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Biomedical subjects

W Ritzerfeld

Publications and source records attributed to W Ritzerfeld.

At least 19 recordsLinked to original sources

[Resorbable antibiotic delivery systems in local treatment of chronic osteitis--polyglycolic acid/poly-L-lactide as drug carrier. Experimental studies in vitro].

Resorbable polyglycolic acid (PGA)- and poly-L-lactic acid (PLLA) cylinders were investigated in vitro to explore their properties as an antibiotic deposit (Ciprobay, Bayer Leverkusen) with prolonged release. PGA cylinders sized 3.2 x 5 mm, 4.5 x 5 mm and 4.5 x 7 mm respectively were shaped in monofil and polyfil technique. The Ciprofloxacin concentration varied from 0.5 mg to 5.0 mg of each cylinder. The cylinders were eluated in phosphate buffer, pH-value of 7.4, at 37 degrees C. The daily antibiotic release was measured by high performance liquid chromatography. Best combinations we could find demonstrated an initial delivery of Ciprofloxacin in vitro of 67 mg/l. The average daily release was about 16 mg/l during the first 36 days. After complete hydrolysis of the PGA carriers the recovery of Ciprofloxacin reached up to 6.5% and 11.6% respectively. For 40 bioactive cylinders (size phi 3.5 mm x 5 mm, containing 4 mg Ciprofloxacin) were eluated with phosphate buffer (pH 7.4 at 37 degrees C) respectively fresh human blood plasma and tested under various conditions. A gentamicin-polymethylmetacrylate (PMMA) chain (Septopal, E. Merck, Darmstadt) was exposed to equal test conditions for comparison. The quantities of released Ciprofloxacin and Gentamicin were analysed by a microbiological method (bioassay). Initially released rates of Ciprofloxacin were measured very high (up to 180 mg/l) but decreased rapidly within the first 5 days (4.2-22.5 mg/l). The release of Gentamicin produces an initial sharp decrease in concentration during the first 3 days (from 227.5 mg/l to 77.5 mg/l); this is then followed by an almost constant release over a long period of time (about 20 mg/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Ciprofloxacin↗

Ciprofloxacin-impregnated poly-L-lactic acid drug carrier. New aspects of a resorbable drug delivery system in local antimicrobial treatment of bone infections.

Resorbable poly-L-lactic acid (PLLA) cylinders (3.5 mm diameter, 5 mm in length) carrying 6% of weight ciprofloxacin (Ciprobay, Bayer AG, Leverkusen, FRG) were investigated in vitro to explore their properties as a slow-release antibiotic deposit. Forty bioactive cylinders stored in test tubes were covered with phosphate buffer (pH 7.4 at 37 degrees C) and 40 with fresh human blood plasma and tested under various conditions. For comparison a gentamicin-polymethylmethacrylate (PMMA) chain (Septopal, E. Merck, Darmstadt, FRG) was exposed to similar test conditions. The quantities of ciprofloxacin and gentamicin released were analysed by a microbiological method (bioassay). The concentrations of ciprofloxacin released were analysed by a microbiological method (bioassay). The concentrations of ciprofloxacin released from 40 cylinder were initially very high (up to 180 mg/l) but they decreased rapidly within the first 5 days (4.2-22.5 mg/l). Early release of gentamicin reached up to 227.5 mg/l but dropped to of 22 mg/l on the 14th day. Complete degradation of the PLLA-cylinders was not seen in the observed period of 92 days. The mean loss of mass was 8.4%. The recovery of incorporated ciprofloxacin was 6.5% on average.

Biological Assay↗

Effect of selective flora suppression on colonization, infection, and mortality in critically ill patients: a one-year, prospective consecutive study.

