Christian Ruef

Etiologic Diagnosis of Infective Endocarditis by Broad-Range Polymerase Chain Reaction: A 3-Year Experience

We analyzed surgically resected endocardial specimens from 49 patients by broad-range PCR. PCR results were compared with (1) results of previous blood cultures, (2) results of culture and Gram staining of resected specimens, and (3) clinical data (Duke criteria). Molecular analyses of resected specimens and previous blood cultures showed good overall agreement. However, in 18% of patients with sterile blood cultures, bacterial DNA was found in the resected materials. When data from patients with definite or rejected cases of infective endocarditis (IE) were included, the sensitivity, specificity, and positive and negative predictive values of broad-range PCR were 82.6%, 100%, 100%, and 76.5%, respectively, overall, and 94.1%, 100%, 100%, and 90%, for cases of native valve endocarditis. The sensitivity, specificity, and positive and negative predictive values of culture of resected specimens from patients with native valve endocarditis were 17.6%, 88.9%, 75%, and 36.4%. We recommend broad-range PCR of surgically resected endocardial material in cases of possible IE, in cases of suspected IE in which blood cultures are sterile, and in cases in which organisms grow in blood cultures but only Duke minor criteria are met. We propose to add molecular techniques to the pathologic criteria of the Duke classification scheme.

Cryopreserved arterial allografts in the treatment of major vascular infection: A comparison with conventional surgical techniques

OBJECTIVE Recent findings with cryopreserved heart valve allografts in the treatment of infectious endocarditis suggest that the use of cryopreserved arterial allografts may improve the outcome in patients with vascular infections. METHODS Seventy-two patients with mycotic aneurysms (n = 29) or infected vascular prostheses (n = 43) of the thoracic (n = 26) or abdominal aorta (n = 46) were treated with in situ repair and extra-anatomic reconstruction using prosthetic material (n = 38) or implantation of a cryopreserved arterial allograft (n = 34). Disease-related survival and survival free of reoperation were assessed. Morbidity, cumulative lengths of intensive care, hospitalization, antibiotic treatment, and costs were calculated per year of follow-up. RESULTS The use of cryopreserved arterial allografts was superior to conventional surgery in terms of disease-related survival (P =.008), disease-related survival free of reoperation (P =.0001), duration of intensive care per year of follow-up (median 1 vs 11 days; range 1 to 42 vs 2 to 120 days; P =.001), hospitalization (14 vs 30 days; range 7 to 150 vs 15 to 240 days; P =.002), duration of postoperative antibiotic therapy (21 vs 40 days; range 21 to 90 vs 60 to 365 days; P =.002), incidence of complications (24% vs 63%; P =.005), and elimination of infection (91% vs 53%; P =.001). In addition, costs were 40% lower in the group treated by allografts (P =.005). CONCLUSIONS The use of cryopreserved arterial allografts is a more effective treatment for mycotic aneurysms and infected vascular prostheses than conventional surgical techniques.

Influenza Vaccination of Healthcare Workers and Vaccine Allocation for Healthcare Workers During Vaccine Shortages

Influenza causes substantial morbidity and mortality annually, particularly in high-risk groups such as the elderly, young children, immunosuppressed individuals, and individuals with chronic illnesses. Healthcare-associated transmission of influenza contributes to this burden but is often under-recognized except in the setting of large outbreaks. The Centers for Disease Control and Prevention has recommended annual influenza vaccination for healthcare workers (HCWs) with direct patient contact since 1984 and for all HCWs since 1993. The rationale for these recommendations is to reduce the chance that HCWs serve as vectors for healthcare-associated influenza due to their close contact with high-risk patients and to enhance both HCW and patient safety. Despite these recommendations as well as the effectiveness of interventions designed to increase HCW vaccination rates, the percentage of HCWs vaccinated annually remains unacceptably low. Ironically, at the same time that campaigns have sought to increase HCW vaccination rates, vaccine shortages, such as the shortage during the 2004-2005 influenza season, present challenges regarding allocation of available vaccine supplies to both patients and HCWs. This two-part document outlines the position of the Society for Healthcare Epidemiology of America on influenza vaccination for HCWs and provides guidance for the allocation of influenza vaccine to HCWs during a vaccine shortage based on influenza transmission routes and the essential need for a practical and adaptive strategy for allocation. These recommendations apply to all types of healthcare facilities, including acute care hospitals, long-term-care facilities, and ambulatory care settings.

Quantitative antibiotic use in hospitals: comparison of measurements, literature review, and recommendations for a standard of reporting.

