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Biomedical subjects

Daniel J Sexton

Publications and source records attributed to Daniel J Sexton.

At least 37 records · Page 2Linked to original sources

Risk of endocarditis among patients with prosthetic valves and Staphylococcus aureus bacteremia.

PURPOSE: Staphylococcus aureus is a common cause of bacteremia and of native valve infective endocarditis. However, the risk of endocarditis in patients with a prosthetic valve who develop S. aureus bacteremia is unclear. The aim of this study was to define the risk of prosthetic valve endocarditis in patients with S. aureus bacteremia. SUBJECTS AND METHODS: All patients with a prosthetic valve or ring who developed S. aureus bacteremia during the 94-month study period were prospectively evaluated. The modified Duke criteria were used for the diagnosis of endocarditis. Patients were followed up for 12 weeks after the initial diagnosis of S. aureus bacteremia. RESULTS: The overall rate of definite prosthetic valve endocarditis among the study patients was 26/51 (51%). The risk of endocarditis was similar in patients with late (>or=12 months after valve implantation) vs. early S. aureus bacteremia (<12 months after prosthetic valve implantation) (50% vs. 52%, P=1.0), mitral vs. aortic prostheses (62% vs. 48%, P=0.24), and mechanical vs. bioprosthetic valves (62% vs. 44%, P=0.29). The 12-week mortality was higher among patients with definite vs. possible endocarditis (62% vs. 28%, P=0.019). CONCLUSION: In this investigation, approximately half of all patients with prosthetic valves who developed S. aureus bacteremia had definite endocarditis. The risk of endocarditis was independent of the type, location, or age of the prosthetic valve. The mortality of prosthetic valve endocarditis is high. All patients with a prosthetic valve who develop S. aureus bacteremia should be aggressively screened and followed for endocarditis.

Bacteremia↗

Early predictors of in-hospital death in infective endocarditis.

BACKGROUND: Data on early determinants of outcome in infective endocarditis (IE) are limited. We evaluated the prognostic significance of early clinical characteristics in a large, prospective cohort of patients with IE. METHODS AND RESULTS: Two hundred sixty-seven consecutive patients with definite or possible IE by modified Duke criteria and echocardiography performed within 7 days of presentation were evaluated. Acute physiology was assessed by the Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) score at the time of presentation, and early heart failure was diagnosed by Framingham criteria. In-hospital mortality rate in the cohort was 19% and similar for patients with definite or possible IE (20% versus 16%, respectively; P=0.464). Independent predictors of death determined by logistic regression modeling were diabetes mellitus (OR 2.48; 95% CI, 1.24 to 4.96), Staphylococcus aureus as causative organism (OR, 2.06; 95% CI, 1.01 to 4.20), APACHE II score (OR, 1.07; 95% CI, 1.01 to 1.12), and embolic event (OR, 2.79; 95% CI, 1.15 to 6.80). Early echocardiographic findings of the Duke criteria were not predictive of death. CONCLUSIONS: Early in the course of IE, readily available clinical characteristics that reflect the host-pathogen interaction are predictive of in-hospital death. These factors may identify those patients with IE for more aggressive treatment.

APACHE↗

Surgical-site infection due to Staphylococcus aureus among elderly patients: mortality, duration of hospitalization, and cost.

OBJECTIVES: To examine the impact of surgical-site infection (SSI) due to Staphylococcus aureus on mortality, duration of hospitalization, and hospital charges among elderly surgical patients and the impact of older age on these outcomes by comparing older and younger patients with S. aureus SSI. DESIGN: A nested cohort study. SETTING: A 750-bed, tertiary-care hospital and a 350-bed community hospital. PATIENTS: Ninety-six elderly patients (70 years and older) with S. aureus SSI were compared with 2 reference groups: 59 uninfected elderly patients and 131 younger patients with S. aureus SSI. RESULTS: Compared with uninfected elderly patients, elderly patients with S. aureus SSI were at risk for increased mortality (odds ratio [OR], 5.4; 95% confidence interval [CI95], 1.5-20.1), postoperative hospital-days (2.5-fold increase; CI95, 2.0-3.1), and hospital charges (2.0-fold increase; CI95, 1.7-2.4; dollar 41,117 mean attributable charges per SSI). Compared with younger patients with S. aureus SSI, elderly patients had increased mortality (adjusted OR, 2.9; CI95, 1.1-7.6), hospital-days (9 vs 13 days; P = .001), and median hospital charges (dollar 45,767 vs dollar 85,648; P < .001). CONCLUSIONS: Among elderly surgical patients, S. aureus SSI was independently associated with increased mortality, hospital-days, and cost. In addition, being at least 70 years old was a predictor of death in patients with S. aureus SSI.

Academic Medical Centers↗

Staphylococcus aureus bacteremia after median sternotomy: clinical utility of blood culture results in the identification of postoperative mediastinitis.

