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Biomedical subjects

J M Schierholz

Publications and source records attributed to J M Schierholz.

At least 19 recordsLinked to original sources
PubMed2004

[Special aspects of implant-associated infection in orthopedic surgery. From the pathophysiology to custom-tailored prevention strategies].

One of the most important risk factors in orthopedic surgery is implant-associated infection. Adhesion and colonization mediated implant infections are extremely resistant to antibiotics and host defences and frequently persist until the biomaterial or foreign body is removed, which is standard therapy. Tissue damage caused by surgery and foreign body implantation increases the susceptibility to infections, activates host defences and stimulates the generation of inflammatory mediators including radicals that are further aggravated by bacterial activity and toxins. Nearly one third of implant-related infections can be prevented by strictly following established infection control guidelines. However, a significant number of implant-associated infections remains. The escape of bacteria from host defence and antibiotic therapy makes the development of infection-resistant materials as anti-microbial drug delivery systems feasible. This concept consists of the sustained delivery of antimicrobial drugs into the local microenvironment of implants avoiding systemic side effects exceeding usual systemic concentrations by magnitudes of order.

Anti-Bacterial Agents↗
PubMed2003

[Psoas abscesses. Genesis, diagnosis, and therapy].

BACKGROUND: A psoas abscess is a rarely encountered entity with various etiologies and nonspecific clinical presentation, frequently resulting in delayed diagnosis, increased morbidity, and prolonged or recurrent hospitalization. PATIENTS AND METHODS: Between January 1996 and January 2002 we treated ten patients (approximately 54.8, 5 males,5 females). These cases were analyzed retrospectively relative to a review of the literature. RESULTS: CT scanning was decisive in the final diagnosis of psoas abscess. Primary psoas abscess occurred in four cases and six patients had secondary abscesses. In all except one case, the psoas abscess was located on the right side. The causes of primary abscesses were retroperitoneal perforated appendicitis, paravertebral injections for lumboischialgia, Pott's disease, and repeated intravenous drug application in the groin. Five patients underwent retroperitoneal open drainage and four patients CT-guided drainage. One patient with retroperitoneal perforated appendicitis was treated by laparotomy. Staphylococcus aureus, Bacteroides fragilis, and Escherichia coli were the most common infective agents. There was no postoperative mortality and no cases of abscess recurred. CONCLUSIONS: CT scan is a diagnostic "gold standard" for psoas abscess. CT-guided drainage is the method of first choice, but is not possible in all cases. Open retroperitoneal drainage is a standard method of treatment. Postoperative antibiotic therapy is obligatory and should be adapted individually.

Adult↗
PubMed2003

Pharmacokinetics of the antimicrobial agents rifampicin and miconazole released from a loaded central venous catheter.

The time course of rifampicin and miconazole concentrations after insertion of a polyurethane catheter loaded with these antibiotics were studied. Data from controlled release experiments in vitro were used, and the concentration time courses of the antimicrobials in serum were calculated by pharmacokinetic simulations. Systemic therapy using typical dosages (rifampicin 600 mg/day iv, miconazole 3 x 200 mg/day iv) results in rifampicin concentrations between 54 and 8424 microg/L, and miconazole concentrations between 3567 and 4676 microg/L. After insertion of a polyurethane catheter loaded with these antibiotics, the maximal concentrations after catheter placement were determined as 6 microg/L at 10.7h for rifampicin, and 13 microg/L at 28.6 h for miconazole. Assuming that the total amount of antibiotics incorporated in the catheter matrix were bioavailable ('worst case'), the resulting maximal concentrations calculated by simulation are 10 microg/L for rifampicin and 65 microg/L for miconazole. Maximal concentrations of rifampicin or miconazole resulting from the insertion of a polyurethane catheter loaded with these antibiotics are, therefore, far below the concentrations resulting from a systemic therapy with the same antimicrobial agents. Even in the worst case, the danger of selecting resistant bacterial strains seems remote because the systemic drug levels are magnitudes of order below subinhibitory concentrations.

