Use Of Vancomycin Research Articles

Vancomycin vs metronidazole use for the treatment of Clostridioides difficile infection in a tertiary care hospital in Saudi Arabia

BackgroundThe 2017 Infectious Diseases Society of America (IDSA) Clostridioides difficile infection (CDI) guidelines recommendation for oral vancomycin as preferred treatment was based on studies conducted in North America, Australia, and Europe. According to recent published data, metronidazole remains a reasonable option. No studies have been conducted in Saudi Arabia to compare prescribing patterns before and after the release of the guidelines. Due to low CDI burden in Saudi Arabia, the aim is to assess the effectiveness and outcomes of vancomycin vs metronidazole treatment options. MethodsThis was a retrospective cohort study conducted in a tertiary care hospital in Jeddah which was approved by the Institutional Review Board (IRB 2020–53). Data was collected from January 2017 to April 2020. Eligible patients were adults (>18 years old) diagnosed with CDI who either received oral metronidazole (500 mg 3 times daily) or oral vancomycin (125–500 mg 4 times daily). Patients who received a combination of treatment or who were diagnosed with fulminant CDI were excluded. Demographic data were collected. The primary outcome was to assess treatment response to initial therapy with oral metronidazole versus oral vancomycin. Secondary outcomes included assessing early treatment response, time to discharge after diagnosis, proportion of patients with a positive VRE surveillance culture within 6 months of diagnosis, 30-day recurrence and 30-day all-cause mortality. Chi-square or Fisher's exact test were used to examine differences in categorical variables while student t-test or Mann–Whitney test, were used to examine differences in continuous variables. P value < 0.05 was considered as significant. ResultsA total of 166 patients were included in the analysis. Demographic characteristics were not significantly different between the two groups. There was no difference in treatment response between vancomycin and metronidazole (96.4 % versus 94.3 %, p = 0.682). However, compared with metronidazole, vancomycin treatment was significantly associated with better early response (94.0 % versus 77.8 %, p = 0.008). Other outcomes were not significantly different between the two drug groups for time to discharge after diagnosis (P = 0.522), 30-day recurrence (P > 0.99) and 30-day all-cause mortality (P = 0.782). Of note, the vancomycin versus metronidazole use before the 2017 IDSA guidelines (26 % versus 74 %) was completely reversed after the release of the guidelines (83.3 % versus 16.7 %), p < 0.001). ConclusionThe results of this study demonstrate that vancomycin and metronidazole have comparable outcomes in regards to treatment response for non-fulminant CDI. The study also reveals the high and quick impact of international guidelines on local prescription patterns. Further studies are needed in Saudi Arabia to guide the treatment of CDI.

Use of vancomycin and gentamicin-impregnated calcium sulfate beads for the prevention of surgical site infection in adult spinal deformity

Use of vancomycin and gentamicin-impregnated calcium sulfate beads for the prevention of surgical site infection in adult spinal deformity

Real-Life Vancomycin Therapeutic Drug Monitoring in Coagulase-Negative Staphylococcal Bacteremia in Neonatal and Pediatric Intensive Care Unit: Are We Underestimating Augmented Renal Clearance?

Bloodstream infections (BSI) from coagulase-negative-staphylococci (CoNS) are among the most frequent healthcare-related infections. Their treatment involves the use of vancomycin, a molecule whose optimal pharmacokinetic/pharmacodynamic (PK/PD) target for efficacy and safety is an area-under-curve/minimum inhibitory concentration (AUC/MIC) ratio ≥ 400 with AUC < 600. BSIs from CoNS in pediatric and neonatal intensive care unit that occurred at the Gaslini Institute over five years were evaluated to investigate the efficacy of vancomycin therapy in terms of achieving the desired PK/PD target and determining whether any variables interfere with the achievement of this target. AUC/MIC ≥ 400 with AUC < 600 at 48 and 72 h after therapy initiation was achieved in only 21% of the neonatal population and 25% of the pediatric population. In the pediatric population, an inverse correlation emerged between estimated glomerular filtration rate (eGFR) and achieved AUC levels. Median eGFR at 72 h was significantly higher (expression of hyperfiltration) in events with AUC < 400, compared with those with AUC ≥ 400 (p < 0.001). A cut-off value of eGFR in the first 72 h has been identified (145 mL/min/1.73 m2), beyond which it is extremely unlikely to achieve an AUC ≥ 400, and therefore a higher dose or a different antibiotic should be chosen.

