Strategies to enhance rational use of antibiotics in hospital: a guideline by the German Society for Infectious Diseases.

INTRODUCTION: In the time of increasing resistance and paucity of new drug development there is a growing need for strategies to enhance rational use of antibiotics in German and Austrian hospitals. An evidence-based guideline on recommendations for implementation of antibiotic stewardship (ABS) programmes was developed by the German Society for Infectious Diseases in association with the following societies, associations and institutions: German Society of Hospital Pharmacists, German Society for Hygiene and Microbiology, Paul Ehrlich Society for Chemotherapy, The Austrian Association of Hospital Pharmacists, Austrian Society for Infectious Diseases and Tropical Medicine, Austrian Society for Antimicrobial Chemotherapy, Robert Koch Institute. MATERIALS AND METHODS: A structured literature research was performed in the databases EMBASE, BIOSIS, MEDLINE and The Cochrane Library from January 2006 to November 2010 with an update to April 2012 (MEDLINE and The Cochrane Library). The grading of recommendations in relation to their evidence is according to the AWMF Guidance Manual and Rules for Guideline Development. CONCLUSION: The guideline provides the grounds for rational use of antibiotics in hospital to counteract antimicrobial resistance and to improve the quality of care of patients with infections by maximising clinical outcomes while minimising toxicity. Requirements for a successful implementation of ABS programmes as well as core and supplemental ABS strategies are outlined. The German version of the guideline was published by the German Association of the Scientific Medical Societies (AWMF) in December 2013.

Chronic hepatitis C in Austria, 1992-2006: genotype distribution and demographic factors.

Chronic hepatitis C is a leading cause of end-stage liver disease and, with a worldwide prevalence of up to 3%, is a pandemic infectious disease. Austria, like most western European countries can be considered as a low prevalence country. This analysis aimed to assess the distribution of hepatitis C virus (HCV) genotypes in patients with chronic HCV infection in Upper Austria. Between September 1992 and December 2006, we identified 1,318 consecutive patients who tested positive for HCV RNA. Genotyping was routinely performed in 1,239 of the 1,318 patients, and in a subgroup of 617 patients data on the source of transmission were collected. Additionally we obtained data on liver histology and body mass index in a subsample of 273 of the 617 patients. Hepatitis C genotypes 1, 2, 3, 4, 6 and co-infections were found in 80.4%, 4.5%, 12.3%, 2.7%, 0.1% and 0.2% of the patients, respectively. There was a highly significant age difference in relation to gender at the time of diagnosis of chronic hepatitis C, with women being older than men (men: 45.0 years; women: 49.3 years; p<0.0001). The number of new cases of chronic hepatitis C decreased substantially over the last decade, but although risk factors for obtaining HCV are well established, we did not find a decrease in the age of first diagnosis. Besides consistent screening in defined risk groups it is important to raise awareness for risk factors for HCV acquisition and liver disease progression.

Antimicrobial stewardship.

The aim of antimicrobial management or stewardship programmes is to ensure proper use of antimicrobial agents in order to provide the best treatment outcomes, to lessen the risk of adverse effects (including antimicrobial resistance), and to promote cost-effectiveness. Increasingly, long-term sustainability is found to be the major focus of antimicrobial stewardship. Implementing structural measures in healthcare institutions is therefore a major, but not the sole, focus of attention in promoting prudent use of antibiotics. The problem of antimicrobial resistance requires common strategies at all levels--for the prescribers and at ward, departmental, hospital, national and international levels.

MRSA in Austria--an overview.

The aim of this study was to provide an overview of predominant and sporadic methicillin-resistant Staphylococcus aureus (MRSA) strains in large regions of Austria, and to compare the results with those from other European countries. In total, 1439 MRSA isolates, collected routinely between January 1996 and June 2006 from five Austrian federal provinces, were investigated. The isolates were confirmed as MRSA using mecA/femA multiplex PCR assays. Genes encoding Panton-Valentine leukocidin (PVL), which are characteristic of community-acquired MRSA, were also detected by PCR. Subtyping was performed using SmaI macrorestriction digestion of genomic DNA, followed by pulsed-field gel electrophoresis (PFGE) and cluster analysis. Isolates that could not be assigned to clusters were further analysed by spa typing and/or multilocus sequence typing. The predominant clones detected in Austria were ST228 (southern German epidemic clone), ST5 (Rhine-Hessen MRSA), the ST8 Austrian clone and CC8/ST8. Whereas the frequencies of lineages corresponding to ST247, ST45 and ST22 remained comparably low, an increase in the frequency of lineages corresponding to ST5 and to ST228 was recorded. Overall, 20 different MRSA types and 321 subtypes were recognised according to PFGE analysis. The prevalence of different strains varied considerably in the different Austrian regions. When compared to other European countries, the situation in Austria was most similar to that found in Germany.

