Vancomycin Therapy In Patients Research Articles

Methicillin-Resistant Staphylococcus aureus Nasal Screening With Polymerase Chain Reaction for Early De-escalation of Empiric Vancomycin in the Treatment of Suspected/Confirmed Respiratory Infection in Critically Ill Patients.

Vancomycin empirically for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia coverage often is prolonged. With high negative predictive value for MRSA pneumonia, we evaluated the efficacy of MRSA nasal screening with polymerase chain reaction for early de-escalation of empiric vancomycin for treatment of respiratory infections in patients admitted to the intensive care units. The impact of MRSA nasal screening on early de-escalation of vancomycin for respiratory infections. A retrospective, single-center cohort study was conducted to evaluate the outcomes of vancomycin therapy in patients admitted to the intensive care units with diagnosis of pneumonia before (control group) and after (study group) implementation of MRSA nasal screening. The primary end point was the difference in duration of vancomycin drug therapy in patients with suspected/confirmed pneumonia between the control and study groups. Secondary end points included the number of vancomycin trough levels obtained, discordance between polymerase chain reaction and sputum culture results, and clinical outcomes. In total, 123 patients (control: n = 76; study: n = 47) were included. The median vancomycin duration in the control group and the study group was 73.3 hours (54.3-110.6) and 30.2 hours (20.3-39.7), respectively, P < 0.0001. The control group had 2.73 times (95% CI: 2.15-3.45, P < 0.0001) longer vancomycin duration than the study group. There was a significant difference in the number of trough levels obtained between the 2 groups. The median in the control and study groups were 1 (1-3) and 1 (0-1), respectively, P < 0.0001. There was no difference between groups for length of stay, 30-day readmission for MRSA infection, reinitiation of anti-MRSA therapy for infection, vancomycin-resistant enterococci infection within 30 days, acute kidney injury, and in-hospital all-cause mortality. The implementation of a MRSA nasal screening for critically ill patients treated with vancomycin for pneumonia resulted in a significantly shorter duration of vancomycin treatment without negatively affecting patient outcomes.

Clinical benefits of therapeutic drug monitoring of vancomycin therapy in patients with postoperative intracerebral hemorrhage: a retrospective cohort study

ObjectiveThe objective of this study was to investigate the clinical efficacy and safety of conducting therapeutic drug monitoring (TDM) of vancomycin in patients with postoperative intracerebral haemorrhage.MethodsWe conducted a retrospective...

Impact of methicillin‐resistant Staphylococcus aureus polymerase chain reaction nasal swabs on vancomycin utilisation in patients admitted to the intensive care unit with respiratory infections

AbstractBackgroundMethicillin‐resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) screening has a negative predictive value as high as 96% for pneumonia. Using nasal PCR, care providers can detect the presence or absence of MRSA earlier and potentially decrease the duration of vancomycin therapy in patients with negative results.AimsThe primary objective was to assess the impact of MRSA nasal PCR on vancomycin length of therapy in patients admitted to the intensive care unit (ICU) with respiratory infections.MethodsThis was a retrospective, quasi‐experimental, uncontrolled before—after study, comparing patients receiving screening versus those who did not. Patients over the age of 18, admitted to ICU with respiratory infections who received at least one dose of vancomycin were included in this study. This investigation received exemption from the South Nassau Communities Hospital and Western Institutional Review Board (reference number SNCH‐E14) and was conducted in accordance with the tenets espoused in the Declaration of Helsinki.ResultsA total of 77 patients, 22 in the study group and 55 in the comparator group were included in the analysis. There was a reduction in median length of vancomycin therapy in the MRSA PCR group compared to the unscreened group (1.7 days vs. 6 days, IQR: 4.15 vs. 4.8, p &lt; 0.001). There was a reduction in median vancomycin levels performed (3 levels vs. 1 level, p = 0.619).ConclusionsThe use of nasal PCR screening for MRSA was associated with a reduction in median vancomycin length of therapy for patients admitted to the ICU with respiratory infections.

