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.

Mucosal Candida infection and colonisation as well as associated risk factors in solid organ transplant recipients.

More detailed information on Candida colonisation and infection of the mucous membranes in organ transplant recipients (OTR) is of particular interest. Therefore, this issue was prospectively evaluated in 400 different OTR in different posttransplantation periods as well as in 405 healthy age- and sex-matched controls. In addition, possible risk factors and the clinical condition in the OTR were evaluated. Independent of the transplanted organ there is a statistically significant decrease in the number of positive culture results, of symptomatic candidiasis and an increase of isolated non-albicans Candida species corresponding to length of the posttransplantation period. No significant differences could be observed in the OTR in association with different immunosuppressive regimen; however, higher dosages of corticosteroids and tacrolimus correlated with symptomatic candidiasis. As Candida spp. may also cause systemic infection and dissemination, additional knowledge about cofactors and associated strains may have an impact on therapeutic decisions.

Prevalence and incidence of surgical site infections in the European Union/European Economic Area: how do these measures relate?

BACKGROUND: In 2011-2012, the European Centre for Disease Prevention and Control (ECDC) initiated the first European point prevalence survey (PPS) of healthcare-associated infections (HCAIs) in addition to targeted surveillance of the incidence of specific types of HCAI such as surgical site infections (SSIs). AIM: To investigate whether national and multi-country SSI incidence can be estimated from ECDC PPS data. METHODS: In all, 159 hospitals were included from 15 countries that participated in both ECDC surveillance modules, aligning surgical procedures in the incidence surveillance to corresponding specialties from the PPS. National daily prevalence of SSIs was simulated from the incidence surveillance data, the Rhame and Sudderth (R&S) formula was used to estimate national and multi-country SSI incidence from the PPS data, and national incidence per specialty was predicted using a linear model including data from the PPS. FINDINGS: The simulation of daily SSI prevalence from incidence surveillance of SSIs showed that prevalence fluctuated randomly depending on the day of measurement. The correlation between the national aggregated incidence estimated with R&S formula and observed SSI incidence was low (correlation coefficient = 0.24), but specialty-specific incidence results were more reliable, especially when the number of included patients was large (correlation coefficients ranging from 0.40 to 1.00). The linear prediction model including PPS data had low proportion of explained variance (0.40). CONCLUSION: Due to a lack of accuracy, use of PPS data to estimate SSI incidence is recommended only in situations where incidence surveillance of SSIs is not performed, and where sufficiently large samples of PPS data are available.

Impact of participation in a surgical site infection surveillance network: results from a large international cohort study.

BACKGROUND: Surveillance of surgical site infections (SSIs) is a core component of effective infection control practices, though its impact has not been quantified on a large scale. AIM: To determine the time-trend of SSI rates in surveillance networks. METHODS: SSI surveillance networks provided procedure-specific data on numbers of SSIs and operations, stratified by hospitals' year of participation in the surveillance, to capture length of participation as an exposure. Pooled and procedure-specific random-effects Poisson regression was performed to obtain yearly rate ratios (RRs) with 95% confidence intervals (CIs), and including surveillance network as random intercept. FINDINGS: Of 36 invited networks, 17 networks from 15 high-income countries across Asia, Australia and Europe participated in the study. Aggregated data on 17 surgical procedures (cardiovascular, digestive, gynaecological-obstetrical, neurosurgical, and orthopaedic) were collected, resulting in data concerning 5,831,737 operations and 113,166 SSIs. There was a significant decrease in overall SSI rates over surveillance time, resulting in a 35% reduction at the ninth (final) included year of surveillance (RR: 0.65; 95% CI: 0.63-0.67). There were large variations across procedure-specific trends, but strong consistent decreases were observed for colorectal surgery, herniorrhaphy, caesarean section, hip prosthesis, and knee prosthesis. CONCLUSION: In this large, international cohort study, pooled SSI rates were associated with a stable and sustainable decrease after joining an SSI surveillance network; a causal relationship is possible, although unproven. There was heterogeneity in procedure-specific trends. These findings support the pivotal role of surveillance in reducing infection rates and call for widespread implementation of hospital-based SSI surveillance in high-income countries.

Combating implant infections. Remarks by a women's team.

