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Biomedical subjects

Adolf W Karchmer

Publications and source records attributed to Adolf W Karchmer.

At least 19 recordsLinked to original sources

Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus.

BACKGROUND: Alternative therapies for Staphylococcus aureus bacteremia and endocarditis are needed. METHODS: We randomly assigned 124 patients with S. aureus bacteremia with or without endocarditis to receive 6 mg of daptomycin intravenously per kilogram of body weight daily and 122 to receive initial low-dose gentamicin plus either an antistaphylococcal penicillin or vancomycin. The primary efficacy end point was treatment success 42 days after the end of therapy. RESULTS: Forty-two days after the end of therapy in the modified intention-to-treat analysis, a successful outcome was documented for 53 of 120 patients who received daptomycin as compared with 48 of 115 patients who received standard therapy (44.2 percent vs. 41.7 percent; absolute difference, 2.4 percent; 95 percent confidence interval, -10.2 to 15.1 percent). Our results met prespecified criteria for the noninferiority of daptomycin. The success rates were similar in subgroups of patients with complicated bacteremia, right-sided endocarditis, and methicillin-resistant S. aureus. Daptomycin therapy was associated with a higher rate of microbiologic failure than was standard therapy (19 vs. 11 patients, P=0.17). In 6 of the 19 patients with microbiologic failure in the daptomycin group, isolates with reduced susceptibility to daptomycin emerged; similarly, a reduced susceptibility to vancomycin was noted in isolates from patients treated with vancomycin. As compared with daptomycin therapy, standard therapy was associated with a nonsignificantly higher rate of adverse events that led to treatment failure due to the discontinuation of therapy (17 vs. 8, P=0.06). Clinically significant renal dysfunction occurred in 11.0 percent of patients who received daptomycin and in 26.3 percent of patients who received standard therapy (P=0.004). CONCLUSIONS: Daptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis. (ClinicalTrials.gov number, NCT00093067 [ClinicalTrials.gov].).

Adult↗

Diagnosis and treatment of diabetic foot infections.

