Impact of Vancomycin Loading Doses and Dose Escalation on Glomerular Function and Kidney Injury Biomarkers in a Translational Rat Model.

Vancomycin-induced kidney injury is common, and outcomes in humans are well predicted by animal models. This study employed our translational rat model to investigate temporal changes in the glomerular filtration rate (GFR) and correlations with kidney injury biomarkers related to various vancomycin dosing strategies. First, Sprague-Dawley rats received allometrically scaled loading doses or standard doses. Rats that received a loading dose had low GFRs and increased urinary injury biomarkers (kidney injury molecule 1 [KIM-1] and clusterin) that persisted through day 2 compared to those that did not receive a loading dose. Second, we compared low and high allometrically scaled vancomycin doses to a positive acute kidney injury control of high-dose folic acid. Rats in both the low- and high-dose vancomycin groups had higher GFRs on all dosing days than the positive-control group. When the two vancomycin groups were compared, rats that received the low dose had significantly higher GFRs on days 1, 2, and 4. Compared to low-dose vancomycin, the KIM-1 was elevated among rats in the high-dose group on dosing day 3. The GFR correlated most closely with the urinary injury biomarker KIM-1 on all experimental days. Vancomycin loading doses were associated with significant losses of kidney function and elevations of urinary injury biomarkers. In our translational rat model, both the degree of kidney function decline and urinary biomarker increases corresponded to the magnitude of the vancomycin dose (i.e., a higher dose resulted in worse outcomes).

Saireito, a Japanese herbal medicine, alleviates leaky gut associated with antibiotic-induced dysbiosis in mice.

Antibiotics disrupt normal gut microbiota and cause dysbiosis, leading to a reduction in intestinal epithelial barrier function. Disruption of the intestinal epithelial barrier, which is known as "leaky gut", results in increased intestinal permeability and contributes to the development or exacerbation of gastrointestinal diseases such as inflammatory bowel disease and irritable bowel syndrome. We have previously reported on a murine model of intestinal epithelial barrier dysfunction associated with dysbiosis induced by the administration of ampicillin and vancomycin. Saireito, a traditional Japanese herbal medicine, is often used to treat autoimmune disorders including ulcerative colitis; the possible mechanism of action and its efficacy, however, remains unclear. In this study, we examined the efficacy of Saireito in our animal model for leaky gut associated with dysbiosis. C57BL/6 mice were fed a Saireito diet for the entirety of the protocol (day1-28). To induce colitis, ampicillin and vancomycin were administered in drinking water for the last seven consecutive days (day22-28). As previously demonstrated, treatment with antibiotics caused fecal occult bleeding, cecum enlargement with black discoloration, colon inflammation with epithelial cell apoptosis, and upregulation of pro-inflammatory cytokines. Oral administration of Saireito significantly improved antibiotics-induced fecal occult bleeding and cecum enlargement by suppressing inflammation in the colon. Furthermore, Saireito treatment ensured the integrity of the intestinal epithelial barrier by suppressing apoptosis and inducing cell adhesion proteins including ZO-1, occludin, and E-cadherin in intestinal epithelial cells, which in turn decreased intestinal epithelial permeability. Moreover, the reduced microbial diversity seen in the gut of mice treated with antibiotics was remarkably improved with the administration of Saireito. In addition, Saireito altered the composition of gut microbiota in these mice. These results suggest that Saireito alleviates leaky gut caused by antibiotic-induced dysbiosis. Our findings provide a potentially new therapeutic strategy for antibiotic-related gastrointestinal disorders.

Outpatient vancomycin therapy: Acute kidney injury in individualized AUC-based goal trough ranges versus traditional trough dosing.