Evaluation of Vancomycin Utilization in the Medical and Gynecology Wards of Felege Hiwot Comprehensive Specialized Hospital, Northwest Ethiopia

Background. Drug use evaluation is an approach that focuses on evaluating and optimizing drug use practices to achieve the best possible patient outcomes. The purpose of this study was to assess the appropriateness of vancomycin usage patterns and their practical application in hospitalized patients. Methods. An institutional-based descriptive retrospective cross-sectional study design was carried out among 265 hospitalized patients from May 1, 2022, to July 30, 2022. The study participants were selected using a simple random sampling method. Result. Among the 265 study participants, 60.4% were male respondents, while 86.8% of vancomycin was administered for treatment; however, 13.2% was administered for prophylaxis. In addition, 41.9% and 27.5% of vancomycin were ordered for treatment of meningitis and pneumonia, respectively. The culture was performed for only 17.4% of patients, and 82.6% of vancomycin was used for empiric therapy. Most (66.8%) of vancomycin was given in the dose range of 800–1000 mg. The finding indicates that 57.36% and 39.25% were due to incorrect doses and durations, respectively. Only 17.4% of patients had sensitivity tests. Conclusions. Vancomycin inappropriateness was common with the indication, dose, frequency, and duration of therapy according to the guidelines. Vancomycin was mostly indicated as empiric therapy, even though the sensitive test was performed in a small amount. Given the widespread use of vancomycin as an empiric drug, its utilization should be monitored closely. Therefore, the usual sensitive test is recommended to identify those intermediate and resistant results and to predict the outcomes of the treatment.

Impact of the sequential implementation of a pharmacy-driven methicillin-resistant Staphylococcus aureus (MRSA) nasal-swab ordering policy and vancomycin 72-hour restriction protocol on standardized antibiotic administration ratio (SAAR) data for antibiotics used for resistant gram-positive infections.

Vancomycin is often initiated in hospitalized patients; however, it may be unnecessary or continued for longer durations than needed. Oversight of all vancomycin orders may not be feasible with widespread prescribing and strategies to enlist other clinicians to serve as stewards of vancomycin use are needed. We implemented 2 sequential interventions: a protocol in which the pharmacist orders MRSA nasal swab followed by a protocol requiring approval from pharmacists to continue vancomycin for >72 hours. In this single-center, retrospective, quasi-experimental study, we evaluated vancomycin use after implementation of a pharmacy-driven MRSA nasal-swab ordering protocol and a vancomycin 72-hour restriction protocol. The primary outcome was the change in the standardized antibiotic administration ratio (SAAR) for antibacterial agents for resistant gram-positive infections. We also evaluated the impact on antibiotic utilization. Following the MRSA swab protocol, the SAAR decreased from 1.26 to 1.13 (P < .001; 95% confidence interval [CI], 1.16-1.25). After the 72-hour approval process, the SAAR was 0.96 (P < .001; 95% CI, 1.0-1.12). Vancomycin utilization decreased from 138.9 to 125.3 days of therapy per 1,000 patient days following the MRSA swab protocol (P < .001) and to 112.7 (P < .001) following the 72-hour approval protocol. Interrupted time-series analysis identified a similar rate of decline in utilization following the 2 interventions (-0.3 and -0.5; P = .16). Both interventions combined resulted in a significant reduction (-1.5; P < .001). Implementation of a pharmacist-driven MRSA nasal-swab ordering protocol, followed by a 72-hour approval protocol, was associated with a significant reduction in the SAAR for antibiotics used in the treatment of resistant gram-positive infections and a reduction in vancomycin utilization. Leveraging the oversight of primary service clinical pharmacists through these protocols proved to be an effective strategy.

Antibiotic Use in Adult Spine Deformity Surgery: Results From the AO Spine Surveillance of the Management of Patients With Adult Spine Deformity.

