Utilizing Ceftazidime/Avibactam Therapeutic Drug Monitoring in the Treatment of Neurosurgical Meningitis Caused by Difficult-to-Treat Resistant Pseudomonas aeruginosa and KPC-Producing Enterobacterales.

Background: Central nervous system (CNS) infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales and difficult-to-treat resistant (DTR) Pseudomonas aeruginosa represent a formidable clinical challenge. Antimicrobial regimens that efficiently penetrate the cerebrospinal fluid (CSF) and achieve sufficient concentrations associated with microbiologic and clinical cure are limited. We evaluated therapy with ceftazidime-avibactam (CAZ-AVI) in order to guide precise dosing in the treatment of CNS infections. Methods: Therapeutic drug monitoring (TDM) was performed in 3 patients with health care-associated ventriculitis and meningitis (HAVM) using CAZ-AVI 2.5 g infused intravenously every 8 hours as standard and extended infusion. Simultaneous CSF and plasma samples were obtained throughout the dosing interval in each patient. Concentrations of CAZ and AVI were determined by liquid chromatography/mass spectrometry. Results: Bacterial identification revealed KPC-producing Klebsiella pneumoniae (KPC-Kp), DTR Pseudomonas aeruginosa, and KPC-producing Enterobacter cloacae (KPC-Ent.c). All isolates were resistant to carbapenems. The minimum inhibitory concentrations (MICs) of CAZ-AVI were 0.25/4, 4/4, and 0.25/4 µg/mL, respectively. CAZ and AVI concentrations were determined in CSF samples ranging from 29.0 to 15.0 µg/mL (CAZ component) and 4.20 to 0.92 µg/mL (AVI component), respectively. AVI achieved concentrations ≥1 µg/mL in 11 out of 12 CSF samples collected throughout the dosing interval. Clinical and microbiologic cure were attained in all patients. Conclusions: Postinfusion concentrations of CAZ-AVI were measured in plasma and CSF samples obtained from 3 patients with complicated CNS infections caused by antimicrobial-resistant isolates. The measured concentrations revealed that standard CAZ and AVI exposures sufficiently attained values correlating to 50% fT > MIC, which are associated with efficient bacterial killing.

Comparative Plasma Pharmacokinetics of Ceftriaxone and Ertapenem in Normoalbuminemia, Hypoalbuminemia, and Albumin Replacement in a Sheep Model.

Optimal concentrations of unbound antimicrobials are essential for a maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare the effects of different albumin states on total and unbound concentrations of ertapenem and ceftriaxone using an ovine model. The study design was a prospective, three-phase intervention observational study. The subjects were healthy Merino sheep. Eight sheep were subjected to three experimental phases: normoalbuminemia, hypoalbuminemia using plasmapheresis, and albumin replacement using a 25% albumin solution. In each phase, ceftriaxone at 40 mg/kg of body weight and ertapenem at 15 mg/kg were given intravenously. Blood samples were collected at predefined intervals and analyzed using an ultrahigh-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters such as the area under the curve from 0 to 24 h (AUC0-24), plasma clearance (CL), and apparent volume of distribution in the terminal phase (V) were estimated and compared between the phases. The protein and albumin concentrations were significantly different between phases. Hypoalbuminemia resulted in a significantly lower AUC0-24 and higher CL of total and unbound concentrations of ceftriaxone than in the other phases, whereas albumin replacement led to higher AUC0-24 and lower CL than in the other phases for both drugs. The V values for total drug concentrations for both drugs were significantly lower with albumin replacement. For highly protein-bound drugs such as ceftriaxone and ertapenem, both hypoalbuminemia and albumin replacement may affect unbound drug exposure.

Comparison between two metabolic monitors in the measurement of resting energy expenditure and oxygen consumption in diabetic and non-diabetic ambulatory and hospitalized patients.

OBJECTIVE: The aim of this study was to assess the validity and reliability of the Fitmate metabolic system in measuring the oxygen consumption and resting metabolic rate (RMR) in ambulatory and hospitalized patients. METHODS: We conducted a prospective simultaneous clinical comparison. We enrolled 37 patients (19 women and 18 men) for the four groups of the study. Group 1 (n = 12) included patients receiving home parenteral nutrition. Group 2 (n = 5) included diabetic overweight outpatients with body mass index >30 kg/m(2) and hemoglobin A1c > 8 g/dL. Group 3 (n = 10) included hospitalized patients receiving artificial nutrition. Group 4 (n = 10) included patients with congenital heart disease, pulmonary hypertension of any etiology, and other heart disease who have had hemodynamic evaluation during catheterization by the adult congenital team. The patients were tested successively during the same session using the Fitmate metabolic system for 15 min and the Deltatrac II metabolic monitor for 20 min, measuring resting energy expenditure and oxygen consumption. The test was conducted in random order. RESULTS: No significant differences were found between Fit Mate and Deltatrac II for oxygen consumption (238 ± 18 and 240 ± 18 mL/min, respectively, P = 0.72, r = 0.86, mean ± SD absolute difference 22.32 ± 16.99 mL/min) or RMR (1659 ± 122.34 and 1625 ± 118.4 kcal/d, P = 0.28, r = 0.87, mean ± SD absolute difference 152.9 ± 111.95 kcal/d). A degree of limit of agreement (403 kcal) was observed using the Bland-Altman test. When compared with Harris-Benedict predictive equations, Fitmate was found to be superior in accuracy. CONCLUSIONS: These data indicate that the Fitmate using a mask provided a fair evaluation of REE despite a large limit of agreement. It remains a reliable and valid system for measuring oxygen consumption and RMR in nonventilated patients.

Functional significance of using tissue adhesive substance in nephron-sparing surgery: assessment by quantitative SPECT of 99m Tc-Dimercaptosuccinic acid scintigraphy.

OBJECTIVES: To compare changes in renal function following nephron-sparing surgery (NSS) using tissue adhesive only versus NSS using standard suturing technique, as measured by quantitative SPECT of 99m Tc-dimercaptosuccinic acid uptake by the kidney (QDMSA). MATERIALS AND METHODS: QDMSA was done before and 3-6 mo after the operation in 32 patients who underwent standard suturing technique and in 24 patients in whom tissue adhesive sealant (19 with albumin glutaraldehyde tissue adhesive [BioGlue]; 5 with CoSeal) was used to close the parenchymal defect. Individual kidney uptake was measured and retrospectively compared between the two groups. RESULTS: Average tumor diameter was 3.4cm (range: 2.2-6) in the suture group and 3.56 (range: 1.7-6) in the tissue sealant group. In the tissue sealant group following surgery, we observed an average individual renal function loss of 11.49% compared with the suture group in whom an average individual renal function loss of 20.36% (p = 0.02) was measured by 99m Tc-DMSA. CONCLUSIONS: The use of tissue sealant to close the parenchymal defect during NSS demonstrated a statistically significant advantage in reducing functioning renal loss as measured by the absolute uptake of QDMSA. Further clinical studies are required to establish the role of tissue sealants in NSS.