[The challenge of infections and multiresistant bacteria among the elderly living in long-term care facilities]. / Herausforderungen durch Infektionen und mehrfach-resistente Bakterien bei alten Menschen in Heimen.

Healthcare-associated infections not only affect patients in acute care hospitals but also patients in need of long-term care. As the elderly are generally most affected, the demographic change in Germany faces a range of increasing challenges in the field of infection control. The ageing process itself is accompanied by several physiological and pathological changes which may result in an increase in the risk of infectious diseases. Elderly living in long-term care facilities (LTCFs) may in addition be exposed to further risks due to their everyday life in a community, nursing care and the, to some extent, inappropriate use of antibiotics. Bacteria that have become resistant to commonly used antimicrobial agents are meanwhile prevalent in nursing homes. Caregivers often feel left alone when facing the task of achieving a balance between the need for a comfortable familiar environment and the application of infection control measures according to a resolute prevention strategy. This review aims to give an overview about the characteristics of infections among the elderly, especially with respect to long-term care.

[Epidemiology, diagnosis and treatment of adult patients with nosocomial pneumonia. S-3 Guideline of the German Society for Anaesthesiology and Intensive Care Medicine, the German Society for Infectious Diseases, the German Society for Hygiene and Microbiology, the German Respiratory Society and the Paul-Ehrlich-Society for Chemotherapy]. / Epidemiologie, Diagnostik und Therapie erwachsener Patienten mit nosokomialer Pneumonie. S-3 Leitlinie der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin e.V., der Deutschen Gesellschaft für Infektiologie e.V., der Deutschen Gesellschaft für Hygiene und Mikrobiologie e.V., der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e.V. und der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V.

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However infections on general wards are also increasing. A central issue are infections with multi drug resistant (MDR) pathogens which are difficult to treat particularly in the empirical setting potentially leading to inappropriate use of antimicrobial therapy. This guideline was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and therapy of HAP on the basis of quality of evidence and benefit/risk ratio. The guideline has two parts. First an update on epidemiology, spectrum of pathogens and antiinfectives is provided. In the second part recommendations for the management of diagnosis and treatment are given. Proper microbiologic work up is emphasized for knowledge of the local patterns of microbiology and drug susceptibility. Moreover this is the optimal basis for deescalation in the individual patient. The intensity of antimicrobial therapy is guided by the risk of infections with MDR. Structured deescalation concepts and strict limitation of treatment duration should lead to reduced selection pressure.

Do patients need advice and information to prevent infections - results of a single centre structured survey.

Background: Healthcare-associated infections are a major burden for hospitals, leading to morbidity and mortality and unnecessary medical costs. They can probably be reduced through what is known as patient empowerment. This study aims to address the question of whether patients are interested in receiving infection prevention and control information. Methods: Patients were asked in structured interviews whether they would like more information on infection prevention and control. Inclusion criteria comprised 2 groups of patients. Group 1 were patients undergoing elective total endoprosthesis (TEP) and Group 2 were patients tested positive for meticillin-resistant Staphylococcus aureus (MRSA). Results: The response rate was 38.4 % (163/425 patients). Approximately 75 % of the patients were interested in information on infection prevention and control. The topics of interest differed between the two patient groups: MRSA patients had a higher need for infection prevention and control information. TEP patients showed a high acceptance of antiseptic body wash and a willingness to pay for it themselves. Information given to patients should be group-specific and timely. Conclusion: Our data suggest a lack of information on infection prevention and control among patients and underline the importance of patient empowerment. The willingness of patients to pay personally for antiseptic wash should be assessed further.

Epidemiology and antifungal resistance in invasive candidiasis.

The epidemiology of Candida infections has changed over the last two decades: The number of patients suffering from such infections has increased dramatically and the Candida species involved have become more numerous as Candida albicans is replaced as an infecting agent by various non-C. albicans species (NAC). At the same time, additional antifungal agents have become available. The different Candida species may vary in their susceptibility for these various antifungals. This draws more attention to in vitro susceptibility testing. Unfortunately, several different test methods exist that may deliver different results. Moreover, clinical breakpoints (CBP) that classify test results into susceptible, intermediate and resistant are controversial between CLSI and EUCAST. Therefore, clinicians should be aware that interpretations may vary with the test system being followed by the microbiological laboratory. Thus, knowledge of actual MIC values and pharmacokinetic properties of individual antifungal agents is important in delivering appropriate therapy to patients.