Cross-sectional international survey with literature review. To evaluate the evidence for these strategies and to understand the current trends in prophylactic antibiotic use during ASD surgery through an international survey. An online survey was conducted among international AO Spine members regarding the peri-operative management of patients with ASD. The details of perioperative systemic and topical antibiotic use were solicited. Descriptive data were summarized for the responding surgeons who perform at least 10 long-segment fusions of >5 levels extending to the pelvis annually. The literature supports the use of prophylactic antibiotic effective against gram positive organisms. The use of topical vancomycin remains debated, and there is limited evidence for topical tobramycin use. A total of 116 responses were received. 74 (64%) surgeons use topical vancomycin, most usually deep to the fascia only 45 (61%). The most usual dose used is 1-2g. 4 (3%) surgeons use topical tobramycin deep to fascia. Following surgery, 90 (78%) surgeons use prophylactic cephalosporin with 3 (3%) using cloxacillin, 5 (4%) using ciprofloxacin and 9 (8%) using vancomycin and 6 (5%) using clindamycin either in addition or alone. The present survey identifies a trend towards systemic and topical antibiotic prophylaxis primarily targeted at gram positive pathogens. The use of topical tobramycin, proposedly effective against gram negative infections, remains uncommon. There is a lack of consensus in the selection of perioperative antibiotic prophylaxis, thus a prospective study of the rates of infection with each strategy would be useful to inform guidelines.

Perioperative Means to Prevent Surgical Site Infections following Elective Craniotomies: A Single-Center Experience.

Background Postoperative surgical site infections are a recognized complication following craniotomies with an associated increase in morbidity and mortality. Several studies have attempted to identify bundles of care to reduce the incidence of infections. Our study aims to clarify which perioperative measures play a role in reducing surgical infection rates further. Methods This study is a retrospective audit of all elective craniotomies in years 2018 to 2019. The primary endpoint was the surgical site infection rate at 30 days and 4 months after the procedure. Univariate analysis was used to identify factors predictive of postoperative infection. Results 344 patients were included in this study. Postoperative infections were observed in 5.2% of our cohort. No postoperative infections occurred within 4 months in patients receiving perioperative hair wash and intrawound vancomycin powder. In univariate analysis, craniotomy size (Fisher's exact test, p = 0.05), lack of perioperative hair wash, and vancomycin powder use (Fisher's exact test, p = 0.01) were predictive of postoperative infection. No complications relative to the use of intrawound vancomycin were observed. Conclusion Our study demonstrates that simple measures such as perioperative hair wash combined with intrawound vancomycin powder in addition to standard practice can help reducing infection rates with negligible risks and acceptable costs. Our results should be validated further in future prospective studies.

Bleeding Complications in Vancomycin-Induced Thrombocytopenia: A Real-world Postmarketing Pharmacovigilance Analysis

PurposeVancomycin and linezolid are first-line drugs used for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Vancomycin is well known as the best alternative drug when linezolid-induced thrombocytopenia occurs. However, several cases with vancomycin-induced thrombocytopenia, especially with bleeding complications, have been reported recently, which has attracted attention. The objective of this study is to assess the potential relevance between vancomycin and bleeding complications in thrombocytopenia. MethodsThis is a real-world pharmacovigilance study conducted in October 2022 using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. We performed a disproportional analysis to assess the risk of bleeding complications in vancomycin-induced thrombocytopenia by calculating reporting odds ratios (RORs) and information components (ICs), with a weak signal defined as a lower limit of the IC 95% CI of 0 to 1.5, a middle signal defined as a lower limit of the IC 95% CI of 1.5 to 3.0, and a strong signal defined as a lower limit of the IC 95% CI of >3.0. FindingsThere were 21,854 cases in the FAERS database that listed vancomycin as a suspected drug from quarter 1 of 2004 to quarter 2 of 2022. There were 800 cases of vancomycin-induced thrombocytopenia and 125 cases of bleeding complications in vancomycin-induced thrombocytopenia. Teicoplanin, tigecycline, and vancomycin (3 middle signals) were sequentially less associated with thrombocytopenia than linezolid (strong signal). However, bleeding complications in thrombocytopenia were significant associated with vancomycin (ROR = 9.641; 95% CI, 8.105–11.468; IC = 3.184; 95% CI, 2.929–3.440 [middle signal]), followed by linezolid (ROR = 9.350; 95% CI, 7.318–11.947; IC = 3.106; 95% CI, 2.745–3.466 [middle signal]), teicoplanin (ROR = 6.399; 95% CI, 2.869–14.272; IC = 2.059; 95% CI, 0.881–3.283 [weak signal]), and daptomycin (ROR = 2.784; 95% CI, 1.496–5.180; IC = 1.287; 95% CI, 0.374–2.201 [weak signal]). Tigecycline and daptomycin were the least likely anti-MRSA drug to cause thrombocytopenia (middle signal and weak signal, respectively) and bleeding complications in thrombocytopenia (no signal and weak signal, respectively). Middle signals of bleeding complication in vancomycin-induced thrombocytopenia were found in all group except those <45 to ≥80 years of age (weak signal). ImplicationsBleeding complications in thrombocytopenia were significantly associated with vancomycin use, and the risk was highest among all the anti-MRSA drugs. Physicians should be aware of this possible serious adverse reaction.