EXECUTIVE SUMMARY: 1. Foot infections in patients with diabetes cause substantial morbidity and frequent visits to health care professionals and may lead to amputation of a lower extremity. 2. Diabetic foot infections require attention to local (foot) and systemic (metabolic) issues and coordinated management, preferably by a multidisciplinary foot-care team (A-II). The team managing these infections should include, or have ready access to, an infectious diseases specialist or a medical microbiologist (B-II). 3. The major predisposing factor to these infections is foot ulceration, which is usually related to peripheral neuropathy. Peripheral vascular disease and various immunological disturbances play a secondary role. 4. Aerobic Gram-positive cocci (especially Staphylococcus aureus) are the predominant pathogens in diabetic foot infections. Patients who have chronic wounds or who have recently received antibiotic therapy may also be infected with Gram-negative rods, and those with foot ischemia or gangrene may have obligate anaerobic pathogens. 5. Wound infections must be diagnosed clinically on the basis of local (and occasionally systemic) signs and symptoms of inflammation. Laboratory (including microbiological) investigations are of limited use for diagnosing infection, except in cases of osteomyelitis (B-II). 6. Send appropriately obtained specimens for culture before starting empirical antibiotic therapy in all cases of infection, except perhaps those that are mild and previously untreated (B-III). Tissue specimens obtained by biopsy, ulcer curettage, or aspiration are preferable to wound swab specimens (A-I). 7. Imaging studies may help diagnose or better define deep, soft-tissue purulent collections and are usually needed to detect pathological findings in bone. Plain radiography may be adequate in many cases, but MRI (in preference to isotope scanning) is more sensitive and specific, especially for detection of soft-tissue lesions (A-I). 8. Infections should be categorized by their severity on the basis of readily assessable clinical and laboratory features (B-II). Most important among these are the specific tissues involved, the adequacy of arterial perfusion, and the presence of systemic toxicity or metabolic instability. Categorization helps determine the degree of risk to the patient and the limb and, thus, the urgency and venue of management. 9. Available evidence does not support treating clinically uninfected ulcers with antibiotic therapy (D-III). Antibiotic therapy is necessary for virtually all infected wounds, but it is often insufficient without appropriate wound care. 10. Select an empirical antibiotic regimen on the basis of the severity of the infection and the likely etiologic agent(s) (B-II). Therapy aimed solely at aerobic Gram-positive cocci may be sufficient for mild-to-moderate infections in patients who have not recently received antibiotic therapy (A-II). Broad-spectrum empirical therapy is not routinely required but is indicated for severe infections, pending culture results and antibiotic susceptibility data (B-III). Take into consideration any recent antibiotic therapy and local antibiotic susceptibility data, especially the prevalence of methicillin-resistant S. aureus (MRSA) or other resistant organisms. Definitive therapy should be based on both the culture results and susceptibility data and the clinical response to the empirical regimen (C-III). 11. There is only limited evidence with which to make informed choices among the various topical, oral, and parenteral antibiotic agents. Virtually all severe and some moderate infections require parenteral therapy, at least initially (C-III). Highly bioavailable oral antibiotics can be used in most mild and in many moderate infections, including some cases of osteomyelitis (A-II). Topical therapy may be used for some mild superficial infections (B-I). 12. Continue antibiotic therapy until there is evidence that the infection has resolved but not necessarily until a wound has healed. Suggestions for the duration of antibiotic therapy are as follows: for mild infections, 12 weeks usually suffices, but some require an additional 12 weeks; for moderate and severe infections, usually 24 weeks is sufficient, depending on the structures involved, the adequacy of debridement, the type of soft-tissue wound cover, and wound vascularity (A-II); and for osteomyelitis, generally at least 46 weeks is required, but a shorter duration is sufficient if the entire infected bone is removed, and probably a longer duration is needed if infected bone remains (B-II). 13. If an infection in a clinically stable patient fails to respond to 1 antibiotic courses, consider discontinuing all antimicrobials and, after a few days, obtaining optimal culture specimens (C-III). 14. Seek surgical consultation and, when needed, intervention for infections accompanied by a deep abscess, extensive bone or joint involvement, crepitus, substantial necrosis or gangrene, or necrotizing fasciitis (A-II). Evaluating the limb's arterial supply and revascularizing when indicated are particularly important. Surgeons with experience and interest in the field should be recruited by the foot-care team, if possible. 15. Providing optimal wound care, in addition to appropriate antibiotic treatment of the infection, is crucial for healing (A-I). This includes proper wound cleansing, debridement of any callus and necrotic tissue, and, especially, off-loading of pressure. There is insufficient evidence to recommend use of a specific wound dressing or any type of wound healing agents or products for infected foot wounds. 16. Patients with infected wounds require early and careful follow-up observation to ensure that the selected medical and surgical treatment regimens have been appropriate and effective (B-III). 17. Studies have not adequately defined the role of most adjunctive therapies for diabetic foot infections, but systematic reviews suggest that granulocyte colony-stimulating factors and systemic hyperbaric oxygen therapy may help prevent amputations (B-I). These treatments may be useful for severe infections or for those that have not adequately responded to therapy, despite correcting for all amenable local and systemic adverse factors. 18. Spread of infection to bone (osteitis or osteomyelitis) may be difficult to distinguish from noninfectious osteoarthropathy. Clinical examination and imaging tests may suffice, but bone biopsy is valuable for establishing the diagnosis of osteomyelitis, for defining the pathogenic organism(s), and for determining the antibiotic susceptibilities of such organisms (B-II). 19. Although this field has matured, further research is much needed. The committee especially recommends that adequately powered prospective studies be undertaken to elucidate and validate systems for classifying infection, diagnosing osteomyelitis, defining optimal antibiotic regimens in various situations, and clarifying the role of surgery in treating osteomyelitis (A-III).

Journal Article↗

Circulating resistin levels are not associated with fat redistribution, insulin resistance, or metabolic profile in patients with the highly active antiretroviral therapy-induced metabolic syndrome.