Biological Availability↗
PubMed2001

Application of standardized mistletoe extracts augment immune response and down regulates metastatic organ colonization in murine models.

The immunomodulatory and antimetastatic activity of standardized aqueous mistletoe extracts from plants grown on fir trees (ME-A) and pine trees (ME-P) were evaluated in BALB/c-mice. Regular subcutaneous (s.c.) and intraperitoneal (i.p.) applications (three times per week for 14 consecutive days; 5 and 50 microg per injection and mouse) upregulated thymus weight and peripheral blood leukocyte counts in tumor bearing mice. To check the influence of ME-A and ME-P treatment on growth of experimental metastases, RAW 117 H 10 lymphosarcoma cells and L-1 sarcoma cells were intravenously inoculated into BALB/c-mice to establish liver and lung colonization. ME-A and ME-P were regularly administered starting 24 h after tumor cell challenge. Organ colonization was investigated on day 14 after tumor cell inoculation and demonstrated statistically significant (P<0.05) reductions of experimental liver and lung metastases for ME-A and ME-P treated mice.

Adjuvants, Immunologic↗
PubMed2001

Treatment of staphylococcal implant infection with rifampicin-ciprofloxacin in stable implants.

Infection following total joint replacement remains a problem that has not been solved so far. The treatment options include removal of the implant and a delayed reconstruction or a direct exchange operation. Among patients with stable implants and short duration of infection as well as in patients who for certain reasons are inoperable, antibiotic therapy with a combination of rifampicin-ciprofloxacin may be a reasonable treatment option for curing staphyloccocal infection without removal of the implant. A case study of a Staphylococcus epidermidis (coagulase-negative) infection following delayed revision total knee replacement after septic loosening of a knee arthroplasty and its successful conservative treatment with rifampicin-ciprofloxacin is described. Alternative rifampicin combinations are discussed with respect to recently developed pharmacodynamical and pharmacokinetical findings of biofilm active drugs.

Anti-Bacterial Agents↗
PubMed2001

In vitro adherence and accumulation of Staphylococcus epidermidis RP 62 A and Staphylococcus epidermidis M7 on four different bone cements.

Bacterial resistance of Staphylococcus epidermidis, a serious pathogen of implant-related infections, to antibiotics is related to the production of a glycocalyx slime that impairs antibiotic access and the killing by host defense mechanisms. In vitro studies of different bone cements containing antibiotics, developed for the prevention of biomaterial-associated infection, could not always demonstrate complete eradication of biomaterial-adherent bacteria. We have investigated four different bone cements in regard to bacterial accumulation of a slime-producing strain RP 62 A and its isogenic mutant M7 lacking the ability to produce exopolysaccharide slime using a bacterial adhesion assay and modified Kirby-Bauer technique. A significant effect of exopolysaccharide production for the accumulation on bone cement could be demonstrated. The gentamicin/clindamycin bone cement was the only tested biomaterial that produced a large zone of bacterial inhibition in the inoculated area adjacent to the biomaterial. The bacterial adhesion was not reduced significantly and there was no correlation between zones of inhibition on blood agar plates and the quantitative adhesion assay. The clinical efficacy of the gentamicin/clindamycin bone cement must be proven in vivo.

Analysis of Variance↗
PubMed2001

Implant infections: a haven for opportunistic bacteria.

