piperacillin--tazobactam-drug-combination and Acute-Kidney-Injury

The combination of vancomycin and piperacillin/tazobactam (VAN + PTZ) provides a broad spectrum of activity against multiple pathogens. However, a major issue in previous research concerned significant nephrotoxicity associated with this drug combination, and most studies have been conducted in American and European countries, with no similar data available from China. Therefore, this study evaluated the nephrotoxic effects of VAN + PTZ in a large-scale Chinese cohort to determine the prevalence of acute kidney injury (AKI) in this population by comparing PTZ and vancomycin monotherapies and the combined use of vancomycin and β-lactam antibiotics.. This retrospective cohort study identified adult patients who received vancomycin either as monotherapy or in combination with PTZ or carbapenem (VAN + CAR) for at least 48 hours at Jiangsu Province Hospital from January 1, 2017, to December 31, 2018. Patients were also evaluated for the development of AKI, defined according to the Kidney Disease Improving Global Outcome criteria. Duration of vancomycin exposure, steady-state trough vancomycin concentrations, and other risk factors for AKI were assessed. A Bayesian network meta-analysis was conducted to validate our results and comparatively evaluate the nephrotoxicity of β-lactam antibiotics in combination with vancomycin.. In all, 752 patients were included in the present study. The prevalence of AKI was higher in the VAN + PTZ group than in the VAN and VAN + CAR groups (15.2% vs 4.0% and 6.0%, respectively). After adjustment for confounding factors, VAN + PTZ was still related to AKI (odds ratio [OR] = 4.37; 95% CI, 1.65-11.59; P = 0.003). The network meta-analysis indicated that VAN + PTZ was associated with a significantly higher risk for AKI than was VAN (OR = 3.23; 95% CI, 2.50-4.35), PTZ (OR = 2.86; 95% CI, 1.92-4.12), VAN + cefepime (FEP) (OR = 2.37; 95% CI, 1.80-3.19), or VAN + CAR (OR = 2.28; 95% CI, 1.64-3.21). However, there was no significant difference with respect to AKI prevalence among the VAN, PTZ, VAN + FEP, and VAN + CAR groups.. The prevalence of AKI was higher with VAN + PTZ therapy than with VAN or PTZ monotherapy or with the concurrent use of VAN and FEP or CAR in our study. Clinicians should adequately assess renal function and consider this differential risk for nephrotoxicity when choosing empiric antibiotics in hospitalized patients to minimize the rates of AKI.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Bayes Theorem; Cohort Studies; Drug Therapy, Combination; Humans; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prevalence; Retrospective Studies; Vancomycin

Recent studies have identified the combination of vancomycin with piperacillin-tazobactam (VPT) to be associated with increased nephrotoxicity. Multiple, large cohort studies have found this widely used combination to have a higher risk of nephrotoxicity than other regimens in a variety of populations.. This review summarizes the epidemiology and clinical features of VPT-associated acute kidney injury (AKI). Potential mechanisms involved in the pathogenesis of this phenomenon are also discussed. Key Message: VPT-associated nephrotoxicity is a recently recognized clinical entity. Clinical strategies to minimize the risk of toxicity in this setting include antimicrobial stewardship, monitoring of kidney function, and emerging data supporting the potential role for novel biomarkers in predicting and managing AKI.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Antimicrobial Stewardship; Creatinine; Critical Illness; Drug Therapy, Combination; Humans; Kidney Tubules; Nephritis; Patient Acuity; Piperacillin, Tazobactam Drug Combination; Risk Factors; Vancomycin

The antibiotic combination of vancomycin (VAN) and piperacillin-tazobactam (PTZ) has been associated with an increased risk of acute kidney injury (AKI) in both adult and pediatric patients. In this review, we highlight some of the limitations of existing pediatric studies evaluating the combination of VAN/PTZ, focusing on AKI risk in specific pediatric patient populations. We also review the variability in defining AKI in children and provide guidance to clinicians for use of prospective surveillance and stewardship in mitigating the risk of AKI in pediatric patients treated with combination of VAN/PTZ. Based on review of available pediatric studies, if the combination of VAN/PTZ is selected as an empirical antibiotic combination, it should be used in those at low risk for AKI and should be used with extreme caution in patients with additional nephrotoxic risks. Systems should be in place to monitor the use of VAN/PTZ and associated renal function in those receiving this antibiotic combination.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Child; Drug Therapy, Combination; Humans; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Retrospective Studies; Risk Factors; Vancomycin

Acute kidney injury is a devastating consequence observed with antibiotic therapy. The objective of this review was to summarize available data regarding the rates of acute kidney injury with vancomycin plus piperacillin/tazobactam compared to other beta-lactam combinations.. A PubMed search from 2011 to May 2020 was conducted using the following search terms: vancomycin AND piperacillin/tazobactam AND acute kidney injury. Additional references were identified from a review of citations. Articles evaluating exclusively paediatric patients and articles evaluating vancomycin monotherapy as the comparator group were excluded. Case reports and case series were also excluded.. There were 18 studies included. Ten studies adjusted for potential confounders of acute kidney injury. Fourteen retrospective studies, one prospective study and three meta-analyses found the combination of vancomycin/piperacillin/tazobactam to be associated with a higher rate of acute kidney injury than the comparator group(s).. Although there are data to support that the combination of vancomycin plus piperacillin-tazobactam increases the risk of acute kidney, much of the data come from small retrospective studies with variable adjustment for confounders. Furthermore, study heterogeneity on inclusion criteria and evaluation of long-term outcomes should be cautiously interpreted. Finally, additional data suggest that the risk of acute kidney injury seems to be minimized with shorter courses of therapy. Without prospective studies available, antimicrobial stewardship efforts should continue to target reducing broad-spectrum regimens, often limiting the need for long-term vancomycin/piperacillin/tazobactam combination.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Piperacillin, Tazobactam Drug Combination; Risk; Vancomycin

The objective of this systematic review and meta-analysis was to assess acute kidney injury with combination therapy of vancomycin plus piperacillin-tazobactam, in general, adult patients and in critically ill adults. Rates of acute kidney injury, time to acute kidney injury, and odds of acute kidney injury were compared with vancomycin monotherapy, vancomycin plus cefepime or carbapenem, or piperacillin-tazobactam monotherapy.. Studies were identified by searching Pubmed, Embase, Web of Science, and Cochrane from inception to April 2017. Abstracts from selected conference proceedings were manually searched.. Articles not in English, pediatric studies, and case reports were excluded.. Two authors independently extracted data on study methods, rates of acute kidney injury, and time to acute kidney injury. Effect estimates and 95% CIs were calculated using the random effects model in RevMan 5.3.. Literature search identified 15 published studies and 17 conference abstracts with at least 24,799 patients. The overall occurrence rate of acute kidney injury was 16.7%, with 22.2% for vancomycin plus piperacillin-tazobactam and 12.9% for comparators. This yielded an overall number needed to harm of 11. Time to acute kidney injury was faster for vancomycin plus piperacillin-tazobactam than vancomycin plus cefepime or carbapenem, but not significantly (mean difference, -1.30; 95% CI, -3.00 to 0.41 d). The odds of acute kidney injury with vancomycin plus piperacillin-tazobactam were increased versus vancomycin monotherapy (odds ratio, 3.40; 95% CI, 2.57-4.50), versus vancomycin plus cefepime or carbapenem (odds ratio, 2.68; 95% CI, 1.83-3.91), and versus piperacillin-tazobactam monotherapy (odds ratio, 2.70; 95% CI, 1.97-3.69). In a small subanalysis of 968 critically ill patients, the odds of acute kidney injury were increased versus vancomycin monotherapy (odds ratio, 9.62; 95% CI, 4.48-20.68), but not significantly different for vancomycin plus cefepime or carbapenem (odds ratio, 1.43; 95% CI, 0.83-2.47) or piperacillin-tazobactam monotherapy (odds ratio, 1.35; 95% CI, 0.86-2.11).. The combination of vancomycin plus piperacillin-tazobactam increased the odds of acute kidney injury over vancomycin monotherapy, vancomycin plus cefepime or carbapenem, and piperacillin-tazobactam monotherapy. Limited data in critically ill patients suggest the odds of acute kidney injury are increased versus vancomycin monotherapy, and mitigated versus the other comparators. Further research in the critically ill population is needed.

Topics: Acute Kidney Injury; Adult; Critical Care; Drug Therapy, Combination; Humans; Observational Studies as Topic; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Randomized Controlled Trials as Topic; Vancomycin

As a tricyclic glycopeptide antibiotic used to treat acute infections, Vancomycin (VAN) is often administered with piperacillin/tazobactam (PT) to treat various infections in clinical practice. However, whether the combination of these two drugs, compared to VAN alone, can cause an increased risk of acute kidney injury (AKI) remains controversial.. This study aims to identify the correlation between the development of AKI and the combined use of VAN and PT.. We conducted a meta-analysis of eight observational cohort studies (a total of 10727 participants received VAN and PT versus VAN and other β-lactams). PubMed, Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI) Database, Wan Fang Digital Periodicals Database (WFDP), and China Science Citation Database (CSCD) were searched through April 2017 using "vancomycin" and "piperacillin" and "tazobactam" as well as "acute kidney injury" or "acute renal failure" or "AKI" or "ARF" or "nephrotoxicity." Two reviewers extracted the data and assessed the risk of bias.. A correlation was found between the development of AKI and concurrent use of VAN and PT compared with concomitant VAN and β-lactams (OR 1.57; 95% CI, 1.13-2.01; I. Regarding β-lactam therapy in clinical practice, an elevated risk of AKI due to the combined use of VAN and PT should be considered.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; beta-Lactams; Drug Therapy, Combination; Humans; Piperacillin, Tazobactam Drug Combination; Vancomycin

Vancomycin use is often associated with nephrotoxicity. It remains uncertain, however, to what extent vancomycin is directly responsible, as numerous potential risk factors for acute kidney injury frequently coexist. Herein, we critically examine available data in adult patients pertinent to this question. We review the pharmacokinetics/pharmacodynamics of vancomycin metabolism. Efficacy and safety data are discussed. The pathophysiology of vancomycin nephrotoxicity is considered. Risk factors for nephrotoxicity are enumerated, including the potential synergistic nephrotoxicity of vancomycin and piperacillin-tazobactam. Suggestions for clinical practice and future research are given.

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Risk Factors; Vancomycin

Acute kidney injury (AKI) is a common complication in the critically ill population, is multifactorial and associated with increased mortality. Drug-induced kidney injury is a significant contributor to the development of AKI. The purpose of this review is to provide updates in the epidemiology, susceptibility and management of drug-induced kidney disease (DIKD).. Recent changes in guidelines for the management of serious infections in the critically ill have resulted in an increased frequency of DIKD. Varying definitions employed in clinical trials has complicated the awareness of this adverse event. Causality assessment is often missing from studies as it is complicated by the need to evaluate competing AKI risk factors. This has led to uncertainty in the nephrotoxic risk of commonly used drugs.. Standard criteria for DIKD should be applied in clinical trials to improve our understanding of the frequency of these events. Adjudication of these events will improve the clinician's ability to evaluate the causal relationship and relative contribution of specific drugs to the AKI event.

Topics: Acute Kidney Injury; Critical Illness; Disease Susceptibility; Drug Therapy, Combination; Humans; Intensive Care Units; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Renal Replacement Therapy; Risk Factors; Vancomycin

Bile cast nephropathy is a condition of renal dysfunction in the setting of hyperbilirubinemia. There are very few cases of this condition reported in the last decade and a lack of established treatment guidelines. While the exact etiology remains unknown, bile cast nephropathy is presumed to be secondary to multiple concurrent insults to the kidney including direct toxicity from bile acids, obstructive physiology from bile casts, and systemic hypoperfusion from vasodilation. Therapy directed at bilirubin reduction may improve renal function, but will likely need dialysis or plasmapheresis as well. We report our case of bile cast nephropathy and the therapeutic measures undertaken in a middle-aged male with chronic renal insufficiency that developed hyperbilirubinemia and drug-induced liver injury secondary to antibiotic use. He developed acute renal injury in the setting of rising bilirubin. He subsequently had a progressive decline in renal and hepatic function, requiring dialysis and plasmapheresis with some improvement, ultimately requiring transplantation.

Topics: Acute Kidney Injury; Adrenal Cortex Hormones; Anion Exchange Resins; Anti-Bacterial Agents; Biopsy; Chemical and Drug Induced Liver Injury, Chronic; Cholagogues and Choleretics; Cholestyramine Resin; Humans; Hyperbilirubinemia; Jaundice, Obstructive; Male; Middle Aged; Osteomyelitis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Plasmapheresis; Renal Dialysis; Renal Insufficiency, Chronic; Ursodeoxycholic Acid

To evaluate the association of the development of acute kidney injury (AKI) when piperacillin-tazobactam is used in combination with vancomycin compared with vancomycin with or without a β-lactam.. Meta-analysis of 15 observational cohort studies.. A total of 3258 adult inpatients who received vancomycin + piperacillin-tazobactam versus vancomycin alone (10 studies); vancomycin + piperacillin-tazobactam versus vancomycin + β-lactam (four studies); or vancomycin + piperacillin-tazobactam versus vancomycin alone or vancomycin + other antibiotics (one study).. Vancomycin + piperacillin-tazobactam was associated with an increased risk of AKI compared with vancomycin ± β-lactam. Practitioners need to be vigilant about this association when prescribing this combination of antibiotics.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Vancomycin

Antibiotics are time-critical in the management of sepsis. When infectious organisms are unknown, patients are treated with empiric antibiotics to include coverage for gram-negative organisms, such as antipseudomonal cephalosporins and penicillins. However, in observational studies, some antipseudomonal cephalosporins (eg, cefepime) are associated with neurologic dysfunction while the most common antipseudomonal penicillin (piperacillin-tazobactam) is associated with acute kidney injury (AKI). No randomised control trials have compared these regimens. This manuscript describes the protocol and analysis plan for a trial designed to compare the effects of antipseudomonal cephalosporins and antipseudomonal penicillins among acutely ill patients receiving empiric antibiotics.. The Antibiotic Choice On ReNal outcomes trial is a prospective, single-centre, non-blinded randomised trial being conducted at Vanderbilt University Medical Center. The trial will enrol 2500 acutely ill adults receiving gram-negative coverage for treatment of infection. Eligible patients are randomised 1:1 to receive cefepime or piperacillin-tazobactam on first order entry of a broad-spectrum antibiotic covering gram-negative organisms. The primary outcome is the highest stage of AKI and death occurring between enrolment and 14 days after enrolment. This will be compared between patients randomised to cefepime and randomised to piperacillin-tazobactam using an unadjusted proportional odds regression model. The secondary outcomes are major adverse kidney events through day 14 and number of days alive and free of delirium and coma in 14 days after enrolment. Enrolment began on 10 November 2021 and is expected to be completed in December 2022.. The trial was approved by the Vanderbilt University Medical Center institutional review board (IRB#210591) with a waiver of informed consent. Results will be submitted to a peer-reviewed journal and presented at scientific conferences.. NCT05094154.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Cefepime; Cephalosporins; Humans; Kidney; Penicillins; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies

Recent studies have shown an increased risk of acute kidney injury (AKI) induced by vancomycin + piperacillin-tazobactam (VPT) combination. In this study, the efficacy of intravenous magnesium sulfate in prevention of VPT induced AKI in critically ill patients admitted to the ICU has been evaluated.. In an open-label, placebo-controlled, randomized clinical trial, 72 adults (≥ 18 years old) who had indications to receive VPT as empiric therapy were assigned to the magnesium or control group in 1:1 ratio. Concomitant with VPT, intravenous infusion of magnesium sulfate was started for patients in the magnesium group. The target serum level of magnesium was defined 3 mg/dl. Patients in the control group received normal saline as placebo. The target serum level of magnesium was defined 1.9 mg/dl in this group. The study's primary outcome was incidence of AKI during and up to 48 h after the treatment course. Escalation and de-escalation of VPT regimen, duration of hospitalization, length of ICU stay and 28-day mortality were secondary outcomes.. Thirty patients in each group completed the examination. Five patients in the magnesium group and 11 patients in the control group experienced AKI (p = 0.072). De-escalation of VPT regimen was done approximately in 60% of patients. Duration of hospitalization and length of ICU stay were not statistically different between the groups. Finally, 28-day mortality was 23.33% in each group. Although the incidence of AKI was not statistically different between the groups in unadjusted logistic regression model, it became significant after adjusting for confounding factors [unadjusted model (OR = 0.34; 95% CI: 0.10-1.16, p = 0.084), adjusted model: (OR = 0.26; 95% CI: 0.07-0.96, p = 0.04)].. Administration of magnesium sulfate with the target serum levels around 3 mg/dL reduced the incidence of AKI in critically ill patients who were receiving VPT as empric therapy.

