High-dose Vancomycin Research Articles

Experience with High Dose Once-daily Vancomycin for Patients with Skin and Soft-tissue infections in an Ambulatory Setting

BackgroundIntravenous (IV) vancomycin is commonly used to treat MRSA (methicillin-resistant Staphylococcus aureus) infections and is typically dosed at 15 mg/kg every 12 hours. Pharmacokinetic studies, animal models, and limited human study suggest that once-daily high dose (30 mg/kg) vancomycin is similar in efficacy for certain types of infection in the hospital setting, but there is little evidence for its use in outpatient antibiotic therapy (OPAT).We have used a high dose vancomycin regimen for MRSA skin and soft-tissue infections (SSTI) since 2011. We describe our experience with this regimen in an ambulatory setting supervised by Infectious Diseases (ID) physicians and evaluate its efficacy and safety.MethodsThis retrospective observational study included patients treated with vancomycin for SSTI from Jan 1, 2014 to July 31, 2015. Exclusion criteria included noncompliance with treatment. Patients with initial renal impairment were also excluded as they would be given 15 mg/kg vancomycin daily. Patient demographics, response to vancomycin, duration of therapy, readmission to emergency department (ER), and side effects experienced by patients were collected. A successful outcome was defined as no further requirement for IV vancomycin on the last day of therapy with either oral step down therapy or no further antibiotic.Results407 charts were reviewed and 208 patients qualified for inclusion. The mean age of included patients was 38 years. Of the 208 patients, 31% were people who inject drugs, 39% had preceding SSTI in the 12 months prior, and 48% had been on antibiotics in the previous 8 weeks. Incision and drainage was done in 50% of the patients. There were 135 positive wound cultures, of which 58% grew MRSA. The average duration of treatment was 4.7 days.A successful outcome was achieved in 162 patients (79%). Side effects including red man syndrome and phlebitis were seen in 19 patients (9.3%). 42 patients (20.5%) were readmitted to ER within 30 days of initial referral, and 18 of those were related to the original infections.ConclusionHigh dose (30 mg/kg) once-daily vancomycin for SSTI was effective and safe when used for select patients under the supervision of ID physicians in an ambulatory setting.Disclosures All authors: No reported disclosures.

Incidence and risk factors of acute kidney injury associated with continuous intravenous high-dose vancomycin in critically ill patients

For vancomycin therapy of severe infections, the Infectious Diseases Society of America recommends high vancomycin trough levels, whose potential for inducing nephrotoxicity is controversial. We evaluated the incidence and risk factors of acute kidney injury (AKI) in critically ill patients given continuous intravenous vancomycin with target serum vancomycin levels of 20 to 30 mg/L.We retrospectively studied 107 continuous intravenous vancomycin treatments of ≥48 hours’ duration with at least 2 serum vancomycin levels ≥20 mg/L in critically ill patients. Nephrotoxicity was defined according to the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for AKI (ie, serum creatinine elevation by ≥26.5 μmoL/L or to ≥1.5 times baseline). Risk factors for AKI were identified by univariate and multivariate analyses.AKI developed in 31 (29%) courses. Higher serum vancomycin levels were associated with AKI (P < 0.01). Factors independently associated with AKI were highest serum vancomycin ≥40 mg/L (odds ratio [OR], 3.75; 95% confidence interval [CI], 1.40–10.37; P < 0.01), higher cumulative number of organ failures (OR, 2.63 95%CI, 1.42–5.31; P < 0.01), and cirrhosis of the liver (OR, 5.58; 95%CI, 1.08–31.59; P = 0.04).In this study, 29% of critically ill patients had AKI develop during continuous intravenous vancomycin therapy targeting serum levels of 20 to 30 mg/L. Serum vancomycin level ≥40 mg/L was independently associated with AKI.

Elution and Mechanical Strength of Vancomycin-Loaded Bone Cement: In Vitro Study of the Influence of Brand Combination.

