Targeted versus universal antifungal prophylaxis among liver transplant recipients.

Guidelines recommend targeted antifungal prophylaxis for liver transplant (LT) recipients based on tiers of risk, rather than universal prophylaxis. The feasibility and efficacy of tiered, targeted prophylaxis is not well established. We performed a retrospective study of LT recipients who received targeted prophylaxis (n = 145; voriconazole [VORI; 54%], fluconazole [8%], no antifungal [38%]) versus universal VORI prophylaxis (n = 237). Median durations of targeted and universal prophylaxis were 11 and 6 days, respectively (p < 0.0001). The incidence of invasive fungal infections (IFIs) in targeted and universal groups was 6.9% and 4.2% (p = 0.34). Overall, intra-abdominal candidiasis (73%) was the most common IFI. Posttransplant bile leaks (p = 0.001) and living donor transplants (p = 0.04) were independent risk factors for IFI. IFIs occurred in 6% of high-risk transplants who received prophylaxis and 4% of low-risk transplants who did not receive prophylaxis (p = 1.0). Mortality rates (100 days) were 10% (targeted) and 7% (universal) (p = 0.26); attributable mortality due to IFI was 10%. Compliance with prophylaxis recommendations was 97%. Prophylaxis was discontinued for toxicity in 2% of patients. Targeted antifungal prophylaxis in LT recipients was feasible and safe, effectively prevented IFIs and reduced the number of patients exposed to antifungals. Bile leaks and living donor transplants should be considered high-risk indications for prophylaxis.

Prosthetic joint infection in solid organ transplant recipients: a retrospective case-control study.

BACKGROUND: The clinical features and outcome of prosthetic joint infection (PJI) among solid organ transplant (SOT) recipients have not been characterized. We performed a retrospective, matched case-control study to examine potential risk factors. METHODS: We reviewed cases of PJI among transplant recipients who were evaluated at the Mayo Clinic between 1989 and 2009. Cases were matched to non-infected controls based on transplant type, prosthetic joint type, and order of organ transplantation/joint implantation. RESULTS: Among 367 patients with both a joint prosthesis and an SOT, there were 12 cases of infection in those receiving immunosuppression. These occurred in 8 renal recipients, 3 liver recipients, and 1 heart transplant recipient. Six subjects had hip and 6 had knee arthroplasty infections. The observed time to prosthesis failure ranged from 0.5 to 148 months after implantation. Gram-positive bacteria (staphylococci and streptococci) caused the infection in 8 subjects. Two cases were caused by nontuberculous mycobacteria, whereas the remaining 2 cases were culture-negative in the setting of antimicrobial use. We did not find a statistically significant association between obesity, diabetes mellitus, or antimicrobial prophylaxis (given in the setting of immunosuppression) and development of PJI. A marginal association was seen between surgical site infection and the risk of PJI; however, this did not reach statistical significance. CONCLUSION: In our series, infection was mainly caused by gram-positive bacterial pathogens, similar to the commonly encountered organisms in the immunocompetent host, although opportunistic pathogens were also isolated.

False-positive Aspergillus galactomannan assay in solid organ transplant recipients with histoplasmosis.

Post-transplantation histoplasmosis may be acquired via inhalation, may result from endogenous reactivation, or may be derived from the allograft. The Histoplasma and Aspergillus enzyme-linked immunoassays are increasingly being relied upon for rapid diagnosis of fungal infections, especially in immunocompromised patients. We describe 4 cases of solid organ transplant recipients who had histoplasmosis and a falsely positive Aspergillus galactomannan (GM) obtained from the serum or bronchoalveolar lavage (BAL) fluid. We also report our experience, testing for Histoplasma antigen (Ag) in specimens positive for Aspergillus GM. From January 2007 through December 2010, of 2432 unique patients who had positive Aspergillus GM tests, 514 (21%) were tested for Histoplasma Ag, and 27 were found to be positive. Most specimens that tested positive for both Aspergillus and Histoplasma were obtained by BAL. False-positive tests for Aspergillus GM can occur in immunosuppressed patients who have histoplasmosis, and may obscure the correct diagnosis.

High-volume culture and quantitative real-time PCR for the detection of Aspergillus in sputum.