Outbreak of wound botulism in injecting drug users.

Between October and December 2005, 16 cases of wound botulism were notified to the health authorities of North Rhine-Westphalia, Germany. All patients were injecting drug users (IDU) and the epidemiological investigations suggested contaminated injection drugs as the most probable source of infection. Clostridium botulinum was cultivated from clinical samples of six patients and molecular typing revealed that the different isolates were clonally identical. Two samples of heroin, one of them provided by a patient, were examined but C. botulinum could not be isolated. This outbreak demonstrates that IDU are at risk for acquiring wound botulism by injecting contaminated drugs. A greater awareness of this disease is needed by physicians and a close cooperation between public health authorities, street workers, operators of sheltered injecting facilities, and medical centres focusing on IDU is essential to prevent and manage outbreaks in IDU in a timely manner.

Rapid identification of oral anaerobic bacteria cultivated from subgingival biofilm by MALDI-TOF-MS.

INTRODUCTION: To facilitate the identification of anaerobes cultivated from periodontal disease, whole cell bacterial identification by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was evaluated. METHODS: A total of 84 strains (nine reference strains and 75 recent clinical isolates from 33 patients with aggressive periodontitis) previously identified with phenotypic methods were used. All the references and 10 clinical isolates belonging to the same species as the reference strains were genotypically identified by sequence analysis of the 16S ribosomal RNA gene. All the strains were then analyzed using MALDI-TOF-MS. RESULTS: The reference strains of anaerobic bacteria used showed characteristic MALDI-TOF-MS spectra with peaks between m/z 2000 and up to about m/z 13,000. On visual inspection, the similarity of spectra produced by strains of a single genus could be recognized. Obvious differences between spectra produced by strains of different species were also easily noticed. The reproducibility of the method was proved by the similarity of spectra belonging to the same species. The spectra of the Prevotella intermedia strains identified with MALDI clustered together and clustered separately from the spectra of Prevotella nigrescens, proving that MALDI-TOF-MS is an accurate method that is capable of separating these two species. The quality of clustering was characterized by calculating an inconsistency coefficient (Mathworks:/Matlab Reference Manual v2007a/, Statistical toolbox). CONCLUSION: Our results suggest that MALDI-TOF-MS might become a useful method for the identification of anaerobic bacteria, especially for those that cannot be readily identified by biochemical analysis. It may become an attractive system even for the routine identification of clinical isolates.

[Streptococcal Toxic Shock-like Syndrome associated with detectable autoantibodies]. / Toxisches Streptokokken Schock Syndrom in Verbindung mit serologisch nachgewiesenen Autoantikörpern.

We report on the severe course of a Streptococcal Toxic Shocklike Syndrome (STSLS). The initial diagnosis as well as the causal therapeutic approaches were complicated and prolongated definitely by the serological detection of auto-antibodies. Besides the presentation of clinical and paraclinical findings the report responds to relevant differential diagnoses and the corresponding strategies of therapeutic intervention.

[First Results of the German consulting center for infection control outbreak registry]. / Infektionen und Kolonisationen: Was können wir verbessern?

BACKGROUND: Outbreaks of infectious diseases and / or colonization pose an increasing burden on hospitals and the health system in general and can be a threat to patient safety. METHODS: At the end of 2013 we implemented a quality assurance registry of outbreak investigations performed by the Deutsches Beratungszentrum für Hygiene (German Consulting Center for Infection Control and prevention) in Freiburg. Now we analyzed the registered outbreaks until January 2015. RESULTS: Norovirus was the leading causative organism and gram negative bacteria dominated the group of bacterial outbreaks. Outbreaks lasted between 6 and 185 days. 24 % of outbreaks were related to colonization only. Within 29 outbreaks we had 187 infected patients, 50 colonized patients und 92 infected health care workers (64 x norovirus, 20 x influenza, 8 x scabies). No deaths were recorded. Several risk factors and improvement potentials for future outbreaks could be identified. CONCLUSION: Lack of staff compliance with vaccination or prophylactic therapy, misuse of personal protective equipment and lapses in absence from work for the required time can play an important role for prolonged outbreak situations esp. with viral outbreaks and scabies. A structured and goal directed outbreak management especially in the initial phase of an outbreak seems to be important for an efficient and fast termination of an outbreak.

Antecedent use of fluoroquinolones is associated with resistance to moxifloxacin in Clostridium difficile.