Optimizing Empiric Vancomycin Use in Febrile Neutropenia Patients

Introduction: National guidelines do not support routine empiric vancomycin use in the initial management of febrile neutropenia (FN) and only recommend it in patients with specific clinical indications. This bi-phasic quality improvement project aimed to evaluate current vancomycin use in FN and improve compliance with a guideline-driven algorithm (GDA) to ensure appropriate prescribing and therapy duration in a community hospital. Methods: Phase I was a retrospective review of charts of adults receiving empiric vancomycin therapy for FN at a community hospital. Phase II was a prospective review of charts of patients with FN, who received pharmacist-led interventions, to improve de-escalation of vancomycin as warranted. Results: A total of 48 and 32 patients were included in phase I and phase II, respectively. While initiation of vancomycin therapy according to guideline-recommended clinical indications was comparable among phases, appropriate de-escalation of vancomycin increased from 23% in phase I to 78% in phase II. Overall compliance with the GDA increased from 15% in phase I to 38% in phase II. Average duration of therapy in phase I was 4.77 days versus 2.69 days in phase II and there were less patients who continued vancomycin beyond 48 hours in phase II. The pharmacy intervention rate was 56% (18 of 32) and the health-care practitioner acceptance rate was 100%. Discussion: Pharmacist interventions had an impact in increasing compliance with national guideline recommendations and decreasing the duration of empiric vancomycin therapy in patients with FN.

232. Safety and Effectiveness of Intravenous to Oral De-escalation Compared to Continued Vancomycin Therapy in Orthopedic Infections

BackgroundThe Oral versus Intravenous Antibiotics for Bone and Joint Infection (OVIVA) trial determined oral antibiotics administered during the first six weeks of therapy were non-inferior to parenteral antibiotics. There was no difference in the incidence of serious adverse effects. The objective of this study was to evaluate the safety and effectiveness of de-escalating to oral therapy compared to continuing parenteral vancomycin therapy in patients with orthopedic infections in a real-world setting.MethodsWe conducted a single-center, retrospective cohort study of patients discharged between April 1, 2018 and April 1, 2020 with an orthopedic infection, a prescription for at least four weeks of parenteral vancomycin, and documented follow-up. The primary outcome was incidence of adverse events defined as provider documentation of the event and changes to therapy. The secondary outcome was incidence of 6-month treatment failure defined as repeat surgical intervention or therapy escalation. ResultsOne hundred fifty-seven patients were included. Twenty-nine (18.5%) patients were de-escalated to oral therapy. Three (10%) patients in the oral therapy group had an adverse event compared to 35 (27%) in the vancomycin group (p=0.058). Of the 35 patients with an adverse event in the vancomycin group, eight were due to parenteral access-related complications. Treatment failure occurred in three (10%) patients in the oral therapy group compared to 27 (21%) patients in the vancomycin group (p=0.29). Three (10%) patients in the oral therapy group had an unplanned readmission compared to 25 (20%) patients in the vancomycin group (p=0.24).Baseline Characteristics, Unplanned Readmission Rates, and Incidence of Adverse Events and 6-Month Treatment Failure ConclusionPatients de-escalated to oral therapy had fewer adverse events and similar incidences of treatment failure compared to patients maintained on parenteral vancomycin. Switching to oral therapy avoids some adverse events related to parenteral access. Our results in an uncontrolled, real-world setting are consistent with the OVIVA trial. Though limited by sample size, our data indicate switching to oral therapy in patients with an orthopedic infection improves safety outcomes without compromising effectiveness compared to continued parenteral vancomycin therapy.Disclosures Russell J. Benefield, PharmD, Paratek Pharmaceuticals (Grant/Research Support)

79. Outcomes Associated with the Utilization of the Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Polymerase Chain Reaction (PCR) Assay to De-escalate Vancomycin Therapy in Patients with Suspected Pneumonia at a Rural Community Hospital

