Assessment of the current knowledge about infective endocarditis prevention among dental hygienists in Italy: A national survey.

OBJECTIVES: To date, there is a lack of data regarding the acceptance of the guidelines for infective endocarditis (IE) prevention among dentists in Italy, and similarly, there are no data on the understanding and compliance of those among dental hygienists (DH). Thus, we tried to assess the ability of DH to recognize and manage categories of patients at high risk of EI, to identify which dental procedures are at increased risk and to assess the level of knowledge of doses and how antibiotic prophylaxis should be administered in specific cases. METHODS: An anonymous questionnaire was prepared and made accessible online by sharing a Google Forms® link; general personal data and educational background information were collected to obtain a profile of the participants. RESULTS: A total of 362 DH answered to our web-based survey, showing a prevalent female percentage (86.7%) and the most represented age group of 30-39 years old (43.1%). Regarding the gender differences, there were not overall statistically significant differences; similarly, we did not find any differences regarding the overall number of wrong questions if considering the different ages of the participant and the year of graduation. Graduates in Northern Italy have mistaken fewer questions than graduates in other geographical areas. CONCLUSION: To the best of our knowledge, this is the largest survey about the knowledge of IE for DH ever performed. Because the overprescription of antibiotics contributes to the development of drug resistance, antibiotic stewardship should be at the forefront of patient care. Our data reflect the need for placing a greater emphasis on IE prophylaxis education in training and during continuing professional development events for DH.

Comparison of dalbavancin with standard of care in the management of infective endocarditis: efficacy, safety, and cost analysis.

OBJECTIVES: Due to its long half-life, dalbavancin offers benefits for long-duration treatments, especially osteoarticular and infective endocarditis (IE). We evaluated the efficacy and costs of IE treatment, comparing dalbavancin with standard of care (SOC). METHODS: Retrospective multicenter cohort study of adult patients with Gram-positive cocci definite IE. Dalbavancin was used as a sequential therapy before discharge. Efficacy was a combined variable of clinical cure and absence of recurrence in 12-month follow-up. Length of hospital stay and the associated costs were analyzed in both groups of treatment. RESULTS: Twenty-two patients received dalbavancin and 47 SOC. The efficacy was similar between the groups (dalbavancin 18 [72%] vs SOC 44 [94%], P = 0.198). Hospital stay was shorter in the dalbavancin group (dalbavancin 22 days [16-34] vs SOC 37 days [23-49], P = 0.001), especially in those with E. faecalis IE (dalbavancin 30 days [20-36] vs SOC 65 days [46-74], P <0.001). A reduction of cost was observed between both groups (dalbavancin, 12,206 € [8998-17,283] vs SOC 16,249 € [11,496-22,367], P = 0.032). CONCLUSION: Dalbavancin could be a safe and effective option in the sequential treatment of patients with IE. Also, a cost reduction was detected, due to a significant shortness of hospital stay.

The Assessment of Antimicrobial Resistance in Gram-Negative and Gram-Positive Infective Endocarditis: A Multicentric Retrospective Analysis.

Background and Objectives: Multidrug-resistant microorganisms have made treating bacterial infections challenging. Resistance to antibiotics is expected to overcome efforts to produce new, effective antibacterial medication that is lifesaving in many situations. Infective endocarditis (IE) is a life-threatening infection that affects 5-15 per 100,000 patients annually and requires rapid antibiotic therapy to prevent morbidity and mortality. Materials and Methods: The present research assessed IE cases over five years, from a multicentric database, with the main objective of determining the degree of antibiotic resistance in these patients, stratified by Gram-positive and Gram-negative bacteria. Results: Bad oral hygiene was present in 58.6% of patients from the Gram-negative group (vs. 38.7% in the Gram-positive group). Non-valvular heart disease was identified in approximately 40% of all patients, and valvopathies in approximately 20%. It was observed that 37.9% of Gram-negative IE bacteria were resistant to three or more antibiotics, whereas 20.7% were susceptible. Among Gram-positive infections, S. aureus was the most commonly involved pathogen, with a multidrug-resistant pattern in 11.2% of patients, while Acinetobacter baumannii had the highest resistance pattern of all Gram-negative pathogens, with 27.4% of all samples resistant to three or more antibiotics. Patients with Gram-negative IE were 4.2 times more likely to die. The mortality risk was 4 times higher when bacteria resistant to two or more antibiotics was involved and 5.7 times higher with resistance patterns to three or more antibiotics than the reference group with no antibiotic resistance. Peripheral catheters were the most common cause of multi-resistant IE, followed by heart surgery, dental procedures, and ENT interventions. Conclusions: Even though Gram-positive infections were the most frequent (83.0% of all cases), Gram-negative IE infections are substantially more deadly than Gram-positive IE infections. However, it was also observed that patients with Gram-negative infections were more likely to have underlying comorbidities, be institutionalized, and be underweight. Although the Gram-negative infections were more severe, their resistance patterns were similar to Gram-positive bacteria. As resistance patterns increase, more efforts should be made to prevent a healthcare catastrophe. At the same time, careful prophylaxis should be considered in patients at risk, including those with central catheters, undergoing dental procedures, and with poor oral hygiene.

