Preparing and administering injectable antibiotics: How to avoid playing God

Longuet, P; Lecapitaine, Anne-Lise; Cassard, Bruno; Batista, Rui; Gauzit, R.; Lesprit, Philippe; Haddad, Raymond N.; Vanjak, Dominique; Diamantis, S.

doi:10.1016/j.medmal.2016.01.010

Cited by 36 publications

(20 citation statements)

References 35 publications

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“…That study was, however, impaired by the lack of drug monitoring. Until these results are confirmed, the continuous administration of ceftriaxone should be discouraged, given the poor stability of the molecule after reconstitution (18). Maximizing the quality of antibiotic prescriptions must remain of major importance in terms of adequate preparation and administration modalities.…”

Section: Discussionmentioning

confidence: 99%

Are Standard Dosing Regimens of Ceftriaxone Adapted for Critically Ill Patients with Augmented Creatinine Clearance?

Ollivier¹,

Carrié

d’Houdain³

et al. 2019

Antimicrob Agents Chemother

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The objective of the present study was to determine whether augmented renal clearance (ARC) impacts negatively on ceftriaxone pharmacokinetic (PK)/pharmacodynamic (PD) target attainment in critically ill patients. Over a 9-month period, all critically ill patients treated with ceftriaxone were eligible. During the first 3 days of antimicrobial therapy, every patient underwent 24-h creatinine clearance (CLCR) measurements and therapeutic drug monitoring of unbound ceftriaxone. ARC was defined by a CLCR of ≥150 ml/min. Empirical underdosing was defined by a trough unbound ceftriaxone concentration under 2 mg/liter (percentage of the time that the concentration of the free fraction of drug remained greater than the MIC [fT>MIC], 100%). Monte Carlo simulation (MCS) was performed to determine the probability of target attainment (PTA) of different dosing regimens for various MICs and three groups of CLCR (<150, 150 to 200, and >200 ml/min). Twenty-one patients were included. The rate of empirical ceftriaxone underdosing was 62% (39/63). A CLCR of ≥150 ml/min was associated with empirical target underdosing with an odds ratio (OR) of 8.8 (95% confidence interval [CI] = 2.5 to 30.7; P < 0.01). Ceftriaxone PK concentrations were best described by a two-compartment model. CLCR was associated with unbound ceftriaxone clearance (P = 0.02). In the MCS, the proportion of patients who would have failed to achieve a 100% fT>MIC was significantly higher in ARC patients for each dosage regimen (OR = 2.96; 95% CI = 2.74 to 3.19; P < 0.01). A dose of 2 g twice a day was best suited to achieve a 100% fT>MIC. When targeting a 100% fT>MIC for the less susceptible pathogens, patients with a CLCR of ≥150 ml/min remained at risk of empirical ceftriaxone underdosing. These data emphasize the need for therapeutic drug monitoring in ARC patients.

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Section: Discussionmentioning

confidence: 99%

Are Standard Dosing Regimens of Ceftriaxone Adapted for Critically Ill Patients with Augmented Creatinine Clearance?

Ollivier¹,

Carrié

d’Houdain³

et al. 2019

Antimicrob Agents Chemother

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“…The answers available for these multiple-choice questions were: <2 h; 2e4 h; 4e12 h; >12 h and I don't know. The theoretical duration of stability of each antibiotic after its reconstitution in optimal conditions at 25 C is listed in parentheses after its name [25]. Table 2 Bivariate and multivariate analysis of factors associated with the frequent use of prolonged infusion for b-lactams and vancomycin in the eight clinical vignettes (score > 4) a…”

Section: Discussionmentioning

confidence: 99%

“…Only half the respondents reported easy access to methods of b-lactam and vancomycin infusions (and half through personal information sources). To meet this need, a practical guide detailing the methods and procedures for reconstituting and infusing b-lactam will soon be available (in English and French) [25]. Regular contacts with members of the antimicrobial stewardship team (infectious disease specialists, microbiologists, pharmacists) is also probably insufficient, since 36% of the respondents reported that they never had regular contact with these specialists; this variable was however associated with greater use of prolonged infusion in the vignettes.…”

mentioning

confidence: 99%

The ANTIBIOPERF study: a nationwide cross-sectional survey about practices for β-lactam administration and therapeutic drug monitoring among critically ill patients in France