OBJECTIVE: To study the effect of enterally administered polymyxin E, tobramycin, and amphotericin B (selective flora suppression) on bacterial colonization, infection, resistance, and mortality rate. DESIGN: Prospective, consecutive crossover controlled study. SETTING: Two surgical ICUs in a university hospital; ICU I with ten beds, ICU II with eight beds. PATIENTS: Two hundred patients entered the 1-yr trial. Fifty of 111 patients received selective flora suppression during the first 6 months in ICU I (test group), while 61 of 111 patients served as the control group in the following 6 months. In ICU II, 49 of 89 patients received no selective flora suppression in the first 6 months (control group), followed by 40 of 89 patients receiving selective flora suppression during the second 6-month period (test group). INTERVENTIONS: The test group got a mixture of nonabsorbable antibiotics (paste and suspension) in the digestive tract. The control group received paste and suspension without antimicrobial agents. All 200 patients received cefotaxime during the first 4 days. MEASUREMENTS AND MAIN RESULTS: With the use of selective flora suppression, colonization with aerobic Gram-negative bacilli was significantly (p less than .01) reduced. There was also a significant reduction in nosocomial bronchopulmonary (ICU I and II; p less than .001) and urinary tract (ICU II; p less than .001) infections. The difference in mortality was not significant. There was no development of resistance against the antibiotics used during the limited period evaluated. CONCLUSIONS: Selective flora suppression is effective in reducing secondary colonization by aerobic Gram-negative bacilli. Reduction of bronchopulmonary and urinary tract infections most likely occurs with colonization prevention.

Administration, Oral↗

[Nosocomial infections in surgical intensive medicine. Results of a 5-year prospective study].

All the ICU patients were continuously studied during the first quarter of 5 consecutive years for infections according to a standard protocol. The investigators--the infection control officer and a well-trained infection control nurse--decided if the patient was infected by referring to medical and nursing record, temperature charts, laboratory and x-ray reports and, where necessary, by clinical examination. Definitions and criteria for infections comply with the CDC and the algorithms of the Senic Project. Only the first quarter of each year from 1980-1984 was analysed. The first quarter of 1980 was analysed retrospectively, the following years were examined prospectively. In 1984 a new ICU (ICU I) in addition to the old ICU (ICU II) was opened. The two ICUs differ in building construction but have similar patients, nursing staff and medical standards. The frequency of nosocomial infection was not affected by the different building constructions. The number of patients surveyed was 1009, 60% were males and 40% females. The average age was 45.5 years and the average period of stay about 4 days. 733 patients (72.6%) were intubated and artificially ventilated for 3 days. A fatal outcome resulted in 13.2% of all patients. 1129 nosocomial infections were registered in 311 patients, which means an infection rate of 32.8%. The most frequent nosocomial infections were those of the respiratory tract. Wound infections developed in 16.6%. The urinary tract was affected in 8.8%. Nosocomial septicaemias were observed in 8.7%. Catheter-associated infections were noticed in 6.7% of the patients. A fatal outcome resulted in 26% of the patients with nosocomial infections and in 6.9% of the non-infected patients, respectively.

Adult↗

Controlled prospective study of oral amoxycillin/clavulanate vs ciprofloxacin in acute exacerbations of chronic bronchitis.

This investigation compared the efficacy of oral formulations of amoxycillin/clavulanate and ciprofloxacin in acute exacerbations of chronic bronchitis. Forty patients were randomized to receive either Augmentin (1,000 mg amoxycillin +250 mg clavulanate) tds or ciprofloxacin (500 mg) bd. During and before therapy sputum samples were taken for bacteriology, sputum volume measurement and histamine determination. Lung function was also monitored. From sputum, 143 bacterial isolates and 15 yeast strains were obtained before therapy. During therapy with amoxycillin/clavulanate the incidence of Gram-positive isolates decreased significantly whereas ciprofloxacin left their frequency unchanged. On the other hand, ciprofloxacin more effectively diminished the incidence of Gram-negative isolates. Yeasts were grown from the sputum of several patients before and during therapy. Their number did not increase during amoxycillin/clavulanate therapy while it increased under ciprofloxacin. The groups showed no significant differences with regard to sputum production, histamine concentration or lung function. The majority of patients (28/40) acknowledged improvement of their symptoms. There was no significant difference between the groups. On the basis of these results both amoxycillin/clavulanate and ciprofloxacin appear of similar value for treatment of patients with exacerbations of chronic bronchitis.

Aged↗

[Selective flora suppression for control of infection in surgical intensive care medicine].