Topics: Acute Kidney Injury; Administration, Intravenous; Aged; Critical Illness; Female; Humans; Incidence; Length of Stay; Logistic Models; Magnesium Sulfate; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Treatment Outcome; Vancomycin

Empiric antimicrobials are frequently utilized in the pre-engraftment phase after hematopoietic cell transplantation (HCT). Recent evidence suggests an increased risk of acute kidney injury (AKI) from combination of vancomycin with piperacillin/tazobactam; however, this has not specifically been evaluated in the HCT population. A single-center, retrospective review was conducted from 2011 to 2017 on 110 autologous and 60 allogeneic HCT patients with the primary objective of comparing incidence of AKI for those who received vancomycin with piperacillin/tazobactam versus vancomycin with cefepime in the pre-engraftment phase. Demographics and outcomes were compared for all patients who received vancomycin with piperacillin/tazobactam versus vancomycin with cefepime as well as within the autologous and allogeneic subgroups. The primary endpoint of incidence of AKI, defined as increase in serum creatinine by .3 mg/dL or >50% from baseline (whichever was larger), was significantly higher for those who received vancomycin with piperacillin/tazobactam versus cefepime for the overall cohort (68% versus 27%; P < .001) resulting in an odds ratio (OR) of 5.16 (95% confidence interval [CI], 2.5 to 10.5) when adjusting for hypotension. Results were similar within the autologous (59% versus 22%; P < .001; OR, 4.63; 95% CI, 1.85 to 11.6) and allogeneic (79% versus 39%; P= .0021; OR, 5.41; 95% CI, 1.60 to 18.3) subgroups. Within the overall cohort between those who received vancomycin with piperacillin/tazobactam versus cefepime the time to onset of AKI was more commonly within 48 hours of concomitant antimicrobial use (53% versus 26%; P= .012), whereas resolution of AKI by discharge date was not different (39% versus 26%; P= .23). No difference in percentage of patients requiring at least 1 session of dialysis, duration of hospital stay, or 30-day mortality was found between overall cohorts. Further studies of HCT patients are warranted to fully elucidate the risk of various combination antimicrobial regimens on renal outcomes.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Allografts; Autografts; Cefepime; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Survival Rate; Vancomycin

Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactams (BLs) such as piperacillin-tazobactam (TZP) but has not been evaluated with ceftolozane-tazobactam (C/T). Our aim was to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared with VAN in combination to TZP (VAN-TZP).. We conducted a multicenter, observational, comparative study across the United States. The primary analysis was a composite outcome of AKI and risk, injury, failure, loss, end stage renal disease; Acute Kidney Injury Network; or VAN-induced nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis was conducted to adjust for confounding variables and stratified Kaplan-Meir analysis to assess the time to nephrotoxicity between the 2 groups.. We included VAN/C/T (n = 90) and VAN-TZP (n = 284) at an enrollment ratio of 3:1. The primary outcome occurred in 12.2% vs 25.0% in the VAN-C/T and VAN-TZP groups, respectively (P = .011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with VAN-C/T; with an adjusted odds ratio of 3.308 (95% confidence interval, 1.560-6.993). Results of the stratified Kaplan-Meir analysis with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients who received VAN-TZP (P = .004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = .001).. Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to piperacillin, which is a component in VAN-TZP but not in VAN-C/T.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; beta-Lactams; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Humans; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Tazobactam; Vancomycin

The use of regional citrate anticoagulation during continuous venovenous hemodiafiltration (CVVHDF) has increased worldwide. However, data on its effect on the pharmacokinetics of antibiotics are limited. In this study, the authors aimed to measure the clearance of piperacillin-tazobactam and vancomycin in patients receiving CVVHDF with regional citrate anticoagulation.. This study measured piperacillin-tazobactam and vancomycin concentrations in patients receiving CVVHDF with regional citrate anticoagulation. Dosing regimens were independently selected by intensivists. Arterial blood and effluent fluid samples were obtained over a single dosing interval and analyzed using ultra-high-performance liquid chromatography with tandem mass spectrometry.. Seventeen sampling intervals in 15 patients (9 receiving piperacillin-tazobactam only, 4 receiving vancomycin only, and 2 receiving both) were used. The median overall clearance for piperacillin was 35.2 mL/min [interquartile range (IQR): 32.2-38.6], 70 mL/min (IQR: 62.7-76.2) for tazobactam, and 29.5 mL/min (IQR: 26.2-32) for vancomycin.. This is the first study to quantify the pharmacokinetics of vancomycin and piperacillin-tazobactam in patients receiving CVVHDF with regional citrate anticoagulation. These results indicate high clearance and provide key information to guide optimal dosing.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Anticoagulants; Citrates; Citric Acid; Critical Illness; Humans; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tazobactam; Vancomycin

To evaluate the effects of prophylactic piperacillin-tazobactam (PT) on inpatient acute kidney injury (AKI) and fracture-related infection (FRI) in patients with open fractures.. The study was conducted at a Level 1 trauma center.. We reviewed 358 Gustilo-Anderson type II and III open fractures at our institution from January 2013 to December 2017.. Administration of PT (the PT group) or antibiotics other than PT (the historical control group) during the first 48 hours of arrival for open fracture antibiotic prophylaxis.. The main outcome measurements were rates of inpatient AKI and FRI within six months after definitive fixation.. There were 176 patients in the PT group and 182 patients in the historical control group. The PT group had worse American Society of Anesthesiologists class ( P = 0.004) and injury severity scores ( P < 0.001), a higher average number of debridements before closure/coverage ( P = 0.043), and higher rates of gross soil contamination ( P = 0.049) and staged procedures ( P = 0.008) compared with the historical control group.There was no difference in the rate of AKI between the PT and historical control groups (5.7% vs. 2.7%, P = 0.166) nor when stratified by Gustilo-Anderson fracture classification (type II: 5.8% vs. 3.6%, P = 0.702; type III: 5.6% vs. 2.0%, P = 0.283). There was no significant difference in the rate of FRI between the PT and historical control groups (23.6% vs. 19.6%, P = 0.469).. The use of PT in prophylactic antimicrobial treatment in patients with Gustilo-Anderson type II and III open fractures does not increase the rate of AKI or FRI. We believe PT can be used as an effective monotherapy in these patients without an increased risk of renal injury, but future investigations are necessary.. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Topics: Acute Kidney Injury; Antibiotic Prophylaxis; Fractures, Open; Humans; Piperacillin, Tazobactam Drug Combination; Surgical Wound Infection; Tibial Fractures; Treatment Outcome

There is uncertainty about whether piperacillin/tazobactam (PT) increases the risk of acute kidney injury (AKI) in patients without concomitant use of vancomycin. This study compared the risk of hospital-acquired AKI (HA-AKI) among adults treated with PT or antipseudomonal β-lactams (meropenem, ceftazidime) without concomitant use of vancomycin.. This real-world study analysed the data from China Renal Data System and assessed the risk of HA-AKI in adults hospitalized with infection after exposure to PT, meropenem or ceftazidime in the absence of concomitant vancomycin. The primary outcome was any stage of HA-AKI according to the Kidney Disease Improving Global Outcomes guidelines. A multi-variable Cox regression model and different propensity score (PS) matching models were used.. Among the 29,441 adults [mean (standard deviation) age 62.44 (16.84) years; 17,980 females (61.1%)] included in this study, 14,721 (50%) used PT, 9081 (31%) used meropenem and 5639 (19%) used ceftazidime. During a median follow-up period of 8 days, 2601 (8.8%) develped HA-AKI. The use of PT was not associated with significantly higher risk of HA-AKI compared with meropenem [adjusted hazard ratio (aHR) 1.07, 95% confidence interval (CI) 0.97-1.19], ceftazidime (aHR 1.09, 95% CI 0.92-1.30) or both agents (aHR 1.07, 95% CI 0.97-1.17) after adjusting for confounders. Results were consistent in stratified analyses, PS matching using logistic regression or random forest methods to generate a PS, and in an analysis restricting outcomes to AKI stage 2-3.. Without concomitant use of vancomycin, the risk of AKI following PT therapy is comparable with that of meropenem or ceftazidime among adults hospitalized with infection.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Ceftazidime; Data Analysis; Drug Therapy, Combination; Female; Humans; Meropenem; Middle Aged; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Piperacillin/tazobactam, a commonly used antibiotic, is associated with acute kidney injury (AKI). The relationship between piperacillin concentrations and AKI remains unknown.. Estimate piperacillin exposures in critically ill children and young adults administered piperacillin/tazobactam to identify concentrations and clinical factors associated with piperacillin-associated AKI.. We assessed piperacillin pharmacokinetics in 107 patients admitted to the paediatric ICU who received at least one dose of piperacillin/tazobactam. Piperacillin AUC, highest peak (Cmax) and highest trough (Cmin) in the first 24 hours of therapy were estimated. Piperacillin-associated AKI was defined as Kidney Disease: Improving Global Outcomes (KDIGO) Stage 2/3 AKI present >24 hours after initial piperacillin/tazobactam dose. Likelihood of piperacillin-associated AKI was rated using the Naranjo Adverse Drug Reaction Probability Scale. Multivariable logistic regression was performed to identify patient and clinical predictors of piperacillin-associated AKI.. Out of 107 patients, 16 (15%) were rated as possibly or probably having piperacillin-associated AKI. Estimated AUC and highest Cmin in the first 24 hours were higher in patients with piperacillin-associated AKI (2042 versus 1445 mg*h/L, P = 0.03; 50.1 versus 10.7 mg/L, P < 0.001). Logistic regression showed predictors of piperacillin-associated AKI included higher Cmin (OR: 5.4, 95% CI: 1.7-23) and age (OR: 1.13, 95% CI: 1.05-1.25).. We show a relationship between estimated piperacillin AUC and highest Cmin in the first 24 hours of piperacillin/tazobactam therapy and piperacillin-associated AKI, suggesting total piperacillin exposure early in the course is associated with AKI development. These data could serve as the foundation for implementation of model-informed precision dosing to reduce AKI incidence in patients given piperacillin/tazobactam.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Child; Drug Therapy, Combination; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Tazobactam; Vancomycin; Young Adult

Patients with cystic fibrosis (CF) may be treated with piperacillin-tazobactam (PZT) for acute pulmonary exacerbations. Extending the infusion of PZT is one strategy to increase efficacy. Direct comparison, with respect to the incidence of acute kidney injury (AKI), between these two strategies has not been evaluated in pediatric patients with CF. The primary objective of this study was to compare the incidence of AKI in pediatric CF patients receiving extended infusion (EI) PZT versus traditional infusion (TI).. This IRB-approved, retrospective analysis included patients ages 30 days to 18 years that received PZT for at least 48 h between January 1, 2008, and January 1, 2020. PZT was infused over 30 min (TI group) or 4 h (EI group).. Two hundred and four patients were included (TI: 109, EI: 95). Median age was 8 years (4-13) and 7 years (3-12) in the TI and EI groups (p = 0.15). The groups did not differ significantly in their baseline characteristics. There were 12 (11%) AKIs in the TI group and 8 (8.4%) in the EI group (p = 0.53). There was one occurrence of serum sickness in the TI group and none in the EI group. The incidence of thrombocytopenia was similar between the two groups. Median treatment duration was 8 days (5-11) and 9 days (5-13) for the TI and EI groups, respectively (p = 0.24).. There was no significant increase in AKI in pediatric patients with CF receiving PZT by EI compared with TI. EI may be utilized to optimize the pharmacokinetics of PZT in pediatric CF patients.

Topics: Acute Kidney Injury; Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Cystic Fibrosis; Drug Therapy, Combination; Humans; Infant, Newborn; Infusions, Intravenous; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

Rates of nephrotoxic AKI are not well described in adults due to lack of a clear definition, debate over which drugs should be considered nephrotoxins, and illness-related confounding. Nephrotoxic Injury Negated by Just-in Time Action (NINJA), a program that reduces rates of nephrotoxic AKI in pediatric populations, may be able to address these concerns, but whether NINJA can be effectively applied to adults remains unclear.. In this retrospective cohort study conducted at the University of Iowa Hospital, we included adult patients admitted to a general hospital floor for ≥48 hours during 2019. The NINJA algorithm screened charts for high nephrotoxin exposure and AKI. After propensity score matching, Cox proportional hazard modeling was used to evaluate the relationship between nephrotoxic exposure and all-stage AKI, stage 2-3 AKI, or death. Additional analyses evaluated the most frequent nephrotoxins used in this population.. Of 11,311 patients, 1527 (16%) had ≥1 day of high nephrotoxin exposure. Patients with nephrotoxic exposures subsequently developed AKI in 29% of cases, and 22% of all inpatient AKI events met nephrotoxic AKI criteria. Common nephrotoxins were vancomycin, iodinated contrast dye, piperacillin-tazobactam, acyclovir, and lisinopril. After propensity score matching, Cox proportional hazard models for high nephrotoxin exposure were significantly associated with all AKI (hazard ratio [HR] 1.43, 1.19-1.72, P<0.001), stage 2-3 AKI (HR 1.78, 1.18-2.67, P=0.006), and mortality (HR 2.12, 1.09-4.11, P=0.03).. Nephrotoxin exposure in adults is common and is significantly associated with AKI development, including stage 2-3 AKI.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Child; Hospitalization; Humans; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Evidence regarding acute kidney injury associated with concomitant administration of vancomycin and piperacillin-tazobactam is conflicting, particularly in patients in the ICU.. Does a difference exist in the association between commonly prescribed empiric antibiotics on ICU admission (vancomycin and piperacillin-tazobactam, vancomycin and cefepime, and vancomycin and meropenem) and acute kidney injury?. This was a retrospective cohort study using data from the eICU Research Institute, which contains records for ICU stays between 2010 and 2015 across 335 hospitals. Patients were enrolled if they received vancomycin and piperacillin-tazobactam, vancomycin and cefepime, or vancomycin and meropenem exclusively. Patients initially admitted to the ED were included. Patients with hospital stay duration of < 1 h, receiving dialysis, or with missing data were excluded. Acute kidney injury was defined as Kidney Disease: Improving Global Outcomes stage 2 or 3 based on serum creatinine component. Propensity score matching was used to match patients in the control (vancomycin and meropenem or vancomycin and cefepime) and treatment (vancomycin and piperacillin-tazobactam) groups, and ORs were calculated. Sensitivity analyses were performed to study the effect of longer courses of combination therapy and patients with renal insufficiency on admission.. Thirty-five thousand six hundred fifty-four patients met inclusion criteria (vancomycin and piperacillin-tazobactam, n = 27,459; vancomycin and cefepime, n = 6,371; vancomycin and meropenem, n = 1,824). Vancomycin and piperacillin-tazobactam was associated with a higher risk of acute kidney injury and initiation of dialysis when compared with that of both vancomycin and cefepime (Acute kidney injury: OR, 1.37 [95% CI, 1.25-1.49]; dialysis: OR, 1.28 [95% CI, 1.14-1.45]) and vancomycin and meropenem (Acute kidney injury: OR, 1.27 [95%, 1.06-1.52]; dialysis: OR, 1.56 [95% CI, 1.23-2.00]). The odds of acute kidney injury developing was especially pronounced in patients without renal insufficiency receiving a longer duration of vancomycin and piperacillin-tazobactam therapy compared with vancomycin and meropenem therapy.. VPT is associated with a higher risk of acute kidney injury than both vancomycin and cefepime and vancomycin and meropenem in patients in the ICU, especially for patients with normal initial kidney function requiring longer durations of therapy. Clinicians should consider vancomycin and meropenem or vancomycin and cefepime to reduce the risk of nephrotoxicity for patients in the ICU.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Cefepime; Critical Illness; Drug Therapy, Combination; Humans; Meropenem; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Cephalosporins; Clinical Trials as Topic; Coma; Critical Illness; Delirium; Drug Therapy, Combination; Humans; Piperacillin, Tazobactam Drug Combination

Recent clinical studies have reported additive nephrotoxicity with the combination of vancomycin and piperacillin-tazobactam. However, preclinical models have failed to replicate this finding. This study assessed differences in iohexol-measured glomerular filtration rate (GFR) and urinary injury biomarkers among rats receiving this antibiotic combination. Male Sprague-Dawley rats received either intravenous vancomycin, intraperitoneal piperacillin-tazobactam, or both for 96 h. Iohexol-measured GFR was used to quantify real-time kidney function changes. Kidney injury was evaluated with the urinary biomarkers kidney injury molecule-1 (KIM-1), clusterin, and osteopontin. Compared to the control, rats that received vancomycin had numerically lower GFRs after drug dosing on day 3. Rats in this group also had elevations in urinary KIM-1 on experimental days 2 and 4. Increasing urinary KIM-1 was found to correlate with decreasing GFR on experimental days 1 and 3. Rats that received vancomycin plus piperacillin-tazobactam (vancomycin+piperacillin-tazobactam) did not exhibit worse kidney function or injury biomarkers than rats receiving vancomycin alone. The combination of vancomycin and piperacillin-tazobactam does not cause additive nephrotoxicity in a translational rat model. Future clinical studies investigating this antibiotic combination should employ more sensitive biomarkers of kidney function and injury, similar to those utilized in this study.

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Biomarkers; Drug Therapy, Combination; Glomerular Filtration Rate; Iohexol; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Rats; Rats, Sprague-Dawley; Retrospective Studies; Vancomycin

The incidence of acute kidney injury (AKI) caused by vancomycin hydrochloride (VCM) was reported to be 5-43%. VCM-induced AKI was reported to be more likely to occur 4-17 days after initiating VCM treatment; however, it may occur earlier. The aim of this study was therefore to investigate risk factors for the development of AKI within two (AKI2days) and seven (AKI7days) days of VCM administration.. This was a single-center, retrospective study including patients who underwent VCM therapy between April 1, 2013, and December 31, 2019. AKI was evaluated based on the Kidney Disease: Improving Global Outcomes criteria.. In total, 287 patients were enrolled. The incidence of VCM-induced AKI within 7 days was 10.8% (31/286 cases), and the incidence of AKI within 2 days was 5.9% (15/252 cases). Serum VCM trough concentrations and tazobactam-piperacillin (TZP) were shown to be a risk factor for VCM-induced AKI. The serum VCM trough concentration was 12.67 μg/mL within the 48 h threshold (AKI2days) and 19.03 μg/mL within the 7-day threshold (AKI7days).. Our study demonstrated that high serum VCM trough concentrations and the combination of VCM and TZP were independent risk factors for VCM-induced AKI. Avoiding the concomitant use of TZP, or thorough monitoring of renal function with the concomitant use of TZP, may be helpful in reducing the occurrence of AKI. Furthermore, monitoring serum VCM trough concentrations within 2 days may effectively reduce the incidence of AKI.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Vancomycin

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial.. To determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction.. The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022.. Patients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam.. The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days.. There were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, -1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]).. Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction.. ClinicalTrials.gov Identifier: NCT05094154.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Cefepime; Coma; Delirium; Drug Therapy, Combination; Female; Humans; Kidney; Male; Middle Aged; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis

Acute kidney injury (AKI) is common among hospitalized patients with community-acquired pneumonia (CAP). We aimed to estimate and compare the risk of AKI for various antibiotic combinations in adults hospitalized for CAP.. We conducted a retrospective cohort study of the Premier Healthcare Database containing all admissions for 660 US hospitals from 2010 to 2015. We included adults aged ≥18 years hospitalized with CAP and considered 6 different antibiotic combinations based on continuous use in the first 3 hospital days. The primary outcome was incident AKI, defined by ICD-9 codes 584.5-584-9. We evaluated associations of AKI with in-hospital mortality and length-of-stay. We excluded patients who were admitted directly to the intensive care unit, had AKI codes present on admission or had dialysis in the first 2 days. We used generalized linear mixed models with the hospital as a random effect and covariate adjustment for patient demographics, comorbidities, other treatments on day 0/1, and hospital characteristics.. The total sample included 449,535 patients, 3.15% of whom developed AKI. All other regimens but fluoroquinolones exhibited higher AKI odds than 3rd generation cephalosporin with or without macrolide. The combination of piperacillin/tazobactam and vancomycin with or without other antibiotics was associated with the highest AKI odds (OR = 1.89; 95% CI: 1.73-2.06). Patients with incident AKI had an increased odds of hospital mortality (OR = 6.37; 95% CI: 6.07-6.69) and longer length-of-stay (mean multiplier = 1.84; 95% CI: 1.82, 1.86).. Compared to 3rd generation cephalosporin with or without macrolide, piperacillin/tazobactam, vancomycin, and their combination were associated with higher odds of developing AKI, which in turn were associated with worse clinical outcomes.