CONTEXT: The mechanisms underlying the development of the highly active antiretroviral therapy (HAART)-induced metabolic syndrome remain to be fully elucidated. OBJECTIVE: The objective of this study was to investigate whether the adipocyte-secreted hormone, resistin, is associated with anthropometric and metabolic abnormalities of the HAART-induced metabolic syndrome. DESIGN, SETTING, AND PATIENTS: We conducted a cross-sectional study of 227 HIV-positive patients (37 women and 190 men) recruited from the infectious diseases clinics. On the basis of history, physical examination, dual-energy x-ray absorptiometry, and single-slice computed tomography, patients were classified into four groups: non-fat redistribution (n = 85), fat accumulation (n = 42), fat wasting (n = 35), and mixed fat redistribution (n = 56). MAIN OUTCOME MEASURES: The main outcome measures were serum resistin levels and anthropometric and metabolic variables. RESULTS: Mean serum resistin levels were not significantly different among subjects with fat accumulation, fat wasting, or mixed fat redistribution or between these groups and the non-fat redistribution group. We found a weak, but significant, positive correlation between resistin and percent total body fat (r = 0.20; P < 0.01), total extremity fat (r = 0.18; P < 0.01), and abdominal sc fat (r = 0.19; P < 0.01), but not abdominal visceral fat (r = -0.10; P = 0.16) or waist to hip ratio (r = -0.05; P = 0.43). When adjustments were made for gender (women, 3.92 +/- 2.71 ng/ml; men, 2.96 +/- 2.61 ng/ml; P = 0.05), correlations between resistin and the above parameters were no longer significant. Importantly, resistin levels were not correlated with fasting glucose, insulin, homeostasis model assessment of insulin resistance index, triglycerides, or cholesterol levels in the whole group. CONCLUSIONS: Resistin is related to gender, but is unlikely to play a major role in the insulin resistance and metabolic abnormalities of the HAART-induced metabolic syndrome.

Adipose Tissue↗

Improvement in highly active antiretroviral therapy-induced metabolic syndrome by treatment with pioglitazone but not with fenofibrate: a 2 x 2 factorial, randomized, double-blinded, placebo-controlled trial.

We designed a 2 x 2 factorial, randomized, double-blinded, placebo-controlled trial to evaluate the effects of treatment with pioglitazone and/or fenofibrate in patients with highly active antiretroviral therapy (HAART)-induced metabolic syndrome. We found that the administration of pioglitazone, but not fenofibrate, improved insulin resistance, blood pressure, and lipid profile over a 12-month period.

Anti-HIV Agents↗

Prosthetic joint infections.

Success in the treatment of infected orthopedic prosthesis requires the best surgical approach in combination with prolonged optimum targeted antimicrobial therapy. In choosing the surgical option, one must consider the type of infection, condition of the bone stock and soft tissue, the virulence and antimicrobial susceptibility of the pathogen, the general health and projected longevity of the patient, and the experience of the surgeon. If surgery is not possible, an alternative is long-term oral antimicrobial suppression to maintain a functioning prosthesis. Treatment must be individualized for a specific infection in a specific patient.

Anti-Bacterial Agents↗

The impact of methicillin resistance in Staphylococcus aureus bacteremia on patient outcomes: mortality, length of stay, and hospital charges.

OBJECTIVE: To evaluate the impact of methicillin resistance in Staphylococcus aureus on mortality, length of hospitalization, and hospital charges. DESIGN: A cohort study of patients admitted to the hospital between July 1, 1997, and June 1, 2000, who had clinically significant S. aureus bloodstream infections. SETTING: A 630-bed, urban, tertiary-care teaching hospital in Boston, Massachusetts. PATIENTS: Three hundred forty-eight patients with S. aureus bacteremia were studied; 96 patients had methicillin-resistant S. aureus (MRSA). Patients with methicillin-susceptible S. aureus (MSSA) and MRSA were similar regarding gender, percentage of nosocomial acquisition, length of hospitalization, ICU admission, and surgery before S. aureus bacteremia. They differed regarding age, comorbidities, and illness severity score. RESULTS: Similar numbers of MRSA and MSSA patients died (22.9% vs 19.8%; P = .53). Both the median length of hospitalization after S. aureus bacteremia for patients who survived and the median hospital charges after S. aureus bacteremia were significantly increased in MRSA patients (7 vs 9 days, P = .045; 19,212 dollars vs 26,424 dollars, P = .008). After multivariable analysis, compared with MSSA bacteremia, MRSA bacteremia remained associated with increased length of hospitalization (1.29 fold; P = .016) and hospital charges (1.36 fold; P = .017). MRSA bacteremia had a median attributable length of stay of 2 days and a median attributable hospital charge of 6916 dollars. CONCLUSION: Methicillin resistance in S. aureus bacteremia is associated with significant increases in length of hospitalization and hospital charges.