Simulated Cost-effectiveness and Long-term Clinical Outcomes of Addiction Care and Antibiotic Therapy Strategies for Patients With Injection Drug Use-Associated Infective Endocarditis.

IMPORTANCE: Emerging evidence supports the use of outpatient parenteral antimicrobial therapy (OPAT) and, in many cases, partial oral antibiotic therapy for the treatment of injection drug use-associated infective endocarditis (IDU-IE); however, long-term outcomes and cost-effectiveness remain unknown. OBJECTIVE: To compare the added value of inpatient addiction care services and the cost-effectiveness and clinical outcomes of alternative antibiotic treatment strategies for patients with IDU-IE. DESIGN, SETTING, AND PARTICIPANTS: This decision analytical modeling study used a validated microsimulation model to compare antibiotic treatment strategies for patients with IDU-IE. Model inputs were derived from clinical trials and observational cohort studies. The model included all patients with injection opioid drug use (N = 5 million) in the US who were eligible to receive OPAT either in the home or at a postacute care facility. Costs were annually discounted at 3%. Cost-effectiveness was evaluated from a health care sector perspective over a lifetime starting in 2020. Probabilistic sensitivity, scenario, and threshold analyses were performed to address uncertainty. INTERVENTIONS: The model simulated 4 treatment strategies: (1) 4 to 6 weeks of inpatient intravenous (IV) antibiotic therapy along with opioid detoxification (usual care strategy), (2) 4 to 6 weeks of inpatient IV antibiotic therapy along with inpatient addiction care services that offered medication for opioid use disorder (usual care/addiction care strategy), (3) 3 weeks of inpatient IV antibiotic therapy along with addiction care services followed by OPAT (OPAT strategy), and (4) 3 weeks of inpatient IV antibiotic therapy along with addiction care services followed by partial oral antibiotic therapy (partial oral antibiotic strategy). MAIN OUTCOMES AND MEASURES: Mean percentage of patients completing treatment for IDU-IE, deaths associated with IDU-IE, life expectancy (measured in life-years [LYs]), mean cost per person, and incremental cost-effectiveness ratios (ICERs). RESULTS: All modeled scenarios were initialized with 5 million individuals (mean age, 42 years; range, 18-64 years; 70% male) who had a history of injection opioid drug use. The usual care strategy resulted in 18.63 LYs at a cost of $416 570 per person, with 77.6% of hospitalized patients completing treatment. Life expectancy was extended by each alternative strategy. The partial oral antibiotic strategy yielded the highest treatment completion rate (80.3%) compared with the OPAT strategy (78.8%) and the usual care/addiction care strategy (77.6%). The OPAT strategy was the least expensive at $412 150 per person. Compared with the OPAT strategy, the partial oral antibiotic strategy had an ICER of $163 370 per LY. Increasing IDU-IE treatment uptake and decreasing treatment discontinuation made the partial oral antibiotic strategy more cost-effective compared with the OPAT strategy. When assuming that all patients with IDU-IE were eligible to receive partial oral antibiotic therapy, the strategy was cost-saving and resulted in 0.0247 additional discounted LYs. When treatment discontinuation was decreased from 3.30% to 2.65% per week, the partial oral antibiotic strategy was cost-effective compared with OPAT at the $100 000 per LY threshold. CONCLUSIONS AND RELEVANCE: In this decision analytical modeling study, incorporation of OPAT or partial oral antibiotic approaches along with addiction care services for the treatment of patients with IDU-IE was associated with increases in the number of people completing treatment, decreases in mortality, and savings in cost compared with the usual care strategy of providing inpatient IV antibiotic therapy alone.