OBJECTIVE: Moxifloxacin is characterized by high activity against Gram-positive cocci and some Gram-positive and -negative anaerobes, including Clostridium difficile. This study investigates the role of prior quinolone use in relation to patterns of susceptibility of C. difficile to moxifloxacin. METHODS: Sixty-three clinical isolates of C. difficile were investigated for toxigenicity, susceptibility to moxifloxacin, and mutations in the DNA gyrase gene. The medical histories for 50 of these patients were available and used to identify previous fluoroquinolone use. RESULTS: Thirty-three (52.4%) strains showed resistance to moxifloxacin (MICs > or = 16 mg/L). All moxifloxacin-resistant strains harbored a mutation at amino acid codon Ser-83 of gyrA. Forty-five isolates (71.4%) were toxigenic; all moxifloxacin-resistant strains were in this group. Resistance to moxifloxacin was associated with prior use of fluoroquinolones (P-value 0.009, chi-square). CONCLUSIONS: Although the use of moxifloxacin to treat C. difficile-associated diarrhea is not likely to be common, these data show a relationship between antecedent fluoroquinolone use and resistance to moxifloxacin in C. difficile isolates, and raise questions regarding selection pressure for resistance placed on colonizing bacteria exposed to fluoroquinolones. Mutations in gyrA are involved in moxifloxacin resistance.

Endothelial cell compatibility of clarithromycin for intravenous use.

OBJECTIVES: Tolerance of intravenously applied clarithromycin has been tested on marginal ear veins of rabbits. Use of human umbilical venous endothelial cells (HUVEC) for testing antibiotic solutions for intravenous compatibility provides a valuable alternate model. DESIGN AND METHODS: In order to evaluate the effect of clarithromycin on intracellular purines, reflecting cell viability, energy production, signal transduction and DNA/RNA synthesis, intracellular adenosine 5' triphosphate (ATP), adenosine 5' diphosphate (ADP), guanosine 5' triphosphate (GTP), and guanosine 5' diphosphate (GDP) levels were measured by means of high performance liquid chromatography (HPLC). RESULTS: Incubation of cells with 2 mg/mL clarithromycin resulted in a rapid decrease of the intracellular ATP from 12.6 +/- 1.1 to 8.87 +/- 0.82 nmol/million cells or 1.5 +/- 0.6 nmol/million cells, after 20 or 60 min, respectively. In addition, ADP was extensively depleted. Purine nucleotide profiles were markedly different following exposure to 1 mg/mL clarithromycin. There was no significant decline of intracellular high energy phosphate levels after 20 min. CONCLUSION: These results show that clarithromycin has a better endothelial compatibility if diluted to a final concentration of 1 mg/mL. These data are in line with our clinical observations that the occurrence of phlebitis could be minimized by diluting the manufacturers' preparation of clarithromycin to 1 mg/mL.

In vitro activities of fourteen antimicrobial agents against obligately anaerobic bacteria.

The in vitro activities of fourteen antimicrobial agents were tested against 292 clinical isolates of obligately anaerobic bacteria using the broth microdilution technique. Taking all strains as a group the MIC(50/90) (mg/l) values were metronidazole and imipenem 0.25/1, meropenem 0.25/0.5, trovafloxacin 0.25/1, gatifloxacin and moxifloxacin 0.5/2, levofloxacin 2/16, ciprofloxacin 4/32, clindamycin 0.5/8, amoxycillin/clavulanate 1/4, doxycycline and chloramphenicol 2/4, erythromycin 4/>32 and penicillin G 16/>32.

Effects of imipenem and meropenem on purine content of endothelial cells.

