Antibiotics and host defence with special reference to phagocytosis by human polymorphonuclear leukocytes.
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Biomedical subjects
Publications and source records attributed to F D Daschner.
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The in vitro activity of piperacillin at 1/4, 1 and 4 X MHK against 5 strains each of Pseudomonas aeruginosa, Escherichia coli and Streptococcus faecalis was compared in Mueller-Hinton-bouillon and human serum. Serum without piperacillin was bacteriostatic against P. aeruginosa for 8 hrs., against E. coli for 24 hrs. Subinhibitory piperacillin concentrations were bacteriostatic against E. coli, but had no effect against P. aeruginosa and S. faecalis. Bactericidal activity against E. coli was achieved at 1 X MHK against P. aeruginosa and S. faecalis at 4 X MHK. Except for P. aeruginosa in concentrations of 1/4 and 1 X MHK the piperacillin activity in bouillon and serum was almost identical.
Twenty-nine women received 7 g of cefmenoxime before abdominal or vaginal hysterectomy; 20 adult patients received 2 g of cefmenoxime 24 hours and immediately before open heart surgery. In the gynecologic patients, peak cefmenoxime serum concentrations of 23.4 mg/liter were reached within one to two hours after administration of the antibiotic. Cefmenoxime concentrations in myometrium, endometrium, and salpinges also reached their peak one to two hours after administration. Two to three hours later tissue concentrations varied between 1.1 and 5.2 micrograms/g; four hours after application, tissue concentrations were below detectable levels. Cefmenoxime plasma and tissue concentrations were significantly higher in patients undergoing open heart surgery. Subcutaneous tissue and muscle concentrations varied between 2.7 and 38.0 micrograms/g. Cefmenoxime concentrations in cardiac valvular tissue were higher than those in muscle and fat.
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Nosocomial infections consume a significant amount of the total hospital budget. This article describes some practical aspects for cost reduction in hospital infection control. Within one year total savings of 91.000 DM could be achieved by discontinuing unnecessary disinfection procedures. Within six years 2,27 million DM could be saved by discontinuing unnecessary infection control procedures or employing cheaper methods. Of the total antibiotic costs 25% can be reduced by certain measures.
In two prospective, randomized studies conducted in West Germany and involving 80 patients, netilmicin-ticarcillin was compared to tobramycin-ticarcillin in the treatment of serious systemic infections. Both regimens were essentially identical with respect to the clinical and bacteriological results they produced. The netilmicin group developed significantly less nephrotoxicity than the tobramycin group (0% versus 15%, P = 0.03). Ototoxicity also occurred less frequently in the netilmicin-treated patients (3% versus 10%, P = 0.4). In a large collaborative study involving 15 centres, 254 patients were enrolled. Clinical and bacteriological responses were excellent, with netilmicin and tobramycin equally effective, but the incidences of nephrotoxicity and ototoxicity were lower in patients treated with netilmicin than those receiving tobramycin.
19 patients received an intravenous 5-min bolus injection of 2 g ceftriaxone at various times before thoracic surgery. Lung tissue concentrations of 31.8 micrograms/g could be maintained for at least 5 h. Serum and lung tissue concentrations of ceftriaxone are high enough to inhibit most organisms causing nosocomial and community-acquired respiratory tract infections.
24 patients received an intravenous 5-min bolus injection of 2 g cefotetan at various times prior to abdominal or vaginal hysterectomy. Cefotetan concentrations in salpinges were significantly higher than in myometrium and endometrium. Tissue concentrations of 16 micrograms/g could be attained for at least 5 h. At this concentration, 90% of most aerobic and anaerobic bacteria causing genital tract infections are inhibited.
The in vitro efficacy of cefotetan in combination with gentamicin, tobramycin, amikacin, netilmicin against Staphylococcus aureus, Staphylococcus epidermidis and Enterobacter cloacae and with piperacillin and mezlocillin against Escherichia coli, Klebsiella pneumoniae, Serratia marcescens and Enterobacter cloacae was compared by use of the checkerboard agar dilution technique. On average, 60% of the gram-negative and 46% of the gram-positive strains were inhibited by additive, but only 22% of the gram-negative and 2% of the gram-positive bacteria were inhibited by synergistic cefotetan-aminoglycoside combinations. Netilmicin combinations were least active. On gram-negative bacteria, 63% of the cefotetan-penicillin combinations were additive and 11% synergistic. No antagonism occurred with any of the combinations.
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In 57 patients undergoing heart surgery concentrations of netilmicin in plasma, heart valves, muscle, and subcutaneous tissue were determined after a 5 min intravenous bolus injection of 1.5 mg/kg body weight. Within 8 h netilmicin serum concentration declined from 3 micrograms/ml to 1 microgram/ml. In heart valves the concentrations during heart surgery were high enough to inhibit most staphylococci, Klebisiella, Enterobacter and Escherichia coli strains. No different serum and tissue concentrations in patients with and without extracorporal circulation could be found.