Surgical site infection prophylaxis with intra-wound vancomycin powder for uninstrumented spine surgeries: a meta-analysis.

It is unclear if intra-wound vancomycin powder significantly reduces the infection rate for uninstrumented spine surgery. The purpose of this study is to compare the rate of surgical site infection (SSI) in uninstrumented spine surgery that used vancomycin powder against controls. A search was performed on PUBMED/MEDLINE, Cochrane Database and Embase on 14 October 2022. Search keywords were "vancomycin, spine surgery, uninstrumented and spinal surgery." Instrumented cases were excluded. Type of surgery, type of treatment and incidence of infection among experimental or control were recorded. 288 articles were obtained from a literature search. 16 studies met inclusion criteria. 6/16 studies that reported on the infection rate using vancomycin were obtained. There were 1376 control cases with 20 cases of post-operative infection (1.45% overall). There were 795 cases that received prophylactic intra-wound vancomycin powder with 10 cases of infection reported (1.26%). There was no significant difference in infections between cases that received vancomycin compared to control. On subgroup analysis, studies that had a high rate of infection (Strom and Cannon) had a significant difference on the rate of infection with the use of vancomycin compared to control. The current study was unable to conclude that vancomycin decreased the rate of surgical site infections. Vancomycin use may be useful in populations that have a high rate of infection. Limitations in this study include the small number of studies that report on the use of vancomycin on uninstrumented spine surgery.

120. Use of vancomycin and gentamicin-impregnated calcium sulfate beads for the prevention of surgical site infection in adult spinal deformity

120. Use of vancomycin and gentamicin-impregnated calcium sulfate beads for the prevention of surgical site infection in adult spinal deformity

Clostridioides difficile Infection in Inflammatory Bowel Disease Patients: A Systematic Review of Risk Factors and Approach in Management.

Clostridioides difficile infection (CDI) is one of the most common diseases associated with medical care, having a more significant impact on patients with inflammatory bowel disease (IBD). The latest studies have proposed a change in management for CDI in IBD patients. This study aims to perform a systematic review that explores the risk factors associated with the infection and the most optimal approach in management. Multiple databases were used for this research, including PubMed, Google Scholar, Science Direct, and Cochrane Library. Studies published in the last five years in the English language were selected based on pre-established criteria. The quality assessment used was the Assessment of Multiple Systematic Review, the Newcastle-Ottawa Scale, and the Scale for the Assessment of Narrative Review Articles. Twelve studies met the inclusion criteria in this systematic review, including literature reviews, a case and control study, and systematic reviews and meta-analyses. Based on the findings in this research, we conclude that the treatment for an initial episode of CDI in IBD patients is the use of antibiotics, vancomycin, or fidaxomicin. For episodes of recurrent CDI (rCDI), fetal microbiota transplantation should be considered. The most common risk factors associated are gut microbiota disturbances, the use of antibiotics, and hospitalization. Due to a wide range of risk factors mentioned in some studies but disregarded in others, further research is needed to determine the most prevalent risk factors.