Background:Reports on antibiotic use often lack complete definitions of the units of measurement, hampering the comparison of data between hospitals or hospital units.Patients and Methods:To compare methods of measures of in-hospital antimicrobial use, we determined aggregate in-hospital consumption data at a tertiary care university hospital using variations of nominators and denominators. Means of defined daily doses (DDD) of individual antimicrobials per 100 bed-days and per 100 admissions at each hospital and intensive care unit (ICU) were calculated. Furthermore, a literature review was performed for benchmarking purposes.Results:Antibiotic use in different hospital units ranged from 0.105 to 323.37 DDD/100 bed-days and from 4.23 to 6737.92 DDD/100 admissions, respectively. Including the day of discharge in the denominator ‘bed-days’ underestimated antibiotic use in various hospital wards by up to 27.7 DDD/100 bed-days (26.0%). Equating ‘numbers of patients admitted to the hospital’ and ‘numbers of admissions’ on a hospital level resulted in a difference of 192.6 DDD/100 admissions (64%) because patients transferred between hospital units accounted for multiple admissions. Likewise, reporting antimicrobial (Anatomical Therapeutic Chemical [ATC] group ‘J’) instead of antibiotic (ATC group ‘J01’) use led to a difference of 16.5 DDD/100 bed-days (19.3%). The literature review revealed underreporting of complete definitions of antibiotic use measurements.Conclusions:Data on in-hospital antimicrobial use vary widely not only due to different antibiotic policies at different institutions but also due to different methods of measures. Adherence to the standard of reporting the methods of measurement is warranted for benchmarking and promotion of rational antimicrobial use.

Epidemic Spread of a Single Clone of Methicillin-Resistant Staphylococcus aureus among Injection Drug Users in Zurich, Switzerland

We describe an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) among injection drug users (IDUs). From August 1994 through December 1999, we registered 31 IDUs with MRSA infections (12 with soft-tissue infection, 7 with pneumonia [fatal in 1], 7 with endocarditis [fatal in 1], 2 with osteomyelitis, 2 with septic arthritis, and 1 with ulcerative tonsillitis), with a marked increase in the number of IDUs registered during 1998 and 1999. Of 31 patients, 15 (48%) were infected with human immunodeficiency virus. A point-prevalence study among IDUs who frequented outpatient facilities in Zurich revealed an MRSA carriage rate of 10.3% (range, 0%-28.6%) in various facilities. In all but 1 case, pulsed-field gel electrophoresis banding patterns of isolates obtained from these patients were indistinguishable from isolates of the initial 31 IDUs registered. Risk factors for MRSA carriage were disability and prior hospitalization in a hospice. In summary, MRSA became endemic in IDUs in Zurich as a result of the spread of a single clone. This clone caused major morbidity and was responsible for a lethal outcome in 2 cases.

Incidence and Predictors of Virologic Failure of Antiretroviral Triple-Drug Therapy in a Community-Based Cohort

Highly active antiretroviral therapy fails to reach its recommended goal of sustained suppression of viral replication in a substantial proportion of patients. We analyzed incidence and predictors of virologic failure of the first regimen of a triple-drug combination therapy, including a protease inhibitor and two nucleoside analog reverse transcriptase inhibitors (NRTIs), in 274 HIV-infected patients. Long-term virologic response to combination therapy including salvage regimens was assessed 2.5 years after treatment initiation. During an initial observation period of up to 1.8 years (median, 0.8 years) 152 patients (55%) experienced sustained suppression of HIV-1 RNA to <500 copies/ml. Failure to reduce viral load to <500 copies/ml within 6 months (initial failure) was observed in 51 patients (19%). Independent risk factors for initial failure included higher baseline viral load; addition of a protease inhibitor to an unchanged NRTI regimen; use of saquinavir hard-gel capsules; and longer duration of prior NRTI treatment. Within a median of 7 months viral load rebound above 500 copies/ml occurred in 71 of 223 patients (32%) whose viral load had initially decreased below this threshold. In proportional hazard analysis none of the potential risk factors was significantly associated with viral load rebound. However, in 40 patients (56%) with viral load rebound, incomplete adherence to therapy or treatment interruptions preceded the rebound. Virologic outcome after 2.5 years correlated with initial response to the first regimen: viral load was <500 copies/ml in 88, 55, and 21% of patients with sustained suppression, viral load rebound, and initial failure, respectively.

Impact of an outbreak of norovirus infection on hospital resources.

OBJECTIVE To describe a nosocomial norovirus outbreak, its management, and its financial impact on hospital resources. DESIGN A matched case-control study and microbiological investigation. METHODS We compared 16 patients with norovirus infection with control-patients matched by age, gender, disease category, and length of stay. Bed occupancy-days during the peak incidence period of the outbreak were compared with the corresponding periods in 2001 and 2002. Expenses due to increased workload were calculated based on a measuring system that records time spent for nursing care per patient per day. RESULTS The attack rates were 13.9% among patients and 29.5% among healthcare workers. The median number of occupied beds was significantly lower due to bed closure during the peak incidence in 2003 (29) compared with the median number of occupied beds in 2001 and 2002 combined (42.5). Based on this difference and a daily charge of 562.50 dollars per patient, we calculated a revenue loss of 37,968 dollars. Additional expenses totaled 10,300 dollars for increased nursing care. Extra costs for microbiological diagnosis totaled 2707 dollars. Lost productivity costs due to healthcare workers on sick leave totaled 12,807 dollars. The expenses for work by the infection control team totaled 1408 dollars. The financial impact of this outbreak on hospital resources comprising loss of revenue and extra costs for microbiological diagnosis but without lost productivity costs, increased nursing care, and expenses for the infection control team totaled 40,675 dollars. CONCLUSIONS Nosocomial norovirus outbreaks result in significant loss of revenue and increased use of resources. Bed closures had a greater impact on hospital resources than increased need for nursing care

