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D L Paterson

Publications and source records attributed to D L Paterson.

At least 19 recordsLinked to original sources
PubMed2006

Variation in antifungal prophylaxis strategies in lung transplantation.

We conducted a survey of 50 lung transplant centers across the world to evaluate the variation in antifungal prophylaxis practices. These 50 centers performed 63% of the world's lung transplants reported in 2001. Eighty-six percent (43/50) of the centers responded to the survey. Sixty-nine percent (30/43) of centers used universal antifungal prophylaxis. Aerosolized amphotericin B deoxycholate (AmBd) alone or in combination with itraconazole was used at 56% (24/43) of centers. The median duration of prophylaxis with aerosolized AmBd and itraconazole was 30 and 90 days, respectively. Seventy-four percent of the centers surveyed agreed to participate in future research prophylaxis protocols, which they felt should include both diagnostic and therapeutic arms. Our survey is the first documentation of the international variation in antifungal prophylactic strategies in lung transplant recipients, and underscores the need for multicenter, randomized trials of antifungal prophylaxis in lung transplant recipients.

Amphotericin B↗
PubMed2006

Aerosol deposition of lipid complex amphotericin-B (Abelcet) in lung transplant recipients.

Lung transplant recipients exhibit a high incidence of invasive aspergillosis. The inhalation of lipid complex amphotericin-B (Abelcet; ABLC) offers a possible prophylactic strategy. The goals of this study were to select the optimal nebulizer delivery system for ABLC and to measure deposited aerosol dose in 12 lung transplant recipients. In vitro testing was performed to select a nebulizer delivery system, and an empirical model was used to estimate lung deposition. Estimated pulmonary doses varied by as much as 2-fold between different nebulizers. Aerosol deposition testing was performed in six single and six double lung recipients, each of whom received one 7 mL (35 mg) nebulized dose of Technetium-labeled ABLC using the selected nebulizer. In single lung recipients, the average deposited doses were 3.9 +/- 1.6 mg (mean +/- S.D.) in the allograft versus 2.1 +/- 1.1 mg in the native lung. Double lung recipients deposited on average 2.8 +/- 0.8 mg (left lung) and 4.0 +/- 1.3 mg (right lung). The drug was well distributed throughout the lungs, but delivery to the native lung was in some cases suboptimal. These studies provide an important precursor to studies of the efficacy of inhaled ABLC as a prophylaxis of invasive aspergillosis after lung transplant.

Aerosols↗
PubMed2006

Voriconazole prophylaxis in lung transplant recipients.

Lung transplant recipients have one of the highest rates of invasive aspergillosis (IA) in solid organ transplantation. We used a single center, nonrandomized, retrospective, sequential study design to evaluate fungal infection rates in lung transplant recipients who were managed with either universal prophylaxis with voriconazole (n = 65) or targeted prophylaxis (n = 30) with itraconazole +/- inhaled amphotericin in patients at high risk (pre- or posttransplant Aspergillus colonization [except Aspergillus niger]). The rate of IA at 1 year was better in lung transplant recipients receiving voriconazole prophylaxis as compared to the cohort managed with targeted prophylaxis (1.5% vs. 23%; p = 0.001). Twenty-nine percent of cases in the targeted prophylaxis group were in patients colonized with A. niger who did not receive itraconazole. A three-fold or higher increase in liver enzymes was noted in 37-60% of patients receiving voriconazole prophylaxis as compared to 15-41% of patients in the targeted prophylaxis cohort. Fourteen percent in the voriconazole group as compared to 8% in the targeted prophylaxis group had to discontinue antifungal medications due to side effects. Voriconazole prophylaxis can be used in preventing IA in lung transplant recipients. Regular monitoring of liver enzymes and serum concentrations of calcineurin inhibitors are required to avoid hepatotoxicity and nephrotoxicity.

Antifungal Agents↗
PubMed2004

New clinical presentations of invasive aspergillosis in non-conventional hosts.

