/1000pd), piperacillin-tazobactam (115 DOT/1000pd), and cefazolin (111 DOT/1000pd). On NICU wards, the antimicrobials with the highest use were ampicillin (102 DOT/1000pd), gentamicin/tobramycin (78 DOT/1000pd), and cefotaxime (38 DOT/1000pd).CONCLUSIONS:This study represents the largest collection of antimicrobial use data among hospitalized paediatric inpatients in Canada to date. In 2017/2018, overall AMU was 481 DOT/1000pd. National surveillance of AMU among paediatric inpatients is necessary for establishing benchmarks and informing antimicrobial stewardship efforts.

Two sodium-dependent vitamin C transporter isoforms (SVCT1 and SVCT2) were identified as ascorbic acid transporters, but their roles in skin have, as yet, not been elucidated. Here we analyze the expression and function of SVCTs in healthy human skin cells and skin tissues, and in UVB-induced cutaneous tissue injury. SVCT1 was primarily found in the epidermis expressed by keratinocytes, whereas SVCT2 expression was in the epidermis and dermis in keratinocytes, fibroblasts, and endothelial cells. Uptake experiments revealed that ascorbic acid affinity of SVCT1 was lower than SVCT2 (K(m)=75 muM and K(m)=44 muM, respectively), but maximal velocity was 9-times higher (36 nmol/min/well). In keratinocytes, SVCT1 was found to be responsible for vitamin C transport, although SVCT2 gene expression was higher. On UVB irradiation, SVCT1 mRNA expression in murine skin declined significantly in a time- and dose-dependent manner, whereas SVCT2 mRNA levels were unchanged. Furthermore, UVB irradiation of keratinocytes in vitro was accompanied by reduced ascorbic acid transport. In summary, these data indicate that the two vitamin C transporter isoforms fulfill specific functions in skin: SVCT1 is responsible for epidermal ascorbic acid supply, whereas SVCT2 mainly facilitates ascorbic acid transport in the dermal compartment. UVB-induced oxidative stress in mice resulted in depletion of SVCT1 mRNA levels and led to significantly decreased ascorbic acid uptake in keratinocytes, providing evidence on why ascorbic acid levels are decreased on UVB irradiation in vivo.

Considering the aminoglycosides' characteristics in terms of efficacy and toxicity, multiple dosing recommendations and nomograms have been suggested over several decades. The objective is to describe the dosing and monitoring practices of amikacin, gentamicin, and tobramycin in critically ill patients across health care institutions in the province of Quebec.This survey was developed with multiple-choices and short answers and targeted the lead pharmacist responsible of antimicrobial stewardship in each health care institution.Gentamicin and tobramycin dosing regimens were in-line with guidelines from different countries. Amikacin was not commonly used in Quebec. Therapeutic targets were generally consistent with the literature.Dosing adaptation were mostly done based on clinician judgment or with homemade software. Given the variability seen across practices in Quebec institutions, standardization and optimization of aminoglycosides therapeutic drug monitoring may be considered.

BACKGROUND:Acute pulmonary exacerbations (APEs) in patients with adult cystic fibrosis (CF) are treated with a beta-lactam and an aminoglycoside for activity against Pseudomonas aeruginosa (PA). Emerging drug resistance and changing pharmacokinetic profile in an aging population involve a reevaluation of tobramycin dosing recommendations. The objective of this study was to develop a population pharmacokinetic model and establish optimal dosing recommendations for tobramycin using Monte Carlo simulations.METHODS:This retrospective clinical study and data collection were performed at the CF center of the McGill University Health Center (MUHC), Canada. Model development and simulations were performed using a nonlinear mixed-effect modeling approach (NONMEM, version 7.4.2). The ratios of maximal concentration (C max ) to the minimal inhibitory concentration (MIC) (C max /MIC ≥8 and ≥10) and area under the curve (AUC) to the MIC (AUC/MIC ≥70 and ≥100) were evaluated.RESULTS:Adult patients with CF (n = 51) treated with tobramycin were included in the study. Plasma concentrations of tobramycin were obtained for 699 samples from the MUHC database. The two-compartmental model best described the pharmacokinetics of tobramycin. The association of patient height with the central volume of distribution significantly improved this model. Height, rather than weight, induced the best reduction in objective function. According to simulations, doses between 3.4 mg/cm and 4.4 mg/cm were necessary to achieve C max /MIC values of ≥8 and ≥10, respectively. However, higher doses were required to achieve the AUC/MIC targets.CONCLUSIONS:This study demonstrated that height of the patients seems to be more suitable than their weight for dosing adjustments in adult patients with CF. According to this model, initial doses of tobramycin between 3.4 and 4.4 mg/cm should be recommended for patients with a median height of 164 cm and weight of 55 kg to achieve the target plasma concentrations.