Antibiotic-loaded bone cement (ALBC) is widely used in orthopaedic surgery for both prevention and treatment of infection. Little is known about the effect of different brand combinations of antibiotic and bone cement on the elution profile and mechanical strength of ALBC. Standardized specimens that consisted of one of the 4 brands of bone cement and one of the 3 brands of vancomycin were fashioned, producing 12 combinations of ALBC. Two dosages of vancomycin in 40g bone cement were used to represent the high (4g vancomycin) and low (1g vancomycin) dose groups. Concentrations of vancomycin elution from ALBC was measured for up to 336 hours. The ultimate compression strength was tested at axial compression using a material testing machine before and after elution. In both high-dose and low-dose groups, Lyo-Vancin in PALACOS bone cement resulted in the highest cumulative elution and Vanco in Simplex P bone cement resulted in the lowest elution (458% and 65% higher in high- and low-dose groups, respectively). The mechanical strength was not significantly compromised in all groups with low dose vancomycin (range: 70.31 ± 2.74 MPa to 87.28 ± 8.26MPa after elution). However, with the addition of high dose vancomycin, there was a mixed amount of reduction in the ultimate compression strength after cement aging, ranging from 5% (Vanco in Simplex P, 81.10 ± 0.48 MPa after elution) to 38% (Sterile vancomycin in CMW, 60.94 ± 5.74 MPa after elution). We concluded that the selection of brands of vancomycin and bone cement has a great impact on the release efficacy and mechanical strength of ALBC.

High Single-dose Vancomycin Loading Is Not Associated With Increased Nephrotoxicity in Emergency Department Sepsis Patients.

Vancomycin loading doses are recommended; however, the risk of nephrotoxicity with these doses is unknown. The primary objective of this study was to compare nephrotoxicity in emergency department (ED) sepsis patients who received vancomycin at high doses (>20 mg/kg) versus lower doses (≤20 mg/kg). A retrospective cohort study was performed in three academic EDs. Inclusion criteria were age ≥ 18 years, intravenous vancomycin order, and hospital admission. Exclusion criteria were no documented weight, hemodialysis-dependent, and inadequate serum creatinine (SCr) values for the measured outcome. Analyses compared the incidence of nephrotoxicity for patients who received vancomycin at high dose (>20 mg/kg) versus low dose (≤20 mg/kg). A total of 2,131 consecutive patients prescribed vancomycin over 6 months were identified. Of these, 1,330 patients had three SCr values assessed for the primary outcome. High-dose initial vancomycin was associated with a significantly lower rate of nephrotoxicity (5.8% vs. 11.1%). After age, sex, and initial SCr were adjusted for, the risk of high-dose vancomycin compared to low-dose was decreased for the development of nephrotoxicity (relative risk = 0.60; 95% confidence interval = 0.44 to 0.82). Initial dosing of vancomycin > 20 mg/kg was not associated with an increased rate of nephrotoxicity compared with lower doses. Findings from this study support compliance with initial weight-based vancomycin loading doses.

The effect of vancomycin powder on bone healing in a rat spinal rhBMP-2 model.

