Estimating Creatinine Clearance: A Meta‐analysis

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: Methodsmentioning

confidence: 99%

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

Cox

Martin

et al. 2017

“…This endpoint was met if creatinine clearance (CrCL) decreased by 25% or greater from baseline at any time between treatment initiation and 48 h after the end of polymyxin therapy. Creatinine clearance was determined using the modified Cockroft-Gault equation (23). Multiple variables were evaluated as risk factors for AKI, including age, CCI, admission to an intensive care unit (ICU) or progressive care unit (PCU), polymyxin agent used (PMB versus CMS), loading dose, high polymyxin dose (CMS, Ն270 mg/day colistin base activity [CBA]; PMB, Ն200 mg/day), duration of therapy (Ͼ10 days), concurrent nephrotoxins (aminoglycosides, amphotericin B, vancomycin, calcineurin inhibitors, intravenous contrast, loop diuretics, nonsteroidal antiinflammatory drugs [NSAIDs], vasopressors), elevated baseline serum creatinine (Ͼ1.5 mg/dl), elevated total bilirubin (Ͼ3 mg/dl), and hypoalbuminemia (Ͻ3 g/dl) (10,11).…”

Section: Methodsmentioning

confidence: 99%

Nephrotoxicity in Patients with or without Cystic Fibrosis Treated with Polymyxin B Compared to Colistin

Crass

Burgess

et al. 2017

Nephrotoxicity is the primary adverse effect of the polymyxins. The relative rates of toxicity of polymyxin B and colistin have not been fully elucidated, especially in patients with cystic fibrosis (CF). A retrospective cohort study of adults treated with polymyxin B or colistin for at least 48 h was conducted. The primary endpoint was the incidence of kidney injury assessed by RIFLE (i.e., risk, injury, failure, loss, end-stage renal disease) criteria. Risk factors for kidney injury were evaluated using multivariate Cox regression. A total of 414 patients were evaluated, 220 of whom had CF. In patients without CF, there was no difference in kidney injury with polymyxin B and colistin (42.9% versus 50.3%, P ϭ 0.46). Loop diuretic exposure was a risk factor for kidney injury (adjusted hazard ratio [aHR], 1.82; 95% confidence interval [CI], 1.16 to 2.83) in this population. In patients with CF, polymyxin B and colistin were associated with similar rates of kidney injury (34.5% versus 29.8%, P ϭ 0.77). Diabetes (aHR, 2.68; 95% CI, 1.01 to 7.11), loop diuretics (aHR, 3.02; 95% CI, 1.36 to 6.73), and progressive care unit admission (aHR, 8.21; 95% CI, 2.55 to 26.46) were risk factors for kidney injury, while higher baseline serum creatinine levels (per 1 mg/dl) were protective (aHR, 0.08; 95% CI, 0.01 to 0.48). Total unadjusted kidney injury in polymyxin-treated patients was less frequent in those who had CF (30.5% versus 48.5%, P Ͻ 0.001). Polymyxin B and colistin are associated with a high incidence of kidney injury; cystic fibrosis may be protective against polymyxin nephrotoxicity, but further investigation is needed to confirm this conjecture.

“…Data collected included demographics, hospital visit data (length of stay, admitting and primary diagnosis codes), laboratory values and vital signs obtained throughout admission, immunosuppression status, receipt of concomitant nephrotoxins (listed in Table 1), severity of underlying comorbidity as defined by the Charlson comorbidity index (12), and mortality information. Baseline creatinine clearance was calculated with the adjusted Cockcroft-Gault equation from the first documented serum creatinine level measured during admission (13). Concomitant nephrotoxins were defined as receipt of at least 1 dose of a nephrotoxic agent during or within 24 h of treatment with ␤-lactams.…”

Section: Methodsmentioning

confidence: 99%

Influence of β-Lactam Infusion Strategy on Acute Kidney Injury

Cotner

Burgess

et al. 2017

Limited literature is available assessing nephrotoxicity with prolonged ␤-lactam infusions. This study compared the incidence of acute kidney injury (AKI) associated with a prolonged ␤-lactam infusion or an intermittent infusion. This was a retrospective, matched-cohort study at an academic medical center from July 2006 to September 2015. Adult patients who received piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) for at least 48 h were evaluated. Patients were excluded for preexisting renal dysfunction or pregnancy. The primary outcome was difference in incidence of AKI evaluated using the RIFLE (risk, injury, failure, loss, and end-stage) criteria. Patients in the intermittent group were matched 3:1 to patients in the prolonged-infusion group based on the following: ␤-lactam agent, age, gender, Charlson comorbidity index, baseline creatinine clearance, hypotension, receipt of vancomycin, and treatment in an intensive care unit. A total of 2,390 patients were included in the matched analysis, with 1,700 receiving intermittent infusions and 690 receiving prolonged infusion. The incidence of AKI was similar in the prolonged-infusion group to that in the intermittent-infusion group (21.6% versus 18.6%; P ϭ 0.1). After multivariate regression, prolonged infusion was not associated with increased odds of AKI (odds ratio [OR], 1.07; 95% confidence interval [95% CI], 0.83 to 1.39). Independent predictors of AKI included TZP therapy, concomitant nephrotoxins, hypotension, and heart failure. Although AKIs were numerically more common in patients receiving prolonged ␤-lactam infusions than those receiving intermittent infusions, prolonged infusion was not an independent risk factor for AKI.