The recently released revised vancomycin consensus guideline endorsed area under the concentration-time curve (AUC) guided monitoring. Means to AUC-guided monitoring include pharmacokinetic (PK) equations and Bayesian software programs, with the latter approach being preferable. We aimed to evaluate the predictive performance of these two methods when monitoring using troughs or peaks and troughs at varying single or mixed dosing intervals (DIs), and evaluate the significance of satisfying underlying assumptions of steady-state and model transferability. Methods included developing a vancomycin population PK model and conducting model-informed precision dosing clinical trial simulations. A one-compartment PK model with linear elimination, exponential between-subject variability, and mixed (additive and proportional) residual error model resulted in the best model fit. Conducted simulations demonstrated that Bayesian-guided AUC can, potentially, outperform that of equation-based AUC predictions depending on the quality of model diagnostics and met assumptions. Ideally, Bayesian-guided AUC predictive performance using a trough from the first DI was equivalent to that of PK equations using two measurements (peak and trough) from the fifth DI. Model transferability diagnostics can guide the selection of Bayesian priors but are not strong indicators of predictive performance. Mixed versus single fourth and/or fifth DI sampling seems indifferent. This study illustrated cases associated with the most reliable AUC predictions and showed that only proper Bayesian-guided monitoring is always faster and more reliable than equations-guided monitoring in pre-steady-state DIs in the absence of a loading dose. This supports rapid Bayesian monitoring using data as sparse and early as a trough at the first DI.

Abstract Objectives: The Canadian Nosocomial Infection Surveillance Program conducted point-prevalence surveys in acute-care hospitals in 2002, 2009, and 2017 to identify trends in antimicrobial use. Methods: Eligible inpatients were identified from a 24-hour period in February of each survey year. Patients were eligible (1) if they were admitted for ≥48 hours or (2) if they had been admitted to the hospital within a month. Chart reviews were conducted. We calculated the prevalence of antimicrobial use as follows: patients receiving ≥1 antimicrobial during survey period per number of patients surveyed × 100%. Results: In each survey, 28−47 hospitals participated. In 2002, 2,460 (36.5%; 95% CI, 35.3%−37.6%) of 6,747 surveyed patients received ≥1 antimicrobial. In 2009, 3,566 (40.1%, 95% CI, 39.0%−41.1%) of 8,902 patients received ≥1 antimicrobial. In 2017, 3,936 (39.6%, 95% CI, 38.7%−40.6%) of 9,929 patients received ≥1 antimicrobial. Among patients who received ≥1 antimicrobial, penicillin use increased 36.8% between 2002 and 2017, and third-generation cephalosporin use increased from 13.9% to 18.1% (P < .0001). Between 2002 and 2017, fluoroquinolone use decreased from 25.7% to 16.3% (P < .0001) and clindamycin use decreased from 25.7% to 16.3% (P < .0001) among patients who received ≥1 antimicrobial. Aminoglycoside use decreased from 8.8% to 2.4% (P < .0001) and metronidazole use decreased from 18.1% to 9.4% (P < .0001). Carbapenem use increased from 3.9% in 2002 to 6.1% in 2009 (P < .0001) and increased by 4.8% between 2009 and 2017 (P = .60). Conclusions: The prevalence of antimicrobial use increased between 2002 and 2009 and then stabilized between 2009 and 2017. These data provide important information for antimicrobial stewardship programs.

