Pharmacokinetic variability of beta-lactams in critically ill patients: A narrative review.

The use of antibacterial drugs is very common in critically ill patients and beta-lactam agents are widely used in this context. Critically ill patients show several characteristics (e.g., sepsis, renal impairment or conversely augmented renal clearance, renal replacement therapy) that may alter beta-lactam pharmacokinetics (PK) in comparison with non-critically ill patients. This narrative literature review aims to identify recent studies quantifying the variability of beta-lactams volume of distribution and clearance and to determine its main determinants. Seventy studies published between 2000 and 2018 were retained. Data on volume of distribution and clearance variability were reported for 5 penicillins, 3 beta-lactamase inhibitors, 6 cephalosporins and 4 carbapenems. Data confirm specific changes in PK parameters and important variability of beta-lactam PK in critically ill patients. Renal function, body weight and use of renal replacement therapy are the principal factors influencing PK parameters described in this population. Few studies have directly compared beta-lactam PK in critically ill versus non-critically ill patients. Conclusions are also limited by small study size and sparse PK data in several studies. These results suggest approaches to assess this PK variability in clinical practice. Beta-lactam therapeutic drug monitoring seems to be the best way to deal with this issue.

Combination of ß-(1, 3)-D-glucan testing in serum and qPCR in nasopharyngeal aspirate for facilitated diagnosis of Pneumocystis jirovecii pneumonia.

BACKGROUND: Currently, the biological diagnosis of Pneumocystis jirovecii pneumonia (PjP infection) usually relies on microbiological investigations in bronchial-alveolar lavage fluid (BALF) by conventional staining methods and/or molecular biology. However, bronchial-alveolar lavage is sometimes complicated to manage, especially in weakened patients. Therefore, alternative clinical samples-easier to collect-are warranted in such specific contexts. OBJECTIVE: Over a four-year period, diagnostic performance of an original method based on combination of quantitative real-time polymerase chain reaction (qPCR) in nasopharyngeal aspirate (NPA) with measurement of ß-(1, 3)-D-glucan antigen (BDG) in serum was prospectively assessed in a single centre. PATIENTS/METHODS: Results were compared with those obtained in BALF through direct staining methods and qPCR. True positives were defined by an independent committee based on clinical, radiological and biological data. Overall, 48 individuals with a definitive diagnosis of PjP infection were included, and 48 controls were selected upon matching for age, sex and underlying disease(s). RESULTS: qPCR results were strongly correlated between BALF and NPA (P < .0001). Altogether, greater diagnostic performance was achieved when establishing the positive cut-off of BDG antigen at 143 pg/mL. In such conditions, sensitivity of the testing based on either positive BDG measurement or positive qPCR in NPA was then calculated at 93.75%, 95% CI [82.37%-98.40%], and specificity at 97.87%, 95% CI [87.66%-100.00%]. CONCLUSIONS: Further validation through multicentre studies is now required, especially for establishing clear cut-offs. However, one could already state that combination of qPCR in the NPA with BDG measurement in serum may be a valuable substitute for BALF examination.