[Value of antibacterial therapy in chronic obstructive urinary tract infections]. / Wertigkeit der antibakteriellen Therapie bei chronisch-obstruktiven Harnweginfektionen.

On the basis of a clinical study an analysis about 86 patients with obstructing bilateral nephrolithiasis and chronic obstructive infection of the urinary tract is elaborated. In order to illustrate the change of resistance of the causative agents during a period of 10 years (1973-1982) two separated 5-year analyses are compared. It is made evident that the relations of sensitivity to seven chemotherapeutic drugs in Coli, Proteus and Pseudomonas infections have changed in favour of increasing resistances of causative agents. The results obtained are an expression of the unstableness of antibiotic therapies under palliative purpose when urological basic diseases are not removed. From the analysis the demand for changing the general problems of obstructive pyelonephritis without possible operative sanation becomes evident. early diagnosis and treatment of predisposing factors are the two keystones of our efforts, when the chronic obstructive infection of the urinary tract by resistant causative agents shall not remain a therapeutic problem in the same measure as hitherto.

[Mezlocillin in neonatal medicine]. / Mezlocillin in der Neonatalmedizin.

The acylureido penicillin mezlocillin was tested clinically and pharmacologically in neonates and young infants who received the antibiotic for prophylactic and therapeutic reasons. On the basis of blood level determinations following the administration of various dosages, we consider a dose of 200 mg/kg per day necessary for premature babies and 300-400 mg/kg per day for full-term babies. Pharmacokinetic data showed age-dependent features. The clinical results were good in 40 children treated with mezlocillin. Twenty of these children received a combination of mezlocillin and gentamicin. No child died of an infection. Therapy was not successful in three babies suffering from productive bronchopulmonary infections. Important side-effects were not observed.

[Intravenous administration of doxycycline vibravenös in childhood--clinical and pharmacokinetic problems]. / Zur intravenösen Verabfolgung von Doxycyclin (Vibravenös) im Kindesalter--klinische und pharmakokinetische Probleme

The paper describes special advantages of doxycycline, especially also in comparison with other tetracyclines, the possbile side-effects of the preparation, and the various ways of application-under special consideration of the pathogenetic spectrum. Pharmacokinetic examination were carried out in eight permature babies, nine new-born, eight normal babies, and in two groups of school children, comprising 7 and 8 test persons each. During these examinations, the serum levels after 1, 6, 10, and 24 hours were evaluated. The values found showed levels in the range of bacteriologic efficiency as far as premature babies and new-born - after 24 hours and with 0.6 gamma/ml - were concerned. In older babies and school children, the values had decreased, after a single application, within 24 hours to 0.2 to 0.15 gamma/ml. However, it has been possible to achieve final values of about 1.5 gamma by applying the preparation twice, i. e. 2 x 2 mg/kg body-weight, within 24 hours. The complete course of elimination of Vibravenös was determined in 8 school children by blood sample taking after 5, 10, 15, and 20 minutes as well as after 1, 3, 6 hours. The values found herein were calculated by means of computer analyses. Half-life of doxycyclin in infantile individuals is subject to rather strong variations. Therefore, a higher dose than usual so far is recommended, viz 6 MG/KG B.W. as initial dose and 3 mg/kg b.w. as maintenance dose.

[Experiences using acylureido-penicillins (azlocillin, mezlocillin) in pediatrics]. / Erfahrungen mit Acylureido-Penicillinen (Azlocillin-Mezlocillin) in der Pädiatrie.

The acylureidopenicillins azlocillin and mezlocillin cover a broad spectrum of bacteria, including gramnegative and grampositive species as well as anaerobes. Azlocillin is especially active against P. aeruginosa. Mezlocillin has a good activity against Klebsiella. Both antibiotics inhibit Hemophilus, N. meningitidis and D. pneumoniae in low concentrations. Clinical and kinetic studies were made in more than 300 pediatric patients. Elimination-constant halflife, distribution volume and area under the curve were determined to propose dosage recommendations. Concentrations of azlocillin (44) and mezlocillin (77) were measured in the bronchial secretions. Up to hour 5 after i.v. injection a wide range of concentration values were observed. Azlocillin was found in the meconium in different concentrations after a single injection into the newborn. Mezlocillin diffused into the CSF even in uninflamed meninges, 3 h after injection the mean concentrations were 5.5 mg/l. 39 patients, 35 of them infected by P. aeruginosa, were treated by azlocillin. Urinary tract infections, wound infections and dacryocystitis were cured with one exception. Less convincing were the results in complicated bronchopulmonary diseases. The clinical efficacy of mezlocillin was similar. In a group of 59 patients there were only 3 without effect and some with improvement again in complicated pulmonary diseases. Side effects worth to be mentioned were not seen. In 2 patients the azlocillin injection caused nausea. Mezlocillin led to some minor transitory elevations of the transaminases and dyspepsia in some patients.

