Single Dose Of Vancomycin Research Articles

P1349CATHETER RELATED BACTERAEMIA AND EFFECTIVENESS OF UNIVERSAL MEASURES: 11-YEAR PROSPECIVE STUDY

Abstract Background and Aims Tunnelled catheter-related bacteraemia (BRC) of the patient in chronic hemodialysis program results in high morbidity and mortality. Antibiotic catheter lock has been suggested to reduce the incidence of BRC in clinical trials. Aim: To demonstrate the effectiveness of universal aseptic measures in obtaining an optimal BRC rate in a long-term single-centre study. Method Design: Prospective cohort study, single-centre. Follow-up time: 11 years (2008-2018) Tunneled catheters: Optiflow, Hemostar, Hemosplit, Equistream, Hemoglide (Bard Access Systems, New Jersey, USA) and Palindrome (Covidien, - Medtronic, Mansfield, Massachusets, USA). Days / catheter analyzed: 207,320. Catheter placement: Ultrasound-guided interventional radiology equipment, with fluoroscopy and universal aseptic measures + 1 single dose of Vancomycin / cefazolin. Follow-up: Nursing and Nephrology and Infectious physicians. Universal aseptic measures. Heparin lock. BRC is considered to be the presence of a positive blood culture after discarding another focus and related to the negative catheter or blood culture with no other focus than the catheter. All available samples at the time of bacteraemia are analyzed: blood, sputum, urine, faeces, pleural fluid, peritoneal fluid, cerebrospinal fluid, exudates, smears etc, and their results. The BRC rate x 1000 days / catheter is evaluated Results Results BRC 2008 to 2018: 0.57, 0.47, 0.31, 0.1, 0.43, 0.37, 0.42, 0.16, 0.2, 0.18 and 0.04 respectively. The evaluated catheters, follow-up days, catheter-related bacteraemias, germ typing and treatment are analyzed: antibiotic vs. catheter removal in Table 1. Conclusion 1. The use of universal measures only, without the use in the antibiotics lock or anticoagulants other than heparin, can achieve a bacteraemia rate related to the optimal catheter, being cost / effective and avoiding possible resistance to antibiotics and side effects of other anticoagulant drugs. 2. Antibiotic sealing should be reserved for cases of difficult epidemiological control of BRC.

Vancomycin Pharmacokinetics in Obese Patients with Sepsis or Septic Shock.

Obese patients with sepsis or septic shock may have altered vancomycin pharmacokinetics compared with the general population that may result in improper dosing or inadequate drug concentrations. The objective of this study was to characterize vancomycin pharmacokinetics in obese patients with sepsis or septic shock, and to develop a novel pharmacokinetic dosing model based on pharmacokinetic-pharmacodynamic target requirements. Prospective observational pharmacokinetic study. Large quaternary academic medical center. Sixteen obese (body mass index [BMI] 30kg/m2 or higher) adults with sepsis and either a gram-positive bacteremia or requiring vasopressor support (septic shock), who were receiving vancomycin between November 2016 and June 2018, were included. Patients were excluded if they were receiving renal replacement therapy or extracorporeal membrane oxygenation, treatment for central nervous system infections, pregnant, or receiving vancomycin for surgical prophylaxis. Four blood samples per patient were collected following a single dose of vancomycin: one peak serum vancomycin level (within 1-2hrs of infusion completion), two random levels during the dosing interval, and one trough level (within 30-60min of the next dose) were measured. A population pharmacokinetic model was developed to describe vancomycin concentrations over time. Simulations to determine optimal dosing were performed using the pharmacokinetic model with different ranges of creatinine clearance (Clcr ) and different vancomycin daily doses. Median age of the patients was 62years; median BMI was 36.1kg/m2 , Acute Physiology and Chronic Health Evaluation II score was 26, and Sequential Organ Failure Assessment score was 11. Eleven patients (69%) had an acute kidney injury. Median initial vancomycin dose was 15mg/kg; median vancomycin trough concentration was 17mg/L. A one-compartment model best characterized the pharmacokinetics of vancomycin in obese patients with sepsis or septic shock. Volume of distribution was slightly increased in this population (0.8L/kg) compared with the general population (0.7L/kg). Only Clcr effect on drug clearance was found to be significant (decrease in the objective function value by 16.4 points), confirming that it is a strong predictor of vancomycin clearance. To our knowledge, this study provides the first population-based pharmacokinetic model in obese patients with sepsis or septic shock. The nomograms generated from this pharmacokinetic model provide a simplified approach to vancomycin dosing in this patient population.