OBJECTIVE This study aims to quantify the impact of vancomycin powder application on new bone formation and spine fusion rates in a rat posterolateral arthrodesis model. METHODS Thirty-six female Sprague-Dawley rats underwent a posterolateral lumbar spinal fusion (PLF) at the L-4 and L-5 vertebrae. Fusion was elicited via implantation of an absorbable collagen sponge containing 3 µg rhBMP-2. Rats were divided into 3 groups: no vancomycin (control), standard-dose vancomycin, and high-dose vancomycin, based on what was applied to the fusion bed. Clinical studies typically describe the application of 1 g vancomycin into the surgical wound. Presuming an average individual patient weight of 70 kg, a weight-based equivalent dose of vancomycin powder was applied subfascially in the PLF model constituting a "standard-dose" treatment group (14.3 mg/kg, n = 12). To determine whether there is a critical threshold beyond which vancomycin increases the risk of pseudarthrosis, a 10-fold higher dose was administered to a "high-dose" treatment group (143 mg/kg, n = 12). No vancomycin powder was applied to the surgical site in the control group (n = 12). Fusion was evaluated with plain radiographs at 4 and 8 weeks after surgery. The spines were harvested after the 8-week radiographs were obtained and evaluated using manual palpation, microCT analysis, and histological analysis. RESULTS Radiographs demonstrated equivalent bridging bone formation in all groups. No significant differences in fusion scores were seen in the standard-dose (mean 2.25) or high-dose (2.13) treatment groups relative to untreated control animals (1.78). Similarly, fusion rates did not differ significantly different between vancomycin-treated animals (100% for both groups) and control animals (92%). Quantification of new bone formation via microCT imaging revealed no significant between-groups differences in the volume of newly regenerated bone (control vs standard-dose vancomycin, p = 0.57; control vs high-dose vancomycin, p = 0.53). CONCLUSIONS This is the first in vivo study to specifically address the development of pseudarthrosis after intrawound application of vancomycin during fusion surgery. Our results demonstrate that vancomycin powder does not inhibit fusion rates at a dose that is the weight-percentage equivalent of what is routinely used by surgeons. Moreover, bone formation and fusion rates were not reduced even after administration of a vancomycin dose that is 10-fold higher than that which is typically administered clinically. Our findings suggest that if there is a critical threshold above which vancomycin inhibits bone healing, such a dose is out of the range which might be considered reasonable for clinical use.

Pre-Treatment Serum C-Reactive Protein Level Is An Independent Risk Factor for Development of Nephrotoxicity in Patients Receiving High-Dose Vancomycin

High-dose vancomycin treatment increases the likelihood of vancomycin-related nephrotoxicity. C-reactive protein (CRP) is a sensitive marker of systemic inflammation. In this study, we evaluated the pre-treatment serum CRP level as a risk factor of the development of nephrotoxicity in patients receiving high total daily doses (>2.5 g) of vancomycin. Data extracted from medical records for 174 patients who received total daily doses of >2.5 g of intravenous vancomycin for a minimum of 48 h and had their serum CRP level and erythrocyte sedimentation rate tested within 24 h before vancomycin treatment were subject to final analyses. Univariate analyses showed that patients who developed nephrotoxicity during vancomycin treatment had significantly higher median vancomycin serum concentration, duration of vancomycin treatment, and the serum CRP level within 24 h before vancomycin treatment than the non-nephrotoxicity group. Multivariate logistic regression analysis showed that after adjustment for potential confounders, median vancomycin serum concentration, duration of treatment, serum CRP level within 24 h before vancomycin treatment, and nephrotoxic medication were found significantly associated with the development of nephrotoxicity. This was confirmed by multivariate hazard ratio analysis after adjustment for potential confounders. In conclusion, this study provides the first evidence supporting the fact that the serum CRP level within 24 h before vancomycin treatment is an independent risk factor for the development of nephrotoxicity in patients receiving total daily doses of >2.5 g of vancomycin. Therefore, the serum CRP level within 24 h before vancomycin treatment could be a potential biomarker or prognostic factor for the development of vancomycin nephrotoxicity.

Comparison of High-Dose Versus Low-Dose Vancomycin Regimens for Treatment of Clostridium difficile Infection

Comparison of High-Dose Versus Low-Dose Vancomycin Regimens for Treatment of Clostridium difficile Infection

PIN6 - High Dose Vancomycin Loading Versus Low Dose is Associated With Decreased Nephrotoxicity In Emergency Department Sepsis Patients

PIN6 - High Dose Vancomycin Loading Versus Low Dose is Associated With Decreased Nephrotoxicity In Emergency Department Sepsis Patients

Conventional- versus high-dose vancomycin regimen in patients with acute bacterial meningitis: a randomized clinical trial

Objective: Efficacy of the conventional- versus high-dose vancomycin regimen in patients with acute bacterial meningitis was compared.Methods: In a randomized clinical trial 44 patients with acute bacterial meningitis were randomly assigned to the conventional- or high-dose vancomycin groups. Clinical and laboratory parameters were used for evaluation of response to the treatment regimens.Results: In the high-dose group, leukocytosis and fever resolved significantly faster than those in the conventional group. Furthermore, the length of hospitalization was shorter and Glasgow Coma Scale at the end of 10th day was significantly lower in the high dose compared to the conventional group. Trend of creatinine clearance changes did not differ significantly between the two groups.Conclusion: In comparison to the conventional-dose regimen, the high-dose vancomycin regimen was associated with significantly more favorable clinical response without increase in the incidence of nephrotoxicity in patients with acute bacterial meningitis.

