Computer-controlled in-vitro simulation of multiple dosing regimens

The bactericidal effect of gentarrucin on Pseudomonas aeruginosa ATCC 27853 was investigated in a computer controlled dynamic in-vitro model, which allows the simultaneous simulation of three different dosing regimens for several days. The same total dose reduced cfu-counts of Pseudomonas aeruginosa most effectively, when administered with peak concentrations of 32 mg/l every 32 h, whereas the other dosing regimens with peak concentrations of 16 mg/l every 16 h and 8 mg/l every 8 h were distinctly less effective following the second and subsequent doses. It was shown that the use of a microcomputer facilitates the in-vitro investigation of multiple dosing regimens but counting of cfu cannot be substituted by automatic measurements of turbidity when rapid bactericidal effects occu

Antiretroviral prophylaxis for community exposure to the human immunodeficiency virus in Switzerland, 1997-2000.

To analyse the data from Swiss nationwide voluntary reporting on non-occupational HIV-postexposure prophylaxis (HIV-PEP) by prescribing physicians. One hundred and seventy-six persons, who received antiretroviral prophylaxis for community exposure to HIV between December 1997 and March 2000, were included in this prospective cohort study with standardised data collection. Information on the source, the exposed person, type of exposure, treatment, and outcome was reported by physicians on a voluntary basis to three co-ordinating centers. HIV-PEP was prescribed predominantly following sexual exposure (69%). Needle injury was the second most common type of exposure (19% of all exposures), mostly occurring in a non-healthcare related "professional" setting (i.e., housekeepers, concierges [caretakers], and policemen). Needle sharing accounted for only 4% of all cases of exposure. The HIV status of the source often remained unknown (56%). Most patients received a combination of three antiretroviral drugs (zidovudine/lamivudine/nelfinavir in 34.1%; zidovudine/lamivudine/indinavir in 22.8%; zidovudine/lamivudine/nevirapine in 18.6%; various triple combinations in 13.8%). Follow-up information was available for 86 patients. In this group 78 (91%) completed at least one week of prophylaxis. Side-effects were common (70.9%), particularly diarrhoea (29.6%) and nausea (20.9%). Two patients experienced severe side effects, nephrolithiasis with sepsis, and toxic hepatitis, respectively. In most of the cases where HIV-PEP was prescribed the indication was questionable, with the HIV status of the source unknown. The role of HIV-PEP as part of HIV prevention programs should be well defined in view of the cost and potential for causing severe side-effects

Risks Factors for Infections with Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae at a Tertiary Care University Hospital in Switzerland

Abstract : Background: : There are considerable geographical differencesin the occurrence of extended-spectrum beta-lactamase(ESBL)-producing bacteria, both in the community and in thehospital setting. Our aim was to assess risk factors forbloodstream, urinary tract, and vascular catheter-associatedinfections with ESBL-producing Escherichia coli and Klebsiellapneumoniae at a tertiary care hospital in a low-prevalencecountry. Methods: : We performed a case-control study comparing 58patients with infections due to ESBL-producing E. coli orK. pneumoniae vs 116 controls with infections due to non-ESBL producing organisms at the University Hospital Zurich,Switzerland, between 1 July 2005 and 30 June 2007. Results: : Cases included 15 outpatients and 43 inpatients.Multivariable analyses found three risk factors for ESBL-producingisolates: begin of symptoms or recent antibioticpre-treatment in a foreign country (odds ratio [OR] 27.01,95% confidence interval [CI] 2.38-1,733.28], p = 0.042),antibiotic therapy within the year preceding the isolation ofthe ESBL-producing strain (OR 2.88, 95% CI 1.13-8.49,p = 0.025), and mechanical ventilation (OR 10.56, 95% CI1.06-579.10, p = 0.042). Conclusions: : The major risk factors for infections due toESBL-producing bacteria were travel in high-prevalencecountries, prior antibiotic use, and mechanical ventilationduring a stay in the intensive care unit. Community-acquiredinfections were documented in 17% of the patients.An early identification of risk factors is crucial to providingthe patients an optimal empiric antibiotic therapy and tokeep the use of carbapenems to a minimu

Initial management of and outcome in patients with pneumococcal bacteremia: a retrospective study at a Swiss university hospital, 2003-2009