Enhancing Antibiotic Stewardship Team (AST) Efforts in Decreasing Inappropriate Vancomycin Usage in Neutropenic Fever (NF) Patients through Unit Based Pharmacist Intervention

BackgroundThe Infectious Diseases Society of America and the National Comprehensive Cancer Network guidelines recommend adding vancomycin to the empiric treatment of NF in patients meeting specific criteria. After 48 hours, the guidelines recommend discontinuing vancomycin if resistant Gram-positive organisms are not identified. An analysis of vancomycin use for NF at our institution revealed 35% of patients had vancomycin discontinued appropriately at 48 hours. Based on these results, a vancomycin stewardship team defined criteria for continuation of vancomycin past 48 hours and increased surveillance of vancomycin usage through AST oversight. The objective of this study is to assess the incidence of vancomycin discontinuation at 48 hours with the new criteria of use and the addition of pharmacist led stewardship.MethodsThis study included NF patients who were treated with an antipseudomonal β-lactam and vancomycin from January to April 2017. Criteria for vancomycin continuation beyond 48 hours included culture-documented Gram-positive infection, positive Methicillin Resistant S.aureus (MRSA) nasal swab with evidence of pneumonia, or hemodynamic instability due to septic shock. Patients who received aztreonam, or a single dose of vancomycin were excluded. Patient characteristics, previous MRSA infection, MRSA nasal swab collection and results, culture results, fever status, duration of vancomycin, rationale for continuation of vancomycin past 48 hours, re-initiation of vancomycin, and AST recommendations were collected.ResultsSixty-nine patients with 73 admissions were initiated on vancomycin for NF during the study period. Vancomycin was appropriately discontinued in 63% (46/73) compared with 35% (19/54) previously. An additional 8% (6/73) was discontinued between 48 and 72 hours, and 20% (15/73) was continued past 72 hours inappropriately. The most common reasons for continuation was lack of neutrophil recovery (5) and cellulitis (4). AST recommended discontinuation on 5 patients, all of which were accepted.ConclusionEstablishing criteria for vancomycin use along with pharmacist led antibiotic surveillance, AST, and provider education improved the use of vancomycin with the discontinuation rate increasing from 35% to 63%.(P = 0.002)Disclosures All authors: No reported disclosures.

Nonvalvular cardiovascular device-related infections.

More than a century ago, Osler took numerous syndrome descriptions of cardiac valvular infection that were incomplete and confusing and categorized them into the cardiovascular infections known as infective endocarditis. Because he was both a clinician and a pathologist, he was able to provide a meaningful outline of this complex disease. Technical advances have allowed us to better subcategorize infective endocarditis on the basis of microbiological etiology. More recently, the syndromes of infective endocarditis and endarteritis have been expanded to include infections involving a variety of cardiovascular prostheses and devices that are used to replace or assist damaged or dysfunctional tissues (Table 1). Taken together, infections of these novel intracardiac, arterial, and venous devices are frequently seen in medical centers throughout the developed world. In response, the American Heart Association’s Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease wrote this review to assist and educate clinicians who care for an increasing number of patients with nonvalvular cardiovascular device–related infections. Because timely guidelines1,2 exist that address the prevention and management of intravascular catheter–related infections, these device-related infections are not discussed in the present Statement. View this table: TABLE 1. Nonvalvular Cardiovascular Device–Related Infections This review is divided into two broad sections. The first section examines general principles for the evaluation and management of infection that apply to all nonvalvular cardiovascular devices. Despite the marked variability in composition, structure, function, and frequency of infection among the various types of nonvalvular cardiovascular devices reviewed in this article, there are several areas of commonality for infection of these devices. These include clinical manifestations, microbiology, pathogenesis, diagnosis, treatment, and prevention. The second section addresses each device and describes unique clinical features of infection. Each device is placed into one of 3 categories—intracardiac, arterial, or venous—for discussion. ### Clinical Manifestations The specific signs and symptoms associated with an infection of a …

