High Vancomycin Research Articles

Multidrug resistance in anaerobes.

Multidrug resistance (MDR) in anaerobes is not a well-known topic. Bacteroides fragilis group isolates have numerous resistance determinants such as multidrug efflux pumps, cfiA and nimB genes and activating insertion sequences, and some isolates exhibited extensive drug-resistant patterns. MDR rates in B. fragilis group were from 1.5 to >18% and up to >71% in cfiA and nimB positive isolates carrying insertion sequences. MDR was present in >1/2 of Clostridioides difficile isolates, most often in epidemic/hypervirulent strains and unusually high metronidazole or vancomycin resistance has been reported in single studies. MDR was found in Prevotella spp. (in ≤10% of isolates), Finegoldia magna, Veillonella spp. and Cutibacterium acnes. Resistance in the anaerobes tends to be less predictable and anaerobic microbiology is required in more laboratories. New hopes may be new antibiotics such as eravacycline, cadazolid, surotomycin, ridinilazol or C. difficile toxoid vaccines; however, more efforts are needed to track the MDR in anaerobes.

Detection of antibiotic susceptibility by colorimetric minimum inhibitory concentration in staphylococcal isolates.

Assess performance of broth microdilution (BMD) as well as agar dilution methods for antimicrobial susceptibility testing of Staphylococci using tetrazolium salt. Minimum inhibitory concentration (MIC) of eight antimicrobials; vancomycin (VA), linezolid, oxacillin, gentamicin (CN), tetracycline, ciprofloxacin, erythromycin and clindamycin was investigated for 80 isolates of Staphylococci by BMD with the addition of dimethyl thiazole diphenyl tetrazolium bromide (MTT), agar dilution with the addition of MTT and triphenyl tetrazolium chloride at the standard bacterial concentration together with addition of MTT at an experimental bacterial concentration. BMD (MTT) showed the highest agreement in comparison with the standard BMD. Colorimetric BMD was rapid and easy to interpret. Colorimetric agar dilution (MTT) was less tedious than BMD. Colorimetric antibiotic susceptibility is a good option to provide rapid reliable results for critically ill patients. In addition, agar dilution (MTT) helps to investigate outbreaks of methicillin-resistant Staphylococcus aureus (MRSA), VISA or VRSA. BMD (MTT) can be performed routinely to detect VA MIC in MRSA blood stream infections and hospital acquired pneumonia, where, high VA MIC is associated with a higher mortality rate.

A new population pharmacokinetic model for vancomycin in patients with variable renal function: Therapeutic drug monitoring based on extended covariate model using CKD-EPI estimation.

WHAT IS KNOWN ANDOBJECTIVE: Although patients may have received vancomycin therapy with therapeutic drug monitoring (TDM), those treated with high-strength and long-term vancomycin therapy might have unstable and time-varying renal function. The methods used to estimate renal function should not be considered interchangeable with pharmacokinetic (PK) modeling and model-based estimation of vancomycin pharmacokinetics. While Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for renal function estimation has been widely integrated into clinical practice, a population PK model including CKD-EPI has not been established.The study was aimed at developing a new population PK model for optimal vancomycin prediction in patients with time-varying and variable renal function to evaluate the interchangeability of estimation methods. METHODS: The most suitable population PK model was explored and evaluated using non-linear mixed-effect modelling for the best fit of vancomycin concentrations from patients who needed to maintain high trough vancomycin concentrations of >10mg/L or >15mg/L. Renal function was estimated using the Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD) and CKD-EPI equations. NONMEM 7.4 was used to develop the population PK model. RESULTS: A total of 328 vancomycin concentrations in 99 patients were used to develop the population PK model. Vancomycin pharmacokinetics was best described by a two-compartment model. The CKD-EPI equation for vancomycin clearance was included in the final model among the estimation methods of renal function. A new covariate model, including extended covariate parameters that explain changes in renal function from the population-predicted value and individual dosing time, provided the best explanation for vancomycin pharmacokinetics among the various models tested. WHAT IS NEW ANDCONCLUSION: A new extended covariate model for vancomycin using the CKD-EPI method may afford suitable dose adjustment for high-strength and long-term vancomycin therapy that results in unstable renal function.