DALBACEN cohort: dalbavancin as consolidation therapy in patients with endocarditis and/or bloodstream infection produced by gram-positive cocci.

OBJECTIVES: To analyse the effectiveness of dalbavancin (DBV) in clinical practice as consolidation therapy in patients with bloodstream infection (BSI) and/or infective endocarditis (IE) produced by gram-positive cocci (GPC), as well as its safety and pharmacoeconomic impact. METHODS: A multicentre, observational and retrospective study was conducted of hospitalised patients with IE and/or BSI produced by GPC who received at least one dose of DBV. Clinical response was assessed during hospitalization, at 3 months and at 1 year. RESULTS: Eighty-three patients with median age of 73 years were enrolled; 73.5% were male; 59.04% had BSI and 49.04% IE (44.04% prosthetic valve IE, 32.4% native IE, 23.5% pacemaker lead). The most frequently isolated microorganism was Staphylococcus aureus in BSI (49%) and coagulase-negative staphylococci in IE (44.1%). All patients with IE were clinically cured in hospital; at 12 months, there was 2.9% loss to follow-up, 8.8% mortality unrelated to IE, and 2.9% therapeutic failure rate. The percentage effectiveness of DBV to treat IE was 96.7%. The clinical cure rate for BSI was 100% during hospital stay and at 3 months; there were no recurrences or deaths during the follow-up. No patient discontinued treatment for adverse events. The saving in hospital stay was 636 days for BSI (315,424.20€) and 557 days for IE (283,187.45€). CONCLUSIONS: DBV is an effective consolidation antibiotic therapy in clinically stabilized patients with IE and/or BSI. It proved to be a cost-effective treatment, reducing the hospital stay, thanks to the pharmacokinetic/pharmacodynamic profile of this drug.

Benefits of a Pre-Treatment Comprehensive Geriatric Assessment in a Rare Case of Gemella Haemolysans Endocarditis in an 86-Year-Old Patient and a Review of the Literature.

Infective endocarditis is a serious condition, which is associated with high mortality in elderly patients. Gemella haemolysans (GH) is a microorganism from the Streptococcus family, rarely involved in infective endocarditis. Here, we present a case of Gemella haemolysans endocarditis in an 86-year-old patient, successfully treated by antibiotics and surgery following a pre-treatment comprehensive geriatric assessment (CGA). This case is discussed in the context of a review of all published cases of Gemella haemolysans endocarditis. We illustrate the benefit of a systematic pre-treatment comprehensive geriatric assessment in elderly patients with infective endocarditis.

Methicillin-Resistant Staphylococcus aureus Prosthetic Valve Endocarditis: Pathophysiology, Epidemiology, Clinical Presentation, Diagnosis, and Management.

Staphylococcus aureus prosthetic valve endocarditis (PVE) remains among the most morbid bacterial infections, with mortality estimates ranging from 40% to 80%. The proportion of PVE cases due to methicillin-resistant Staphylococcus aureus (MRSA) has grown in recent decades, to account for more than 15% of cases of S. aureus PVE and 6% of all cases of PVE. Because no large studies or clinical trials for PVE have been published, most guidelines on the diagnosis and management of MRSA PVE rely upon expert opinion and data from animal models or related conditions (e.g., coagulase-negative Staphylococcus infection). We performed a review of the literature on MRSA PVE to summarize data on pathogenic mechanisms and updates in epidemiology and therapeutic management and to inform diagnostic strategies and priority areas where additional clinical and laboratory data will be particularly useful to guide therapy. Major updates discussed in this review include novel diagnostics, indications for surgical management, the utility of aminoglycosides in medical therapy, and a review of newer antistaphylococcal agents used for the management of MRSA PVE.