High-Dose Intravenous Vancomycin Therapy and the Risk of Nephrotoxicity

PurposeNational guidelines recommend higher serum trough concentrations when using vancomycin to treat certain clinical conditions, but there is concern that higher-dose vancomycin therapy causes nephrotoxicity. We evaluated risk factors associated with nephrotoxicity in patients receiving high-dose intravenous vancomycin. MethodsThis retrospective cohort study evaluated the clinical outcome of 80 hospitalized adult patients with normal baseline renal function who received ≥4 g/d of intravenous vancomycin for ≥48 hours between January 1, 2011, and December 31, 2011. After abstracting clinical risk factors, we used an analysis by methods of best clinical subsets to develop a multivariable model predicting nephrotoxicity in patients receiving high-dose vancomycin. FindingsThe overall rate of nephrotoxicity in the study population was 6%. Trough concentrations >20 mg/L were identified in a similar proportion of patients who did and did not develop nephrotoxicity. Patients who developed nephrotoxicity trended toward having a lower body mass index, higher daily dose, longer duration of therapy, and greater exposure to intravenous contrast and nephrotoxic medications. In a multivariable model, the combination of intravenous contrast and nephrotoxic medications was a significant predictor of nephrotoxicity, and duration of high-dose vancomycin was a significant confounder. ImplicationsAdministration of high-dose intravenous vancomycin may have less associated nephrotoxicity than previously reported, although duration of vancomycin therapy may play a role. Concomitant exposure to intravenous contrast and other nephrotoxic medications is a more significant predictor of developing nephrotoxicity than vancomycin dose or trough.

PS-097 Complications after vancomycin perfusion by central venous catheter

BackgroundInfections and thrombotic events related to Central Venous Catheters (CVC) are iatrogenic complications that may aggravate the initial prognosis. To the best of our knowledge, the risk associated with vancomycin...

Combination Prophylactic Therapy with Rifampin Increases Efficacy against an Experimental Staphylococcus epidermidis Subcutaneous Implant-Related Infection

The incidence of infections related to cardiac devices (such as permanent pacemakers) has been increasing out of proportion to implantation rates. As management of device infections typically requires explantation of the device, optimal prophylactic strategies are needed. Cefazolin and vancomycin are widely used as single agents for surgical prophylaxis against cardiac device-related infections. However, combination antibiotic prophylaxis may further reduce infectious complications. To model a localized subcutaneous implant-related infection, a bioluminescent strain of Staphylococcus epidermidis was inoculated onto a medical-procedure-grade titanium disc, which was placed into a subcutaneous pocket in the backs of mice. In vivo bioluminescence imaging, quantification of ex vivo CFU from the capsules and implants, variable-pressure scanning electron microscopy (VP-SEM), and neutrophil enhanced green fluorescent protein (EGFP) fluorescence in LysEGFP mice were employed to monitor the infection. This model was used to evaluate the efficacies of low- and high-dose cefazolin (50 and 200 mg/kg of body weight) and vancomycin (10 and 110 mg/kg) intravenous prophylaxis with or without rifampin (25 mg/kg). High-dose cefazolin and high-dose vancomycin treatment resulted in almost complete bacterial clearance, whereas both low-dose cefazolin and low-dose vancomycin reduced the in vivo and ex vivo bacterial burden only moderately. The addition of rifampin to low-dose cefazolin and vancomycin was highly effective in further reducing the CFU harvested from the implants. However, vancomycin-rifampin was more effective than cefazolin-rifampin in further reducing the CFU harvested from the surrounding tissue capsules. Future studies in humans will be required to determine whether the addition of rifampin has improved efficacy in preventing device-related infections in clinical practice.

