Differences In Nephrotoxicity Research Articles

Propensity score matched analysis for the safety and effectiveness of remdesivir in COVID-19 patients with renal impairment.

Remdesivir (RDV) is an antiviral agent approved for the treatment of coronavirus disease 2019 (COVID-19); however, is not recommended for patients with renal impairment. Due to limitations associated with prospective clinical trials, real-world data on the safety and efficacy of RDV in patients with renal impairment are necessary. Propensity score-matched (PSM) retrospective analysis was conducted between March 2020 and September 2022 in COVID-19 patients with an eGFR < 30mL/min in four Korean hospitals. The RDV treatment group was matched to the untreated control group. The safety and clinical outcomes in patients who received RDV were analyzed. A total of 564 patients were enrolled; 229 patients received RDV either for treatment or prophylaxis. On day 5, no difference in nephrotoxicity was observed between the two groups, and liver enzyme levels were within the normal range. In multivariate analysis for new dialysis, RDV treatment was not a risk factor for new dialysis. Among the 564 patients, 417 were indicated for a 5-day course of RDV treatment and 211 patients were treated with RDV. After PSM, no differences in the clinical outcomes were observed between the two groups. RDV use in COVID-19 patients with renal impairment did not result in significant nephrotoxicity or hepatotoxicity.

Neonatal Serum Gentamicin Concentrations and Outcomes Following Maternal Once-Daily Gentamicin Dosing.

This study evaluated newborn gentamicin serum concentrations after birth and the effects on the newborn after extended interval gentamicin dosing in peripartum mothers. This was a single-center, retrospective chart review of neonates born to mothers that received peripartum once-daily gentamicin dosing of approximately 5 mg/kg within 12 hours of delivery. A gentamicin serum concentration was obtained immediately after birth in the newborn. The primary outcome was initial neonatal gentamicin serum concentration after birth. Several secondary outcomes were evaluated including nephrotoxicity and ototoxicity. A subgroup analysis comparing baseline demographics of mother-newborn dyads with birth neonatal serum concentrations of less than 2 mcg/mL versus 2 mcg/mL or greater was performed. A total of 32 mother-newborn dyads were included. Newborns had a median gestational age of 39.4 weeks and median birth weight of 3.4 kg. The mean initial gentamicin serum concentration was elevated at 3.1 ± 1.9 mcg/mL among all newborns. The median maternal dose based on actual body weight in newborns with gentamicin serum concentrations less than 2 mcg/mL was 3.5 (IQR, 3.3-4.8) mg/kg versus 4.8 (IQR, 4.3-5.2) mg/kg in those that had serum concentrations of 2 mcg/mL or greater (p = 0.025). All newborn gentamicin serum concentrations were less than 2 mcg/mL for maternal doses given less than 1 hour prior to delivery (n = 8). There were no significant differences in nephrotoxicity or ototoxicity. Peripartum once daily dosing of gentamicin administered between 1 to 12 hours of birth may lead to clinically significant serum concentrations in newborns.

Differences in p38-STAT3-S100A11 signaling after the administration of aristolochic acid I and IVa may account for the disparity in their nephrotoxicity

BackgroundThe safety of herbs containing aristolochic acids (AAs) has become a widespread concern. Previous reports indicate that AAs are highly nephrotoxic and carcinogenic, although there are more than 170 analogues of aristolochic acid. Not all AAs have the same degree of nephrotoxicity or carcinogenicity. Previous studies have found that aristolochic acid IVa (AA-IVa), the principal component of AAs within members of the Aristolochiaceae family, especially Asarum, a commonly used herb in China, has essentially no significant nephrotoxicity. However, several studies, including ours, have shown that aristolochic acid I (AA-I) is clearly nephrotoxic. PurposeThe focus of the study was to elucidate the molecular mechanism responsible for the difference in nephrotoxicity between the AA-I and AA-IVa. Study design/methodMice were administered with AA-I or AA-IVa for 22 weeks through the oral route, followed by a 50-week recovery time. The kidney tissues of mice were extracted at the end of 22 weeks. Pathological examination and proteomic detection (tandem mass tagging (TMT) and phosphorylated proteomics) were performed on the kidney tissue to investigate the key signaling pathways and targets of AAs-induced renal interstitial fibrosis (RIF). The key signaling pathways and targets were verified by Western blot (WB), siRNA transfection, and luciferase assays. ResultsAA-I caused severe nephrotoxicity, high mortality, and extensive RIF. However, the same AA-IVa dosage exhibited almost no nephrotoxicity and does not trigger RIF. The activation of the p38-STAT3-S100A11 signaling pathway and upregulated expression of α smooth muscle actin (α-SMA) and Bcl2-associated agonist of cell death (Bad) proteins could be the molecular mechanism underlying AA-I-induced nephrotoxicity. On the other hand, AA-IVa did not regulate the activation of the p38-STAT3-S100A11 signaling pathway and had relatively little effect on the expression of α-SMA and Bad. Consequently, the difference in the regulation of p38-STAT3-S100A11 pathway, α-SMA, and Bad proteins between AA-I and AA-IVa may be responsible for the divergence in their level of nephrotoxicity. ConclusionThis is the first study to reveal the molecular mechanism underlying the difference in nephrotoxicity between AA-I and AA-IVa. Whether STAT3 is activated or not may be the key factor leading to the difference in nephrotoxicity between AA-I and AA-IVa.

