Incidence of Acute Kidney Injury among Patients Treated with Piperacillin-Tazobactam or Meropenem in Combination with 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 (P \u3c 0.001). TZP+VAN was associated with increased AKI compared to the level with MEM+VAN (odds ratio [OR], 2.53; 95% confidence interval [CI], 1.82 to 3.52), after controlling for confounders. Use of MEM+VAN should be considered an appropriate alternative therapy to TZP+VAN if nephrotoxicity is a major concern. The results of this study demonstrate that judicial use of TZP+VAN for empirical coverage of infection is needed

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

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 \u3c 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 \u3c 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

Nephrotoxicity in Patients With or Without Cystic Fibrosis Treated With Polymyxin B Compared to Colistin

Nephrotoxicity is the primary adverse effect of the polymyxins. The relative rates of toxicity of polymyxin B and colistin have not been fully elucidated, especially in patients with cystic fibrosis (CF). A retrospective cohort study of adults treated with polymyxin B or colistin for at least 48 h was conducted. The primary endpoint was the incidence of kidney injury assessed by RIFLE (i.e., risk, injury, failure, loss, end-stage renal disease) criteria. Risk factors for kidney injury were evaluated using multivariate Cox regression. A total of 414 patients were evaluated, 220 of whom had CF. In patients without CF, there was no difference in kidney injury with polymyxin B and colistin (42.9% versus 50.3%, P = 0.46). Loop diuretic exposure was a risk factor for kidney injury (adjusted hazard ratio [aHR], 1.82; 95% confidence interval [CI], 1.16 to 2.83) in this population. In patients with CF, polymyxin B and colistin were associated with similar rates of kidney injury (34.5% versus 29.8%, P = 0.77). Diabetes (aHR, 2.68; 95% CI, 1.01 to 7.11), loop diuretics (aHR, 3.02; 95% CI, 1.36 to 6.73), and progressive care unit admission (aHR, 8.21; 95% CI, 2.55 to 26.46) were risk factors for kidney injury, while higher baseline serum creatinine levels (per 1 mg/dl) were protective (aHR, 0.08; 95% CI, 0.01 to 0.48). Total unadjusted kidney injury in polymyxin-treated patients was less frequent in those who had CF (30.5% versus 48.5%, P \u3c 0.001). Polymyxin B and colistin are associated with a high incidence of kidney injury; cystic fibrosis may be protective against polymyxin nephrotoxicity, but further investigation is needed to confirm this conjecture

Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy

Pseudomonas aeruginosa is a common pathogen implicated in nosocomial infections with increasing resistance to a limited arsenal of antibiotics. Monte Carlo simulation provides antimicrobial stewardship teams with an additional tool to guide empiric therapy. We modeled empiric therapies with antipseudomonal β-lactam antibiotic regimens to determine which were most likely to achieve probability of target attainment (PTA) of ≥90%. Microbiological data for P. aeruginosa was reviewed for 2012. Antibiotics modeled for intermittent and prolonged infusion were aztreonam, cefepime, meropenem, and piperacillin/tazobactam. Using minimum inhibitory concentrations (MICs) from institution-specific isolates, and pharmacokinetic and pharmacodynamic parameters from previously published studies, a 10,000-subject Monte Carlo simulation was performed for each regimen to determine PTA. MICs from 272 isolates were included in this analysis. No intermittent infusion regimens achieved PTA ≥90%. Prolonged infusions of cefepime 2000 mg Q8 h, meropenem 1000 mg Q8 h, and meropenem 2000 mg Q8 h demonstrated PTA of 93%, 92%, and 100%, respectively. Prolonged infusions of piperacillin/tazobactam 4.5 g Q6 h and aztreonam 2 g Q8 h failed to achieved PTA ≥90% but demonstrated PTA of 81% and 73%, respectively. Standard doses of β-lactam antibiotics as intermittent infusion did not achieve 90% PTA against P. aeruginosa isolated at our institution; however, some prolonged infusions were able to achieve these targets

Influence of \u3cem\u3eβ\u3c/em\u3e-Lactam Infusion Strategy on Acute Kidney Injury

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%; P = 0.1). After multivariate regression, prolonged infusion was not associated with increased odds of AKI (odds ratio [OR], 1.07; 95% confidence interval [95% CI], 0.83 to 1.39). Independent predictors of AKI included TZP therapy, concomitant nephrotoxins, hypotension, and heart failure. Although AKIs were numerically more common in patients receiving prolonged β-lactam infusions than those receiving intermittent infusions, prolonged infusion was not an independent risk factor for AKI

Accuracy Assessment of the eBee Using RTK and PPK Corrections Methods as a Function of Distance to a GNSS Base Station

