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Biomedical subjects

D J Sexton

Publications and source records attributed to D J Sexton.

At least 37 records · Page 2Linked to original sources
PubMed1999

Recurrent Staphylococcus aureus bacteremia: pulsed-field gel electrophoresis findings in 29 patients.

To identify risk factors for relapse among 309 prospectively identified cases of Staphylococcus aureus bacteremia, patients with recurrent S. aureus bacteremia were identified, and pulsed-field gel electrophoresis (PFGE) was performed on isolates from both episodes. PFGE banding patterns from both isolates were identical in 23 patients, consistent with relapsed infection. Patients with PFGE-confirmed relapse were more likely by both univariate and multivariate analyses to have an indwelling foreign body (odds ratio [OR]=18.2, 95% confidence interval [CI]=7. 6-43.6; P<.001), to have received vancomycin therapy (OR=4.1, 95% CI=1.5-11.6; P=.008), or be hemodialysis-dependent (OR=4.1, 95% CI=1. 8-9.3; P=.002) than patients who did not develop recurrent bacteremia. These results suggest that recurrent episodes of S. aureus bacteremia are primarily relapses and are associated with an indwelling foreign body, receiving vancomycin therapy, and hemodialysis dependence.

Adult↗
PubMed1999

The incidence of ehrlichial and rickettsial infection in patients with unexplained fever and recent history of tick bite in central North Carolina.

We examined the clinical and laboratory findings of a consecutive series of patients from central North Carolina presenting with fever and a history of tick bite within the preceding 14 days. Evidence of a tick-transmitted pathogen was detected in 16 of 35 patients enrolled over a 2-year period. Nine patients were infected with Ehrlichia chaffeensis, and 6 were infected with a spotted fever group rickettsia; 1 patient had evidence of coinfection with E. chaffeensis and a spotted fever group rickettsia. Four patients had detectable antibodies against the human granulocytic ehrlichiosis agent; however, only 2 had a 4-fold antibody titer rise without detectable antibodies against E. chaffeensis. The other 2 were thought to have cross-reacting antibodies to E. chaffeensis. We conclude that ehrlichial infections may be as common as spotted fever group rickettsial infections in febrile patients from central North Carolina with a recent history of tick bite.

Adult↗
PubMed1999

The impact of surgical-site infections in the 1990s: attributable mortality, excess length of hospitalization, and extra costs.

OBJECTIVE: To determine mortality, morbidity, and costs attributable to surgical-site infections (SSIs) in the 1990s. DESIGN: A matched follow-up study of a cohort of patients with SSI, matched one-to-one with patients without SSI. SETTING: A 415-bed community hospital. STUDY POPULATION: 255 pairs of patients with and without SSI were matched on age, procedure, National Nosocomial Infection Surveillance System risk index, date of surgery, and surgeon. OUTCOME MEASURES: Mortality, excess length of hospitalization, and extra direct costs attributable to SSI; relative risk for intensive care unit (ICU) admission and for readmission to the hospital. RESULTS: Of the 255 pairs, 20 infected patients (7.8%) and 9 uninfected patients (3.5%) died during the postoperative hospitalization (relative risk [RR], 2.2; 95% confidence interval [CI95], 1.1-4.5). Seventy-four infected patients (29%) and 46 uninfected patients (18%) required ICU admission (RR, 1.6; CI95, 1.3-2.0). The median length of hospitalization was 11 days for infected patients and 6 days for uninfected patients. The extra hospital stay attributable to SSI was 6.5 days (CI95, 5-8 days). The median direct costs of hospitalization were $7,531 for infected patients and $3,844 for uninfected patients. The excess direct costs attributable to SSI were $3,089 (CI95, $2,139-$4,163). Among the 229 pairs who survived the initial hospitalization, 94 infected patients (41%) and 17 uninfected patients (7%) required readmission to the hospital within 30 days of discharge (RR, 5.5; CI95, 4.0-7.7). When the second hospitalization was included, the total excess hospitalization and direct costs attributable to SSI were 12 days and $5,038, respectively. CONCLUSIONS: In the 1990s, patients who develop SSI have longer and costlier hospitalizations than patients who do not develop such infections. They are twice as likely to die, 60% more likely to spend time in an ICU, and more than five times more likely to be readmitted to the hospital. Programs that reduce the incidence of SSI can substantially decrease morbidity and mortality and reduce the economic burden for patients and hospitals.

Adult↗
PubMed1999

Nosocomial methicillin-resistant and methicillin-susceptible Staphylococcus aureus primary bacteremia: at what costs?