Infections by Aspergillus spp. are most typically associated with invasive pulmonary aspergillosis. However, an increasing number of reports deal with unusual manifestations of invasive aspergillosis. In the lung this may take the form of chronic invasive pulmonary aspergillosis, bronchocentric granulomatosis or tracehobronchitis. A number of extrapulmonary infections have been noted, sometimes in immunocompetent individuals. Examples include vertebral osteomyelitis, primary cutaneous aspergillosis (such as in premature neonates), prosthetic vascular graft infection and infective endocarditis. Early recognition of these entities, prompt initiation of new, highly active antifungal therapies and adjunctive surgical management may improve the prognosis of these conditions.

Aspergillosis↗
PubMed2003

Appropriate antimicrobial treatment in nosocomial infections-the clinical challenges.

Resistance to antimicrobial agents is emerging in a wide variety of pathogens, particularly those that cause nosocomial infections. As a consequence of this increasing resistance, morbidity and mortality in nosocomial infections is also increasing. It is therefore critical to treat nosocomial infections appropriately by starting antimicrobial treatment early in the course of infection, using the correct agent, at the most appropriate dose, and for an adequate duration. Indeed, early 'appropriate' antibiotic prescribing has been shown significantly to reduce mortality, length of intensive care unit and hospital stay and overall costs. Early use of the correct antibiotic at the appropriate dose and for an adequate duration are key to initial appropriate antibiotic prescribing. Choosing the right antibiotic depends mainly on the likely pathogen(s) and the expected local susceptibility patterns. Selection of appropriate antimicrobial therapy requires a thorough understanding of the likely microbial cause of the infection, including local susceptibility patterns, as well as the properties of the antimicrobials available for treating these infections, namely spectrum of activity and potency (including activity versus known resistance mechanisms), pharmacokinetic profile and tolerability and safety. This review, based on a series of presentations at the 5th International Conference of the Hospital Infection Society (Edinburgh, 2002) examines the importance of appropriate antimicrobial therapy in nosocomial infections, and provides guidance on how to achieve this.

Anti-Infective Agents↗
PubMed2001

Control of an outbreak of infection due to extended-spectrum beta-lactamase--producing Escherichia coli in a liver transplantation unit.

We report an outbreak of infection due to genotypically identical extended-spectrum beta-lactamase--producing Escherichia coli among patients in a liver transplantation unit. Control of the outbreak was achieved by a combination of contact isolation, feedback on hand hygiene, and gut decontamination with an orally administered fluoroquinolone. These interventions led to abrupt curtailment of the outbreak.

Disease Outbreaks↗
PubMed2001

Preemptive prophylaxis with a lipid preparation of amphotericin B for invasive fungal infections in liver transplant recipients requiring renal replacement therapy.

BACKGROUND: Posttransplant renal replacement therapy has been shown to be an independently significant risk factor for invasive fungal infections after liver transplantation. We assessed the efficacy of a lipid preparation of amphotericin B as prophylaxis for invasive fungal infections, directed toward liver transplant recipients requiring renal replacement therapy. METHODS: A total of 148 patients transplanted between 1990 and 1997 received no antifungal prophylaxis. Since 1997, 38 patients underwent liver transplantation; antifungal prophylaxis with a lipid preparation of amphotericin B was used in patients requiring renal replacement therapy. RESULTS: Fifteen percent (22 of 148) of the patients transplanted before 1997 required renal replacement therapy. In this cohort, the incidence of invasive fungal infections (36% vs. 7%, P=0.0007) and invasive aspergillosis (14% vs. 2%, P=0.02) was significantly higher in patients who required renal replacement therapy compared with those who did not. Since 1997, 29% (11 of 38) of the patients required renal replacement therapy and received antifungal prophylaxis. Invasive fungal infections occurred in 36% (8 of 22) of the patients who received no prophylaxis (patients before 1997), and 0% (0 of 11, P=0.03) in those who received antifungal prophylaxis (since 1997). Antifungal prophylaxis was independently associated with protection from fungal infection (P=0.017). No reduction in mortality with antifungal prophylaxis was documented. CONCLUSION: Prophylaxis with a lipid preparation of amphotericin B was associated with a significant reduction in invasive fungal infections in high-risk liver transplant recipients, i.e., those requiring renal replacement therapy. However, no beneficial effect on survival could be documented.