Area-Under-Curve-Guided Versus Trough-Guided Monitoring of Vancomycin and Its Impact on Nephrotoxicity: A Systematic Review and Meta-Analysis.

Conventionally, vancomycin trough levels have been used for therapeutic drug monitoring (TDM). Owing to the increasing evidence of trough levels being poor surrogates of area under the curve (AUC) and the advent of advanced pharmacokinetics software, a paradigm shift has been made toward AUC-guided dosing. This study aims to evaluate the impact of AUC-guided versus trough-guided TDM on vancomycin-associated nephrotoxicity. A systematic review was conducted using PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Google scholar, and Cochrane library databases; articles published from January 01, 2009, to January 01, 2021, were retrieved and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Studies that evaluated trough-guided or AUC-guided vancomycin TDM and vancomycin-associated nephrotoxicity were included. Random-effects models were used to compare the differences in nephrotoxicity. Of the 1191 retrieved studies, 57 were included. Most studies included adults and older adults (n = 47, 82.45%). The pooled prevalence of nephrotoxicity was lower in AUC-guided TDM [6.2%; 95% confidence interval (CI): 2.9%-9.5%] than in trough-guided TDM (17.0%; 95% CI: 14.7%-19.2%). Compared with the trough-guided approach, the AUC-guided approach had a lower risk of nephrotoxicity (odds ratio: 0.53; 95% CI: 0.32-0.89). The risk of nephrotoxicity was unaffected by the AUC derivation method. AUC thresholds correlated with nephrotoxicity only within the first 96 hours of therapy. The AUC-guided approach had a lower risk of nephrotoxicity, supporting the updated American Society of Health-System Pharmacists guidelines. Further studies are needed to evaluate the optimal AUC-derivation methods and clinical utility of repeated measurements of the AUC and trough levels of vancomycin.

193. Rapid Diagnostic Testing and Vancomycin Utilization for Contaminated Blood Cultures

Abstract Background Bacteremia is a prevalent hospital acquired infection that affects nearly one in ten hospitalized patients. Rates of contaminated blood cultures have ranged from 0.6% to 6% in the literature. Vancomycin is often chosen as empiric coverage for gram positive organisms while awaiting bacterial identification. The purpose of this study was to evaluate the impact of GenMark ePlex Blood Culture Identification Panel (BCID) implementation on the duration of vancomycin therapy for blood cultures contaminated with coagulase negative staphylococci (CoNS). Methods A retrospective chart review was conducted on patients meeting inclusion criteria during a six month period prior to BCID implementation and post BCID implementation, from 03/01/2019 to 08/31/2019 and 03/01/2021 to 08/31/2021. The primary outcome analyzed was the duration of vancomycin therapy, in hours, in patients with a contaminated blood culture. Contaminated blood cultures was defined as a single blood culture growing CoNS. Secondary outcomes included hospital length of stay, readmission for treatment of contaminated blood cultures, and nephrotoxicity. Results This IRB-approved study included 190 patients, 75 in the pre-BCID group and 115 in the post-BCID group. The average duration of vancomycin therapy was 53.7 hours in the pre-BCID group and 20.5 hours in the post-BCID group (p = 0.04). Time to organism identification was reduced from 22.8 hours in the pre-BCID group to 12 hours in the post-BCID group (p = 0.5). Additionally, our study did not find a difference in nephrotoxicity, hospital length of stay, or readmissions between the two groups. Conclusion Following implementation of the GenMark ePlex Blood Culture Identification Panel (BCID), there was a reduction in both duration of vancomycin therapy and time to culture identification for blood cultures contaminated with CoNS. Rapid diagnostic testing is helpful in clinical decision-making and can lead to earlier discontinuation of empiric antibiotics, such as vancomycin. Disclosures All Authors: No reported disclosures.