BACKGROUND: Recent changes to vancomycin guidelines recommend area under the curve concentration (AUC) monitoring in most patients, owing to similar effectiveness and reduced rates of acute kidney injury (AKI). OBJECTIVE: The purpose of this study was to assess the incidence of AKI in patients receiving vancomycin dosed by AUC-based goal troughs and vancomycin dosed by traditional trough goals (15-20 mcg/mL) in the outpatient setting. METHODS: Patients were included if they received vancomycin outpatient for at least 1 week. The primary objective was comparing the incidence of AKI in patients receiving vancomycin as an outpatient with trough goals derived from patient-specific AUC calculations determined as an inpatient with that of patients receiving vancomycin by traditional goal troughs. Secondary objectives included assessing the rate of treatment failure, AUC estimated trough range, and number of regimen changes required. RESULTS: There were 65 patients in the traditional trough dosing group and 53 patients in the AUC trough dosing group. The incidence of AKI was lower in the AUC trough group (5.7% vs. 23.1%; P = 0.01). There were no differences in the incidence of treatment failure. The median AUC estimated trough range was 11.4-17.1 mcg/mL. There were statistically significant less average regimen changes required in the AUC dosing group (1.13 vs. 1.64; P = 0.006). CONCLUSION: There was a statistically significant lower incidence of AKI in patients receiving vancomycin dosed by individualized AUC-based trough ranges compared with that of patients receiving traditional trough dosing. Developing a process for individualized AUC-based trough ranges can facilitate a convenient monitoring method to use the benefits of vancomycin AUC dosing as an outpatient.

Renoprotective Effects of Melatonin against Vancomycin-Related Acute Kidney Injury in Hospitalized Patients: a Retrospective Cohort Study.

Vancomycin is associated with nephrotoxicity, and the mechanism may in part be related to oxidative stress. In vitro and preclinical studies suggest that melatonin supplementation decreases oxidative stress. The objective of this study was to evaluate concomitant use of melatonin and vancomycin and the incidence of acute kidney injury (AKI). We performed a retrospective cohort study at a large community medical center. All consecutive patients admitted to the medical center between January 2016 and September 2020 who received vancomycin therapy alone or concomitantly with melatonin as part of ordinary care were considered for inclusion. The primary endpoint was the development of AKI, defined as an absolute increase in serum creatinine of ≥0.3 mg/dl or a ≥50% increase in serum creatinine. All data were analyzed using descriptive statistics. A multivariable logistic regression was constructed to account for potential confounding variables. We identified a total of 303 adult patients meeting inclusion and exclusion criteria treated with vancomycin, 101 of which received melatonin concomitantly. Overall baseline characteristics were similar between the two groups except for the incidence of bacteremia/sepsis. After controlling for the vancomycin area under the curve, baseline creatinine clearance, and intensive care unit admission in a multivariable logistic regression analysis, melatonin use was associated with a 63% decrease in AKI (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.14 to 0.96; P = 0.041). Melatonin use was associated with a significant reduction in vancomycin-related AKI. Although this was a retrospective study with a small sample size, given the magnitude of the difference seen, further large prospective studies are warranted.

Outcomes of a pharmacist-driven vancomycin monitoring initiative in a community hospital.

WHAT IS KNOWN AND OBJECTIVE: Vancomycin, an antibiotic commonly used to treat MRSA infections, can be nephrotoxic. Administering vancomycin requires close monitoring of serum vancomycin levels and appropriate dosing based on patients' renal function, underlying infection type and serum concentration levels. This article discusses the results and implications of a pharmacist-driven vancomycin monitoring initiative, which was implemented at Mercy Catholic Medical Center's Philadelphia Campus (MPC) in July 2016. METHODS: MPC pharmacists were trained on how to give appropriate vancomycin dosing recommendations based on patients' vancomycin trough levels, renal function and underlying infection. This retrospective observational study consisted of patients who presented to MPC and were administered vancomycin over a 3-month period in 2015 for pre-implementation cohort and over a 3-month period in 2018 for post-implementation cohort. Patients with age ≥18 and receiving vancomycin for a minimum of 48 hours were included, whereas ESRD patients were excluded. Primary goal evaluated whether the incidence of AKI decreased with the pharmacist-driven initiative. Secondary goal assessed whether vancomycin level monitoring and achievement of goal serum levels improved with the initiative. RESULTS AND DISCUSSION: A total of 214 patients were included in the final data analysis, with 110 patients in the pre-implementation cohort and 104 patients in the post-implementation cohort. Although not statistically significant, a higher incidence of AKI was observed in the post-implementation cohort. However, compared to pre-implementation cohort, post-implementation group had higher percentage of patients with underlying comorbidities (such as CKD), higher number of cases of severe sepsis and septic shock, and greater number of patients with concomitant exposure to CT contrast and piperacillin-tazobactam-all of which were confounding factors that likely increased the AKI incidence in post-implementation cohort. With the initiative, there was a significant increase in the number of patients with appropriate vancomycin trough level monitoring (27.3% vs 55.8%, p value < 0.001) in the post-implementation cohort and a decrease in the number of patients with no trough level monitoring (30% vs. 7.6%, p value < 0.001). WHAT IS NEW AND CONCLUSION: Pharmacist-driven vancomycin monitoring significantly improved the monitoring compliance of vancomycin trough levels. In patients who developed AKI during their hospital course, pharmacist interventions improved the total percentage of patients attaining desired trough goals and helped reduce further renal insult from supratherapeutic vancomycin level. Incorporation of AUC-guided dosing and monitoring has the potential to further optimize vancomycin efficacy and safety.