Vancomycin Concentrations in Necrotic Pancreatic Tissue: A Pilot Study

Purpose: To determine vancomycin concentrations in necrotic pancreatic tissue of intensive care unit (ICU) patients with acute necrotizing pancreatitis. Methods: The prospective, observational pilot study was conducted at a university-based tertiary hospital. The patient population consisted of 11 patients with necrotizing pancreatitis receiving vancomycin and undergoing necrosectomy. Tissue samples taken during surgical debridement were assayed for vancomycin by immunoassay. Patients were divided into steady state and nonsteady-state groups. Two patients were excluded because necrosectomy was not performed, and one tissue sample could not be assayed because of contamination. Results: The mean tissue concentration was 5.84 mcg/mL (ranging from 3.1 mcg/mL to 8.94 mcg/mL). Four patients in the nonsteady-state group, who each received a single dose of vancomycin, had a mean tissue concentration of 4.5 ± 1.68 mcg/mL, compared with 7.76 ± 1.05 mcg/mL for the four steady-state patients. Conclusion: The data shows that vancomycin is detectable in necrotic pancreas tissue but possibly not in concentrations sufficient to prevent or treat bacterial contamination in patients with pancreatic necrosis.

The need for a center-tailored treatment protocol for peritonitis.

Despite many improvements in connectology, peritonitis continues to be a major burden in peritoneal dialysis. Because of the high variety in causative organisms and of the differences in their sensitivity patterns, surveillance of the epidemiology of peritonitis and the appropriate adaptation of the therapy are necessary. This study was performed to evaluate the influence of the nature of causative bacteria on the effectiveness of empirical treatment protocols. Based on this information, a new empiric treatment protocol was proposed. Peritoneal dialysis program of a university hospital. All episodes of peritonitis at the University Hospital Gent between 1 January 1994 and 31 December 1996 were analyzed retrospectively. Results of microbiological cultures, microscopic evaluation of dialysate, and clinical course were noted. During 1240 patient-months at risk, 50 episodes of peritonitis with identifiable responsible bacteria were observed. Gram-positive organisms were cultured in 34 episodes, and gram-negative organisms were found in 16 episodes. No responsible organism could be identified in 25 additional cases. Resistance to methicillin was registered in 33% of the cultures with staphylococci. There was no resistance to vancomycin. A new empirical treatment protocol was proposed, using a single dose of vancomycin and gentamicin intraperitoneally the first day, followed by oral treatment with ciprofloxacin. With this protocol, a 96% coverage rate is obtained, as opposed to a 78% coverage by using the Ad Hoc Advisory Committee protocol (p < 0.01). Individual centers should continue to monitor the epidemiology of peritoneal dialysis-related peritonitis and the epidemiology of the causative organisms and their sensitivity patterns in order to adapt general guidelines into a center-tailored empirical treatment protocol.

Vancomycin-Induced Thrombocytopenia

Vancomycin-induced thrombocytopenia has only been reported once previously in the medical literature. We describe a patient in whom sudden severe reversible thrombocytopenia developed on two separate occasions after exposure to vancomycin hydrochloride. A 54-year-old man was admitted to the hospital for bilateral swelling and erythema of his extremities. At the time of admission he received 2 days of vancomycin therapy without incident. On day 14 he was reexposed to vancomycin and thrombocytopenia developed, with a nadir value of 17 x 10(9)/L. On day 30, a single dose of vancomycin was administered, and thrombocytopenia once again developed, with a nadir value of 11 x 10(9)/L. Hematologic cytopenias are infrequent adverse effects of vancomycin therapy. It is postulated that these effects may be due to an immunologically mediated mechanism. With the increasing use of vancomycin due to the emergence of methicillin-resistant Staphylococcus aureus, this case should alert clinicians to this rare but potentially lethal manifestation of vancomycin.