Vancomycin powder embedded in collagen sponge decreases the rate of prosthetic shoulder infection.

Shoulder arthroplasty is a successful procedure to treat degenerative and traumatic diseases of the glenohumeral joint. Periprosthetic infection represents an infrequent but dreaded complication (2%-4%). Application of intrawound vancomycin powder seems to reduce periprosthetic infections, but limited information is available on its efficiency in shoulder arthroplasty. The purpose of this study was to evaluate if the vancomycin powder embedded in a collagen sponge could decrease the rate of prosthetic shoulder infection. A retrospective analysis of 827 patients undergoing total shoulder arthroplasty was performed. The study involved a control group of 405 patients and a group of 422 with the intraoperative insertion of intrawound vancomycin powder. Incidence of periprosthetic infection was evaluated comparing the 2 groups at a minimum follow-up of 12 months. Patient demographics, comorbidities, and perioperative information were compared between the 2 groups. No infection was observed in the group treated with intrawound vancomycin, and 13 cases of infection were observed in the control group (3.2%) (P value <.001) without subacromial vancomycin application. No wound complications requiring revision were observed as a result of intrawound vancomycin application. Intrawound vancomycin powder significantly reduces the rate of periprosthetic shoulder infections without any increase in local and systemic aseptic complications at a minimum follow-up of 12 months. Our results support the use of intrawound local vancomycin for prophylaxis of shoulder periprosthetic infections.

Development of methodological approaches to the formation of a risk-based model to minimize the prevalence of adverse reactions in drug application in medical organizations of Moscow

Objective: development of approaches to predict the likelihood of adverse reactions (ARs) when using drugs based on a comprehensive assessment of risk factors.Material and methods. We used a database containing 1,450 drug-related ARs reports from January through December 2021. A list of antibacterial drugs by international nonproprietary name (INN) with 4 or more ARs reports was selected as a reference group to perform various types of statistical analysis. A cumulative multivariate regression analysis was carried out on a database of 187 ARs notifications for 13 INN of antibacterial drugs. The study was performed in two stages. In the first stage, a statistical method was used (classical multiple regression, linear discriminant analysis, factor analysis, principal component regression, partial least squares regression, estimation of variance accuracy); at the second stage a modeling method was used. As part of the modeling stage, the integral score of the risk of ARs was presented as a sum of values for individual risk factors. Two groups of risks were proposed to be assessed: 1) intrinsic risk value for each factor (attribute), which was equal to the sum of risks of all factors (conditions) in which the drug had been used; 2) intrinsic risk value for antibacterial drugs by each INN. The total risk value was defined as the sum of the risk of the drug and all factors (conditions) in which this drug had been used.Results. The results were visualized in the form of a two-level risk-based model matrix, with a “heat map” of the risk level overlaid on it. The maximum total risk of ARs was obtained for ceftriaxone – 404.96 points, depending on patient’s gender. The minimum total risk was calculated for azithromycin and cefotaxime depending on the International Classification of Diseases (10th revision) code – 88.46 points. The proposed methodological approach also allows combining all possible combinations of drugs and conditions of their use. For example, for the use of vancomycin in hospital conditions by intravenous administration: intrinsic risk of use – 42.93 points; risk of use in hospital conditions – 183.68 points; risk when administered intravenously – 209.95 points; the total risk value in the designated situation – 436.56 points.Conclusion. The proposed approach can allow medical organizations to reduce significantly the number of ARs when using drugs by categorizing and preventing risks before they occur. It also has significant prospects of application at the federal level, given its modification on a large volume of data.

Impact of common comorbidities on antimicrobial consumption and mortality amongst critically ill COVID-19 patients: A retrospective two center study in Saudi Arabia.