Staphylococcal toxic epidermal necrolysis: species and tissue susceptibility and resistance.

The staphylococcal exfoliatin, which is responsible for the "scalded skin syndrome" in man, cleaves the epidermis directly beneath the stratum granulosum. Its activity in vivo is paralleled in organ cultures, providing a rapid and convenient assay. The cutaneous responses of several mammalian and nonmammalian species were examined both in vivo and in vitro. Human and murine skin, as well as that of hamsters and monkeys exfoliated, while all other species tested (rat, rabbit, guinea pig, dog, frog, and chicken) were refractory. Results were identical in vivo and in vitro. Susceptibility and resistance are inherent, presumably genetic, attributes of the epidermis, since neither dermal elements nor circulating factors interfered with or influenced sensitivity to staphylococcal exfoliatin. Besides possessing species specificity, this exfoliatin is also tissue specific, failing to cleave all mouse nonkeratinizing epithelia tested, while the reactions of some extracutaneous keratinizing epithelia were equivocal. The species and tissue specificity of the staphylococcal scalded-skin syndrome may be attributable to either keratinocyte receptors specific for exfoliatin or the presence of specific, as yet undefined, substances in the intercellular space.

Influence of temocillin on human bowel flora.

The influence of temocillin on intestinal flora was investigated in 6 healthy volunteers, each of whom received intravenous temocillin 1g twice daily over a period of 6 to 7 days. Dilution series of stool samples were investigated before, during and immediately after treatment, as well as 9 to 14 days after treatment had been stopped. The basic effect of temocillin was a pronounced reduction in Enterobacteriaceae during and immediately after treatment. Nine to 14 days after conclusion of treatment, the Enterobacteriaceae had almost reattained their original numbers. No clear influence could be established for temocillin on the total numbers of aerobic bacteria, strict anaerobes, or the members of the Bacteroides fragilis group. The number of enterococci increased slightly during treatment, but antibiotic-resistant Enterobacteriaceae were not selected by treatment. It can be concluded that in these volunteers the colonisation resistance of the colon was maintained during treatment, and that temocillin exerted an influence comparable to a selective decontamination of the intestine.

An open randomised comparison of ofloxacin and doxycycline in lower respiratory tract infections.

The efficacy and tolerance of ofloxacin and doxycycline were compared in patients with lower respiratory tract infections. Doses used were 200 or 400mg twice daily for ofloxacin and 100mg twice daily for doxycycline. Of 230 patients treated, 219 could be assessed for effectiveness. 88 patients were treated for exacerbations of chronic bronchitis and 131 for pneumonia. Clinical cure was achieved in 18 of 52 patients with bronchitis treated with ofloxacin. Improvement occurred in 29 and failure in 5. In the doxycycline-treated bronchitis group 11 of 36 patients were cured, 22 improved and 1 failure occurred. Of 62 patients with pneumonia who were administered ofloxacin, 34 were cured, 26 improved and treatment failed in 2. In the doxycycline-treated group of patients with pneumonia 39 of 69 were cured, 23 improved and 7 failed to respond. Two patients experienced adverse effects during ofloxacin treatment and 7 while receiving doxycycline.

European recommendations for antimicrobial resistance surveillance.

The problem of antimicrobial resistance surveillance in Europe has been debated extensively in many excellent documents issued by national committees that often assume the value of national guidelines. However, a comprehensive document addressing the whole matter from a European perspective, as well as reviewing its present status and drafting future perspectives, has been lacking. The present recommendations have been produced by the ESCMID Study Group for Antimicrobial Resistance Surveillance (ESGARS) through a consensus process involving all members of the Study Group. The recommendations focus on the detection of bacterial resistance and its reporting to clinicians, public health officers and a wider-and ever-increasing-audience. The leading concept is that the basis for resistance monitoring is microbiological diagnostics. The prerequisites for resistance monitoring are findings of adequate quality and quantity, which have been recorded properly and evaluated correctly. Different types of surveillance studies should fulfil different requirements with regard to data collection and reporting, the expected use of data, and the prerequisites for networking such activities. To generate relevant indicators, bacterial resistance data should be reported using adequate denominators and stratification. Reporting of antimicrobial resistance data is necessary for selection of empirical therapy at the local level, for assessing the scale of the resistance problem at the local, national or international levels, for monitoring changes in resistance rates, and for detecting the emergence and spread of new resistances types. Any type of surveillance study should conclude, where appropriate, with a proposal for intervention based on the data obtained.

