This weekend I started listening to the Curbsiders end of the year spectacular. Matt’s pick of the year was an upcoming meta-analysis about the risk of the vanc/pip-tazo combination. We developed awareness of the renal toxicity from this combination a couple of years ago. At our community hospital program we almost never use the combination.
Several months ago we reviewed this article at our journal club – Risk of Acute Kidney Injury in Patients on Concomitant Vancomycin and Piperacillin–Tazobactam Compared to Those on Vancomycin and Cefepime
This study used a retrospective matched cohort technique – not a randomized controlled trial, but a reasonable methodology.
Patients in both VC and VPT groups had similar baseline characteristics in terms of age, length of ICU stay, Charlson comorbidity index score, baseline creatinine, and use of concomitant nephrotoxins.
The groups had great similarity.
The rate of AKI was higher among patients receiving VPT compared to those receiving VC combination therapy. Based on RIFLE criteria, 81 patients in the VPT group developed AKI compared to 31 patients in the VC group (29.0% vs 11.1%; hazard ratio [HR] = 4.0; 95% confidence interval [CI], 2.6–6.2; P < .0001). Rates of AKI were also higher per AKIN criteria (32% in the VPT vs 14% in the VC group; HR = 3.5; 95% CI, 2.3–5.2; P < .0001) and per vancomycin consensus guidelines definition (24% in VPT vs 8.2% in VC; HR = 4.4; 95% CI, 2.7–7.3; P < .0001). In multivariate analysis, after controlling for residual differences between the VPT and VC groups (race, gender, admission from home, comorbid conditions, presence of septic shock, baseline serum white blood cell count, and source of infection), VPT was independently associated with RIFLE-defined AKI (HR = 4.3; 95% CI, 2.7–6.7; P < .0001).
The multivariate analysis adjust for major potential confounders, thus the groups are equalized for potential characteristics that might have increased the risk for AKI.
The median length of stay after initiation of combination therapy was longer for VPT patients compared to VC patients (8 days vs 6 days; P = .01). There was no difference in mortality between the 2 groups.
The cost of increasing LOS by 2 days is huge.
Rates of AKI among patients receiving VPT were approximately 3 times greater than rates in patients receiving VC, regardless of type of AKI definition used. In multivariate modeling and controlling for residual differences between these 2 closely matched groups, receipt of VPT was associated with a greater than 4-fold increased risk of AKI. These findings are particularly robust and convincing as, unlike previous analyses comparing toxicity risk in patients on VPT and VC, this analysis was adequately powered and groups were matched on 5 widely recognized risk factors for AKI in patients receiving vancomycin.
And in the discussion:
These findings are strengthened by 3 additional important and notable findings. First, among patients who developed AKI, the onset was more rapid in VPT patients compared to VC patients (3 days vs 5 days; P < .0001.) Second, the daily rate of AKI among the at-risk population remained higher throughout the first week of therapy among VPT patients. This rapid onset and persistently increased AKI risk are both consistent with VPT being more toxic than VC.
The third finding supporting an association between VPT and increased toxicity was both interesting and unexpected. Data from this study show discordance in the impact of vancomycin troughs on toxicity in patients receiving VPT compared to those receiving VC. Among patients receiving VPT, there was no discernable impact of vancomycin trough on the incidence of AKI. Conversely, a distinct trough–toxicity association was noted in patients receiving VC
While I particularly like this article, other articles have also documented this problem.
In hospital practice in 2018, we should always ask the important question – Do we need both antibiotics? If we are just worried about pseudomonas coverage, cefepime is a satisfactory choice. If we are worried about anaerobes, pseudomonas and MRSA then we might legitimately use the VPT combination – although some would just add anaerobic coverage to VC.
The instinct to order VPT should become muted in 2018. Matt Watto was correct to point this out in the year end podcast.