BACKGROUND: Mediastinitis is a complication of coronary artery bypass graft surgery (CABG) that can be difficult to diagnose. This study evaluated the utility of blood culture results in identifying patients with mediastinitis. METHODS AND RESULTS: All unique patients undergoing CABG at our institution over a 60-month study period (n=5500) and all blood cultures performed on these patients or=1 blood culture drawn within 90 days of CABG. Mediastinitis occurred in 46 of 60 (76.7%) patients with blood cultures positive for Staphylococcus aureus, 15 of 126 (11.9%) patients with blood cultures positive for other pathogens, 37 of 669 (5.5%) patients with blood cultures with no growth, and 44 of 4645 (0.9%) patients with no blood cultures obtained. The isolation of S aureus from even 1 blood culture drawn after or=1 blood culture obtained after CABG. CONCLUSIONS: Among patients with blood cultures drawn after CABG, S aureus bacteremia strongly suggests the presence of mediastinitis.

Academic Medical Centers↗

The value of an infectious diseases specialist.

Infectious diseases (ID) specialists have played a major role in patient care, infection control, and antibiotic management for many years. With the rapidly changing nature of health care, it has become necessary for ID specialists to articulate their value to multiple audiences. This article summarizes the versatile attributes possessed by ID specialists and delineates their value to patients, hospitals, and other integral groups in the health care continuum.

Anti-Bacterial Agents↗

Risk factors for pediatric ventriculoperitoneal shunt infection and predictors of infectious pathogens.

Identification of risk factors for shunt infection and predictors of infectious pathogens may improve current methods to prevent and treat shunt infections. We reviewed data on 820 consecutive ventriculoperitoneal (VP) shunt placement procedures in 442 pediatric patients at our institution during 1992-1998. Ninety-two shunts (11%) developed infection a median of 19 days (interquartile range, 11-35 days) after insertion. Premature birth (relative risk [RR], 4.81; 95% confidence interval [CI], 2.19-10.87), previous shunt infection (RR, 3.83; 95% CI, 2.40-6.13), and intraoperative use of the neuroendoscope (RR, 1.58; 95% CI, 1.01-2.50) were independent risk factors for shunt infection. The bacterial organisms early after shunt surgery (<14 days) were the same as those late after shunt surgery (>14 days). As determined by an analysis of the 92 infected shunts, hospital stay of >3 days at the time of shunt insertion (odds ratio [OR], 5.27; 95% CI, 1.15-25.3) and prior Staphylococcus aureus shunt infection (OR, 5.91; 95% CI, 1.35-25.9) independently increased the odds that S. aureus was the causal pathogen.

Adolescent↗

Novel peptide inhibitors of angiotensin-converting enzyme 2.

Angiotensin-converting enzyme 2 (ACE2), a recently identified human homolog of ACE, is a novel metallocarboxypeptidase with specificity, tissue distribution, and function distinct from those of ACE. ACE2 may play a unique role in the renin-angiotensin system and mediate cardiovascular and renal function. Here we report the discovery of ACE2 peptide inhibitors through selection of constrained peptide libraries displayed on phage. Six constrained peptide libraries were constructed and selected against FLAG-tagged ACE2 target. ACE2 peptide binders were identified and classified into five groups, based on their effects on ACE2 activity. Peptides from the first three classes exhibited none, weak, or moderate inhibition on ACE2. Peptides from the fourth class exhibited strong inhibition, with equilibrium inhibition constants (K(i) values) from 0.38 to 1.7 microm. Peptides from the fifth class exhibited very strong inhibition, with K(i) values < 0.14 microm. The most potent inhibitor, DX600, had a K(i) of 2.8 nm. Steady-state enzyme kinetic analysis showed that these potent ACE2 inhibitors exhibited a mixed competitive and non-competitive type of inhibition. They were not hydrolyzed by ACE2. Furthermore, they did not inhibit ACE activity, and thus were specific to ACE2. Finally, they also inhibited ACE2 activity toward its natural substrate angiotensin I, suggesting that they would be functional in vivo. As novel ACE2-specific peptide inhibitors, they should be useful in elucidation of ACE2 in vivo function, thus contributing to our better understanding of the biology of cardiovascular regulation. Our results also demonstrate that library selection by phage display technology can be a rapid and efficient way to discover potent and specific protease inhibitors.

Amino Acid Sequence↗

Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection.