AUCs and 123s: a critical appraisal of vancomycin therapeutic drug monitoring in paediatrics.

The revised vancomycin guidelines recommend implementing AUC24-based therapeutic drug monitoring (TDM) using Bayesian methods in both adults and paediatrics. The motivation for this change was accumulating evidence showing aggressive dosing to achieve high troughs, as recommended in the first guidelines for adults and extrapolated to paediatrics, is associated with increased nephrotoxicity without improving clinical outcomes. AUC24-based TDM requires substantial resources that may need to be diverted from other valuable interventions. It can therefore be justified only after certain assumptions are shown to be true: (i) there is a clear relationship between vancomycin efficacy and/or toxicity and the proposed therapeutic range; and (ii) maintaining exposure within the target range with AUC24-based TDM improves clinical outcomes and/or decreases toxicity. In this review, we critically appraise the scientific basis for these assumptions. We find studies evaluating the relationship between vancomycin AUC24/MIC and efficacy in adults and children do not offer strong support for the recommended lower limit of the proposed therapeutic range (i.e. AUC24/MIC ≥400). Nephrotoxicity in children increases in a stepwise manner along the vancomycin exposure continuum but it is unclear if one parameter (AUC24 versus trough) is a superior predictor. Overall, evidence in children suggests good-to-excellent correlation between AUC24 and trough. Most importantly, there is no convincing evidence that the method of vancomycin TDM has a causal role in improving efficacy or reducing toxicity. These findings question the need to transition to resource-intensive AUC24-based TDM over retaining trough-based TDM with lower targets to minimize nephrotoxicity in paediatrics.

Reduced nephrotoxicity with vancomycin therapeutic drug monitoring guided by area under the concentration-time curve against a trough 15-20 µg/mL concentration.

Vancomycin is often employed as an antibacterial agent against Gram-positive bacteria, although dose-dependent nephrotoxicity is a concern. Although the risk may be reduced by therapeutic drug monitoring (TDM) guided by area under the concentration-time curve (an attempt to target an AUC > 400 µg•h/mL by Bayesian prediction: AUC400-guided TDM), the clinical efficacy of AUC400-guided TDM compared with trough concentration-guided TDM within 15-20 µg/mL (Trough15-20-guided TDM) has yet to be determined. We aimed to retrospectively evaluate the difference in the incidence rate of acute kidney injury (AKI), classified according to the Acute Kidney Injury Network, between these TDM groups. Individual AUC in the AUC400-guided TDM group was calculated by Bayesian prediction using trough and peak concentrations (within 3 h after the end of infusion). The AKI incidence in the Trough15-20-guided TDM group was 28.8% (15/52 patients) compared with an AKI incidence in the AUC400-guided TDM group of 9.1% (2/22 patients). Application of AUC400-guided TDM was identified as an independent factor for avoiding the incidence of AKI by Cox hazard regression analysis [hazard ratio = 0.168, 95% confidence interval (CI) 0.034-0.839] and logistic regression analysis (odds ratio = 0.037, 95% CI 0.003-0.285). As the estimated glomerular filtration rate (eGFR) improved, the surrogate target trough concentration for an AUC > 400 µg•h/mL was lowered (intercept 15.0074, slope -0.0598). In conclusion, AUC400-guided TDM may be superior to Trough15-20-guided TDM for the reduction of nephrotoxicity during vancomycin therapy.

Chlorogenic acid prevents vancomycin-induced nephrotoxicity without compromising vancomycin antibacterial properties.

