Antibiotic dosing recommendations in critically ill patients receiving new innovative kidney replacement therapy.

BACKGROUND: The Tablo Hemodialysis System is a new innovative kidney replacement therapy (KRT) providing a range of options for critically ill patients with acute kidney injury. The use of various effluent rate and treatment durations/frequencies may clear antibiotics differently than traditional KRT. This Monte Carlo Simulation (MCS) study was to develop antibiotic doses likely to attain therapeutic targets for various KRT combinations. METHODS: Published body weights and pharmacokinetic parameter estimates were used to predict drug exposure for cefepime, ceftazidime, imipenem, meropenem and piperacillin/tazobactam in virtual critically ill patients receiving five KRT regimens. Standard free ß-lactam plasma concentration time above minimum inhibitory concentration targets (40-60%fT> MIC and 40-60%fT> MICx4) were used as efficacy targets. MCS assessed the probability of target attainment (PTA) and likelihood of toxicity for various antibiotic dosing strategies. The smallest doses attaining PTA ≥ 90% during 1-week of therapy were considered optimal. RESULTS: MCS determined ß-lactam doses achieving ∼90% PTA in all KRT options. KRT characteristics influenced antibiotic dosing. Cefepime and piperacillin/tazobactam regimens designed for rigorous efficacy targets were likely to exceed toxicity thresholds. CONCLUSION: The flexibility offered by new KRT systems can influence ß-lactam antibiotic dosing, but doses can be devised to meet therapeutic targets. Further clinical validations are warranted.

Vancomycin and daptomycin dosing recommendations in patients receiving home hemodialysis using Monte Carlo simulation.

BACKGROUND: Few drug dosing recommendations for patients receiving home hemodialysis (HHD) have been published which has hindered the adoption of HHD. HHD regimens vary widely and differ considerably from conventional, thrice weekly, in-center hemodialysis in terms of treatment frequency, duration and blood and dialysate flow rates. Consequently, vancomycin and daptomycin clearances in HHD are also likely to be different, consequently HHD dosing regimens must be developed to ensure efficacy and minimize toxicity when these antibiotics are used. Many HHD regimens are used clinically, this study modeled ten common HHD regimens and determined optimal vancomycin and daptomycin dosing for each HHD regimen. METHODS: Monte Carlo simulations using pharmacokinetic data derived from the literature and demographic data from a large HHD program treating patients with end stage kidney disease were incorporated into a one-compartment pharmacokinetic model. Virtual vancomycin and daptomycin doses were administered post-HHD and drug exposures were determined in 5,000 virtual patients receiving ten different HHD regimens. Serum concentration monitoring with subsequent dose changes was incorporated into the vancomycin models. Pharmacodynamic target attainment rates were determined for each studied dose. The lowest possible doses that met predefined targets in virtual patients were chosen as optimal doses. RESULTS: HHD frequency, total dialysate volumes and HHD durations influenced drug exposure and led to different dosing regimens to meet targets. Antibiotic dosing regimens were identified that could meet targets for 3- and 7-h HHD regimens occurring every other day or 4-5 days/week. HHD regimens with 3-day interdialytic periods required higher doses prior to the 3-day period. The addition of vancomycin serum concentration monitoring allowed for calculation of necessary dosing changes which increased the number of virtual subjects meeting pharmacodynamic targets. CONCLUSIONS: Doses of vancomycin and daptomycin that will meet desired pharmacodynamic targets in HHD are dependent on patient and HHD-specific factors. Doses used in conventional thrice weekly hemodialysis are unlikely to meet treatment goals. The antibiotic regimens paired with the HHD parameters studied in this analysis are likely to meet goals but require clinical validation.

Comparison of antimicrobial dosing recommendations in patients receiving intermittent hemodialysis among drug information resources.