Data for 479 patients were analyzed to assess the impact of methicillin resistance on the outcomes of patients with Staphylococcus aureus surgical site infections (SSIs). Patients infected with methicillin-resistant S. aureus (MRSA) had a greater 90-day mortality rate than did patients infected with methicillin-susceptible S. aureus (MSSA; adjusted odds ratio, 3.4; 95% confidence interval, 1.5-7.2). Patients infected with MRSA had a greater duration of hospitalization after infection (median additional days, 5; P<.001), although this was not significant on multivariate analysis (P=.11). Median hospital charges were 29,455 dollars for control subjects, 52,791 dollars for patients with MSSA SSI, and 92,363 dollars for patients with MRSA SSI (P<.001 for all group comparisons). Patients with MRSA SSI had a 1.19-fold increase in hospital charges (P=.03) and had mean attributable excess charges of 13,901 dollars per SSI compared with patients who had MSSA SSIs. Methicillin resistance is independently associated with increased mortality and hospital charges among patients with S. aureus SSI.

Female↗

Current best practices and guidelines. Assessment and management of complications in infective endocarditis.

The most important complications of endocarditis are congestive heart failure, paravalvular abscess formation, and embolism, especially stroke. In addition, endocarditis may be complicated by septic arthritis, vertebral osteomyelitis, pericarditis, metastatic abscesses and an array of renal problems ranging from immune-complex glomerulonephritis to renal abscesses. Adverse reactions associated with medical treatment of endocarditis can also result in significant complications such as ototoxicity and nephrotoxicity, skin rashes, and serum sickness. This review focuses on the cardiac, embolic, neurologic and renal complications of endocarditis and discusses how these complications influence the clinical management of individual cases in daily practice.

Embolism↗

Elevated preoperative fasting serum glucose levels increase the risk of postoperative mediastinitis in patients undergoing open heart surgery.

We conducted a case-control study to investigate the relationship between preoperative fasting serum glucose and postoperative mediastinitis in patients undergoing open heart surgery. Multivariate analysis revealed that a glucose level of 126 mg/dL or greater was associated with a significantly increased risk of mediastinitis (OR, 5.25; P = .002).

Blood Glucose↗

Health care--associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections.

BACKGROUND: Bloodstream infections occurring in persons residing in the community, regardless of whether those persons have been receiving health care in an outpatient facility, have traditionally been categorized as community-acquired infections. OBJECTIVE: To develop a new classification scheme for bloodstream infections that distinguishes among community-acquired, health care-associated, and nosocomial infections. DESIGN: Prospective observational study. SETTING: One academic medical center and two community hospitals. PATIENTS: All adult patients admitted to the hospital with bloodstream infection. MEASUREMENTS: Demographic characteristics, living arrangements before hospitalization, comorbid medical conditions, factors predisposing to bloodstream infection, date of hospitalization, dates and number of positive blood cultures, results of microbiological susceptibility testing, dates of hospital discharge or death, and mortality rates at 3 to 6 months of follow-up. RESULTS: 504 patients with bloodstream infections were enrolled; 143 (28%) had community-acquired bloodstream infections, 186 (37%) had health care-associated bloodstream infections, and 175 (35%) had nosocomial bloodstream infections. Of the 186 patients with health care-associated bloodstream infection, 29 resided in a nursing home, 64 were receiving home health care, 78 were receiving intravenous or intravascular therapy at home or in a clinic, and 117 had been hospitalized in the 90 days before their bloodstream infection. Cancer was more common in patients with health care-associated or nosocomial bloodstream infection than in patients with community-acquired bloodstream infection. Intravascular devices were the most common source of health care-associated and nosocomial infections, and Staphylococcus aureus was the most frequent pathogen in these types of infections. Methicillin-resistant S. aureus occurred with similar frequency in the groups with health care-associated infection (52%) and nosocomial infection (61%) but was uncommon in the group with community-acquired bloodstream infection (14%) (P = 0.001). Mortality rate at follow-up was greater in patients with health care-associated infection (29% versus 16%; P = 0.019) or nosocomial infection (37% versus 16%; P < 0.001) than in patients with community-acquired infection. CONCLUSIONS: Health care-associated bloodstream infections are similar to nosocomial infections in terms of frequency of various comorbid conditions, source of infection, pathogens and their susceptibility patterns, and mortality rate at follow-up. A separate category for health care-associated bloodstream infections is justified, and this new category will have obvious implications for choices about empirical therapy and infection-control surveillance.

Adult↗

Acute terminal ileitis associated with pneumococcal bacteremia: case report and review of pneumococcal gastrointestinal diseases.

In this report, we describe a patient with acute terminal ileitis due to Streptococcus pneumoniae, review 3 previously reported cases of isolated enteritis due to S. pneumoniae, and summarize the English-language literature on primary and secondary pneumococcal gastrointestinal diseases. Various theories have been advanced to explain the pathogenesis of this rare and potentially life-threatening form of pneumococcal infection, but the mechanism by which S. pneumoniae causes gastrointestinal disease is still unknown.

Acute Disease↗

Changing patient characteristics and the effect on mortality in endocarditis.