To determine the association between common comorbidities, ICU mortality and antimicrobial consumption among critically ill COVID 19 patients in Saudi Arabia. A retrospective observational study of patients admitted to the ICU from March 1st, 2020, through August 31st, 2021. We excluded patients who stayed <24h in the ICU and with no confirmed COVID-19 PCR testing. Of the 976 screened ICU patients, 848 were included. While there was no difference in mortality between patients with and without comorbidities, those with at least one comorbidity had a higher severity of illness (p=0.013). Compared to survivors, non-survivors were more likely to require mechanical ventilation and vasopressor support (P<0.001). Almost all patients received at least one antimicrobial therapy. Predictors independently associated with ICU mortality were: older age (adjusted odds ratio [AOR], 1.03; 95% confidence interval [CI], 1.01-1.04), vancomycin use (AOR, 2.69; 95% [CI], 1.65-4.37), linezolid use (AOR, 2.65; 95% [CI], 1.65-4.04), sepsis or septic shock (AOR, 6.39; 95% [CI], 3.68-11.08), Acute Kidney Injury (AKI) (AOR, 2.51; 95% [CI], 1.61-3.92) and Acute Respiratory Distress Syndrome (ARDS) (AOR, 2.03; 95% [CI], 1.61-3.92). Older age, vancomycin and linezolid use, sepsis/septic shock, AKI, and ARDS were negative prognostic factors in critically ill COVID-19 patients. More studies are needed to evaluate the outcomes of survived critically ill patients in relation to their vaccination status.

Assessing use of vancomycin powder in craniotomy: randomized controlled trial (AVIC)

Background: Surgical-site infections (SSIs) can lead to greater postoperative morbidity, mortality, and health care costs. Despite current prophylactic measures, rates of SSIs have been reported in up to 5% of patients post craniotomy. Intrawound vancomycin powder has been studied extensively in spinal fusion surgeries and been found to reduce rates of surgical site infections (SSIs) significantly. Despite its success in spinal surgeries, topical vancomycin has not been extensively studied with respect to cranial neurosurgery. Methods: Our study is Prospective Randomized clinical trial. Patients will be divided in this Trial into two groups, first group (intervention arm) they will receive the drug (vancomycin) in the wound before the closure of the skin at the end of the surgical procedure. The second group (control arm) they will not receive the drug, otherwise both groups they will receive identical measure to decrease the postoperative SSI. The primary outcome variable will be SSI rate factored by cohort. Secondary outcome will be to monitor the safety and any complication related to the use of vancomycin . SSI found to be around 0.49% when vancomycin was used, while SSI in standard care found to be 5%, to get power of study 80% and level of significance 5%. Sample size will be 250 in each group using sample size calculator. Discussion: This study is designed to evaluate the efficacy of vancomycin compared to standard method in neuro-surgical cases undergoing craniotomy . Additionally, safety of vancomycin will be assessed in these patients.

The Trend of Cefepime-Induced Neurotoxicity: A Systematic Review.

There has been increased use of cefepime due to concerns about the nephrotoxic effects of the combined use of vancomycin and Zosyn. However, cefepime is associated with neurotoxicity. We conducted a systematic review using online data to explore the trend of cefepime-induced neurotoxicity over the last 10 years. Forty-six articles met our inclusion criteria, including 73 cases of cefepime-induced neurotoxicity. We noticed a steady increase in the reports of cefepime-induced neurotoxicity, from one case in 2013 to 11 cases in 2022. Individuals aged 65 and older accounted for most cefepime-induced neurotoxicity cases (52%). The top three indications for cefepime administration included bone and joint infections (25%), urinary tract infections (22.7%), and pneumonia (22.7%). Most patients with renal impairment have never had a renal adjustment of their cefepime dosage (either 2 g 12 hours a day or 2 g eight hours a day). Most cases of cefepime-induced neurotoxicity occurred between days two and five (n=29, 71%), while most resolution occurred between days one and five (n=29, 85%). While cefepime continues to be a popularly used and effective antibiotic against gram-negative bacteria like Pseudomonas aeruginosa, its dosage needs to be adjusted in patients with renal impairment to avoid neurotoxicity.