WHAT IS KNOWN AND OBJECTIVE: Tertiary drug information resources are frequently consulted for the optimal antimicrobial dosing in intermittent hemodialysis (IHD) patients. Yet, significant discrepancy may exist in dosing recommendations between resources. This study was to evaluate the consistency of antimicrobial dosing recommendations in IHD among four different drug information resources and the relevance of referenced pharmacokinetic studies. METHODS: Dosing recommendations of 29 commonly prescribed antimicrobials in IHD patients were collected from Micromedex, LexiComp, Clinical Pharmacology and Drug Prescribing in Renal Impairment to compare dosing categorization and the total daily dose (TDD). Significant dosing discrepancies were defined as ≥30% difference. Referenced pharmacokinetic studies were evaluated for their relevance in current practice, using sample size, hemodialyzer types, the use of optimal pharmacodynamic targets and the consideration of different interdialytic dosing periods. RESULTS AND DISCUSSION: A significant variation was found both in dosing categorization and recommended doses between resources. Seventeen drugs were compared for TDD with significant dosing discrepancy in 8 drugs. Among 42 referenced pharmacokinetic studies, 40 were evaluated. Mean patient numbers of pharmacokinetic studies were 13 ranging from 3 to 70. Sixty per cent of studies utilized contemporary hemodialyzers (e.g., high-flux and/or high efficiency). The optimal pharmacodynamic targets and the impact of different interdialytic intervals were assessed only in 27.5% and 7.5% respectively. WHAT IS NEW AND CONCLUSION: Inconsistent antimicrobial dosing recommendations for IHD patients exist among four well-established resources. Many referenced pharmacokinetic studies utilized outdated or less pharmacodynamically relevant study methods. Newer studies are warranted to reflect contemporary dialysis practice and assess its impact on optimal antimicrobial dosing.

Telavancin pharmacokinetics in patients with chronic kidney disease receiving haemodialysis.

BACKGROUND: Telavancin is a lipoglycopeptide antibiotic with limited pharmacokinetic data to guide drug dosing in patients receiving haemodialysis. OBJECTIVES: This study characterized telavancin pharmacokinetics in patients receiving haemodialysis. PATIENTS AND METHODS: This was a Phase IV, prospective, open-label, single-centre, crossover pharmacokinetic study (ClinicalTrials.gov: NCT02392208). Eight subjects with end-stage kidney disease requiring maintenance haemodialysis (mean ±â€ŠSD: 47 ±â€Š20 years, 69.5 ±â€Š17.1 kg) received 5 mg/kg telavancin IV 3 h before starting a 3.5 hour haemodialysis treatment with a high-permeability haemodialyser (haemodialysis period). After a 14 day washout period, a second 5 mg/kg dose was administered post-haemodialysis (control period). Telavancin plasma concentrations were measured over a 2 day period after each dose and non-compartmental pharmacokinetic analyses were performed. RESULTS: The geometric mean (GM) of telavancin overall clearance was 11.2 mL/h/kg (intrinsic clearance and dialytic clearance) in the haemodialysis period and 5.9 mL/h/kg (off-haemodialysis clearance) in the control period [GM ratio (GMR) = 1.89; 90% CI: 1.70-2.10; P < 0.01]. The GM t½ was 13.1 h when haemodialysis occurred 3 h post-dosing in the haemodialysis period but extended to 20.9 h with post-haemodialysis dosing in the control period (GMR = 0.63; 90% CI: 0.54-0.73; P < 0.01). The GM of telavancin plasma concentrations removed by haemodialysis was 27.7%. The GMR of peak plasma concentration and volume of distribution of the haemodialysis period and the control period were 0.88 (90% CI: 0.79-0.98; P = 0.08) and 1.17 (90% CI: 1.05-1.30; P = 0.048), respectively. CONCLUSIONS: Haemodialysis with high-permeability haemodialysers removes telavancin considerably (∼⅓ of body load). Telavancin 5 mg/kg every 48 h post-haemodialysis dosing is recommended, but dose adjustments may be warranted if haemodialysis starts within 3 h of telavancin administration.

Ex vivo Ceftolozane/Tazobactam Clearance during Continuous Renal Replacement Therapy.