Topics: Acute Kidney Injury; Adolescent; Adult; Anti-Bacterial Agents; Cephalosporins; Community-Acquired Infections; Female; Humans; Macrolides; Male; Piperacillin, Tazobactam Drug Combination; Pneumonia; Retrospective Studies; Vancomycin

The risk of acute kidney injury (AKI) associated with concomitant vancomycin and piperacillin/tazobactam in the intensive care unit (ICU) remains controversial. The aim of this study was to compare the AKI incidence associated with concomitant vancomycin and piperacillin/tazobactam compared to either cefepime or meropenem with vancomycin in the ICU.. A multicenter, retrospective, propensity score-matched cohort study was conducted in adult ICU patients administered vancomycin in combination with either piperacillin/tazobactam, cefepime, or meropenem were included. Patients developing AKI ≤48 h following combination therapy initiation were excluded. The primary endpoint was to compare the incidence of AKI associated with concomitant antimicrobial therapy. Multivariable Cox regression modeling in predicting AKI was also conducted.. A total of 1044 patients were matched. The AKI incidence in vancomycin- piperacillin/tazobactam and vancomycin-cefepime/meropenem groups were 21.9% and 16.8%, respectively (p = 0.068). Multivariable prediction models showed concomitant vancomycin-piperacillin/tazobactam was an independent risk factor of AKI using serum creatinine only (HR 1.52, 1.10-2.10, p = 0.011) and serum creatinine with urine output-based KDIGO criteria (HR 1.77, 1.18-2.67, p = 0.006). No significant differences between groups were observed for AKI recovery patterns or mortality.. Concomitant vancomycin and piperacillin/tazobactam administration in adult ICU patients was independently associated with an increased risk of AKI.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Cefepime; Cohort Studies; Critical Illness; Drug Therapy, Combination; Humans; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Propensity Score; Retrospective Studies; Vancomycin

Topics: Acute Kidney Injury; Administration, Oral; Age Factors; Aged; Aged, 80 and over; Databases as Topic; Drug Therapy, Combination; Female; Humans; Japan; Male; Middle Aged; Pharmacovigilance; Piperacillin, Tazobactam Drug Combination; Risk Factors; Sex Factors; Vancomycin

Late-onset sepsis is common in extremely low birth weight (ELBW) infants, and it leads to the use of antibiotics to cover resistant organisms, which can be nephrotoxic. Here we have investigated the role of vancomycin plus piperacillin-tazobactam on the rate of acute kidney injury (AKI).. In a retrospective case-control study, medical records of all ELBW infants who were admitted to our Neonatal Intensive Care Unit (NICU) with late onset sepsis who were prescribed vancomycin plus piperacillin-tazobactam were reviewed for demographics, clinical characteristics, use of potential nephrotoxic medications and outcomes.. During the study period, 264 patients were admitted, of whom 28.4%(75/264) received vancomycin plus piperacillin-tazobactam and were matched with 64 controls. There were no differences in gestational age or birth weight between cases and controls [688±160 vs. 689±162 grams (p = 0.99), and 24.7±1.8 vs. 24.7±1.6 weeks (p = 0.99) respectively]. There was no difference in the rate of sepsis between cases and controls [76%(55/72) vs. 64%(41/64) respectively, p = 0.11]. Infants exposed to vancomycin plus piperacillin-tazobactam had a higher percentage of concomitant use of vasopressors and amphotericin. To adjust for confounders, a logistic regression analysis was conducted with AKI as the dependent variable. Use of vasopressors and vancomycin plus piperacillin-tazobactam were the only risk factors associated with AKI with an adjusted OR (95%CI) of 4.08 (1.90-8.74), p < 0.001; and 2.87 (1.26-6.53), p = 0.01 respectively.. The use of vancomycin plus piperacillin-tazobactam in ELBW infants is associated with an increased risk for AKI.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Case-Control Studies; Drug Therapy, Combination; Female; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Vancomycin

Several factors related to vancomycin-induced nephrotoxicity (VIN) have not yet been clarified. In the present study, we used Japanese big data to investigate novel factors and their high-risk combinations that influence VIN.. We employed a large Japanese electronic medical record database and included patients who had been administered intravenous vancomycin between June 2000 and December 2020. VIN was defined as an increase in serum creatinine ≥0.5 mg/dL or 1.5-fold higher than the baseline. The outcomes were: (1) factors affecting VIN that were identified using multiple logistic regression analysis, and (2) combinations of factors that affect the risk of VIN according to a decision tree analysis, which is a typical machine learning method.. Of the 7306 patients that were enrolled, VIN occurred in 14.2% of them (1035). A multivariate analysis extracted 22 variables as independent factors. Concomitant ramelteon use (odds ratio 0.701, 95% confidence interval 0.512-0.959), ward pharmacy service (0.741, 0.638-0.861), duration of VCM < 7 days (0.748, 0.623-0.899) and trough concentrations 10-15 mg/L (0.668, 0.556-0.802) reduce the risk of VIN. Meanwhile, concomitant piperacillin-tazobactam use (2.056, 1.754-2.409) and piperacillin use (2.868, 1.298-6.338) increase the risk. The decision tree analysis showed that a combination of vancomycin trough concentrations ≥20 mg/L and concomitant piperacillin-tazobactam use was associated with the highest risk.. We revealed that the concomitant ramelteon use and ward pharmacy service may decrease the risk of VIN, while the concomitant use of not only piperacillin-tazobactam but also piperacillin may increase the risk.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Big Data; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Humans; Japan; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Colistimethate sodium and tobramycin are important systemic antibiotics for treatment of cystic fibrosis (CF) pulmonary exacerbations but can induce acute kidney injury (AKI). We characterize the rate of AKI in CF patients treated with systemic colistimethate sodium compared with tobramycin.. This single-centre, retrospective cohort study included hospitalized CF patients treated with IV colistimethate sodium or tobramycin. The primary outcome was AKI defined using the RIFLE criteria. Multivariate logistic regression using a mixed model was performed to identify variables that were independently associated with AKI.. Overall, 156 patients representing 507 care encounters were included. The OR of AKI was not increased with IV colistimethate sodium relative to IV tobramycin after adjusting for other potential predictor variables (aOR 1.00; 95% CI 0.16-6.03). The frequency of AKI was 9.5% across all encounters, 6.9% with IV colistimethate sodium and 9.9% with IV tobramycin, with RIFLE category R (risk) being the most common stage, accounting for 4.2% of encounters with IV colistimethate sodium and 9.2% with IV tobramycin. The concomitant use of another nephrotoxin (aOR 2.51; 95% CI 1.27-4.95) or the combination of vancomycin and piperacillin/tazobactam (aOR 5.95; 95% CI 2.05-17.3) were both associated with increased odds of AKI.. Systemic treatment with colistimethate sodium or tobramycin in the CF patient population is associated with a similar rate of nephrotoxicity. However, clinicians should be mindful of the increased risk for AKI in patients treated with either IV colistimethate sodium or IV tobramycin when used concurrently with other nephrotoxic agents, particularly the combination of vancomycin and piperacillin/tazobactam.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Humans; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Tobramycin; Vancomycin

Although dozens of studies have associated vancomycin + piperacillin-tazobactam with increased acute kidney injury (AKI) risk, it is unclear whether the association represents true injury or a pseudotoxicity characterized by isolated effects on creatinine secretion. We tested this hypothesis by contrasting changes in creatinine concentration after antibiotic initiation with changes in cystatin C concentration, a kidney biomarker unaffected by tubular secretion.. We included patients enrolled in the Molecular Epidemiology of SepsiS in the ICU (MESSI) prospective cohort who were treated for ≥ 48 h with vancomycin + piperacillin-tazobactam or vancomycin + cefepime. Kidney function biomarkers [creatinine, cystatin C, and blood urea nitrogen (BUN)] were measured before antibiotic treatment and at day two after initiation. Creatinine-defined AKI and dialysis were examined through day-14, and mortality through day-30. Inverse probability of treatment weighting was used to adjust for confounding. Multiple imputation was used to impute missing baseline covariates.. The study included 739 patients (vancomycin + piperacillin-tazobactam n = 297, vancomycin + cefepime n = 442), of whom 192 had cystatin C measurements. Vancomycin + piperacillin-tazobactam was associated with a higher percentage increase of creatinine at day-two 8.04% (95% CI 1.21, 15.34) and higher incidence of creatinine-defined AKI: rate ratio (RR) 1.34 (95% CI 1.01, 1.78). In contrast, vancomycin + piperacillin-tazobactam was not associated with change in alternative biomarkers: cystatin C: - 5.63% (95% CI - 18.19, 8.86); BUN: - 4.51% (95% CI - 12.83, 4.59); or clinical outcomes: dialysis: RR 0.63 (95% CI 0.31, 1.29); mortality: RR 1.05 (95%CI 0.79, 1.41).. Vancomycin + piperacillin-tazobactam was associated with creatinine-defined AKI, but not changes in alternative kidney biomarkers, dialysis, or mortality, supporting the hypothesis that vancomycin + piperacillin-tazobactam effects on creatinine represent pseudotoxicity.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Biomarkers; Cefepime; Creatinine; Critical Illness; Cystatin C; Drug Therapy, Combination; Humans; Penicillanic Acid; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Renal Dialysis; Retrospective Studies; Vancomycin

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Aorta; Drug Therapy, Combination; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Thrombocytopenia; Vancomycin

Acute kidney injury (AKI) is a complication associated with vancomycin. Previous studies demonstrated that the combination of vancomycin and piperacillin-tazobactam increases the risk of AKI compared to vancomycin with meropenem or cefepime. These studies did not utilize area under the curve (AUC)-based dosing, which reduces vancomycin exposure and may decrease nephrotoxicity compared with trough-based dosing. This study evaluated the incidence of AKI in patients receiving AUC-dosed vancomycin with either concomitant piperacillin-tazobactam (VPT) or meropenem or cefepime (VMC). This retrospective cohort study included patients admitted to Sentara Norfolk General Hospital between October 2019 and September 2020 who received AUC-dosed vancomycin and concomitant piperacillin-tazobactam, meropenem, or cefepime for at least 48 h. The primary outcome was the incidence of AKI during treatment or within 24 h of discontinuation. A total of 435 patients (VPT,

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Cefepime; Drug Therapy, Combination; Humans; Incidence; Meropenem; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Vancomycin plus piperacillin-tazobactam (VPT) is a commonly used antimicrobial regimen for septic patients. VPT is more nephrotoxic than other regimens such as vancomycin plus cefepime (VC) when given over several days. This risk of nephrotoxicity is less clear when VPT is given for initial empiric therapy in sepsis and de-escalated quickly based on evolving clinical information. The objective of this study was to assess nephrotoxicity among septic patients empirically treated with either VPT or VC at initial clinical presentation. We conducted a retrospective study of septic patients who received VPT or VC within 12 h of presentation to the emergency department. The primary outcomes were acute kidney injury (AKI) and renal recovery 72 h after presentation. For the total of 418 patients, 306 received VPT and 112 received VC. Rates of AKI at 72 h were 15.2% for VPT patients and 11.0% for VC patients [p = 0.44]. Among patients with AKI at presentation, 16.3% of VPT patients had AKI at 72 h compared to 8.9% of VC patients [p = 0.19]. Among those without AKI at presentation, 14.2% VPT patients and 16.7% VC patients had AKI at 72 h [p = 0.71]. Renal recovery rates for patients with AKI at presentation were 42.3% for VPT patients versus 40.3% for VC patients [p = 0.78]. In-hospital renal replacement therapy occurred in 6.2% VPT patients and 0.9% VC patients [p = 0.024]. Therefore, initial empiric therapy with VPT in sepsis may not confer increased risk of AKI when de-escalated appropriately.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Cefepime; Drug Therapy, Combination; Female; Humans; Male; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Vancomycin

Recent studies have shown that the incidence of nephrotoxicity increases when vancomycin is combined with a beta-lactam antibiotic. The objective of this study was to compare the incidence of acute kidney injury (AKI) in adult patients who received vancomycin with either piperacillin-tazobactam (VPT), cefepime (VC), or meropenem (VM). This was a single center retrospective chart review. Patients were included if they were 18 years or older, received 48 hours of combination therapy and antibiotics were started within 24 hours of each other. Exclusion criteria were receiving more than one combination of antibiotics, serum creatinine > 1.2 mg/dL, AKI at the time of inclusion, or any form of renal replacement therapy. Two hundred patients met inclusion criteria. A total of 27 (13%) patients experienced AKI. The incidence of AKI was 21.6%, 9%, and 7.4% in the VPT, VC and VM groups, respectively. A patient who received VPT was 5 times more likely to develop AKI when compared to a patient who received VC (adjusted OR 5.09 95% CI (1.51-17.08),

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Cefepime; Drug Therapy, Combination; Humans; Incidence; Meropenem; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Risk for vancomycin-induced nephrotoxicity (VIN) is reportedly reduced by AUC-guided vancomycin dosing. However, it remains unknown whether the increased VIN risk in combination treatment with vancomycin and tazobactam/piperacillin, which is a VIN risk factor, can be diminished by AUC-guided vancomycin dosing (vancomycin-AUC). The aim of this study was to assess whether the evaluation of vancomycin-AUC + tazobactam/piperacillin (VT) combination therapy could prevent VIN.. The data from patients who received VT or vancomycin + cefepime (VC; the control group) at Tokushima University Hospital (Kuramoto, Japan) between April 2010 and March 2020 were analyzed in this retrospective study. The between-group difference in the prevalence of VIN onset, stratified by AUC, was investigated. The AUC of vancomycin was calculated using the Bayesian method with the blood concentration of vancomycin. The risk factors and probability of VIN onset from the vancomycin exposure-toxicity curve were evaluated using the logistic model.. The prevalences of VIN were 29.5% (18/61) and 7.1% (3/42) in the VT and VC groups, respectively. Multivariate logistic regression analysis of data from all patients revealed concurrent use of tazobactam/piperacillin (odds ratio [OR] = 4.59; P = 0.039) and AUC increase (OR = 1.01; P < 0.01) as risk factors for VIN, but only concurrent use of tazobactam/piperacillin was identified as a risk factor in patients with an AUC of <600 μg · h/mL, the guideline-recommended value (OR = 9.52; P = 0.041). Moreover, the vancomycin exposure-toxicity curve showed that in the guideline-recommended AUC range, VIN probability was consistently higher and the slope of VIN probability was greater in the VT group than in the VC group.. VIN risk was higher with VT than with VC, even when the AUC was controlled to the guideline-recommended range. These results strongly suggest that VIN prevention may be difficult with AUC-guided vancomycin dosing in patients receiving VT.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Bayes Theorem; Cefepime; Drug Therapy, Combination; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prevalence; Retrospective Studies; Vancomycin

Previous data suggested several risk factors for vancomycin-induced nephrotoxicity (VIN), including higher daily dose, long-term use, underlying renal disease, intensive care unit (ICU) admission, and concomitant use of nephrotoxic medications. We conducted this study to investigate the prevalence and risk factors of VIN and to estimate the cut-off serum trough level for predicting acute kidney injury (AKI) in non-ICU pediatric patients. This was a retrospective, observational, single-center study at Samsung Medical Center tertiary hospital, located in Seoul, South Korea. We reviewed the medical records of non-ICU pediatric patients, under 19 years of age with no evidence of previous renal insufficiency, who received vancomycin for more than 48 h between January 2009 and December 2018. The clinical characteristics were compared between patients with AKI and those without to identify the risk factors associated with VIN, and the cut-off value of serum trough level to predict the occurrence of VIN was calculated by the Youden's index. Among 476 cases, 22 patients (4.62%) developed AKI. The Youden's index indicated that a maximum serum trough level of vancomycin above 24.35 μg/mL predicted VIN. In multivariate analysis, longer hospital stay, concomitant use of piperacillin-tazobactam and serum trough level of vancomycin above 24.35 μg/mL were associated independently with VIN. Our findings suggest that concomitant use of nephrotoxic medication and higher serum trough level of vancomycin might be associated with the risk of VIN. This study suggests that measuring serum trough level of vancomycin can help clinicians prevent VIN in pediatric patients.

Topics: Acute Kidney Injury; Adolescent; Adult; Anti-Bacterial Agents; Child; Child, Preschool; Drug Therapy, Combination; Female; Hospitalization; Humans; Incidence; Infant; Intensive Care Units; Male; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Seoul; Tertiary Care Centers; Vancomycin; Young Adult

Vancomycin plus piperacillin-tazobactam (VPT) is a commonly used empiric combination of antimicrobials. Recently, studies have demonstrated an increase in acute kidney injury (AKI) associated with combination therapy of VPT. However, the majority of studies required patients to be on VPT for a minimum of 48 to 72 hours to be considered for inclusion and had extended treatment durations longer than most empiric, short course regimens.. To assess the incidence of AKI in noncritically ill patients being treated with VPT for short-courses (24 to 60 hours) compared to patients receiving extended-courses (72 hours to 7 days).. This was a retrospective cohort study comparing the incidence of AKI in noncritically ill patients receiving VPT for short and extended durations between January 2016 and August 2018. Fishers exact tests were used for differences in nominal data between groups and Mann-Whitney. Of the 2567 screened, 154 patients were included in the short-course group and 106 were included in the extended-course group. The incidence of AKI for patients in the short-course group was 12% (19/154) versus 26% (28/106) in the extended-course group (odds ratio: 2.55, 95% CI: 1.33-4.87;. In noncritically ill patients, a short-course of VPT experienced less AKI compared to an extended-course. Clinicians should continue to practice strict antimicrobial stewardship for VPT therapies expected to continue beyond 72 hours.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Incidence; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

While several intoxications can be successfully treated with specific antidotes, intoxications with the steroid glycoside digitoxin still represent a major challenge. Besides conventional approaches, CytoSorb® hemoadsorption might be another treatment option. We report on an 81-year-old female patient treated in our intensive care unit (ICU) with severe digitoxin intoxication, acute renal failure, and urinary tract infection (UTI). As physiological digitoxin elimination kinetics are known to appear slow, and also in regard to the renal failure, the decision was made to initiate continuous renal replacement therapy combined with CytoSorb hemoadsorption. The patient was hemodynamically stabilized within the first 4 h of treatment and initially required catecholamines to be stopped within 24 h of treatment. Pre- and post-adsorber drug level measurements showed a rapid elimination of digitoxin. Antibiotic treatment with piperacillin/tazobactam was initiated, and despite CytoSorb hemoadsorption therapy and its known potential to reduce plasma concentrations of several drugs, the UTI was successfully treated. After 3 days of CytoSorb treatment, digitoxin plasma levels were stable and almost normalized, and no clinical signs of intoxication were present. Five days after presentation, the patient was transferred from the ICU in a stable condition. CytoSorb hemoadsorption may be an easily available, efficient, and less cost-intensive therapy option than treatment with the Fab fragment, which is the currently recommended therapy for digitalis intoxications. Therefore, the use of CytoSorb might represent an alternative treatment for life-threatening complications of digitoxin intoxications.