BackgroundVancomycin is often added to standard inpatient community acquired pneumonia therapy, but the incidence of MRSA pneumonia is relatively low. The MRSA nasal PCR assay is used to detect if a patient’s nares are colonized with MRSA. Studies have found that this test has an excellent negative predictive value at ruling out MRSA pneumonia. In practice, there is reluctance to utilize this data to de-escalate vancomycin, possibly because little data exists investigating clinical outcomes associated with this intervention. The purpose of this study was to evaluate how this assay, in combination with antimicrobial stewardship, impacts de-escalation of vancomycin and consequently, length of stay, days of therapy, readmission, and mortality.MethodsWe performed a cohort study of patients who received vancomycin for pneumonia during the period 2017–2019. In July 2018, we implemented a pharmacy-led process to de-escalate vancomycin in pneumonia patients based on the results of the nasal MRSA PCR. Patient were excluded if they had concomitant skin/skin structure infection, osteomyelitis, were transferred to another facility, signed out against medical advice, or required mechanical ventilation. Data on patient characteristics, disease severity, length of stay, days of therapy, readmission, and mortality were compared between the groups.Figure 1: Patient disposition with reasons for exclusion from study Results101 and 107 patients were included in the before and after group, respectively. The average length of stay was 5.31 (before group) vs 4.33 days (after group), resulting in a 0.98 day decrease (p=0.0095). Days of therapy was 3.16 (before group) vs 1.96 days (after group), resulting in a 1.2 day reduction (p< 0.0001). 30-day mortality was significantly higher in the before group (19.8%) than the after group (9.3%) (RR 0.47, 95% CI 0.23–0.96). 30-day readmission was similar between the two groups (21.8% pre-intervention vs 19.6% post-intervention, p=0.7).Figure 2: Length of Stay and Duration of therapy reductions between the pre- and post-intervention groups. Figure 3: 30-day readmission rate and 30-day mortality rate in the pre- and post-intervention groups. Figure 4: Vancomycin days of therapy per 1000 patient days from July 2017 to May 2020 ConclusionUse of the MRSA nasal PCR to deescalate vancomycin therapy appears to significantly reduce length of stay and days of vancomycin therapy. Use of this assay did not negatively impact readmission but, may have a positive impact on mortality. Further research is needed to determine the impact of this intervention on length of stay and mortality.Disclosures All Authors: No reported disclosures

1489. Safety and Performance of a Pharmacist-Driven Nasal MRSA PCR Protocol for De-escalation of Empiric Vancomycin for Suspected Pneumonia at an Academic Medical Center

BackgroundLimited published data supports the de-escalation of empiric anti-methicillin resistant Staphylococcus aureus (MRSA) antibiotics for suspected pneumonia upon negative nasal MRSA screening. Besides limited sample sizes, special populations, such as those who are immunocompromised and/or critically ill, have been underrepresented in these reports. We describe real-world efficacy and safety of a pharmacist-driven nasal MRSA PCR testing protocol implemented at Stanford Health Care in May 2018 across a diverse patient population.MethodsThis was an observational cohort study of adult patients who received vancomycin for empiric pneumonia before (PRE) vs after (POST) implementation of a pharmacist-driven nasal MRSA PCR testing protocol (between 05/01/2017 - 08/31/2017 (PRE) and 5/7/2018 - 12/31/2019 (POST). The primary outcome measure was duration of vancomycin administration. Secondary outcomes included time to vancomycin discontinuation, frequency of restarting vancomycin for empiric pneumonia within 7 days, acute kidney injury (defined as “risk” by RIFLE criteria), and MRSA respiratory cultures. Statistical methods are described in Figure A.Figure A. Statistical methods ResultsTotal of 610 patients were included in this study with 116 in the PRE group and 494 in the POST group. Over 40% were critically ill and approximately 37% were immunocompromised in both groups (Table 1). For the primary outcome, median vancomycin duration was significantly shorter in the POST group (1.29 days; 95% CI 1.13-1.45) vs. PRE group (1.98 days; 95% CI 1.49-2.46) (p < 0.0005), a 34.8% reduction (Figure 1). Median vancomycin duration was lower in patients with a negative vs positive nasal MRSA PCR (1.20 days [95% CI 1.08-1.33] vs 2.53 days [95% CI 1.77-3.29], p < 0.0005), a 52.6% reduction (Figure 2). MRSA was recovered in respiratory cultures in 1.7% vs 1.4% in the PRE vs POST groups. One (0.002%) patient had a negative nasal MRSA PCR but culture-confirmed MRSA pneumonia and recovered after completing a treatment course. Secondary safety outcomes were similar between groups (Table 2).Tables 1 and 2: Baseline Characteristics and Secondary Outcomes Figure 1. Primary Outcome: Kaplan–Meier Estimates of Cumulative Active Vancomycin Therapy Before and After Implementation of Nasal MRSA PCR protocol Figure 2. Secondary Outcome: Figure 2. Kaplan–Meier Estimates of Cumulative Active Vancomycin Therapy in Patients with Negative vs Positive Nasal MRSA PCR ConclusionPharmacist-driven nasal MRSA PCR testing is effective and safe in early de-escalation of empiric vancomycin used for pneumonia treatment in a diverse population including critically ill and immunocompromised patients.Disclosures All Authors: No reported disclosures

