Fluconazole non-susceptible breakthrough candidemia after prolonged low-dose prophylaxis: a prospective FUNGINOS study.

OBJECTIVES: Breakthrough candidemia (BTC) on fluconazole was associated with non-susceptible Candida spp. and increased mortality. This nationwide FUNGINOS study analyzed clinical and mycological BTC characteristics. METHODS: A 3-year prospective study was conducted in 567 consecutive candidemias. Species identification and antifungal susceptibility testing (CLSI) were performed in the FUNGINOS reference laboratory. Data were analyzed according to STROBE criteria. RESULTS: 43/576 (8%) BTC occurred: 37/43 (86%) on fluconazole (28 prophylaxis, median 200 mg/day). 21% BTC vs. 23% non-BTC presented severe sepsis/septic shock. Overall mortality was 34% vs. 32%. BTC was associated with gastrointestinal mucositis (multivariate OR 5.25, 95%CI 2.23-12.40, p < 0.001) and graft-versus-host-disease (6.25, 1.00-38.87, p = 0.05), immunosuppression (2.42, 1.03-5.68, p = 0.043), and parenteral nutrition (2.87, 1.44-5.71, p = 0.003). Non-albicans Candida were isolated in 58% BTC vs. 35% non-BTC (p = 0.005). 63% of 16 BTC occurring after 10-day fluconazole were non-susceptible (Candida glabrata, Candida krusei, Candida norvegensis) vs. 19% of 21 BTC (C. glabrata) following shorter exposure (7.10, 1.60-31.30, p = 0.007). Median fluconazole MIC was 4 mg/l vs. 0.25 mg/l (p < 0.001). Ten-day fluconazole exposure predicted non-susceptible BTC with 73% accuracy. CONCLUSIONS: Outcomes of BTC and non-BTC were similar. Fluconazole non-susceptible BTC occurred in three out of four cases after prolonged low-dose prophylaxis. This implies reassessment of prophylaxis duration and rapid de-escalation of empirical therapy in BTC after short fluconazole exposure.

Key priorities in the prevention and control of healthcare-associated infection: a survey of European and other international infection prevention experts.

PURPOSE: Prevention and control of healthcare-associated infection (HCAI) are important within and beyond Europe. However, it is unclear which areas are considered important by HCAI prevention and control professionals. This study assesses the priorities in the prevention and control of HCAI as judged by experts in the field. METHODS: A survey was conducted by the European Society of Clinical Microbiology and Infectious Diseases focussing on seven topics using SurveyMonkey®. Through a newsletter distributed by email, about 5000 individuals were targeted throughout the world in February and March 2013. Participants were asked to rate the importance of particular topics from one (low importance) to ten (extraordinary importance), and there was no restriction on giving equal importance to more than one topic. RESULTS: A total of 589 experts from 86 countries participated including 462 from Europe (response rate: 11.8 %). Physicians accounted for 60 % of participants, and 57 % had ten or more years' experience in this area. Microbial epidemiology/resistance achieved the highest priority scoring with 8.9, followed by surveillance 8.2, and decolonisation/disinfection/antiseptics with 7.9. Under epidemiology/resistance, highly resistant Gram-negative bacilli scored highest (9.0-9.2). The provision of computerised healthcare information systems for the early detection of outbreaks was accorded the top priority under surveillance. The prevention of surgical site and central line infections ranked highest under the category of specific HCAI and HCAI in certain settings. Differences between regions are described. CONCLUSION: These findings reflect the concerns of experts in HCAI prevention and control. The results from this survey should inform national and international agencies on future action and research priorities.

Antibiotic susceptibility of Clostridium difficile is similar worldwide over two decades despite widespread use of broad-spectrum antibiotics: an analysis done at the University Hospital of Zurich.