Topics: Acute Kidney Injury; Aged, 80 and over; Continuous Renal Replacement Therapy; Digitoxin; Female; Hemoperfusion; Humans; Piperacillin, Tazobactam Drug Combination; Urinary Tract Infections

Piperacillin/tazobactam combined with vancomycin has been associated with a decline in renal function when compared with monotherapy. Teicoplanin is a glycopeptide similar to vancomycin. We investigated whether piperacillin/tazobactam combined with teicoplanin is associated with a decline in renal function as well.. We conducted a single-centre retrospective cohort study with data from our electronic health records from 9 August 2013 to 15 November 2019, including all adult patients that received either piperacillin/tazobactam, teicoplanin or piperacillin/tazobactam + teicoplanin. The incidence of acute kidney injury (AKI) at 48-72 h served as the primary outcome, whereas change in serum creatinine served as a secondary outcome.. Of the 4202 included patients, 3188 (75.9%) received piperacillin/tazobactam, 791 (18.8%) received teicoplanin and 223 (5.3%) received piperacillin/tazobactam + teicoplanin. The incidence of AKI at 48-72 h after commencement of antibiotic therapy was 5.4% for piperacillin/tazobactam, 3.4% for teicoplanin and 11.7% for piperacillin/tazobactam + teicoplanin (P < 0.001). However, mean serum creatinine at 48-72 h was slightly higher in the piperacillin/tazobactam + teicoplanin group therapy compared with baseline [+1.61% (95% CI -2.25 to 5.70)], indicating a slight decrease in renal function, and decreased for piperacillin/tazobactam [-1.98% (95% CI -2.73 to -1.22)] and teicoplanin [-8.01% (95% CI -9.54 to -6.45)]. After correcting for significant confounders in a multivariate linear regression analysis, these patterns remained.. Our study suggests that piperacillin/tazobactam + teicoplanin is associated with a higher prevalence of AKI compared with monotherapy. However, as the overall decline in renal function with piperacillin/tazobactam + teicoplanin is very small, its clinical relevance is likely limited. Therefore, piperacillin/tazobactam + teicoplanin can probably be safely combined.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Teicoplanin; Vancomycin

The concurrent use of vancomycin and piperacillin/tazobactam increases the risk of acute kidney injury (AKI) compared with vancomycin use with other anti-pseudomonal β-lactams (OAPBs). Teicoplanin is a glycopeptide antibiotic with lower nephrotoxicity than that of vancomycin. Whether the concomitant use of teicoplanin and piperacillin/tazobactam also increases the risk of AKI remains unknown.. To evaluate the AKI risk between teicoplanin-piperacillin/tazobactam and teicoplanin-OAPBs.. This was a retrospective, propensity score-matched cohort study. Adult patients receiving teicoplanin-based combination therapy were included. OAPBs included cefepime, cefoperazone/sulbactam, ceftazidime, doripenem, imipenem/cilastatin and meropenem. Propensity score matching was performed to balance demographic and confounding factors. The primary endpoint was AKI during combination therapy.. After propensity score matching, 954 patients (teicoplanin-piperacillin/tazobactam: teicoplanin-OAPBs, 1:3 matched, 243 pairs in total) were included for analysis. The mean age was 66.3 years in the matched cohort and 17.1% of patients had shock. Use of nephrotoxic medications (45.7% versus 48.7%) and baseline renal function (78.88 ± 31.26 versus 81.05 ± 31.53 mL/min/1.73 m2) were similar in the two groups. The median teicoplanin dose was 10.7 mg/kg in both groups. The groups did not differ significantly in terms of AKI risk (14.8% versus 14.2%, P = 0.815). However, the time to AKI appeared shorter in the teicoplanin-piperacillin/tazobactam group (4.64 ± 2.33 versus 6.29 ± 4.72 days, P = 0.039).. The combination of teicoplanin and piperacillin/tazobactam was not associated with an increased risk of AKI compared with teicoplanin and OAPBs.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; beta-Lactams; Cohort Studies; Drug Therapy, Combination; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Teicoplanin

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Therapy, Combination; Febrile Neutropenia; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Recent studies suggest that the combination of piperacillin-tazobactam (P-T) and vancomycin increases the risk for acute kidney injury (AKI). The purpose of this study was to determine if area under the concentration-time curve (AUC)-guided vancomycin dosing reduced the incidence of AKI in a sample of patients who also received P-T.. This single-centre, retrospective, pre-post quasi-experimental study compared the incidence of AKI before and after a health-system-wide change from trough- to AUC-guided vancomycin dosing using two post-distribution levels. The primary outcome was AKI, defined as an increase in serum creatinine ≥0.5 mg/dL or 50% from baseline for two consecutive measurements, in patients who received vancomycin with or without concomitant P-T.. In total, 636 patients were included in this study (308 trough-guided, 328 AUC-guided); of these, 118 patients in each group received concomitant P-T. The primary outcome occurred in 35 (11.4%) patients in the trough-guided group and 24 (7.3%) patients in the AUC-guided group (P=0.105). There was no difference in the incidence of AKI in the population receiving concomitant P-T between dosing strategies. The incidence of AKI was significantly higher in patients who received concomitant P-T compared with patients who did not receive concomitant P-T in both the trough-guided group [21/118 (17.8%) versus 14/190 (7.4%), respectively; P=0.003] and the AUC-guided group [16/118 (13.6%) versus 8/210 (3.8%), respectively; P=0.0011].. The incidence of AKI did not differ significantly between trough- and AUC-guided vancomycin dosing. Caution should be taken when combining vancomycin and P-T regardless of dosing strategy. Larger studies are needed to confirm these findings.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Area Under Curve; Drug Therapy, Combination; Female; Humans; Incidence; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Treatment Outcome; Vancomycin

Empiric antimicrobial therapy for healthcare-acquired infections often includes vancomycin plus an anti-pseudomonal beta-lactam (AP-BL). These agents vary in risk for adverse events, including acute kidney injury (AKI) and Clostrioides difficile infection (CDI). Studies have only examined these risks separately; thus, our objective was to evaluate AKI and CDI risks simultaneously with AP-BL in the same patient cohort.. This retrospective cohort study included 789 200 Veterans Health Administration medical admissions from 1 July 2010 through 30 June 2016. The antimicrobials examined were vancomycin, cefepime, piperacillin/tazobactam, and meropenem. Cox proportional hazards regression was used to contrast risks for AKI and CDI across individual target antimicrobials and vancomycin combination therapies, including adjustment for known confounders.. With respect to the base rate of AKI among patients who did not receive a target antibiotic (4.6%), the adjusted hazards ratios for piperacillin/tazobactam, cefepime, and meropenem were 1.50 (95% CI: 1.43-1.54), 1.00 (.95-1.05), 0.92 (.83-1.01), respectively. Co-administration of vancomycin increased AKI rates (data not shown). Similarly, against the base rate of CDI (0.7%), these ratios were 1.21 (1.07-1.36), 1.89 (1.62-2.20), and 1.99 (1.55-2.56), respectively. Addition of vancomycin had minimal impact on CDI rates (data not shown).. Piperacillin/tazobactam increased AKI risk, which was exacerbated by concurrent vancomycin. Cefepime and meropenem increased CDI risk relative to piperacillin/tazobactam. Clinicians should consider the risks and benefits of AP-BL when selecting empiric regimens. Further well-designed studies evaluating the global risks of AP-BL and patient specific characteristics that can guide empiric selection are needed.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Cefepime; Clostridioides; Drug Therapy, Combination; Humans; Meropenem; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Vancomycin (VAN) is a broad-spectrum antibiotic against Gram-positive cocci used empirically with other broad-spectrum antibiotics, such as piperacillin/tazobactam (TZP), cefepime, or meropenem (MEM). Conflicting literature on the rates of acute kidney injury (AKI) of VAN with TZP is reported, and studies on AKI rate with MEM are limited. This study aimed to evaluate AKI rates in patients receiving VAN with either TZP or MEM. This was a retrospective cohort study of patients received either VAN-TZP or VAN-MEM for ≥ 72 h. Patients with a baseline serum creatinine (SCr) of ≥ 1.5 mg/dL were excluded. The primary outcome was rate of AKI as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. SCr was recorded at baseline and 3-5 days post antibiotics initiation. 158 patients were included, 77 in the VAN-TZP group versus 81 in the VAN-MEM group. While the percentage of patients meeting AKI definition was numerically higher in the VAN-MEM group, the difference was not significant (10.4% vs. 21%; P = 0.07). As such, change in SCr was not significantly different between the two groups (- 7.4 vs. - 6.1%; P = 0.7). In-hospital mortality was higher in the VAN-MEM group (23.4% vs. 39.5%; P = 0.03) possibly because the majority of this group's patients were critically ill. This study showed that combining MEM with VAN did not offer the benefit of a lower rate of AKI compared with a combination with TZP. Therefore, patients with no risk factors for infections resistant to TZP can continue to receive TZP with VAN without risking AKI development.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Saudi Arabia; Vancomycin

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Azabicyclo Compounds; Cilastatin, Imipenem Drug Combination; Drug Therapy, Combination; Male; Mice; Mice, Inbred C57BL; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Excess of acute kidney injury (AKI) secondary to the association of vancomycin plus piperacillin is debated.. To detect a signal for an increased risk of AKI with the vancomycin and piperacillin combination compared with other vancomycin-based regimens.. Using VigiBase, the WHO global database of individual case safety reports (ICSR) from 1997 to 2019, we conducted a disproportionality analysis comparing the reporting of AKI cases between different vancomycin-based regimens (vancomycin plus piperacillin, cefepime or meropenem). To take into account a possible notoriety bias, we secondarily restricted the study period to before 2014, the date of the first publication of AKI in patients receiving vancomycin plus piperacillin. Results are expressed using the reporting OR (ROR) and its 95% CI.. From 1997 to 2019, 53 701 ICSR concerning vancomycin have been registered in the database, including 6016 reports of AKI (11.2%), among which 925 (15.4%) were reported with vancomycin/piperacillin, 339 (5.6%) with vancomycin/cefepime and 197 (3.7%) with vancomycin/meropenem. ROR (95% CI) for AKI was 2.6 (2.4-2.8) for vancomycin/piperacillin, 2.5 (2.2-2.9) for vancomycin/cefepime and 0.5 (0.4-0.6) for vancomycin/meropenem versus other vancomycin-containing regimens. After restriction of the study period to 1997-2013, the ROR for AKI remains significant only for vancomycin/piperacillin [ROR (95% CI) = 2.1 (1.8-2.4)].. We found a disproportionality in reports of AKI in patients receiving vancomycin plus piperacillin compared with vancomycin in other regimens. This suggests a drug-drug interaction between these two antibiotics resulting in an increased risk of AKI.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Pharmacovigilance; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

We compared the rates of acute kidney injury (AKI), 7-day and 30-day mortalities, and resolution of AKI at discharge in combination therapies involving either teicoplanin (TEI) or vancomycin (VAN) with piperacillin-tazobactam (TZP) or meropenem (MER). In a single-center, retrospective cohort study, adult patients (>18 years) who had a baseline serum creatinine level within 24 h of admission and who received study antibiotics for at least 48 h were included. The primary outcome was AKI incidence after therapy per RIFLE criteria. Multivariate logistic regression and propensity score match analyses were employed for statistical comparisons. Data from 379 patients were evaluated. In multivariate analysis (MVA) of the whole cohort, TZP-VAN combination was associated with significantly higher rate of AKI as compared with TZP-TEI (aOR: 3.21, 95% CI, 1.36-7.57; p = 0.008) or with MER-VAN (aOR: 2.28, 95% CI, 1.008-5.18; p = 0.048). In MVA of the matched cohorts, TZP-VAN as compared with TZP-TEI and MER-VAN was associated with 3.96 times (95% CI, 1.48-10.63, p = 0.006) and 3.11 times (95% CI, 1.12-8.62; p = 0.028) increased risk of AKI, respectively. No differences between MER-TEI and MER-VAN combinations were detected. Seven-day and 30-day mortalities and resolution rates of AKI were similar in all comparisons. Teicoplanin can be preferred instead of VAN when combination with TZP is used particularly for patients with high AKI risk.

Topics: Acute Kidney Injury; Administration, Intravenous; Adult; Aged; Anti-Bacterial Agents; Female; Humans; Kidney; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Teicoplanin; Tertiary Care Centers; Vancomycin

several studies have been reported piperacillin-tazobactam (TAZ / PIPC)-associated AKI with various frequencies. The aim of this study was to determine the frequency of TAZ/PIPC- associated AKI among our patients and to identify the risk factors for this clinical entity.. this retrospective cross-sectional study was conducted at Hamad General Hospital; it involved adult patients who were admitted from January 2017 to December 2017.. we involved 917 patients, of whom 635 (69.25%) were males and 282 (30.75%) were females. The mean age of the patients was 52 (SD 19) years, and 98 (10.7%) patients were diagnosed with AKI. The patients with AKI were significantly older than without AKI [59.71 (SD 19.79) versus 51.06 (SD 18.67); P <0.001]. After TAZ/PIPC initiation, the mean creatinine level in the AKI group was higher than the mean creatinine level in the non-AKI group, [158.91 (SD 81.93) versus 66.78 (SD 21.42); P<001]. The mean time of onset of AKI after PIPC/TAZ initiation was 4.46 (SD 3.20) (1-12 days). AKI was significantly associated with low mean serum albumin (P<0.001), high mean fasting blood glucose (P<0.001), coronary artery diseases (P<0.001), heart failure (P<0.001), liver diseases (P=0.047), diabetes mellitus (P=0.021) and hypertension (P<0.001). The in-hospital mortality was significantly higher in the AKI group [38.78% versus 5.13% in the non-AKI group; P<0.001], and only advanced age and heart failure were found as independent risk factors for TAZ/PIPC-associated AKI.. TAZ/PIPC was significantly associated with AKI. Advanced age and heart failure were identified as independent risk factors for TAZ/PIPC-associated AKI.

Topics: Acute Kidney Injury; Adult; Age Factors; Aged; Anti-Bacterial Agents; Cross-Sectional Studies; Female; Heart Failure; Hospital Mortality; Humans; Logistic Models; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Qatar; Retrospective Studies; Risk Factors

Combined use of vancomycin (VCM) and piperacillin/tazobactam (PIPC/TAZ) has been reported to increase the incidence of acute kidney injury (AKI). However, the risk factors associated with AKI after VCM and PIPC/TAZ (VPT) administration have not yet been identified. Therefore, we retrospectively assessed patients treated with VPT to investigate the risk factors for AKI development.. The study involved patients who were treated with VPT from January 1, 2016 to March 31, 2020. The patients were divided into the AKI or non-AKI group. The clinical characteristics of patients and antimicrobial therapy were compared between the groups. Their association with AKI risk was evaluated using multivariate logistic regression analysis.. In total, 182 patients were included, with 118 in the non-AKI group and 64 in the AKI group. Therefore, the incidence of AKI was 35.2 %. The initiation of VPT combination therapy on the same day and concomitant use of vasopressors were associated with an increased risk of AKI (odds ratio [OR] 2.55, 95 % confidential interval [CI] 1.20-5.44 and OR 3.22, 95 % CI 1.31-7.89, respectively).. Our findings suggest that the concomitant use of vasopressors and initiating VPT combination therapy on the same day are likely risk factors for AKI development.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Vancomycin

Combination therapy with vancomycin (VCM) and piperacillin/tazobactam (PIPC/TAZ) increases the risk of acute kidney injury (AKI). Teicoplanin (TEIC) has a lower risk of AKI than VCM. Currently, the difference in AKI risk after TEIC-PIPC/TAZ combination therapy and VCM-PIPC/TAZ combination therapy is controversial. This study aimed to compare AKI incidence after treatment with these two drug combinations using propensity score matching analysis.. This single-center cohort study used data extracted from patients' medical records. We included patients who received TEIC-PIPC/TAZ therapy (TEIC group) or VCM-PIPC/TAZ therapy (VCM group). After propensity score matching, AKI incidence, AKI stage, 30-day mortality, and time to AKI incidence were compared between the groups.. After propensity score matching, 94 patients were matched in each group. AKI incidence was significantly lower in the TEIC group than in the VCM group (10.6% vs. 23.4%, odds ratio [95% confidence interval]: 0.39 [0.17-0.88], p = 0.03). AKI stage, 30-day mortality, and time to AKI incidence were not significantly different between the groups.. This study suggested that AKI incidence may be lower in patients undergoing combination therapy with TEIC-PIPC/TAZ than in those receiving therapy with VCM-PIPC/TAZ. To prevent the occurrence of AKI, clinicians may need to choose TEIC instead of VCM for patients receiving PIPC/TAZ.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Cohort Studies; Drug Therapy, Combination; Humans; Incidence; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Propensity Score; Retrospective Studies; Teicoplanin; Vancomycin

We investigated the incidence of acute kidney injury (AKI) and risk factors associated with vancomycin (VAN) and piperacillin-tazobactam (TZP) combination therapy in non-intensive care unit (ICU) and ICU settings.. In this single-center retrospective cohort study, adults who received VAN for ≥48 h during the period from 1 January 2016 through 31 December 2017 were included. The primary endpoint was incidence of AKI.. Data from 593 adults were analyzed. The incidence of AKI was 10.6% overall, 8.0% in the non-TZP group, and 19.8% in the TZP group. In univariate analysis, the odds ratio (OR) for AKI was higher in the TZP group than in the non-TZP group (2.84, 95% CI = 1.64-4.90). In both the non-ICU and ICU settings, the OR for AKI was higher in the TZP group than in the non-TZP group (non-ICU: OR = 3.04, 95% CI = 1.52-6.09; ICU: OR = 2.51, 95% CI = 1.03-6.08). Furthermore, in propensity score analysis, the OR for AKI was higher in the TZP group than in the non-TZP group (OR = 2.81, 95% CI = 1.52-5.17). In both the non-ICU and ICU settings, the OR for AKI was higher in the TZP group than in the non-TZP group (non-ICU: OR = 2.57, 95% CI = 1.17-5.64; ICU: OR = 3.51, 95% CI = 1.05-11.6).. Combined use of TZP in patients receiving VAN increased AKI incidence in non-ICU and ICU settings.

Topics: Acute Kidney Injury; Cohort Studies; Critical Care; Humans; Piperacillin, Tazobactam Drug Combination; Propensity Score; Retrospective Studies; Risk Factors; Vancomycin

This exploratory study aimed to develop a risk prediction model of vancomycin-associated nephrotoxicity (VANT) in elderly patients. Clinical information of elderly patients who received vancomycin therapy from January 2016 to June 2018 was retrieved. A total of 255 patients were included in this study. Univariate analysis and multivariable logistic regression analysis revealed that vancomycin trough concentration ≥ 20 mg/L (odds ratio (OR) = 3.009; 95% confidence interval (CI) 1.345-6.732), surgery (OR = 3.357; 95% CI 1.309-8.605), the Charlson Comorbidities Index ≥ 4 points (OR = 2.604; 95% CI 1.172-5.787), concomitant use of cardiotonic drug (OR = 3.283; 95% CI 1.340-8.042), plasma volume expander (OR = 3.459; 95% CI 1.428-8.382), and piperacillin/tazobactam (OR = 2.547; 95% CI 1.680-6.007) were risk factors for VANT in elderly patients. Furthermore, a VANT risk prediction model was developed, which had good discriminative power and was well-calibrated.