Infective Endocarditis: Update on Epidemiology, Outcomes, and Management.

PURPOSE OF REVIEW: Infective endocarditis remains a highly mortal disease, yet the diagnosis often is missed or made only late in the disease course. The spectrum of patients presenting with endocarditis is shifting with different risk factors, predisposing patient characteristics, and treatment recommendations than in the past. This review addresses changes in the epidemiology of infective endocarditis, along with current diagnostic imaging modalities, treatment recommendations, and mortality trends. RECENT FINDINGS: Risk factors for endocarditis now include the growing population of adults with congenital heart disease and patients with frequent healthcare contact for other comorbidities, as well as patients who are hemodialysed and immunocompromised or use intravenous drugs. Although transthoracic and transesophageal echocardiography are essential for diagnosis, additional testing (nuclear, computed tomographic, and magnetic resonance imaging) is helpful in selected patients. Early surgical management, even in high-risk patients, has a mortality benefit because eradication of infection with antibiotics alone is difficult and because valve destruction often results in hemodynamic compromise. As part of a broad differential diagnosis, clinicians should consider the diagnosis of endocarditis in patients with risk factors, even when the clinical presentation is nonspecific. Blood cultures and echocardiography are the first steps for diagnosis. Other imaging modalities can enhance diagnosis, particularly in patients with intracardiac devices or prosthetic material. Evidence from observational studies support early surgical intervention to reduce morbidity and mortality from this lethal condition.

Efficiency of a self-administered outpatient parenteral antimicrobial therapy (s-opat) for infective endocarditis within the context of a shortened hospital admission based on hospital at home program.

OBJECTIVE: This study aimed to evaluate the efficiency of treatment of infectious endocarditis (IE) via Self-administered Outpatient Parenteral Antimicrobial Therapy (S-OPAT) supported by a shortening hospital admission program in a hospitalization-at-home unit (HAH), including a short review of the literature. METHODS: Ambispective cohort study of 57 episodes of IE in 54 patients treated in an HAH unit between 1988 and 2014 who receive S-OPAT after prior intra-hospital clinical stabilization. Characteristics of each episode of IE, safety and efficiency of the care model, were analyzed. RESULTS: Forty-three (76%) patients were males with a median age of 61 years (SD = 16.5). A total of 37 (65%) episodes affected the native valve (42% the aortic valve). In 75%, a micro-organism was isolated, of which 88% were Gram-positive bacteria. No deaths occurred during HAH program, clinical complications appeared in 30% of episodes, only 6 patients were re-admitted to hospital although no patient died. In the 12 months' follow-up 3 cases had a recurrence. The average cost of a day stay in HAH was €174 while in traditional cardiology hospitalization was €1100. The total average cost of treatment of each episode of IE managed entirely in hospital was calculated as €54,723. Application of the S-OPAT model based on HAH meant a cost reduction of 32.72%. CONCLUSIONS: In suitably selected patients, treatment of IE based on S-OPAT supported by a shortening hospital admission care program by means of referral to a HAH unit is a safe and efficient care model which entails a significant cost saving for the public healthcare system.

AUC/MIC Pharmacodynamic Target Is Not a Good Predictor of Vancomycin Efficacy in Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis.

The aim of this in vivo study was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistant Staphylococcus aureus (MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested. Overall, for VAN-SD and VAN-AD, the rates of sterile vegetations were 15/45 (33.3%) and 21/49 (42.8%) (P = 0.343), while the medians (interquartile ranges [IQRs]) for log10 CFU/g of vegetation were 2 (0 to 6.9) and 2 (0 to 4.5) (P = 0.384), respectively. In conclusion, this VAN AUC/MIC pharmacodynamic target was not a good predictor of vancomycin efficacy in MRSA experimental endocarditis.

Evaluation of Daptomycin Exposure and Efficacy and Safety Endpoints To Support Risk-versus-Benefit Considerations.