Pharmacokinetics of azlocillin in neonates.

The pharmacokinetics of the acylureido-penicillin, azlocillin, were studied after intravenous or intramuscular injections in 53 premature and full-term infants with infections. Effective concentrations wer" achieved in premature babies after doses of 50 mg/kg every 12 h and in full-term infants with 100 mg/kg every 12 h. No untoward effects of azlocillin were observed. On the basis of these studies, a dosage schedule for azlocillin has been established.

[Pharmacokinetic investigations on sisomicin in children (author's transl)]. / Pharmakokinetische Untersuchungen von Sisomicin unter besonderer Berücksichtigung des frühen Kindesalters.

Sisomicin is an aminoglycoside effective against gramnegative germs. The sensitiveness of coli, proteus, pseudomonas and klebsiella ranges from 0,1 to 0,4 mcg/ml. Germs with inhibition-values of up to 1 mcg/ml are certainly Sisomicin-sensitive. The side-effects of Sisomicin resemble those of other aminoglycosides, as for instance lesions of the VIIth cranial nerve and the kidney. Since aminoglycosides have a relatively small therapeutic range between toxicity and effective minimal-concentration, investigations are important especially in children. 66 children of different age groups received Sisomicin in doses of 3 mg/kg, 2 mg/kg and 1 mg/kg, and examined pharmacokineticly. Serum-levels were measured after 30 min 1, 2, and 4h, in some cases also after 6 and 8 h. In a separate group we determined the values after 5, 10, 15, 20, 30 and 40 min. The urinary output was controlled and the content of Sisomicin in meconium determined. Based on these results we recommend an individual, Sisomicin dosage for each age group. Clinically the Sisomicin proved to be well tolerated and effective antibioticum.

Experience with amoxycillin in neonates and premature babies.

Amoxycillin, a semi-synthetic penicillin, resembles ampicillin in many respects. There is cross-resistance between the two antibiotics. Numerous Gram-positive and Gram-negative organisms are sensitive to amoxycillin at relatively low dosage. Investigations using oral amoxycillin, 50 mg/kg body weight were carried out in neonates and premature babies in the first days of life. Peak values of 38 microng/ml and 59 microng/ml at 4 1/4 hours were obtained for the neonates and premature babies respectively. The 10-hour value for the first group was 13 microng/ml and for the second 19 microng/ml. With a single dose of amoxycillin, serum levels of 0.9 microng/ml were still obtained after 24 hours. In children who received the same dose twice daily, the serum values were 6.5 microng/ml after 24 hours. The urinary excretion of amoxycillin was, on an average, 41% in 24 hours. Amoxycillin was also found in the meconoium, but the quantity in the different portions showed a large dispersion. Amoxycillin can, therefore, be recommended as an effective and well tolerated antibiotic for use in the neonatal and premature period. In general the drug should be administered 12-hourly at a dose of 50 mg/kg body weight. Only in severe illnesses is 8-hourly administration required.

[In vitro model for the study of the concentration kinetics of antibiotic combinations and their antibacterial activity]. / In vitro-Modell zur Untersuchung der Konzentrationsverläufe von Antibiotikakombinationen und deren antibakterieller Aktivität.

The concentration kinetics of combinations of antibiotics similar to those taking place after i.v. administration was simulated in an in vitro model taking into account the different half-life periods of the antibiotics. A hose pump was used for continuous supply of sterile nutrient to a liquid bacterial culture containing both antibiotics in a preselected concentration and for removal of fluid from the system at an identical flow rate. To account for the different half-life periods of the antibiotics, a solution containing the antibiotic having a longer half-life in a corresponding concentration was continuously added by pumping. Samples were taken at fixed intervals to determine bacterial counts and check the expected concentrations of active substance did not contain antibiotics. This model has been developed to enable a determination of the dynamic relationship between the course of concentrations of antibiotics and their antibacterial activity. To permit a statement on the synergistic, indifferent or antagonistic activity of the combination, in analogy to the FIC indices in the checkerboard technique, the relative reduction of the bacterial count by the combination as compared to the individual components at time t was calculated. The model has been demonstrated by the example of the combined action of azlocillin and gentamicin against a strain of Klebsiella pneumoniae. In a simple way, the model permits any increase in the number of combination partners having different half-life periods. The mathematical development of the model is explained in detail.