The insertion of implants and medical devices has emerged as a common and often life-saving procedure. A current estimate of the rate of total hip replacement in the world is approximately one million a year, and knee replacements more than 250000. More than 30% of hospitalized patients have one or more vascular catheters in place. More than 10% of hospitalized patients have an indwelling urinary catheter. Some patients require multiple joint replacements. In the United States, approximately 2 million nosocomial infections cost nearly $11 billion annually. Exposure to invasive medical devices is one of the most important risk factors.(1)Devices predispose to infection by damaging or invading epithelial or mucosal barriers and by supporting growth of micro-organisms, thus serving as reservoirs. Invasive medical devices impair host defence mechanisms and, when contaminated, can result in resistant chronic infection or tissue necrosis, the major objections to extended use of implant devices. Implant devices today account for approximately 45% of all nosocomial infections.(2)Implant infections are extremely resistant to antibiotics and host defences and frequently persist until the implant is removed, which is the standard therapy. Tissue damage caused by surgery and foreign body implantation further increases the susceptibility to infections, activates host defences and stimulates the generation of inflammatory mediators; these are enhanced by bacterial activity and toxins.(3)The ability of bacteria such as Staphylococcus epidermidis, which are otherwise virtually avirulent, to escape from host defences and antibiotic therapy, has led to the development of alternative methods of control such as infection-resistant materials acting as antimicrobial drug-delivery systems. By these methods, there is a sustained delivery of antimicrobial drugs into the local micro-environment of implants, which avoids systemic side-effects and exceeds usual systemic concentrations by several orders of magnitude. Bioengineering of hybrid implant materials in order to achieve optimal performance and to prevent inflammatory reactions and interface cellular disorganization is a field undergoing rapid development. Hybrid materials that slowly deliver antimicrobial drugs may reduce implant infections in the future.

Anti-Bacterial Agents↗
PubMed2001

Novel strategies to prevent catheter-associated infections in oncology patients.

Aggressive cytotoxic treatment of cancer contributes to the growing number of life-threatening infections. Vascular catheters create predominant risks for staphylococcal, enterococcal and candida blood stream infections. Although the contaminating microorganisms may be few in number, the altered host immune response in the presence of such implants as well as disease-associated immunosuppression implies that even small bacterial counts have to be regarded as highly virulent species. Diagnosis of catheter-related infection (CRI) remains difficult before withdrawal of the suspected catheter. Positive culture of catheter surface, lumen and hub and positive peripheral blood probes (paired quantitative blood culture) are predictive for catheter related bacteremia (CRB). Diligent catheter care and effective antimicrobial catheters may reduce prolonged hospital stay, increased morbidity or mortality and serious economical consequences. The most promising approach features the incorporation of antimicrobial drugs into the polymer matrices that entrap but do not bind the drugs, allowing for extended release. For the efficacious prevention of colonization in the microenvironment of the implantable device the concentration of the antimicrobial substances must exceed usual antibiotic concentrations by a thousand-fold. This is the desired effect--high concentration near the device surface and very low systemic concentration. Incorporation of antimicrobials in the bulk material that constitutes a device can be effective as shown in several in vitro and in vivo studies. In the future, modification of both short-term and long-term catheters by biofilm-active antimicrobials creating slow delivery systems may provide an effective method to protect patients from nosocomial infection in oncology.

Anti-Infective Agents↗
PubMed2000

Thymosin alpha(1) application augments immune response and down-regulates tumor weight and organ colonization in BALB/c-mice.

The immunomodulatory and antimetastatic/antitumor activity of thymosin alpha(1) (Talpha(1)) was evaluated in BALB/c-mice. Daily subcutaneous application (7 consecutive days, 0.01-10 microg of Talpha(1)/injection per mouse) upregulated the number of thymocytes and peripheral blood cells in tumor bearing mice. To check the influence of Talpha(1) treatment on growth of experimental metastases, RAW H10 lymphosarcoma cells or L-1 sarcoma cells were intravenously injected into BALB/c-mice to establish liver or lung metastases. Local tumor growth was induced by subcutaneous injection of L-1 sarcoma cells. Talpha(1) was subcutaneously administered daily for 7 consecutive days starting 24 h after tumor cell challenge. Organ colonization, as well as local tumor growth, were investigated on day 14 after tumor cell inoculation, and demonstrated a statistically significant (P<0.05) reduction of experimental liver and lung metastases and local tumor growth for Talpha(1) treated mice.

Adjuvants, Immunologic↗
PubMed2000

Measurement of ultrasonic-induced chlorhexidine liberation: correlation of the activity of chlorhexidine-silver-sulfadiazine-impregnated catheters to agar roll technique and broth culture.