Purpose: The aim of this quality control study was to assess the time to initial diagnostic procedures and the time to the first dose of antibiotics in patients with pneumococcal bacteremia, and to investigate whether the timeliness of these interventions influenced outcome. Methods: We retrospectively studied patient characteristics, chronological sequence of diagnostic and therapeutic steps, and the course of disease of all patients with pneumococcal bacteremia at a Swiss university hospital between 2003 and 2009, and we analyzed associations between these factors and the length of hospital stay (LOS) and mortality. Results: A total of 102 episodes of pneumococcal bacteremia in 98 patients were analyzed, of whom 15.7% died during hospitalization. The median time (interquartile range [IQR]) to the first antibiotic dose was 4.0 (2.0-5.9)h, and the median times (IQR]) to blood cultures, chest radiograph, lumbar puncture, and brain computed tomography (CT) scan or magnetic resonance imaging (MRI) were 1.4 (0.5-3.3), 2.5 (1.2-4.2), 4.2 (2.7-7.2), and 2.3 (0.6-6.2)h, respectively. The time to diagnostic procedures and therapy were not associated with LOS or death. Risk factors for death in the univariable analysis were: Charlson comorbidity index [odds ratio [OR] (95% confidence interval) per unit increase, 1.3 (1.1-1.6)], neutropenia [OR 10.1 (2.0-51.0)], human immunodeficiency virus (HIV) infection [OR 3.9 (1.1-13.8)], chronic respiratory disease [OR 4.4 (1.2-16.0)], chronic liver disease [OR 3.2 (1.0-9.7)], smoking [OR 3.8 (1.1-13.5)], injection drug use [OR 9.7 (1.5-63.7)], and antibiotic therapy within 6months before admission [OR 4.0 (1.3-12.5)]. The multivariable analysis revealed age >60years (P=0.048) and alcoholism (P=0.009) as risks for prolonged LOS. Conclusions: The outcome of pneumococcal bacteremia may be more influenced by patient characteristics than by minor differences in the timeliness of initial diagnostic and therapeutic measures within the first several hours after hospital admissio

A stringent preemptive protocol reduces cytomegalovirus disease in the first 6 months after kidney transplantation

Background: The optimal strategy to prevent cytomegalovirus (CMV) disease after kidney transplantation continues to be open to debate. The preemptive approach requires regular determination of CMV viremia and prompt initiation of therapy. Methods: We retrospectively compared the incidence of CMV disease during two periods at our center: A first phase (P1, n=84 kidney recipients), during which time the intensity of surveillance was determined by the responsible physician, was compared to a second phase (P2, n=74), when a stringent protocol of CMV surveillance was required for all patients. The preemptive approach was applied for all CMV risk groups; prophylaxis was optional in the case of treatment for rejection or delayed graft function in the intermediate- and high-risk group. Follow-up was truncated at 6months after transplant surgery. CMV syndrome was differentiated from asymptomatic replication by the presence of at least one systemic symptom, while diagnosis of CMV end-organ disease required histological confirmation. Results: Immunosuppression was similar in the two periods. CMV prophylaxis was used equally (26%) in both periods. The probability for asymptomatic viremia episodes was not different for patients in P1 and P2 regardless of the prevention strategy. For patients following the preemptive strategy, the probability for CMV disease was increased during P1 (p=0.016), despite fewer PCR assays being performed in phase 2. Protocol violations were only observed during P1. Conclusions: The probability of CMV disease episodes (CMV syndrome and CMV end-organ disease) was substantially reduced using a very stringent protocol. This study highlights the crucial importance of a stringent protocol with optimal adherence by all caregivers if the preemptive strategy is to be successfu

Quantitative Antibiotic Use in Hospitals: Comparison of Measurements, Literature Review, and Recommendations for a Standard of Reporting

Abstract : 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 us

Zoonotic pathogens and antimicrobial resistance in ‘animal-friendly’ pig production systems in Switzerland

In a cross-sectional study, the impact of ‘animal-friendly’ housing systems on the prevalence of Salmonella species, Campylobacter species, and Yersinia enterocolitica in finishing pigs and pork was investigated. Furthermore, antimicrobial resistance patterns of isolated campylobacter strains were analysed. In faecal samples of two out of 88 fattening pig farms salmonellae were isolated. All 865 samples of pork were found to be negative. Campylobacter was isolated on 98.9 % of the farms but only from 0.2 % of the pork samples. Yersiniae were found in samples of 63.3 % of the farms and in 15.4 % of pork samples. For all three bacteria, there was no statistically significant difference in the prevalence between conventional and ‘animal-friendly’ housing systems. In ‘animal-friendly’ farms, antimicrobial resistance of campylobacter isolates to fluoroquinolones and streptomycin was significantly less frequent than in conventional farms. Furthermore, fewer isolates had resistance to three or more antimicrobials in ‘animal-friendly’ farms