Risk of acute kidney injury and cost-effectiveness analysis comparing vancomycin and linezolid for the treatment of pediatric patients infected with Gram-positive bacteria

Objective: This study aimed to compare the occurrence of acute kidney injury (AKI) in pediatric patients who used vancomycin (VAN) or linezolid (LNZ) to treat Gram-positive coccus (GPC) infections and to assess which treatment (VAN or LNZ) is the most cost-effective considering a pediatric hospital perspective. Methods: A retrospective cohort was performed to evaluate the occurrence of nephrotoxicity in pediatric patients without previous AKI, with GPC infections that used LNZ, or VAN monitored by serum VAN levels. Initially, descriptive analysis and Fisher and chisquare test were performed for this comparison. Then, a cost-effectiveness analysis was conducted through a decision tree model. The outcomes of interest were the rate of AKI related to the drug and the rate of admission to the intensive care unit (ICU) and cure. Results: In patients without previous acute kidney injury (AKI), 20% developed nephrotoxicity associated with VAN versus 9.6% in the LNZ group (p = 0.241). As there was no difference in nephrotoxicity between VAN andlinezolid (LNZ), vancomycin (VAN) monitored by serum VAN levels can optimize and rationalize the treatment. The nephrotoxicity risk criterion should not guide the prescription for LNZ. Furthermore, the average global cost of treatment with VAN was approximately R$ 43,000, while for LNZ, it was R$ 71,000. Conclusion: VAN was considered dominant (lower cost and greater effectiveness) over LNZ for treating patients with GPC infection.

Effectiveness and Nephrotoxicity of Loading Dose Colistin-Meropenem versus Loading Dose Colistin-Imipenem in the Treatment of Carbapenem-Resistant Acinetobacter baumannii Infection.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is becoming more widely recognized as a serious cause of nosocomial infections, and colistin has been reintroduced in recent years for the treatment of CRAB infection. Combinations of colistin and meropenem or imipenem have been found to be effective against CRAB isolates, whereas clinical investigations have not definitively demonstrated the theoretical benefits of colistin combined therapy in patients with CRAB infections. The objective of this study was to compare the primary outcome (30-day survival rate) and secondary outcomes (clinical response, microbiological response and nephrotoxicity) between patients who received loading dose (LD) colistin–meropenem and LD colistin–imipenem for the treatment of CRAB infection. A retrospective cohort analysis was performed at Chiang Mai University Hospital in patients with CRAB infection who received LD colistin–meropenem or LD colistin–imipenem between 2011 and 2017, and 379 patients fulfilled the requirements for the inclusion criteria. The results of this study showed that patients who received LD colistin–imipenem had a lower 30-day survival rate (adjusted HR = 0.57, 95% CI: 0.37–0.90; p = 0.015) and a lower clinical response (aHR = 0.56, 95% CI: 0.35–0.90; p = 0.017) compared with those who received LD colistin–meropenem. The microbiological response in patients with LD colistin–imipenem was 0.52 times (aHR) lower than that in those who received colistin–meropenem (95% CI: 0.34–0.81; p = 0.004); however, there was no significant difference in nephrotoxicity (aHR = 1.03, 95% CI: 0.67–1.57; p = 0.897) between the two combination regimens. In conclusion, when comparing the combination of LD colistin with imipenem or meropenem, the combination of LD colistin and meropenem provides a better survival rate for treating CRAB. Thus, we suggest that combinations of LD colistin and meropenem should be considered when treating CRAB infections.