The diagnosis of intravascular catheter-related infections continues to be a challenge to both the clinician and the microbiologist. To assess the antiseptic effects of silver-sulfadiazine-chlorhexidine-impregnated central venous catheters (SSC) on catheter culture systems, segments of fresh antiseptic- and non antiseptic-impregnated catheters as well as extracted catheters following five days of immersion in PBS were sonicated. The chlorhexidine liberated from the catheter material by ultrasonication was measured by HPLC. Fresh antiseptic-impregnated catheter segments rolled on seeded agar plates produced inhibition zones unlike catheters which had been extracted for >five days in phosphate buffered saline (PBS). Scanning electron microscopy (SEM) revealed that chlorhexidine-silversulfadiazine crystals were located in the superficial catheter matrix. Direct contact of superficially located drug particles with seeded agar plates probably caused the inhibition of bacterial growth. The study suggests that antiseptic compounds readily elute from fresh catheters during solid medium-based culturing processes and ultrasonication. The addition of inhibitors of silversulfadiazine-chlorhexidine to media may be prudent especially when culturing antimicrobial loaded catheters removed after short inwelling times.

Anti-Infective Agents, Local↗
PubMed2000

The antimicrobial efficacy of a new central venous catheter with long-term broad-spectrum activity.

Indwelling vascular catheters are a major cause of nosocomial sepsis. Prevention of colonization of polymeric surfaces by continuous release of bactericidal, highly biocompatible antimicrobials incorporated into polymers has been investigated as a promising new approach. An antimicrobial polyurethane catheter was investigated by HPLC and various antimicrobial assays. Controlled drug delivery governed by the physico-chemical mass transfer from the polyurethane bulk provided long-term release of the antimicrobial substances from the material to the outer surface and catheter lumen. The in vitro activity of catheters coated with miconazole and rifampicin against 158 clinical isolates of catheter-associated infections was evaluated. Incubated in physiological NaCl at 37 degrees C, the half-life of inhibitory activity of catheters coated with miconazole or rifampicin exceeded 3 weeks. In static and dynamic adhesion assays, coated catheters were able to prevent colonization with Staphylococcus aureus, Staphylococcus epidermidis and enterococci. To produce catheters resistant to infection, a potent antimicrobial efficacy combined with an excellent biocompatibility over time is needed. The long lasting efficacy of the antimicrobial polyurethane alloy as well as the increased antifungal activity of miconazole combined with rifampicin may be regarded as a promising improvement for long-term central venous access.

Anti-Bacterial Agents↗
PubMed2000

"Difficult to treat infections" pharmacokinetic and pharmacodynamic factors--a review.

"Difficult to cure infections" are characterized by poor penetration of antibiotics into infected vegetations, altered metabolic state of bacteria within the vegetation, absence of adequate host defense/cellular response. These infections typically include endocarditis, urinary tract infections (infected urinary tract stones), abscesses, infected fibrin clots (septic thromboemboli, haematomas, catheter-related infections) and foreign body infections. Four main aspects are discussed for the influence on human therapy: 1. the kinetics of antibiotic diffusion into vegetations 2. the specificity of some pharmacodynamic aspects and pharmacokinetic regimes 3. fibrin as one of the main constituents associated with infectious processes and 4. synergistical activities of antibiotic combinations on bacterial vegetations.

Anti-Bacterial Agents↗
PubMed2000

Sophisticated medical devices as local drug-delivery systems.

The sustained release of antimicrobial substances from catheters, endoprostheses, wound-dressings and arterial grafts may be prudent for the prevention of device-associated infections. The release of heparin, synthetic prostacycline, hirudin and anti-inflammatory dexamethasone and related compounds from stent coatings may further reduce the risk of thrombosis, intimal hyperplasia and the requirement for long-term anticoagulation treatments. The delivery of cytokines and growth factors from wound dressings and bone grafts may accelerate wound healing and implant integration.

Anti-Infective Agents↗