UNLABELLED: Intravenous compatibility of antibacterial agents has been tested in animal models. Use of human umbilical venous endothelial cells (HUVEC) to test antibiotic solutions for intravenous tolerance provides a valuable alternate model. OBJECTIVE: Evaluation of the effect of imipenem and meropenem on intracellular purines reflecting viability, energy production, signal transduction, and DNA/RNA synthesis of these cells. MATERIALS AND METHODS: Levels of intracellular adenosine 5' triphosphate (ATP), adenosine 5' diphosphate (ADP), guanosine 5' triphosphate (GTP) and guanosine 5' diphosphate (GDP) were measured by means of high performance liquid chromatography (HPLC). RESULTS: The total amount of ATP after incubation of cells with 10.0 mg/ml imipenem and meropenem for 20 minutes (12.93 +/- 0.93 nmol/million cells and 13.27 +/- 0.89 nmol/million cells, respectively) did not result in a decrease compared to controls (12.34 +/- 0.87 nmol/million cells). In addition, ATP levels were maintained or actually increased after 60 minutes. Incubation of cells with 5.0 mg/ml and 2.5 mg/ml of imipenem or meropenem for 20 and 60 minutes showed similar results. Purine nucleotide profiles of ADP, GTP, GDP following exposure of 10.0 mg/ml, 5.0 mg/ml and 2.5 mg/ml of imipenem and meropenem did not differ markedly. CONCLUSIONS: These in vitro data show an excellent endothelial compatibility of imipenem and meropenem even in high concentrations.

Endothelial cell compatibility of fluoroquinolone solutions for intravenous use.

One local side-effect closely related to the use of parenteral fluoroquinolones is phlebitis. The occurrence of this phenomenon is largely thought due to the damage of endothelial cells with subsequent inflammation. In order to evaluate the effect of ciprofloxacin, fleroxacin, and ofloxacin on the viability of human umbilical venous endothelial cells (HUVEC), intracellular ATP levels were measured by a luciferin-luciferase assay. Prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined by means of direct radioimmunoassay. Commercially available preparations of ciprofloxacin (2 mg/ml) and fleroxacin (4 mg/ml) reduced the intracellular ATP content by 75.9 +/- 1.9% and 82.1 +/- 0.6%, respectively, within 20 minutes, indicating severe damage of endothelial cells. Incubation with ofloxacin (2 mg/ml) did not have any detrimental effect. All fluoroquinolones were tolerated well by endothelial cells at low concentrations up to 20 micrograms/ml. Concentrations between 100-200 micrograms/ml gradually led to functional alterations such as increased PGI2 release. The tolerance of intravenously applied antibiotics has been tested in animal models. Use of human venous endothelial cells for testing antibiotic solutions for intravenous application provides a valuable alternate model for tolerability.

Nosocomial infections in internal medicine, University of Frankfurt, Germany--a prospective surveillance study.

Nosocomial infections (NI) are serious complications associated with high morbidity and mortality. In the present study, NI were analyzed prospectively at the Center of Internal Medicine (CIM) (300 beds) of the J. W. Goethe-University -a 1380-bed major tertiary care teaching hospital- during a study period of six month. During the study period a single physician evaluated all patients with signs and symptoms of an infection during his daily rounds. NI was defined as body temperature >38 degrees C and evidence of an infection not before the third day of admission to the hospital. NI was diagnosed in 127 patients (3.5%) of the 3605 patients studied. The data of 126 patients with NI could be collected and analyzed completely. Of the 126 patients 34 patients died. The mean length of hospitalization before the diagnosis of NI was 12.0 days (standard-deviation: +/-13.1 days; median: 7 days). Compared to all patients with NI significantly more patients of the Internal Intensive care unit (11.3%), of the HIV-ward (10.3%), and of the hematology / oncology ward (5.8%) acquired a NI (p<0.05). With respect to other groups of patients the frequency of NI ranged from 0.5 to 4.6 per 100 admitted inpatients. The lower rate was in patients admitted for invasive diagnostic procedures who were hospitalized only for 3 days or less.

Phagocytosis of Escherichia coli and Staphylococcus aureus by neutrophils of human immunodeficiency virus-infected patients.

To study the influence of human immunodeficiency virus (HIV) infection on phagocytosis of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by polymorphonuclear neutrophils (PMN) from HIV-infected patients in vitro. PMN were isolated from the blood of 25 HIV-infected patients (group 1: CD subset4 250/microL: 11 patients ) by Percoll density gradient and incubated with E. coli and S. aureus. Subculture technique was used to determine PMN function at 0, 0.5, 1, 2, 4, 6, and 24 hours. Controls were run with PMN from healthy volunteers. Phagocytosis of E.coli and S.aureus by PMN of HIV-infected patients was significantly lower in group 1 (p <0.05). Reduced phagocytosis of E. coli and S. aureus was found in HIV-infected patients with low CD subset4-cell counts. Our findings may contribute to increased susceptibility to bacterial infection in HIV-infected patients with low CD subset4-cell counts.

Experience with imipenem in internal medicine--a postmarketing surveillance study.