The bactericidal activity of azlocillin and piperacillin was tested at concentrations of 1/4 the MIC, the MIC and four-fold the MIC agents a serum-resistant Staphylococcus aureus and a serum-resistant Pseudomonas aeruginosa strain in broth, in serum and in the presence of leukocytes. The antibacterial activity of azlocillin and piperacillin in serum against Staphylococcus aureus was slightly better than in broth (p greater than 0.05); both compounds were distinctly less active against Pseudomonas aeruginosa in serum than in broth (p less than 0.05). Both antibiotics enhanced susceptibility of Pseudomonas aeruginosa to leukocyte killing without serum (p less than 0.05), whereas leukocyte killing of Staphylococcus aureus was hardly improved even at the MIC and four-fold the MIC of both compounds. The antibacterial activity of azlocillin and piperacillin against both bacterial strains was most pronounced in the presence of leukocytes and serum. A marked bactericidal effect was achieved at 1/4 the MIC, the effect not being further significantly enhanced (p greater than 0.05) at the MIC or four-fold the MIC.
In a prospective study, 50 women patients were given 2 g Ceftriaxon (Rocephin) as a short infusion before performing hysterectomy. A control group of 50 patients remained without any antibiotic treatment. In 31 patients, the concentration of Ceftriaxon in the serum and tissue was determined at the time the uterus was removed. Due to the long half-life of Ceftriaxon (8 hours), high serum and tissue levels were found for a period of many hours. After 4-5 hours, the serum level was still 100 micrograms/ml, whereas the concentration in the endometrium, myometrium and in the salpinges were 21 micrograms/g, 24 micrograms/g and 31 micrograms/g, respectively. Due to these long-lasting serum and tissue levels, the protective effect against infections was also very high. 15 infections in the control group are contrasted by one infection only in the treated group. The efficacy of the prophylaxis is objectively assessed by measuring the temperature curve and by determining the number and the spectrum of the postoperatively isolated germs. The germs isolated in the treated group are exclusively such germs which are resistant to Ceftriaxon (enterococci) or which are only moderately sensitive to Ceftriaxon, such as Bacteroides.
Thirty-one patients received an intravenous bolus injection of 2 g ceftazidime over 5 min at various times before abdominal or vaginal hysterectomy. Ceftazidime concentrations in myometrium, endometrium and salpinges reached 34% to 43% of the corresponding serum levels. Subcutaneous tissue concentrations were significantly lower. Tissue concentrations of 8 mg/l were maintained for at least 5 h.
31 patients received an intravenous 15-min injection of 2 g ceftriaxone at various times before abdominal or vaginal hysterectomy. Ceftriaxone concentrations in salpinges were significantly higher than in myometrium and endometrium. Tissue concentrations of 20 micrograms/g could be maintained for at least 5 h. Due to its high tissue concentrations maintained for the whole operative procedure, ceftriaxone does seem to be one of the antibiotics of choice for single-dose prophylaxis of postoperative infections in gynecology.
The bactericidal activity of ceftazidime against 5 serum resistant Staphylococcus epidermidis and 5 serum sensitive Pseudomonas aeruginosa strains was compared in Mueller-Hinton broth and normal human serum. Except for the first 4 hours incubation time ceftazidime was less active in serum as compared to broth against the serum resistant staphylococci at subinhibitory concentrations. Against the serum sensitive Pseudomonas aeruginosa strains the in vitro activity of ceftazidime in serum was significantly higher than in broth at all concentrations investigated. In vitro activity of ceftazidime was best in combination with leukocytes and serum against a Staphylococcus aureus and a Pseudomonas aeruginosa strain. Leukocytes in serum enhanced the bactericidal activity of ceftazidime against a Pseudomonas aeruginosa strain already at 1/4 MIC, which could only slightly be improved at 1 MIC, but not at 4 MIC.
In a three-year prospective investigation, a total of 6,952 patients were investigated prospectively in nine intensive care wards and their rate of nosocomial infections was analysed. The frequency of the nosocomial infections varied between 3% and 27%. The most frequent nosocomial infections were urinary tract infections, sepsis, infections of the skin and of the subcutaneous tissue, pneumonia and wound infections. The most frequent causes of sepsis were ventilation pneumonia, venous catheters, wound infections and urinary tract infections. The pathogen spectrum was analysed. By specific control of infection with employment of an infection control nurse, the frequency of nosocomial infections on intensive care wards was lowered from 17.2% to 14.3% within one year in one of the hospitals.
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