Top Guns: The “Maverick” and “Goose” of Empiric Therapy

Antimicrob Agents Chemother

Cox

Martin

et al. 2017

Recent reports have demonstrated that vancomycin (VAN) may lead to an increase in the incidence of acute kidney injury (AKI) when it is combined with antipseudomonal beta-lactams. This study compared the incidence of AKI associated with VAN plus piperacillin-tazobactam (TZP) or cefepime (FEP). This was a retrospective, matched cohort study that was conducted at an academic medical center between September 2010 and September 2014 and that included adult patients without severe chronic or structural kidney disease, dialysis, pregnancy, cystic fibrosis, or a hospital transfer receiving TZP-VAN or FEP-VAN for at least 48 h. The primary outcome was the difference in the AKI incidence between the TZP-VAN and FEP-VAN groups, evaluated using the risk, injury, failure, loss of kidney function, and endstage kidney disease (RIFLE) criteria. Patients in the two groups were matched on the basis of age, sex, severity of illness, baseline creatinine clearance, hypotension, number of nephrotoxicity risk factors, and intravenous contrast exposure. In total, 4,193 patients met all inclusion criteria (3,605 received TZP-VAN and 588 received FEP-VAN). The unadjusted AKI incidence was 21.4% in patients receiving TZP-VAN, whereas it was 12.6% in patients receiving FEP-VAN (P Ͻ 0.001). After the patients were matched, 1,633 patients receiving TZP-VAN and 578 patients receiving FEP-VAN were evaluated. The AKI incidence remained higher in patients receiving TZP-VAN than in those receiving FEP-VAN (21.4% versus 12.5%, P Ͻ 0.0001). This trend remained true for all classifications of the RIFLE criteria. After controlling for remaining confounders, TZP-VAN therapy was associated with 2.18 times the odds of AKI than FEP-VAN therapy (95% confidence interval, 1.64 to 2.94 times) in logistic regression. AKI was significantly more common in patients receiving vancomycin in combination with piperacillin-tazobactam than in those receiving vancomycin in combination with cefepime. This finding reinforces the need for the judicious use of combination empirical antimicrobial therapy.

Section: Discussionsupporting

confidence: 86%

Nephrotoxicity during Vancomycin Therapy in Combination with Piperacillin-Tazobactam or Cefepime

Antimicrob Agents Chemother

Cox

Martin

et al. 2017

“…The estimated AKI incidence of 21% in the combination therapy group at our institution is consistent with literature that ranges from 16.3% to 34.8%. 4–8, 13 …”

Section: Discussionmentioning

confidence: 99%

Acute Kidney Injury in Patients Treated with Vancomycin and Piperacillin‐Tazobactam: A Retrospective Cohort Analysis

Journal of Hospital Medicine

Burgess

Talbert

et al. 2017

BACKGROUND Empiric antimicrobial therapy often consists of the combination of gram-positive coverage with vancomycin (VAN) and gram-negative coverage, specifically an antipseudomonal beta-lactam such as piperacillin-tazobactam (PTZ). Nephrotoxicity is commonly associated with VAN therapy; however, recent reports show higher nephrotoxicity rates among patients treated with the combination of VAN and PTZ. OBJECTIVE This study evaluated the effect of the VAN/PTZ combination on acute kidney injury (AKI) compared to VAN and PTZ monotherapies. DESIGN, SETTING, AND PATIENTS This is a retrospective cohort analysis of adult patients without renal disease receiving VAN, PTZ, or the combination from September 1, 2010 through August 31, 2014 at an academic medical center. MEASUREMENTS The primary outcome was AKI incidence as defined by the Risk, Injury, Failure, Loss, End-stage (RIFLE) criteria. METHODS Continuous and categorical variables were assessed with appropriate tests. Univariate and multivariate logistic regressions were performed to assess for associations between variables and AKI incidence. Subanalyses based on severity of illness were performed. RESULTS Overall, 11,650 patients were analyzed, with 1647 (14.1%) developing AKI. AKI was significantly more frequent in the VAN/PTZ group (21%) compared to either monotherapy group (VAN 8.3%, PTZ 7.8%, P < 0.001 for both). Combination therapy was independently associated with higher AKI odds compared to monotherapy with either agent (adjusted odds ratio [aOR], 2.03; 95% confidence interval [CI], 1.74–2.39; aOR, 2.31; 95% CI, 1.97–2.71, for VAN and PTZ, respectively). Receipt of concomitant nephrotoxic drugs was independently associated with increased AKI rates, as were increased duration of therapy, hospital length of stay, increasing severity of illness, and increasing baseline renal function. CONCLUSIONS In this study of more than 10,000 patients, VAN combined with PTZ was associated with twice the odds of AKI development compared to either agent as monotherapy. This demonstrates the need for judicious use of combination empiric therapy.