Adult↗
PubMed2001

Spontaneous gram-negative cellulitis in a liver transplant recipient.

A 47-year-old liver transplant recipient developed fever and cellulitis on the 8th post-transplant day. The clinical appearances were of a rapidly advancing cellulitis. The patient had a past history of severe peripheral edema and hypoalbuminemia. Blood cultures and skin biopsy grew Escherichia coli. To our knowledge, this is the first reported case of E. coli cellulitis in a liver transplant recipient. However, cases have previously been described in patients with cirrhosis or idiopathic nephritic syndrome, conditions which share predisposing features of peripheral edema and hypoalbuminemia. Bacteremic gram-negative cellulitis should be considered in compromised patients with unusual presentations of cellulitis.

Biopsy↗
PubMed2001

Extended-spectrum beta-lactamases: the European experience.

Extended-spectrum beta-lactamases mediate resistance to cephalosporin antibiotics and were first discovered in Europe in the early 1980s. They have become a widespread problem, particularly in Klebsiella pneumoniae, but increasingly in non-typhoid Salmonella species. Traditionally, extended-spectrum beta-lactamases have been derivatives of TEM and SHV parent enzymes. The last year, however, has seen an explosion of developments in extended-spectrum beta-lactamases of non-TEM, non-SHV lineage in Europe. The CTX-M type extended-spectrum beta-lactamases have become particularly widespread. At the same time, European clinical microbiology laboratories have become more aware of the pressing need for detection methods given increasing awareness of the lack of reliability of cephalosporins in the treatment of extended-spectrum beta-lactamase producers.

Bacteria↗
PubMed2001

Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum beta-lactamases: implications for the clinical microbiology laboratory.

Although extended-spectrum beta-lactamases (ESBLs) hydrolyze cephalosporin antibiotics, some ESBL-producing organisms are not resistant to all cephalosporins when tested in vitro. Some authors have suggested that screening klebsiellae or Escherichia coli for ESBL production is not clinically necessary, and when most recently surveyed the majority of American clinical microbiology laboratories did not make efforts to detect ESBLs. We performed a prospective, multinational study of Klebsiella pneumoniae bacteremia and identified 10 patients who were treated for ESBL-producing K. pneumoniae bacteremia with cephalosporins and whose infecting organisms were not resistant in vitro to the utilized cephalosporin. In addition, we reviewed 26 similar cases of severe infections which had previously been reported. Of these 36 patients, 4 had to be excluded from analysis. Of the remaining 32 patients, 100% (4 of 4) patients experienced clinical failure when MICs of the cephalosporin used for treatment were in the intermediate range and 54% (15 of 28) experienced failure when MICs of the cephalosporin used for treatment were in the susceptible range. Thus, it is clinically important to detect ESBL production by klebsiellae or E. coli even when cephalosporin MICs are in the susceptible range (<or = 8 microg/ml) and to report ESBL-producing organisms as resistant to aztreonam and all cephalosporins (with the exception of cephamycins).

Adolescent↗
PubMed2001

Dyslipidaemia in HIV-infected patients: association with adherence to potent antiretroviral therapy.