[Rapid photometric method for determination of in vitro effectiveness of various antibiotic combinations]. / Photometrische Schnellmethode zur Bestimmung der In-vitro-Wirksamkeit verschiedener Antibiotikakombinationen.

Combinations of antimicrobial agents are often used in medical practice. The combination therapy aims a broader spectrum of chemotherapy and/or synergistic effects. The effect of combination of chemotherapeutics on bacteria may be described as synergistic, indifferent or antagonistic. Therefore, it is essential to test the effectivity of antimicrobial combinations in vitro. The checker-board-technique is the most frequently used test to assess antibacterial combinations. For this standard test macroscopically read an incubation time of 18-24 hours is necessary. To reduce this incubation time to 4 hours a rapid nephelometric method was developed. The results of this method showed a good correlation with the standard test.

[Computer-assisted evaluation and analysis of bacteriologic findings]. / Computergestützte Erfassung und Analyse bakteriologischer Befunde.

A computer-aided information system was developed for registration and analysis of microbiological findings. The base of the system is a microcomputer with a 16-bit-processor and a hard disc ensuring the analysis of a great number of material. Besides the printing of bacteriological findings for the senders detailed questions can be analysed to give informations about the distribution and frequency of bacterial species in certain specimens, about the bacterial resistance in dependence on a definite time and about the choice of combinations of chemotherapeutics as well as the existence of multiple resistances.

[Pediatric pharmacology of azlocilin (author's transl)]. / Pädiatrisch-klinische Pharmakologie von Azlocillin.

Pharmacokinetic investigations of acylureido-penicillins azlocillin in newborns, infants and school shildren showed age dependend results. The differences were especially evident in a prolongation of the serum half-life to 2,56 hours in newborns compared to 0.94 hours in school children. On the basis of our pharmacokinetic results and of the dosages resulting from the data the antibiotic was used clinically in twenty eight patients with Pseudomonas aeruginosa infections and one patient with a Proteus mirabilis infection. The results were much better in infections of the urinary tract than in infections of the respiratory tract. This might be due to an observe bacterial presistence in spite of highly effective levels of azlocillin in bronchial secretion. The tolerance to the antibiotic was good.

[Experience with sisomicin in pediatrics (author's transl)]. / Erfahrungen mit Sisomicin in der Pädiatrie.

Sisomicin, an aminoglycoside antibiotic, is especially effective against Escherichia coli, Klebsiella, Enterobacter, Citrobacter, Serratia, indole-positive and indole-negative Proteus species, Pseudomonas aeruginosa, Salmonella and Staphylococcus aureus. It has a bactericidal action. Although sisomicin is similar to the other aminoglycoside antibiotics, there is not complete cross-resistance to them. Our own pharmacokinetic investigations showed that a dose of 2--3 mg/kg body weight of sisomicin twice daily is necessary in the neonatal period. Infants should be given 2.5 mg/kg body weight three times daily, and school children 1.5--20 mg/kg body weight, likewise three times daily. Excretion of sisomicin in the urine is lower in children than in adults, amounting within 24 hours to only 10--20% in newborns, and 30--40% in school-children. Sisomicin induces excretion of some enzymes in higher quantities from the tubular part of the kidneys, especially alaninaminopeptidase. A report is given on 58 patients, especially newborns and prematures, who were treated for about seven days with sisomicin. The results obtained with a wide variety of infections (such as omphalitis, aspiration of amniotic fluid with broncho-pneumonia, phlegmons of the galea, and also pyelonephritis and mucoviscidosis with pulmonary complications) can be described as good, with a success rate of 85%. On only seven occasions were insignificant transitory side-effects, such as slight increase in transaminases, toxic-allergic exanthema and pain in the region in injection, observed.

Amoxicillin in paediatrics, with special reference to its excretion into bronchial secretion.