Vancomycin (VCM) is an effective chemotherapeutic agent commonly used against gram-positive microorganisms but has serious nephrotoxic side effects that limit its effectiveness. New therapeutics and strategies are urgently needed to combat VCM associated nephrotoxicity. In this study, we determined the protective effect of chlorogenic acid (CA) in a rat model of VCM-induced nephrotoxicity. VCM administration led to markedly elevated blood urea nitrogen and serum creatinine levels that could be prevented with CA co-administration. VCM-mediated oxidative stress was also significantly attenuated by CA as reflected by decreased malondialdehyde and nitric oxide in VCM-treated kidneys. CA administration also prevented the VCM-mediated decrease in the renal antioxidative enzyme activities of glutathione reductase, glutathione peroxidase, and catalase and led to increased levels of reduced glutathione that had been depleted by VCM. Moreover, CA administration clearly inhibited VCM-induced expression of nuclear factor-kappa B, inducible nitric oxide synthase and the downstream pro-inflammatory mediators tumor necrosis factor-α and interleukins 1ß and 6. Apoptotic markers were also markedly down-regulated with CA. Overall, CA treatment mitigated VCM-induced oxidative and nitrosative stresses and countered the apoptotic and inflammatory effects of VCM. Notably, CA did not affect the antibacterial activity of VCM in vitro.

[High dose vitamin C significantly reduces the nephrotoxicity of vancomycin in critically ill patients].

OBJECTIVE: To observe the changes of renal function in critically ill patients using vancomycin and analyze the renal protective effect of high dose vitamin C (VC) on vancomycin nephrotoxicity. METHODS: Retrospective analysis was carried out to enroll the patients who were hospitalized in emergency intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2012 to October 2019. All patients were administered with vancomycin or VC infusion in addition. According to the infusion of vancomycin alone or in combination with VC, the patients were divided into vancomycin group and vancomycin in combination with VC group; vancomycin group was further divided into two groups according to before vancomycin or after vancomycin usage; combination group were further divided into two groups according to before VC use or after VC. The initial dosage of vancomycin was calculated according to the actual weight of the patient and adjusted according to the renal function. The dosage of VC was determined according to the disease severity of the patient, and the dosage range was 50-200 mg×kg-1×d-1, continuously infused into the body. The age, gender, weight and renal function etc. were recorded and analyzed. RESULTS: A total of 245 patients who met the requirements were included in the analysis. There were 127 patients in the vancomycin group and 118 patients in the combination group. The causes of patients admitted to ICU were pulmonary infection, sepsis, severe acute pancreatitis, etc. Among them, pulmonary infection accounted for 63.0% in vancomycin group, while severe acute pancreatitis accounted for 61.9% in combination group. The quick sequential organ failure assessment (qSOFA) score of combination group was significantly higher than that of vancomycin group [1.0 (0, 1.0) vs. 0 (0, 0.2), P < 0.01], its basic renal function was also significantly worse [serum creatinine (SCr, µmol/L): 98.0 (65.0, 178.2) vs. 56.0 (42.2, 71.0), blood urea nitrogen (BUN, mmol/L): 11.30 (6.48, 18.38) vs. 4.70 (3.45, 8.10), both P < 0.05], and the average daily dose of vancomycin was also significantly lower than that of vancomycin group (mg×kg-1×d-1: 23.0±9.4 vs. 26.6±8.5, P < 0.01). Compared with vancomycin before administration, the renal function was getting worse significantly after vancomycin administration [SCr (µmol/L): 68.0 (50.2, 104.5) vs. 56.0 (42.2, 71.0), BUN (mmol/L): 5.35 (3.75, 9.83) vs. 4.70 (3.45, 8.10), both P < 0.05]. Combination with VC significantly improved renal function compared with that before VC treatment [SCr (µmol/L): 79.0 (58.0, 129.0) vs. 98.0 (65.0, 178.2), P < 0.05; BUN (mmol/L): 9.60 (6.10, 18.30) vs. 11.30 (6.48, 18.38), P > 0.05] and shortened the length of ICU stay [days: 28.5 (14.8, 54.2) vs. 37.0 (25.0, 55.0), P < 0.01]. CONCLUSIONS: The incidence of drug-induced renal injury caused by vancomycin is high. Intravenous high dose VC can significantly reduce the nephrotoxicity of vancomycin and shorten the length of hospital stay. When vancomycin is used in critically ill patients, VC can be used in combination to reduce or avoid drug-induced renal injury, improve curative effect and reduce toxic effects.

Vancomycin-resistant Enterococcus faecium pneumonia in a uremic patient on hemodialysis: a case report and review of the literature.