BACKGROUND/AIMS: To determine ceftolozane/tazobactam transmembrane clearances (CLTM) in continuous hemofiltration (CHF) and continuous hemodialysis (CHD) and to determine optimal ceftolozane/tazobactam dosing regimens for patients receiving continuous renal replacement therapy (CRRT). METHOD: Validated, ex vivo CHF and CHD bovine blood models using polysulfone (HF1400) and AN69 (Multiflow 150-M) hemofilters were used to evaluate adsorption and CLTM at different effluent flow rates. Monte Carlo simulations (MCS) using pharmacokinetic parameters from published studies and CLTM from this study were used to generate ceftolozane/tazobactam dosing for patients receiving CRRT. RESULTS: CHF and CHD CLTM did not differ at equivalent effluent rates. CLTM approximated effluent flow rates. No adsorption of ceftolozane/tazobactam occurred for either hemofilter. Effluent flow was the most important determinant of MCS-derived doses. CONCLUSION: CRRT clearances of ceftolozane/tazobactam depended on effluent flow rates but not hemofilter types. MCS-derived ceftolozane/tazobactam doses of 750 (500/250)-1,500 (1,000/500) mg every 8 h met pharmacodynamic targets for virtual patients receiving CRRT at contemporary effluent rates.

Antibiotic Dosing in Patients With Acute Kidney Injury: "Enough But Not Too Much".

Increasing evidence suggests that antibiotic dosing in critically ill patients with acute kidney injury (AKI) often does not achieve pharmacodynamic goals, and the continued high mortality rate due to infectious causes appears to confirm these findings. Although there are compelling reasons why clinicians should use more aggressive antibiotic dosing, particularly in patients receiving aggressive renal replacement therapies, concerns for toxicity associated with higher doses are real. The presence of multisystem organ failure and polypharmacy predispose these patients to drug toxicity. This article examines the pharmacokinetic and pharmacodynamic consequences of critical illness, AKI, and renal replacement therapy and describes potential solutions to help clinicians give "enough but not too much" in these very complicated patients.

Exploratory longitudinal cohort study of associations of fatigue after stroke.

BACKGROUND AND PURPOSE: The pathogenesis of poststroke fatigue is unclear. In this prospective study, we explored whether reduced physical activity might contribute to poststroke fatigue or be a consequence of it. METHODS: Patients with a recent acute stroke were assessed at 1, 6, and 12 months with, Fatigue Assessment Scale (FAS), a fatigue case definition, Hospital Anxiety and Depression Score, sleepiness, quality of life, and accelerometry (ActivPAL). Bivariate analyses determined associations between fatigue and step count at each time point. Multiple linear regression tested whether 1-month step count independently predicted 6- and 12-month FAS. RESULTS: A total of 136 participants (mean age, 72 years; 64% men) attended ≥1 assessment. ActivPAL data were available for 84 (64%), 69 (66%), and 58 (64%) participants at 1, 6, and 12 months, respectively. At 6 and 12 months, a positive fatigue case definition was associated with lower daily step counts (P=0.014 and 0.013, respectively). At 1, 6, and 12 months, higher FAS (more fatigue) was associated with lower step count (P<0.001, 0.01, and 0.007), higher depression (P<0.001), anxiety scores (P<0.001) and sleepiness (P<0.001), and poorer quality of life (P<0.001). Lower daily step count (P<0.002 and 0.006) and greater anxiety (P<0.001 for both) at 1 month independently predicted higher FAS at 6 and 12 months. CONCLUSIONS: Lower step counts at 1 month independently predicted greater FAS for ≤12 months. Physical activity might be a therapeutic target for poststroke fatigue.

Tedizolid Adsorption and Transmembrane Clearance during in vitro Continuous Renal Replacement Therapy.

BACKGROUND/AIMS: To study transmembrane clearance (CLTM) and adsorption of tedizolid, a novel oxazolidinone antibiotic, in continuous hemofiltration (CVVH) and continuous hemodialysis (CVVHD). METHODS: In vitro CVVH/CVVHD models with polysulfone and AN69 hemodiafilters were used. Tedizolid CLTM during CVVH/CVVHD was assessed at various ultrafiltrate (Quf) and dialysate rates (Qd). Tedizolid adsorption was tested in a recirculating CVVH model over 4 h. RESULTS: In CVVH, CLTM did not differ between filter types. In CVVHD, tedizolid CLTM was significantly higher with the polysulfone hemodiafilter at Qd 6 l/h (p < 0.02). Tedizolid exhibited irreversible adsorption to the CRRT apparatus and bound significantly higher to the polysulfone hemodiafilter. CONCLUSION: Tedizolid's CLTM is dependent on Qd, Quf, and hemodiafilter type. At conventional CRRT rates, tedizolid CLTM appears modest relative to total body clearance and is unlikely to require dose adjustments. CRRT adsorption in the clinical setting is likely less than what we observed in this in vitro, continuously recirculating blood model.