The use of unmanned aircraft systems to collect data for photogrammetry models has grown significantly in recent years. The accuracy of a photogrammetric model can depend on image georeferencing. The distance from a reference base station can affect the accuracy of the results. Positioning corrections data relies on precise timing measurements of satellite signals. The signals travel through the Earth\u27s atmosphere, which introduces errors due to ionospheric and tropospheric delays. The aim of this research was to examine the eBee X and its global GNSS accuracy by comparing the RTK and PPK methods at different base station distances in photogrammetry models. Three factors were compared: 1) RTK and PPK methods, 2) local GNSS receiver via caster and NTRIP service corrections sources, and 3) base station distances between 2.4 km and 42.0 km. The eBee X flights occurred in 2023, at three different flying sites in Southwest Arizona in the United States. The RMSEXYZ values from eight Check Points at each of three flying sites were measured with traditional GNSS survey methods. Through ANOVA testing, there were no statistical differences in RMSEXYZ accuracy between RTK and PPK methods as well as between using a local Reach RS2 GNSS receiver via caster and NTRIP service for the eBee X; however, there was a statistical difference in RMSEXYZ accuracy between base station distances of 2.4 km to 42.0 km, whereas, F(5, 33) = 11.99, p = 0.000. Specifically, base station distances of less than 16.2 km were significantly less than larger distances up to 42.0 km. These data suggest there was a significant difference in total accuracy based on the distance from the GNSS receiver base station providing corrections for the eBee X

Treatment of Klebsiella Pneumoniae Carbapenemase (KPC) infections: a review of published case series and case reports

Grace C. Lee is with the Pharmacotherapy Education and Research Center, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX and the College of Pharmacy, University of Texas at Austin, Austin, TX USA David S. Burgess is with the Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY, USAThe emergence of Klebsiella pneumoniae carbapenemases (KPCs) producing bacteria has become a significant global public health challenge while the optimal treatment remains undefined. We performed a systematic review of published studies and reports of treatment outcomes of KPC infections using MEDLINE (2001–2011). Articles or cases were excluded if one of the following was fulfilled: no individual patient data provided, no treatment regimen specified, no treatment outcome specified, report of colonization, or greater than three antibiotics were used to treat the KPC infection. Data extracted included patient demographics, site of infection, organism, KPC subtype, antimicrobial therapy directed at KPC-infection, and treatment outcome. Statistical analysis was performed in an exploratory manner. A total of 38 articles comprising 105 cases were included in the analysis. The majority of infections were due to K. pneumoniae (89%). The most common site of infection was blood (52%), followed by respiratory (30%), and urine (10%). Forty-nine (47%) cases received monotherapy and 56 (53%) cases received combination therapy directed at the KPC-infection. Significantly more treatment failures were seen in cases that received monotherapy compared to cases who received combination therapy (49% vs 25%; p= 0.01). Respiratory infections were associated with higher rates of treatment failure with monotherapy compared to combination therapy (67% vs 29% p= 0.03). Polymyxin monotherapy was associated with higher treatment failure rates compared to polymyxin-based combination therapy (73% vs 29%; p= 0.02); similarly, higher treatment failure rates were seen with carbapenem monotherapy compared to carbapenem-based combination therapy (60% vs 26%; p= 0.03). Overall treatment failure rates were not significantly different in the three most common antibiotic-class combinations: polymyxin plus carbapenem, polymyxin plus tigecycline, polymyxin plus aminoglycoside (30%, 29%, and 25% respectively; p=0.6). In conclusion, combination therapy is recommended for the treatment of KPC infections; however, which combination of antimicrobial agents needs to be established in future prospective clinical [email protected]

Geometric Origin of CP Violation in an Extra-Dimensional Brane World

The fermion mass hierarchy and finding a predictive mechanism of the flavor mixing parameters remain two of the least understood puzzles facing particle physics today. In this work, we demonstrate how the realization of the Dirac algebra in the presence of two extra spatial dimensions leads to complex fermion field profiles in the extra dimensions. Dimensionally reducing to four dimensions leads to complex quark mass matrices in such a fashion that CP violation necessarily follows. We also present the generalization of the Randall-Sundrum scenario to the case of a multi-brane, six-dimensional brane-world and discuss how multi-brane worlds may shed light on the generation index of the SM matter content.Comment: 24 pages, 1 figure; references adde

Predicting diffuse microbial pollution risk across catchments: The performance of SCIMAP and recommendations for future development

Microbial pollution of surface waters in agricultural catchments can be a consequence of poor farm management practices, such as excessive stocking of livestock on vulnerable land or inappropriate handling of manures and slurries. Catchment interventions such as fencing of watercourses, streamside buffer strips and constructed wetlands have the potential to reduce faecal pollution of watercourses. However these interventions are expensive and occupy valuable productive land. There is, therefore, a requirement for tools to assist in the spatial targeting of such interventions to areas where they will have the biggest impact on water quality improvements whist occupying the minimal amount of productive land. SCIMAP is a risk-based model that has been developed for this purpose but with a focus on diffuse sediment and nutrient pollution. In this study we investigated the performance of SCIMAP in predicting microbial pollution of watercourses and assessed modelled outputs of E. coli, a common faecal indicator organism (FIO), against observed water quality information. SCIMAP was applied to two river catchments in the UK. SCIMAP uses land cover risk weightings, which are routed through the landscape based on hydrological connectivity to generate catchment scale maps of relative in-stream pollution risk. Assessment of the model's performance and derivation of optimum land cover risk weightings was achieved using a Monte-Carlo sampling approach. Performance of the SCIMAP framework for informing on FIO risk was variable with better performance in the Yealm catchment (rs = 0.88; p 0.05). Across both catchments much uncertainty was associated with the application of optimum risk weightings attributed to different land use classes. Overall, SCIMAP showed potential as a useful tool in the spatial targeting of FIO diffuse pollution management strategies; however, improvements are required to transition the existing SCIMAP framework to a robust FIO risk-mapping tool