Metabolic complications are being increasingly recognized among HIV-infected patients treated with potent combination antiretroviral therapies. We sought to assess the association of dyslipidaemia with adherence to protease inhibitor (PI) therapy and with the markers of clinical response to antiretroviral therapy (CD4 count, HIV RNA viral level) through a prospective, cross-sectional cohort study. Fifty-six HIV-infected patients who were already on, or who were started on PI-containing antiretroviral therapy were monitored for the development of dyslipidaemias. Therapy with PI-containing antiretroviral therapy was significantly associated with elevated serum triglyceride level (>250 mg/dl) (52% vs 8%, P=0.001). Patients with an adherence rate of at least 80% to a PI-containing regimen were significantly more likely to have elevated low density lipoprotein (LDL) cholesterol level as compared to patients with an adherence rate of <80% (79% vs 26%, P=0.03). Patients with an adherence rate of at least 80% to a PI-containing regimen were also significantly more likely to have severe hypertriglyceridaemia (>800 mg/dl) as compared to patients with an adherence rate of <80% (21% vs 4%, P=0.04). Viral load at the last study visit did not correlate with total cholesterol (r=-0.39, P=0.30), LDL cholesterol (r=0.57, P=0.30), or triglyceride level (r=0.55, P=0.20). However, there was a significant correlation between the last viral load and high density lipoprotein (HDL) cholesterol (r=0.79, P=0.035), i.e. lower viral load was associated with higher HDL cholesterol level. In conclusion, dyslipidaemia in patients with HIV infection was significantly associated with adherence to PI-containing antiretroviral therapy. Patients who are adherent to PI-containing regimens at least 80% of the time warrant close monitoring for the development of dyslipidaemia.

Adult↗
PubMed2001

Rapid method of extraction and analysis of extended-spectrum beta-lactamases from clinical strains of Klebsiella pneumoniae.

The extraction of periplasmic beta-lactamases from Gram-negative bacilli is a necessary preliminary step to analytical isoelectric focusing. Previously described methods are time-consuming and require large amounts of broth. We describe a lysozyme-based method which needs just 5 mL broth and requires less than 24 h to perform. The method was reproducible in extracting beta-lactamases from reference strains containing known beta-lactamases. We applied the method to a collection of more than 70 extended-spectrum beta-lactamase-producing isolates from a multinational study of bacteremic isolates of Klebsiella pneumoniae. Further studies are being undertaken to assess the method's applicability to other bacterial species.

Humans↗
PubMed2000

Cytomegalovirus antigenemia directed pre-emptive prophylaxis with oral versus I.V. ganciclovir for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, controlled trial.

BACKGROUND: The efficacy of pre-emptively administered oral ganciclovir in preventing cytomegalovirus (CMV) disease has not been documented in liver transplant recipients. We sought to compare the efficacy of pre-emptive oral ganciclovir with that of i.v. ganciclovir for the prevention of CMV disease after liver transplantation, and to determine whether withholding prophylaxis in the absence of CMV antigenemia, reliably identified patients in whom no prophylaxis was necessary. METHODS: Surveillance cultures for CMV pp65 antigenemia were performed in all patients at weeks 2, 4, 6, 8, 12, and 16. Patients with CMV antigenemia were randomized into two study groups. The experimental group received oral ganciclovir for 6 weeks (2 g t.i.d. for 2 weeks, then 1 g t.i.d. for 4 weeks), and the control group received i.v. ganciclovir (5 mg/kg q 12 hr) for 7 days. RESULTS: Of 72 consecutive liver transplant recipients studied, CMV antigenemia occurred in 31% (22 of 72). Twenty-two patients with asymptomatic antigenemia were randomized to two study groups. CMV disease (viral syndrome) occurred in 9% (1 of 11) of the patients in the i.v. ganciclovir group and in 0% (0 of 11) of the patients in the oral ganciclovir group. None of the study patients developed tissue invasive CMV disease. The median reduction in antigenemia level with oral ganciclovir was 55% at week 1, and 100% at week 2. Overall, 64% of the patients by week 1, 93% by week 2, and 100% by week 4 had antigenemia levels below the baseline after oral ganciclovir. Of 50 patients without CMV antigenemia, none developed CMV disease. CONCLUSIONS: Pre-emptive prophylaxis based on CMV antigenemia can effectively target the patients for CMV prophylaxis; 69% of the patients never received antiviral prophylaxis and did not develop CMV disease. Antiviral therapy instituted upon detection of antigenemia prevented tissue invasive CMV in both ganciclovir groups. Pre-emptively administered oral ganciclovir was effective as prophylaxis for CMV disease after liver transplantation.