Continuous-Infusion Vancomycin in Neonates: Assessment of a Dosing Regimen and Therapeutic Proposal.

Introduction: Vancomycin remains the reference antibiotic in neonates for care-related infections caused by ß-lactam–resistant Gram-positive bacteria. Achieving the optimal serum vancomycin level is challenging because of high inter-individual variability and the drug's narrow therapeutic window. Continuous infusion might offer pharmacokinetic and practical advantages, but we lack consensus on the dosing regimen. The aim was to determine the proportion of neonates achieving an optimal therapeutic vancomycin level at the first vancomycin concentration assay and which dosing regimen is the most suitable for neonates.Methods: All neonates receiving continuous-infusion vancomycin (loading dose 15 mg/kg and maintenance dose 30 mg/kg/d) in a neonatal intensive care unit were retrospectively analyzed. The proportion of neonates reaching the target serum vancomycin level was calculated. After reviewing the literature to identify all published articles proposing a dosing regimen for continuous-infusion vancomycin for neonates, regimens were theoretically applied to our population by using maintenance doses according to covariate(s) proposed in the original publication.Results: Between January 2013 and December 2014, 75 neonates received 91 vancomycin courses by continuous infusion. Median gestational age, birth weight, and postnatal age were 27 weeks (interquartile range 26–30.5), 815 g (685–1,240), and 15 days (9–33). At the first assay, only 28/91 (30.8%) courses resulted in vancomycin levels between 20 and 30 mg/L (target level), 23/91 (25.3%) >30 mg/L and 40/91 (43.9%) <20 mg/L. We applied six published dosing regimens to our patients. One of these dosing regimens based on corrected gestational age (CGA) and serum creatinine level (SCR) would have allowed us to prescribe lower doses to neonates with high vancomycin levels and higher doses to neonates with low levels.Conclusions: A simplified dosing regimen of continuous-infusion vancomycin did not achieve therapeutic ranges in neonates; a patient-tailored dosing regimen taking into account CGA and SCR level or an individualized pharmacokinetic model can help to anticipate the inter-individual variability in neonates and would have been more suitable.

Comparison of biochemical and genotypic speciation methods for vancomycin-resistant enterococci isolated from urban wastewater treatment plants

Enterococci species in wastewater including Enterococcus faecalis, Enterococcus faecium, Enterococcus casseliflavus and Enterococcus gallinarum isolates (n = 308) with low or high level vancomycin resistance were determined and compared using a phenotypic method (RapID™ STR system), 16S rRNA sequencing, and multi-locus (atpA, groESL, and pheS) sequence analysis (MLSA). Error rates for the RapID™ STR system were E. faecalis (15.9%), E. faecium (21.5%), and E. casseliflavus/E. gallinarum (56.9%) when referenced to the consensus of all methods tested. Comparison of single nucleotide polymorphism (SNP) distances and phylogenetic trees suggested that the groESL locus delineated species more effectively than other loci. The groESL locus was the most reliable loci for the correct identification of Enterococcus spp., including E. casseliflavus and E. gallinarum, with high congruence compared to the consensus (Adjusted Rand Index = 0.954; Adjusted Wallace Co-efficient = 0.941). All of the methods were compared to whole genome sequencing, which acted as a gold standard, for the isolates from this study and those downloaded from NCBI.

The association of vancomycin trough levels with outcomes among patients with methicillin-resistant Staphylococcus aureus (MRSA) infections: Retrospective cohort study.