Research on implant infections requires cooperative efforts and integration between basic and clinical expertises. An international group of women scientists is acting together in this field. The main research topics of the participants of this group are described. Formation of bacterial biofilms, antibiotic resistance and production of virulence factors like adhesins and toxins are investigated. New biomaterials, coatings and drugs designed to inhibit microbial adhesion are evaluated, and infection-resistant biomaterials are under study, such as a novel heparinizable polycarbonate-urethane (Bionate) or incorporation of diamino-diamide-diol (PIME) to reduce bacterial attachment. The correlation between biofilm production and the accessory-gene-regulator (agr) is investigated in Staphylococcus aureus. The ability to form biofilm has also been shown to be one of the important virulence factors of Enterococcus faecalis, favouring colonization of inert and biological surfaces. The study of quorum sensing has led to the discovery of a quorum sensing inhibitor termed RIP that suppresses staphylococcal biofilm and infections. The immune response and the local defence mechanisms of the host against implant-associated infections, activation and infiltration of immunocompetent cells into the sites of infection have been studied in patients with implant-associated osteomyelitis. Production of monoclonal antibodies (mAbs) as possible vaccines against the staphylococcal collagen-binding MSCRAMMs is in progress.

A survey on current knowledge, practice and beliefs related to preoperative antimicrobial decolonization regimens for prevention of surgical site infections among Austrian surgeons.

BACKGROUND: Various measures are considered to reduce the risk of surgical site infection (SSI), including preoperative decolonization. Details of preoperative decolonization practices in surgical departments have not been investigated in Austria. AIM: To analyse the current situation of pre-surgical patient decolonization in national hospitals and to assess the current knowledge on this procedure among surgeons of different surgical disciplines. METHODS: A 12-point structured questionnaire was distributed to all Austrian hospitals with at least one surgical department. FINDINGS: Two-thirds (103/158; 65%) of responding surgeons stated that any type of preoperative decolonization is implemented in their surgical department. There was heterogeneity of different protocols, ranging from decolonization of only known S. aureus carriers, of a subgroup of patients, or universal decolonization of all patients before elective surgery. Octenidine was the most frequently used antimicrobial compound (60.2%), followed by mupirocin (38.8%), triclosan (14.6%), polyhexanide (12.6%), chlorhexidine (11.7%), and didecyldimonium chloride (7.8%). CONCLUSION: Preoperative decolonization seems to be performed in Austrian hospitals on a routine basis. However, this measure is implemented using a variety of modalities, antimicrobial compounds, and staff. Since our survey also demonstrated that those who are better informed about preoperative decolonization are also those who are more convinced of the usefulness of the preventive measure, future activities should not only focus on generating more comparable studies in this field, but should also include targeted education.

Changing pattern of candidaemia 2001-2006 and use of antifungal therapy at the University Hospital of Vienna, Austria.

A retrospective survey of candidaemia between 2001 and 2006 was performed at the University Hospital of Vienna, a 2200-bed centre with large organ transplantation and haematology-oncology units. The incidence rate of Candida spp. in blood cultures increased from 0.27 cases/1000 admissions in 2001 to 0.77 cases/1000 admissions in 2006 (p <0.005). The incidence of candidaemia caused by Candida albicans and by non-albicans Candida spp. both increased during this period; although there was a trend towards an increased incidence (37%) of non-albicans Candida spp., particularly Candida glabrata, in surgical wards, C. albicans remained the predominant pathogen (63%). In the haematology-oncology unit, C. albicans remained the leading pathogen (23/29 isolates, 79%), followed by Candida tropicalis and C. glabrata (2/29, 7% each), Candida sake and Candida lusitaniae (1/29, 3% each). The overall survival rate was 43.8%, ranging from 32.8% in 2004 to 63.6% in 2002. In total, 108 (33.2%) patients died within 4 weeks of the first isolation of Candida spp. from blood; 58 (54%) of these patients died within the first 7 days, and a further 34 patients died within the next 3 months. Fluconazole was used extensively (24 701.5 defined daily doses), followed by amphotericin B (8981.4 defined daily doses), during 2005. The consumption of antifungal agents increased continuously (p <0.05) because of increased use of voriconazole and caspofungin. Although the numbers of susceptible patients remained unchanged, the net increase in the number of cases of candidaemia warrants a re-evaluation of the risk-factors and the use of improved diagnostic procedures for invasive fungal infections.