The choice of an antimicrobial agent must balance optimization of efficacy endpoints with the minimization of safety events. The risk versus benefit of daptomycin for patients with Staphylococcus aureus bacteremia with or without infective endocarditis receiving daptomycin at 6, 8, and 10 mg/kg of body weight/day was assessed. The relationships between the area under the concentration-time curve over 24 h (AUC)/MIC ratio and both clinical response and time to decreased susceptibility were evaluated using data from patients with such infections who received daptomycin at 6 mg/kg/day. Using these relationships, plus the previously identified relationship between the minimum concentration and an elevation in the creatine phosphokinase (CPK) concentration (CPK elevation) (S. M. Bhavnani, C. M. Rubino, P. G. Ambrose, and G. L. Drusano, Clin Infect Dis 50:1568-1574, 2010) and Monte Carlo simulation, the probability of each outcome by MIC for daptomycin at 6, 8, and 10 mg/kg/day was calculated. The function for exposure-response relationships for clinical response (P = 0.06) and time to decreased susceptibility (P = 0.01) resembled U and inverted U shapes, respectively. Multivariable analyses demonstrated AUC/MIC ratio, creatinine clearance, albumin concentration, and disease category to be predictors of clinical response. The results of simulations failed to demonstrate large improvements in the probabilities of clinical success among cohorts of simulated patients defined by the above-described predictive factors or the probability of decreased susceptibility at 30 days when the daptomycin dose was increased from 6 to 10 mg/kg/day. The probability of CPK elevation increased from 0.073 to 0.156 over this dose range. These data can be used to inform risk-versus-benefit decisions for daptomycin dose selection in patients with S. aureus bacteremia with or without infective endocarditis. The risk of CPK elevation, which is reversible, should be weighed in the context of the mortality and severe morbidity associated with these types of serious staphylococcal infections.

Two- and live/real time three-dimensional transthoracic echocardiographic assessment of infective endocarditis of a valved pulmonary conduit.

We describe the use of a nonstandard left infraclavicular approach in making the diagnosis of an infected valved conduit with two-dimensional transthoracic echocardiography. The patient was an adult with tetralogy of Fallot and pulmonary atresia who had undergone multiple surgical repair procedures. The initial diagnosis of infective endocarditis was made by transesophageal echocardiography. Both techniques demonstrated a single, large vegetation in the conduit. Live/real time three-dimensional transthoracic echocardiography, on the other hand, provided further information by demonstrating several additional vegetations in the conduit and more comprehensively assessed their size by enabling measurement of their azimuthal dimensions and volumes. The patient was treated with antibiotics with complete resolution of the vegetations.

Daptomycin pharmacokinetics and pharmacodynamics in a pooled sample of patients receiving thrice-weekly hemodialysis.

While the pharmacokinetic (PK) properties of daptomycin in hemodialysis (HD) patients have been evaluated previously by three groups, resultant dosing recommendations have varied. To address this clinical conundrum, this study combined concentration-time data from these PK evaluations and derived uniform dosing recommendations among patients on HD receiving daptomycin. A two-compartment model with separate HD and non-HD clearance terms was fit to the PK data from these studies by using BigNPAG. Embedded with PK parameters from the population PK analysis, 5,000-subject Monte Carlo simulations (MCS) were performed to identify HD dosing schemes that provided efficacy (cumulative and daily area under the concentration-time curve [AUC] values) and toxicity (trough concentrations of ≥ 24.3 mg/liter) profiles comparable to those from simulations employing the daptomycin PK model derived from the Staphylococcus aureus bacteremia-infective endocarditis (SAB-IE) study. Separate HD dosing schemes were sought for the two weekly interdialytic periods (48 and 72 h). For the 48-h interdialytic period, intra- and post-HD dosing provided the most isometric cumulative and daily AUCs. For the 72-h interdialytic period, all HD dosing schemes provided noncumulative AUC values from 48 to 72 h (AUC(48-72)) that were <50% of the SAB-IE AUC(48-72) values. Increasing the parent dose by 50% intra- or post-HD provided comparable AUC(48-72) values, while maintaining acceptable trough concentration (C(min)) values. When efficacy and toxicity profiles were evaluated for each individual study, higher probabilities for C(min) reaching ≥ 24.3 mg/liter were observed in one of the three studies. Given the high probability of C(min) being ≥ 24.3 mg/liter in one of the three studies, more intensive creatine phosphokinase (CPK) monitoring may be warranted in HD patients receiving daptomycin.

