Infective Endocarditis In Intravenous Drug Users Research Articles

Daptomycin Pharmacokinetics and Pharmacodynamics in Patients on Methadone Substitution Therapy.

When administered for severe infections in intravenous drug users (IDUs) at a daily dose of 6 mg/kg, daptomycin displayed abnormal pharmacokinetic parameters compared with those seen in healthy volunteers; specifically, decreased trough and maximum concentrations (Ctrough; Cmax) and increased clearance (CL). The objective of this study was to evaluate the pharmacokinetics and pharmacodynamics of daptomycin administered at a daily dosage of 12 mg/kg for Staphylococcus aureus infective endocarditis (IE) in patients concomitantly treated with methadone, and to compare the results with those published in the literature for healthy controls treated with the same daily dose. Antibiotic treatment included daptomycin (12 mg/kg daily) in combination with an antistaphylococcal β-lactam (cefazolin 2 g three times a day). The minimum inhibitory concentration (MIC) of Staphylococcus aureus isolated through blood cultures was used to calculate pharmacokinetic and pharmacodynamic parameters such as the ratio of the area under the concentration-time curve over 24 h to the MIC (AUC0-24/MIC) and Cmax/MIC. Five IDUs hospitalized for IE were enrolled. The mean measured daptomycin Cmax and Ctrough were 54.1μg/mL (CV: 0.32) and 8.7 μg/mL (CV: 0.59), respectively; the mean calculated AUC0-24 was 742.7 μg×h/mL (CV: 0.31). The estimated average volume of distribution at the steady state (Vd,ss) and the half-life (t1/2) were 316.5 mL/kg (CV: 0.53) and 14.4 h (CV: 0.30), respectively. The mean daptomycin clearance from plasma normalized for body weight (CLwp) was 17.3 mL/(h×kg) (CV: 0.33). The calculated average Cmax and AUC0-24 (183.7 µg/mL and 1277.4 µg×h/mL, respectively) were lower than and statistically significantly different from (p<0.001 and p=0.001, respectively) those expected for healthy volunteers. Treatment of Staphylococcus aureus IE in IDUs on methadone treatment requires the use of high daptomycin daily doses in order to achieve satisfactory pharmacodynamic parameters. Close monitoring of the daptomycin plasma concentration is suggested.

698. 8 Years of Infective Endocarditis in Intravenous and Non-Intravenous Drug Users a Single Center Experience

BackgroundDespite advances in diagnosis and management, infective endocarditis (IE) is associated with considerable morbidity and mortality. Given the emergence of drug- resistant organisms, it is unclear whether this has impacted the characteristics and outcomes of IE among intravenous drug users (IDUs) and non-IDUs.MethodsWe conducted a single center retrospective cohort study. 306 records of hospitalized adults diagnose with IE by ICD-9/ICD-10 codes were identified from 2011 to 2018. 244 patients met criteria. IRB approval was obtained. The baseline demographic, microbiologic, echocardiographic variables and outcomes were extracted from the chart, and compared between IDUs and non-IDUs.Results112 (45.9%) patients were IDUs and significantly younger (mean age 36 vs. 64, p< 0.001). Both methicillin-sensitive (44.6% vs. 23.5%, p< 0.001) and methicillin-resistant (29.5% vs. 13.6%, p= 0.002) Staphylococcus aureus associated IE were more prevalent in IDUs compared to non-IDUs. Streptococcus species (22.7% vs 11.6%, p=0.02), excluding Enterococcus species, and coagulase-negative Staphylococcus (12.1% vs 1.8%, p=0.002) were significantly more prevalent in non-IDUs. IE in IDUs were more likely to have tricuspid valve vegetations (56.3% vs. 13.6%, p< 0.001), whereas non-IDUs were more likely to have mitral valve (39.4% vs. 25%, p=0.02) and aortic valve vegetations (46.2% vs. 15.2%, p< 0.001). 19% of patients with IE underwent valve replacement within 6 months, and 17% died within 90 days. A multivariable model that included age, gender, and IDU status, age was the only variable that remained independently associated with 90-day mortality (adjusted OR 1.031; 95% CI 1.006, 1.057; p< 0.01).ConclusionIn this single-center experience, we found that methicillin-sensitive Staphylococcus aureus was the dominant organism among IDUs and non-IDUs. We also found that methicillin-resistant Staphylococcus aureus was significantly more prevalent among IDUs with IE. Provably related to an increase prevalence of colonization with resistant organisms in the community. Despite the shift in prevalence of methicillin-resistant Staphylococcus aureus among IDUs, there was no increased 90-day mortality risk after adjustment for age and gender.Disclosures All Authors: No reported disclosures