Long-term Conventionally Dosed Vancomycin Therapy In Patients With Orthopaedic Implant-related Infections Seems As Effective And Safe As Long-term Penicillin Or Clindamycin Therapy. A Retrospective Cohort Study Of 103 Patients.

Objectives: Antimicrobial therapy is one of the cornerstones of orthopaedic implant-related infections (OIRI) treatment. Infections with Gram-positive bacteria are often treated with vancomycin, penicillin or clindamycin. A recent IDSA guideline suggests increasing the dose of vancomycin to increase the trough vancomycin target serum concentrations. This is deemed necessary because of an observed decrease in vancomycin susceptibility among Gram-positive bacteria. However, elevated vancomycin concentrations are correlated with the risk of nephrotoxicity, especially with prolonged therapy. Compared to most countries, rates of resistance against antibiotics among bacteria in the Netherlands are lower for currently available antibiotics, therefore lower target concentrations of vancomycin are probably efficacious for the treatment of infections.In this study we evaluated the efficacy and safety of long-term conventionally dosed vancomycin therapy, as an initial therapy for OIRI, and compared this with long-term penicillin and clindamycin therapy, as initial therapy, in patients with Gram-positive orthopaedic implant-related infections.Methods: A retrospective, observational study was conducted in 103 adult patients treated for OIRI, with vancomycin, penicillin or clindamycin for at least 10 days. The target trough serum concentration of vancomycin was 10-15 mg/l.Results: 74% of our patients were treated successfully with vancomycin, as initial therapy, (no reinfection within 1 year) versus 55% of our patients treated with either an antibiotic of the penicillin class (mostly flucloxacillin) or clindamycin (p=0.08), as initial therapy. For patients treated with vancomycin we observed a serum creatinine increase of 6 μmol/l, for patients treated with either an antibiotic of the penicillin class or clindamycin the serum creatinine increase was 4 μmol/l (p=0.395).Conclusions: In our population of patients with OIRI long-term treatment with conventionally dosed vancomycin, as initial therapy, was not significantly less effective and safe as long-term treatment with an antibiotic of the penicillin class or clindamycin, as initial therapy.

Outcomes from Rectal Vancomycin Therapy in Patients with Severe-Complicated Clostridium difficile Infection

Outcomes from Rectal Vancomycin Therapy in Patients with Severe-Complicated Clostridium difficile Infection

A Trial of Discontinuation of Empiric Vancomycin Therapy in Patients with Suspected Methicillin-Resistant Staphylococcus aureus Health Care-Associated Pneumonia

Healthcare-associated pneumonia (HCAP) guidelines recommend de-escalating initial antibiotic therapy based on results from lower-respiratory-tract cultures. In the absence of adequate lower respiratory cultures, physicians are sometimes reluctant to discontinue empirical vancomycin, which is given for suspected methicillin-resistant Staphylococcus aureus (MRSA) HCAP. We evaluated a strategy of discontinuing vancomycin if both nasal and throat cultures were negative for MRSA when lower-respiratory-tract cultures were not available. An antimicrobial stewardship team identified patients receiving empirical vancomycin for suspected or proven HCAP but for whom adequate lower-respiratory-tract cultures were not available. Nasal and throat swab specimens were obtained and plated on MRSA selective media. If both nasal and throat MRSA cultures were negative, the stewardship team recommended discontinuation of empirical vancomycin. Demographic and clinical aspects, a clinical pulmonary infection score (CPIS) on the day of the stewardship recommendation, and mortality of patients for whom vancomycin was discontinued were obtained by retrospective chart review. A convenience sample of 91 patients with nasal and throat cultures negative for MRSA in the absence of adequate respiratory cultures had empirical vancomycin therapy discontinued. A retrospective review revealed that 88 (97%) patients had a CPIS of ≤6 on the day of the stewardship recommendation. In-hospital mortality (7.7%) was similar to that of a previous study of de-escalation of antibiotics in pneumonia patients without adequate cultures. In the absence of adequate lower-respiratory-tract cultures, it is reasonable to discontinue empirical vancomycin HCAP therapy in patients with negative MRSA nasal and throat cultures and a CPIS of <6.