Clinical Efficacy and Nephrotoxicity of the Loading Dose Colistin for the Treatment of Carbapenem-Resistant Acinetobacter baumannii in Critically Ill Patients

Carbapenem-resistant Acinetobacter baumannii (CRAB) is one of the most common causes of nosocomial infections in critically ill patients. Colistin methanesulfonate (CMS), an inactive prodrug, has been considered as a last-resort treatment for CRAB infection in critically ill patients. The objective of this study was to assess 30-day survival and nephrotoxicity in critically ill patients who received non-loading dose (LD) versus LD of CMS for CRAB infection treatment. Between 2012 and 2017, this retrospective cohort analysis was performed at Chiang Mai University Hospital (CMUH), focusing on critically ill patients with CRAB infection who received either non-LD or LD of CMS. A total of 383 patients met the criteria for inclusion. At the 30th day of treatment, the survival rate of patients in the LD CMS group was 1.70 times (adjusted HR) of those in the non-LD group (95% CI = 1.17–2.50, p = 0.006). Clinical response was significantly higher in the LD CMS group than non-LD CMS group (aHR, 1.35, 95% CI, 1.01–1.82, p = 0.046). In addition, a microbiological response—eradication of pre-treatment isolated pathogens in post-treatment cultures—in patients with LD CMS was 1.57 times that of patients with non-LD CMS (95% CI, 1.15–2.15, p = 0.004). Additionally, there was a significant difference in nephrotoxicity between LD CMS and non-LD CMS (aHR, 1.57, 95% CI, 1.14–2.17, p = 0.006). Based on these results, LD CMS should be used to increase the opportunity of patients to achieve favourable outcomes. However, LD CMS was found associated with an increase in nephrotoxicity, so renal function should be closely monitored when LD colistin was administered.

1097. A Comparison of Area-Under Curve (AUC)-Guided vs Trough-Guided Monitoring of Vancomycin and Its Impact on Nephrotoxicity: A Systematic Review and Meta-analysis

BackgroundTrough levels have been used for Vancomycin (VAN) therapeutic drug monitoring (TDM) historically due to its practicality. A paradigm shift towards the use of area under curve (AUC)-guided dosing TDM has been made due to availability of advanced pharmacokinetics software, variability between trough levels and AUC values and the potential for reducing toxicity. This review aims to evaluate the impact of AUC-guided vs trough-guided vancomycin TDM on nephrotoxicity-related outcomes.MethodsA systematic review was conducted using PubMed®, Embase®, Web of Science®, CINAHL®, Google scholar and Cochrane library® up till 1st January 2021 and was reported according to the PRISMA checklist. Studies which evaluated AUC-guided or trough-guided VAN TDM and vancomycin-associated nephrotoxicity were included. Random effects models were used to compare differences in nephrotoxicity between trough level or AUC based vancomycin TDM due to expected heterogeneity in study designs. PRISMA Flowchart PRISMA flow chart depicting the selection process of studies included in the meta-analysisResultsOf 1191 records retrieved, 57 studies were included. Majority of studies included adult and elderly patients (n=47, 82.5%). The pooled prevalence of nephrotoxicity was lower using the AUC-guided TDM [6.2%, 95% confidence interval (CI): 2.9 – 9.5%] compared to trough-guided TDM [17.0%; 95% CI: 14.7 – 19.2%]. The risk of nephrotoxicity was lower with the AUC-guided approach as compared with the trough-guided approach [OR: 0.53, 95% CI: 0.32–0.89]. AUC thresholds correlated with risk of nephrotoxicity only for the first 96 hours of therapy. A frequency analysis of significant multivariable factors showed that concomitant use of nephrotoxins, VAN trough levels and duration of VAN therapy were most commonly associated with nephrotoxicity.Forest plot comparing the risk of nephrotoxicity of AUC-guided vs trough-guided Forest plot comparing the risk of nephrotoxicity of AUC-guided vs trough-guidedPooled nephrotoxicity rates from AUC-guided monitoring Pooled nephrotoxicity rates from AUC-guided monitoringPooled nephrotoxicity rates from trough-guided monitoring Pooled nephrotoxicity rates from trough-guided monitoringConclusionThe AUC-guided approach appeared to have lower risk of nephrotoxicity which supports the updated American Society of Health-System Pharmacists recommendations. More studies should be performed to evaluate the optimal derivation of AUC and clinical utility of repeated measurements of vancomycin AUC and trough levels.Disclosures All Authors: No reported disclosures

Comparison of Adverse Events With Vancomycin Diluted in Normal Saline vs Dextrose 5.