Imipenem was registered for clinical use in Germany in 1985. It is recommended for initial treatment in either severe nosocomial infections or infections in ICU or immunocompromised patients. In this study, we evaluated 1,215 patients who were prescribed imipenem at our Zentrum der Inneren Medizin-a major tertiary care university hospital-over a 6 year period. 650 of 1,215 patients (53.5%) had rapidly fatal disease; and the main indication for imipenem was pneumonia and fever of unknown origin. 56.2% received 500 mg imipenem t.i.d., 40.4% 500 mg b.i.d., 0.9% 1000 mg b.i.d.; and 2.5% 1000 mg t.i.d. Average duration of treatment was 11 days. Lower dose (500 mg b.i.d.) was used in patients with renal insufficiency; highest dose was used in severe infections or infections caused by moderately sensitive organisms. Imipenem was used as a single initial antibacterial agent in the majority of the patients. Success was seen in 80% of the episodes, irrespective of the dosage used; 89% at 500 mg b.i.d., 74% at 500 mg t.i.d., 77% at 1,000 mg b.i.d.; and 69% at 1,000 mg t.i.d. We observed the highest favourable response (91.5%) in the episodes treated initially with imipenem monotherapy. Overall, imipenem was well tolerated. The majority of the patients with untoward effects was on multiple-drug regimens. The most frequent untoward event observed involved the gastrointestinal tract.

Effect of amphotericin B alone or in combination with rifampicin on phagocytosis of Candida species by human polymorphonuclear leukocytes.

The influence of amphotericin B and rifampicin alone and in combination on the killing of Candida albicans, Candida tropicalis and Cryptococcus neoformans by human polymorphonuclear leukocytes was investigated in vitro. Granulocytes were harvested from the blood of healthy volunteers and resuspended with the above mentioned fungi. After 6 hours, 81.5% of C. albicans, 97% of C. tropicalis but only 34% of C. neoformans were killed. The activity of amphotericin B against C. albicans and C. tropicalis was better in granulocyte-free medium. A synergism between amphotericin B and rifampicin towards Candida could be detected. It was also demonstrated in the presence of polymorphonuclear leukocytes with a factor > 1 log in reduction of colony count. However, whether granulocytes were present or not, rifampicin (4 mcg/mL) alone did not exert any influence on growth of Candida.

Influence of free or liposomal amphotericin B on killing of Candida species by human peritoneal macrophages.

The influence of free and liposomal amphotericin B at subinhibitory and inhibitory concentrations on killing of Candida albicans (ATCC 10231), Candida tropicalis (ATCC 13803) and Cryptococcus neoformans (930) by human peritoneal macrophages was investigated in vitro. Peritoneal macrophages were harvested from overnight peritoneal dialysate of 10 patients undergoing regular continuous ambulatory peritoneal dialysis and incubated with Candida species (1:2), pooled human serum, fetal calf serum, Medium 199 and Sabouraud broth (with or without amphotericin B) for 6 hours. The killing of Candida species was determined using subculture technique. The combination of amphotericin B (free or liposomal) with peritoneal macrophages enhanced the killing of the Candida species. Candidacidal activity of free and liposomal amphotericin B resulted in comparable effects; however, the killing of the yeasts by liposomal amphotericin B was slower than by free amphotericin B.

Activity of the investigational fluoroquinolone finafloxacin and seven other antimicrobial agents against 114 obligately anaerobic bacteria.

The activity of finafloxacin against 73 strains of the Bacteroides fragilis group, 10 other Gram-negative anaerobic rods and 31 Clostridium difficile strains was determined by the broth microdilution technique. The activity was compared with that of moxifloxacin, levofloxacin, ciprofloxacin, clindamycin, imipenem, piperacillin/tazobactam and metronidazole. MIC(50/90) values (minimum inhibitory concentration, in µg/mL, at which 50% and 90% of the isolates tested are inhibited, respectively) for finafloxacin for the different species were determined: B. fragilis group, 0.5/2; other Gram-negative rods, 0.06/0.25; and C. difficile, 4/16. Furthermore, the MICs against 11 selected B. fragilis strains were determined under acidic conditions and resulted in MIC(50/90) values for finafloxacin of 0.25/4 µg/mL. Thus, finafloxacin shows promising activity against several pathogenic species of anaerobes. Furthermore, finafloxacin has increased activity against selected B. fragilis strains under acidic conditions compared with activity at neutral pH.