Topics: Acute Kidney Injury; Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Comorbidity; Drug Therapy, Combination; Female; Humans; Logistic Models; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Multivariate Analysis; Pilot Projects; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Assessment; Risk Factors; Staphylococcal Infections; Vancomycin

Vancomycin and piperacillin/tazobactam are reported in clinical studies to increase acute kidney injury (AKI). However, no clinical study has demonstrated synergistic toxicity, only that serum creatinine increases.. To clarify the potential for synergistic toxicity between vancomycin, piperacillin/tazobactam and vancomycin + piperacillin/tazobactam treatments by quantifying kidney injury in a translational rat model of AKI and using cell studies.. (i) Male Sprague-Dawley rats (n = 32) received saline, vancomycin 150 mg/kg/day intravenously, piperacillin/tazobactam 1400 mg/kg/day intraperitoneally or vancomycin + piperacillin/tazobactam for 3 days. Urinary biomarkers and histopathology were analysed. (ii) Cellular injury was assessed in NRK-52E cells using alamarBlue®.. Urinary output increased from Day -1 to Day 1 with vancomycin but only after Day 2 for vancomycin + piperacillin/tazobactam-treated rats. Plasma creatinine was elevated from baseline with vancomycin by Day 2 and only by Day 4 for vancomycin + piperacillin/tazobactam. Urinary KIM-1 and clusterin were increased with vancomycin from Day 1 versus controls (P < 0.001) and only on Day 3 with vancomycin + piperacillin/tazobactam (P < 0.001, KIM-1; P < 0.05, clusterin). The histopathology injury score was elevated only in the vancomycin group when compared with piperacillin/tazobactam as a control (P = 0.04) and generally not so with vancomycin + piperacillin/tazobactam. In NRK-52E cells, vancomycin induced cell death with high doses (IC50 48.76 mg/mL) but piperacillin/tazobactam did not, and vancomycin + piperacillin/tazobactam was similar to vancomycin.. All groups treated with vancomycin demonstrated AKI; however, vancomycin + piperacillin/tazobactam was not worse than vancomycin. Histopathology suggested that piperacillin/tazobactam did not worsen vancomycin-induced AKI and may even be protective.

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Rats; Rats, Sprague-Dawley; Retrospective Studies; Vancomycin

To study the incidence of vancomycin-associated acute kidney injury (VA-AKI) in Hong Kong and identify risk factors for VA-AKI.. Patients with vancomycin prescription and blood level measurement in 2012-2016 were identified using the Hong Kong Hospital Authority Clinical Data Analysis and Reporting System. Acute kidney injury was defined using KDIGO criteria. Patients without creatinine measurements, steady-state trough vancomycin level or who had vancomycin treatment < 3 days were excluded. Results were analyzed using SPSS version 22.0. Logistic regression was used to identify the predictors for VA-AKI. Odds ratio and 95% confidence interval were estimated.. One thousand four hundred fifty patients were identified as VA-AKI from 12,758 records in Hong Kong in 2012-2016. The incidence was respectively 10.6, 10.9, 11.3, 12.2, 11.2% from 2012 to 2016. The incidence of VA-AKI was 16.3, 12.2, 11.3 and 6.2% in patients aged 1-12, 12-60, elderly aged > 60 and newborn and infants, respectively. Baseline creatinine, serum trough vancomycin level, systematic disease history including respiratory failure, hypertension, congestive heart failure, chronic renal failure, anemia and type II diabetes, and concomitant diuretics, piperacillin-tazobactam (PTZ) and meropenem prescription were significantly higher in VA-AKI patients older than 12 years. Logistic regression showed that older age group, higher baseline creatinine, serum trough vancomycin level, respiratory failure, chronic renal failure and congestive heart failure, concomitant diuretics, PTZ and meropenem prescription, and longer hospital stay were all associated with increased risk of VA-AKI.. The incidence of VA-AKI in Hong Kong is low but shows no decline. Patients with higher baseline creatinine, multi-organ diseases and multiple drugs administration should have their vancomycin level monitored to decrease the risk of VA-AKI.

Topics: Acute Kidney Injury; Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Child; Child, Preschool; Comorbidity; Creatinine; Diuretics; Female; Heart Failure; Hong Kong; Humans; Incidence; Infant; Infant, Newborn; Length of Stay; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Renal Insufficiency, Chronic; Respiratory Insufficiency; Risk Factors; Vancomycin; Young Adult

In the hospital, antibiotics are widely used to treat infections. We report a case of acute kidney injury (AKI) caused by an antibiotic drug combination. A 30-year-old Japanese male presented with lung metastases, pneumothorax, empyema, and methicillin-resistant Staphylococcus aureus (MRSA) infection. The patient received a combination of vancomycin and piperacillin/tazobactam, which resulted in elevated vancomycin trough concentration and subsequently in AKI. Renal function was restored upon vancomycin and piperacillin/tazobactam cessation. Though this patient had AKI most likely due to the combined use of two agents as has been reported in many cases, vancomycin trough concentration showed an unexpected abnormal increase when halting vancomycin treatment. This is the first report indicating a drug-drug interaction between vancomycin and piperacillin/tazobactam with unexpected abnormal vancomycin trough concentration, leading to AKI, additionally we think that there was a situation that he stressed against the kidney by a history of medications caused renal dysfunction and co-administration. We suggest that when using vancomycin in combination with piperacillin/tazobactam, the trough concentration of vancomycin must be confirmed simultaneously with renal function and evaluation, and that the combination of these two drugs should be minimized.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Drug Interactions; Drug Therapy, Combination; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Piperacillin, Tazobactam Drug Combination; Staphylococcal Infections; Vancomycin

During a recent shortage of small-volume parenteral solutions, some hospitals administered piperacillin/tazobactam via continuous infusion to utilize larger fluid volumes. Although the incidence of acute kidney injury (AKI) is well documented for patients receiving intermittent or extended-infusion piperacillin/tazobactam with concomitant vancomycin, no literature exists documenting the incidence of AKI in patients receiving continuous-infusion piperacillin/tazobactam.. The objective of this study is to examine the incidence and predictors of AKI in patients who received continuous-infusion piperacillin/tazobactam with concomitant intermittent-infusion vancomycin (VPT-CI) at a community hospital.. A retrospective cohort study was performed on patients who received VPT-CI between December 2017 and March 2018. Patients were eligible for inclusion if they were at least 19 years of age and received at least 48 hours of combination therapy. The primary outcome was incidence of AKI. The secondary outcome was an assessment of patient and treatment characteristics to determine predictors of AKI.. A total of 120 patients were included in the study. The incidence of AKI in patients who received VPT-CI was 31.7%. Based on binary logistic regression analysis, risk factors associated with increased risk of AKI included admission to the intensive care unit and baseline creatinine clearance less than 60 mL/min.. The incidence of AKI for VPT-CI found in this study was comparable to that found with intermittent and extended-infusion piperacillin/tazobactam with concomitant vancomycin in prior literature. Additional research should further analyze risk factors for the development of AKI for patients on concomitant vancomycin and piperacillin/tazobactam therapy.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Drug Administration Schedule; Drug Therapy, Combination; Female; Hospitalization; Humans; Incidence; Infusions, Intravenous; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Vancomycin; Young Adult

The use of piperacillin/tazobactam with vancomycin as empirical antimicrobial therapy (EAT) for prosthetic joint infection (PJI) has been associated with an increased risk of acute kidney injury (AKI), leading us to propose cefepime as an alternative since 2017 in our reference centre.. To compare microbiological efficacy and tolerance of these two EAT strategies.. All adult patients with PJI empirically treated with vancomycin+cefepime (n = 89) were enrolled in a prospective observational study and matched with vancomycin+piperacillin/tazobactam-treated historical controls (n = 89) according to a propensity score including age, baseline renal function and concomitant use of other nephrotoxic agents. The two groups were compared using Kaplan-Meier curve analysis, and non-parametric tests regarding the proportion of efficacious empirical regimen and the incidence of empirical therapy-related adverse events (AE).. Among 146 (82.0%) documented infections, the EAT was considered efficacious in 77 (98.7%) and 65 (98.5%) of the piperacillin/tazobactam- and cefepime-treated patients, respectively (P = 1.000). The rate of AE, particularly AKI, was significantly higher in the vancomycin+piperacillin/tazobactam group [n = 27 (30.3%) for all AE and 23 (25.8%) for AKI] compared with the vancomycin+cefepime [n = 13 (14.6%) and 6 (6.7%)] group (P = 0.019 and <0.001, respectively), leading to premature EAT discontinuation in 20 (22.5%) and 5 (5.6%) patients (P = 0.002). The two groups were not significantly different regarding their comorbidities, and AKI incidence was not related to vancomycin plasma overexposure.. Based on the susceptibility profile of bacterial isolates from included patients, microbiological efficacy of both strategies was expected to be similar, but vancomycin + cefepime was associated with a significantly lower incidence of AKI.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Cefepime; Cohort Studies; Drug Therapy, Combination; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Vancomycin and piperacillin-tazobactam are commonly used antibiotics. There is increasing evidence to indicate that these therapies in combination predispose patients to acute kidney injury (AKI). However, studies of intensive care unit (ICU) patients with these antibiotics have produced conflicting results. In this single-centre, retrospective cohort study, data was collected on ICU patients prescribed combination vancomycin and piperacillin-tazobactam (VPT) for at least 48 h, compared with patients prescribed vancomycin with either cefepime or meropenem (VMC) for the same time period. Primary outcome was incidence of AKI; secondary outcomes included a desirability of outcome ranking (DOOR) scale, and association between antibiotic duration and kidney injury. A total of 260 patients were included. AKI was observed in 27% of cases overall. Incidence of AKI was higher with VPT compared with VMC on bivariate (relative risk reduction [RRR] 1.9, 95% confidence interval [CI] 0.9-4.1, P = 0.08) and multivariate (RRR 2.2, 95% CI 1.0-4.9, P = 0.05) analyses. Longer duration of antibiotic therapy was associated with increased rates of AKI independent of which antibiotics were prescribed: RRR 4.9, 95% CI 2.1-11.1, P = <0.001 for 5-6 days compared with <5 days, and RRR 2.3, 95% CI 1.0-5.5, P = 0.05 for >7 days compared with <5 days. This study demonstrated an association between increased risk of nephrotoxicity and combination VPT therapy in ICU patients. The concept remains controversial, with recent suggestions that VPT does not truly cause nephrotoxicity. Given our findings and the weight of previous studies, there is a strong mandate to undertake prospective trials to resolve the issue.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Cefepime; Critical Care; Duration of Therapy; Female; Humans; Intensive Care Units; Kidney; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Nephrotoxic medication exposure and associated acute kidney injury (AKI) occur commonly in hospitalized children. At Cincinnati Children's Hospital Medical Center, there is an initiative to increase awareness of nephrotoxic medication exposure and decrease rates of associated AKI. The oncology service utilized these data in a quality improvement project to drive reductions in AKI rates.. Three interventions were implemented targeted at decreasing the incidence of nephrotoxic exposure, as well as protecting against the conversion of exposures to AKI episodes. Cefepime replaced piperacillin-tazobactam for febrile neutropenia, vancomycin stewardship limited empiric courses to 72 hours, and nephroprotection for intravenous contrast administration was standardized for defined high-risk patients.. The study cohort comprised 42 520 noncritically ill patient days admitted to the oncology service at Cincinnati Children's Hospital Medical Center. A total of 273 unique patients were exposed to combination nephrotoxic medications, leading to 111 AKI episodes. The rate of nephrotoxic medication exposure within the oncology service decreased by 49% from 16.08 to 8.17 per 1000 patient days. Episodes of AKI associated with nephrotoxic medication exposure decreased by 45% from 3.48 to 1.92 per 1000 patient days.. Interventions to decrease AKI took a three-pronged approach. Collectively, this approach was proven successful with significant reductions in both rates of nephrotoxic medication exposure and associated AKI among hospitalized oncology patients.

Topics: Acute Kidney Injury; Adolescent; Cefepime; Child; Child, Preschool; Databases, Factual; Febrile Neutropenia; Female; Humans; Infant; Male; Neoplasms; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Recent studies have corroborated that the co-administration of vancomycin (VCM) and piperacillin/tazobactam (PT) is correlated with an increased incidence of acute kidney injury (AKI). However, evidence directed at the Japanese population is scarce. Therefore, we conducted a retrospective study to compare the occurrence of AKI among Japanese patients who received VCM with PT (VP therapy) and VCM with another β-lactams (VA therapy).. The present study, performed at Tsuyama Chuo Hospital between June 2012 and December 2018, included adult patients who received VCM and β-lactam antibiotics for ≥48 h. We defined the primary outcome as the incidence of AKI based on the risk, injury, failure, loss, and end-stage kidney disease criteria. Patients' clinical characteristics and outcomes were reviewed and compared between the two groups with univariate and multivariate logistic regression analyses. Subgroup analysis was conducted by stratifying the patients' baseline hospital admittance status, as intensive care unit or general wards.. We analyzed 272 patients (92 V P therapy and 180 VA therapy). Univariate analysis revealed a significant difference in AKI development between VP and VA therapy (25.0% vs 12.2%; p < 0.01). A multivariate analysis demonstrated that VP therapy and VCM initial trough levels ≥15 μg/mL were associated with an incidence of AKI. Patients at general wards, rather than those admitted at an intensive care unit, developed AKI with VP therapy (p = 0.02).. VP therapy was associated with an increased risk of AKI compared to that with VA therapy among the Japanese population.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Japan; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Piperacillin/tazobactam (PT), when combined with vancomycin, is associated with an increased risk of acute kidney injury (AKI). It is not known whether PT alone is associated with a higher incidence of AKI compared to other β-lactams among critically ill patients. The objective of this study was to compare the incidence of AKI associated with the use of PT to other β-lactams among adult critically ill patients METHODS: This retrospective study was conducted in the surgical and the medical intensive care units at two hospitals within Hamad Medical Corporation (HMC) in Qatar and included adult critically ill patients who received at least one dose of anti-pseudomonal β-lactams. The primary outcome was acute kidney injury, defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multiple logistic regression with adjustment for pre-specified potential confounders was used for the primary outcome analysis.. A total of 669 patients were included in the analysis: 507 patients in the PT group and 162 patients in the control (meropenem/cefepime) group. AKI occurred in 136 (26.8%) members of the PT group and 38 (23.5%) members of the control group [odds ratio (OR) 1.2; 95% confidence interval (CI) 0.79-1.8]. The results were not significantly altered after adjusting for the pre-specified potential confounders (adjusted OR 1.38; 95% CI 0.88-2.15).. In this study, PT was not associated with a higher risk of AKI compared to cefepime or meropenem among adult critically ill patients.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Critical Illness; Female; Humans; Incidence; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Qatar; Retrospective Studies; Risk Factors

Cystic fibrosis (CF) patients, with Pseudomonas aeruginosa infection, often require repeated aminoglycoside courses for the management of acute pulmonary exacerbations (APEs). Acute kidney injury (AKI) due to aminoglycosides has been reported; little data exist regarding long-term nephrotoxicity with repeated exposure. The objective of this study was to describe the incidence of acute and chronic nephrotoxicity due to cumulative intravenous (IV) aminoglycoside exposure. This is a retrospective, observational study of pediatric and adult CF patients admitted to an academic medical center between January 1, 2006 and October 1, 2018 for APE management. Patients were eligible for inclusion if they received at least five courses of an IV aminoglycoside for at least 7 days each. Cumulative weight-based aminoglycoside dose was reported in milligrams per kilogram. For each admission, baseline and highest serum creatinine were collected to assess the incidence of AKI. The baseline and final estimated glomerular filtration rate (eGFR) were calculated to assess long-term effects on renal function. Sixty-six patients, representing greater than 700 courses, were included in the final analysis. The median cumulative weight-based aminoglycoside dose was 1183 mg/kg of tobramycin or tobramycin equivalent. Twenty percent of courses resulted in AKI; 86% were Stage 1. A repeated measure multivariate model showed colistin, piperacillin/tazobactam, vancomycin, and age were significant AKI risk factors. There was no correlation between cumulative aminoglycoside dose and change in eGFR. AKI from IV aminoglycoside exposure occurred in 20% of courses. Cumulative exposure to IV aminoglycosides in APE management was not correlated with long-term renal dysfunction.

Topics: Acute Kidney Injury; Adolescent; Adult; Age Factors; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Cystic Fibrosis; Female; Humans; Incidence; Infant; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Retrospective Studies; Risk Factors; Tobramycin; Vancomycin; Young Adult

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Critical Illness; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

There continues to be uncertainty about whether piperacillin/tazobactam (TZP) increases the risk of AKI in critically ill pediatric patients. We sought to compare rates of AKI among critically ill children treated with TZP or cefepime, an alternative frequently used in intensive care units, with and without vancomycin.. We conducted a retrospective cohort study assessing the risk of AKI in pediatric intensive care unit patients after exposure to vancomycin, TZP, and cefepime, alone or in combination, within 48 hours of admission. The primary outcome was development of stage 2 or 3 AKI or an increase in AKI stage from 2 to 3 within the 6 days after the 48-hour exposure window. Secondary outcomes included lengths of stay, need for RRT, and mortality.. Of 5686 patients included, 494 (8.7%) developed stage 2 or 3 AKI. The adjusted odds of developing AKI after medication exposure were 1.56 for TZP (95% confidence interval [95% CI], 1.23 to 1.99), 1.13 for cefepime (95% CI, 0.79 to 1.64), and 0.86 for vancomycin (95% CI, 0.69 to 1.07). The adjusted odds of developing AKI for vancomycin plus TZP versus vancomycin plus cefepime was 1.38 (95% CI, 0.85 to 2.24).. Observational data in critically ill children show that TZP use is associated with increased odds of AKI. A weaker, nonsignificant association between vancomycin plus TZP and AKI compared with vancomycin plus cefepime, creates some uncertainty about the nature of the association between TZP and AKI. However, cefepime is an alternative not associated with AKI.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Cefepime; Child; Child, Preschool; Critical Illness; Female; Humans; Infant; Male; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Appropriate use of vancomycin (VCM) is important in preventing acute kidney injury (AKI). Because of the high frequency of VCM use for febrile neutropenia and concomitant use of other nephrotoxic drugs, haematologic patients have a different nephrotoxic background compared with patients with other diseases. Therefore, it is unclear whether the risk factors of VCM-induced AKI identified in other patient groups are also applicable to haematologic patients. Herein, we performed a single-centre retrospective analysis to identify the factors associated with VCM-induced AKI in haematologic patients.. We retrospectively analysed 150 haematologic patients to whom VCM was administered between April 2010 and March 2018 at Tokushima University Hospital. VCM-induced AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multivariate logistic regression analyses were performed to identify risk factors for VCM-induced AKI.. Seventeen patients had VCM-induced AKI. Multivariate analysis revealed that the risk factors of VCM-induced AKI were an initial VCM trough concentration of > 15 mg/L and concomitant use of tazobactam/piperacillin (TAZ/PIPC) and liposomal amphotericin B (L-AMB). Patients with an initial VCM trough concentration of < 10 mg/L showed significantly lower efficacy in febrile neutropenia. Interestingly, concomitant L-AMB use increased the incidence of VCM-induced AKI in a VCM concentration-dependent manner, whereas concomitant TAZ/PIPC increased the incidence in a VCM concentration-independent manner.. The optimal initial VCM trough concentration was 10-15 mg/L in haematologic patients, considering safety and effectiveness. There were differences in the effect of VCM-induced AKI between nephrotoxic drugs.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; Drug Interactions; Female; Humans; Leukemia, Myeloid, Acute; Lymphoma; Male; Middle Aged; Multiple Myeloma; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Surveys and Questionnaires; Vancomycin