OBJECTIVES: Sputum culture is an insensitive method for the diagnosis of pulmonary aspergillosis. Growth of the organism allows identification of the causative species and susceptibility testing, both of which can inform treatment choices. The current practice is to culture an aliquot of diluted sputum. We assessed the value of culturing large volumes of unprocessed sputum, a method that we have termed high-volume culture (HVC). METHODS: Specimens were processed by conventional culture (using an aliquot of homogenized, diluted sputum on Sabouraud agar at 37°C and 45°C for up to 5 days) and HVC (using undiluted sputum on Sabouraud agar at 30°C for up to 14 days). A separate specimen was tested by quantitative real-time PCR. Antifungal susceptibility testing was performed by the EUCAST standard. RESULTS: We obtained sputum specimens from 229 individuals with the following conditions: chronic pulmonary aspergillosis (66.8%, 153/229), allergic bronchopulmonary aspergillosis (25.3%, 58/229) and Aspergillus bronchitis (7.9%, 18/229). Individuals with invasive pulmonary aspergillosis were not included. The positivity rate of conventional culture was 15.7% (36/229, 95% CI 11.6%-21.0%) and that of HVC was 54.2% (124/229, 95% CI 47.7%-60.5%) (p < 0.001). The higher positivity rate of HVC was demonstrated regardless of administration of antifungal treatment. Quantitive real-time PCR had an overall positivity rate of 49.2% (65/132, 95% CI 40.9%-57.7%), comparable to that of HVC. CONCLUSION: Detection of Aspergillus spp. in sputum is greatly enhanced by HVC. HVC allows for detection of azole-resistant isolates that would have been missed by conventional culture. This method can be performed in any microbiology laboratory without the need for additional equipment.

Irrigation with antibiotic-containing solutions for the prevention and treatment of infections.

Administration routes for antimicrobial agents used in clinical practice include the topical, inhaled, enteral and parenteral routes. An antibiotic administration route used frequently worldwide, although not well-studied, involves the irrigation of wounds with antibiotic-containing solutions for the prevention and treatment of infections. This review considers the data available from various experimental and clinical studies in order to provide an update on the use of antibiotic-containing solutions in modern clinical practice. Although irrigation with antibiotic-containing solutions has been suggested to be beneficial in the prevention or treatment of infections in several settings and patient populations, no firm, evidence-based recommendations can be made regarding its use until additional data from well-designed, randomised clinical trials become available. Current exceptions include empyema following lobectomy, or pneumonectomy and pyocystis (vesical empyema), since irrigation with solutions containing antimicrobial agents seems to be a crucial component of the management of these conditions.

Vaccination against typhoid fever in travellers: a cost-effectiveness approach.

Analysis of data on the incidence of typhoid fever and the costs of vaccination of travellers to the developing world indicates that vaccination may not be cost-effective for travel to countries with a moderate-to-high endemicity. It may be reasonable to selectively vaccinate travellers to countries with a very high incidence of typhoid fever, and particularly those who are visiting relatives or who will be in close contact with the local population. Vaccination of travellers on standard tourist itineraries is probably not necessary. The basic preventative measure for typhoid fever should be the avoidance of potentially contaminated food and drink.

Under-diagnosis of common chronic diseases: prevalence and impact on human health.

AIMS: The disability-adjusted life years (DALY) and its components, namely the years lived with disability and the years of life lost, are measures of the impact of disease on human health. Our impression was that several common chronic diseases responsible for many DALYs are frequently under-diagnosed. METHODS: We attempted to summarise data regarding the under-diagnosis of common chronic diseases of the developed world, which are associated with considerable mortality and/or disability. We searched PubMed and Current Contents to identify relevant studies (1980-2005). Two reviewers extracted data concerning DALYs and prevalence of under-diagnosis of common chronic diseases. RESULTS: Studies regarding the first 15 diseases (or group of diseases) based on DALYs were reviewed. The under-diagnosis of common chronic diseases in the developed world ranges from about 20% for dementia and cirrhosis to 90% for depression and osteoarthritis. The delay in the prompt diagnosis and initiation of treatment is associated with increased morbidity and mortality for most of the reviewed diseases. CONCLUSION: The available evidence suggests that the prevalence of under-diagnosis of common chronic diseases is considerable. Physicians should be aware of the prevalence of under-diagnosis of chronic diseases and its impact on human health.

Regression of subcorneal pustular dermatosis type of IgA pemphigus lesions with azithromycin.

We present our experience with a 56-year-old man who complained for generalized dermatopathy, manifested by skin lesions with diameter from 0.5 to 5 cm. The lesions did not respond to a 20-day systemic steroid regimen. The results of biopsies of three excised lesions, in combination with the clinical manifestations, led to the diagnosis of subcorneal pustular dermatosis type of IgA pemphigus. An unexpected improvement was noted after treatment with azithromycin (which was provided for management of concurrent non-specific urethritis) and local non-potent steroid plus keratolytic agent ointment.

Bibliometric analysis of global trends for research productivity in microbiology.

In order to expand upon the limited literature estimating the quantity and quality of worldwide research production in the field of microbiology, a bibliometric analysis was conducted for the period 1995-2003 using the PubMed and Journal Citation Reports databases. By searching the "microbiology" category of the Journal Citation Reports database, a total of 74 journals were identified that were also included in PubMed. From these journals, a total of 89,527 articles were identified for analysis, and data on the country in which the research originated was available for 88,456 (98.8%) of them. The individual countries were separated into nine world regions. In terms of research production for the period studied, Western Europe exceeded all other world regions, with the USA ranking second. The mean impact factor was highest for the USA at 3.4, while it was 2.8 for Western Europe and 2.4 for the rest of the world combined. The research productivity per unit of expenditure for research and development was higher for Canada and Western Europe than for the USA. The three regions in which research productivity increased the most were Asia, Latin America, and Eastern Europe.