Administration, Oral↗
PubMed2000

Adherence to protease inhibitor therapy and outcomes in patients with HIV infection.

BACKGROUND: Combination antiretroviral therapy with protease inhibitors has transformed HIV infection from a terminal condition into one that is manageable. However, the complexity of regimens makes adherence to therapy difficult. OBJECTIVE: To assess the effects of different levels of adherence to therapy on virologic, immunologic, and clinical outcome; to determine modifiable conditions associated with suboptimal adherence; and to determine how well clinicians predict patient adherence. DESIGN: Prospective, observational study. SETTING: HIV clinics in a Veterans Affairs medical center and a university medical center. PATIENTS: 99 HIV-infected patients who were prescribed a protease inhibitor and who neither used a medication organizer nor received their medications in an observed setting (such as a jail or nursing home). MEASUREMENTS: Adherence was measured by using a microelectronic monitoring system. The adherence rate was calculated as the number of doses taken divided by the number prescribed. Patients were followed for a median of 6 months (range, 3 to 15 months). RESULTS: During the study period, 45,397 doses of protease inhibitor were monitored in 81 evaluable patients. Adherence was significantly associated with successful virologic outcome (P < 0.001) and increase in CD4 lymphocyte count (P = 0.006). Virologic failure was documented in 22% of patients with adherence of 95% or greater, 61% of those with 80% to 94.9% adherence, and 80% of those with less than 80% adherence. Patients with adherence of 95% or greater had fewer days in the hospital (2.6 days per 1000 days of follow-up) than those with less than 95% adherence (12.9 days per 1000 days of follow-up; P = 0.001). No opportunistic infections or deaths occurred in patients with 95% or greater adherence. Active psychiatric illness was an independent risk factor for adherence less than 95% (P = 0.04). Physicians predicted adherence incorrectly for 41% of patients, and clinic nurses predicted it incorrectly for 30% of patients. CONCLUSIONS: Adherence to protease inhibitor therapy of 95% or greater optimized virologic outcome for patients with HIV infection. Diagnosis and treatment of psychiatric illness should be further investigated as a means to improve adherence to therapy.

Adult↗
PubMed2000

Encephalitis caused by human herpesvirus-6 in transplant recipients: relevance of a novel neurotropic virus.

BACKGROUND: Human herpesvirus-6 (HHV-6) is a neurotropic virus. Encephalitis is a significant clinical manifestation of HHV-6; however, sparse data on this entity exist in transplant recipients. METHODS: Cases of HHV-6 encephalitis reported in the literature (13 bone marrow transplant recipients and 1 liver transplant recipient) were reviewed. The diagnosis was established in all by viral isolation and/or detection of HHV-6 DNA in the cerebrospinal fluid by polymerase chain reaction or histopathologic method. RESULTS: HHV-6 encephalitis occurred a median of 45 days (range 10 days to 15 months) after transplantation. Mental status changes, ranging from confusion to coma (92%), seizures (25%), and headache (25%) were the predominant clinical presentations. Focal neurologic findings occurred in only 17% of the patients. Twenty-five percent of the patients had fever; however, the height of fever (< or =40 degrees C) in febrile patients was striking. Cerebrospinal fluid pleocytosis was generally lacking. Abnormal neuroimaging findings, characterized by low-attenuation lesions in the posterior cerebral lobes, were present only in 17% of the patients. Overall mortality in patients with HHV-6 encephalitis was 58% (7 of 12); 42% (5 of 12) of the deaths were caused by HHV-6. Cure was documented in 7 of 8 patients who received ganciclovir or foscarnet for > or =7 days, compared with 0% (0 of 4) in those who did not receive these drugs or received them for < 7 days (P=.01). CONCLUSIONS: HHV-6 may be associated with encephalitis after transplantation and warrants consideration in transplant recipients with encephalitis of unidentifiable etiology.