Antibiotic Treatment and Timing of Reimplantation

PJI is traditionally treated with intravenous (IV) antibiotics in order to obtain the minimum inhibitory concentration in the shortest time possible. Once this goal is met and there is clinical evidence of improvement, some IV antibiotic regimens can be switched to oral regimens. There is scarce literature reporting on the use of oral (combined or single) antibiotic therapy for the treatment of PJIs without an initial IV regimen [1–5]. Most of these studies were conducted in cases where the prosthesis was retained. There is one study in which no oral or prolonged IV regimen was used after debridement and the use of an antibiotic-impregnated cement spacers led to a 87% eradication rate [6]. No literature conclusively supports the use of only oral (combined or single) antibiotic therapy prior to reimplantation. The recently-published guidelines of the Infectious Diseases Society of America (IDSA) [7] suggest that pathogen-specific, highly bioavailable oral therapy (e.g. linezolid or fluoroquinolones) may be an alternative as initial therapy for some cases of PJI. Concerns against the routine use of appropriate oral agents in the treatment of PJI largely comprise questions of patient medication compliance and the long-term use of medication therapy with less intensive efficacy and toxicity monitoring.

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Introduction: Vancomycin dosing of 15 to 20 mg/kg to achieve target serum trough concentrations of 15 to 20 mg/L is recommended in several national guidelines. However, there is limited data describing the performance of this dosing strategy, especially in patients with obesity, acute kidney injury, altered fluid status, sepsis requiring vasopressor therapy, and/or concomitant nephrotoxic agents. A high dose vancomycin nomogram (HDVN) was developed to recommend a dose and frequency to target troughs of 15 to 20 mg/L. Methods: Adult patients 18 years or older who were started on vancomycin using the HDVN and had at least one vancomycin trough drawn at steady state between July 2011 and June 2012 were included. Patients with creatinine clearance < 25 ml/min or were on any form of renal replacement therapy were excluded. Multivariate regression analysis was performed to evaluate risk factors for supratherapeutic and subtherapeutic vancomycin troughs, and nephrotoxicity. Potential risk factors evaluated include age > 65 years, body mass index > 35, ICU admission, nephrotoxic medications, Charlson Index > 5, daily vancomycin dose > 4 grams, baseline renal dysfunction, IV contrast, and vasopressor therapy. Results: Mean vancomycin trough was 17.28 mg/L (range of 4.8 to 59 mg/L), with 60 (35.5%) patients admitted to the ICU during vancomycin therapy. A large proportion of vancomycin troughs were not therapeutic; 76 (46%) patients had subtherapeutic troughs and 54 (32%) patients had supratherapeutic troughs. Age > 65 years (OR 1.98, CI 0.264 – 0.926, p = 0.033) was the only statistically significant risk factor for subtherapeutic troughs, and BMI > 35 (OR 2.454, CI 1.035-5.819, p = 0.042) was the only statistically significant risk factor for supratherapeutic vancomycin troughs. Vasopressors (OR 0.040, CI 1.042 – 6.010, p=0.04) and concomitant nephrotoxic agents (OR 1.043 – 6.845, p=0.41) were associated with nephrotoxicity. Conclusions: This was the first study that assessed the use of a high dose vancomycin nomogram in a wide variety of hospitalized patients. Utilization of a high dose vancomycin nomogram resulted in a large proportion of patients with subtherapeutic or supratherapeutic vancomycin serum concentrations. Deviation from the HDVN and frequent monitoring should be strongly considered in patients who are older than 65 years of age, morbidly obese, receiving nephrotoxic medications, or on vasopressor therapy.