Antibiotic dosing in critically ill patients receiving CRRT: underdosing is overprevalent.

Published CRRT drug dosing algorithms and other dosing guidelines appear to result in underdosed antibiotics, leading to failure to attain pharmacodynamic targets. High mortality rates persist with inadequate antibiotic therapy as the most important risk factor for death. Reasons for unintended antibiotic underdosing in patients receiving CRRT are many. Underdosing may result from lack of the recognition that better hepatic function in AKI patients yields higher nonrenal antibiotic clearance compared to ESRD patients. Other factors include the variability in body size and fluid composition of patients, the serious consequence of delayed achievement of antibiotic pharmacodynamic targets in septic patients, potential subtherapeutic antibiotic concentrations at the infection site, and the influence of RRT intensity on antibiotic concentrations. Too often, clinicians weigh the benefits of overcautious antibiotic dosing to avoid antibiotic toxicity too heavily against the benefits of rapid attainment of therapeutic antibiotic concentrations in critically ill patients receiving CRRT. We urge clinicians to prescribe antibiotics aggressively for these vulnerable patients.

Stability and compatibility of intraperitoneal antimicrobials in peritoneal dialysate solutions.

To optimise antimicrobial administration in patients with peritoneal dialysis (PD)-related peritonitis, healthcare providers need literature-based information to develop patient-centred pharmacotherapeutic plans. Traditional PD solutions promote osmosis using dextrose or icodextrin with a lactate buffer. Newer PD solutions have modified the osmotic vehicle and buffer. Knowledge of antimicrobial compatibility and stability with newer PD solutions will assist with determining the route of antimicrobial administration as compatible and stable solutions could be delivered directly to the peritoneum using intraperitoneal administration. This review updates the compatibility and stability of antimicrobial additives in newer PD solutions for PD-related peritonitis.

Erratum to "Impact of pharmacist intervention to deprescribe inappropriate aspirin therapy in an outpatient anticoagulation clinic at a community hospital" [Am. Heart J. Plus: Cardiol. Res. Pract. volume 17, May 2022, 100165].

[This corrects the article DOI: 10.1016/j.ahjo.2022.100165.].

The use of pedometers in stroke survivors: are they feasible and how well do they detect steps?

OBJECTIVES: To determine (1) the feasibility of pedometers for stroke patients and (2) the level of agreement between pedometers and actual step count. DESIGN: Observational agreement study. SETTING: Six stroke units. PARTICIPANTS: Independently mobile stroke patients (N=50) ready for hospital discharge. INTERVENTIONS: Patients were asked to apply 3 pedometers: 1 around the neck and 1 above each hip. Patients performed a short walk lasting 20 seconds, then a 6-minute walk test 6MWT. Video recordings determined the criterion standard step count. MAIN OUTCOME MEASURE: Agreement between the step count recorded by pedometers and the step count recorded by viewing the criterion standard video recordings of the 2 walks. RESULTS: Five patients (10%) needed assistance to put on the pedometers, and 5 (10%) could not read the step count. Thirty-nine (78%) would use pedometers again. Below a gait speed of about 0.5 m/s, pedometers did not generally detect steps. Agreement analyses showed that even above 0.5 m/s, pedometers undercounted steps for both the short walk and 6MWT; for example, the mean difference between the video recorder and pedometer around the neck was 5.93 steps during the short walk and 32.4 steps during the 6MWT. CONCLUSIONS: Pedometers are feasible but generally do not detect steps at gait speeds below about 0.5 m/s, and they undercount steps at gait speeds above 0.5 m/s.

Optimal antipseudomonal ꞵ-lactam drug dosing recommendations in critically-ill Asian patients receiving CRRT.