Adolescent↗
PubMed2000

Predicting bacteremia and bacteremic mortality in liver transplant recipients.

Predictors of bacteremia and mortality in bacteremic liver transplant recipients were prospectively assessed. One hundred eleven consecutive episodes of fever or infections were documented in 59 patients over a 4-year period. Forty-nine percent (29 of 59 patients) of the patients had bacteremia, 39% (23 of 59 patients) had nonbacteremic infections, and 12% (7 of 59 patients) had fever of noninfectious cause. Primary (catheter-related) bacteremia (31%; 9 of 29 patients), pneumonia (24%; 7 of 29 patients), abdominal and/or biliary infections (14%; 4 of 29 patients), and wound infections (10%; 3 of 29 patients) were the predominant sources of bacteremia. Diabetes mellitus (odds ratio, 6.9; P =.03) and serum albumin level less than 3.0 mg/dL (odds ratio, 0.14; P =.02) were independently significant predictors of bacteremia compared with nonbacteremic infections. Mortality at 14 days was 28% (8 of 29 patients) in those with bacteremia compared with 4% (1 of 23 patients) in those with nonbacteremic infections and 0% (0 of 7) in patients with fever of noninfectious cause (P =.03). Intensive care unit stay at the time of bacteremia (100% v 47%; P =.005), absence of chills (0% v 53%; P =.005), lower temperature at the onset of bacteremia (99.2 degrees F v 101.5 degrees F; P =.009), lower maximum temperature during the course of bacteremia (99.3 degrees F v 102 degrees F, P =.008), greater serum bilirubin level (7.6 v 1.5 mg/dL; P =.024), presence of abnormal blood pressure (80% v 16%; P =. 0013), and greater prothrombin time (15.6 v 13.3 seconds; P =.013) were significantly predictive of greater mortality in the bacteremic patients. These data have implications for discerning the likelihood of bacteremia and initiation of empiric antibiotics pending cultures. Lack of febrile response in bacteremic liver transplant recipients portended a poorer outcome.

Antibiotic Prophylaxis↗
PubMed2000

Quality of life in long-term survivors after liver transplantation: impact of recurrent viral hepatitis C virus hepatitis.

Post liver transplant recurrence of infection with hepatitis C virus (HCV) occurs in approximately 50% of patients transplanted because of HCV-related liver disease. The aim of this study was to assess long-term quality of life, psychologic distress, and coping in patients with recurrent HCV after liver transplantation in comparison to patients transplanted for other etiologies of underlying liver disease. All liver transplant recipients transplanted at a University affiliated Veterans Affairs Medical Center who had greater than 6 months follow-up were sent a questionnaire investigating quality of life (assessed by Medical Outcomes study health survey SF-36), depression (assessed by Beck Depression Inventory), total mood disturbance (assessed by Profile of Mood States scale), coping (assessed by Billing and Moos Inventory of coping with illnesses), and employment status. Lower Beck Depression Inventory score (p = 0.001), lower mood disturbance score (p = 0.0001), overall satisfaction with present work (p = 0.0001), and lesser use of avoidant coping (p = 0.06) were predictors of better quality of life in long-term survivors of liver transplantation. At a mean follow-up of 4 yr after liver transplantation, patients with histopathologically diagnosed recurrent viral HCV hepatitis had significantly lower global quality of life score (mean score of 76.4 versus 86.2, p = 0.011) and physical functioning score (mean score 20 versus 25, p = 0.015), as compared to all other patients. In summary, quality of life and physical functioning were significantly impaired in liver transplant recipients with histopathologically diagnosed recurrent HCV hepatitis, as compared to those whose HCV hepatitis had not recurred or those transplanted for other reasons.

Adaptation, Psychological↗