Association of Acute Kidney Injury With Antibiotic Loaded Cement Used for Treatment of Periprosthetic Joint Infection

BackgroundAntibiotic-loaded bone cement (ALBC) is commonly used in the treatment of periprosthetic joint infections (PJIs) to increase the local concentration of antibiotic at the site of infection. Use of ALBC has been associated with rare instances of acute kidney injury (AKI) despite low systemic absorption of the nephrotoxic antibiotics; however, the incidence of AKI is unknown. The purpose of this study was to determine the incidence of and risk factors for AKI associated with ALBC. MethodsThis single-site, retrospective cohort study compared 162 PJI patients who underwent Stage 1 revision to a spacer with ALBC to 115 PJI patients who underwent debridement, antibiotics, and implant retention (DAIR) without the use of ALBC. Both groups received similar systemic antibiotics postoperatively. Descriptive statistics and multivariable logistic regressions were used to analyze risk factors for AKI. ResultsThere was no statistically significant difference in the rate of AKI: 29 patients (17.9%) in the ALBC group and 17 (14.7%) in DAIR group developed AKI (odds ratio 1.43; 95% CI 0.70 to 2.93). There was a trend toward increased severity of AKI in the ALBC group. Chronic kidney disease, systemic vancomycin, and diuretic use were independent factors associated with the risk of AKI. ConclusionAn AKI occurred in 17% of PJI patients receiving either a spacer with ALBC or a DAIR. The use of ALBC was not associated with a significant increased risk of AKI. However, the use of systemic vancomycin and diuretic use were independent predictors of AKI in this patient population.

Pharmacokinetic and Biomarker Quantification Studies on Vancomycin-Loaded PEGylated Liposomes and Its Potential to Reduce Vancomycin-Induced Kidney Injury: A Rat Study.

Vancomycin is a commonly used antibiotic in hospital settings, especially against Methicillin-resistant staphylococcus aureus (MRSA). One of the major adverse events of vancomycin use in adults is kidney injury. The drug concentration, specifically the area under the concentration curve, predicts kidney injury in adults receiving vancomycin. To attempt to reduce vancomycin-induced nephrotoxicity, we have successfully encapsulated vancomycin in polyethylene glycol-coated liposomes (PEG-VANCO-lipo). We have previously carried out in vitro cytotoxicity studies on kidney cells using PEG-VANCO-lipo and found it to be minimally toxic compared to the standard vancomycin. In this study, we have dosed male adult rats with PEG-VANCO-lipo or vancomycin HCl and compared plasma vancomycin concentrations and KIM-1 as an injury biomarker in rat urine. Male Sprague Dawley rats (350 ± 10 g) were administered vancomycin (n = 6) or PEG-VANCO-lipo (n = 6) 150 mg/kg/day for three days using an IV infusion in the left jugular vein catheter. Blood was collected for plasma at 15, 30, 60, 120, 240, and 1440 min after the first and the last IV dose. Urine was collected 0-2, 2-4, 4-8, and 8-24 h after the first and the last IV infusions using metabolic cages. The animals were observed for three days after the last compound administration. Vancomycin was quantified in plasma by LC-MS/MS. Urinary KIM-1 analysis was done by using an ELISA kit. Three days after the last dose, under terminal anesthesia with IP ketamine (65-100 mg/kg) and xylazine (7-10 mg/kg), rats were euthanized. Vancomycin urine and kidney concentrations and KIM-1 were lower on day three in the PEG-Vanco-lipo group compared to the vancomycin group (p < 0.05, ANOVA and/or t-test). There was a significant reduction in plasma vancomycin concentration on day one and day three (p < 0.05, t-test) in the vancomycin group compared to the PEG-VANCO-lipo group. Vancomycin-loaded PEGylated liposomes resulted in lower levels of kidney injury, as noted by a decrease in KIM-1 values. Moreover, longer circulation in plasma with increased concentration in plasma as opposed to the kidney was observed with the PEG-VANCO-lipo group. The results indicate the high potential of PEG-VANCO-lipo in decreasing the nephrotoxicity of vancomycin clinically.