IntroductionCurrent guidelines recommend maintaining vancomycin trough concentrations between 15–20 mg/L for serious methicillin resistant staphylococcus aureus (MRSA) infections. This recommendation is based on limited evidence.MethodsA retrospective study including patients with vancomycin susceptible MRSA infections (MIC< = 2 mg/L), treated with vancomycin. We compared outcomes among patients attaining high (> = 15mg/L) vs low (<15mg/L) trough vancomycin levels. We used a propensity score to matching patients achieving low and high levels and conducted an adjusted analysis in the propensity score (PS)-matched cohort using regression analysis. Primary outcome was 30-day all-cause mortality.ResultsAmong 285 patients included, there were no significant differences between patients achieving high and low vancomycin levels in mortality (46/131, 35.1% vs 41/154, 26.6%), clinical success, microbiological success, or nephrotoxicity. Similarly, in the PS-matched cohort (n = 162), there was no significant difference in mortality between patients with high and low vancomycin levels (24/53, 45.3% vs 57/109, 52.3%, respectively), adjusted odds ratio for mortality with high levels 0.63 (95% confidence interval 0.28–1.43). In both cohorts, patients with pneumonia achieving high levels had significantly higher clinical and microbiological success (PS-matched cohort: clinical success: 16/32, 50.0% vs 5/27, 18.5%, p = 0.012; microbiological success: 19/32, 59.4% vs 7/27, 25.9%, p = 0.010), without significant differences in mortality.ConclusionsWe found no association between vancomycin levels > = 15 mg/L and clinical outcomes in patients with MRSA infections. In patients with MRSA pneumonia, vancomycin levels > = 15 mg/L were associated with higher clinical success rates. Further larger cohort studies are needed to define optimal vancomycin levels according to the site of infection.

Acute Tubular Necrosis Associated With High Serum Vancomycin and Tobramycin Levels After Revision of Total Knee Arthroplasty With Antibiotic-Containing Calcium Sulfate Beads.

We present the case of a 59-year-old male who developed acute tubular necrosis with a serum tobramycin level of 15.9 mg/L after instillation of tobramycin and vancomycin calcium sulfate beads for infected total knee arthroplasty. We emphasize standardizing surgical protocols to mitigate nephrotoxicity based on current efficacy and safety data.

Vancomycin-Associated Acute Kidney Injury in Critically Ill Adolescent and Young Adult Patients

Background: Risk factors for the development of vancomycin-associated acute kidney injury (AKI) have been evaluated in both pediatric and adult populations; however, no previous studies exist evaluating this in the critically ill adolescent and young adult patients. Objective: Identify the incidence of AKI and examine risk factors for the development of AKI in critically ill adolescents and young adults on vancomycin. Methods: This retrospective review evaluated the incidence of AKI in patients 15 to 25 years of age who received vancomycin, while admitted to an intensive care unit. Acute kidney injury in this population was defined as an increase in serum creatinine by 0.5 mg/dL or 50% from baseline. Patients who developed AKI were evaluated for specific risk factors compared to those who did not develop AKI. Results: A total of 50 patients (20 developed AKI) were included in the study. There was no difference in vancomycin daily dose or duration of vancomycin therapy. Maximum vancomycin trough (31.15 mg/dL vs 12.5 mg/dL, P = .006), percentage of patients with concurrent nephrotoxic medication (95% vs 60%, P = .012) and concurrent vasopressor (55% vs 23%, P = .029) were higher in those who developed AKI. Percentage of patients who underwent a procedure while on vancomycin (35% vs 6.7%, P = .021) was also higher within the AKI group. Conclusions: Vancomycin-associated AKI occurred in 40% of critically ill adolescent and young adult patients. These patients may be more likely to develop vancomycin-associated AKI if they had undergone a procedure, as well as in the presence of high vancomycin trough levels, concurrent nephrotoxic agents, and concurrent vasopressor therapy.

Vancomycin elution from a biphasic ceramic bone substitute.