The question to be answered in this study was: Is prophylactic selective florasuppression advantageous compared to conventional antibiotic policy as far as microbial colonisation, infection, mortality and development of resistance are concerned? A prospective, consecutive, placebo-controlled study in two ICU's was carried out during four 6-months periods. 200 patients who were intubated for at least 3 days, required intensive care for a minimum of 5 days, and belonged to either class III or IV according to the "Therapeutic Intervention Scoring System" were included in the study. They received either placebo or the prophylaxis regimen described by Stoutenbeek et al., consisting of polymyxin E, tobramycin and amphotericin B. Oropharyngeal, tracheobronchial and rectal colonisation with aerobic gram-negative bacilli markedly decreased in the test groups. The rates of nosocomial bronchopulmonary infections (ICU I and II) and urinary tract infections (ICU II) were significantly reduced. There was no significant reduction in wound infection, septicaemia and mortality rates. No development of resistance and no increase of multi-resistant strains occurred. Selective florasuppression is effective in reducing infection rates in critically ill patients without development of resistant strains.

Adult↗

Resistance-pattern-analysis--a step toward predictable differentiated antibiotic therapy.

The Resistance-Pattern-Analysis (RPA)-the procedure will be described- makes possible a comparison of susceptibility test results of different antibiotics independent of patient and test related factors. Using two examples, the comparative assessment of a more recent antibiotic with well-tried older antibiotics and the selection of antibiotics for an interventive therapy, whereby the pathogen being unknown the therapy is based upon the probable pathogen, the expected susceptibility and the localization of the infection the practicability will be illustrated. A RPA of 1526 bacterial isolates was carried out using aztreonam, gentamicin and amikacin. Aztreonam was superior to amikacin against all species tested. In comparison to gentamicin, aztreonam showed the best results against Pseudomonadaceae. Using common combinations of antibiotics for the initial interventive therapy the possible use of RPA for a cost-risk-analysis from a medical microbiological viewpoint will be demonstrated.

Amikacin↗

Comparative studies of fleroxacin and ofloxacin in experimental pyelonephritis.

Two quinolones, fleroxacin and ofloxacin were used as oral treatment in a model of experimental pyelonephritis in rats. The infecting strains were Escherichia coli, Klebsiella oxytoca and Pseudomonas aeruginosa. Compared to untreated control rats, the rats treated with the quinolones showed a great reduction in bacterial counts in kidney tissue and urine. At lower dosages, fleroxacin had a greater bacterial killing effect than ofloxacin.

Animals↗

[Results of ofloxacin treatment of experimental urinary tract infections].

The antibacterial activity of ofloxacin, a new gyrase inhibitor, was tested in experimental acute occlusive pyelonephritis in rats caused by Escherichia coli O4:H5 and Pseudomonas aeruginosa A 9532. Therapy was performed using increasing concentrations of the substance during three days. Effectiveness of therapy was investigated by determination of the bacterial counts in the tissue of kidneys and in the urine obtained by puncture of the bladder. As little as 3 X 3.75 mg/kg/day of the substance was effective and reduced the E. coli counts. The dosage of 3 X 7.5 mg/kg/day was effective in pseudomonas infections.

Animals↗

[The perfusate culture--bacteriologic monitoring of kidney grafts].

Since the kidney recipient's immune system is entirely suppressed, any bacterial contamination from a graft might be hazardous. Major statistics [1,3,4,5] reveal a mortality as high as 10% due to infectious and gastrointestinal complications. From July 1979 to December 1983 114 kidney grafts have been done in our center. After transplantation none of the patients died as a result of complications due to infection. Microbiologic examination of the perfusate is obligatory to detect contamination. It was used in 145 donor nephrectomies; 28% of the perfusate culture samples were positive: In 4 of 5 cases (81%) the bacteria isolated were of the non-pathogenic type seen in the normal flora of the skin (Staphylococcus epidermidis). Introduction of cover drapes lowered the positive culture rate to 8%. Isolation of S. epidermidis after desinfection of the skin (6x) with 70% spore-free alcohol is proof of the extraordinary sensitivity of the method used. The outstanding clinical importance of this method is the rapid information obtained on any contamination and the early suggestion concerning the first choice of antibiotic. Though E.coli and Pseudomonas aeruginosa were found in the culture, no clinical infection was seen under adequate antimicrobial therapy. Among 114 kidney transplantations in our center no patient died of bacterial infection. Our experience points out that the effect of general antibiotic prophylaxis is negligible. Instead, the effect of early application of antibiotics in accordance with the results of the perfusate culture is superior.