(105) A Multicenter Analysis of the AUA Recommended Antibiotic Prophylaxis for Penile Implantation Results in Higher, not Lower, Infection Risk

Abstract Introduction The American Urological Association (AUA) recommendations on antibiotic prophylaxis in penile implant surgery are based on low quality evidence and expert opinion. Recent evidence suggests the recommended regimens may be suboptimal. Objective To determine if the AUA recommended antibiotic regimen (vancomycin + gentamicin) for primary penile implant surgery is associated with a higher infection risk than non-standard regimens. Methods We performed a multicenter, retrospective cohort study of patients undergoing primary IPP surgery. Patients undergoing revision surgery or with a history of IPP placement were excluded. Additionally, patients who underwent concomitant procedures for Peyronie’s disease or stress urinary incontinence were excluded. Patients were divided into those receiving standard AUA antibiotic prophylaxis (vancomycin + gentamicin) and those receiving any other (non-standard) antibiotic prophylaxis. The time to postoperative device explanation due to infection via a Cox regression model, the microorganisms involved, and the management of patients with device infection were evaluated. A subgroup analysis to identify the appropriate dosage of gentamicin was also performed. Results 4,161 patients underwent primary IPP placement (2,411 received vancomycin + gentamicin and 1,750 received other regimens). The infection rate was similar between groups, 1.0 vs 1.2% for standard vs non-standard prophylaxis. In the multivariate Cox regression analysis, the use of vancomycin + gentamicin (HR: 2.74, 95%CI: 1.38-5.41, p=0.004) and diabetes (HR: 1.87, 95%CI: 1.03-3.39, p=0.04) were significantly associated with higher risk of device explantation due to infection. Concomitant infusion of antifungals (HR: 0.08, 95%CI: 0.03-0.19, p&amp;lt;0.001) was associated with lower risk of infection. Staphylococcus aureus and Escherichia coli were the most frequently cultured microorganisms. Device infection was most commonly managed with salvage using a malleable prosthesis (40.4%). In patients of both groups receiving gentamicin as part of perioperative antibiotic prophylaxis, the use of weight-based gentamicin compared to 80 mg gentamicin was associated with similar risk of device explantation due to infection (HR: 2.88, 95% CI: 0.83 to 10, p = 0.1). Conclusions Vancomycin + gentamicin for antibiotic prophylaxis in primary penile implant surgery is independently associated with a higher infection risk than non-standard antibiotic regimens while antifungal use is associated with lower infection risk. There does not appear to be a difference in weight-based vs low dose (80mg) gentamicin on infection risk. Our results further demonstrate the importance of antifungal use in prophylaxis regimens. Additionally, a critical review of the recommended prophylactic regimens is needed. Tailoring individual regimens to local antibiograms may provide the best infection prevention. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast, Boston Scientific, Antares Pharma, Clarus Therapeutics, Cynosure, Promescent, Sprout, Viome.

Necessity of vancomycin trough concentrations to manage uncomplicated acute bacterial skin and skin structure infections: a laboratory stewardship analysis.

Recent recommendations by the American Society of Health System Pharmacists and Infectious Disease Society of America have provided guidance regarding vancomycin dosing and monitoring in serious infections (including methicillin-resistant Staphylococcus aureus); however, trough monitoring for uncomplicated acute bacterial skin and skin structure infections (ABSSSI) were not addressed. Vancomycin use appears to lead to a low incidence of acute kidney injury with short durations and a low trough goal (10-15 mg/L). Nevertheless, clinical studies have found no difference in clinical outcomes for ABSSSI regardless of vancomycin level. Therefore, it can be posed whether trough monitoring is necessary in this patient population. This is a retrospective cohort study comparing vancomycin therapy duration for ABSSSI in adult, general medicine patients who received scheduled vancomycin with an initial creatinine clearance rate of ≥50 mL/minute and had at least one vancomycin trough. The objective of this study was to determine if vancomycin treatment duration differs for patients with ABSSSI with a sub-therapeutic vancomycin trough (ST; <10 mg/L) compared with therapeutic trough (TT; ≥10 mg/L). There were 39 (67.2%) patients with ST compared with 19 (32.8%) with TT. A similar median vancomycin treatment duration for ST (48.25 hours) and TT (59.5 hours; p=0.65) was found. There was no statistical difference for hospital duration, time from last trough to vancomycin discontinuation, or incidence of acute kidney injury (p>0.05 for all). Patients with ST and TT had similar vancomycin durations and clinical outcomes. It may be prudent for institutions to address vancomycin trough laboratory stewardship and associated costs.