Background Acute pulmonary exacerbation (APE) in cystic fibrosis patients is frequent and associated with a decline in pulmonary function, quality of life and survival. Tobramycin is often used in regimens requiring activity against Pseudomonas aeruginosa, however, an important number of centers do not use official dosing recommendation. The current dosing strategy may be suboptimal. Methods This retrospective cohort analysis was performed on all adult cystic fibrosis patients that were admitted at a tertiary care facility for treatment of APE and with tobramycin between January 2015 and December 2019. The primary objective was to evaluate the predictive performance of previously published pharmacokinetic (PK) models and, secondly, to evaluate potential factors that impact clinical outcomes. Clinical outcomes were only evaluated in a sub-group of patients with cultures positive for P. aeruginosa. Results A total of 202 APEs from 51 patients were included in the PK analysis. Two population PK models were assessed and failed to fit our data. In all, 109 APEs from 32 patients were included in the clinical analysis. Factors that significantly impacted clinical outcome were the number of prior APE and concomitant antibiotics. Clinical success rate for regimens containing at least one active agent against P. aeruginosa according to its susceptibility was 67%. Conclusion Population PK models evaluated in this study cannot be used to perform simulations. A new model must be developed for our population. In patients positive for P. aeruginosa, Ceftazidime in combination to tobramycin may be a superior regimen. APE history remains predictive for outcomes in adult CF patients treated for an APE.

The purpose of this study was to evaluate the impact of augmented prophylaxis (ciprofloxacin augmented with an aminoglycoside) compared with that of empirical prophylaxis (ciprofloxacin alone) on transrectal post-prostate biopsy infectious complication (PBIC) rates. A retrospective cohort study evaluated 2835 patients receiving either augmented or empirical prophylactic regimen before undergoing a transrectal ultrasound-guided prostate biopsy between January 2010 and October 2018. The patients were compared according to prophylactic regimen received. The incidence of PBICs and the impact of risk factors were evaluated. A total of 1849 patients received the empirical regimen, and 986 patients received the augmented regimen. The composite PBIC rate was 2.1% (n = 39) and 0.9% (n = 9) (p = 0.019), respectively, and the SIRS rate was 1.9% and 0.8% (p = 0.020), respectively. Of the 50 patients presenting with a PBIC, 29 (58%) had positive cultures (blood and/or urine) for Escherichia coli, of which 28 (97%) were ciprofloxacin-resistant. Taking a fluoroquinolone in the previous 6 months and having a previous urinary tract infection within 1 year prior to the biopsy had significant impact on PBIC rates (p = 0.009 and p = 0.011, respectively). Compared with ciprofloxacin alone, augmented prophylaxis was associated with significantly lower PBICs.

Background: The revised vancomycin guidelines recommend replacing trough-only with trough or peak/trough Bayesian and first-order equations monitoring, citing their better AUC predictions and poor AUC-trough R2. Yet, evidence suggesting good AUC-trough correlation has been overlooked, and the optimality of peak/trough samples has been doubted. The guidelines recommend Bayesian programs implement richly-sampled PopPK priors despite their scarcity. Therefore, whether complex Bayesian and sample-demanding first-order equations can bring significant advantages to the practice over simple trough-only monitoring is worth weighing. Objectives: The primary aim is to compare the predictive performance of the AUC monitoring methods. Then, we investigate the impact of not adhering to trough sampling on the Bayesian-based predictions. Moreover, we report the nature of PopPK priors used in Bayesian programs to assess the applicability of the guideline recommendations. Methods: We calculated the predictive performance of the monitoring methods using a standard PopPK modeling and simulation approach. We thoroughly explored the prior PK models implemented in Bayesian programs. Results: Predictive performances of the monitoring methods were comparable at steady-state relative to the number of samples. Contrary to the recommendation, Bayesian trough monitoring did not result in better predictive performances compared to using random levels. Very few programs implemented richly-sampled priors. Conclusion: All the monitoring methods can be, relatively, reliable at steady-state, if properly implemented. Although only Bayesian-based monitoring can be used pre-steady-state, its predictive performance can be modest. Trough-only monitoring is the simplest approach. Constraints regarding trough sampling times could be relaxed. The scarcity of richly-sampled Bayesian priors questions the applicability of the revised guidelines recommendation.