Aged↗

Preventing the influx of vancomycin-resistant enterococci into health care institutions, by use of a simple validated prediction rule.

BACKGROUND: The goal of this study was to develop a validated prediction rule for identification of patients harboring vancomycin-resistant enterococci (VRE) at hospital admission. METHODS: A model for the prediction of patients harboring VRE at admission was created and validated by assigning weighted point values to independent risk factors associated with harboring VRE at admission, in 2 different cohorts of patients from 2 tertiary care hospitals in Boston, Massachusetts. Patients with VRE isolated from clinical culture samples collected within 48 h of hospital admission were compared with patients not harboring VRE. To assess the diagnostic accuracy of the prediction rule, the main outcome measures were patient demographic characteristics, comorbid illnesses, hospitalizations, and antibiotic exposure. RESULTS: A total of 412 patients were enrolled. A risk index score was derived by using the following 6 independent risk factors associated with VRE recovery within 48 h of hospital admission: previous isolation of methicillin-resistant Staphylococcus aureus (MRSA), whether the patient was receiving long-term hemodialysis, transfer from a long-term care facility, antibiotic exposure, prior hospitalization, and age >60 years. On the basis of a point score >or=10, the sensitivity, specificity, and positive and negative predictive values of this prediction rule were 44%, 98%, 81%, and 90%, respectively. CONCLUSIONS: This validated clinical prediction rule provides a novel strategy for the identification of patients at high risk of harboring VRE at hospital admission. Implementation of this rule may reduce the influx of VRE into health care institutions and the overall prevalence of VRE, by targeting VRE-screening measures and contact isolation precautions for these high-risk patients.

Adult↗

Increased antibiotic resistance in respiratory tract pathogens: PROTEKT US--an update.

Three major North American surveillance programs have tracked antimicrobial resistance patterns among isolates of Streptococcus pneumoniae and other common respiratory tract pathogens. The Canadian Bacterial Surveillance Network shows the progressive increase in resistance among pneumococcal S. pneumoniae to penicillin, trimethoprim-sulfamethoxazole, macrolides, and fluoroquinolones. The data from the Tracking Resistance in the United States Today study also show a steady rise in pneumococcal resistance among common antibiotics as well as an increase in multidrug-resistant S. pneumoniae. The US component of the Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin study has detected increasing resistance to many antimicrobial agents among common respiratory isolates, with marked geographic variations in resistance patterns. The patterns of resistance detected by these major surveillance programs are a warning signal regarding the continued emergence of resistance among community-acquired respiratory tract pathogens.

Canada↗

Epidemiological comparison of true methicillin-resistant and methicillin-susceptible coagulase-negative staphylococcal bacteremia at hospital admission.

We performed 2 case-control studies among 108 patients with true coagulase-negative staphylococcal (CoNS) bacteremia diagnosed within 48 h of hospital admission. Seventy-nine patients (73%) with methicillin-resistant (MR) CoNS bacteremia and 29 patients (27%) with methicillin-susceptible (MS) CoNS bacteremia were compared with 79 randomly selected control patients without CoNS bacteremia. The presence of a central venous catheter was an independent risk factor for both MR- and MS-CoNS bacteremia (P<.001). Patients with MR-CoNS bacteremia were more frequently admitted from health care facilities (P=.02), more likely to have had previous MR Staphylococcus aureus infection or colonization (P=.02), and more likely to have received antibiotics in the previous 30 days (P=.02). The probability that bacteremia was caused by an MR strain, rather than an MS strain, was 62% among patients admitted from the community and 84% among patients admitted from health care facilities. This study identified epidemiological characteristics that can be used to distinguish between MR- and MS-CoNS bacteremia and found high rates of methicillin resistance among CoNS isolates recovered from patients admitted from the community, as well as from health care facilities.

