Extended infusion beta-lactam antibiotic administration is a growing trend in US hospitals. This dosing strategy takes advantage of the pharmacodynamics properties of drugs like Zosyn (piperacillin/tazobactam), improving time over the MIC (T>MIC) to susceptible bacteria while providing cost savings. Based on computer Monte-Carlo simulations, dosing Zosyn 3.375g IV q8 infused over 4 hours, the same probability of achieving a therapeutic T>MIC is reached as dosing Zosyn 3.375g IV q6 infused over 30 minutes. It’s a good strategy that can be beneficial to both patients and the pharmacy budget, in certain situations.[1] That is, if the infecting pathogen is not pseudomonas. [2,3]
In most hospitals in the US, the breakpoint for susceptibility of pseudomonas to Zosyn is and MIC of 64 mg/L. In other words, the pseudomonas isolate will be reported as “S” if the MIC is less than or equal to 64 mg/L. So when the MIC to zosyn is between 32 and 64 mg/L, which would still be reported as “S,” the probability of achieving a therapeutic T>MIC is less than 40%. The closer you get to 64, the chances of having a therapeutic concentration of Zosyn are essentially zero, whether an extended infusion is used or not.
Lodise TP, et al. Clinical Infectious Diseases 2007; 44:357-63
So what can be done for critically ill septic patients that may be infected with pseudomonas isolates? If there is a chance the suspected pathogen is pseudomonas for the sick septic patient in the ED, Zosyn could be considered for use as an empric antibiotic when given as a standard intermittent infusion over 30 min at a dose of 4.5g. If the septic patient is bound for the ICU, and Zosyn is to be continued, utilizing a higher dosing strategy like 4.5g IV q6 infused over 3 hours may offer a theoretically higher chance of achieving therapeutic levels. Although the data for the addition of an aminoglycoside (amikacin or tobramycin) as “double coverage” isn’t favorable I would still recommend it as a logical alternative in the critically ill.[4] Cefepime is one of the few alternative agents with better susceptibilities that could be used empirically to cover pseudomonas. As always, check your hospitals antibiogram to see which agents may be considered appropriate (ceftazidime, aztreonam, levofloxacin/ciprofloxacin).
1. Lodise TP, et al. Clinical Infectious Diseases 2007; 44:357-63
2. Tam VH, et al. Clinical Infectious Diseases 2008; 46:862-7
3. Mah GT, et al. Ann Pharmacother 2012;46:265-75
4. Johnaon SJ, et al. Am J Health-Syst Pharm. 2011; 68:119-24