INTRODUCTION: The average body weight is smaller in Asian patients compared with Western patients, but influence of body weight in antibiotic dosing is unknown. This study was to predict the optimal ceftazidime, cefepime, meropenem, piperacillin/tazobactam doses in Asian patients undergoing continuous venovenous hemofiltration (CVVH). METHODS: Monte Carlo simulations (MCS) were performed using published Asian demographics and pharmacokinetics parameters in 5000 virtual patients at three CVVH effluent rates (Qeff; 20, 30, 40 mL/kg/h). Various dosing regimens were assessed for the probability of target attainments using 60% fT > 1 × MIC or 4xMIC and neurotoxicity risk at 48-h using suggested neurotoxicity thresholds. RESULTS: Ceftazidime 1 g q12h, meropenem 1 g q12h, and piperacillin/tazobactam 3.375 g q6h were optimal for all Qeff settings against fT > 1 × MIC. Cefepime 2 g q24h and 2 g q12h were optimal at 20 and 30-40 mL/kg/h respectively. For the aggressive PD target (4 × MIC), optimal ceftazidime regimens were 1.25 g q8h (20-30 mL/kg/h) and 1.5 g q8h (40 mL/kg/h). Cefepime 2 g q8h and meropenem 1 g q8h were optimal at all Qeff settings. No simulated piperacillin doses attained the aggressive PD target. Increased neurotoxicity risk was predicted with ceftazidime and cefepime doses attaining the efficacy. CONCLUSION: MCS enabled the prediction of optimal ß-lactam dosing regimens for Asian patients receiving CVVH at varying Qeff. Clinical validation is warranted.

An optimal extended-infusion dosing of cefepime and ceftazidime in critically ill patients with continuous renal replacement therapy.

PURPOSE: This study aimed to determine optimal extended-infusion dosing regimens for cefepime and ceftazidime in critically ill patients receiving continuous renal replacement therapy using Monte Carlo Simulations (MCS). MATERIALS AND METHODS: Pharmacokinetic models were built using published pharmacokinetic/demographic data to predict drug disposition in 5000 virtual critically ill patients receiving continuous venovenous hemofiltration (CVVH) with the standard (20-30 mL/kg/h) and a higher (40 mL/kg/h) effluent rates. MCS was performed to assess the probability of target attainment (PTA) of four cefepime and ceftazidime doses administered over 4-h with the target of ≥60% fT > 4×MIC. The lowest dose attaining PTA ≥90% during the first 48-h was considered optimal. Additionally, risk of drug toxicity was assessed at 48-h using suggested neurotoxicity thresholds. RESULTS: Cefepime 2 g loading dose (LD), then extended-infusion of 2 g q8hr was optimal in CVVH at 20 mL/kg/h and the same ceftazidime dose was optimal in CVVH at 20-30 mL/kg/h. Higher cefepime and ceftazidime doses were required to be optimal at higher effluent rates. This optimal dose particularly for cefepime likely increases neurotoxicity risk in most virtual patients with all CVVH settings. CONCLUSIONS: Cefepime and ceftazidime 2 g LD, followed by extended-infusion 2 g q8hr may be optimal in CVVH with standard effluent rates.

Impact of pharmacist intervention to deprescribe inappropriate aspirin therapy in an outpatient anticoagulation clinic at a community hospital.

Study objective: This study describes a pharmacist-led process to identify and discontinue inappropriate aspirin in patients receiving concomitant anticoagulant therapy and to evaluate the effectiveness of the intervention. Setting: The study took place in an outpatient anticoagulation clinic within a small community hospital. Participants: Patients ≥40 years old on indefinite anticoagulation therapy for atrial fibrillation and/or venous thromboembolism were included. Design: This is a quality improvement initiative. Interventions: Utilizing the electronic medical record and patient interview, use and indication for daily aspirin therapy was confirmed. Prospectively collected patient demographics and past medical history were used to determine appropriateness of aspirin therapy. For patients identified as receiving inappropriate aspirin therapy, a fax was sent to the referring provider recommending aspirin discontinuation. Main outcome measures: To assess the effectiveness of the intervention, outcomes were retrospectively measured. The primary outcome was the percentage of "accepted" recommendations. Secondary outcomes included the prevalence, dosing, and indications for aspirin therapy. Results: Eighty (33 %) of 242 patients were on aspirin. Fifty-two patients with atrial fibrillation and/or venous thromboembolism were assessed and aspirin was deemed inappropriate in 22 patients. The provider agreed with deprescribing aspirin therapy in 45 %. The most common dose and indication of aspirin therapy was 81 mg (98 %) and primary prevention (40 %) respectively. Conclusions: In our small practice, pharmacist-led interventions were an effective means to recommend aspirin discontinuation in our identified patients. Further studies are needed to optimize a pharmacist's role and address the long-term effects of deprescription.