[Pharmacoeconomic analysis of the treatment of methicillin-resistant Staphylococcus aureus with daptomycin or vancomycin]. / Análisis farmacoeconómico del tratamiento de la bacteriemia por Staphylococcus aureus resistente a meticilina con daptomicina y vancomicina.

INTRODUCTION: The increased morbidity, mortality and high costs associated with bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) is a major public health problem. Pharmacoeconomic analysis was performed to compare the efficiency of daptomycin (DAP) against vancomycin (VAN) in the treatment of this infection. METHODS: Retrospective, deterministic and probabilistic cost-effectiveness analysis. The effectiveness of the treatments was estimated from the results of a randomized clinical trial, which compared DAP (6 mg / kg IV daily) and VAN (1 g IV every 12 hours), both with or without gentamicin (1 mg / kg IV every 8 hours). Resource utilization was estimated from the clinical trial of the drug datasheets and Spanish sources, the unit costs were obtained also from Spanish sources. Monte Carlo probabilistic analysis and deterministic analysis were performed. RESULTS: The clinical trial cure rates were higher with DAP (44.4%, 95% CI 43.5 to 45.4%) than with VAN (31.8%, 95% CI 30.9 to 32.7%) not statistically significant (p = 0.2203) but with economic impact. With DAP would occur less costs due to treatment failure (rescue antibiotics, additional tests, prolonged hospital stay and adverse reactions) than with VAN. In the base case the average cost of disease per patient was € 12,329 to € 12,696 with DAP and VAN (difference of 367 €). DAP treatment was dominant (more effective, with lower costs than VAN) both in the deterministic and probabilistic analysis. In the Monte Carlo simulation, DAP was the most cost-effective treatment in 100% of the 10,000 simulations, for a willingness to pay € 12,000 per additional cure (approximate cost of MRSA bacteraemia episode). CONCLUSIONS: According to this model, daptomycin is more cost-effective than vancomycin in treating MRSA bacteremia. The higher cost of acquisition of daptomycin does not imply a higher cost of treating this infection.

Assessment of interindividual variability of plasma concentrations after administrazion of high doses of intravenous amoxicillin or cloxacillin in critically ill patients.

The aim of the present retrospective observational clinical study was to assess the interindividual pharmacokinetic variability of plasma concentrations of amoxicillin or cloxacillin administered in high doses intravenously in critically ill patients, related to renal function or administration method.Four hundred and two plasma concentrations were measured at steady-state with a high performance liquid chromatography technique in 162 patients treated with 100 - 300 mg/kg/day of intravenous amoxicillin or cloxacillin.For both drugs and administration methods, plasma concentrations were significantly higher for patients with creatinine clearance below 60 ml/min, even though doses were adapted for renal impairment. the correlations calculated between plasma concentrations and creatinine level, creatinine clearance or doses were all low. There were fewer outlying drug concentrations in patients receiving continuous rather than intermittent regimens.Our results are in favor of adapting dosages of these beta-lactam antibiotics based on plasma concentrations, especially in cases of renal impairment.

Outcomes and costs associated with a history of vancomycin exposure in patients with MRSA-related complicated bacteremia and infective endocarditis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is the primary cause of complicated bacteremia (CB) and infective endocarditis (IE). Studies have compared the costs of treatment with vancomycin to those of other agents, as well as the efficacy and tolerability of these treatments. However, a literature search found no published studies of the effects of vancomycin exposure on outcomes and hospital costs in patients with CB or IE due to MRSA. OBJECTIVE: The aim of this study was to determine whether there is a quantitative relationship between the duration of vancomycin treatment or cumulative vancomycin exposure and outcomes or costs in patient with CB or IE due to MRSA. METHODS: Electronic medical records of confirmed cases of MRSA-related CB or IE from July 1, 2006, to June 30, 2008, were retrospectively reviewed to identify patients with a history of vancomycin exposure or no vancomycin exposure. Those who received vancomycin were stratified by the amount of drug administered or the duration of treatment to determine the relationship between treatment and outcomes. Data collected included demographic information, treatment information, attributable mortality, MIC data, and hospital costs. Classification and regression tree analysis (CART) was used to determine whether a history of vancomycin exposure was associated with treatment failure, attributable mortality, or both. The Mann-Whitney U test and the Fisher exact test were used for univariate analyses, and logistic regression was used for multivariate modeling. RESULTS: Data from 50 patients were evaluated (CB, 32; IE, 18). Overall rates of failure and attributable mortality were 32% and 16%, respectively. No significant differences were observed between the variables and costs. The CART break points for failure were ≥18.75 g and ≥14 days of vancomycin treatment in the previous 3 years; for attributable mortality, the CART break points were ≥45 g and ≥31 days. In the final multivariate model for failure, ≥18.75 g and ≥14 days of vancomycin treatment in the previous 3 years were predictors of failure (both, P = 0.002). Acute Physiology and Chronic Health Evaluation (APACHE) II score (P = 0.04), ≥45 g (P = 0.002), and ≥31 days of treatment (P = 0.002) in the previous 3 years were predictors of attributable mortality after adjustment for all covariates. CONCLUSIONS: Using the present model, cumulative vancomycin amount and duration were associated with attributable mortality and clinical failure but not with costs.