ObjectivesThe aim of this study was to analyze drain fluid, blood, and urine simultaneously to follow the long-term release of vancomycin from a biphasic ceramic carrier in major hip surgery. Our hypothesis was that there would be high local vancomycin concentrations during the first week with safe low systemic trough levels and a complete antibiotic release during the first month.MethodsNine patients (six female, three male; mean age 75.3 years (sd 12.3; 44 to 84)) with trochanteric hip fractures had internal fixations. An injectable ceramic bone substitute, with hydroxyapatite in a calcium sulphate matrix, containing 66 mg of vancomycin per millilitre, was inserted to augment the fixation. The vancomycin elution was followed by simultaneously collecting drain fluid, blood, and urine.ResultsThe antibiotic concentration in the drain reached a peak during the first six hours post-surgery (mean 966.1 mg/l), which decreased linearly to a mean value of 88.3 mg/l at 2.5 days. In the urine, the vancomycin concentration reached 99.8 mg/l during the first two days, followed by a logarithmic decrease over the next two weeks to reach 0 mg/l at 20 days. The systemic concentration of vancomycin measured in blood serum was low and decreased linearly from 2.17 mg/l at one hour post-surgery to 0 mg/l at four days postoperatively.ConclusionThis is the first long-term pharmacokinetic study that reports vancomycin release from a biphasic injectable ceramic bone substitute. The study shows initial high targeted local vancomycin levels, sustained and complete release at three weeks, and systemic concentrations well below toxic levels. The plain ceramic bone substitute has been proven to regenerate bone but should also be useful in preventing bone infection.Cite this article: M. Stravinskas, M. Nilsson, A. Vitkauskiene, S. Tarasevicius, L. Lidgren. Vancomycin elution from a biphasic ceramic bone substitute. Bone Joint Res 2019;8:49–54. DOI: 10.1302/2046-3758.82.BJR-2018-0174.R2.

Low Serum Trough Concentrations and High Vancomycin Minimum Inhibitory Concentration in Methicillin-Sensitive Staphylococcus aureus From Hemodialysis Patients in Brazil.

The empiric antimicrobial therapy for bacteremia of long-term hemodialysis (HD) outpatients is currently based on the combination of vancomycin and gentamicin because of the high frequency of isolated Staphylococcus species. The vancomycin trough level range from 15 to 20 mcg/mL is expected for therapeutic success against methicillin-resistant Staphylococcus aureus with vancomycin minimum inhibitory concentration (MIC) ≥1.0 mcg/mL. Despite the availability of clinical practice guidelines for vancomycin therapeutic drug monitoring, these target serum concentrations are not reached in many patients. In this study, the authors investigated the vancomycin trough levels in 20 HD patients with S. aureus bacteremia and the antimicrobial susceptibility pattern of 45 S. aureus strains isolated from 45 HD patients. The vancomycin serum concentration was determined by chemiluminescent assay. The MIC was determined by broth microdilution method. None of the HD patients included in this study had vancomycin trough concentrations within the therapeutic range. Also, the vancomycin MIC for most methicillin-sensitive S. aureus isolated from bacteremia was ≥1.0 mcg/mL. The therapeutic range of vancomycin was not achieved, and vancomycin MIC was surprisingly high in methicillin-sensitive S. aureus.

Association between single trough-based area under the curve estimation of vancomycin and treatment outcome among methicillin-resistant Staphylococcus aureus bacteremia patients.