BACKGROUND: Clostridium difficile infection (CDI) remains a major health problem worldwide. Antibiotic use, in general, and clindamycin and ciprofloxacin, in particular, have been implicated in the pathogenesis of CDI. Here, we hypothesized that antibiotics that are highly active in vitro against C. difficile are less frequently associated with CDI than others. The primary goals of our study were to determine if antibiotic susceptibility and CDI are associated and whether the antimicrobial susceptibility of C. difficile changed over the years. METHODS AND RESULTS: We examined a large panel of C. difficile strains collected in 2006-2008 at the University Hospital of Zurich. We found that the antimicrobial susceptibilities to amoxicillin/clavulanate, piperacillin/tazobactam, meropenem, clindamycin, ciprofloxacin, ceftriaxone, metronidazole and vancomycin were similar to those reported in the literature and that they are similar to those reported in other populations over the last two decades. Antibiotic activity did not prevent CDI. For example, thre use of meropenem, which is highly active against all strains tested, was a clear risk factor for CDI. Most of the antibiotics tested also showed a higher minimum inhibitory concentration distribution than that of EUCAST. All strains were susceptible to metronidazole. One strain was resistant to vancomycin. CONCLUSIONS: Antibiotic susceptibilities of the collection of C. difficile from the University Hospital of Zurich are similar to those reported by others since the 1980. Patients treated with carbapenems and cephalosporins had the highest risk of developing CDI irrespective of the antimicrobial activity of carbapenems.

High proportion of healthcare-associated urinary tract infection in the absence of prior exposure to urinary catheter: a cross-sectional study.

BACKGROUND: Exposure to urinary catheters is considered the most important risk factor for healthcare-associated urinary tract infection (UTI) and is associated with significant morbidity and substantial extra-costs. In this study, we assessed the impact of urinary catheterisation (UC) on symptomatic healthcare-associated UTI among hospitalized patients. METHODS: A nationwide period prevalence survey of healthcare-associated infections was conducted during 1 May to 30 June 2004 in 49 Swiss hospitals and included 8169 adult patients (4313 female; 52.8%) hospitalised in medical, surgical, intermediate, and intensive care wards. Additional data were collected on exposure to UC to investigate factors associated with UTI among hospitalised adult patients exposed and non-exposed to UC. RESULTS: 1917 (23.5%) patients were exposed to UC within the week prior to survey day; 126 (126/8169; 1.5%) developed UTI. Exposure to UC preceded UTI only in 73 cases (58%). By multivariate logistic regression analysis, UTI was independently associated with exposure to UC (odds ratio [OR], 3.9 [95% CI, 2.6-5.9]), female gender (OR, 2.1 [95% CI, 1.4-3.1]), an American Society of Anesthesiologists' score > 2 points (OR, 3.2 [95% CI, 1.1-9.4], and prolonged hospital stay >20 days (OR, 1.9 [95% CI, 1.4-3.2]. Further analysis showed that the only significant factor for UTI with exposure to UC use was prolonged hospital stay >40 days (OR, 2.9 [95% CI, 1.3-6.1], while female gender only showed a tendency (OR, 1.6 [95% CI, 1.0-2.7]. In the absence of exposure to UC, the only significant risk factor for UTI was female gender (OR, 3.3 [95% CI, 1.7-6.5]). CONCLUSIONS: Exposure to UC was the most important risk factor for symptomatic healthcare-associated UTI, but only concerned about half of all patients with UTI. Further investigation is warranted to improve overall infection control strategies for UTI.

Incidence of sternal wound infection after reexploration in the intensive care unit and the use of local gentamycin.

BACKGROUND: Reoperation for bleeding is a known emergency complication after cardiac operations. When performed in the intensive care unit (ICU), sterility issues arise. Our aim was to examine the incidence of sternal wound infection (SWI) after reexploration in the ICU for bleeding with routine use of local gentamycin. METHODS: From January 2003 until December 2009, 4,863 patients underwent cardiac operations through a median sternotomy at our institution. We conducted a retrospective database review identifying all patients who required reoperations. The occurrence of SWI in this group was compared with the general cardiac surgical population. Reoperations for bleeding during this period were conducted routinely in the ICU with prophylactic application of a gentamycin sponge between the sternal halves before closure in all cases. RESULTS: Reexploration for bleeding was necessary in 302 patients (6.2%), and SWI occurred in 11, for a rate of 3.6%. SWI occurred in 174 of the 4,561 non-reexplored patients, for a similar rate of 3.8% (p>0.9). These values are similar to our overall rate of SWI of 3.8% (n=185) in the total cohort of 4,863 patients. CONCLUSIONS: The incidence of SWI was not increased in our study group after emergency reoperation for bleeding in the ICU after the local use of gentamycin. Our data suggest that reexploration in an ICU setting for bleeding does not pose a sterility challenge and that life-threatening delays due to transfer to the operating theater may be avoided.

Intramural aortic abscess mimicking chronic aortic dissection.

A 77-year-old patient was referred for progressive fatigue and dyspnea on exertion. Preoperative imaging evaluations including transthoracic echocardiography and computed tomography were suggestive of a chronic ascending aortic dissection with an intramural hematoma. Intraoperatively, the intramural structure was identified as an abscess cavity.