Culture-negative Periprosthetic Joint Infection Does Not Preclude Infection Control

Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty. Lack of confirmation of an infecting organism poses a challenge with regard to the selection of an appropriate antibiotic agent and surgical treatment. It is unclear whether patients with negative cultures presumed to have infections achieve similar rates of infection-free survival as those with positive cultures. The purposes of this study were (1) to report the infection control rates using irrigation and débridement and two-stage exchange for treatment of culture-negative PJIs; and (2) to compare infection control rates in culture-negative cases with those in culture-positive cases. We retrospectively reviewed 55 patients with culture-negative PJI treated between 2000 and 2007. We compared the infection-free survival rate in the culture-negative patients with that of 295 culture-positive cases of PJI. Overall infection control rate in culture-negative cases was 73% at minimum 1-year followup (mean, 47 months; range, 12-119 months). We found similar infection control rates in culture-negative and culture-positive PJI. Infection-free survival rates in both groups were highest after two-stage exchange arthroplasty and postoperative vancomycin therapy. Our observations suggest aggressive two-stage exchange arthroplasty and postoperative parenteral vancomycin therapy in patients with culture-negative PJI achieves similar rates of infection-free survival as with patients having culture-positive PJI. Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Vancomycin-induced nephrotoxicity: mechanism, incidence, risk factors and special populations. A literature review

Treatment failures following vancomycin therapy in patients with methicillin-resistant Staphylococcus aureus infections have led to the utilization of higher doses of this antibiotic to achieve the trough concentrations of 10-20 μg/mL recommended by the Infectious Diseases Society of America clinical practice guideline. However, many questions remain on the safety of such high doses of vancomycin, specifically their nephrotoxic effects. In this review, we have collected available evidence on the nephrotoxicity of vancomycin, particularly in terms of its mechanism, incidence, predisposing factors and special target populations. The data were collected by searching Scopus, PubMed, Medline, and Cochrane database systematic reviews. The key words used as search terms were "vancomycin", "nephrotoxicity", "renal failure", "renal damage", "risk factors", "infants", "children", "adult", "elderly" and "pregnancy". We have included all relevant animal and human studies up to the date of publication. Vancomycin-induced renal toxicity was reported in 10-20 % and 30-40 % of patients following conventional and high doses of vancomycin therapy, respectively .The most probable mechanism for its nephrotoxicity can be at least partially attributable to an increased production of reactive oxygen species and oxidative stress. There are a number of different risk factors which could accelerate or potentiate the occurrence of vancomycin-induced nephrotoxicity, with the most documented risk factors being high trough vancomycin level (especially >20 mg/L) or doses (>4 g/day), concomitant treatment with nephrotoxic agents, prolonged therapy (even more than 7 days), and admittance to an intensive care unit (especially prolonged stay). It is necessary to carry out more studies, especially those focused on the association between nephrotoxicity and high trough levels of vancomycin.

Relationship of Vancomycin Minimum Inhibitory Concentration to Mortality in Patients With Methicillin-Resistant Staphylococcus aureus Hospital-Acquired, Ventilator-Associated, or Health-care-Associated Pneumonia

