G. Pulverer

Efficacy of silver-coated medical devices.

Silver coating of medical devices is believed to prevent device-associated infection. Several in-vitro and in-vivo studies, as well as clinical observations on silver-nylon, silver-intramedullary pins, silver oxide Foley catheters and silver-coated vascular prostheses have been performed during the past 30 years. Nevertheless, randomized clinical studies showing efficacy of such coated medical devices in high-risk patient populations are rare, have dealt with very small numbers of patients or are controversial. Physico-chemical, pharmacological and microbiological data explaining the antimicrobial efficacy of silver in prophylaxis of implants are presented here, as well as the scientific background for the established clinical benefits of silver-preparations in burns.

NOSOCOMIAL BACTEREMIA DUE TO ACINETOBACTER BAUMANNII: CLINICAL FEATURES, EPIDEMIOLOGY, AND PREDICTORS OF MORTALITY

To study the possible predisposing factors, clinical features, molecular epidemiology, and factors affecting mortality associated with bacteremia due to Acinetobacter baumannii, we reviewed 87 episodes of A. baumannii bacteremia occurring in 79 patients hospitalized at 2 university tertiary care centers and 4 community-based hospitals during a recent 18-month period. Plasmid DNA analysis and analysis of genomic DNA with pulsed-field gel electrophoresis was performed to investigate possible epidemiologic relationship. All patients acquired their infections in the hospital, and no seasonal variation was observed. Among patients with A. baumannii bacteremia, 91% were hospitalized in an intensive care unit, 99% had indwelling vascular catheters, 81% received prior broad spectrum antimicrobial therapy, 70% were mechanically ventilated, and 47% had major surgical procedures. In 39 cases (45%) the infection was related to indwelling vascular access devices. Other infections included pneumonia (9%), tracheobronchitis (22%), meningitis (2%), and burn wound infections (4%). Septic shock occurred in 30% of patients. All isolates were multidrug resistant. Polymicrobial bacteremia was observed in 35% of cases. The crude mortality rate was 44%. Death was considered attributable to A. baumannii bacteremia in 15 (19%) patients. All patients with pneumonia as the primary site of infection died. Using multivariate analysis, we identified 3 independent predictors of mortality: the presence of a rapidly or ultimately fatal underlying disease (p = 0.0009), septic shock at the onset of bacteremia (p = 0.0013), and mechanical ventilation (p = 0.016). Epidemiologic typing revealed that 82 episodes were associated with different hospital outbreaks of infection, and only 7 episodes were due to epidemiologically unrelated strains.

Antimicrobial susceptibility of Acinetobacter species.

The in vitro activities of 16 antimicrobial agents against 180 Acinetobacter strains isolated from blood cultures (n = 162), central venous catheters (n = 11), and cerebrospinal fluids (n = 7) were studied. MICs were determined by a microtiter broth dilution method. Considerable differences in antimicrobial drug susceptibility against strains belonging to different species could be demonstrated. Acinetobacter baumannii isolates (n = 108) were generally more resistant than isolates identified as species other than A. baumannii. Multidrug resistance was common among A. baumannii isolates. Of the antimicrobial agents tested, imipenem was highly active against all A. baumannii isolates, and the other agents tested were only moderately active or inactive. Good activity against Acinetobacter species strain 3 was demonstrated for imipenem, amikacin, and ciprofloxacin. Most of the strains belonging to other species were susceptible to imipenem, ciprofloxacin, expanded-spectrum cephalosporins, amoxicillin-clavulanate, and the aminoglycosides but were resistant to ampicillin and older cephalosporins.

