Exposure levels and target attainment of piperacillin/tazobactam in adult patients admitted to the intensive care unit: a prospective observational study.

PURPOSE: The objective of this study was to evaluate the exposure and the pharmacodynamic target attainment of piperacillin/tazobactam (PTZ) in adult critically ill patients. METHODS: We conducted a prospective observational study in the intensive care unit (ICU) of the Hôpital du Sacré-Cœur de Montréal (a Level I trauma centre in Montreal, QC, Canada) between January 2021 and June 2022. We included patients aged 18 yr or older admitted to the ICU who received PTZ by intravenous administration. Demographic and clinical characteristics were collected, and clinical scores were calculated. On study day 1 of antimicrobial therapy, three blood samples were collected at the following timepoints: one hour after PTZ dose administration and at the middle and at the end of the dosing interval. The sampling schedule was repeated on days 4 and 7 of therapy if possible. Samples were analyzed by ultra-high performance liquid chromatography with diode array detector to determine the total piperacillin concentration. Middle- and end-of-interval concentrations were used for target attainment analyses, and were defined as a concentration above the minimal inhibitory concentration of 16 mg·L-1, corresponding to the breakpoint of Enterobacteriaceae and Pseudomonas aeruginosa. RESULTS: Forty-three patients were recruited and 202 blood samples were analyzed. The most prevalent dose was 3/0.375 g every six hours (n = 50/73 doses administered, 68%) with a 30-min infusion. We observed marked variability over the three sampling timepoints, and the median [interquartile range] piperacillin concentrations at peak, middle of interval, and end of interval were 109.4 [74.0-152.3], 59.3 [21.1-74.4], and 25.3 [6.8-44.6] mg·L-1, respectively. When assessing target attainment, 37% of patients did not reach the efficacy target of a trough concentration of 16 mg·L-1. The majority of patients who were underexposed were patients with normal to augmented renal clearance. CONCLUSION: In this prospective observational study of adult ICU patients receiving intravenous PTZ, a large proportion had subtherapeutic concentrations of piperacillin. This was most notable in patients with normal to augmented renal clearance. More aggressive dosage regimens may be required for this subpopulation to ensure attainment of efficacy targets.

RéSUMé: OBJECTIF: L'objectif de cette étude était d'évaluer l'exposition et l'atteinte des cibles pharmacodynamiques de la pipéracilline/tazobactam (PTZ) chez la patientèle adulte aux soins intensifs. MéTHODES: Nous avons réalisé une étude observationnelle prospective dans l'unité de soins intensifs (USI) de l'Hôpital du Sacré-Cœur de Montréal (un centre de traumatologie de niveau 1 à Montréal, QC, Canada) entre janvier 2021 et juin 2022. Nous avons inclus les patient·es adultes âgé·es de 18 ans ou plus admis·es à l'USI ayant reçu de la PTZ par administration intraveineuse. Les caractéristiques démographiques et cliniques ont été recueillies, et les scores cliniques ont été calculés. Au jour 1 de la thérapie antimicrobienne, trois échantillons sanguins ont été prélevés aux moments suivants : 1 h après l'administration de la dose de PTZ, au milieu et à la fin de l'intervalle d'administration. Le calendrier d'échantillonnage a été répété aux jours 4 et 7 de la thérapie si possible. Les échantillons ont été analysés par chromatographie liquide à ultra-haute performance avec détecteur à diodes pour déterminer la concentration totale de pipéracilline. Les concentrations du milieu et de fin d'intervalle ont été utilisées pour les analyses d'atteinte de cible, définie comme une concentration supérieure à la concentration minimale inhibitrice de 16 mg·L-1, associée aux Enterobacteriaceae et au Pseudomonas aeruginosa. RéSULTATS: Quarante-trois patient·es ont été recruté·es et 202 échantillons sanguins ont été analysés. La dose la plus prévalente était une dose de 3/0,375 g aux 6 h (n = 50/73 doses administrées, 68 %) avec une perfusion sur 30 min. Nous avons observé une variabilité marquée aux trois temps de prélèvement, et les concentrations médianes [intervalle interquartile] de pipéracilline au pic, au milieu et à la fin de l'intervalle étaient respectivement de 109,4 [74,0-152,3], 59,3 [21,1-74,4] et 25,3 [6,8-44,6] mg·L−1. Lors de l'évaluation de l'atteinte de la cible, 37 % des patient·es n'ont pas atteint la cible d'efficacité d'une concentration de 16 mg·L−1 à la fin de l'intervalle posologique. La majorité des patient·es sous-exposé·es étaient des personnes dont la clairance rénale était normale ou augmentée. CONCLUSION: Dans cette étude observationnelle prospective de patient·es adultes aux soins intensifs recevant de la PTZ par voie intraveineuse, une grande proportion de patient·es présentait des concentrations sous-thérapeutiques de pipéracilline. Ceci était plus marqué chez les patient·es ayant une clairance rénale normale ou augmentée. Des schémas posologiques plus agressifs pourraient être nécessaires pour cette sous-population afin de favoriser l'atteinte des cibles d'efficacité.

Healthcare-associated bloodstream infection trends under a provincial surveillance program.