Educational programmes for infection control in Austria.

Educational aims and strategies (simply arousing awareness, sensitivity and understanding; and/or training in practical skills and knowledge; or the ability to teach infection control, and to convince those taught) depend on the target group. Infection control is part of the curriculum for students of medicine and other health care professions, and is included in course examinations. Postgraduate doctors may seek training on courses which are organized by the Hygiene Institute of the University of Vienna in co-operation with the Austrian Society of Hygiene, Microbiology and Preventive Medicine. Registered nurses may enroll in the Austrian Nurses' Association training scheme (6 weeks of theory with professional work for 2 years), leading to approval as Hygieneschwester/-pfleger. Postgraduate in-hospital education for all health-care professions occurs in many Austrian hospitals, with resources from Vienna and Linz. Hospital managements, health authorities and politicians are influenced via their own educational activities and via publications.

Non-touch fittings in hospitals: a possible source of Pseudomonas aeruginosa and Legionella spp.

Non-touch fittings are gradually becoming very common in the bathrooms and toilets of public facilities and restaurants. Hospitals and other healthcare facilities have recently started to install these types of water taps to lower water consumption, thus saving costs, and to prevent healthcare workers from touching the tap, thus promoting hygiene. This study analysed the bacteriological water quality of 38 non-touch water taps in different settings in a 450-bed secondary-care hospital in Upper Austria. Two different tap types were installed: 23 taps were without temperature selection and 15 were with temperature selection (cold and warm). A membrane filtration method was used, and the authors screened for both indicator organisms and Pseudomonas aeruginosa in 100 ml water samples. In 10 non-touch taps without temperature selection, the authors also screened for Legionella spp. in 500 ml water samples. Seventy four percent of the taps without temperature selection and 7% of the taps with temperature selection showed contamination with P. aeruginosa (P<0.001). None of the taps showed contamination with indicator organisms. Detailed analysis of the source of contamination revealed that the magnetic valve and the outlet itself were heavily contaminated, whereas the junction from the central pipe system was free of contamination. All 10 analysed taps showed contamination with Legionella spp. It was concluded that the local contamination of non-touch fittings is a result of the low amount of water that flows through the outlet, the low water pressure and the column of water, which is 'still-standing' and has a temperature of about 35 degrees C, thus providing nearly ideal growth conditions for P. aeruginosa. Additionally, the presence of materials such as rubber, PVC, etc. in the fittings enhances the adhesion of P. aeruginosa and thus the production of biofilms. In conclusion, the authors wish to encourage infection control teams to evaluate the use of non-touch fittings in hospitals, especially when they are installed in risk areas.

Vibrio cholerae non-O1 septicaemia in a patient with liver cirrhosis and Billroth-II-gastrectomy.

This report deals with the first diagnosed case of Vibrio cholerae non-O1 septicaemia in Austria. After a vacation in Tunisia, a 51-year-old male patient with liver cirrhosis and Billroth-II-gastrectomy was admitted to hospital because of abdominal pain, growing ascites, and jaundice. Four days later, the patient developed a single peak of high fever (39.6 degrees C). A blood culture was drawn and treatment with amoxycillin/clavulanic acid commenced. The blood culture yielded Gram-negative comma-like rods which were identified as V. cholerae non-O1.

Single dose cefuroxime/metronidazole versus metronidazole alone in elective colorectal surgery.

Sixty assessable patients undergoing elective colonic and rectal surgery were randomly allocated to receive prophylaxis with a combination of 1.5 g cefuroxime plus 500 mg metronidazole or 500 mg metronidazole alone as single doses by the intravenous route, given at the beginning of anesthesia. The two groups were matched for age, sex, malignancy, and type of operation. Primary wound infections were observed in one patient (3.7%) in the combination group and six (18.2%) in the group given metronidazole alone. This trend was not statistically significant. Bacteriologic examination of the anastomoses, abdominal walls, and wounds showed significantly more sterile cultures in the combination group, although more aerobic cefuroxime-resistant isolates were seen in this group. There is no evidence that the emergence of resistant strains had any influence on the outcome of patients in the study. It was concluded that an appropriate antibiotic prophylactic regimen for colorectal surgery should be directed against aerobic and anaerobic organisms. Cefuroxime plus metronidazole is an effective regimen for the prevention of postoperative infection.

Augmentin in acute exacerbations of chronic bronchitis.