Vancomycin-resistant Enterococcus.

The reported prevalence of vancomycin-resistant Enterococcus faecium (VRE) in Switzerland for the years 2008-2010 has been low at <5%. At the University Hospital Zurich, 17 cases of VRE were detected between 28 December 2009 and 15 February 2010. Nine cases were diagnosed clinically; eight cases were detected by rectal screening. The centre of the outbreak was the cardiac surgery department. Four patients suffered from VRE-infections; four patients died. In order to investigate and contain the outbreak, the following measures were taken: prevalence surveys using weekly rectal screening, environmental screening; selective enrichment culturing; pulsed field gel electrophoresis (PFGE) for clonal typing and polymerase chain reaction-analysis (PCR) for resistance determinants and virulence factors detection. Contact isolation in single rooms and enhanced surface-disinfection methods were implemented. Ward nurses were assigned as link nurses. Regular teaching was carried out aiming to improve hand disinfection among healthcare workers. PFGE revealed two main pulsotypes each including seven patients. Five minor pulsotypes originated from three additional patients and one sample collected from a keyboard. Two of three patients with minor pulsotypes had been treated abroad. PCR-analysis identified vanB resistance-genotypes with exception of one vanA resistance-genotype. The outbreak was associated with environmental contamination and insufficient compliance with hand-hygiene. Enhanced awareness and infection control measures resulted in termination of the VRE outbreak within eight weeks. The complexity of the outbreak with several clones in parallel suggests a higher baseline prevalence of VRE in Switzerland than previous surveillance data indicate.

Low meningitis-incidence in primary spontaneous compared to secondary cerebrospinal fluid rhinorrhoea.

OBJECTIVE: Spontaneous cerebrospinal fluid (CSF) rhinorrhoea is a separate clinical entity with elevated intracranial pressure as its most probable pathophysiological mechanism. Having the clinical impression of distinct courses of diseases in primary spontaneous (PS) compared to secondary CSF rhinorrhoea, our objective was to identify whether the two forms differ in the duration of CSF rhinorrhoea and the incidence of meningitis. METHODS: Chart review performed on all patients referred with a CSF leak to our tertiary-care medical center over a 20-year period from 1990 to 2010. RESULTS: In total, 58 cases suffering from CSF rhinorrhoea could be included. The aetiology was primary spontaneous in 23 (40%) and secondary in 35 (60%) patients. The duration of CSF rhinorrhoea was notably longer in patients with PS CSF rhinorrhoea. Moreover, we could show a significantly lower incidence of meningitis with PS CSF rhinorrhoea compared to the secondary group (annual incidence of 0.12 vs. 1.22 episodes). CONCLUSION: A significantly lower incidence and delayed onset of meningitis in patients suffering from PS CSF rhinorrhoea could be explained by an elevated intracranial pressure that hinders the ascension of bacteria. The closure of a leak in secondary CSF fistula seems more urgent than in PS CSF fistulas.

Clearance of an epidemic clone of methicillin-resistant Staphylococcus aureus in a drug-use network: a follow-up study in Switzerland.

BACKGROUND: A single clone of methicillin-resistant Staphylococcus aureus (MRSA) was observed in a drug-use network starting in 1994, and was found to persist throughout 2001, with up to 19% MRSA colonization of intravenous drug users (IDUs). Recent clinical observations have shown low prevalences of this endemic drug clone among MRSA isolates. The goal of this study was to assess the evolution of MRSA carriage among IDUs. METHODS: The survey took place from November 2008 to September 2009. Ten drug dispensary facilities took part. Demographic and clinical data including sex, history of MRSA, past hospitalization, use of antibiotics, and presence of wounds were collected. Screening of the nares, throat, and wounds was done. RESULTS: Five hundred and fourteen swab specimens were obtained; 497 of them were nose/throat samples and 17 were wound swabs. MRSA was identified in 5 samples (1%). Four MRSA were found in nose/throat samples and 1 in a wound swab. Pulsed-field gel electrophoresis typing of the MRSA isolates revealed 2 different common endemic types: 4 were identified as the Zurich IDU clone and 1 as the Grison clone. CONCLUSIONS: The study shows a significant decline of MRSA colonization among IDUs. The underlying causes for this decline could not be determined fully, but we hypothesize a bundle of interventions as contributing: enhanced medical care, better wound management, isolation management, teaching IDUs basic hygiene techniques, and the national 'Four Pillars' policy. Hospital epidemiological policies such as pre-emptive isolation, length of isolation time, and screening procedures were adapted accordingly.