Is fatigue after stroke associated with physical deconditioning? A cross-sectional study in ambulatory stroke survivors.

OBJECTIVE: To determine the relationship between a measure of fatigue and 2 indices of physical fitness, lower limb extensor power (LLEP) and walking economy. DESIGN: This was a cross-sectional study of patients with stroke. Fatigue was assessed by vitality (VIT) score of the Medical Outcomes Study 36-Item Short-Form Health Survey version 2 (SF-36v2). LLEP of the unaffected limb was measured using a lower leg extensor power rig. Walking economy was calculated by measuring oxygen consumption (mL·kg(-1)·m(-1)) during walking at a comfortable speed. Bivariate analyses were performed relating VIT to indices of fitness. Multiple regression analyses were also performed and included age, sex, and either SF-36v2 emotional role function or SF-36v2 mental health, as predictors of VIT. SETTING: Community setting. PARTICIPANTS: Participants (N=66; 36 men; mean age ± SD, 71.0±9.9y) were all community dwelling, had survived a stroke, were able to walk independently, and had completed their stroke rehabilitation. INTERVENTIONS: Not applicable MAIN OUTCOME MEASURES: The main outcome measure is SF-36v2 (VIT), with walking economy and LLEP of the limb unaffected by the stroke being independent variables. RESULTS: Walking economy was not significantly related to VIT (R=-.024, P=.86, n=60). LLEP was positively related to VIT in bivariate analysis (R=.38, P=.003, n=58). After controlling for age, sex, and SF-36 emotional role function (or SF-36v2 mental health if the extreme outlier was excluded), LLEP remained a significant predictor of VIT. CONCLUSIONS: We found an association between fatigue and reduced LLEP. If a larger study confirms these findings, it would support the need to develop and test interventions to increase LLEP as a treatment for fatigue after stroke.

Evaluation and Development of Vancomycin Dosing Schemes to Meet New AUC/MIC Targets in Intermittent Hemodialysis Using Monte Carlo Simulation Techniques.

Published vancomycin dosing recommendations for patients receiving maintenance hemodialysis were not designed to meet newly recommended 24-hour area under the curve/minimum inhibitory concentration (AUC24h /MIC) pharmacokinetic/pharmacodynamic targets. The aims of this study were to predict pharmacokinetic/pharmacodynamic target attainment rates with a commonly used vancomycin regimen and to design a new dosing scheme incorporating therapeutic drug monitoring (TDM) to maximize target attainment in patients receiving vancomycin and hemodialysis with high- or low-flux hemodialyzers. Vancomycin pharmacokinetic- and dialysis-specific parameters were incorporated into Monte Carlo simulations (MCS). A commonly used vancomycin regimen was modeled to determine its likelihood of attaining AUC24h /MIC targets for 1 week of thrice-weekly hemodialysis treatments. MCS was then used to develop optimal initial vancomycin dosing for patients receiving intradialytic or postdialytic vancomycin administration with either high- or low-flux hemodialyzers. Finally, a new MCS model incorporating TDM was built to further optimize the probability of pharmacokinetic/pharmacodynamic target attainment. Traditional vancomycin dosing methods are unlikely to meet AUC24h /MIC targets. Vancomycin doses necessary to attain AUC24h /MIC targets are significantly influenced by hemodialyzer permeability and whether vancomycin is administered intradialytically or after hemodialysis. Depending on dialyzer type and whether vancomycin is administered during or after hemodialysis, loading doses of 25 to 35 mg/kg followed by maintenance doses of 7.5 to 15 mg/kg are necessary to reach minimum AUC24h /MIC targets in 90% of virtual patients. For a 3-day interdialytic period, a 30% higher maintenance dose is required to maintain target attainment. Dosing based on a single vancomycin serum concentration obtained prior to the second dialysis session greatly enhances the probability of target attainment.