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and health-care-associated pneumonia (HCAP). These infections are associated with significant morbidity, mortality, and cost. The impact of vancomycin minimum inhibitory concentration (MIC) on mortality for patients with MRSA pneumonia has not been determined. Adult patients in ICUs with a diagnosis of MRSA HAP, VAP, or HCAP were entered in the study. Clinical and laboratory information were prospectively collected. Vancomycin MIC and heteroresistance were determined for each MRSA isolate. Data were collected from February 2006 through August 2007. The primary outcome variable was all-cause mortality at day 28. A propensity score approach was used to adjust for confounding variables. The study sample consisted of 158 patients. All-cause mortality at day 28 was 32.3%. The majority of MRSA isolates had a vancomycin MIC ≥ 1.5 mg/mL (115/158, 72.8%). Propensity score analysis demonstrated an increase in 28-day mortality as vancomycin MIC increased from 0.75 to 3 mg/mL (P ≤ .001). Heteroresistance to vancomycin, demonstrated in 21.5% isolates, was not associated with mortality. Mortality in patients with MRSA HAP, VAP, and HCAP increases as a function of the vancomycin MIC, even for strains with MIC values within the susceptible range. Evaluation of vancomycin MICs should be contemplated at the institutional level and for individual cases of MRSA pneumonia. The use of vancomycin therapy in patients with MRSA pneumonia caused by isolates with MICs between 1 and 2 mg/mL should be undertaken with caution, and alternative therapies should be considered.

Analysis of Risk Factors and Effect of Vancomycin for Sternal Infection after Coronary Artery Bypass Graft

Background: Sternal wound infection (SWI) is an important complication after cardiac surgery. The aim of this study was to investigate the predictors affecting sternal wound infection and preventive factors including short term Vancomycin therapy in patients who underwent coronary artery bypass grafting (CABG). Material and Method: A retrospective study was done using data collected from January 2001 through December 2007. This included 219 patients who had isolated CABG. The definition of SWI was documentation from a microbiological study and a requirement for simple closure or other surgical revision. Result: The overall incidence of SWI was 7.8% (n=17). The causative organisms were methicillin resistant Staphylococcus aureus (MRSA, n=13), methicillin resistant Staphylococcus epidermidis (n=2), Pseudomonas aeruginosa (n=1), and Candida albicans (n=1). Ten cases had deep sternal wound infection with mediastinitis; 7 cases had a superficial wound infection. Infection-related mortality was low (1/17; 6%). Diabetes mellitus (p=0.006) and smoking history (p=0.020) were factors that predicted high risk. Short term use of vancomycin decreased the incidence of MRSA-associated SWI (p=0.009). For treatment, curettage and rewiring or flap were needed in most cases (88%, n=14). Conclusion: Patients who had diabetes mellitus and a smoking history need careful management. Short term use of vancomycin is effective for prevention of SWI with MRSA.

Factors Influencing Time to Vancomycin‐Induced Clearance of Nonendocarditis Methicillin‐ResistantStaphylococcus aureusBacteremia: Role of Platelet Microbicidal Protein Killing andagrGenotypes

Vancomycin susceptibility, the accessory gene global regulator (agr) genotype and function, staphylococcal cassette chromosome (SCC) mec type, and susceptibility to cationic thrombin-induced platelet microbicidal protein 1 (tPMP-1) have been individually predictive of duration of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. This investigation evaluated the interrelationship of these factors with time to clearance of MRSA bacteremia during vancomycin therapy in patients without endocarditis. Vancomycin minimum inhibitory concentration and in vitro killing, agr function (delta-hemolysin activity), agr group, SCCmec type, and survival in tPMP-1 killing assays were determined for 29 MRSA bacteremia isolates. Increased resistance to tPMP-1 killing was observed with agr group III MRSA (P = .025) and MRSA with reduced or absent agr function (P = .023). The median time to clearance of MRSA bacteremia was earlier for agr group III (3 days) versus group I (10.5 days) or II (15 days) (P = .001). In multivariate analysis, agr group II, reduced tPMP-1 killing in vitro, and prior vancomycin exposure were significant independent predictors of longer MRSA bacteremia duration. Specific genotypic, phenotypic, and clinical parameters appear to correlate with persistent MRSA bacteremia. The interrelationship of these and other factors probably contributes to vancomycin-mediated clearance of MRSA bacteremia.