IV vancomycin is widely used for infections caused by Gram-positive bacteria; however, nephrotoxicity is commonly associated with its use. Clinical trials have shown an increased incidence of acute kidney injury (AKI) using normal saline (NS) for fluid resuscitation. This study evaluated differences in AKI and other patient outcomes associated with vancomycin diluted in NS compared with dextrose 5% in water (D5W). This retrospective cohort study conducted at a single US Department of Veterans Affairs hospital included veterans who received vancomycin for at least 48 hours between July 1, 2015 and June 30, 2020. This study compared adverse events (AEs) of patients receiving vancomycin diluted in either NS or D5W. The primary outcome was incidence of AKI. Secondary outcomes included incidence of hyperglycemia, hyperchloremia, hypernatremia, metabolic acidosis, in-hospital mortality, and 30-day posthospitalization mortality. The study included 123 patients in each group (N = 246). The percentage of AKI was 22.8% in the D5W group compared with 14.6% the NS group (P = .14). There were no significant differences in the rates of hyperglycemia, hyperchloremia, hypernatremia, or metabolic acidosis between the 2 groups. In-hospital mortality and 30-day posthospitalization mortality were similar between the groups. This study comparing the AEs of IV vancomycin diluted in NS and D5W found no significant differences in AKI or other patient outcomes. These study results do not suggest the crystalloid used to dilute IV vancomycin is associated with differences in nephrotoxicity or other relevant AEs.

Pediatric Antibiotic Stewardship: Optimization of Vancomycin Therapy Based on Individual Pharmacokinetics.

Vancomycin has been a first-line treatment for Gram-positive infections for decades. However, strategies for therapeutic drug monitoring (TDM) and dose-optimization in pediatrics remain controversial. In this study, we analyzed the impact of specific antibiotic stewardship interventions on efficacy and safety of vancomycin therapy. From September 2014 to May 2017, we conducted a prospective study to compare a control and a TDM intervention group in our tertiary care center. As part of an antibiotic stewardship program, we implemented internal guidelines on correct vancomycin dosing, TDM timing, as well as targeted trough level range and installed a pharmacokinetic (PK) consultation service to adapt vancomycin dosing to individually calculated PK parameters. As primary clinical outcomes, the percentage of patients with sustained therapeutic vancomycin trough levels and treatment days with therapeutic vancomycin trough levels, that is, 10-15 mg/L were analyzed. Secondary outcomes included nephrotoxicity, readmission rate and mortality. Median daily dose required to achieve therapeutic trough levels was examined. Clinical outcomes for 90 control patients were compared with outcomes for 19 patients guided by a PK consultation service. Percentage of patients with sustained therapeutic vancomycin trough levels increased from 17.8% to 94.7% (P < 0.001) and percentage of treatment days with therapeutic vancomycin trough levels increased from 18.4% (117/637) to 665% (155/233, P < 0.001). Readmission rate decreased from 24.4% to 5.3% (P = 0.07). No differences in nephrotoxicity or mortality rate were observed between groups. A median daily dose of 72 mg/kg/d was required to achieve therapeutic trough levels. Our data demonstrate that implementation of internal guidelines and a PK consultation service was associated with a profound improvement of vancomycin therapy and, therefore, patient safety.

Short-Course Versus Long-Course Colistin for Treatment of Carbapenem-Resistant A.baumannii in Cancer Patient.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is one of the most commonly reported nosocomial infections in cancer patients and could be fatal because of suboptimal immune defenses in these patients. We aimed to compare clinical response, microbiological response, nephrotoxicity, and 30-day mortality between cancer patients who received short (<14 days) and long (≥14 days) courses of colistin for treatment of CRAB infection. A retrospective cohort study was conducted in cancer patients with CRAB infection who received short or long courses of colistin between 2015 to 2017 at Chiang Mai University Hospital (CMUH). A total of 128 patients met the inclusion criteria. The results of this study show that patients who received long course of colistin therapy had a higher rate of clinical response; adjusted odds ratio (OR) was 3.16 times in patients receiving long-course colistin therapy (95%CI, 1.37–7.28; p value = 0.007). Microbiological response in patients with long course was 4.65 times (adjusted OR) higher than short course therapy (95%CI, 1.72–12.54; p value = 0.002). Moreover, there was no significant difference in nephrotoxicity (adjusted OR, 0.91, 95%CI, 0.39–2.11; p value = 0.826) between the two durations of therapy. Thirty-day mortality in the long-course therapy group was 0.11 times (adjusted OR) compared to the short-course therapy group (95%CI, 0.03–0.38; p value = 0.001). Propensity score analyses also demonstrated similar results. In conclusion, cancer patients who received a long course of colistin therapy presented greater clinical and microbiological responses and lower 30-day mortality but similar nephrotoxicity as compared with those who a received short course. Therefore, a long course of colistin therapy should be considered for management of CRAB infection in cancer patients.