Failure of antibiotic treatment increases mortality of critically ill patients. This study investigated the association between the treatment resolution of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and vancomycin pharmacokinetic variables. A total of 28 critically ill patients were included in this study. All data were collected from medical, microbiology and pharmacokinetic records. The clinical response was evaluated on the basis of clinical and microbiological parameters. The 24-h area under the curve (AUC<SUB>0-24</SUB>) was estimated from a single trough level using established equations. Out of the 28 patients, 46% were classified as responders to vancomycin treatment. The trough vancomycin concentration did not differ between the responders and non-responders (15.02 ± 6.16 and 14.83 ± 4.80 μg mL^-1; P = 0.929). High vancomycin minimum inhibitory concentration (MIC) was observed among the non-responders (P = 0.007). The ratio between vancomycin trough concentration and vancomycin MIC was significantly lower in the non-responder group (8.76 ± 3.43 vs. 12.29 ± 4.85 μg mL^-1; P = 0.034). The mean ratio of estimated AUC<SUB>0-24</SUB> and vancomycin MIC was 313.78 ± 117.17 μg h mL^-1 in the non-responder group and 464.44 ± 139.06 μg h mL^-1 in the responder group (P = 0.004). AUC<SUB>0-24</SUB>/MIC of ≥ 400 μg h mL^-1 was documented for 77% of the responders and 27% of the non-responders (c² = 7.03; P = 0.008). Ratio of trough concentration/MIC and AUC<SUB>0-24</SUB>/MIC of vancomycin are better predictors for MRSA treatment outcomes than trough vancomycin concentration or AUC<SUB>0-24</SUB> alone. The single trough-based estimated AUC may be sufficient for the monitoring of treatment response with vancomycin.

Effect of intrasite vancomycin powder on development of epidural fibrosis

Placement of vancomycin powder into the surgical wound prior to closure has been shown to reduce postoperative infections in spine surgery. This study examines the effect of vancomycin powder on formation of epidural fibrosis (EF). Twenty-two rats underwent a two-level lumbar laminectomy. A control group, a low-dose and a high dose vancomycin powder (applied prior to closure) group was formed. Rats were sacrificed at 30 days and a blinded fellowshiptrained pathologist evaluated the laminectomy segments for EF. 50% of the samples in the high-dose vancomycin group were EF grade 3, compared to 20% of the low-dose and 16.7% of control samples. The average fibrosis grade for the high dose, low dose and control groups were 2.4, 1.4 and 1.8, respectively. There were more grade 3 EF specimens in the high dose vancomycin group. While the average EF grade was also higher in this group, there was not a statistical difference compared with the other groups.

Administration of Vancomycin at High Doses in Patients with Post Neurosurgical Meningitis: A Comprehensive Comparison between Continuous Infusion and Intermittent Infusion.

Poor penetration of vancomycin into Central Nervous System (CNS) can lead to treatment failure. The aim of this study was to evaluate and compare CSF concentration and serum pharmacokinetics of high dose vancomycin by continuous infusion vs. intermittent infusion in post neurosurgical meningitis patients. Twenty patients were divided into two groups. Patients in intermittent infusion group received vancomycin as a loading dose of 25 mg/kg over two hours, followed by 25 mg/kg over two hours every 12 h. In the Continuous Infusion group, patients received vancomycin as a loading dose of 25 mg/kg over two hours, followed by 50 mg/kg/day by continuous infusion. In the intermittent infusion group, mean ± SD of serum trough, peak and CSF concentrations were 17.49 ± 2.46 mg/L, 41.33 ± 2.73 mg/L, and 4.83 ± 1.05 mg/L, respectively. Mean of CSF/trough% ratio was 27.39 ± 2.43%. A positive linear correlation was found between the serum trough levels and CSF levels (r = 0.970, P < 0.001). In continuous infusion group, mean ± SD of serum and CSF concentrations were 24.76 ± 2.02 mg/L and 6.20 ± 1.31 mg/L respectively. Mean ± SD of CSF/serum% ratio was 24.84% ± 3.54%. The serum and CSF levels revealed positive linear correlation (r = 0.902, P < 0.001). The mean of CSF concentration in CI group was 6.20 ± 1.31 mg/L which was significantly higher than II group (4.83 ± 1.05 mg/L, P < 0.019). CSF/serum ratio did not show any significant difference between the two groups. Continuous infusion of vancomycin makes it possible to achieve faster and constant target level in serum but did not have any significant effect on the penetration (CSF/Serum ratio) of vancomycin in to the CNS.