Ceftriaxone plus gentamicin or ceftriaxone alone for streptococcal endocarditis in Japanese patients as alternative first-line therapies.

This study included 31 patients who had definite or possible infectious endocarditis as defined by the modified Duke's criteria Of these patients, 27 were treated with ceftriaxone plus gentamycin combination therapy and four with ceftriaxone monotherapy. Of these 31 cases, 29 had infections with Streptococcus species, and showed good responses to penicillin G and cefotaxime. Excluding one patient who died because of the underlying disease, all patients achieved clinical cure after treatment with either of the two regimens, showing no recurrence during a follow-up period of 6 months after completion of drug treatment. Although valve replacement was performed in 10 patients during the follow-up period, there were no recurrences in any of these patients 6 months postoperatively. Ceftriaxone allows a simple regimen of once-daily administration. Although indications are limited, ceftriaxone therapy is feasible on an outpatient basis, offering favorable medical economics. Consistent with previous reports, the therapeutic effect of ceftriaxone was equivalent to that of penicillin G in this study, showing this agent to be an alternative first-line drug for infectious endocarditis.

Cost-Effectiveness of daptomycin versus vancomycin and gentamicin for patients with methicillin-resistant Staphylococcus aureus bacteremia and/or endocarditis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an increasingly common cause of bacteremia and endocarditis. The cost-effectiveness (CE) of daptomycin was compared with that of vancomycin-gentamicin in patients with MRSA bacteremia with or without endocarditis. METHODS: With use of data from an open-label, randomized study comparing daptomycin with vancomycin-gentamicin in the aforementioned patient population, 3 cost strata were considered: (1) study drug acquisition (daptomycin, $0.37/mg; vancomycin, $7/g; and gentamicin, $0.12/mg); (2) stratum 1 plus the cost of therapy for treatment failures and adverse events, therapeutic drug monitoring, and preparation and administration of all medications; and (3) stratum 2 plus hospital bed costs. Drug costs were based on mean wholesale price, with other costs based on those for a typical community hospital. Cost-effectiveness ratios were calculated as cost divided by proportion of successes. Sensitivity analyses were performed by varying the study drug cost. RESULTS: Forty-five (20 successes) and 44 (14 successes) patients received daptomycin and vancomycin-gentamicin, respectively. The respective median cost-effectiveness ratios for daptomycin and vancomycin-gentamicin for each cost stratum were as follows: $4082 (range, $1062-$13,893) and $560 (range, $66-$1649) for stratum 1 (P < .001); $4582 (range, $1109-$21,882) and $1635 (range, $163-$33,444) for stratum 2 (P = .026); $23,639 (range, $6225-$141,132) and $26,073 (range, $5349-$187,287) for stratum 3 (P = .82). Sensitivity analyses indicated that if the cost of vancomycin was $0, strata 3 cost-effectiveness ratios did not differ ($23,639 and $25,668, respectively; P = .85). Similar results between groups were seen among patients with bacteremia. CONCLUSIONS: When all costs of therapy were considered, the cost-effectiveness of daptomycin and vancomycin-gentamicin was similar, even if the cost of vancomycin was $0.