“…One group reported the rate of PTZ monotherapy‐associated AKI to be 15.4%, which was not significantly different from the combination therapy arm (18.8%) . AKI rates when PTZ is combined with VAN range from 9.5% to 34.8% . Few studies have compared AKI incidence among different treatment regimens, but the most common comparator is cefepime.…”

Section: Discussionmentioning

confidence: 99%

“…The use of piperacillin‐tazobactam (PTZ) in combination with vancomycin (VAN) has been associated with elevated rates of acute kidney injury (AKI) in many small retrospective studies. Incidence rates of AKI range from 9.5% to 34.8%, depending on the target population, with critically ill populations having higher incidence of AKI . The most common comparator agent in these studies was cefepime, because PTZ and cefepime share a similar niche in antipseudomonal therapy.…”

mentioning

confidence: 99%

“…Incidence rates of AKI range from 9.5% to 34.8%, depending on the target population, with critically ill populations having higher incidence of AKI. [1][2][3][4][5][6][7][8] The most common comparator agent in these studies was cefepime, [4][5][6] because PTZ and cefepime share a similar niche in antipseudomonal therapy. In these comparisons, PTZ was associated with higher rates of AKI versus cefepime.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Acute Kidney Injury in Patients Treated with IV Beta‐Lactam/Beta‐Lactamase Inhibitor Combinations

Burgess

2017

Pharmacotherapy

Study Objective Increased acute kidney injury (AKI) incidence has been reported in patients receiving piperacillin-tazobactam (PTZ) therapy compared to other beta-lactams. This study sought to determine if the addition of beta-lactamase inhibitors impact AKI incidence by comparing patients treated with PTZ or ampicillin-sulbactam (SAM). Design Retrospective cohort study Setting Large academic tertiary care hospital Patients Overall, 2,448 patients received PTZ (n=1,836) or SAM (n=612) for at least 48 hours between September 1, 2007 and September 30, 2015. Patients were excluded for pregnancy, cystic fibrosis, chronic kidney disease, and initial creatinine clearance (CrCl) < 30 mL/min. Patients were matched on Charlson Comorbidity Index (CCI), initial CrCl, hypotension exposure, various nephrotoxic drug exposures, history of diabetes, heart failure, and hypertension. Measurements and Main results AKI occurred in 265 patients at similar rates for both groups (PTZ 11.4% vs SAM 9.2%; p=0.14). After stratifying by vancomycin exposure and controlling for confounders, there was no difference in the risk of AKI for SAM or PTZ (adjusted OR 0.87, 95% CI 0.59–1.25). The addition of vancomycin to PTZ increased the likelihood of AKI compared to PTZ alone (adjusted OR 1.77, 95% CI 1.26–2.46). Concomitant SAM and VAN therapy was not associated with a significant increase in AKI compared to SAM monotherapy (adjusted OR 1.01, 95% CI 0.48–1.97). Conclusion Rates of AKI were similar for PTZ and SAM in a matched cohort. The addition of a beta-lactamase inhibitor is not likely the mechanism in the observed increased rates of AKI in patients treated with vancomycin and PTZ.