Current profile of infective endocarditis in intravenous drug users: The prognostic relevance of the valves involved

Intravenous drug use is a well-known predisposing condition for infectious diseases [1], such as infective endocarditis (IE). In fact, this condition represents a minor diagnostic criterion for IE. Although incidence of IE in intravenous drug users (IDUs) has decreased during the last decades [2], it is still responsible for 5% to 10% of deaths in IDUs [3]. Even though IDUs have been classically related to right-sided IE (RSIE), left-sided IE (LSIE) has been reported with similar frequency [4]. Nonetheless, the profile and outcome of LSIE in IDUs are not well known and the few reported data about this topic are outdated.

Oral antibiotic therapy for the treatment of infective endocarditis: a systematic review

BackgroundThe role of oral antibiotic therapy in treating infective endocarditis (IE) is not well established.MethodsWe searched MEDLINE, EMBASE and Scopus for studies in which oral antibiotic therapy was used for the treatment of IE.ResultsSeven observational studies evaluating the use oral beta-lactams (five), oral ciprofloxacin in combination with rifampin (one), and linezolid (one) for the treatment of IE caused by susceptible bacteria reported cure rates between 77% and 100%. Two other observational studies using aureomycin or sulfonamide, however, had failure rates >75%. One clinical trial comparing oral amoxicillin versus intravenous ceftriaxone for streptococcal IE reported 100% cure in both arms but its reporting had serious methodological limitations. One small clinical trial (n = 85) comparing oral ciprofloxacin and rifampin versus conventional intravenous antibiotic therapy for uncomplicated right-sided S. aureus IE in intravenous drug users (IVDUs) reported cure rates of 89% and 90% in each arm, respectively (P =0.9); however, drug toxicities were more common in the latter group (62% versus 3%; P <0.01). Major limitations of this trial were lack of allocation concealment and blinding at the delivery of the study drug(s) and assessment of outcomes.ConclusionReported cure rates for IE treated with oral antibiotic regimens vary widely. The use of oral ciprofloxacin in combination with rifampin for uncomplicated right-sided S. aureus IE in IVDUs is supported by one small clinical trial of relatively good quality and could be considered when conventional IV antibiotic therapy is not possible.

Clinical and Molecular Epidemiology of Infective Endocarditis in Intravenous Drug Users

Infective endocarditis (IE) in intravenous drug users has been increasing in incidence. The major pathogen used to be methicillin-susceptible Staphylococcus aureus, but resistant isolates have also been increasing. This study aimed to investigate the clinical characteristics of IE in intravenous drug users and to evaluate the molecular patterns of methicillin-resistant S. aureus (MRSA) that cause IE in these drug users. A total of 37 episodes of IE in intravenous drug users hospitalized from 1980 to 2006 at a 1,250-bed teaching hospital in Southern Taiwan were evaluated retrospectively. The genetic relatedness of S. aureus strains was assessed using pulsed-field gel electrophoresis. Polymerase chain reaction was used to detect Panton-Valentine leukocidin (PVL) and staphylococcal gamma-hemolysin (Hlg), and to determine the staphylococcal chromosomal cassette carrying the mecA methicillin-resistant gene (SCCmec) type. The patients had a mean +/- standard deviation age of 31.5 +/- 9.25 years, with a male predominance of 76%. Hepatitis C was present in all patients. Methicillin-susceptible S. aureus accounted for 76% of infections, and the most common clinical symptoms were fever (97%) and embolic phenomenon (68%). There were 4 MRSA isolates, 3 of which were SCCmec type III. PVL and Hlg genes were found in 2 and 3 MRSA isolates, respectively. Eighty percent similarity was found among the MRSA isolates by pulsed-field gel electrophoresis. Our results suggest that coinfection with hepatitis C was common in intravenous drug users with IE, and that molecular patterns of MRSA isolates had high similarity. SCCmec type III, which is usually hospital-acquired, could have caused the community-associated MRSA endocarditis in our patients.