Effects of tigecycline, linezolid and vancomycin on biofilms of viridans streptococci isolates from patients with endocarditis.

BACKGROUND: Endocarditis, and prosthetic valve endocarditis in particular, is a serious disease with high morbidity and mortality. We investigate the effects of tigecycline, linezolid and vancomycin on biofilms of viridans group streptococci (VGS) isolated from patients with definite native or prosthetic valve endocarditis. METHODS AND RESULTS: Ten of 20 VGS blood stream isolates from patients with endocarditis formed biofilms in the microtiter plate biofilm model. The minimal inhibitory concentrations (MIC) for tigecycline, linezolid and vancomycin were determined using the microdilution broth method. Biofilms were grown for 24 hours and were incubated with tigecycline, linezolid and vancomycin at increasing concentrations from 1-128x MIC of the isolate being tested. Biofilm thickness was quantified by measuring the optical density (OD) after dyeing it with crystal violet. The incubation of the biofilms with tigecycline, linezolid or vancomycin resulted in a significant reduction of OD compared to the control biofilm without antibiotic (p<0.05). The optical density ratio (Odr) decreased significantly at 2x MIC for tigecycline, and at 8x MIC for linezolid and vancomycin (p<0.05). Although biofilms persisted even at the highest antibiotic concentrations of 128x MIC, bacterial growth was eradicated starting at concentrations of 16x MIC for vancomycin and of 32x MIC for linezolid, but not for tigecycline, up to a concentration of 128x MIC. CONCLUSIONS: In the present study on viridans streptococci isolated from patients with endocarditis, tigecycline and linezolid reduced the density of the biofilms as effectively as vancomycin. However, linezolid and vancomycin were bactericidal at higher concentrations. Linezolid and vancomycin at very high doses may be useful in the treatment of biofilm-associated diseases caused by VGS infections.

PCR based identification and discrimination of agents of mucormycosis and aspergillosis in paraffin wax embedded tissue.

BACKGROUND: Invasive fungal infections are often diagnosed by histopathology without identification of the causative fungi, which show significantly different antifungal susceptibilities. AIMS: To establish and evaluate a system of two seminested polymerase chain reaction (PCR) assays to identify and discriminate between agents of aspergillosis and mucormycosis in paraffin wax embedded tissue samples. METHODS: DNA of 52 blinded samples from five different centres was extracted and used as a template in two PCR assays targeting the mitochondrial aspergillosis DNA and the 18S ribosomal DNA of zygomycetes. RESULTS: Specific fungal DNA was identified in 27 of 44 samples in accordance with a histopathological diagnosis of zygomycosis or aspergillosis, respectively. Aspergillus fumigatus DNA was amplified from one specimen of zygomycosis (diagnosed by histopathology). In four of 16 PCR negative samples no human DNA was amplified, possibly as a result of the destruction of DNA before paraffin wax embedding. In addition, eight samples from clinically suspected fungal infections (without histopathological proof) were examined. The two PCR assays detected a concomitant infection with Absidia corymbifera and A fumigatus in one, and infections with Rhizopus arrhizus and A fumigatus in another two cases. CONCLUSIONS: The two seminested PCR assays described here can support a histopathological diagnosis of mucormycosis or aspergillosis, and can identify the infective agent, thereby optimising antifungal treatment.

Clinical behavior of implant infections due to Staphylococcus epidermidis.