A new regimen for continuous infusion of vancomycin during continuous renal replacement therapy

Continuous infusion (CI) of high-dose vancomycin is often used to treat life-threatening infections caused by less-susceptible Gram-positive bacteria. However, this approach has not been well studied in patients on continuous renal replacement therapy (CRRT). The aim of this study was to evaluate the adequacy of a new CI vancomycin regimen in septic patients undergoing CRRT. In this prospective study we measured vancomycin concentrations obtained with a new CI regimen for CRRT, which included a loading dose of 35 mg/kg given over a 4 h period followed by a daily dose of 14 mg/kg. Vancomycin concentrations were measured: at the end of the loading dose (T1); 12 h after the onset of therapy (T2); and 24 h after the onset of therapy (T3). Drug concentrations (at T2 and T3) were considered adequate if between 20 and 30 mg/L. CRRT intensity was calculated as: dialysate rate (mL/kg/h) + ultrafiltration rate (mL/kg/h). Vancomycin population pharmacokinetics were calculated using non-linear mixed-effects modelling. We studied 32 patients who received median (IQR) loading and daily vancomycin doses of 2750 mg (2250-3150) and 1100 mg (975-1270), respectively. Drug concentrations were: T1, 44 mg/L (38-58); T2, 27 mg/L (24-31); and T3, 23 mg/L (19-31). Vancomycin concentrations were adequate in 22/32 patients (69%) at T2 and in 20/32 (63%) at T3. The two relevant covariates that significantly affected drug concentrations were body weight and CRRT intensity. This new vancomycin regimen allowed the rapid achievement of target drug concentrations in the majority of patients. CRRT intensity had an influence on vancomycin clearance.

Randomised clinical trial: vancomycin or metronidazole in patients with primary sclerosing cholangitis ‐ a pilot study

Emerging data suggest that oral antibiotics may have therapeutic effects in primary sclerosing cholangitis (PSC), but published studies are limited. To investigate the safety and efficacy of oral vancomycin and metronidazole in patients with PSC. Thirty-five patients with PSC were randomised in a double-blind manner into four groups: vancomycin 125 mg or 250 mg four times/day, or metronidazole 250 mg or 500 mg three times/day for 12 weeks. The primary endpoint was decrease in alkaline phosphatase (ALK) at 12 weeks. Secondary end points included serum bilirubin and Mayo PSC risk score; pruritus; and adverse effects (AEs). Nonparametric tests were used for analysis. The primary endpoint was reached in the low-dose (-43% change in ALK, P = 0.03) and high-dose (-40%, P = 0.02) vancomycin groups, with two patients in the former experiencing ALK normalisation. Bilirubin decreased significantly in the low-dose metronidazole group (-20%, P = 0.03) and trended towards significance in the low-dose vancomycin group (-33%, P = 0.06). Mayo PSC risk score decreased significantly in the low-dose vancomycin (-0.55, P = 0.02) and low-dose metronidazole group (-0.16, P = 0.03). Pruritus decreased significantly in the high-dose metronidazole group (-3.4, P = 0.03). AEs led to medication discontinuation in six patients, four of whom were receiving metronidazole. Both vancomycin and metronidazole demonstrated efficacy; however, only patients in the vancomycin groups reached the primary endpoint, and with less adverse effects. Larger, longer-term studies are needed to further examine the safety and efficacy of antibiotics as a potential treatment for patients with primary sclerosing cholangitis (clinicaltrials.gov NCT01085760).

Continuous high-dose vancomycin combination therapy for methicillin-resistant staphylococcal prosthetic hip infection: a prospective cohort study

Few data are available on treatment and outcome of methicillin-resistant (MR) staphylococcal prosthetic joint infections. Vancomycin remains the treatment of choice for these infections, but its efficacy and safety in bone-and-joint infections are insufficiently documented. We conducted a prospective cohort study on 60 patients treated between November 2002 and December 2008 for chronic MR staphylococcal (44 S. epidermidis, nine other coagulase-negative Staphylococcus and seven S. aureus) prosthetic hip infections (PHIs). Twentytwo patients had previously undergone surgery for their PHI and 21 had previously received antibiotics. All patients had surgery (exchange arthroplasty for 58 patients, resection arthroplasty for two) and received an antibiotic regimen combining high-dose continuous intravenous vancomycin infusion (target serum concentration 30–40 mg/L) with another antibiotic for 6 weeks, followed by an additional 6 weeks of oral intake. Two years after surgery, infection was considered cured in 41 (68%) patients and only two relapses occurred after one-stage exchange arthroplasty. Nineteen (32%) patients experienced nephrotoxicity that was generally mild (RIFLE class R for 14 patients, class I for four patients and class F for one patient) and most often reversible. Continuous high-dose intravenous vancomycin combination therapy is an effective, feasible and reasonably safe treatment of chronic MR staphylococcal PHI.