Impact of a computerised clinical decision support system on vancomycin loading and the risk of nephrotoxicity

BackgroundA vancomycin loading dose is recommended for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However, clinicians often do not adhere to these recommendations, mainly due to nephrotoxicity risk, unfamiliarity with the guideline, or complexity of calculating an individual dose. Therefore, we introduced a computerised clinical decision support system (CDSS) for vancomycin loading (hereafter Vancomycin CDSS) to promote the use of vancomycin loading dose. MethodsWe describe a quasi-experimental study spanning 6 months before and 18 months after the deployment of a Vancomycin CDSS. The Vancomycin CDSS was integrated into the hospital’s electronic medical record system in the form of a vancomycin order set. Our primary endpoint was the incidence of nephrotoxicity; the secondary endpoint was mean initial vancomycin trough levels. We also conducted a survey to evaluate the reasons why clinicians opted not to utilise a vancomycin loading dose. ResultsAfter implementation of Vancomycin CDSS, 363 out of 746 patients (49 %) who were first administered vancomycin received a loading dose. We did not find significant differences in nephrotoxicity between the pre- and post-intervention groups, nor between the loading- and non-loading groups. In the pre-intervention group, the mean initial vancomycin trough level was 7.10 mg/L, which was significantly lower than that in the post-intervention group of 11.11 mg/L. In the vancomycin loading group, the mean initial trough level was 11.95 mg/L, compared to 7.55 mg/L in the non-loading group. The main reason stated for not prescribing a vancomycin loading dose was concern about nephrotoxicity. ConclusionIntroduction of the Vancomycin CDSS did not increase nephrotoxicity and increased the mean initial dose and trough level of vancomycin.

1314. Neonatal Serum Gentamicin Concentrations following Maternal Once-daily Gentamicin Dosing

BackgroundGentamicin is commonly used for peripartum infections. Given literature supporting efficacy of once-daily dosing (ODD) of 5 mg/kg for chorioamnionitis, University of Chicago Medicine made the change from three times daily dosing (TIDD) to ODD. As gentamicin readily cross the placenta, it would be expected that maternal ODD would result in higher gentamicin neonatal serum concentrations following birth.MethodsThis was a single-center, retrospective chart review of all neonates born to mothers receiving peripartum ODD gentamicin within 12 hours of delivery between October 2019 and March 2020. A STAT random gentamicin serum concentration was obtained upon admission in neonates when initiation of antibiotics was desired. Specific dosing recommendations (Table 1) were developed utilizing neonatal population-based pharmacokinetics. The primary outcome was initial neonatal gentamicin serum concentration at birth. Other outcomes were also evaluated. Results were evaluated in two groups based on neonatal serum concentrations of less than 2 mcg/mL (Group 1) versus 2 mcg/mL or greater (Group 2).Table 1: Neonatal gentamicin dosing algorithm ResultsThirty-two mother-newborn dyads were included in this study. Baseline demographics are shown in Table 2. Newborns had a median gestational age of 39.4 weeks and median birth weight of 3.39 kilograms. The mean initial gentamicin concentration was supratherapeutic at 3.06 + 1.92 mcg/mL among all newborns (Table 3). The mean maternal dose in Group 1 (n=11) was 3.52 mg/kg (3.34, 4.77) based on actual body weight and 4.78 mg/kg (4.34, 5.18) in Group 2 (n=21) (p=0.025). The median time between maternal gentamicin administration and time of delivery varied between the groups at 0.5 hours versus 2.63 hours, respectively (p=0.005). All newborn gentamicin concentrations were less than 2 mcg/mL for maternal doses given less than 1 hour prior to delivery (n=8) (Figure 1). Overall protocol compliance rate was 81.3%. There were no significant differences in nephrotoxicity or ototoxicity between groups.Table 2. Baseline Demographics Table 3. Outcomes Figure 1. Comparison of maternal gentamicin time from administration to delivery and neonatal serum gentamicin concentrations ConclusionThis study suggests peripartum ODD of gentamicin may lead to clinically significant serum concentrations in neonates if administered between 1 to 12 hours of birth. Further studies are warranted to evaluate the effects of maternal ODD of gentamicin on newborns.Disclosures All Authors: No reported disclosures

A Comparison of Colistin versus Colistin Plus Meropenem for the Treatment of Carbapenem-Resistant Acinetobacter baumannii in Critically Ill Patients: A Propensity Score-Matched Analysis.