UNLABELLED: Surgical implants and other foreign material are increasingly used in modern medicine to restore or to improve the function of the human body. Infection of an implant is associated with considerable morbidity due to frequent hospitalizations, surgery and antimicrobial treatment. The underlying mechanism is the formation of a bacterial biofilm on the surface of the implanted body. The recognition and diagnosis of implant infections is essential for further therapy and, above all, the decision to remove and exchange the implant. METHODS: We compared the data of 60 patients with implant infections with those of 60 patients with transient bacteremia caused by Staphylococcus epidermidis. The pathogens isolated from blood were characterized with regard to antimicrobial susceptibility and formation of biofilms using a static microtiter plate model. Wild type skin isolates from non-hospitalized healthy volunteers served as control with regard to antimicrobial susceptibility and biofilm formation. RESULTS: Clinical signs and symptoms, underlying diseases and outcome were not different in either group. However, patients with implant infection had fever over a longer time (mean 12 days versus 3 days, respectively, p < 0.05) and more often positive blood cultures than patients with transient bacteremia (3.1 versus 1.2, p < 0.05). Thrombocytopenia was observed in patients with implant infections but not in patients with transient bacteremia (p < 0.05). Biofilms were formed in 86.4 % of the isolates in implant infection, in 88.8 % in transient bacteremia and in 76.9 % of the isolates from healthy volunteers (not significant). Multi-resistance to penicillin, oxacillin, erythromycin, clindamycin, ciprofloxacin and trimethoprim was more common in the hospital strains than in the wild type strains (75.6 % versus 48.7 %, p < 0.05). CONCLUSIONS: The clinical features of implant infections are indistinguishable from those of transient bacteremia. Persisting fever and multiple blood culture yielding the growth of skin flora bacteria are strong indicators for infection of implanted material. Biofilm formation and antimicrobial multi-resistance, as common in implant infection as in transient bacteremia, seem to be accessory factors in infections due to Staphylococcus epidermidis.

Management of serious staphylococcal infections in the outpatient setting.

Patients with serious staphylococcal infections, e.g. endocarditis and osteomyelitis, need prompt and prolonged parenteral antibiotic treatment to ensure eradication of the causative pathogen. The major cost in the treatment of these infections is the long period of hospitalisation required for the administration of intravenous antibiotics. To shorten the hospitalisation period, outpatient treatment can be given to some patients. In this study, patients with acute exacerbations of chronic osteomyelitis (n = 44) or endocarditis (n = 10) were treated with intravenous teicoplanin. The pathogens were Staphylococcus aureus (n = 41, 13 of which were methicillin resistant) and coagulase-negative staphylococci (n = 13, one of which was methicillin resistant). After a mean loading dose of 15 mg/kg for 3 to 10 days, patients received teicoplanin 3 times a week at a dose (mean 15 mg/kg) individualised to achieve serum trough concentrations of approximately 10 mg/L for osteomyelitis and 20 mg/L for endocarditis. Treatment duration ranged from 28 to 150 (mean 62) days for patients with osteomyelitis and from 28 to 88 (mean 49) days for patients with endocarditis. 37 (84%) patients with osteomyelitis and 8 (80%) patients with endocarditis were treated successfully. Adverse events were observed in 9 patients and included rash (n = 3), thrombocytopenia (n = 3), and drug fever, pseudomembranous colitis, nausea, leucopenia and transient hearing impairment (one patient each). In conclusion, this study demonstrates that teicoplanin can be administered successfully in an outpatient setting according to a 3-times weekly schedule for the treatment of patients with staphylococcal osteomyelitis and endocarditis.

Influence of pentoxifylline on cytokine levels and inflammatory parameters in septic shock.

OBJECTIVE: To evaluate the influence of pentoxifylline (PTX), a phosphodiesterase inhibitor, on cytokines and inflammatory proteins in patients suffering from septic shock. DESIGN: Prospective study comparing a therapy group to a matched control group. SETTING: Medical intensive care unit at a university hospital. PATIENTS: Twenty four patients fulfilling the criteria of septic shock were included in this study. Twelve patients received PTX (therapy group) and 12 patients matched for diagnosis, age and gender served as the control group. INTERVENTIONS: Pentoxifylline at 1 mg/kg per hour over 24 h in the therapy group. MEASUREMENTS AND RESULTS: Cytokine levels [tumor necrosis factor-alpha (TNF)], soluble TNF receptor [TNF-R], and interleukin-6 [IL-6] and inflammatory proteins [C-reactive protein, alpha-1-antitrypsin (AAT), fibronectin, and haptoglobin], as well as hemodynamic parameters and the APACHE III score were evaluated before initiation of therapy and 24 h-later. After 24 h, TNF levels were significantly lower in the therapy group (p = 0.013), while IL-6 levels were significantly higher in the therapy group (p = 0.030). Within the 24 h TNF declined significantly in the therapy group (p = 0.006), while IL-6 showed a significant increase (p = 0.043). AAT and the APACHE III score tended to differ significantly after 24 h between the groups [AAT levels higher in the therapy group (p = 0.05), APACHE III score lower (p = 0.05)]. In the therapy group, the systemic vascular resistance index was significantly higher after 24 h (p = 0.0026) whereas the cardiac index declined (p = 0.035). CONCLUSIONS: PTX does influence TNF levels in septic shock patients. Nevertheless, inhibiting a single mediator in severe septic shock cannot stop the inflammatory overreaction.