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cohort Studies; Doripenem; Drug Therapy, Combination; Female; Humans; Incidence; Logistic Models; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk; Vancomycin

Recent studies in adults have found an incidence of acute kidney injury (AKI) in patients treated with a combination of vancomycin and piperacillin-tazobactam (TZP) that is greater than that expected with either medication alone. The purpose of this study was to determine whether combination therapy with vancomycin and TZP is associated with an incidence of AKI in pediatric patients higher than that in those on combination therapy with vancomycin and cefepime.. We performed a retrospective single-center matched-cohort study of pediatric patients who received vancomycin in combination with TZP or cefepime between January 2015 and June 2016. The patients were matched according to chronic disease, age, sex, and number of concomitant nephrotoxic medications at the time of combination antibiotic therapy. The primary outcome was incidence of AKI. Secondary outcomes included differences between groups in time to AKI, resolution of AKI, and effect of vancomycin trough levels on the incidence of nephrotoxicity. Conditional logistic regression was used to compare categorical and continuous variables between treatment groups. Conditional Poisson regression was used to assess the association between AKI and treatment groups. Stratified log-rank tests and Cox proportional hazards models with shared frailty were used to compare the times to AKI according to treatment group.. Two hundred twenty-eight matched patients were included. AKI developed in 9 (7.9%) of 114 and 33 (28.9%) of 114 patients in the cefepime and TZP groups, respectively (P < .001). Type of combination therapy remained a significant predictor for AKI in multivariate conditional Poisson analysis in which adjustments were made for age, sex, use of concomitant nephrotoxins, and vancomycin dose (relative risk, 2.5 [95% confidence interval, 1.1-5.8]; P = .03). AKI developed almost 3 times sooner in the TZP group than in the cefepime group (hazard ratio, 2.9 [95% confidence interval, 1.3-6.1]; P = .006). Sensitivity analyses in which adjustment was made for antibiotic indication in addition to the aforementioned variables and excluding those with gastrointestinal infection revealed similar results.. Among hospitalized children at our institution, combination therapy with vancomycin and TZP was associated with an incidence of AKI higher than that associated with vancomycin and cefepime.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Cefepime; Child; Child, Preschool; Cohort Studies; Combined Modality Therapy; Female; Humans; Incidence; Infant; Infant, Newborn; Male; Multivariate Analysis; Piperacillin, Tazobactam Drug Combination; Regression Analysis; Vancomycin

Nephrotoxins contribute to 20%-40% of acute kidney injury (AKI) cases in the intensive care unit (ICU). The combination of piperacillin-tazobactam (PTZ) and vancomycin (VAN) has been identified as nephrotoxic, but existing studies focus on extended durations of therapy rather than the brief empiric courses often used in the ICU. The current study was performed to compare the risk of AKI with a short course of PTZ/VAN to with the risk associated with other antipseudomonal β-lactam/VAN combinations.. The study included a retrospective cohort of 3299 ICU patients who received ≥24 but ≤72 hours of an antipseudomonal β-lactam/VAN combination: PTZ/VAN, cefepime (CEF)/VAN, or meropenem (MER)/VAN. The risk of developing stage 2 or 3 AKI was compared between antibiotic groups with multivariable logistic regression adjusted for relevant confounders. We also compared the risk of persistent kidney dysfunction, dialysis dependence, or death at 60 days between groups.. The overall incidence of stage 2 or 3 AKI was 9%. Brief exposure to PTZ/VAN did not confer a greater risk of stage 2 or 3 AKI after adjustment for relevant confounders (adjusted odds ratio [95% confidence interval] for PTZ/VAN vs CEF/VAN, 1.11 [.85-1.45]; PTZ/VAN vs MER/VAN, 1.04 [.71-1.42]). No significant differences were noted between groups at 60-day follow-up in the outcomes of persistent kidney dysfunction (P = .08), new dialysis dependence (P = .15), or death (P = .09).. Short courses of PTZ/VAN were not associated with a greater risk of short- or 60-day adverse renal outcomes than other empiric broad-spectrum combinations.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefepime; Cohort Studies; Critical Illness; Female; Humans; Intensive Care Units; Kidney Function Tests; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pseudomonas; Pseudomonas Infections; Severity of Illness Index; Vancomycin

Piperacillin/tazobactam (TZP) has been associated with nephrotoxicity in patients receiving vancomycin. Its impact on nephrotoxicity in patients with Gram-negative bacteraemia (GNB) is unclear. This study evaluated the impact of TZP on nephrotoxicity in patients with GNB. This retrospective cohort included patients aged ≥18 years receiving ≥48 h of therapy for bacteraemia due to Escherichia coli, Pseudomonas aeruginosa, Enterobacter, Klebsiella, Acinetobacter or Stenotrophomonas maltophilia from 1/01/2008-8/31/2011. Patients with baseline serum creatinine (SCr) ≥3.5 mg/dL, polymicrobial infection or recurrent bacteraemia were excluded. Nephrotoxicity was defined as a ≥0.5 mg/dL increase in SCr or ≥50% increase from baseline for ≥2 consecutive days. Any variable demonstrating a 10% change in exposure effect was retained in the final model. All variables biologically reasonable causes of nephrotoxicity were also considered for inclusion. The median age of the cohort (n = 292) was 76 years; 38.0% had a cancer diagnosis and ICU residence was common (21.9%). There was no difference in nephrotoxicity incidence based on days of TZP received (0 days, 13.6%; 1-2 days, 14.7%; 3-4 days, 6.9%; ≥5 days, 16.7%; P = 0.71). In multivariable analysis, baseline SCr, total body weight and vasopressor use were independently associated with nephrotoxicity. Duration of TZP was not associated with nephrotoxicity in multivariable analysis (1-2 days, OR = 0.91, 95% CI 0.39-2.12; 3-4 days, OR = 0.48, 95% CI 0.10-2.46; ≥5 days, OR = 0.57, 95% CI 0.11-3.02). In this cohort of GNB patients, duration of TZP was not associated with nephrotoxicity.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactamase Inhibitors; Female; Gram-Negative Bacterial Infections; Humans; Incidence; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

Topics: Acute Kidney Injury; Aged; Agriculture; Anti-Bacterial Agents; California; Contrast Media; Cough; Diagnosis, Differential; Dyspnea; Fever; Granulomatosis with Polyangiitis; Humans; Lung Neoplasms; Male; Mexico; Piperacillin, Tazobactam Drug Combination; Pneumonia; Tomography, X-Ray Computed; Vancomycin

Results of a study of rates of acute kidney injury (AKI) in pediatric patients treated with vancomycin plus piperacillin-tazobactam or vancomycin plus alternative antipseudomonal β-lactams (APBLs) are reported.. A retrospective, single-center cohort study was performed. Pediatric patients were included in the study cohort if they received combination therapy for at least 48 hours, had documented baseline and follow-up serum creatinine levels, and had a documented serum vancomycin trough concentration. The primary outcome was the frequency of AKI, defined as a 50% or greater increase in serum creatinine concentration from baseline or an increase of at least 0.5 mg/dL from baseline. The secondary outcome was time to AKI onset.. A total of 474 patients were included. Among 100 patients who received vancomycin plus piperacillin-tazobactam, the rate of AKI was higher than the rate in the group treated with vancomycin plus alternative APBLs (27% versus 7%, p < 0.0001). The median time to AKI onset was shorter in the piperacillin-tazobactam group versus the alternative APBL group (3.8 versus 7.9 days, p = 0.0065). Patients who were administered piperacillin-tazobactam were almost 6 times as likely to develop AKI (odds ratio [OR], 5.955; 95% confidence interval [CI], 2.774-12.784), and patients who had a maximum vancomycin trough concentration greater than 20 mg/L were 7.5 times as likely to develop AKI (OR, 7.552; 95% CI, 3.625-15.734).. Pediatric patients treated with concomitant vancomycin and piperacillin-tazobactam had a higher rate of AKI, with faster AKI onset, than those who received vancomycin in combination with other APBLs.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Child; Creatinine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Time Factors; Vancomycin

Results of a study to determine whether obesity is associated with acute kidney injury (AKI) among patients receiving combination therapy with piperacillin-tazobactam and vancomycin are reported.. A retrospective, single-center cohort study of patients who received combination therapy for at least 48 hours was conducted using data from the University of Kentucky Center for Clinical and Translational Science's Enterprise Data Trust. Patients with chronic kidney disease, baseline creatinine clearance of less than 30 mL/min, cystic fibrosis, or missing height or weight information were excluded.. A total of 8,125 patients were included in the cohort. Among the variables evaluated, total body weight of 91 kg or more was the variable most predictive of AKI. Patients with a weight of 91 kg or higher were more likely than lower-weight patients to have diabetes (39% versus 21%, p < 0.00001), hypertension (64% versus 47%, p < 0.00001), and heart failure (15% versus 13%, p = 0.007). The median daily vancomcyin dose was lower in patients with a weight of less than 91 kg (2,000 mg versus 3,000 mg, p < 0.00001); however, weight-based doses were lower in patients weighing 91 kg or more (25.5 mg/kg/day versus 27.9 mg/kg/day, p < 0.00001). AKI was more common in patients weighing 91 kg or more (24% versus 18%, p < 0.00001; adjusted odds ratio, 1.46 [95% confidence interval, 1.28-1.66]).. Increased total body weight increased the rate of AKI among patients concurrently treated with piperacillin-tazobactam and vancomycin independent of clinically important confounders, with an important breakpoint occurring at 91 kg.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Body Weight; Drug Therapy, Combination; Female; Humans; Kentucky; Male; Middle Aged; Obesity; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Vancomycin; Young Adult

Vancomycin is very commonly used in combination with piperacillin-tazobactam (PTZ) as the initial empiric treatment for moderate-severe infection, whenever coverage for both methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa is required. The combination of vancomycin and PTZ in adults has recently been reported to significantly increase the risk of acute kidney injury (AKI) relative to vancomycin monotherapy; such reports in pediatrics, however, are sparse.. A retrospective chart review was conducted of pediatric patients, aged 0-14 years, who were admitted to the general wards or intensive care unit and developed AKI after receiving vancomycin and PTZ concomitantly for >48 h. AKI is defined as a decrease in estimated glomerular filtration rate ≥50% from baseline. Cases were identified by reviewing the Adverse Drug Reaction program database at King Saud University Medical City in Saudi Arabia from January 2015 to June 2016.. Eight children admitted to the present hospital and who received concomitant vancomycin and PTZ treatment for pneumonia (n = 7) or febrile neutropenia (n = 1) developed drug-induced nephrotoxicity. Drug Interaction Probability Scale (DIPS) score for causation assessment was 9 in all cases (highly probable).. Caution in utilizing the combination of vancomycin and PTZ is warranted in pediatric patients. Health-care professionals should be vigilant if this combination is to be initiated, and ensure close monitoring of renal function. Antibiotic therapy de-escalation should be considered as soon as culture results are available.

Topics: Acute Kidney Injury; Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Cohort Studies; Databases, Factual; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Infant; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Saudi Arabia; Vancomycin

Topics: Acute Kidney Injury; Administration, Intravenous; Administration, Oral; Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy-Induced Febrile Neutropenia; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin; Female; Fluoroquinolones; Hospitalization; Humans; Medical Overuse; Neoplasm Staging; Piperacillin, Tazobactam Drug Combination; Risk Assessment; Vancomycin

Patients often receive broad-spectrum antibiotics for nosocomial infections commonly with activity against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Previous retrospective and/or single-center studies have suggested that the combination of vancomycin and piperacillin/tazobactam might be associated with an increased risk of acute kidney injury.. To compare the incidence of nephrotoxicity in patients receiving intravenous vancomycin in combination with cefepime, meropenem, or piperacillin/tazobactam.. This was a prospective, multicenter observational study of patients receiving vancomycin in combination with piperacillin/tazobactam versus cefepime or meropenem. Adult patients 18 years of age or older who were hospitalized and received 72 or more hours of intravenous vancomycin and 72 hours or more of cefepime, meropenem, or piperacillin/tazobactam were eligible. Patient and medication characteristics were examined for the 242 patients included.. The incidence of acute kidney injury for patients treated with vancomycin and piperacillin/tazobactam was significantly higher than for those treated with vancomycin and cefepime or meropenem, 29.8% versus 8.8%, respectively, P < 0.001. Binary logistic regression demonstrated that patients receiving vancomycin and piperacillin/tazobactam were 6.7 times more likely to develop acute kidney injury compared with the other cohort.. The combination of vancomycin with piperacillin/tazobactam significantly increases the risk of acute kidney injury compared with other broad-spectrum antibiotic combinations. Clinicians should be vigilant when employing this regimen.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

The combination of piperacillin/tazobactam (TZP) and vancomycin (VAN) provides a wide spectrum of activity against many pathogens acquired in healthcare settings. However, there have been reports of increased potential for nephrotoxicity with this combination. The aim of this study was to evaluate the nephrotoxic effect of TZP+VAN and to compare it with that of TZP and VAN monotherapies as well as VAN + meropenem (MEM), another broad-spectrum combination. A total of 402 patients receiving any of the antimicrobial regimens for >48 h were evaluated retrospectively over a 2-year period (2012-2013). Patients admitted to the intensive care unit, those with a baseline serum creatinine >2.0 mg/dL, patients on haemodialysis or peritoneal dialysis, pregnant women and those in septic shock were excluded. The presence and severity of acute kidney injury (AKI) was assessed according to the AKIN criteria. The incidence of AKI was significantly higher in the TZP+VAN group (41.3%) compared with the TZP (16.0%), VAN (15.7%) and VAN+MEM (10.1%) groups (P < 0.001). In the multivariate analysis, the risk of AKI increased 3.5-fold in patients treated with TZP+VAN and 1.7-fold in those who were receiving a potentially nephrotoxic drug when the antibiotic regimen was started compared with patients treated with VAN alone. Combined use of TZP+VAN carries a much higher risk of AKI than either antibiotic monotherapy regimen. Therefore, this broad-spectrum combination should be used cautiously in patients with a high likelihood of developing kidney injury.

Topics: Acute Kidney Injury; Adult; Aged; Creatinine; Drug Therapy, Combination; Female; Humans; Kidney; Logistic Models; Male; Meropenem; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Staphylococcal Infections; Thienamycins; Vancomycin

Acute kidney injury (AKI) increases during empirical antimicrobial therapy with the combination of piperacillin-tazobactam (TZP) and vancomycin (VAN) compared to the number of incidences with monotherapy or the combination of cefepime and VAN. Limited data regarding the impact of meropenem (MEM) combined with VAN exist. This study examined the AKI incidence among patients treated with MEM plus VAN (MEM+VAN) or TZP+VAN. Data were collected from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust from September 2007 through October 2015. Adults without previous renal disease who received MEM+VAN or TZP+VAN for at least 2 days were included. AKI was assessed using risk, injury, failure, loss, and end-stage (RIFLE) criteria. Inverse probability of treatment weighting was utilized to control for differences between groups. In total, 10,236 patients met inclusion criteria, with 9,898 receiving TZP+VAN and 338 receiving MEM+VAN. AKI occurred in 15.4% of MEM+VAN patients and in 27.4% of TZP+VAN patients (

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Cefepime; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Though acute kidney injury (AKI) is often multifactorial, investigators are now emphasizing the specific contribution of nephrotoxins. This study examines the epidemiology of nephrotoxin exposure and nephrotoxin-associated AKI among children undergoing congenital heart surgery (CHS).. This is a retrospective cohort study of children admitted following CHS between June 1, 2014, and September 30, 2014. Nephrotoxins were defined according to the Nephrotoxic Injury Negated by Just-in-time-Action (NINJA) collaborative; high nephrotoxin exposure was defined as receipt of ≥ 3 nephrotoxins concurrently. AKI was diagnosed according to KDIGO creatinine criteria. Severe AKI was defined as KDIGO stage ≥ 2. Poisson models were used to compute adjusted relative risk (aRR) of high nephrotoxin exposure for AKI.. One hundred fifty-four children (median age 20.4 months, IQR 2.3-59.5) were included. One hundred thirty-one (85.1%) received at least one nephrotoxin; 32 (20.8%) received ≥ 3 nephrotoxins. The most commonly administered medications were ketorolac (n = 74, 48.1%), aspirin (n = 62, 40.3%), ibuprofen (n = 51, 33.1%), vancomycin (n = 39, 25.3%), piperacillin/tazobactam (n = 35, 22.7%), and enalapril (n = 14, 9.1%). AKI occurred more commonly in those exposed to ≥ 3 nephrotoxins (62.5 vs. 50.8%); this was not statistically significant after adjusting for confounders (aRR = 1.2, 95% CI 0.9-1.7). Severe AKI was similar between those with and without high nephrotoxin exposure (21.9 vs. 19.7%, p = 0.78).. Nephrotoxin use is common following pediatric CHS. While we found no association between high nephrotoxin exposure and AKI, this may be related to the multifactorial nature of AKI in this population. For many common nephrotoxins, less injurious agents exist and nephrotoxin exposure may represent a modifiable risk factor for AKI.

Topics: Acute Kidney Injury; Adolescent; Aspirin; Cardiac Surgical Procedures; Child; Child, Preschool; Critical Illness; Enalapril; Female; Heart Defects, Congenital; Humans; Ibuprofen; Infant; Ketorolac; Male; Piperacillin, Tazobactam Drug Combination; Postoperative Complications; Retrospective Studies; Vancomycin

The objective of this study was to evaluate AKI incidence with concomitant vancomycin and piperacillin/tazobactam (PTZ) compared to vancomycin and cefepime (FEP) in critically ill patients.. A retrospective, cohort study was conducted in adult critically ill patients from January 1, 2014 to December 31, 2017. The primary aim was to compare the incidence of AKI during concomitant therapy or until hospital discharge. Secondary analyses included AKI severity, time to AKI as well as recovery, and clinical outcomes.. Overall, 333 patients were evaluated. The AKI rate in the vancomycin/PTZ group and vancomycin/FEP group were similar (19.5% vs. 17.3%, respectively, p = .612). Renal replacement therapy (RRT) was initiated in 10.0% and 3.8% administered vancomycin/PTZ and vancomycin/FEP groups, respectively (p = .04). Multivariate regression found vancomycin/PTZ was not associated with an increased risk of developing AKI although the presence of shock was identified as an independent risk factor (odds ratio, 3.22; 95% CI, 1.66-6.26). No significant differences in hospital or ICU length of stay or in-hospital mortality were observed between study groups.. Concomitant PTZ and vancomycin in ICU patients was not associated with an increased risk of developing AKI compared to FEP and vancomycin combinations. More patients administered vancomycin/PTZ received RRT.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Cefepime; Critical Illness; Female; Humans; Incidence; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis

Cystic fibrosis (CF) patients often receive prolonged courses of broad spectrum antibiotics, such as piperacillin-tazobactam or cefepime in combination with vancomycin and tobramycin. The objective of this study was to determine the difference in AKI for pediatric CF patients receiving piperacillin-tazobactam or cefepime in combination with vancomycin and tobramycin.. IRB approval from a single CF center was obtained for this retrospective cohort study. Charts were evaluated from December 1, 2008 to June 30,2015. Patients were included if they had a diagnosis of CF, age 30 days to 18 years, and received intravenous vancomycin, tobramycin, and piperacillin-tazobactam or cefepime. The primary outcome was difference of AKI incidence in patients receiving piperacillin-tazobactam or cefepime, as defined by modified pediatric risk, injury, failure, loss, end stage renal disease (pRIFLE) criteria.. Seventy-one patients were included with a median (interquartile range) age 11 years (7-16) and weight 36.2 kg (22.7-50). AKI was identified in 54.5% (18/33) of patients receiving piperacillin-tazobactam and 13.2% (5/38) of patients receiving cefepime (P ≤ 0.0001). One patient receiving piperacillin-tazobactam experienced acute renal failure. There was a slight difference in length of admission (13 vs 10 days, P = 0.042), but no difference in days to maximum SCr (6 vs 3, P = 0.127) nor FEV1 percent predicted on admission (69% vs 65%, P = 1.00).. AKI occurred in nearly 55% of patients with piperacillin-tazobactam therapy versus 13% of patients with cefepime therapy, which suggests cefepime may be preferred in combination with vancomycin and tobramycin for pediatric CF patients.