OBJECTIVE: BACTOT, Quebec's healthcare-associated bloodstream infection (HABSI) surveillance program has been operating since 2007. In this study, we evaluated the changes in HABSI rates across 10 years of BACTOT surveillance under a Bayesian framework. DESIGN: A retrospective, cohort study of eligible hospitals having participated in BACTOT for at least 3 years, regardless of their entry date. Multilevel Poisson regressions were fitted independently for cases of HABSI, catheter-associated bloodstream infections (CA-BSIs), non-catheter-associated primary BSIs (NCA-BSIs), and BSIs secondary to urinary tract infections (BSI-UTIs) as the outcome and log of patient days as the offset. The log of the mean Poisson rate was decomposed as the sum of a surveillance year effect, period effect, and hospital effect. The main estimate of interest was the cohort-level rate in years 2-10 of surveillance relative to year 1. RESULTS: Overall, 17,479 cases and 33,029,870 patient days were recorded for the cohort of 77 hospitals. The pooled 10-year HABSI rate was 5.20 per 10,000 patient days (95% CI, 5.12-5.28). For HABSI, CA-BSI, and BSI-UTI, there was no difference between the estimated posterior rates of years 2-10 compared to year 1. The posterior means of the NCA-BSI rate ratios increased from the seventh year until the tenth year, when the rate was 29% (95% confidence interval, 1%-89%) higher than the first year rate. CONCLUSIONS: HABSI rates and those of the most frequent subtypes remained stable over the surveillance period. To achieve reductions in incidence, we recommend that more effort be expended in active interventions against HABSI alongside surveillance.

Effectiveness of fosfomycin tromethamine prophylaxis in preventing infection following transrectal ultrasound-guided prostate needle biopsy: Results from a large Canadian cohort.

OBJECTIVES: Rates of infection following transrectal ultrasound-guided prostate biopsy (TRUSPB) are increasing. The aim of this study was to evaluate the effectiveness of fosfomycin tromethamine (FMT) prophylaxis in preventing post-TRUSPB infectious complications. METHODS: This nested case-control study included patients undergoing TRUSPB in a Canadian tertiary-care hospital who developed post-TRUSPB bacteraemia or urinary tract infection. Four prophylaxis periods were defined: (i) ciprofloxacin, low-resistance period (CIPRO-LOW), 2002-2009; (ii) ciprofloxacin, high-resistance period (CIPRO-HIGH), 2010-October 2013; (iii) oral FMT, one dose (FOSFO1), December 2013-September 2015; and (iv) oral FMT, two doses (FOSFO2), November 2015-June 2016. Incidence rates of the infection were calculated. RESULTS: TRUSPB (n=9391) resulted in 138 cases of urinary sepsis (58% with bacteraemia). The incidence rates were 1.8% (CIPRO-HIGH), 3.5% (FOSFO1; P=0.004 vs. CIPRO-HIGH) and 2.7% (FOSFO2; P=0.19 vs. CIPRO-HIGH). Although Escherichia coli remained the predominant pathogen with fosfomycin-based regimens, the proportion of infections caused by Klebsiella spp. was higher (20/66; 30.3%) than with ciprofloxacin-based regimens (2/77; 2.6%; P<0.0001). CONCLUSION: Independent risk factors for infection were the prophylactic regimen administered, presence of urological co-morbidities and diabetes. FMT was therefore not an effective alternative to ciprofloxacin for preventing post-TRUSPB urinary sepsis. These results highlight the need for novel antibacterial prophylaxis approaches.

A ten-year review of healthcare-associated bloodstream infections from forty hospitals in Québec, Canada.

OBJECTIVE: Healthcare-associated bloodstream infections (HABSI) are a significant cause of morbidity and mortality worldwide. In Québec, Canada, HABSI arising from acute-care hospitals have been monitored since April 2007 through the Surveillance des bactériémies nosocomiales panhospitalières (BACTOT) program, but this is the first detailed description of HABSI epidemiology. METHODS: This retrospective, descriptive study was conducted using BACTOT surveillance data from hospitals that participated continuously between April 1, 2007, and March 31, 2017. HABSI cases and rates were stratified by hospital type and/or infection source. Temporal trends of rates were analyzed by fitting generalized estimating equation Poisson models, and they were stratified by infection source. RESULTS: For 40 hospitals, 13,024 HABSI cases and 23,313,959 patient days were recorded, for an overall rate of 5.59 per 10,000 patient days (95% CI, 5.54-5.63). The most common infection sources were catheter-associated BSIs (23.0%), BSIs secondary to a urinary focus (21.5%), and non-catheter-associated primary BSIs (18.1%). Teaching hospitals and nonteaching hospitals with ICUs often had rates higher than nonteaching hospitals without ICUs. Annual HABSI rates did not exhibit statistically significant changes from year to year. Non-catheter-associated primary BSIs were the only HABSI type that exhibited a sustained change across the 10 years, increasing from 0.69 per 10,000 patient days (95% CI, 0.59-0.80) in 2007-2008 to 1.42 per 10,000 patient days (95% CI, 1.27-1.58) in 2016-2017. CONCLUSIONS: Despite ongoing surveillance, overall HABSI rates have not decreased. The effect of BACTOT participation should be more closely investigated, and targeted interventions along alternative surveillance modalities should be considered, prioritizing high-burden and potentially preventable BSI types.