Overall burden of healthcare-associated infections among surgical patients. Results of a national study.

OBJECTIVE: To assess the overall burden of healthcare-associated infections (HAIs) in patients exposed and nonexposed to surgery. BACKGROUND: Targeted HAI surveillance is common in healthcare institutions, but may underestimate the overall burden of disease. METHODS: Prevalence study among patients hospitalized in 50 acute care hospitals participating in the Swiss Nosocomial Infection Prevalence surveillance program. RESULTS: Of 8273 patients, 3377 (40.8%) had recent surgery. Overall, HAI was present in 358 (10.6%) patients exposed to surgery, but only in 206 (4.2%) of 4896 nonexposed (P < 0.001). Prevalence of surgical site infection (SSI) was 5.4%. Healthcare-associated infections prevalence excluding SSI was 6.5% in patients with surgery and 4.7% in those without (P < 0.0001). Patients exposed to surgery carried less intrinsic risk factors for infection (age >60 years, 55.6% vs 63.0%; American Society of Anesthesiologists score >3,5.9% vs 9.3%; McCabe for rapidly fatal disease, 3.9% vs 6.6%; Charlson comorbidity index >2, 12.3% vs 20.9%, respectively; all P < 0.001) than those nonexposed, but more extrinsic risk factors (urinary catheters, 39.6%vs 14.1%; central venous catheters, 17.8% vs 7.1%; mechanical ventilation, 4.7% vs 1.3%; intensive care stay, 18.3% vs 8.8%, respectively; all P<0.001). Exposure to surgery independently predicted an increased risk of HAI (odds ratio 2.43; 95% CI 2.0­3.0). CONCLUSIONS: Despite a lower intrinsic risk, patients exposed to surgery carried more than twice the overall HAI burden than those nonexposed; almost half was accountable to SSI. Extending infection control efforts beyond SSI prevention in these patients might be rewarding, especially because of the extrinsic nature of risk factors.

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.

Risk factors for urinary tract infections due to ciprofloxacin-resistant Escherichia coli in a tertiary care urology department in Switzerland.

QUESTIONS UNDER STUDY: Monitoring of antimicrobial resistance is a key component of antibiotic stewardship programs. In 2007, a significantly higher resistance rate of Escherichia coli to ciprofloxacin was found at the Department of Urology, University Hospital Zurich, Switzerland, when compared to other hospital units. Thus, we aimed to determine the risk factors for this increased fluoroquinolone resistance in outpatients and inpatients with urinary tract infection (UTI) or colonisation with E. coli. METHODS: We performed a cross sectional study including 275 patients of the Department of Urology in whom E. coli was isolated from urine or blood cultures between 01.01.2006 and 31.08.2007. Clinical data were collected from patients' records using a structured questionnaire. Multivariable analysis was performed for the detection of risk factors. RESULTS: Ciprofloxacin-resistant E. coli was detected in 22% of patients. Risk factors for ciprofloxacin-resistant E. coli included prior use of fluoroquinolones (odds ratio [OR] (95% confidence intervals): 2.24 (1.08-4.62), p = 0.030), prior urinary tract catheterisation (OR: 2.41 (1.02-5.67), p = 0.044) and recurrent UTIs (OR: 2.26 (1.07-4.78), p = 0.032). 60.8% of all prescriptions in urinary tract infections were for fluoroquinolones, and this antibiotic class was the empiric antibiotic regimen of choice in 72.5% of all acute, uncomplicated, urinary tract infections. CONCLUSIONS: The increasing prevalence of ciprofloxacin-resistant E. coli makes empiric therapy in UTIs with this agent questionable, especially in patients with one or several of the above mentioned risk factors. Due to the increasing resistance rate, continuous surveillance and susceptibility testing in individual patients, particularly with complicated UTIs, is indispensable for adequate therapy.

A deep sternal wound infection caused by Ureaplasma urealyticum.

Ureaplasma species are usually associated with infection of the urogenital tract. An unusual case of a sternal wound infection caused by Ureaplasma urealyticum in a 41-year-old male after aortic valve replacement is described.

Rapid colonization with methicillin-resistant coagulase-negative staphylococci after surgery.