1871. Identifying Time Periods of High and Low Vancomycin Use

BackgroundA national goal has been set to decrease inappropriate antibiotic use by 2020. To quantify decreases in use, consumption metrics and benchmarking strategies are implicit. However, while tracking and reporting antimicrobial use is widely recommended, these data do not address appropriateness. Accordingly, we developed a methodology to identify and report high and low vancomycin use periods which may represent inappropriate or unsafe antimicrobial use.MethodsThis is an observational, retrospective study of facility-wide vancomycin consumption data, aggregated, and examined on a hospital level from three academic medical centers: Northwestern Medicine (NM), Michigan Medicine (UM), and Henry Ford (HF) Hospital. Utilization was quantified as antimicrobial days (AD) per 1,000 days present (DP) on a monthly basis, recorded over 46 consecutive months (January 2014 through October 2017) for NM and HF, and 40 consecutive months (July 2014 through October 2017) for UM. Linear regression models and prediction intervals were generated to identify high-usage months. Use exceeding the upper bound of a prediction interval of 80 percent in a given month was used to define increased use, and the lower bound was used to define decreased use.ResultsVancomycin use averaged 70.3 AD per 1,000 DP at NM, 89 at UM, and 153.8 at HF. Regression models indicated HF and UM consumption decreased at a monthly rate of 1.2 AD per 1,000 DP and 0.1 AD per 1,000 DP, respectively, whereas NM use increased at a rate of 0.1 AD per 1,000 DP over the study period. Overall, we identified n = 6, n = 5 and n = 6 vancomycin increased use months and n = 7, n = 6 and n = 5 decreased use months at NM, UM and HF, respectively.ConclusionOur methodology identified a total of 17 potential instances of increased and 18 decreased use periods for vancomycin. Patient-specific and/or hospital-level factors may contribute to inappropriate vancomycin use and requires further study. The relationship between increased or decreased antibiotic use and appropriateness should be a focus in future efforts. Once the link between use and appropriateness is known, interventions can target specific use periods to maximize benefit of the intervention.Disclosures J. Liu, Merck: Grant fund from Merck, Research grant. S. Davis, Achaogen: Consultant and Scientific Advisor, Consulting fee. Allergan: Consultant and Scientific Advisor, Consulting fee. Melinta: Consultant and Scientific Advisor, Consulting fee. Nabriva: Consultant and Scientific Advisor, Consulting fee. Zavante: Consultant and Scientific Advisor, Consulting fee. T. S. Patel, Merck: Grant Investigator, Research grant. K. Kaye, Zavante Therapeutics, Inc.: Scientific Advisor, Consulting fee. M. H. Scheetz, Merck & Co., Inc.: Grant Investigator, Grant recipient. Bayer: Consultant, Consulting fee.

Rash induced by enteral vancomycin therapy in an older patient in a long-term care ventilator unit: case report and review of the literature

BackgroundOral vancomycin is a first-line treatment for severe Clostridium difficile colitis. Oral vancomycin is perceived to lack systemic absorption or systemic adverse effects; however, a few cases of hypersensitivity to oral vancomycin have been reported, all in hospitalized patients.Case presentationIn the present case, a 66-year-old woman with end-stage neurodegenerative disease residing in a long-term care facility developed a maculopapular rash following treatment with enteral vancomycin for recurrent C. difficile colitis. The rash resolved after withdrawal of the drug.ConclusionRashes associated with oral vancomycin treatment include maculopapular rash, urticaria, red man syndrome, and linear IgA bullous dermatitis. Risk factors for systemic vancomycin absorption include renal insufficiency, severe intestinal inflammation, and high vancomycin dose and duration. Routine serum testing of vancomycin levels, even in these high risk cases, is not recommended. Clinicians should be aware that enteral vancomycin can cause hypersensitivity reactions which may be serious.