Carbapenem-resistant Acinetobacter baumannii (CRAB), an important nosocomial pathogen, occurs particularly in the intensive care unit (ICU). Thus, the aim of this study was to compare the efficacy and safety of documented treatment with colistin monotherapy versus colistin plus meropenem in critically ill patients with CRAB infections at Chiang Mai University Hospital (CMUH). We conducted a retrospective cohort study of critically ill patients with CRAB infections in an ICU from 2015 to 2017, who received colistin monotherapy versus colistin plus meropenem. After propensity score matching, an adjusted odds ratio (aOR) of a 30-day mortality rate in patients who received colistin plus meropenem was 0.43 compared to those who received colistin monotherapy (95% CI, 0.23–0.82, p = 0.01). aORs of clinical response and microbiological response were also higher in patients who received colistin plus meropenem (1.81, 95% CI 1.01–3.26, p = 0.048 and 2.08, 95% CI 1.11–3.91, p = 0.023, respectively). There was no significant difference in nephrotoxicity (aOR, 0.76, 95% CI, 0.43–1.36, p = 0.363) between colistin monotherapy and colistin plus meropenem. In conclusion, the addition of meropenem to colistin caused a reduction in 30-day mortality, higher clinical and microbiological responses, and did not increase nephrotoxicity compared to colistin monotherapy. Furthermore, 30-day mortality was significantly related with age, receiving vasopressor, having malignancy, and the APACHE II score.

1373P Difference in nephrotoxicity caused by cisplatin after a short or long hydration scheme in non-small cell lung cancer: A retrospective cohort study (HYCIS-XL)

1373P Difference in nephrotoxicity caused by cisplatin after a short or long hydration scheme in non-small cell lung cancer: A retrospective cohort study (HYCIS-XL)

Effects of CFTR modulators on pharmacokinetics of tobramycin during acute pulmonary exacerbations in the pediatric cystic fibrosis population.

Individuals with cystic fibrosis (CF) require higher dosages of aminoglycosides due to an increased volume of distribution (Vd ) and clearance. Optimal dosing of aminoglycosides in the CF population is essential as repeated exposure to aminoglycosides during acute pulmonary exacerbations increases risk of nephrotoxicity and ototoxicity. To date, no studies have evaluated whether chronic cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy affects pharmacokinetics of aminoglycoside antibiotics in patients with CF. The objective of this study was to determine if the addition of a CFTR modulator affects elimination rate (Ke ) for intravenously administered tobramycin in the pediatric CF population. This retrospective study included patients aged 2 to 18 years with CF receiving chronic therapy with a CFTR modulator. Patients included had an admission both pre- and post-chronic CFTR modulator therapy during which they received therapy with IV tobramycin. Thirty-four patients were included in the study. The median time between pre- and post-modulator admissions was 16.5 (13.8) months. Duration of CFTR modulator therapy before post-modulator admission was a median of 8 (10.3) months. There was no significant difference in Ke (hr-1 ) between pre- and post-modulator therapy, 0.41 (0.21) pre and 0.39 (0.09) post (P = .5). Vd and peak concentration were similar between both groups. There was no difference in nephrotoxicity as defined by the pRIFLE criteria (P = .25). The pharmacokinetic parameters of intravenously administered tobramycin during admission for acute pulmonary exacerbation do not appear to change significantly after initiating chronic therapy with a CFTR modulator. Empiric dose adjustments for patients on CFTR modulators are not recommended.

The effectiveness and nephrotoxicity of loading dose colistin combined with or without meropenem for the treatment of carbapenem-resistant A. baumannii