Charmillon

Novy

Agrinier

et al. 2016

Clinical Microbiology and Infection

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Our objective was to assess current practices about the administration (intermittent, extended, or continuous infusions) and therapeutic drug monitoring (TDM) of β-lactam antibiotics and vancomycin in France. We conducted a nationwide cross-sectional survey in May-August 2015, using an online questionnaire, sent as an e-mail link to infectious disease specialists and intensive care specialists through national mailing lists. We used clinical vignettes of critically ill patients to assess physicians' practices about administration and TDM practices for amoxicillin, cloxacillin, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime, meropenem and vancomycin. In all, 507 physicians participated (507/1200, response rate 42%). TDM was rarely available for β-lactams (from 16.5% (81/490) for cloxacillin to 30% (145/490) for ceftazidime), whereas vancomycin TDM was available in 97% (477/490) of the cases. In the clinical vignettes, ceftazidime and piperacillin/tazobactam were the β-lactams administered most frequently by extended or continuous infusions (76% (336/440) and 57% (252/444), respectively). Gaps in knowledge about the duration of stability of intravenous β-lactams were common (correct answers ranged from 8% (35/432) for cloxacillin to 33% (146/438) for ceftazidime). Most physicians (77%, 339/442) were convinced of the value of extended or continuous infusions for β-lactams in critically ill patients, but 48% (211/442) did not have access to practical guidelines. Our survey found that most infectious disease and intensive care specialists are favourable to optimized administration of β-lactams in critically ill patients. But the lack of guidelines and limited TDM availability for β-lactams in hospitals are potential barriers to its implementation.

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“…(2) Although continuous or prolonged infusion of beta-lactam antibiotics may be preferable in the above-mentioned indications, continuous administration must take into account the chemical stability of these antibiotics over time [107]. This is of particular importance for carbapenems that have a stability of a few hours (imipenem/cilastatin: 2–3 h, ertapenem and meropenem: from 6 to 12 h depending on the reconstitution concentration) at 25°C in 0.9% NaCl [107, 108], requiring administration of the daily dose in several divided doses prepared just before their infusion.…”

Section: Guidelinesmentioning

confidence: 99%

Optimization of the treatment with beta-lactam antibiotics in critically ill patients—guidelines from the French Society of Pharmacology and Therapeutics (Société Française de Pharmacologie et Thérapeutique—SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Société Française d’Anesthésie et Réanimation—SFAR)

et al. 2019

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Background Beta-lactam antibiotics (βLA) are the most commonly used antibiotics in the intensive care unit (ICU). ICU patients present many pathophysiological features that cause pharmacokinetic (PK) and pharmacodynamic (PD) specificities, leading to the risk of underdosage. The French Society of Pharmacology and Therapeutics (SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (SFAR) have joined forces to provide guidelines on the optimization of beta-lactam treatment in ICU patients. Methods A consensus committee of 18 experts from the two societies had the mission of producing these guidelines. The entire process was conducted independently of any industry funding. A list of questions formulated according to the PICO model (Population, Intervention, Comparison, and Outcomes) was drawn-up by the experts. Then, two bibliographic experts analysed the literature published since January 2000 using predefined keywords according to PRISMA recommendations. The quality of the data identified from the literature was assessed using the GRADE® methodology. Due to the lack of powerful studies having used mortality as main judgement criteria, it was decided, before drafting the recommendations, to formulate only “optional” recommendations. Results After two rounds of rating and one amendment, a strong agreement was reached by the SFPT-SFAR guideline panel for 21 optional recommendations and a recapitulative algorithm for care covering four areas: (i) pharmacokinetic variability, (ii) PK-PD relationship, (iii) administration modalities, and (iv) therapeutic drug monitoring (TDM). The most important recommendations regarding βLA administration in ICU patients concerned (i) the consideration of the many sources of PK variability in this population; (ii) the definition of free plasma concentration between four and eight times the Minimal Inhibitory Concentration (MIC) of the causative bacteria for 100% of the dosing interval as PK-PD target to maximize bacteriological and clinical responses; (iii) the use of continuous or prolonged administration of βLA in the most severe patients, in case of high MIC bacteria and in case of lower respiratory tract infection to improve clinical cure; and (iv) the use of TDM to improve PK-PD target achievement. Conclusions The experts strongly suggest the use of personalized dosing, continuous or prolonged infusion and therapeutic drug monitoring when administering βLA in critically ill patients. Electronic supplementary material The online version of this article (10.1186/s13054-019-2378-9) contains supplementary material, which is available to authorized users.

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Preparing and administering injectable antibiotics: How to avoid playing God

Cited by 36 publications

References 35 publications

Are Standard Dosing Regimens of Ceftriaxone Adapted for Critically Ill Patients with Augmented Creatinine Clearance?

Are Standard Dosing Regimens of Ceftriaxone Adapted for Critically Ill Patients with Augmented Creatinine Clearance?

The ANTIBIOPERF study: a nationwide cross-sectional survey about practices for β-lactam administration and therapeutic drug monitoring among critically ill patients in France

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