BACKGROUND: Limited data exist on recent demographic and microbiological changes in infective endocarditis (IE) and the impact of these changes on patient survival. METHODS: Data were collected from all patients with definite or possible IE at Duke University Medical Center, Durham, NC, from 1993 to 1999. Logistic regression analysis was used to identify demographic and microbiological changes that occurred in patients with IE over the study period. The impact of these changes on survival was evaluated using Cox proportional hazards modeling. RESULTS: Among the 329 study patients, rates of hemodialysis dependence, immunosuppression, and Staphylococcus aureus infection increased during the study period (P=.04, P=.008, and P<.001, respectively), while rates of infection due to viridans group streptococci decreased (P=.007). Hemodialysis was independently associated with S aureus infection (odds ratio, 3.1; 95% confidence interval, 1.6-5.9). Patients with S aureus IE had a higher 1-year mortality rate (43.9% vs 32.5%; P=.04) that persisted after adjustment for other illness severity characteristics (hazard ratio, 1.5; 95% confidence interval, 1.03-2.3). CONCLUSIONS: The demographic and microbiological characteristics of IE at our institution have changed over the past decade in ways that suggest a link between medical practice and IE characteristics. Staphylococcus aureus has emerged as a dominant cause of IE, and is an independent predictor of mortality. These findings identify clinical settings that may warrant closer surveillance and more aggressive measures in the identification and prevention of endocarditis.

Adult↗

Rocky mountain spotted fever.

Rocky mountain spotted fever (RMSF) is a fulminant tick-borne infection by Rickettsia rickettsii. The classical diagnostic triad is fever, headache and rash in a patient with a recent tick bite. With prompt, appropriate antimicrobial therapy, patient outcomes are excellent. However, RMSF is often misdiagnosed, particularly during the initial stages of illness, and as a result, patient outcomes are sometimes suboptimal.

Animals↗

Current best practices and guidelines. Assessment and management of complications in infective endocarditis.

The most important complications of endocarditis are congestive heart failure, paravalvular abscess formation, and embolism, especially stroke. In addition, endocarditis may be complicated by septic arthritis, vertebral osteomyelitis, pericarditis, metastatic abscesses and an array of renal problems ranging from immune-complex glomerulonephritis to renal abscesses. Adverse reactions associated with medical treatment of endocarditis can also result in significant complications such as ototoxicity and nephrotoxicity, skin rashes, and serum sickness. This review focuses on the cardiac, embolic, neurologic and renal complications of endocarditis and discusses how these complications influence the clinical management of individual cases in daily practice.

Abscess↗

The impact of surgical-site infections following orthopedic surgery at a community hospital and a university hospital: adverse quality of life, excess length of stay, and extra cost.

OBJECTIVE: To measure the impact of orthopedic surgical-site infections (SSIs) on quality of life, length of hospitalization, and cost. DESIGN: A pairwise-matched (1:1) case-control study within a cohort. SETTING: A tertiary-care university medical center and a community hospital. PATIENTS: Cases of orthopedic SSIs were prospectively identified by infection control professionals. Matched controls were selected from the entire cohort of patients undergoing orthopedic surgery who did not have an SSI. Matching variables included type of surgical procedure, National Nosocomial Infections Surveillance risk index, age, date of surgery, and surgeon. MAIN OUTCOME MEASURES: Quality of life, duration of postoperative hospital stay, frequency of hospital readmission, overall direct medical costs, and mortality rate. RESULTS: Fifty-nine SSIs were identified. Each orthopedic SSI accounted for a median of 1 extra day of stay during the initial hospitalization (P = .001) and a median of 14 extra days of hospitalization during the follow-up period (P = .0001). Patients with SSI required more rehospitalizations (median, 2 vs 1; P = .0001) and more total surgical procedures (median, 2 vs 1; P = .0001). The median total direct cost of hospitalizations per infected patient was $24,344, compared with $6,636 per uninfected patient (P = .0001). Mortality rates were similar for cases and controls. Quality of life was adversely affected for patients with SSI. The largest decrements in scores on the Medical Outcome Study Short Form 36 questionnaire were seen in the physical functioning and role-physical domains. CONCLUSIONS: Orthopedic SSIs prolong total hospital stays by a median of 2 weeks per patient, approximately double rehospitalization rates, and increase healthcare costs by more than 300%. Moreover, patients with orthopedic SSIs have substantially greater physical limitations and significant reductions in their health-related quality of life.

Cross Infection↗

Rickettsialpox in North Carolina: a case report.

We report a case of rickettsialpox from North Carolina confirmed by serologic testing. To our knowledge, this case is the first to be reported from this region of the United States. Including rickettsialpox in the evaluation of patients with eschars or vesicular rashes is likely to extend the recognized geographic distribution of Rickettsia akari, the etiologic agent of this disease.

Anti-Bacterial Agents↗