Serum levels of erythropoietin in acute Plasmodium falciparum malaria.

The pathophysiologic backgrounds of anemia in malaria are complex and multifactorial. The purpose of the present study was to measure serum concentrations of erythropoietin (EPO) and to evaluate the adequacy of EPO production in patients suffering from acute Plasmodium falciparum malaria. Fifteen patients with complicated malaria were included in the study. Serum samples were taken on the day of admission, and days 7, 14, 21 and 28. Serum EPO concentrations were measured using an enzyme-linked immunosorbent assay. The median serum EPO concentration was 15.6 mU/ml on the day of admission (range 0.5-567) mU/ml, 10.6 mU/ml (1.2-863) on day 7, 11.8 mU/ml (0.5-72.8) on day 14, 10 mU/ml (0.5-74.6) on day 21, and 8.3 mU/ml (2.2-61.6) on day 28. Inadequate EPO production was found in 46.6% of the patients on the day of admission, which increased to 67% and 68% on days 7 and 14, and reached a maximum of 80% on day 21. Almost 54% of patients had inadequate EPO production on day 28. Our data indicate inadequate EPO production in patients suffering from acute P. falciparum malaria, which might contribute to the prolonged anemia observed in these patients.

Quinolones in the treatment of complicated urinary tract infection.

Complicated and recurrent urinary tract infections present intriguing clinical management problems. The underlying conditions in patients with complicated urinary tract infections are anatomical abnormalities of the genitourinary tract, neurologic disorders resulting in urinary stasis, obstruction, instrumentation, surgery, diabeters mellitus, renal transplantation, and renal calculi. In comparative studies the quinolones have been shown to be effective in 7-14-day treatment courses in complicated urinary tract infection. Several comparative trials which compare the fluoroquinolones with beta-lactam antibiotics or cotrimoxazole yielded equal or better results for the quinolones. A cost-saving option is given with some of the fluoroquinolones that can be administered parenterally and orally which enables the patient to be discharged from the hospital earlier. There are few differences in antimicrobial activity between the newer quinolones, but differences in the pharmacokinetic properties are evident. The fluoroquinolones are suitable therapeutics for complicated urinary tract infection, because they offer rapid oral absorption, high tissue concentration, broad activity against most Gram-negative and Gram-positive organisms, the possibility of a once-a-day administration, and relatively few side effects.

Cytokines in sepsis due to Candida albicans and in bacterial sepsis.

Cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and tumor necrosis factor-soluble receptor (TNF-sR), and adhesion molecules, e.g. vascular adhesion molecule-1 (VCAM-1) and E-selectin, play an important role in the pathogenesis of bacterial sepsis. Experimental data on cytokine expression during candidaemia are controversial. In this study, plasma concentrations of cytokines and adhesion molecules were compared between patients with sepsis due to Candida albicans and bacterial sepsis. Plasma levels of TNF-alpha, TNF-sR, IL-6, VCAM-1 and E-selectin, were determined in 20 patients with sepsis due to C. albicans, in 20 patients with bacterial sepsis, and in 20 controls on days 1, 7 and 14. On day 1, elevated plasma levels of TNF-alpha, TNF-sR and IL-6 were detected in both sepsis groups compared to controls. On day 1, VCAM-1 levels were higher, and E-selectin levels were lower in patients with Candida sepsis than in patients with bacterial sepsis (p < 0.05). At any time, VCAM-1 levels were significantly greater in patients with Candida sepsis than in patients with bacterial sepsis (p < 0.05). Non-survivors, regardless of the etiology of sepsis, had higher blood levels of IL-6, TNF-sR and E-selectin than survivors. The cytokines, TNF-alpha, IL-6 and TNF-sR, and the adhesion molecules, VCAM-1 and E-selectin, are involved in sepsis due to C. albicans as in bacterial sepsis.

Influence of glycopeptide antibiotics on purine metabolism of endothelial cells.