IntroductionAcinetobacter baumannii has emerged as an important nosocomial pathogen worldwide. In Thailand, the incidence and mortality rate of carbapenem-resistant A. baumannii (CRAB) is continuously increasing. This organism is a common pathogen that can cause HAP and VAP. CRAB tends to be susceptible to only colistin, so colistin would be the last line of treatment for CRAB. The recent data from in-vitro studies found that colistin and meropenem combination therapy could exert synergistic effects. However, some in-vivo studies have shown no significant difference in antibacterial effect between colistin monotherapy and colistin plus meropenem. Moreover, the clinical data are recently limited and not clear. Thus, the objective of this study was to compare clinical outcome, microbiological response, mortality rate and nephrotoxicity between loading dose (LD) colistin monotherapy and LD colistin-meropenem for treatment of infection caused by CRAB in Maharaj Nakorn Chiang Mai Hospital. Materials and MethodsThis study is a retrospective analytical study. The data were collected from patients who received LD colistin monotherapy or LD colistin plus meropenem combination therapy for treatment of CRAB from 1 January 2013 to 31 August 2017 at Maharaj Nakorn Chiang Mai Hospital. A total of 324 patients met the inclusion criteria. The data were analyzed by descriptive statistics and inferential statistics, and were adjusted for confounding factors by logistic regression analysis. ResultsThe adjusted OR of good clinical outcome of patients who received LD colistin plus meropenem was 1.05 times that of patients who received loading dose colistin monotherapy (95%CI 0.62-1.74, p=0.860). Patients who received LD colistin plus meropenem had 0.93 times (adjusted OR) mortality rate at the end of treatment compared to patients who received LD colistin monotherapy (95%CI=0.51-1.71, p=0.935). In addition, microbiological response was defined as eradication of pre-treatment isolated pathogens in post-treatment cultures. Patients who received LD colistin plus meropenem could eradicate pathogens 1.28 times more than LD colistin monotherapy (95% CI=0.74-2.20, p=0.371). Also there was no significant difference in nephrotoxicity (adjusted OR=0.84, 95% CI 0.52-1.36, p=0.492) between LD colistin monotherapy and LD colistin plus meropenem. ConclusionThere were no significant differences in effectiveness and nephrotoxicity of LD colistin monotherapy versus LD colistin plus meropenem for treatment of CRAB infection, so colistin combination therapy was not necessary for the management of infection caused by CRAB.

Evaluation of Renal Safety Between Imipenem/Relebactam and Colistin Plus Imipenem in Patients With Imipenem-Nonsusceptible Bacterial Infections in the Randomized, Phase 3 RESTORE-IMI 1 Study.

BackgroundIn the randomized controlled RESTORE-IMI 1 clinical trial (NCT02452047), imipenem/cilastatin (IMI) with relebactam (IMI/REL) was as effective as colistin plus IMI for the treatment of imipenem-nonsusceptible gram-negative infections. Differences in nephrotoxicity were observed between treatment arms. As there is no standard definition of nephrotoxicity used in clinical trials, we conducted analyses to further understand the renal safety profile of both treatments.MethodsNephrotoxicity was retrospectively evaluated using 2 acute kidney injury assessment criteria (Kidney Disease Improving Global Outcomes [KDIGO] and Risk, Injury, Failure, Loss, and End-stage Kidney Disease [RIFLE]). Additional outcomes included time to onset of protocol-defined nephrotoxicity and incidence of renal adverse events.ResultsOf 47 participants receiving treatment, 45 had sufficient data to assess nephrotoxicity (IMI/REL, n = 29; colistin plus IMI, n = 16). By KDIGO criteria, no participants in the IMI/REL but 31.3% in the colistin plus IMI group experienced stage 3 acute kidney injury. No IMI/REL-treated participants experienced renal failure by RIFLE criteria, vs 25.0% for colistin plus IMI. Overall, the time to onset of nephrotoxicity varied considerably (2–22 days). Fewer renal adverse events (12.9% vs 37.5%), including discontinuations due to drug-related renal adverse events (0% vs 12.5%), were observed in the IMI/REL group compared with the colistin plus IMI group, respectively.ConclusionsOur analyses confirm the findings of a preplanned end point and provide further evidence that IMI/REL had a more favorable renal safety profile than colistin-based therapy in patients with serious, imipenem-nonsusceptible gram-negative bacterial infections.ClinicalTrials.gov IdentifierNCT02452047.

Comparison of cisplatin-induced nephrotoxicity when using conventional versus short hydration in gastric cancer—a retrospective study

Although a short hydration protocol for cisplatin has been recently developed for use in lung cancer, this has yet to be established for gastric cancer. This study reviewed medical records of patients with gastric cancer who received XPT(capecitabine/cisplatin/trastuzumab) therapy containing cisplatin. Patients received either the conventional or short hydration regimen. Nephrotoxicity was compared between these two regimens by monitoring the serum creatinine. Out of the 26 total patients, 19 received the conventional regimen while 7 received the short hydration regimen. There was a higher nephrotoxicity was observed in the group receiving the conventional regimen (42.1%, 8/19) as compared to the short hydration regimen (0%, 0/7). There was a statistically significant difference in nephrotoxicity between the regimens (P = 0.039). Study results suggest that short hydration may be a feasible regimen for XPT therapy in gastric cancer patients.