BACKGROUND: Antimicrobial resistance may compromise the efficacy of antibiotic prophylaxis before surgery. The aim of this study was to measure susceptibility and clonal distribution of coagulase-negative staphylococci (CoNS) colonizing the skin around the surgery access site before and after the procedure. METHODS: From March to September 2004, a series of 140 patients undergoing elective major abdominal surgery were screened for CoNS colonization at admission and 5 days after surgery. All isolates were tested for antibiotic susceptibility and genotyped by pulsed-field gel electrophoresis (PFGE). RESULTS: Colonization rates with CoNS at admission and after surgery were 85% and 55%, respectively. The methicillin-resistant CoNS rate increased from 20% at admission to 47% after surgery (P = 0.001). The PFGE pattern after surgery revealed more patients colonized with identical clones: 8/140 patients (8/119 strains) and 26/140 patients (26/77 strains), respectively (P < 0.001). CONCLUSIONS: Our results suggest rapid recolonization of disinfected skin by resistant nosocomial CoNS. Larger studies, preferably among orthopedic or cardiovascular patients, are required to clarify whether standard antibiotic prophylaxis with first- or second-generation cephalosporins for CoNS infections may be compromised if the patient requires an additional intervention 5 days or more after the initial surgery.

Non-purulent low-grade infection as cause of pain following shoulder surgery: preliminary results.

Low-grade infection was systematically searched for in all revision shoulder surgeries by harvesting tissue samples. Ten consecutive patients were identified with a non-purulent low-grade infection of the shoulder. All of these patients suffered from pain and eight were stiff. Preoperative aspiration in eight patients yielded bacterial growth in only one case. Serum C-reactive protein levels were normal in seven out of 10 cases. Propionibacterium acnes was identified in seven, coagulase-negative Staphylococcus in two and Staphylococcus saccharolyticus in one case. The delay between harvesting the tissue samples and detection of bacterial growth averaged eight days (range, 2-17). After debridement and antibiotic treatment for a mean of 4.5 months, tissue samples were repeatedly harvested in nine patients due to persistent pain. The infection was microbiologically eradicated in six out of nine cases that had a repeated biopsy. However, nine out of 10 patients continued to suffer from moderate to severe pain. Low-grade infection of the shoulder can be a cause of persistent pain and stiffness. The results of antibiotic treatment are disappointing. Further studies are necessary to analyse this difficult pathology.

Impact of a prevention strategy targeting hand hygiene and catheter care on the incidence of catheter-related bloodstream infections.

OBJECTIVES: To study the impact of a teaching intervention on the rate of central venous catheter-related bloodstream infections (CRBSI) in intensive care patients. DESIGN: Prospective before/after interventional cohort study on medical and surgical intensive care units. SETTING: University hospital with five adult intensive care units. PATIENTS: All patients with a central venous catheter on the five ICUs from September to December 2003 (baseline period) and from March to July 2004 (intervention period). INTERVENTIONS: Educational program with teaching of hand hygiene, standards of catheter care, and preparation of intravenous drugs. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was the rate of CRBSIs per 1000 catheter days during a baseline period of 4 months and an intervention period of 5 months. The secondary outcome variable was compliance with hand hygiene. Of the patients, 499 patients with 6200 catheter days in the baseline period and 500 patients with 7279 catheter days were monitored in the intervention period. The incidence density of CRBSI decreased from 3.9 per 1000 catheter days in the preintervention phase to 1.0 per 1000 catheter days in the intervention phase (p < 0.001). The risk for CRBSI was significantly higher in the baseline period in both univariate and multivariate analysis. Other independent risk factors were hospitalization in the medical ICU and male gender. Time to CRBSI was significantly longer in the intervention period (median 9 days vs. 6.5 days, respectively; p = 0.02). Compliance with hand hygiene improved slightly from 59% in the baseline period to 65% in the intervention period, but the rate of correct performance of the practice increased from 22.5% to 42.6% (p = 0.003). CONCLUSIONS: Evidence-based catheter-care procedures, guided by healthcare workers' perceptions and including bedside teaching, reduce significantly the CRBSI rate and demonstrate that improving catheter care has a major impact on its prevention.

Stratification of cumulative antibiograms in hospitals for hospital unit, specimen type, isolate sequence and duration of hospital stay.