Harmonizing antibiotic regimens with renal replacement therapy.

Introduction: Critically ill patients with acute kidney injury often require renal replacement therapy and antibiotic therapy. Mortality rates are high in these patients, possibly due to ineffective dosing due to altered pharmacokinetic profiles and drug removal by renal replacement therapy. Areas covered: The main types of renal replacement therapies are intermittent hemodialysis, prolonged intermittent renal replacement therapy and continuous renal replacement therapy. Each of these renal replacement therapies may have drastic, yet different, effects on antibiotic serum concentration profiles. Moreover, three antibiotic administration strategies are often used: (1) standard infusion; (2) extended infusion; and (3) continuous infusion. A literature review was conducted on Medline in December 2019 to identify pertinent research. Expert opinion: Renal replacement therapies used in the treatment of acute kidney injury in critically ill patients usually complicates antibiotic use. Although antibiotic toxicity can be seen, most studies find that these patients do not receive sufficient antibiotic doses to achieve desired pharmacodynamic targets. Clinicians should dose antibiotics to match renal replacement therapy drug clearance characteristics to antibiotic pharmacodynamic profiles.

Novel therapeutic agents for the treatment of diabetic kidney disease.

INTRODUCTION: Diabetic kidney disease (DKD) involves multifaceted pathophysiology which increases the risk of cardiorenal events and mortality. Conventional therapy is limited to renin-angiotensin aldosterone system inhibition and management of hyperglycemia and hypertension. Recent clinical trials have demonstrated promising nephroprotective effects of antihyperglycemic agents thus modifying guideline treatment recommendations for type 2 diabetic patients with chronic kidney disease. AREAS OF COVERED: Relevant studies and clinical trials were searched via PubMed and clinicaltrials.gov through August 2020. Authors offer an update on clinical evidence regarding nephroprotective effects and side effects of sodium-glucose-cotransporter-2 (SGLT2) inhibitors, glucagon-like-peptide-1 (GLP1) agonists and dipeptidylpeptidase-4 (DPP4) inhibitors. They discuss the potential benefits of novel therapy targeting DKD pathogenic processes including inflammation, oxidative stress, fibrosis, and vasoconstriction shown in early phases of clinical trials and offer an opinion on key challenges and directions for future progress. EXPERT OPINION: SGLT2 inhibitors are the most promising agents for DKD and improving cardiorenal outcomes. Mineralocorticoid-receptor antagonists and janus kinase inhibitors are also promising investigational therapies that target oxidative stress, nitric oxide synthesis, and inflammation. Novel therapeutic targets and the identification of clinically useful biomarkers may provide future therapies that detect early stages of DKD enabling a slower kidney function decline.

Quinolone Allergy.

Quinolones are the second most common antibiotic class associated with drug-induced allergic reactions, but data on quinolone allergy are scarce. This review article discusses the available evidence on quinolone allergy, including prevalence, risk factors, diagnosis, clinical manifestations, cross-reactivity, and management of allergic reactions. Although the incidence of quinolone allergy is still lower than beta-lactams, it has been increasingly reported in recent decades, most likely from its expanded use and the introduction of moxifloxacin. Thorough patient history remains essential in the evaluation of quinolone allergy. Many diagnostic tools have been investigated, but skin tests can yield false-positive results and in vitro tests have not been validated. The drug provocation test is considered the test of choice to confirm a quinolone allergy but is not without risk. Evidence regarding cross-reactivity among the quinolones is limited and conflicting. Quinolone allergy can be manifested either as an immediate or delayed reaction, but is not uniform across the class, with moxifloxacin posing the highest risk of anaphylaxis. Quinolone should be discontinued when an allergic reaction occurs and avoided in future scenarios, but desensitization may be warranted if no alternatives are available.