The impact of vancomycin trough concentrations on outcomes in non-deep seated infections: a retrospective cohort study

BackgroundGuidelines recommending vancomycin trough concentrations > 10 mg/L in non-deep seated infections are based on expert opinion. The objective of this study was to evaluate patients with non-deep seated infections treated with short-course vancomycin to determine whether there were differences in outcomes with trough concentrations of ≤10 mg/L (low) versus > 10 mg/L (high).MethodsA retrospective cohort study of patients hospitalized between March 10, 2010 and December 31, 2015 who received ≤14 days of vancomycin to treat a non-deep seated infection and had at least one steady state trough concentration was completed. Patient data for the low versus high trough cohorts were compared using appropriate statistical tests and binary logistic regression was used to identify factors associated with clinical outcome.ResultsOf 2098 patients screened, 103 (5%) met inclusion criteria. Baseline characteristics between cohorts were not different. Clinical cure was not different between the low (42/48 [88%]) and high trough (48/55 [87%]) cohorts (p > 0.99) and vancomycin trough concentration was not associated with clinical outcome (p = 0.973). More patients in the high trough group had dosing changes (7/48 [15%] vs. 22/55 [40%], p = 0.0046), with approximately three times more dose adjustments per patient (0.17 vs. 0.55, p = 0.0193). No signal for increased vancomycin resistance associated with vancomycin troughs was identified.Conclusions:No difference in clinical or microbiological outcomes based on vancomycin trough concentrations were observed in patients with non-deep seated infections treated with vancomycin for ≤14 days. Targeting higher vancomycin trough concentrations of > 10 mg/L may be associated with increased workload with no corresponding benefit in clinical or microbiological outcomes in these patients.

A randomized phase 2B trial of vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations \u2013 results of a prematurely terminated study

BackgroundStudies have suggested the reduced effectiveness of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections with high vancomycin minimum inhibitory concentrations. Alternative agents such as daptomycin may be considered. We conducted a randomized controlled study comparing daptomycin against vancomycin in the treatment of MRSA bloodstream infections with high vancomycin minimum inhibitory concentrations.MethodsPatients were randomized to receive vancomycin or daptomycin for a minimum of 14 days. The primary end point was the rate of all-cause mortality at day 60.ResultsA total of 14 patients were randomized in this study, with 7 patients in each treatment arm. The study was terminated early due to slow patient accrual. At day 60, there was one death in the vancomycin arm and none in the daptomycin arm. The median time to microbiological clearance was 4 days in both arms (IQR 3–5 days in the vancomycin arm and 3–7 days in daptomycin arm). Only one patient in the vancomycin arm had recurrence of bacteremia. Rates of adverse events were similar in both arms. There was one case of musculoskeletal toxicity and one case of drug-related nephrotoxicity - both events occurred in the daptomycin arm. None of the patients in either treatment arm required cessation of study treatment or addition of a second anti-MRSA agent because of worsening infection.ConclusionBased on the limited number of patients evaluated in this study, it remains unclear if alternative, more expensive agents such as daptomycin are superior to vancomycin in the treatment of high vancomycin minimum inhibitory concentration MRSA bloodstream infections. More studies are urgently needed but investigators may wish to consider employing novel, alternative trial methodologies to ensure a greater chance of success.Trial registrationClinicalTrials.gov, NCT01975662. Registered on 5 November 2013.

Enhanced Efficacy of High Dose Oral Vancomycin Therapy in Clostridium difficile Diarrhea for Hospitalized Adults Not Responsive to Conventional Oral Vancomycin Therapy: Antibiotic Stewardship Implications.