MRSA tricuspid valve infective endocarditis with multiple embolic lung abscesses treated by combination therapy of vancomycin, rifampicin, and sulfamethoxazole/trimethoprim

A 26-year-old pregnant woman who was an intravenous drug user (IDU) was admitted to our hospital for the treatment of tricuspid valve infective endocarditis (IE) and lung abscesses due to methicillin-resistant Staphylococcus aureus (MRSA). We started to treat her with vancomycin (VCM) alone and then in combination with rifampicin (RFP), but her condition did not improve. Then we added sulfamethoxazole/trimethoprim (SMZ/TMP) to VCM and RFP. After that, she improved rapidly. In Japan, there are very few reports about tricuspid valve IE caused by MRSA in IDUs. This case suggests that the combination of VCM, RFP, and SMZ/TMP may be effective for the treatment of severe MRSA infections.

Infective Endocarditis in Intravenous Drug Users from Italy: the Increasing Importance in HIV-infected Patients

Intravenous drug users (IDUs) are at increased risk of infective endocarditis (IE). Episodes of IE in IDUs were retrospectively analyzed in this multicenter study. Cases were collected between 1986 and 1999. Only definite diagnosis according to the Duke criteria were analyzed. Two hundred and sixty-three cases, including 100 cases in HIV-positive patients, were observed in IDUs. Any right-sided involvement was detected in 167 out of 263 cases (63.5%) and any left-sided involvement in 115 out of 263 cases (43.7%). The tricuspid valve (TV) alone was affected in 135 cases (51.3%), the mitral valve alone in 32 patients (12.1%), the aortic valve alone in 41 cases (15.6%) and the pulmonic valve alone in 3 cases. Staphylococcus aureus was isolated in 156 cases (59.3%) and Streptococcus spp. in 33 cases (12.5%). No major differences were observed between HIV-negative and HIV-positive patients. Any TV valve involvement was significantly associated with female rather than male gender (p = 0.02). There was a significant association between S. aureus etiology and TV involvement (p < 0.0001). The mortality rate was 16%. On multivariate analysis, only left-side IE (p = 0.0006; OR 5.2; 95% CI 2.0-13.5) and age greater than 35 years (p = 0.0068; OR 3.6; 95% CI 1.4-9.0) were independently associated with mortality. Infective endocarditis in IDUs is significantly associated with right-side localization (63.5% for any rightsided heart involvement vs 43.7% for any left-sided heart involvement; OR 2.24; 95% CI 1.55-3.23; p < 0.001). S. aureus is the microorganism most frequently isolated and is significantly associated with TV involvement. Any left-side involvement and age greater than 35 years are independently associated with mortality. HIV infection does not appear to have a significant effect on mortality.

Prospective evaluation of a two-week course of intravenous antibiotics in intravenous drug addicts with infective endocarditis

In a prospective study, a two-week course of antibiotics (cloxacillin 2 g/4 h plus amikacin 7.5 mg/kg/12 h) was evaluated in the therapy of right-sided infective endocarditis in intravenous drug users (IVDU). All IVDU admitted to hospital during the study period who fulfilled the strict criteria for diagnosis of infective endocarditis were analysed. A subgroup of patients with right-sided endocarditis caused by Staphylococcus aureus who had a good prognosis were selected as being eligible for the two-week course of treatment. In a total of 139 episodes of infective endocarditis in IVDU, 72 (51.8%) cases were eligible for the two-week treatment. Of this group, 67 were cured, 4 needed prolongation of treatment to cure the infection and 1 died in hospital of respiratory distress syndrome on day 10 of treatment. In patients not eligible for the two-week treatment, the mortality was higher (24.2% versus 0.7%; p = 0.00015). Drug toxicity in the treated group was low. It can be concluded that administration of cloxacillin and amikacin parenterally for 14 consecutive days was successful in the therapy of right-sided endocarditis in IVDU.