Controlled release of antibiotics from biomedical polyurethanes: morphological and structural features

Polymer-associated infections are of increasing importance. Antistaphylococcal antimicrobial substances (ciprofloxacin, gentamycin, fosfomycin, flucloxacillin) were incorporated into polyurethanes by the solvent casting technique. Drug release rates, bacterial colonization and morphological features were evaluated to predict and understand the antimicrobial activity of these delivery systems. Drug release characteristics were investigated by standard bioassay and high-performance liquid chromatography (HPLC), and the physico-chemical mechanisms of the delivery were discussed. Ciprofloxacin hydrochloride showed a fast initial release rate, whereas gentamicin-base was characterized by a more continuous release type of behaviour. Bacterial colonization to the antibiotic-loaded polyurethanes was inhibited effectively by preparations showing a slower but more sustained antimicrobial delivery. Polyurethane-antibiotic combinations were most homogeneous for gentamicin-base and flucloxacillin as shown by scanning electron microscopy (SEM). In polymers loaded with fosfomycin and ciprofloxacin a granular structure of the crystallized drug embedded in the polyurethane matrix could be demonstrated. Physico-chemical similarity of the polymeric material and the antibiotics is important for the homogeneity of polymer-antibiotic combinations. High homogeneity is required for a sustained and prolonged release over time and effective inhibition of bacterial colonization.

Synergistic role of staphylococcal proteases in the induction of influenza virus pathogenicity

Several strains of Staphylococcus aureus have been found to secrete proteases that activate infectivity of influenza virus by proteolytic cleavage of the hemagglutinin. The enzymes of the bacterial strains Wood 46 and M 86/86 have been characterized in some detail and were found to be serine proteases. In their substrate specificities and inhibitor sensitivities they proved to be similar to, but not identical with trypsin and plasmin. The hemagglutinin of an individual virus strain could be cleaved by the proteases of some but not all staphylococcal strains, and a given enzyme could cleave only some but not all hemagglutinins analyzed. When mice were coinfected intranasally with the appropriate strains of influenza virus and S. aureus, the hemagglutinin was readily activated allowing multiple cycles of virus replication in the lung. Under these conditions, the animals came down with a fatal disease exhibiting extended lesions in the lung tissue. In contrast, after infection with virus or bacteria alone, there were no significant pathological changes. When the staphylococcal strain did not contain a protease that was able to activate the hemagglutinin of the coinfecting virus strain, the animals did not exhibit disease. These observations demonstrate that coinfecting bacteria can play an essential role in the development of influenza pneumonia by providing a protease suitable for cleavage activation of the hemagglutinin.

Attachment of staphylococci to various synthetic polymers

Attachment of staphylococci to different synthetic polymers used for medical purposes was studied in applying the bioluminescent technique. The number of attached bacterial cells was determined by measuring the light emission resulting from the reaction between firefly luciferase and ATP present in adhered staphylococcal cells. It was shown that staphylococci attach to synthetic polymers within a few minutes, although one hour incubation is required to reach a constant maximum value of attached cells. Ten different synthetic polymers and five Staphyloccocus epidermidis strains were investigated in our study. The relationship between surface properties of polymers and bacterial attachment was studied. Various physicochemical parameters of synthetic polymers and bacteria were determined (contact angle, surface tension). It was demonstrated that bacterial attachment decreases with decreasing contact angle and with increasing surface tension of synthetic materials. Modifications of surface charge and hydrophobicity of solid materials were also investigated. It could be proved that especially negatively charged and hydrophilic synthetic polymers show very decreased staphylococcal attachment.

Human cervicofacial actinomycoses: microbiological data for 1997 cases

Actinomycoses are sporadically occurring endogenous polymicrobial inflammatory processes, in which fermentative actinomycetes of the genera Actinomyces, Propionibacterium, or Bifidobacterium act as the principal pathogens. Difficulties in diagnosing the disease in a timely and reliable fashion have led clinicians and microbiologists to grossly underestimate its medical importance. Therefore, we evaluated microbiological and selected clinical data derived from 1997 culture-positive cases of human cervicofacial actinomycoses examined in our laboratories during 1972-1999. The causative actinomycetes belonged to at least 9 different species, among which Actinomyces israelii and Actinomyces gerencseriae predominated. The well-known predisposition of male patients to acquire the disease varied with age and appeared to be especially pronounced in patients aged 20-60 years, the highest incidence being found in female patients aged 11-40 years and in male patients aged 21-50 years. The relevant procedures necessary for diagnosing human actinomycoses reliably, as well as details of their complex etiology, are discussed.