Topics: Acute Kidney Injury; Adolescent; Anti-Bacterial Agents; Cefepime; Cephalosporins; Child; Cystic Fibrosis; Drug Therapy, Combination; Female; Hospitalization; Humans; Incidence; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Tobramycin; Vancomycin

Recent studies have found an association between piperacillin/tazobactam when added to vancomycin and acute kidney injury (AKI) risk. However, studies were limited by the small sample size and residual confounding. The aim of this study was to compare the risk of AKI with vancomycin plus piperacillin/tazobactam (VPT) versus vancomycin plus cefepime (VC) and to examine whether pre-existing renal impairment mediates the risk. This was a retrospective cohort study using electronic health records for patients admitted to two hospitals in 2012-2013. The outcome, AKI, was defined as an increase in serum creatinine level of ≥0.3 mg/dL or ≥50% from baseline. Patients were stratified by level of renal impairment as estimated by baseline creatinine clearance. Inverse probability of treatment weighting was used to balance baseline covariates between groups. Cox proportional hazards regression was used to evaluate VPT risk of AKI compared with VC. A total of 935 (17.53%) AKI cases were identified among 5335 patients receiving VPT or VC. VPT was associated with a higher risk of AKI relative to VC, with an adjusted hazard ratio (aHR) of 1.25 [95% confidence interval (CI) 1.11-1.42] in the total population and 1.70 (95% CI 1.44-2.02) in patients with normal baseline renal function. However, no elevated risk was found in patients with prior renal impairment (aHR = 0.81, 95% CI 0.65-1.01). VPT was associated with a higher risk of AKI relative to VC. The association was true in patients with normal renal function but not in those with pre-existing renal impairment.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Cefepime; Cephalosporins; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Assessment; Vancomycin; Young Adult

Limited literature is available assessing nephrotoxicity with prolonged β-lactam infusions. This study compared the incidence of acute kidney injury (AKI) associated with a prolonged β-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: β-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%;

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Cefepime; Cephalosporins; Drug Therapy, Combination; Female; Humans; Kidney; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Thienamycins

 Tazobactam/piperacillin (TAZ/PIPC) is a combination antibiotic frequently used to treat pneumonia. It has recently been reported that TAZ/PIPC worsens renal function in patients with existing renal impairment. Creatinine clearance is generally between 10 and 40 mL/min in Japanese patients, so TAZ/PIPC is given at a dose of 2.25 g three times daily or 4.5 g twice daily. If pneumonia is severe or intractable, the dose frequency may be increased to 2.25 g four times daily and 4.5 g three times daily. We examined the effect of these different dosing regimens on renal function. We studied a cohort of 57 patients with impaired renal function hospitalized with pneumonia and treated with TAZ/PIPC between January 2015 and November 2016. Patients were classified into four groups according to TAZ/PIPC dose: 2.25 g three times daily (Group A); 2.25 g four times daily (B); 4.5 g twice daily (C) and 4.5 g three times daily (D). We examined the frequency of acute kidney injury (AKI) and treatment effectiveness. In Groups A, B, C and D, AKI occurred in 5.6%, 0.0%, 25.0% and 38.5% of patient. In groups C and D, hydration and dose reduction were required to address early signs of impending AKI. Our findings suggest that the higher TAZ/PIPC dose of 4.5 g was responsible for the decline in renal function, even if the dose frequency was reduced.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Retrospective Studies; Treatment Outcome

Broad-spectrum antibiotics are often used as initial empiric therapy in patients at risk for infections by multidrug-resistant organisms. Emerging literature and anecdotal reports within Tripler Army Medical Center indicate an increased incidence of vancomycin-associated acute kidney injury when used in combination with piperacillin-tazobactam. This is a retrospective, single-center study comparing the incidence of acute kidney injury in noncritically ill patients receiving either vancomycin or vancomycin in combination with piperacillin-tazobactam in a 206-bed tertiary care military training facility.. Data were collected from electronic medical records between May 2012 and October 2014 and evaluated via multivariable logistic regression models. Patients included for analysis were 17 years of age and older, were admitted to medical/surgical wards, and received vancomycin or vancomycin in combination with piperacillin-tazobactam for at least 48 hours. A vancomycin trough level, baseline serum creatinine level, and at least two follow-up serum creatinine levels were required for inclusion. Patients were excluded if they were pregnant, admitted to an intensive care unit while on antimicrobial therapy, or their baseline serum creatinine was equal to or greater than 1.5 mg/dL.. Of 1,133 patients evaluated retrospectively, 455 were included for analysis. Of 202 patients, 49 (24%) taking vancomycin in combination with piperacillin-tazobactam developed acute kidney injury in contrast to 28 of the 253 patients (11%) given vancomycin without piperacillin-tazobactam (unadjusted odds ratio 2.57 [95% confidence interval (CI) 1.55-4.28], p < 0.001). Dual therapy remained significant after adjusting for age, sex, body mass index, concomitant nephrotoxic agents, and preexisting comorbid status as evaluated by Charlson comorbidity index (adjusted odds ratio 2.14 [95% CI 1.26-3.6], p = 0.005). Contrast administration (p < 0.001), fluoroquinolone administration (p < 0.001), and Charlson Comorbidity Index > 6 (p = 0.008) were also found to be independent risk factors for acute kidney injury.. Significant increased incidence of nephrotoxicity was noted with vancomycin and piperacillin-tazobactam as compared to vancomycin within Tripler Army Medical Center. This finding influenced our institution's decision to add ceftaroline as a formulary agent in the treatment of skin and soft-tissue infections and further supported the need for rapid de-escalation of antibiotics within our military training facility.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Drug Therapy, Combination; Female; Hospitals, Military; Humans; Incidence; Logistic Models; Male; Middle Aged; Military Personnel; Odds Ratio; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Tazobactam; Tertiary Care Centers; Vancomycin

Compare the rates of acute kidney injury in critically ill children treated with vancomycin and piperacillin-tazobactam versus vancomycin and ceftriaxone.. Retrospective cohort study.. A large tertiary care children's hospital in an urban setting.. Children greater than or equal to 2 months old admitted to the PICU who received greater than or equal to 48 consecutive hours of vancomycin and piperacillin-tazobactam or vancomycin and ceftriaxone.. None.. Acute kidney injury was defined as a minimum 50% increase in serum creatinine, adjusted for total fluid balance, from baseline over a 48-hour period. Bivariate analysis compared treatment groups and acute kidney injury groups. A multivariable logistic regression model was fit for acute kidney injury including covariable analysis. The study included 93 children. There were no differences between treatment groups in terms of age, severity of illness, baseline renal function, vancomycin dosing, or vancomycin trough concentrations. Children who received vancomycin and piperacillin-tazobactam had a higher cumulative frequency of acute kidney injury than those who received vancomycin and ceftriaxone 915/58 [25.9%] vs 3/35 [8.6%]; p = 0.041). After controlling for vancomycin trough concentration, age, concurrent nephrotoxin exposure, and use of vasopressors, exposure to piperacillin-tazobactam significantly increased the risk of acute kidney injury (adjusted odds ratio, 4.55; 95% CI [1.11-18.7]; p = 0.035) compared with ceftriaxone. Use of vasopressors (adjusted odds ratio, 3.73 [95% CI, 1.14-12.3]) and a vancomycin trough greater than or equal to 15 mg/dL (adjusted odds ratio, 4.12 [95% CI, 1.12-15.2)] was also associated with acute kidney injury. Length of stay was longer in children with acute kidney injury (median, 18.0 days; interquartile range, 7.76-29.7) compared with those without acute kidney injury (median, 6.21 days; interquartile range, 2.92-15.6; p = 0.017).. In critically ill children, acute kidney injury occurred more in patients treated with vancomycin and piperacillin-tazobactam versus vancomycin plus ceftriaxone. After controlling for covariates, exposure to piperacillin-tazobactam was associated with an increased odds of acute kidney injury development.

Topics: Acute Kidney Injury; Adolescent; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Critical Illness; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Infant; Intensive Care Units, Pediatric; Logistic Models; Male; Odds Ratio; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

β-Lactam antibiotics are often coadministered with intravenous (IV) vancomycin hydrochloride for children with suspected serious infections. For adults, the combination of IV vancomycin plus piperacillin sodium/tazobactam sodium is associated with a higher risk of acute kidney injury (AKI) compared with vancomycin plus 1 other β-lactam antibiotic. However, few studies have evaluated the safety of this combination for children.. To assess the risk of AKI in children during concomitant therapy with vancomycin and 1 antipseudomonal β-lactam antibiotic throughout the first week of hospitalization.. This retrospective cohort study focused on children hospitalized for 3 or more days who received IV vancomycin plus 1 other antipseudomonal β-lactam combination therapy at 1 of 6 large children's hospitals from January 1, 2007, through December 31, 2012. The study used the Pediatric Health Information System Plus database, which contains administrative and laboratory data from 6 pediatric hospitals in the United States. Patients with underlying kidney disease or abnormal serum creatinine levels on hospital days 0 to 2 were among those excluded. Patients 6 months to 18 years of age who were admitted through the emergency department of the hospital were included. Data were collected from July 2015 to March 2016. Data analysis took place from April 2016 through July 2017. (Exact dates are not available because the data collection and analysis processes were iterative.).. The primary outcome was AKI on hospital days 3 to 7 and within 2 days of receiving combination therapy. Acute kidney injury was defined using KDIGO criteria and was based on changes in serum creatinine level from hospital days 0 to 2 through hospital days 3 to 7. Multiple logistic regression was performed using a discrete-time failure model to test the association between AKI and receipt of IV vancomycin plus piperacillin/tazobactam or vancomycin plus 1 other antipseudomonal β-lactam antibiotic.. A total of 1915 hospitalized children who received combination therapy were identified. Of the 1915 patients, a total of 866 (45.2%) were female and 1049 (54.8%) were male, 1049 (54.8%) were identified as white in race/ethnicity, and the median (interquartile range) age was 5.6 (2.1-12.7) years. Among the cohort who received IV vancomycin plus 1 other antipseudomonal β-lactam antibiotic, 157 patients (8.2%) had antibiotic-associated AKI. This number included 117 of 1009 patients (11.7%) who received IV vancomycin plus piperacillin/tazobactam combination therapy. After adjustment for age, intensive care unit level of care, receipt of nephrotoxins, and hospital, IV vancomycin plus piperacillin/tazobactam combination therapy was associated with higher odds of AKI each hospital day compared with vancomycin plus 1 other antipseudomonal β-lactam antibiotic combination (adjusted odds ratio, 3.40; 95% CI, 2.26-5.14).. Coadministration of IV vancomycin and piperacillin/tazobactam may increase the risk of AKI in hospitalized children. Pediatricians must be cognizant of the potential added risk of this combination therapy when making empirical antibiotic choices.

Topics: Acute Kidney Injury; Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Databases, Factual; Drug Therapy, Combination; Female; Hospital Mortality; Hospitalization; Humans; Length of Stay; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Assessment; United States; Vancomycin

Burn patients are prone to infections which often necessitate broad antibiotic coverage. Vancomycin is a common antibiotic after burn injury and is administered alone (V), or in combination with imipenem-cilastin (V/IC) or piperacillin-tazobactam (V/PT). Sparse reports indicate that the combination V/PT is associated with increased renal dysfunction. The purpose of this study was to evaluate the short-term impact of the three antibiotic administration types on renal dysfunction.. All pediatric and adult patients admitted to our centers between 2004 and 2016 with a burn injury were included in this retrospective review if they met the criteria of exposition to either V, V/IC, or V/PT for at least 48 h, had normal baseline creatinine, and no pre-existing renal dysfunction. Creatinine was monitored for 7 days after initial exposure; the absolute and relative increase was calculated, and patient renal outcomes were classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria depending on creatinine increases and estimated creatinine clearance. Secondary endpoints (demographic and clinical data, incidences of septicemia, and renal replacement therapy) were analyzed. Antibiotic doses were modeled in logistic and linear multivariable regression models to predict categorical KDIGO events and relative creatinine increase.. Out of 1449 patients who were screened, 718 met the inclusion criteria, 246 were adults, and 472 were children. Between the study cohorts V, V/IC, and V/PT, patient characteristics at admission were comparable. V/PT administration was associated with a statistically higher serum creatinine, and lower creatinine clearance compared to patients receiving V alone or V/IC in adults and children after burn injury. The incidence of KDIGO stages 1, 2, and 3 was higher after V/PT treatment. In children, the incidence of KDIGO stage 3 following administration of V/PT was greater than after V/IC. In adults, the incidence of renal replacement therapy was higher after V/PT compared with V or V/IC. Multivariate modeling demonstrated that V/PT is an independent predictor of renal dysfunction.. Co-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in pediatric and adult burn patients when compared to vancomycin alone or vancomycin plus imipenem-cilastin. The mechanism of this increased nephrotoxicity remains elusive and warrants further scientific evaluation.

Topics: Acute Kidney Injury; Adolescent; Adult; Analysis of Variance; Anti-Bacterial Agents; Burns; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Cohort Studies; Creatinine; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Incidence; Infections; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Texas; Vancomycin

To prospectively evaluate the observed incidence of acute kidney injury (AKI) in adult patients receiving the combination of piperacillin-tazobactam and vancomycin versus the combination of cefepime or meropenem and vancomycin for greater than 72 hours.. This was a prospective, open-label cohort study at a community academic medical center involving adult patients over a 3-month time period who received either the combination of piperacillin-tazobactam and vancomycin or the combination of cefepime or meropenem and vancomycin for greater than 72 hours. The patients were evaluated for AKI, defined using specific criteria introduced by Kidney Disease: Improving global outcomes (KDIGO) acute kidney injury work group in 2012.. A total of 85 patients receiving either antimicrobial combination were evaluated for AKI. The incidence of AKI was significantly higher in the piperacillin-tazobactam and vancomycin group (37.3%) compared with the cefepime or meropenem and vancomycin group (7.7%; χ. The result of this study suggests that the risk of developing AKI is increased in patients receiving the combination of piperacillin-tazobactam and vancomycin versus those receiving the combination of cefepime or meropenem and vancomycin.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefepime; Cephalosporins; Cohort Studies; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Thienamycins; Treatment Outcome; Vancomycin

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 end-stage 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 < 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 < 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.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Cefepime; Cephalosporins; Female; Humans; Kidney; Male; Middle Aged; Multivariate Analysis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Recent evidence suggests that among patients receiving vancomycin, receipt of concomitant piperacillin-tazobactam increases the risk of nephrotoxicity. Well-controlled, adequately powered studies comparing rates of acute kidney injury (AKI) among patients receiving vancomycin + piperacillin-tazobactam (VPT) compared to similar patients receiving vancomycin + cefepime (VC) are lacking. In this study we compared the incidence of AKI among patients receiving combination therapy with VPT to a matched group receiving VC.. A retrospective, matched, cohort study was performed. Patients were eligible if they received combination therapy for ≥48 hours. Patients were excluded if their baseline serum creatinine was >1.2mg/dL or they were receiving renal replacement therapy. Patients receiving VC were matched to patients receiving VPT based on severity of illness, intensive care unit status, duration of combination therapy, vancomycin dose, and number of concomitant nephrotoxins. The primary outcome was the incidence of AKI. Multivariate modeling was performed using Cox proportional hazards.. A total of 558 patients were included. AKI rates were significantly higher in the VPT group than the VC group (81/279 [29%] vs 31/279 [11%]). In multivariate analysis, therapy with VPT was an independent predictor for AKI (hazard ratio = 4.27; 95% confidence interval, 2.73-6.68). Among patients who developed AKI, the median onset was more rapid in the VPT group compared to the VC group (3 vs 5 days P =< .0001).. The VPT combination was associated with both an increased AKI risk and a more rapid onset of AKI compared to the VC combination.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Cefepime; Cephalosporins; Combined Modality Therapy; Drug Therapy, Combination; Female; Humans; Length of Stay; Male; Middle Aged; Odds Ratio; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prognosis; Retrospective Studies; Risk; Severity of Illness Index; Vancomycin

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Bacterial Proteins; Bacterial Toxins; beta-Lactamases; Clostridioides difficile; Enterobacter cloacae; Female; Humans; Imipenem; Kidney Failure, Chronic; Kidney Transplantation; Metronidazole; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Respiratory Insufficiency; Vancomycin

Despite recent reports of relatively high rates (16-37%) of acute kidney injury (AKI) in patients receiving the combination of intravenous piperacillin-tazobactam (PTZ) and vancomycin, data are limited evaluating the impact of PTZ infusion strategy on the occurrence of nephrotoxicity. The objective of this study was to compare the rates of nephrotoxicity in patients receiving vancomycin in combination with PTZ administered as an extended infusion (EI) versus a standard infusion (SI).. Single-center, retrospective, matched-cohort study.. Large academic tertiary care hospital.. Two hundred eighty adults with a creatinine clearance (CrCl) of 40 ml/minute or higher who received at least 96 hours of vancomycin plus PTZ EI (140 patients) or vancomycin plus PTZ SI (140 patients) between January 1, 2009, and December 31, 2011, and between January 1, 2013, and December 31, 2014 (year 2012 was skipped due the closure of inpatient units following Superstorm Sandy); 48 patients in each group were admitted to the intensive care unit.. The median age of all patients was 67 (interquartile range [IQR] 54-77) years, and CrCl was 75 (IQR 55-107) ml/minute. Nephrotoxicity was assessed by the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN) criteria. Rates of AKI, according to these criteria, were similar between groups: 17.9% versus 17.1% (p=1) and 32.9% versus 29.3% (p=0.596) for the PTZ EI and PTZ SI groups, respectively. When controlling for residual differences between groups in a conditional logistic regression analysis, no association was observed between receipt of PTZ EI and RIFLE-defined AKI (odds ratio 0.522, 95% confidence interval 0.043-6.295, p=0.609). Time to onset of nephrotoxicity was 4 (IQR 3-6) days, with no significant difference noted between groups (p=0.887).. Our findings suggest a similar rate of nephrotoxicity between patients who received vancomycin in combination with PTZ EI versus PTZ SI. These results need to be further validated in a prospective randomized controlled study.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Cohort Studies; Creatinine; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Intensive Care Units; Logistic Models; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Tertiary Care Centers; Time Factors; Vancomycin