BACKGROUND: Even though enterococci can cause serious infections in multiple sites, they are a rare cause of pneumonia. We reported a uremic patient with vancomycin-resistant E. faecium (VRE-fm) pneumonia, possibly related to epileptic seizures. CASE PRESENTATION: A 57-year old man with uremia on hemodialysis was admitted to the hospital with complaint of recurrent epileptic seizures, followed by a two-week history of recurrent fever and cough with purulent sputum. Chest CT demonstrated multiple exudation of both lungs. He was diagnosed as community acquired pneumonia. Despite antibiotic combination therapy, abnormal chest shadows aggravated. Sputum and blood cultures were initially negative, but later blood culture grew VRE-fm. We suspected aspiration of gastrointestinal content induced by epilepsy as the most likely mechanism. The patient was successfully treated with a four-week course of linezolid according to the antibiotic susceptibility testing. CONCLUSIONS: Physicians should consider multi-drug resistant organisms such as VRE in uremic patients with pneumonia that fails to resolve with broad-spectrum antibiotics, especially in the cases with aspiration induced by epilepsy, immunocompromised conditions, and repeated or prolonged hospitalizations.

MrgX2 is a promiscuous receptor for basic peptides causing mast cell pseudo-allergic and anaphylactoid reactions.

Activation of MrgX2, an orphan G protein-coupled receptor expressed on mast cells, leads to degranulation and histamine release. Human MrgX2 binds promiscuously to structurally diverse peptides and small molecules that tend to have basic properties (basic secretagogues), resulting in acute histamine-like adverse drug reactions of injected therapeutic agents. We set out to identify MrgX2 orthologues from other mammalian species used in nonclinical stages of drug development. Previously, the only known orthologue of human MrgX2 was from mouse, encoded by Mrgprb2. MrgX2 genes of rat, dog (beagle), minipig, pig, and Rhesus and cynomolgus monkey were identified by bioinformatic approaches and verified by their ability to mediate calcium mobilization in transfected cells in response to the classical MrgX2 agonist, compound 48/80. The peptide GSK3212448 is an inhibitor of the PRC2 epigenetic regulator that caused profound anaphylactoid reactions upon intravenous infusion to rat. We showed GSK3212448 to be a potent MrgX2 agonist particularly at rat MrgX2. We screened sets of drug-like molecules and peptides to confirm the highly promiscuous nature of MrgX2. Approximately 20% of drug-like molecules activated MrgX2 (pEC50 ranging from 4.5 to 6), with the principle determinant being basicity. All peptides tested of net charge +3 or greater exhibited agonist activity, including the cell penetrating peptides polyarginine (acetyl-Arg9-amide) and TAT (49-60), a fragment of HIV-1 TAT protein. Finally, we showed that the glycopeptide antibiotic vancomycin, which is associated with clinical pseudo-allergic reactions known as red man syndrome, is an agonist of MrgX2.

High-Dose Vitamin C Preadministration Reduces Vancomycin-Associated Nephrotoxicity in Mice.

Vancomycin is recommended for treating severe infections caused by Gram-positive cocci, including methicillin-resistant Staphylococcus aureus. However, renal damage often occurs as a side effect because vancomycin is mainly excreted via the kidneys. The mechanism of vancomycin-associated nephrotoxicity is thought to involve the elevation of oxidative stress in the kidneys. Vitamin C (VC) has strong antioxidant properties; therefore, we evaluated the effect of high-dose VC preadministration on vancomycin-associated nephrotoxicity. Vancomycin was intraperitoneally injected into mice once daily for 7 d. Additionally, high-dose VC was intraperitoneally injected into mice at 30 min before vancomycin administration for 7 d. The plasma creatinine and urea nitrogen levels were increased by vancomycin treatment; however, high-dose VC preadministration suppressed the increase in these levels. Histological examination also revealed that high-dose VC preadministration reduced the characteristics of vancomycin-associated nephrotoxicity, such as dilated renal tubules with casts, the dilation of renal proximal tubules, and tubular epithelial desquamation. Furthermore, high-dose VC preadministration reduced the appearance of apoptotic cells presumably derived from the epithelial cells in the dilated proximal tubules. Thus, intraperitoneally injected high-dose VC preadministration reduced vancomycin-associated nephrotoxicity in mice. These novel findings may indicate that vancomycin-associated nephrotoxicity in humans may be reduced by high-dose VC preadministration.

Detection of heterogeneous vancomycin-intermediate Staphylococcus aureus: A preliminary report from south India.