Bacteria↗

How to detect bacterial contamination prior to transplantation.

The mortality of kidney transplantation generally amounts to 10% due to infections and GIT complications. Once grafting a Staphylococcus aureus and Streptococcus contaminated kidney the recipient had to undergo emergency surgery four times. Hence it has become our routine to sample the perfusate on blood culture media. Among 145 donor nephrectomies the microbiologic examination of the kidney perfusate in which the graft is stored and transported turned out to be positive in 28%. Four out of five germs isolated after incubation on blood culture media were of the non-pathogenic type seen in the normal flora of the skin. Making use of the CIT (24-30 hours) we cultured the perfusate on blood media. Since the temporary results of the microbiological examination are obtained within 12 hours we can initiate the first choice antibiotic therapy already at the time of transplantation. Though there was proof of highly pathogenic bacteria clinical infection occurred in none of our patients among a total of 114 grafts. The outstanding clinical importance of this diagnostic tool arises from the time sparing information of any contamination and the early hint at the first choice of antibiotics. The distinct application of antibiotics according to the result of the perfusate culture on blood culture media is superior to a general antibiotic cover.

Abdominal Injuries↗

[Current status of determining bacteria and resistance in urinary tract infections].

A total of 5.584 bacterial strains of different species from urine samples of various University clinics were isolated in 1983. These were tested with regard to their susceptability towards antibacterial substances. E. coli was the most common rod bacteria isolated, followed by Proteus species, Klebsiella und Pseudomonas. Staphylococci and Enterococci were found relatively frequently. A list was set up concerning the resistance pattern of the most important gram-negative rod bacteria toward four penicillin- and three cephalosporin derivatives as well as towards gentamicin and three chemotherapeutics in a stricter sense. For the first substance group mezlocillin supplied the best results. In the second group cefotaxime was most effective. More unfavorable on the whole were the results of the three chemotherapeutics. Enterococci were inhibited most by azlocillin, mezlocillin, ampicillin and nalidixic-acid. Cefsulodin as a special Pseudomonas cephalosporin showed strong activity towards this bacterial species.

Anti-Bacterial Agents↗

[N-Formimidoyl-thienamycin in Animal Studies].

The beta-lactam antibiotic thienamycin is rather unstable and is metabolized in man by renal dehydropeptidase-I. The derivatives of the antibiotic, especially N-formimidoyl-thienamycin (MK-0787) are reported to be more resistant. The antibacterial activity of N-formimidoyl-thienamycin was tested by means of the infection- and therapy model of the acute, occlusive pyelonephritis in rats. Cefotaxime was used as control agent. Even with a low dosage a clear anti-bacterial activity was proved with the E. coli- as well as especially with the Pseudomonas pyelonephritis. In our tests N-formimidoyl-thienamycin was more potent than cefotaxime.

Animals↗

[Mezlocillin concentrations in the serum of children with impaired renal function].

Mezlocillin was administered as an intravenous bolus injection to eight children, aged 4-15, requiring antibiotic therapy; the dose was either 75 mg/kg or 37.5 mg/kg. All of the patients had advanced renal insufficiency. Five of the children required chronic intermittent hemodialysis. The microbiological method of Grove and Randall was used for the quantitative determination of mezlocillin in the serum. Ten minutes after the injection, the concentration of mezlocillin in the serum was approximately 90 mg/l and 40 mg/l, respectively. The determinations 30 and 60 minutes after the injection showed that the mezlocillin concentrations had fallen rapidly to approximately 30 mg/l and 20 mg/l, respectively. The mezlocillin concentrations were still approximately 2 mg/l and 1 mg/l, respectively, 12 hours after administration. For the period between 10 and 60 minutes, the half-lives were between 33 and 57 minutes. In general, we can conclude that a single bolus injection of 75 mg/kg will result in mezlocillin concentrations in the serum of uremic children which allow us to expect good antibacterial efficacy, at least for the first few hours following the injection. On the basis of our studies, half the dosage does not appear to be sufficient.

Adolescent↗