OBJECTIVE: To determine the attributable hospital stay and costs for nosocomial methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) primary bloodstream infections (BSIs). DESIGN: Pairwise-matched (1:1) nested case-control study. SETTING: University-based tertiary-care medical center. PATIENTS: Patients admitted between December 1993 and March 1995 were eligible. Cases were defined as patients with a primary nosocomial S. aureus BSI; controls were selected according to a priori matching criteria. MEASUREMENTS: Length of hospital stay and total and variable direct costs of hospitalization. RESULTS: The median hospital stay attributable to primary nosocomial MSSA BSI was 4 days, compared with 12 days for MRSA (P=.023). Attributable median total cost for MSSA primary nosocomial BSIs was $9,661 versus $27,083 for MRSA nosocomial infections (P=.043). CONCLUSION: Nosocomial primary BSI due to S. aureus significantly prolongs the hospital stay. Primary nosocomial BSIs due to MRSA result in an approximate threefold increase in direct cost, compared with those due to MSSA.

Adult↗
PubMed1999

Infective endocarditis due to Staphylococcus aureus: 59 prospectively identified cases with follow-up.

Fifty-nine consecutive patients with definite Staphylococcus aureus infective endocarditis (IE) by the Duke criteria were prospectively identified at our hospital over a 3-year period. Twenty-seven (45.8%) of the 59 patients had hospital-acquired S. aureus bacteremia. The presumed source of infection was an intravascular device in 50.8% of patients. Transthoracic echocardiography (TTE) revealed evidence of IE in 20 patients (33.9%), whereas transesophageal echocardiography (TEE) revealed evidence of IE in 48 patients (81.4%). The outcome for patients was strongly associated with echocardiographic findings: 13 (68.4%) of 19 patients with vegetations visualized by TTE had an embolic event or died of their infection vs. five (16.7%) of 30 patients whose vegetations were visualized only by TEE (P < .01). Most patients with S. aureus IE developed their infection as a consequence of a nosocomial or intravascular device-related infection. TEE established the diagnosis of S. aureus IE in many instances when TTE was nondiagnostic. Visualization of vegetations by TTE may provide prognostic information for patients with S. aureus IE.

Adult↗
PubMed1999

Imported African tick bite fever: a case report.

We describe a patient with African tick-bite fever who acquired his infection while visiting rural areas of South Africa and then became sick after returning to the United States. The dominant clinical feature of his illness was the presence of multiple, ulcerated lesions (tache noires). Physicians in the United States and other non-African countries who see travelers returning from southern parts of Africa who give a history of recent tick bite and/or present with multiple, crusted or vesicular skin lesions should be alert to this diagnosis and institute treatment with doxycycline.

Aged↗
PubMed1998

Primary care of HIV infection.

Four cases illustrate some of the issues involved in treating HIV-infected patients in a primary care setting. Primary care physicians are hard-pressed to achieve the same results as infectious disease specialists, yet are increasingly responsible for performing the initial tests, choosing the therapeutic regimen, ensuring the patient's compliance with the regimen, and monitoring the results.

Adult↗
PubMed1998

S-nitrosoglutathione/glutathione disulphide/Cu2+-dependent stimulation of L-arginine transport in human platelets.

In this study, we have examined the effects of authentic nitric oxide (NO), NO+ (NOBF4), glutathione (GSH), glutathione disulphide (GSSG), and S-nitrosoglutathione (GSNO) in the presence and absence of Cu2+, which thermally releases NO from S-nitrosothiols on the transport of L-arginine into the human platelet. The K(M,apparent) was unaffected by NO, NO+, GSH, and GSNO. However, Cu2+ lowered K(M,apparent) by approximately 2.85-fold. Cu2+-dependent lowering of K(M,apparent) was also observed, albeit to a smaller extent when this ion was mixed with GSH (approximately 1.9-fold lower) and GSNO (approximately 2.0-fold). GSSG also lowered K(M,apparent) by approximately 1.5-fold. The Vmax,apparent of L-arginine uptake was unaffected by NO, NO+, GSH, and Cu2+. Vmax,apparent was stimulated by to the largest extent by GSNO (approximately 2.28-fold) and GSNO plus Cu2+ (approximately 2.7-fold). GSSG and GSH plus Cu2+ also increased Vmax,apparent by approximately 1.9-fold. When these parameters are expressed in terms of transport efficiency (Vmax/K(M)) the largest effect of nearly 4.7-fold (over controls) was obtained by a combination of GSNO plus Cu2+. These results suggest that platelet L-Arg transport is not affected either by NO or NO+ but by a thiol-disulphide exchange reactions on the platelet L-Arg transporter, brought about by GSNO and GSSG. Based on these results, a GSNO/GSSG/Cu2+ dependent regulatory mechanism for the uptake of L-arginine in human platelets has been proposed.