We provide evidence that the commercially available preparations of glycopeptides for intravenous application are well tolerated by endothelial cells when applied in concentrations less than 5 mg/ml. Since the antibiotics tested are administered at maximal concentrations of 10 mg/ml, the dose range used in our in vitro experiments (5 and 10 mg/ml) mimics possible clinical concentrations at the site of infusion. Similar concentrations may be reached by retrograde intravenous pressure infusion techniques (10-12). We have demonstrated that these high concentrations lead to considerable endothelial cell damage. These findings may explain the common side effect associated with intravenously applied glycopeptides namely pain and phlebitis at the site of infusion (2, 13). Figure 1 shows that a detrimental effect measurable after 20 min occurs only using vancomycin solutions at concentrations of 10 mg/ml, whereas already a dilution to 5 mg/ml renders the solutions more compatible to HUVEC. These data are in line with the observation that slow intravenous application of glycopeptides into large veins can largely prevent the occurrence of local phlebitis. Alternatively, the occurrence of phlebitis should be avoidable by diluting the manufacturers' preparations at least to 2-5 mg/ml and not 10 mg/ml as recommended by the manufacturer of vancomycin. The same aspects need to be considered for use of glycopeptides for retrograde high pressure infusion. The tolerance of intravenously applied antibiotics has previously been tested in animal models (4). Our model of human venous endothelial cells for testing antibiotic solutions for intravenous compatibility provides a valuable alternate model. In conclusion our data show that the commercial preparation of teicoplanin is more compatible for HUVEC than those of vancomycin.

[New aspects in treatment of systemic mycoses]. / Neue Aspekte in der Behandlung systemischer Mykosen.

The incidence of systemic fungal infection has been increasing during the last two decades. Candida and Aspergillus spp. are the classical opportunistic pathogens. Rare fungi, such as Mucor, Rhizopus, Fusarium, Trichosporon, Paecilomyces, Alternaria, Cladosporium and Pseudoallescheria, are emerging as cause of systemic fungal infection in the immunocompromised host. For more than 40 years Amphotericin B has been the gold standard of antifungal treatment because of its broad spectrum comprising yeasts, dimorphic fungi and moulds. Its nephrotoxicity has led to the development of lipid-associated preparations of amphotericin B: liposomal amphotericin B, amphotericin B colloidal dispersion and amphotericin B lipid complex. These preparations are less nephrotoxic, but higher doses than those of conventional amphotericin B are needed to achieve the same effect. The triazole fluconazole is the treatment of choice in infections caused by Candida albicans. New antifungal compounds are voriconazole and the candins, the pradimicin/benanomycin family, nikkomycin Z and a liposomal preparation of nystatin.

[Ineffectiveness of diltiazem in Duchenne muscular dystrophy: a placebo-controlled double-blind study]. / Fehlende Wirksamkeit von Diltiazem bei Duchenne-Muskeldystrophie: eine placebo-kontrollierte Doppelblindstudie.

In a randomized double-blind study the clinical efficacy of the calcium channel blocker, diltiazem was compared to that of a placebo on the clinical course of Duchenne's dystrophy (DMD) over a 12-month period. Altogether 30 patients, mostly in an advanced state of the disease, were evaluated. The 17 patients in the diltiazem group received 90-360 mg diltiazem per day according to their body weight; the 13 patients of the placebo group received the equivalent amount of a placebo. No significant difference was detected between the two groups regarding muscular power, muscle state, muscular functional ability (Vignos), serum myoglobin and serum creative phosphokinase.

[Mucormycosis--a rare complication in patients with diabetes mellitus]. / Mucormykose--Eine seltene Komplikation bei Patienten mit Diabetes mellitus.

Mucormycosis usually occurs in immunocompromised patients or in patients with diabetes mellitus. Pathogens are moulds of the mucorales species. The diagnosis is made by histological examination of biopsies. A 39 year-old patient with insulin-dependent diabetes mellitus was admitted with a tentative diagnosis of a tumour of the maxilla. After diagnosis of hyphae of the mucorales species, the patient's diabetes was stabilised and he was treated over 17 weeks with amphotericin B (40 mg per day) and made a good recovery. A 58 year-old insulin-dependent patient with ethmoidali and sphenoidali sinusitis did not respond to antibiotic therapy. Mucormycosis was diagnosed by means of biopsy. Although treatment with amphotericin B was started, the patient died after 3 weeks due to multiple organ failure.