Intrarenal distribution of vancomycin in endotoxemic rats.

We previously observed that the intrarenal distribution of aminoglycosides was modified by Escherichia coli endotoxin in the absence of any major renal physiological disturbance or histological changes. In the present study, we evaluated the role of E. coli endotoxin on the intrarenal distribution of vancomycin. At the beginning of the experiment, female Sprague-Dawley rats were infused intravenously with saline (control) or endotoxin (0.25 mg/kg) during 15 min. Thereafter, saline was constantly infused for the following 4 h. Two hours after the beginning of the infusion, animals were injected intravenously with a single dose of vancomycin (20 mg/kg). The drug levels in serum; renal cortex, medulla, and papilla; and urine were evaluated from 0.08 to 24 h after injection. Analysis of the area under the curve of the drug concentration in the different kidney components versus time showed a higher accumulation of vancomycin in the renal cortex and medulla in the endotoxin-infused rats than in the normal rats (P less than 0.01). Endotoxin was associated with an increase in the half-life in serum (P less than 0.01) and a lower elimination rate constant. The total clearance of vancomycin from plasma was significantly decreased in endotoxin-treated rats (P less than 0.01). These results demonstrate that endotoxin modifies the renal handling of vancomycin.

Vancomycin Allergy Presenting as Fever of Unknown Origin

A 37-year-old woman receiving long-term hemodialysis was admitted to the hospital with a fever of unknown origin (6 weeks of unexplained, persistent, low-grade fever). Although she had received vancomycin hydrochloride 5 days before the onset of fever, the drug was not suspected as the cause because of the duration of fever, the administration of vancomycin on prior occasions without incident, and the lack of allergic stigmata. After hospitalization, vancomycin and gentamicin sulfate were administered empirically. Immediately thereafter, her temperature rose to 40 degrees C, and over the ensuing 24 hours, eosinophilia and a maculopapular rash developed that resolved entirely when antibiotic therapy was stopped and low-dose steroid therapy was instituted. The prolonged hypersensitivity reaction after a single dose of vancomycin is consistent with the greatly extended half-life of this drug in the population with end-stage renal disease and should alert physicians to the possibility of such persistent idiosyncratic reactions in this group.

Vancomycin pharmacokinetics in continuous ambulatory peritoneal dialysis patients with peritonitis.

Peritonitis has proven to be the major deterrent to the further growth of continuous ambulatory peritoneal dialysis (CAPD) as a treatment strategy for end-stage renal disease. The correct treatment of peritonitis remains unsettled as evidenced by the presence of advocates for oral, intravenous or intraperitoneal antibiotic administration. This study examines the pharmacokinetic parameters of intravenous vancomycin when employed in the therapy of peritonitis. One gram of intravenous vancomycin was administered during 7 episodes of peritonitis in 5 patients. Plasma and end-of-dwell dialysate levels were maintained above the minimum inhibitory concentration for Staphylococcus aureus and S. epidermidis for 7 days following this single dose of vancomycin. These data establish the existence of sustained intraperitoneal entry of intravenous vancomycin during peritonitis and raise for speculation its use as the sole therapy in most episodes of gram-positive peritonitis.

Concentrations of vancomycin in bone and serum of normal rabbits and those with osteomyelitis.

The concentrations of vancomycin in the bone and serum of rabbits with Staphylococcus aureus osteomyelitis were assessed after each rabbit was given a single dose of vancomycin. Simultaneous mean concentrations of vancomycin in infected rabbits 1 h after administration of the antibiotic were 36.4 +/- 4.6 micrograms/ml (serum), 5.3 +/- 0.8 microgram/g (infected bone), and 3.0 +/- 0.2 micrograms/g (noninfected bone). Concentrations of vancomycin in serum of normal controls were higher than concentrations of vancomycin in serum of osteomyelitic rabbits after 1, 2, 3, and 6 h.