Relationship Between Real-time TDM-guided Pharmacodynamic Target Attainment of Continuous Infusion Beta-lactam Monotherapy and Microbiologic Outcome in the Treatment of Critically Ill Children With Severe Documented Gram-negative Infections.

OBJECTIVES: To explore the relationship between real-time therapeutic drug monitoring (TDM)-guided pharmacodynamic target attainment of continuous infusion (CI) beta-lactam monotherapy and microbiological outcome in the treatment of critically ill children with severe documented Gram-negative infections. METHODS: Observational, monocentric, retrospective study of critically ill patients receiving CI piperacillin-tazobactam, ceftazidime, or meropenem in monotherapy for documented Gram-negative infections optimized by means of a real-time TDM-guided strategy. Average steady-state beta-lactam concentrations (C ss ) were calculated for each patient, and the beta-lactam C ss /minimum inhibitory concentration (MIC) ratio was selected as a pharmacodynamic parameter of efficacy. The C ss /MIC ratio was defined as optimal if ≥4, quasi-optimal if between 1 and 4, and suboptimal if <1. The relationship between C ss /MIC and microbiological outcome was assessed. RESULTS: Forty-six TDM assessments were carried out in 21 patients [median age 2 (interquartile range: 1-8) years]. C ss /MIC ratios were optimal in 76.2% of cases. Patients with optimal C ss /MIC ratios had both a significantly higher microbiological eradication rate (75.0% vs. 0.0%; P = 0.006) and lower resistance development rate (25.0% vs. 80.0%; P = 0.047) than those with quasi-optimal or suboptimal C ss /MIC ratios. Quasi-optimal/suboptimal C ss /MIC ratio occurred more frequently when patients had infections caused by pathogens with MIC values above the European Committee on Antimicrobial Susceptibility Testing clinical breakpoint (100.0% vs. 6.3%; P < 0.001). CONCLUSIONS: Real-time TDM-guided pharmacodynamic target attainment of CI beta-lactam monotherapy allowed to maximize treatment efficacy in most critically ill children with severe Gram-negative infections. Attaining early optimal C ss /MIC ratios of CI beta-lactams could be a key determinant associated with microbiologic eradication during the treatment of Gram-negative infections. Larger prospective studies are warranted for confirming our findings.

Hemodynamics in off-pump surgery: normal versus compromised preoperative left ventricular function.

OBJECTIVE: Off-pump coronary surgery (OPCABG), avoiding cardiopulmonary bypass and cardioplegic arrest, seems to be a better choice in patients with poor baseline cardiac function. Since cardiocirculatory collapse could be induced by heart displacement in this group of patients at high risk, a greater pathophysiologic understanding of the hemodynamic derangements occurring in such patients is needed. METHODS: Twenty-eight elective OPCABG patients were evaluated for hemodynamic changes induced by heart displacement, using arterial thermodilution to measure cardiac output and global end-diastolic volume. Hemodynamic parameters were recorded: at baseline; during proper exposure and stabilization of each vessel; and at the end of surgery. Patients were divided into two groups, according to baseline ejection fraction (EF): group A (EF>30%; N=16), group B (EF< or =30%; N=12). RESULTS: Heart displacement induced a significant drop in the cardiac and stroke index, with a lesser decrease of mean arterial pressure because of raised systemic vascular resistance. Preload, measured as global end diastolic volume, significantly decreased in group A, while it remained unchanged or increased in group B. Linear regression between the preload index and left ventricular stroke work was significant only in group A. CONCLUSIONS: Patients with poor baseline cardiac function can well tolerate OPCABG. However, the pathophysiologic modifications underlying the hemodynamic changes are different compared to those in patients with good preoperative cardiac performance.