Forty-five patients with acute chronic bronchitis were treated with Augmentin, an amoxycillin combined with the beta-lactamase inhibitor clavulanic acid, initially by parenteral administration followed by oral treatment after 3 days lasting in the mean 7.1 days. The over-all clinical evaluation showed a cure rate of 93%. Side-effects were comparable to therapy with other amoxycillins. Bacteriological evaluation of the sputum samples demonstrated in 91% of cases an elimination of the initially isolated organism. Prior to therapy we found in 25% of the isolated strains beta-lactamase-producing and Augmentin-sensitive organisms. The parenteral formulation of Augmentin seems to be a valuable addition to the parenteral therapy of lower respiratory tract infections.

[Anaerobic bacteria in clinical specimens of a hospital laboratory (author's transl)]. / Obligat anaerobe Bakterien im Untersuchungsmaterial eines Krankenhauslaboratoriums.

Over a 14-month period 261 clinical specimens were cultured anaerobically, this figure representing about 3% of the total specimens submitted to the microbiological laboratory. Not accepted for anaerobic culture were stools, sputa, urines, vaginal and urethral swabs and swabs from superficial skin lesions. All materials were sent to the laboratory in an anaerobic transport medium and processed according to the recommendations of the American Society for Microbiology and the Center for Disease Control, Atlanta, Georgia. Not included in this figure are blood cultures and cultures from removed venous catheters. 35% of the specimens contained anaerobes. 169 anaerobic strains were isolated. 78 of them belonged to the Bacteroides fragilis group. Clostridium perfringens was found in only 7 cases. 14% of the strains were B. melaninogenicus, 7% other gram-negative non-sporeforming rods. In most of the cases a mixed aerobic-anaerobic flora was found. More than 75% of specimens obtained from infections originating from the lower intestinal tract yielded growth of anaerobes. In infections of the bile duct anaerobes were found in 25% of the cases. In infections of the upper urinary tract anaerobes played no major role. 35% of the isolates of the B. fragilis group were resistant to tetracycline, 17% to cefoxitin and 9% to clindamycin.

[Resistance of blood culture isolates in vitro to 4 aminoglycoside antibiotics in Austria--1982/83]. / Resistenz von Blutkulturisolaten in vitro gegenüber 4 Aminoglykosidantibiotika in Osterreich--1982/83.

Over the period September 1982 to February 1983 268 blood culture isolates were consecutively collected in 4 microbiological laboratories in Austria (Linz, Vienna, Graz, Feldkirch) and 251 of these strains (streptococci excluded) were tested for resistance to Gentamicin (G), Tobramycin (T), Netilmicin (N) and Amikacin (A) using a microtitre broth dilution method. This investigation was part of an international study. Of the bacterial strains examined 57% were staphylococci (34% Staphylococcus aureus) and 43% gram-negative rods (18% E. coli, 17% other enterobacteriaceae and 5% Pseudomonas aeruginosa etc.). 25% of all strains tested were resistant to Gentamicin (MIC greater than 4 mg/l), 27% to Tobramycin (MIC greater than 4 mg/l), 6% to Netilmicin (MIC greater than 4 mg/ml) and 5% to Amikacin (MIC greater than 8 mg/l). The resistance rate of staphylococci was markedly greater towards Gentamicin (35%) and Tobramycin (39%) than Netilmicin (4%) and Amikacin (6%). The respective percentages of resistant gram-negative rods were considerably smaller, except in the case of Netilmicin (G 13%, T 11%, N 8%, A 4%). Regional differences were observed between Linz and Vienna in the resistance of staphylococci to Gentamicin (24% versus 49%) and Tobramycin (33% versus 53%). On a weight basis Netilmicin was the most active substance in combating nearly all groups of bacteria. Also in strains sensitive to the other aminoglycosides the MIC values of Netilmicin were considerably lower than for the other substances. A noteworthy feature in comparison with the results of other countries participating in this international study was the distinctly higher incidence of staphylococci among the blood culture isolates and the considerably higher percentage of aminoglycoside-resistant strains in Austria. Analysis of the data suggests that the high resistance rates among staphylococci are a consequence of selection by frequently used antibiotics. Hence, it appears essential to observe the development of aminoglycoside resistance in Austria closely and to recommend that these substances, of extreme value in the treatment of severe infections, should be used solely for the most stringent indications.