An elderly woman with 'Red Man Syndrome' in association with oral vancomycin therapy: a case report

Introduction'Red Man Syndrome' is a recognized adverse reaction to intravenous vancomycin therapy. This case concerns an elderly woman who developed a 'Red Man Syndrome' reaction whilst on oral vancomycin therapy for Clostridium difficile (C difficile) diarrhoea. Isolated case reports exist recording this reaction in association with oral vancomycin therapy in patients with inflammatory bowel conditions or impaired renal function, of which this patient had both.Case PresentationAn 82 year old Caucasian woman who developed C. difficile diarrhoea after co-amoxiclav therapy for a urinary tract infection. She was treated with oral vancomycin therapy during which she developed a widespread erythematous rash in keeping with that of 'Red Man Syndrome'. This rash resolved on stopping the oral vancomycin.ConclusionThis case is important in the light of the increasing use of oral vancomycin to treat C. difficile diarrhoea, a rising problem in the UK. It also calls us to review our understanding of the mechanism of the 'Red Man Syndrome' reaction. It is possible that significant absorption of orally administered vancomycin occurs in the presence of an inflammatory bowel condition.

Methicillin-resistant Staphylococcus aureus prosthetic aortic valve endocarditis with paravalvular abscess treated with daptomycin

Prosthetic valves have been used extensively for severe cardiac valvular dysfunction for the past 3 decades. Prosthetic cardiac valves may be infected with organisms causing bacteremia, particularly gram-positive cocci. Staphylococcus epidermidis (coagulase negative staphylococci) and Staphylococcus aureus , both methicillin-susceptible S. aureus and methicillin-resistant S. aureus (MRSA) strains, are the most frequent pathogens causing prosthetic valve endocarditis (PVE). Vancomycin has been the cornerstone of therapy for serious MRSA infections including bacteremia and endocarditis. Clinicians have noted that MRSA bacteremias treated with vancomycin often fail to clear even with prolonged therapy. Persistent or prolonged MRSA bacteremia unresponsive to vancomycin therapy has led to the treatment of these infections by other agents, that is, quinupristin, dalfopristin, linezolid, or daptomycin. These antibiotics have been found particularly useful in treating MRSA bacteremias unresponsive to vancomycin therapy. We report a case of a patient who presented with MRSA PVE complicated by perivalvular aortic abscess with persistent MRSA bacteremia unresponsive to vancomycin therapy. The patient's MRSA bacteremia was cleared with daptomycin therapy (6 mg/kg/d). Because the patient refused surgery, daptomycin therapy was continued in hopes of curing the endocarditis and sterilizing the perivalvular aortic abscess. Transesophageal echocardiogram revealed a decrease in abscess in the aortic perivalvular abscess after 1 week of daptomycin therapy. The patient made an uneventful recovery. The cure of PVE and perivalvular abscesses usually requires removal of the prosthetic device and abscess drainage. In this case, in which surgery was not an option, medical therapy of PVE and a decrease in size of the aortic perivalvular abscess were accomplished with daptomycin therapy. Daptomycin is an alternative to vancomycin therapy in patients with prolonged or persistent MRSA bacteremia secondary to endocarditis or abscess.

Area under the inhibitory curve and a pneumonia scoring system for predicting outcomes of vancomycin therapy for respiratory infections by Staphylococcus aureus.

Treatment factors predictive of clinical and microbiological outcomes and the relationship between a pneumonia scoring system and clinical outcomes in vancomycin-treated patients with a Staphylococcus aureus-associated lower-respiratory-tract infection (LRTI) were studied. A computer database review identified patients for whom S. aureus was isolated from a respiratory-tract specimen between January 1 and December 31, 1998, and who had antimicrobials ordered within 72 hours of isolation of that organism. Through further review of individual patient charts, this group was restricted to those treated with vancomycin for a documented S. aureus-associated LRTI. Classification-and-regression-tree (CART) modeling was performed to determine which clinical variables were correlated with clinical outcomes and microbiological outcomes. Median changes in clinical pneumonia scores from baseline in two patient groups (those with clinical success and those with clinical failure) were compared. Seventy patients met the study criteria. CART modeling found that both outcomes were associated with area under the inhibitory curve (AUIC). The pneumonia scoring system was predictive of eventual clinical success as early as day 3 of treatment; having at least a 4-point decrease in the pneumonia score by day 3 was correlated with an 87% clinical success rate. Both AUIC and a pneumonia scoring system were useful for predicting clinical and microbiological outcomes of vancomycin therapy in patients with LRTIs caused by S. aureus.

