Pharmacokinetic/Pharmacodynamic Target Attainment of Ceftazidime in Adult Patients on General Wards with Different Degrees of Renal Function: A Prospective Observational Bicenter Cohort Study.

No prospective evidence exists on the pharmacokinetic/pharmacodynamic (PK/PD) target attainment of ceftazidime in adult patients on general wards. We aimed to investigate whether the PK/PD target of ceftazidime (50% T > MIC) is attained in adult patients on general wards with adequate and impaired renal function receiving regular and guideline-recommended reduced doses of ceftazidime. In this observational, prospective, bicenter cohort study, adult patients admitted to a general ward receiving ceftazidime as part of standard care were included. Three blood samples per patient within 72 h after start of treatment were collected. Data were analyzed with nonlinear mixed effects modeling. The primary endpoint was target attainment of 50% T > MIC during the first 24 h of treatment (50% T0-24 > MIC). Forty patients were included from whom 121 blood samples were obtained. All 25/25 patients with adequate renal function, 9/10 patients with moderately impaired renal function (eGFR 30-50 mL/min/1.73 m2) and 5/5 patients with severe impaired renal function (eGFR < 30 mL/min/1.73 m2) attained 50% T0-24 > MIC when applying the clinical breakpoint MIC for Pseudomonas aeruginosa of 8 mg/L. The one patient not attaining the PK/PD target did not differ in any of the collected patients' characteristics, except that this patient was the oldest in the study population. However, age was not statistically significantly associated with clearance or volume of distribution in the population pharmacokinetic model and, therefore, not likely the cause for this patient not attaining the PK/PD target. Our results suggest ≥90% probability of the PK/PD target attainment of ceftazidime in patients on general wards with adequate and impaired renal function receiving regular and guideline-recommended reduced doses of ceftazidime for treatment of infections with Pseudomonas aeruginosa and all bacteria with lower MIC-values.

Does dose reduction of renally cleared antibiotics in patients with impaired renal function lead to adequate drug exposure? A systematic review.

BACKGROUND: There is inconsistency between many guidelines in the recommended dose reduction of renally cleared antibiotics in patients with impaired renal function. OBJECTIVES: This systematic review summarizes the available evidence on the adequacy of the recommended dose reduction in terms of achieving sufficient antibiotic drug exposure or pharmacokinetic/pharmacodynamic target attainment after treatment with these reduced doses. DATA SOURCES: We systematically searched Ovid Medline and Embase from inception (respectively 1946 and 1947) through July 2019. STUDY ELIGIBILITY CRITERIA: All studies reporting antibiotic drug exposure and/or pharmacokinetic/pharmacodynamic (PK/PD) target attainment after dose reduction of antibiotics in patients with impaired renal function. PARTICIPANTS: Adult patients with or without infections. INTERVENTIONS: Administration of reduced doses of antibiotics (orally, intravenously or intramuscularly). METHODS: The reduced dose was considered adequate when the most relevant parameters of drug exposure or PK/PD target attainment in patients with impaired renal function were within a range of 80% to 125% of that patients with adequate renal function receiving a regular dose (reference) or when PK/PD target attainment was attained in at least 90% of the patients with impaired renal function, regardless of the lack of a reference group. RESULTS: Twenty-seven of the 4202 identified studies were included. The quality of 15 of 27 studies was fair, and most studies were of ß-lactams (12/27). Best evidence was available for meropenem: four studies were included, of which two studies were of good quality. Drug exposure for meropenem is 158% to 286% higher in patients with impaired renal function receiving reduced doses compared to patients with adequate renal function receiving regular doses. For all other antibiotics, a maximum of one good-quality study could be identified. CONCLUSIONS: No good-quality evidence on the recommended dose reduction of renally cleared antibiotics in patients with impaired renal function is present, with the exception of meropenem.

Asthma, bones and corticosteroids: Are inhaled corticosteroids associated with fractures in children with asthma?

AIM: The prevalence of asthma worldwide among older children varies between 10 and 20%. One of the most effective therapies to treat asthma and prevent exacerbations is inhaled corticosteroids (ICSs). Systemic corticosteroids are known to decrease bone mineral density and increase the risk of fractures among children, but little is known about the effect of ICSs on fracture risk in children with asthma. The aim of this study was to investigate the fracture rates in children with asthma using ICSs. METHODS: A survey on fracture history and risk, bone health and asthma was administered by a researcher to children aged 6-18 years attending a tertiary care children's hospital in Melbourne, Australia over a 6-month period. Fracture risks were compared in children on low or high dose ICS with those not on any ICS and non-asthmatics. RESULTS: A total of 216 healthy control participants were compared with 211 children with asthma - 22% (n = 46) on low dose ICS therapy, 44% (n = 94) on high dose ICS and 34% (n = 71) not on any ICS. There was no difference in the incidence of fractures between children with asthma (24.6% n = 53) and healthy controls (24% n = 51) (χ2 = 0.132; P = 0.717). There were no differences in fracture incidence in the sub-groups of children with asthma (P = 0.695). CONCLUSION: ICS use was not associated with fracture risk in children with asthma.