Arginine↗
PubMed1998

Dissecting the order of bacteriophage T4 DNA polymerase holoenzyme assembly.

Most biological organisms rely upon a DNA polymerase holoenzyme for processive DNA replication. The bacteriophage T4 DNA polymerase holoenzyme is composed of the polymerase enzyme and a clamp protein (the 45 protein), which functions as a processivity factor by strengthening the interaction between DNA and the holoenzyme. The 45 protein must be loaded onto DNA by a clamp loader ATPase complex (the 44/62 complex). In this paper, the order of events leading to holoenzyme formation is investigated using a combination of rapid-quench and stopped-flow fluorescence spectroscopy kinetic methods. A rapid-quench strand displacement assay in which the order of holoenzyme component addition is varied provided data indicating that the rate-limiting step in holoenzyme assembly is associated with the clamp loading process. Pre-steady-state analysis of the clamp loader ATPase activity demonstrated that the four bound ATP molecules are hydrolyzed stepwise during the clamp loading process in groups of two. Clamp loading was examined with stopped-flow fluorescence spectroscopy from the perspective of the clamp itself, using a site-specific, fluorescently labeled 45 protein. A mechanism for T4 DNA polymerase holoenzyme assembly is proposed in which the 45 protein interacts with the 44/62 complex leading to the hydrolysis of 2 equiv of ATP, and upon contacting DNA, the remaining two ATP molecules bound to the 44/62 complex are hydrolyzed. Once all four ATP molecules are hydrolyzed, the 45 protein is poised on DNA for association with the polymerase to form the holoenzyme.

Adenosine Triphosphatases↗
PubMed1998

Clamp subunit dissociation dictates bacteriophage T4 DNA polymerase holoenzyme disassembly.

Clamp proteins confer processivity to the DNA polymerase during DNA replication. These oligomeric proteins are loaded onto DNA by clamp loader protein complexes in an ATP-dependent manner. The mechanism by which the trimeric bacteriophage T4 clamp protein (the 45 protein) loads and dissociates from DNA was investigated as a function of its intersubunit protein-protein interactions. These interactions were continuously monitored using a fluorescence resonance energy transfer (FRET) based assay. A cysteine mutant of the 45 protein was constructed to facilitate site-specific incorporation of a fluorescent probe at the subunit interface. This site was chosen such that FRET was observed between the introduced fluorescent probe and a tryptophan residue located on the opposing subunit. By use of this fluorescently labeled 45 protein, it was possible to obtain an estimate of an apparent trimer dissociation constant from either a cooperative (0.08 +/- 0.04 microM2 at 25 degrees C) or a noncooperative (0.51 microM and 0.17 microM at 25 degrees C) model. Upon mixing the fluorescently labeled 45 protein with a 45 protein containing 4-fluorotryptophan, a nonfluorescent tryptophan analogue, subunit exchange between the two variants of the 45 protein was observed according to a reduction in intersubunit FRET. Subunit exchange rate constants measured in the presence or absence of the clamp loader (44/62 complex), the polymerase (43 protein), and/or a primer template DNA substrate demonstrate (a) that the 45 protein is not loaded onto DNA by subunit exchange and (b) that the disassembly dissociation of a stalled holoenzyme from DNA is dictated by 45 protein subunit dissociation.

Bacteriophage T4↗
PubMed1998

Incidence and outcome of Staphylococcus aureus bacteremia in hemodialysis patients.