Background & objectives: Although there are reports of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) across the globe, there is a lack of reliable data on hVISA in India. The present study was undertaken to determine the rate of hVISA among the methicillin-resistant Staphylococcus aureus (MRSA) isolates, and to compare the brain heart infusion agar with vancomycin 4 µg/ml (BHIV4) method with population analysis profile-area under the curve (PAP-AUC) method for the detection of hVISA and to study the distribution of mobile genetic element that carries methicillin-resistance gene SCCmec (Staphylococcal cassette chromosome mec) types among these isolates. Methods: BHIV4 and PAP-AUC methods were employed to detect hVISA among 500 clinical isolates of MRSA. SCCmec typing of these isolates was performed by multiplex polymerase chain reaction. The clinical presentation, treatment with vancomycin and outcome was documented for patients with hVISA. Results: The rate of hVISA was 12.4 per cent by PAP-AUC method. Sensitivity, specificity, PPV, NPV and kappa agreement of BHIV4 with PAP-AUC was 58.06, 93.15, 54.55, 94.01 per cent and 0.498, respectively. The isolation of hVISA was significantly (P<0.01) higher in patients admitted to intensive care units and wards than in patients attending the outpatient departments. Only 38 per cent of the patients received vancomycin as therapy. Majority of the hVISA isolates carried SCCmec type V or IV. Interpretation & conclusions: The rate of hVISA isolation in our study was 12.4 per cent. The sensitivity of the BHIV4 screening test was low, and was in moderate agreement with PAP-AUC test. SCCmec type V was the predominant type seen in half of the isolates. More studies need to be done in different parts of the country on a large number of isolates to confirm our findings.

Rutin attenuates vancomycin-induced renal tubular cell apoptosis via suppression of apoptosis, mitochondrial dysfunction, and oxidative stress.

Vancomycin is a glycopeptide antibiotic widely used to treat infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is a major adverse side effect, and the development of effective nephroprotective agents remains a priority in antimicrobial chemotherapy. In this study, we investigated the cell protective effects of the flavonol glycoside rutin against vancomycin-induced toxicity. Vancomycin added to porcine renal tubular LLC-PK1 cells caused an increase of production of intracellular reactive oxygen species and subsequent apoptotic cell death. Pretreatment of LLC-PK1 cells with rutin at 5, 10, and 20 µM for 2 hr prior to 2-mM vancomycin exposure for 24 hr significantly decreased intracellular reactive oxygen species and increased superoxide dismutase and catalase activities. Rutin pretreatment also protected cells from vancomycin-induced caspase activation, mitochondrial membrane depolarization, and subsequent apoptosis. This study demonstrates a protective effect of rutin and suggests that rutin coadministration is an alternative therapy for treatment of vancomycin-induced nephrotoxicity.

Adjuvant ß-Lactam Therapy Combined with Vancomycin for Methicillin-Resistant Staphylococcus aureus Bacteremia: Does ß-Lactam Class Matter?

We analyzed the impact of vancomycin (VAN) combined with adjuvant ß-lactam therapy (Combo) on persistent (≥5 days) methicillin-resistant Staphylococcus aureus bacteremia versus VAN alone by using pooled data from two previously published observational studies (n = 156). Combo was inversely associated with persistent bacteremia (adjusted odds ratio, 0.460; 95% confidence interval, 0.229 to 0.923). Acute kidney injury was more common with Combo than with VAN (18.9% and 7.6%, respectively; P = 0.062).

Antibacterial gold nanoparticle-based photothermal killing of vancomycin-resistant bacteria.

AIM: The extensive use of vancomycin has given rise to vancomycin-resistant bacterial strains, such as vancomycin-resistant Enterococci (VRE). We aim to explore potent medical treatments that can inhibit the growth of VRE. MATERIALS & METHODS: Vancomycin-immobilized gold nanoparticles (Au@Van NPs) with polygonal shapes from one-pot reactions were generated within approximately 7 min. RESULTS & DISCUSSION: The as-prepared Au NPs exhibit not only antibacterial capability but also photothermal competence. The temperature of the sample solution containing the as-prepared Au@Van NPs can be raised by approximately 15°C under irradiation by a near-infrared laser (λ = 808 nm) within 5 min. CONCLUSION: The required amount of vancomycin on the as-prepared Au@Van NPs combined with near-infrared irradiation for inhibiting VRE is approximately 16-fold lower than that of free-form vancomycin.

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 - results of a prematurely terminated study.

BACKGROUND: Studies 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. METHODS: Patients 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. RESULTS: A 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. CONCLUSION: Based 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 REGISTRATION: ClinicalTrials.gov, NCT01975662 . Registered on 5 November 2013.