Does resistance in severe infections caused by methicillin-resistant Staphylococcus aureus give you the ‘creeps’?

The clinical implications of reduced vancomycin susceptibility amongst methicillin-resistant Staphylococcus aureus (MRSA) are controversial, and crossresistance to daptomycin amongst such strains has been reported. As a consequence of 'MIC creep', higher trough levels were recommended for serious infections. This review focusses on the new data published in the past 18 months that pertain to these issues. Heteroresistant vancomycin-intermediate Staphylococcus aureus reduces the clinical response rates to vancomycin in bacteraemic MRSA patients without impacting on mortality as opposed to 'MIC creep' with vancomycin minimum inhibitory concentration (MIC) levels of ≥1.5 mg/l that are significantly associated with mortality. Although daptomycin resistance is rare, 'concomitant MIC creep' amongst MRSA isolates with increasing vancomycin MICs may occur or exist concurrently amongst such strains. The aggressive vancomycin dosing regimens are still associated with unacceptable high microbiological failure rates and it is not currently possible to achieve probability of target attainment at higher vancomycin MICs of 2 mg/l. The nephrotoxic impact of high-dose vancomycin therapy has been confirmed. Continued monitoring of patients on aggressive vancomycin dosing schedules is advised. Unless alternative dosing strategies prove otherwise efficacious, an alternative antibiotic should be considered for severe MRSA infections with vancomycin MICs greater than 1 mg/l. The utility of vancomycin may be waning but will depend on the prevalence of resistant MRSA phenotypes in a specific ICU.

Treatment of methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia with high-dose vancomycin or linezolid

The purpose of this study was to determine the clinical cure rate of high-dose vancomycin for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) ventilator-associated pneumonia (VAP) in critically ill trauma patients. Recent trials suggest that a traditional dose of 1 g q12 hours results in unacceptable cure rates for MRSA VAP. Thus, more aggressive vancomycin dosing has the potential to improve efficacy. Based on pharmacokinetic principles, the goal initial dose at the study center has been 20 mg/kg q12 hours or q8 hours since the 1990s. All patients admitted to the trauma intensive care unit from 1997 to 2008 diagnosed with MRSA VAP were retrospectively reviewed. Diagnosis required bacterial growth ≥ 100,000 colony forming units/mL from a bronchoscopic bronchoalveolar lavage, new or changing infiltrate, plus at least two of the following: fever, leukocytosis or leukopenia, or purulent sputum. Overall, 125 patients with 141 episodes of MRSA VAP were identified. Mean age was 47 years ± 21 years, median Injury Severity Score was 29 (22-43), 70% of patients were male, and the mean length of intensive care unit stay was 38 days ± 35 days. The mean initial vancomycin dose was 18.1 mg/kg/dose with a mean duration of therapy of 11 days. Clinical success was achieved in 88% (125 of 131) of episodes, with microbiological success in 89% (66 of 74) of episodes with a follow-up bronchoscopic bronchoalveolar lavage. Overall mortality was 20% (25 of 125), with death due to VAP in 12 of 25 deaths. Mean initial vancomycin trough concentrations were 10.6 mg/L in the clinical success group and 13.3 mg/L in the clinical failure group (p = not significant). High-dose vancomycin provided an acceptable cure rate for MRSA VAP in critically ill trauma patients. Therapeutic study, level III.

Continuation of High-Dose Vancomycin despite Nephrotoxicity

In agreement with several other studies ([3][1], [4][2]), Bosso et al. reported that in treating serious methicillin-resistant Staphylococcus aureus (MRSA) infections, vancomycin trough concentrations of >15 mg/liter were independently associated with nephrotoxicity ([1][3]). However, how best to