The Distribution of Acinetobacter Species in Clinical Culture Materials

A total of 584 Acinetobacter strains were isolated from 420 patients from 12 different hospitals over a period of twelve months. Identification of strains at the species level was done according to the new taxonomy proposed by Bouvet and Grimont. A. baumannii strains were isolated most frequently (n = 426; 72.9%), followed by A. species 3 (n = 55), A. johnsonii (n = 29), and A. lwoffii (n = 21). Most isolates were recovered from respiratory tract specimens (n = 251; 42.9%), blood cultures (n = 116; 19.9%), wound swabs (n = 90; 15.4%), catheter tips (n = 75; 12.8%), and urinary tract specimens (n = 20; 3.4%). Strains belonging to species other than A. baumannii were isolated more frequently (n = 158; 27.1%) than previously reported, mainly from blood cultures, respiratory tract specimens, and central venous catheters.

Inhibition of liver metastasis in mice by blocking hepatocyte lectins with arabinogalactan infusions and d-galactose

SummaryAccording to our hypothesis, organ-specific lectins (e.g., the d-galactose-specific hepatic binding protein) play an important role in the organ location of metastatic malignant cells. The rapid clearance and uptake by the liver of tritiated α-acid-(asialo)glycoprotein from the circulation of Balb/c mice was markedly delayed after preinjection of d-galactose or arabinogalactan. The preinjection (1h) and regular application (for 3 days after tumor cell inoculation in Balb/c mice) of the receptor blocking agents d-galactose and arabinogalactan prevented the settling of sarcoma L-1 tumor in the liver completely, but did not influence the settling in the lung. Other galactans, dextrans, and phosphate-buffered saline showed no effect. Therefore, when lectins were blocked with competitive-specific glycoconjugates, colonization was prevented.

PLASMID DNA PROFILES OF ACINETOBACTER BAUMANNII : CLINICAL APPLICATION IN A COMPLEX ENDEMIC SETTING

OBJECTIVE To study the epidemiological, microbiological, and clinical features of infections due to Acinetobacter baumannii in a complex endemic situation over an 18-month period and to determine the clinical usefulness of plasmid DNA analysis of A baumannii in epidemiological investigations. DESIGN Review of medical and laboratory records. Antibiotic resistance patterns, biotyping, and plasmid profile analysis were used to characterize clinical and environmental isolates. Pulsed-field gel electrophoresis (PFGE) of chromosomal DNA was performed to verify results obtained with the other typing methods. SETTING Four different intensive care units of an 800-bed tertiary care center in Cologne, Germany. RESULTS 240 patients were colonized or infected with A baumannii during the study period. No seasonal variations were observed. The majority of isolates (53%) were recovered from the respiratory tract. Major infections occurred in 61 patients; these included 48 bacteremias and eight pulmonary infections. Five different epidemic strains were identified: one each was A baumannii biotype 2 and 6, and three were biotype 9. A baumannii biotype 9 accounted for the vast majority of isolates (88%), which were clustered into three epidemic strains demonstrating distinct plasmid profiles. Two of these were considered genetically related as shown by PFGE. Epidemic strains were multidrug resistant, being uniformly susceptible to imipenem only. An epidemiological investigation failed to identify any point source of infection. Barrier precautions and improved handwashing was instituted in three of the four units and significantly reduced the incidence of colonization and infection in these units. Attack rates remained unchanged, however, in the burns unit where control measures were not implemented. CONCLUSION Acinetobacter strains representing multiple biotypes and plasmid types were present in this endemic setting. Multidrug resistance in A baumannii is an important concern. Plasmid DNA analysis proved to be useful in epidemiological typing of A baumannii strains and may serve as a complementary typing system to traditional epidemiological methods.