Candida species distribution and antifungal susceptibility testing according to European Committee on Antimicrobial Susceptibility Testing and new vs. old Clinical and Laboratory Standards Institute clinical breakpoints: a 6-year prospective candidaemia survey from the fungal infection network of Switzerland

We analyzed the species distribution of Candida blood isolates (CBIs), prospectively collected between 2004 and 2009 within FUNGINOS, and compared their antifungal susceptibility according to clinical breakpoints defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2013, and the Clinical and Laboratory Standards Institute (CLSI) in 2008 (old CLSI breakpoints) and 2012 (new CLSI breakpoints). CBIs were tested for susceptiblity to fluconazole, voriconazole and caspofungin by microtitre broth dilution (Sensititre® YeastOne™ test panel). Of 1090 CBIs, 675 (61.9%) were C. albicans, 191 (17.5%) C. glabrata, 64 (5.9%) C. tropicalis, 59 (5.4%) C. parapsilosis, 33 (3%) C. dubliniensis, 22 (2%) C. krusei and 46 (4.2%) rare Candida species. Independently of the breakpoints applied, C. albicans was almost uniformly (>98%) susceptible to all three antifungal agents. In contrast, the proportions of fluconazole- and voriconazole-susceptible C. tropicalis and F-susceptible C. parapsilosis were lower according to EUCAST/new CLSI breakpoints than to the old CLSI breakpoints. For caspofungin, non-susceptibility occurred mainly in C. krusei (63.3%) and C. glabrata (9.4%). Nine isolates (five C. tropicalis, three C. albicans and one C. parapsilosis) were cross-resistant to azoles according to EUCAST breakpoints, compared with three isolates (two C. albicans and one C. tropicalis) according to new and two (2 C. albicans) according to old CLSI breakpoints. Four species (C. albicans, C. glabrata, C. tropicalis and C. parapsilosis) represented >90% of all CBIs. In vitro resistance to fluconazole, voriconazole and caspofungin was rare among C. albicans, but an increase of non-susceptibile isolates was observed among C. tropicalis/C. parapsilosis for the azoles and C. glabrata/C. krusei for caspofungin according to EUCAST and new CLSI breakpoints compared with old CLSI breakpoints.

Different patterns of inappropriate antimicrobial use in surgical and medical units at a tertiary care hospital in Switzerland: a prevalence survey.

Background Unnecessary or inappropriate use of antimicrobials is associated with the emergence of antimicrobial resistance, drug toxicity, increased morbidity and health care costs. Antimicrobial use has been reported to be incorrect or not indicated in 9–64% of inpatients. We studied the quality of antimicrobial therapy and prophylaxis in hospitalized patients at a tertiary care hospital to plan interventions to improve the quality of antimicrobial prescription. Methodology/Principal Findings Experienced infectious diseases (ID) fellows performed audits of antimicrobial use at regular intervals among all patients—with or without antimicrobials—hospitalized in predefined surgical, medical, haemato-oncological, or intensive care units. Data were collected from medical and nursing patient charts with a standardized questionnaire. Appropriateness of antimicrobial use was evaluated using a modified algorithm developed by Gyssens et al.; the assessment was double-checked by a senior ID specialist. We evaluated 1577 patients of whom 700 (44.4%) had antimicrobials, receiving a total of 1270 prescriptions. 958 (75.4%) prescriptions were for therapy and 312 (24.6%) for prophylaxis. 37.0% of therapeutic and 16.6% of prophylactic prescriptions were found to be inappropriate. Most frequent characteristics of inappropriate treatments included: No indication (17.5%); incorrect choice of antimicrobials (7.6%); incorrect application of drugs (9.3%); and divergence from institutional guidelines (8%). Characteristics of inappropriate prophylaxes were: No indication (9%); incorrect choice of antimicrobials (1%); duration too long or other inappropriate use (6.7%). Patterns of inappropriate antimicrobial varied widely in the different hospital units; empirical prescriptions were more frequently incorrect than prescriptions based on available microbiological results. Conclusions/Significance Audits of individual patient care provide important data to identify local problems in antimicrobial prescription practice. In our study, antimicrobial prescriptions without indication, and divergence from institutional guidelines were frequent errors. Based on these results, we will tailor education, amend institutional guidelines and further develop the infectious diseases consultation service.

NELFINAVIR URINARY STONES

Treatment with an HIV protease inhibitor such as indinavir or nelfinavir is a well established part of drug therapy for patients with HIV.1 In contrast to indinavir,2, 3 nelfinavir has not been reported as a component of urinary stones according to the data provided by the manufacturer.4 To our knowledge we report the first case of nelfinavir nephrolithiasis. CASE REPORT