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.. This study evaluated the effect of the VAN/PTZ combination on acute kidney injury (AKI) compared to VAN and PTZ monotherapies.. 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.. The primary outcome was AKI incidence as defined by the Risk, Injury, Failure, Loss, End-stage (RIFLE) criteria.. 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.. 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.. 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. Journal of Hospital Medicine 2017;12:77-82.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Drug Therapy, Combination; Female; Humans; Incidence; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Increased acute kidney injury (AKI) incidence has been reported in patients receiving piperacillin-tazobactam (PTZ) therapy compared with other β-lactams. The authors sought to determine if the addition of β-lactamase inhibitors impacts AKI incidence by comparing patients treated with PTZ or ampicillin-sulbactam (SAM).. Retrospective cohort study.. Large academic tertiary care hospital.. Overall, 2448 patients received PTZ (n=1836) 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 < 30 ml/min. Patients were matched on Charlson Comorbidity Index, initial creatinine clearance, hypotension exposure, various nephrotoxic drug exposures, history of diabetes, heart failure, and hypertension.. 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 odds ratio [aOR] 0.87, 95% confidence interval [CI] 0.59-1.25). The addition of vancomycin (VAN) to PTZ increased the likelihood of AKI compared with PTZ alone (aOR 1.77, 95% CI 1.26-2.46). Concomitant SAM and VAN therapy was not associated with a significant increase in AKI compared with SAM monotherapy (aOR 1.01, 95% CI 0.48-1.97).. Rates of AKI were similar for PTZ and SAM in a matched cohort. The addition of a β-lactamase inhibitor is not likely the mechanism in the observed increased rates of AKI in patients treated with vancomycin and PTZ.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactams; Cohort Studies; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Treatment Outcome; Vancomycin

This study aimed to determine the safety impact of an antimicrobial stewardship program (ASP) on vancomycin-associated nephrotoxicity and to examine risk factors contributing to the development of toxicity.. This was a retrospective chart review of data from 453 veterans receiving vancomycin in the VA Western New York Healthcare System between October 2006 and July 2014. Nephrotoxicity was defined as an increase in serum creatinine of ≥ 0.5 mg/dL or by 50% of baseline for 2 consecutive days.. Patients receiving vancomycin after the implementation of the ASP were less likely to develop nephrotoxicity (odds ratio [OR] = 2.06; 95% CI, 1.02-4.28). Nephrotoxicity occurred in 6.84% of patients from the pre-ASP cohort and in 3.75% of patients after the implementation of the ASP. Predictors of nephrotoxicity included hospital service (surgical service, OR = 2.29; 95% CI, 1.13-4.64), elevated maximum trough concentration (unit OR = 1.15; 95% CI, 1.10-1.20), and concurrent piperacillin/tazobactam therapy (OR = 3.21; 95% CI, 1.43-7.96). The number of vancomycin trough concentration measurements per patient did not vary between the pre-ASP and ASP groups.. ASPs represent an important aspect of a patient-safety initiative in order to reduce vancomycin-associated nephrotoxicity. Concurrent piperacillin/tazobactam therapy, surgical service, and elevated maximum trough concentration were risk factors for nephrotoxicity.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Creatinine; Drug Therapy, Combination; Female; Hospital Departments; Humans; Interrupted Time Series Analysis; Male; Middle Aged; Patient Safety; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Vancomycin; Veterans

The combination of vancomycin and piperacillin-tazobactam has been associated with an increased risk of acute kidney injury (AKI) in non-critically ill patient populations, but it is still unknown if this association exists in critically ill patients. The objective of this study was to compare the incidence of AKI development during therapy or within 72 hours after completion of therapy in adult critically ill patients who received vancomycin with concomitant piperacillin-tazobactam or cefepime.. Retrospective cohort study.. Medical, surgical, and neuroscience intensive care units (ICUs) within a single tertiary care hospital.. A total of 122 critically ill patients who received at least 48 hours of combination therapy with vancomycin and piperacillin-tazobactam (49 patients) or vancomycin and cefepime (73 patients) during an ICU admission between September 2012 and December 2014.. The primary outcome was AKI development, as determined by the Acute Kidney Injury Network criteria, during combination therapy or within 72 hours of completion of combination therapy. The inverse probability of the treatment-weighting (IPTW) approach was used to account for potential treatment selection bias. AKI incidence was assessed in the unadjusted and propensity score-weighted cohorts. Of the 122 patients, 37 patients (30.3%) developed AKI. In the unadjusted analysis, the incidence of AKI was similar in the piperacillin-tazobactam group compared with the cefepime group (32.7% vs 28.8%, p=0.647). The average treatment effect between the groups was not significant, showing no association between β-lactam choice and AKI (β = -0.004, p=0.958). Secondary outcomes were ICU length of stay, hospital length of stay, AKI duration, and need for renal replacement therapy. The choice of β-lactam was not a significant predictor of any of these outcomes: ICU length of stay (β = 0.436, p=0.780), hospital length of stay (β = 3.819, p=0.125), AKI duration (β = -4.027, p=0.283), and need for renal replacement therapy (β = 2.828, p=0.161).. After adjusting for propensity to receive each of the treatment choices, no significant difference was found in the incidence of AKI development or other outcomes between the groups. The previously described finding that concomitant vancomycin and piperacillin-tazobactam increases AKI in non-critically ill patients may not be generalizable to the critically ill population. Prospective evaluation of this hypothesis is warranted.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Arkansas; Cefepime; Cephalosporins; Critical Illness; Drug Therapy, Combination; Female; Humans; Incidence; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Despite their common use as an empirical combination therapy for the better part of a decade, there has been a recent association between combination therapy with vancomycin and piperacillin-tazobactam and high rates of acute kidney injury (AKI). The reasons for this increased association are unclear, and this analysis was designed to investigate the association. Retrospective cohort and case-control studies were performed. The primary objective was to assess if there is an association between extended-infusion piperacillin-tazobactam in combination with vancomycin and development of AKI. The secondary objectives were to identify risk factors for AKI in patients on the combination, regardless of infusion strategy, and to evaluate the impact of AKI on clinical outcomes. AKI occurred in 105/320 (33%) patients from the cohort receiving combination therapy with vancomycin and piperacillin-tazobactam, with similar rates seen in those receiving intermittent (53/160 [33.1%]) and extended infusions (52/160 [32.5%]) of piperacillin-tazobactam. Independent risk factors for AKI in the cohort included having a documented Gram-positive infection, the presence of sepsis, receipt of a vancomycin loading dose (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.05 to 4.71), and receipt of any concomitant nephrotoxin (OR, 2.44; 95% CI, 1.41 to 4.22). For at-risk patients remaining on combination therapy, the highest rates of AKI occurred on days 4 (10.7%) and 5 (19.3%). The incidence of AKI in patients on combination therapy with vancomycin and piperacillin-tazobactam is high, occurring in 33% of patients. Receipt of piperacillin-tazobactam as an extended infusion did not increase this risk. Modifiable risk factors for AKI include receipt of a vancomycin loading dose, concomitant nephrotoxins, and longer durations of therapy.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Case-Control Studies; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Logistic Models; Male; Michigan; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Infection is the most common cause of death in severe AKI, but many patients receiving continuous RRT do not reach target antibiotic concentrations in plasma. Extended infusion of β-lactams is associated with improved target attainment in critically ill patients; thus, we hypothesized that extended infusion piperacillin-tazobactam would improve piperacillin target attainment compared with short infusion in patients receiving continuous RRT.. We conducted an institutional review board-approved observational cohort study of piperacillin-tazobactam pharmacokinetics and pharmacodynamics in critically ill patients receiving continuous venovenous hemodialysis and hemodiafiltration at three tertiary care hospitals between 2007 and 2015. Antibiotic concentrations in blood and/or dialysate samples were measured by liquid chromatography, and one- and two-compartment pharmacokinetic models were fitted to the data using nonlinear mixed effects regression. Target attainment for piperacillin was defined as achieving four times the minimum inhibitory concentration of 16 μg/ml for >50% of the dosing cycle. The probabilities of target attainment for a range of doses, frequencies, and infusion durations were estimated using a Monte Carlo simulation method. Target attainment was also examined as a function of patient weight and continuous RRT effluent rate.. Sixty-eight participants had data for analysis. Regardless of infusion duration, 6 g/d piperacillin was associated with ≤45% target attainment, whereas 12 g/d was associated with ≥95% target attainment. For 8 and 9 g/d, target attainment ranged between 68% and 85%. The probability of target attainment was lower at higher effluent rates and patient weights. For all doses, frequencies, patient weights, and continuous RRT effluent rates, extended infusion was associated with higher probability of target attainment compared with short infusion.. Extended infusions of piperacillin-tazobactam are associated with greater probability of target attainment in patients receiving continuous RRT.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Critical Illness; Dialysis Solutions; Female; Hemodiafiltration; Humans; Infusions, Intravenous; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Time Factors

The purpose of this study is to compare the incidence of acute renal injury (ARI) in patients on intermittent infusion to extended infusion piperacillin/tazobactam.. Data was collected for the intermittent infusion group from November 2010 to December 2010 until 100 patients were enrolled. The data was then compared to 100 patients in the extended infusion group from November 2011 to December 2011. Patients who received at least three consecutive doses of piperacillin/tazobactam and were inpatient for at least 48 hours were included. Patients were excluded for any of the following: baseline serum creatinine (SCr) ≥4 mg/dL, age less than 18 years old, pregnancy, penicillin allergy, or concurrent use with any cephalosporin or penicillin. The primary endpoint was the incidence of ARI, defined as a SCr two times the baseline or 0.5 mg/dL increase within 24 hours. The secondary endpoint was patient length of stay, measured as actual inpatient days.. Eleven patients in the intermittent infusion group and nine patients in the extended infusion group developed ARI (11% vs. 9%, p = 0.637). The length of stay between the intermittent and extended infusion groups was 19 days vs. 14 days, respectively (p = 0.083).. The incidence of ARI in patients on piperacillin/tazobactam was similar between the intermittent and extended infusion groups. Larger studies should be considered to confirm that the incidence of ARI associated with piperacillin/tazobactam is not infusion-related.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Drug Administration Schedule; Female; Humans; Incidence; Infusions, Intravenous; Longevity; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

Few data are available on the nephrotoxic potential of vancomycin when combined with certain β-lactam antibiotics for the treatment of osteomyelitis (OM). A retrospective cohort study was conducted of all diabetic patients with OM treated with vancomycin plus piperacillin-tazobactam (VPT) or vancomycin plus cefepime (VC) for at least 72 h at a VA Medical Center between 1 January 2006 and 31 December 2011. All patients with a creatinine clearance (CrCl) of ≤ 40 mL/min, a blood urea nitrogen/serum creatinine (SCr) ratio of ≥ 20 : 1 or an absolute neutrophil count of <500 cells/mm(3) were excluded. The primary outcome was development of acute renal failure (ARF), defined as an increase in SCr of 0.5 mg/dL or 50% of baseline. One hundred and thirty-nine patients met the inclusion criteria; 109 in the piperacillin-tazobactam group and 30 in the cefepime group. Among patients receiving VPT, 29.3% (32/109) developed ARF, as compared with 13.3% (4/30) receiving VC (p 0.099). Among patients receiving high-dose therapy (≥ 18 g of piperacillin-tazobactam daily or ≥ 3 g of cefepime daily), 37.5% (9/24) receiving VPT and 17.6% (3/17) receiving VC developed ARF (p 0.29). A multiple logistic regression analysis identified weight and average vancomycin trough as the only significant predictors of ARF; the choice of VPT as therapy yielded an OR of 3.45 (95% CI 0.96-12.40; p 0.057). The authors were unable to detect a statistically significant difference in ARF between groups; however, the power requirement was not met. Further study with a larger patient population seems warranted.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Cefepime; Cephalosporins; Cohort Studies; Diabetes Complications; Drug Therapy, Combination; Humans; Incidence; Middle Aged; Osteomyelitis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

To evaluate the observed incidence of acute kidney injury (AKI) in adult patients receiving either piperacillin-tazobactam and vancomycin or cefepime-vancomycin for more than 48 hours.. Retrospective matched cohort.. Large academic medical center.. Adult patients without preexisting renal dysfunction admitted over an 8-month time period who received either the combination of piperacillin-tazobactam and vancomycin or cefepime-vancomycin for more than 48 hours were evaluated for AKI, defined by the Acute Kidney Injury Network criteria.. A total of 224 patients receiving either antimicrobial combination were evaluated for AKI. The incidence of AKI was significantly higher in the piperacillin-tazobactam and vancomycin group (34.8%) compared with the cefepime-vancomycin group (12.5%) in the unmatched analysis (p<0.0001). After adjusting for potential sources of bias through propensity score matched pairs and conditional logistic regression, piperacillin-tazobactam and vancomycin combination therapy (p=0.003) was an independent predictor of AKI. There were no significant differences in time to AKI or hospital length of stay between groups.. The results of this study suggest that there may be an association between piperacillin-tazobactam and vancomycin combination therapy and increased incidence of AKI.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Cefepime; Cephalosporins; Cohort Studies; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Treatment Outcome; Vancomycin

To determine whether the addition of piperacillin-tazobactam leads to an increased incidence of nephrotoxicity in patients receiving vancomycin and to explore potential confounding factors that may increase the risk of vancomycin-induced nephrotoxicity.. Single-center, retrospective cohort study.. Large, academic, tertiary-care hospital.. One hundred ninety-one adults hospitalized between July 1, 2009, and July 1, 2012, with normal baseline renal function who received a minimum of 48 hours of vancomycin for any indication were included in the analysis. Of these patients, 92 received a minimum of 48 hours of intravenous piperacillin-tazobactam concurrently with vancomycin, with piperacillin-tazobactam being initiated within 48 hours of the initiation of vancomycin (combination group); 99 received vancomycin without piperacillin-tazobactam (vancomycin group).. A univariate analysis was performed to assess the effect of the following risk factors on the incidence of nephrotoxicity within the first 7 days of vancomycin treatment: concomitant nephrotoxic agents, advanced age, steady-state vancomycin trough concentration of 15 μg/ml or greater, elevated Charlson Comorbidity Index, and a total daily vancomycin dose of 4 g or greater. A multivariate model was constructed to compare the incidence of the primary end point of nephrotoxicity, defined as a minimum 1.5-fold increase in serum creatinine concentration, between groups. Nephrotoxicity developed in 8 (8.1%) of 99 patients in the vancomycin group and in 15 (16.3%) of 92 patients in the combination group (1-sided χ(2) test, p=0.041). In the univariate analysis, only vancomycin trough concentration of 15 μg/ml or greater (odds ratio 3.67) was associated with an increased risk of developing nephrotoxicity. In the multivariate analysis, patients with piperacillin-tazobactam added to vancomycin exhibited an increased incidence of nephrotoxicity, with an odds ratio of 2.48 (1-sided χ(2) test, p=0.032).. We observed an increased incidence of nephrotoxicity in vancomycin-treated patients who received concomitant piperacillin-tazobactam. A steady-state vancomycin trough concentration of 15 μg/ml or greater was also associated with an increased risk of the development of nephrotoxicity. These findings should be confirmed in larger, randomized studies.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Cohort Studies; Drug Therapy, Combination; Female; Hospitalization; Humans; Incidence; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Topics: Acidosis, Lactic; Acute Kidney Injury; Anti-Bacterial Agents; Comorbidity; Female; Humans; Hypothermia; Infusions, Intravenous; Metformin; Middle Aged; Multiple Organ Failure; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Renal Replacement Therapy; Sodium Bicarbonate; Urinary Tract Infections; Vasoconstrictor Agents

Current recommendations for piperacillin-tazobactam dosing in patients receiving continuous renal replacement therapy originate from studies with relatively few patients and lower continuous renal replacement therapy doses than commonly used today. This study measured the pharmacokinetic and pharmacodynamic characteristics of piperacillin-tazobactam in patients treated with continuous renal replacement therapy using contemporary equipment and prescriptions.. A multicenter prospective observational study in the intensive care units of two academic medical centers was performed, enrolling patients with AKI or ESRD receiving piperacillin-tazobactam while being treated with continuous renal replacement therapy. Pregnant women, children, and patients with end stage liver disease were excluded from enrollment. Plasma and continuous renal replacement therapy effluent samples were analyzed for piperacillin and tazobactam levels using HPLC. Pharmacokinetic and pharmacodynamic parameters were calculated using standard equations. Multivariate analyses were used to examine the association of patient and continuous renal replacement therapy characteristics with piperacillin pharmacokinetic parameters.. Forty-two of fifty-five subjects enrolled had complete sampling. Volume of distribution (median=0.38 L/kg, intraquartile range=0.20 L/kg) and elimination rate constants (median=0.104 h(-1), intraquartile range=0.052 h(-1)) were highly variable, and clinical parameters could explain only a small fraction of the large variability in pharmacokinetic parameters. Probability of target attainment for piperacillin was 83% for total drug but only 77% when the unbound fraction was considered.. There is significant patient to patient variability in pharmacokinetic/pharmacodynamic parameters in patients receiving continuous renal replacement therapy. Many patients did not achieve pharmacodynamic targets, suggesting that therapeutic drug monitoring might optimize therapy.

Topics: Academic Medical Centers; Acute Kidney Injury; Adult; Aged; Alabama; Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Drug Monitoring; Female; Humans; Kidney Failure, Chronic; Linear Models; Male; Middle Aged; Multivariate Analysis; Ohio; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Renal Dialysis

A 43-year-old female with Staphyloccocus-induced perianal abscess, was admitted to hospital because of a clinical picture of acute renal failure and thrombotic microangiopathy. Schistocytes, thrombopenia, a negative Coombs test and no detectable plasma haptoglobin were diagnostic for thrombotic microangiopathy. Antibiotics, surgical drainage, plasmapheresis and fresh frozen plasma were given with a favourable evolution. We review the prognostic factors determining recovery of renal function and hematological abnormalities.

Topics: Abscess; Acute Kidney Injury; Adult; Amoxicillin-Potassium Clavulanate Combination; Anal Canal; Debridement; Drug Therapy, Combination; Female; Hemolytic-Uremic Syndrome; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Plasma; Plasmapheresis; Staphylococcal Infections; Thrombocytopenia