BACKGROUND: Staphylococcus aureus bacteremia is frequently associated with metastatic complications and infective endocarditis (IE). The Duke criteria for the diagnosis of IE utilize echocardiographic techniques and are more sensitive than previous criteria. The documentation of IE in patients undergoing hemodialysis (HD) has become increasingly important in order to avoid the overuse of empiric vancomycin and the emergence of antibiotic resistance. METHODS: Patients who developed S. aureus bacteremia while undergoing HD at a tertiary medical center or one of four affiliated outpatient HD units were identified. Clinical outcome (death, metastatic complications, IE, and microbiologic recurrence) was assessed during hospitalization and at three months after discharge. Transthoracic and transesophageal echocardiograms were performed and the Duke criteria were used to diagnose IE. Pulse field gel electrophoresis was performed to confirm genetic similarity of recurrent isolates. RESULTS: Four hundred and forty-five patients underwent hemodialysis for 5431.8 patient-months. Sixty-two developed 65 episodes of S. aureus bacteremia (1.2 episodes/100 patient-months). Complications occurred in 27 (44%) patients. Bacteremia recurred in patients who dialyzed through polytetrafluorethylene grafts (44.4% vs. 7.1%, P = 0.0.01), and there was a trend to increased recurrence in patients who received only vancomycin (19.5% vs. 7.1%, P = 0.4). IE was diagnosed in 8 patients (12%), six of whom had normal transthoracic echocardiograms. CONCLUSIONS: Sensitive echocardiographic techniques and the Duke criteria for the diagnosis of IE should be used to determine the proper duration of antibiotic therapy in hemodialysis patients with S. aureus bacteremia. This diagnostic approach, coupled with early removal of hardware, may assist in improving outcomes.

Adult↗
PubMed1998

Outcome of Staphylococcus aureus bacteremia according to compliance with recommendations of infectious diseases specialists: experience with 244 patients.

To determine whether recommendations of infectious diseases specialists affect outcome for patients, we evaluated 244 hospitalized patients with Staphylococcus aureus bacteremia. We offered our management recommendations to each patient's physicians and then assessed the clinical outcome for both patients for whom our consultative advice was followed and those for whom our advice was not heeded. All patients were followed up for 12 weeks after their first positive blood culture. Our management advice was followed for 112 patients (45.9%) and partially or completely ignored for 132 patients (54.1%). Patients for whom our recommendations were followed were more likely to be cured of their S. aureus infection and less likely to relapse (P < .01), despite having significantly more metastatic infections (P < .01) at the outset of therapy, than were those for whom our recommendations were not followed. Failure to follow recommendations to remove an infected intravascular device was the most important risk for treatment failure. After controlling for other factors, logistic regression analysis revealed that patients whose intravascular device was not removed were 6.5 times more likely to relapse or die of their infection than were those whose device was removed. Our findings suggest that patient-specific management advice by infectious diseases consultants can improve the clinical outcome for patients with S. aureus bacteremia.

Algorithms↗
PubMed1998

Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci. Endocarditis Treatment Consortium Group.

This randomized, multicenter, open-label study compared the efficacy and safety of monotherapy with 2 g of intravenous ceftriaxone once daily for 4 weeks with those of combination therapy with 2 g of intravenous ceftriaxone and 3 mg of intravenous gentamicin/kg once daily for 2 weeks as therapy for endocarditis due to penicillin-susceptible streptococci. Sixty-one patients were enrolled in the study. Clinical cure was observed for 51 evaluable patients both at termination of therapy and at the 3-month follow-up: 25 (96.2%) of 26 monotherapy recipients and 24 (96%) of 25 combination therapy recipients. Of the 23 patients in each treatment group who were microbiologically evaluable, 22 (95.7%) in each group were considered cured. No patient had evidence of relapse. Fourteen patients (27.5%) required cardiac surgery after initiation of treatment, including five monotherapy recipients and nine combination therapy recipients. Adverse effects were minimal in both treatment groups. We conclude that 2 g of ceftriaxone once daily for 4 weeks and 2 g of ceftriaxone in combination with 3 mg of gentamicin/kg once daily for 2 weeks are both effective and safe for the treatment of streptococcal endocarditis.

Adolescent↗
PubMed1998

Native valve infective endocarditis in elderly and younger adult patients: comparison of clinical features and outcomes with use of the Duke criteria and the Duke Endocarditis Database.

The effect of age on the presentation and outcome of infective endocarditis (IE) is unclear. Many of the available data are based on analyses of mixed populations of patients including intravenous drug users or those with prosthetic valve endocarditis or native valve IE. We used the Duke criteria to compare the characteristics of 44 episodes of definite native valve IE in elderly patients (> 64 years old) with the characteristics of 64 similarly defined episodes of native valve IE in younger, nonintravenous-drug-using adult patients (> 29 years and < 60 years old). Our data suggest that the clinical presentation, characteristics, and outcome of native valve IE are similar for elderly patients and younger adult patients, although elderly patients were hospitalized an average of 12 days longer. Although we found that the occurrence of renal failure and cerebral embolism during an episode of IE was associated with higher rates of death (odds ratios, 4.8 and 4.0, respectively), age was not a significant contributor to mortality.

Adult↗