[Further experimental investigations on the therapy of gas gangrene with ozone and oxygen (author's transl)]. / Weitere experimentelle Untersuchungen zur Therapie des Gasbrandes mit Ozon und Sauerstoff

In continuation of a recently-published investigation on the effect of intramuscular injections of an ozone-oxygen mixture on experimental gas gangrene in the guinea pig, 2 additional experiments were performed in order to establish the efficacy of the therapy when given twice daily instead of only once. Futhermore, the effect of an analogous therapy was investigated with the use of pure oxygen. The ozone-oxygen therapy reduced the death rate from 100% in untreated control animals to 73.6 and 70.0%, respectively, in the 2 series of experiments. The median survival times were prolonged from 0.56 and 1.33 days to 5.50 and 6.66 days. The use of oxygen twice daily reduced the death rates significantly even further to 57.0 and 47.9%. With this therapy the median survival time was increased to 8 and more than 12 days. The differences in therapeutic effect of the 2 gases were not, however, statistically significant. On account of its simple applicability previous experiments on animals it is proposed that this therapy be employed also in cases of human gas gangrene. In addition, the bactericidal effect of CaCl2, as used in this experimental study, on vegetative forms of Clostridia is demonstrated.

In vitro activity of newer broad spectrum beta-lactam antibiotics against enterobacteriaceae and non-fermenters: a report from Austrian intensive care units. Austrian Carbapenem Susceptibility Surveillance Group.

We compared the in vitro activity of broad spectrum beta-lactam antibiotics against 573 gram-negative isolates (enterobacteriaceae and non-fermenters) collected between November 1996 and May 1997 from 9 laboratories serving intensive care units throughout Austria. MIC's (Minimal Inhibitory Concentration) were obtained with the E-test for meropenem, imipenem, ceftazidime, cefepime, cefpirome and piperacillin/tazobactam. Pseudomonas aeruginosa was the most frequently isolated organism (22%), followed by E. coli (19%), Klebsiella spp. (16%), and Enterobacter spp. (14%). Acinetobacter spp., Proteus spp., Serratia spp., Stenotrophomonas maltophilia, Citrobacter spp., Morganella morganii, Burkholderia cepacia and Salmonella enteritidis were isolated less frequently. Overall meropenem, imipenem and ceftazidime were the most active compounds in vitro, inhibiting 90%, 89%, and 87% of the isolates, respectively. Pseudomonas aeruginosa was inhibited by piperacillin/tazobactam in 89%, by cefepime in 87% and by ceftazidime in 85%. Imipenem, meropenem and cefpirome were less active (79%, 75% and 69% respectively). All E. coli strains were inhibited by meropenem, 99% were inhibited by imipenem, cefepime and cefpirome. Ceftazidime was active against 95% and piperacillin/tazobactam against 92% of E. coli. All Klebsiella spp. were inhibited by meropenem, cefepime and cefpirome. Imipenem inhibited 99% and ceftazidime 98% of the Klebsiella isolates. Piperacillin/tazobactam was active against 95% of Klebsiella spp. In vitro carbapenems are still the most active of all antibiotics tested. The relatively high resistance of Pseudomonas spp. and Acinetobacter spp. to carbapenems reflects the wide use of carbapenems during the last years. However, most bacterial isolates are still sensitive to the tested broad spectrum beta-lactams.

Enterovirus infection--a possible trigger for Graves' disease?

Viruses are potential environmental factors in autoimmune disease. Some evidence suggests a relationship between enteroviral infection (especially Coxsackie B virus) and autoimmunity. We investigated 21 individuals with recent onset of Graves' hyperthyroidism in regard of (subclinical) enterovirus infection. Thyrotoxic symptoms had started about two months before blood sample collection. The patients were from Upper Austria and mainly female (17/21). Their mean free thyroxin levels in blood were twice the maximum normal value and the majority achieved a euthyroid state 1 1/2 years later, after antithyroid medication. We employed a nested PCR reaction with primers of the enterovirus genome on blood samples. All were negative for RNA of the enterovirus group. Coxsackie and related viruses were not identified as a trigger factor in autoimmune thyrotoxic disease.

Trends in the occurrence of MRSA strains in Upper Austria from 2006 to 2009.

Between 2006 and 2009, all MRSA isolates recovered from human patients in Upper Austria were subjected to molecular biological analysis. Whereas the isolate number decreased from year to year, the proportion of the most common sequence types (ST5, ST8 and ST22) as well as the frequency of associated PFGE subtypes and spa-types remained similar. The rate of PVL-positive MRSA increased, whereupon the most common sequence types were ST152, ST8 including clone USA300, ST5, ST777 and ST88. The frequency of ST398 was high (25%) in relation to the PVL-positive clones. Thus, we consider a special focus on community-associated MRSA to be necessary.