Prolonged TZP infusion beneficial for pneumonia in cancer patients
Better clinical efficacy was observed among cancer patients with postoperative hospital-acquired pneumonia (HAP) who received prolonged infusion of the mixed preparation of the broad-spectrum β-lactamase inhibitor tazobactam and β-lactam antibiotic piperacillin (TZP) compared with those who received the traditional regimen, according to a study.
One hundred and twenty cancer patients were randomized 1:1 to receive either a traditional (within 30 minutes) or prolonged (extended to 3 hours) intravenous infusion of TZP 4.5 g/6 hours. Patients were stratified according to disease severity (n=53 and 67 for mild and severe, respectively) based on the SOFA* score (cutoff value≥9). [Ther Clin Risk Manag 2018;14:31-37]
Compared with the traditional regimen, prolonged infusion resulted in a shorter though nonsignificant duration of antibiotic use (11.1 vs 13.2 days; p=0.124) and ventilator time (145.6 vs 152.0 hours; p=0.515). Moreover, there was better bacteriologic (98.3 percent vs 75.0 percent) and clinical efficacy (88.3 percent vs 86.7 percent; p=0.044) and a lower 28-day mortality rate (1.67 percent vs 8.33 percent; p=0.023) with prolonged vs traditional infusion.
On subgroup analysis involving patients with mild disease, bacteriologic efficacy was significantly better with prolonged vs traditional infusion (100 percent vs 83.33 percent; p=0.011).
The effects of prolonged vs traditional infusion were more pronounced in patients with severe disease, as indicated by a shorter duration of antibiotic use (12.9 vs 14.6 days; p=0.041) and ventilator time (126.1 vs 169.4 hours; p=0.043), better bacteriologic efficacy (98.8 percent vs 71.4 percent; p=0.005) and clinical efficacy (78.1 percent vs 57.1 percent; p=0.007), and a lower 28-day mortality rate (3.12 percent vs 14.3 percent; p=0.027).
These results suggest that similar clinical efficacy may be achieved with both the extended or traditional regimens for nonsevere HAP patients, the researchers pointed out. For severe HAP patients, the prolonged approach may boost antibacterial activity, they added.
Although drug efficacy may be enhanced by increasing the dosage and frequency, this consequently increases treatment cost and resource consumption, noted the researchers. Given these factors, as well as the potential kidney damage associated with increased drug dosage, it is important to explore alternatives such as prolonged infusion to optimize drug exposure without increasing dosage. [Diagn Microbiol Infect Dis 2010;68:251-258]
However, prolonged infusion is also associated with increased treatment cost due to the use of infusion pumps, as well as increased risk of venous catheter infection, the researchers pointed out.
“Therefore, it is important to identify patients who need prolonged infusion mode the most,” said the researchers. Given the prevalence of pneumonia among cancer patients, [Crit Care 2013;17(Suppl 4):P28; Curr Opin Pulm Med 2015;21:260-271] this drug optimization strategy would most likely benefit this critically ill population. [Crit Care Resusc 2014;16:190-196; Clin Ther 2012;34:2297-2300]
“[D]rug-resistant strains emerge as the pathogens of HAP … [and] the consequences arising from drug resistance of bacteria may be disastrous,” underscored the researchers. “Maximizing the antibacterial activity of antibiotics and choosing correct, effective, safe, and economical administration of antibiotics are extremely urgent and necessary,” they said, calling for larger studies to validate the results given the small sample size.