Current therapy of Clostridium difficile diarrhea (CDD) is problematic. Optimal treatment for CDD remains oral vancomycin, but there is little data on oral vancomycin dosing regimens. The objective of this C. difficile diarrhea study was to compare the efficacy of “high dose” vancomycin, 500 mg (PO) q6h, as sole treatment and in those who after 72 h failed to respond to conventional doses of oral vancomycin, 125–250 mg (PO) q6h. Hospitalized adults with CDD were evaluated by various oral vancomycin regimens, i.e., a conventional dose group (125–250 mg (PO) q6h), a “high dose escalation” dose group (250 mg → 500 mg (PO) q6h), and a “high dose” group (500 mg (PO) q6h). Oral vancomycin treatment groups were compared by time to improvement, i.e., decrease in >50% of watery stools/day and duration of therapy. The high dose escalation and high dose oral vancomycin groups showed the most rapid resolution of diarrhea. There was marked decrease in stools/day after “high dose” vancomycin escalation from conventional dosing, i.e., 250 mg (PO) q6h → 500 mg (PO) q6h. This study demonstrated that “high dose” escalation or initial high dose oral vancomycin, i.e., 500 mg (PO) q6h was the most efficacious regimen for CDD.

Vancomycin and daptomycin minimum inhibitory concentrations as a predictor of outcome of methicillin-resistant Staphylococcus aureus bacteraemia.

The aim of this study was to determine the persistence of the adverse prognostic effect of elevated vancomycin minimum inhibitory concentration (MIC) in methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in a setting with low vancomycin use. A retrospective study focusing on episodes of bacteraemia due to MRSA diagnosed from January 2010 through December 2015 was designed. The main outcome measures were 30-day mortality and treatment failure. Multivariate logistic regression analysis was used to identify variables associated with patient mortality and treatment outcome. In total, 79 MRSA bacteraemia episodes were included. The vancomycin MIC was >1.0μg/mL in 53 episodes (67.1%). The presence of high vancomycin MIC was not associated with a higher mortality rate or treatment success. A daptomycin MIC≥0.5μg/mL was present in 16 (26.2%) of 61 episodes for which the daptomycin MIC was obtained and was associated with 30-day mortality in the multivariate analysis (odds ratio=4.72, 95% confidence interval 1.19-18.71). None of the antimicrobials used were associated with a lower risk of treatment failure or mortality. The pernicious effect of high vancomycin MIC disappears in the absence of a predominant use of this antibiotic. However, a high daptomycin MIC in MRSA bacteraemia is associated with higher mortality in patients with bacteraemia, irrespective of antimicrobial treatment choice.

Polydopamine-assisted functionalization of heparin and vancomycin onto microarc-oxidized 3D printed porous Ti6Al4V for improved hemocompatibility, osteogenic and anti-infection potencies

Enhanced antiinfection activities, improved hemocompatibility and osteo-compatibility, and reinforced osseointegration are among the most important considerations in designing multifunctional orthopedic biomaterials. Hereby, anti-infective and osteogenic multifunctional 3D printed porous Ti6Al4V implant with excellent hemocompatibility was successfully designed and fabricated. In brief, osteogenic micro-arc oxidation (MAO) coatings with micro/nanoscale porous topography were generated in situ on 3D printed Ti6Al4V scaffolds, on which heparin and vancomycin were easily immobilized. The surface microstructure, morphology, and chemical compositions were characterized employing scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). High loading capacity and sustained vancomycin release profiles were revealed using high performance liquid chromatography (HPLC). Favorable antibacterial and antibiofilm performances against pathogenic Staphylococcus aureus ( S. aureus ) were validated in vitro through microbial viability assays, Live/Dead bacterial staining, and crystal violet staining. Human mesenchymal stem cells (hMSCs) were seeded on the scaffolds and their proliferation and viability were assessed using Cell Counting Kit and Live/Dead cell viability kit. Further, osteoblastic differentiation abilities were evaluated using alkaline phosphatase (ALP) activity as a hall marker. Additionally, the improved hemocompatibility of the heparinized scaffolds was confirmed by activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). Overall, our results show that the surface-modified 3D printed porous Ti6Al4V possesses balanced antibacterial and osteogenic functions while exhibiting extra anticlotting effects, boding well for future application in customized functional reconstruction of intricate bone defects.