Bacteremia↗

Exercise and vitamin E intake are independently associated with metabolic abnormalities in human immunodeficiency virus-positive subjects: a cross-sectional study.

We investigated the relationship among habitual exercise, diet, and the presence of metabolic abnormalities (body fat redistribution, dyslipidemia, and insulin resistance) in a cross-sectional study of 120 human immunodeficiency virus (HIV)-infected subjects with use of bivariate and multivariate regression-analysis models. Total and aerobic exercise were significantly and negatively associated with fasting plasma triglyceride levels in the entire sample and in the fat redistribution group. Inverse associations between total or aerobic exercise and insulin resistance were suggestive but did not achieve statistical significance. Diastolic blood pressure was significantly and inversely associated with supplemental or total but not habitual dietary intake of vitamin E. In conclusion, exercise and vitamin E intake were independently and negatively associated with several phenotypic manifestations of HIV-associated metabolic syndrome, whereas other macro- or micronutrients did not have comparable significance.

Antioxidants↗

A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects.

A randomized, blinded, multicenter trial was conducted to compare fluconazole (800 mg per day) plus placebo with fluconazole plus amphotericin B (AmB) deoxycholate (0.7 mg/kg per day, with the placebo/AmB component given only for the first 5-6 days) as therapy for candidemia due to species other than Candida krusei in adults without neutropenia. A total of 219 patients met criteria for a modified intent-to-treat analysis. The groups were similar except that those who were treated with fluconazole plus placebo had a higher mean (+/- standard error) Acute Physiology and Chronic Health Evaluation II score (16.8+/-0.6 vs. 15.0+/-0.7; P=.039). Success rates on study day 30 by Kaplan-Meier time-to-failure analysis were 57% for fluconazole plus placebo and 69% for fluconazole plus AmB (P=.08). Overall success rates were 56% (60 of 107 patients) and 69% (77 of 112 patients; P=.043), respectively; the bloodstream infection failed to clear in 17% and 6% of subjects, respectively (P=.02). In nonneutropenic subjects, the combination of fluconazole plus AmB was not antagonistic compared with fluconazole alone, and the combination trended toward improved success and more-rapid clearance from the bloodstream.

Adult↗

Human immunodeficiency virus type 1-related lipoatrophy and lipohypertrophy are associated with serum concentrations of leptin.

The relationship between the adipocyte-derived hormone leptin, insulin resistance, and fat redistribution in patients with human immunodeficiency virus (HIV) infection has not been established. We classified a cohort of HIV type 1 (HIV-1)-infected patients with >or=6 months of antiretroviral exposure as having no lipodystrophy (51 patients [43% of the cohort]), lipoatrophy (23 patients [19% of the cohort]), mixed lipodystrophy (29 patients [24% of the cohort]), or lipohypertrophy (17 patients [14% of the cohort]), on the basis of physical examination, anthropometric measurements, and the findings of dual-emission x-ray absorptiometry and computed tomography. Measurements of insulin resistance were higher for patients with each category of lipodystrophy, compared with those observed for patients with no lipodystrophy (P<.001). Mean leptin levels (+/- standard deviation) were lowest in patients with lipoatrophy (1.76+/-1.20 ng/mL), highest in patients with lipohypertrophy (9.10+/-6.86 ng/mL), and significantly different from those in patients without lipodystrophy (3.14+/-2.30 ng/mL; both P<.01). In this cohort of antiretroviral-experienced HIV-infected patients, a low serum level of leptin was independently associated with insulin resistance in patients with lipoatrophy, after controlling for total and regional body fat.

Adult↗

Detection of Staphylococcus aureus in peripheral blood stem cell cultures after sterilization of standard blood cultures.