Determinants of vancomycin clearance by continuous venovenous hemofiltration and continuous venovenous hemodialysis

The clearance of vancomycin is significantly reduced in patients with acute, as well as, chronic renal failure. Although multiple-dosage regimen adjustment techniques have been proposed for these patients, there is little quantitative data to guide the individualization of vancomycin therapy in acute renal failure patients who are receiving continuous renal replacement therapy (CRRT). To determine appropriate vancomycin dosing strategies for patients receiving continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD), we performed controlled clearance studies in five stable hemodialysis patients with three hemofilters: an acrylonitrile copolymer 0.6 m2 (AN69), polymethylmethacrylate 2.1 m2 (PMMA), and polysulfone 0.65 m2 (PS). Patients received 500 mg of vancomycin intravenously at least 12 hours before the start of the clearance study. The concentration of vancomycin in multiple plasma and dialysate/ultrafiltrate samples was determined by EMIT (Syva, Palo Alto, CA). The diffusional clearance and sieving coefficient (SC) of vancomycin were compared by a mixed-model repeated-measures analysis of variance (ANOVA) with filter and blood (Q(B)), dialysate inflow (Q(DI)), or ultrafiltration rate (Q(UF)) as the main effects and patient as a random effect. Vancomycin was moderately protein bound in these patients; free fraction ranged from 49% to 83%. The SCs of the three filters were similar and significantly correlated with the free fraction of vancomycin (P = 0.01; r2 = 0.465). Significant linear relationships were observed between the diffusional clearance of vancomycin and Q(DI) for all three filters: AN69 (slope = 0.482; r2 = 0.880); PMMA (slope = 0.853; r2 = 0.966); and PS (slope = 0.658; r2 = 0.887). The slope of this relationship for the PMMA filter was significantly greater than that of the AN69 and PS filters. The clearance of vancomycin, urea, and creatinine, however, was essentially constant at all Q(B)s for all three filters. Thus, the clearance of vancomycin was not membrane dependent during CVVH. However, during CVVHD, membrane dependence of vancomycin clearance was noted at a Q(DI) greater than 16.7 mL/min; vancomycin clearance with PMMA at a Q(DI) of 25 mL/min was 66% and 43% greater than that with the AN69 and PS filters, respectively. CVVH (62% to 262%) and CVVHD (90% to 540%) can significantly augment the clearance of vancomycin in acute renal failure patients. Dosing strategies for individualization of vancomycin therapy in patients receiving CVVH and CVVHD are proposed. (Am J Kidney Dis 1998 Jun;31(6):1019-27)

Impact of Vancomycin Therapeutic Drug Monitoring on Patient Care

To document differences in the outcome of vancomycin therapy in patients managed through a therapeutic drug monitoring (TDM) service and patients managed empirically, without the participation of a TDM service. Prospective, cohort study. An 1100-bed, tertiary-care, teaching hospital. Those who received vancomycin for more than four days, were at least 18 years old, had an estimated creatinine clearance of more than 0.33 mL/s (20 mL/min), were not neutropenic at the start of vancomycin therapy, and were not treated in a critical care unit were enrolled in the study. A total of 116 patients (61 TDM; 55 non-TDM) were monitored prospectively from June 1990 through March 1991. Patients in the TDM group had vancomycin drug therapy monitored daily by a pharmacist and vancomycin dosages adjusted following a pharmacokinetic analysis of vancomycin serum concentrations. For patients in the non-TDM group, the pharmacist only completed a data collection form. The patients and physicians were unaware of the monitoring. Duration of therapy, total vancomycin dosage, infection site, concomitant antibiotics, body temperature, and white blood cell counts were compared between the two groups. Length of stay data were also compared. Nephrotoxicity was evaluated by comparing serum creatinine concentration and estimated creatinine clearance. TDM of vancomycin appeared to reduce the incidence of vancomycin-related renal insufficiency (TDM 7 percent; non-TDM 24 percent). Patients managed through the TDM service received an average of 5 g less of vancomycin than did the patients in the non-TDM group. The duration of vancomycin therapy was an average of 2 days less for patients in the TDM group. Mean length of stay was 38.0 days for the TDM group and 44.5 days for the non-TDM group. Other measures of efficacy, infection site, and concomitant antibiotics were the same for both groups. TDM of vancomycin was associated with fewer cases of vancomycin-related renal insufficiency. Vancomycin efficacy was not compromised by TDM. Provision of TDM for vancomycin therapy aided in patient management.