BACKGROUND: Empirical antibiotic therapy is based on patients' characteristics and antimicrobial susceptibility data. Hospital-wide cumulative antibiograms may not sufficiently support informed decision-making for optimal treatment of hospitalized patients. METHODS: We studied different approaches to analysing antimicrobial susceptibility rates (SRs) of all diagnostic bacterial isolates collected from patients hospitalized between July 2005 and June 2007 at the University Hospital in Zurich, Switzerland. We compared stratification for unit-specific, specimen type-specific (blood, urinary, respiratory versus all specimens) and isolate sequence-specific (first, follow-up versus all isolates) data with hospital-wide cumulative antibiograms, and studied changes of mean SR during the course of hospitalization. RESULTS: A total of 16 281 isolates (7965 first, 1201 follow-up and 7115 repeat isolates) were tested. We found relevant differences in SRs across different hospital departments. Mean SRs of Escherichia coli to ciprofloxacin ranged between 64.5% and 95.1% in various departments, and mean SRs of Pseudomonas aeruginosa to imipenem and meropenem ranged from 54.2% to 100% and 80.4% to 100%, respectively. Compared with hospital cumulative antibiograms, lower SRs were observed in intensive care unit specimens, follow-up isolates and isolates causing nosocomial infections (except for Staphylococcus aureus). Decreasing SRs were observed in first isolates of coagulase-negative staphylococci with increasing interval between hospital admission and specimen collection. Isolates from different anatomical sites showed variations in SRs. CONCLUSIONS: We recommend the reporting of unit-specific rather than hospital-wide cumulative antibiograms. Decreasing antimicrobial susceptibility during hospitalization and variations in SRs in isolates from different anatomical sites should be taken into account when selecting empirical antibiotic treatment.

Correlation between case mix index and antibiotic use in hospitals.

BACKGROUND: To compare the quantitative antibiotic use between hospitals or hospital units and to explore differences, adjustment for severity of illness of hospitalized patients is essential. The case mix index (CMI) is an economic surrogate marker (i.e. the total cost weights of all inpatients per a defined time period divided by the number of admissions) to describe the average patients' morbidity of individual hospitals. We aimed to investigate the correlation between CMI and hospital antibiotic use. METHODS: We used weighted linear regression analysis to evaluate the correlation between in-hospital antibiotic use in 2006 and CMI of 18 departments of the tertiary care University Hospital Zurich and of 10 primary and 2 secondary acute care hospitals in the Canton of Zurich in Switzerland. RESULTS: Antibiotic use varied substantially between different departments of the university hospital [defined daily doses (DDD)/100 bed-days, 68.04; range, 20.97-323.37] and between primary and secondary care hospitals (range of DDD/100 bed-days, 15.45-57.05). Antibiotic use of university hospital departments and the different hospitals, respectively, correlated with CMI when calculated in DDD/100 bed-days [coefficient of determination (R(2)), 0.57 (P = 0.0002) and 0.46 (P = 0.0065)], as well as when calculated in DDD/100 admissions [R(2), 0.48 (P = 0.0008) and 0.85 (P < 0.0001), respectively]. CONCLUSIONS: Antibiotic use correlated with CMI across various specialties of a university hospital and across different acute care hospitals. For benchmarking antibiotic use within and across hospitals, adjustment for CMI may be a useful tool in order to take into account the differences in hospital category and patients' morbidities.

Treatment options of invasive fungal infections in adults.

A panel of infectious disease specialists, clinical microbiologists and hospital epidemiologists of the five Swiss university hospitals reviewed the current literature on the treatment of invasive fungal infections in adults and formulated guidelines for the management of patients in Switzerland. For empirical therapy of Candida bloodstream infection, fluconazole is the drug of choice in non-neutropenic patients with no severe sepsis or septic shock or recent exposure to azoles. Amphotericin B deoxycholate or caspofungin would be the treatment option for patients with previous azole exposure. In neutropenic patients, empirical therapy with amphotericin B deoxycholate is considered first choice. In patients with severe sepsis and septic shock, caspofungin is the drug of first choice. For therapy of microbiologically-documented Candida infection, fluconazole is the drug of choice for infections due to C. albicans, C. tropicalis or C. parapsilosis. When infections are caused by C. glabrata or by C. krusei, caspofungin or amphotericin B deoxycholate are first line therapies. Treatment guidelines for invasive aspergillosis (IA) were stratified into primary therapy, salvage therapy and combination therapy in critically ill patients. Voriconazole is recommended for primary (ie upfront) therapy. Caspofungin, voriconazole (if not used for primary therapy) or liposomal amphotericin B are recommended for salvage therapy for refractory disease. Combination therapy with caspofungin plus voriconazole or liposomal amphotericin B should be considered in critically ill patients. Amphotericin B deoxycholate is recommended as initial therapy for the empirical therapy in patients with neutropenia and persistent fever with close monitoring of adverse events.