We report central venous catheter (CVC)-associated Staphylococcus aureus bacteremia detected by apheresis product culture after sterilization of standard blood cultures. A 64-year-old man with non-Hodgkin's lymphoma underwent peripheral blood stem cell (PBSC) collection. Five days after placement of a CVC, inflammation was evident at the insertion site. The CVC was removed and cephalexin was begun. Discharge at the site contained neutrophils and gram-positive cocci in pairs and clusters. Cultures of the discharge, of blood drawn via the CVC, of the CVC tip and of the apheresis product collected that day grew methicillin-susceptible S. aureus (MSSA). Cephalexin was discontinued in favor of oxacillin. Three days after removal of the CVC, PBSC collections were resumed via a contralateral CVC. Three sets of standard blood cultures drawn the day the new CVC was placed and the following day were negative, yet apheresis product cultures from each of these days grew MSSA. PBSC collections were halted, the CVC was removed, and oxacillin was continued via a peripherally inserted central catheter. Transesophageal echocardiography after two weeks of therapy revealed thickened mitral leaflets and damage to the posterior leaflet. Transthoracic echocardiography 11 weeks preceding this study had demonstrated normal mitral valve anatomy and function. Oxacillin was continued for six weeks, after which PBSC collections were resumed. Pulsed-field gel electrophoresis of the MSSA isolates revealed a clonal pattern. Cultures of apheresis product may be more sensitive to the presence of bacteremia than standard blood cultures, and they should guide clinical decisions when the bacteria isolated are potential pathogens or suggest clinical infection.

Blood Cells↗

Infections of intracardiac devices.

Intracardiac devices are increasingly used to correct hemodynamically dysfunctional valves and electrophysiologic abnormalities. These devices become infected at relatively low rates. Nevertheless, when these low rates are applied to widely used devices, significant numbers of infections result. Additionally, these infections have been associated with high degrees of morbidity and high mortality rates. This article reviews the epidemiology, microbiology, clinical presentation, and medical as well as surgical therapy of intracardiac device infections.

Defibrillators, Implantable↗

Hypoadiponectinemia is associated with insulin resistance, hypertriglyceridemia, and fat redistribution in human immunodeficiency virus-infected patients treated with highly active antiretroviral therapy.

A lipodystrophic syndrome and metabolic abnormalities have been observed in HIV-infected patients treated with highly active antiretroviral therapy (HAART). A murine model of lipodystrophy is associated with decreased levels of adiponectin, an adipocyte-secreted protein, the administration of which improves the metabolic syndrome in these mice. To investigate the association of adiponectin with metabolic changes in human lipodystrophy, we conducted a cross-sectional study of 112 HIV-infected patients treated with HAART. Mean adiponectin levels were higher in patients with no fat redistribution (FR) vs. FR (4.8 +/- 5.0 vs. 2.2 +/- 2.7 microg/ml, P < 0.01), but no significant differences in adiponectin levels were observed between FR subgroups. The difference in adiponectin levels between subjects with and without FR remained significant after adjusting for age, gender, leptin, HIV medication use, and CD4 count using logistic regression (odds ratio, 0.54, P = 0.008). Adiponectin was significantly correlated with triglycerides (r = -0.40), abdominal visceral fat (r = -0.35), extremity fat (r = 0.37), insulin resistance (HOMA-IR) (r = -0.28), nucleoside reverse transcriptase inhibitor (NRTI) use (r = -0.32), and high-density lipoprotein (HDL) (r = 0.41) using bivariate analysis (all P < 0.01). The association with HDL weakened but remained significant on multivariate analysis (standard beta = 0.29, P = 0.01). However, the association of adiponectin with HOMA-IR became nonsignificant after adjusting for NRTI use (standard beta = -0.15, P = 0.12), suggesting that changes in adiponectin levels may underlie the effect of NRTI use on insulin resistance. The associations of adiponectin with triglycerides and HOMA-IR were also slightly weakened after adjusting for visceral and extremity fat, indicating that adiponectin may, in part, mediate the effect of FR on triglycerides and insulin resistance. This study indicates that adiponectin is inversely correlated with abdominal visceral fat mass, serum triglycerides, and insulin resistance and is directly correlated with HDL and extremity fat in a sample of HIV-infected patients treated with HAART. The results also indicate that NRTI use may worsen insulin resistance by decreasing adiponectin levels. Thus, adiponectin replacement may be a potential treatment option to ameliorate the metabolic changes observed in this patient population.

Abdomen↗