Pharmacokinetic examinations with amoxicillin in neonates and prematures are reported. Good values of up to 5 mcg/ml after 24 hours were achieved with two doses of 50 mg/kg amoxicillin daily. Amoxicillin was also found in the meconium, although quantities varied greatly. Amoxicillin is recommended for the treatment of disorders of the respiratory tract because of its good absorption, tissue penetration and tolerance. Examinations to assess the excretion of amoxicillin into the bronchial secretion were therefore carried out in 88 children in different age groups. Two artificial respiration bronchoscopies were carried out with an interval of 7 days, and the bronchial secretion collected and tested for organisms and for amoxicillin concentrations. After the first bronchoscopy, patients were given amoxicillin for 7 days, in doses of 125 to 750 mg t.i.d., corresponding to 40-100 mg/kg body weight. Some very high amoxicillin values were found, especially in those groups from whom the secretion was taken 2, 3, or 4 hours after the last amoxicillin treatment. The values were widely scattered. We recommended 50-100 mg/kg for broncho-pulmonary diseases.

[Pharmakokinetic and clinical studies with azlocillin in paediatrics (author's transl)]. / Pharmakokinetische und klinische Untersuchungen mit Azlocillin in der Pädiatrie.

Azlocillin, an acylureido penicillin with bactericidal activity, is particularly effective against Pseudomonas, enterococci and Haemophilus influenzae. It is also very active against E. coli, various Proteus species and Bacteroides. Pharmacokinetic studies were carried out in 138 children of various ages (prematures, newborns, infants, schoolchildren) after administering 50-75-100 mg/kg/ body weight azlocillin via the i.v. or i.m. routes; The constant of elimination and the distribution volumes were calculated besides the serum levels. In prematures and newborns, therapeutically effective serum levels were obtained on administering 50 or 100 mg/kg body weight twice daily. Infants and older children required 100 or 75 mg/kg body weight t.i.d. Determination of azlocillin in the bronchial secretion after i.v. doses of 75 mg/kg body weight showed good elimination. Azlocillin was always identified up to the 5th hour post injectionem. Inspite of parenteral administration, azlocillin was identified in different concentrations in the meconium as well. 39 children were treated with azlocillin, 35 of whom had Pseudomonas infection. Very good results were obtained in infections of the urinary tract, wound infections, conjunctivitis, dacryocystitis and in one case of meningitis. Bronchopulmonary diseases did not take an equally good course, but in these cases the conditions had not been favourable. No serious side effects were revealed by testing several laboratory parameters.

[Pharmacokinetic studies of azlocillin in pregnancy]. / Pharmakokinetische Untersuchungen mit Azlocillin während der Schwangerschaft.

Examining blood level values and urinary concentrations taken from pregnant and nonpregnant women, the pharmacokinetic dates of azlocillin have been evaluated. We used a computer program based on the two-compartment model. The evaluation of azlocillin concentrations in serum and urine has been realized with the two following methods: polarography and agar diffusion test. We found nearly equal values of serum concentrations when using both methods. There are no statistical differences between pharmacokinetic dates of pregnant and nonpregnant women. Therefore we state: It is not necessary to change the dosage and the application interval of azlocillin during pregnancy.

[Drug induced nephropathy and enzymes of renal origin in the urine]. / Medikamenteninduzierte Nephropathie und Enzyme renalen Ursprungs im Harn.

A report is given on the excretion of the renal enzymes alaninaminopeptidasis (AAP), N-acetyl-beta-D-glucosaminidasis (NAG), beta-glucoronidasis (GBC) and alpha-galactosidasis (GAC) in urine after administration of Gentamycin, Cephalotin, Dextran, Carbencillin or combinations of these medicaments. Moreover the effective level of Gentamycin in the urine was measured after isolated administration of Gentamycin. A rhythmic excretion of ciliated-border and lysomal enzymes was observed. Gentamycin was also rhythmically excreted with the urine. It is assumed that this reflects cyclic changes in the cells of the renal tubule. Under long-term administration of Gentamycin or Dextran the excretion of enzymes already reduced during therapy. This was interpreted as an adaptation of the kidney to the medicament. On the other hand there are combinations of medicaments whose effect on the epithelium of the renal tubule is potentiated.

[On the excretion of azlocillin with bronchial secretion in children (author's transl)]. / Zur Frage der Ausscheidung von Azlocillin in das Bronchialsekret im Kindesalter.

This pharmacokinetic study involved school children who were treated with 6-[(R)-2-(2-oxo-imidazolidine-1-carboxamido)-2-phenyl-acetamido]-penicillanic acid sodium walt (azlocillin, Securopen) at doses of 50 mg/kg bodyweight or 75 mg/kg body weight i.v. Kinetics of the first order were found for the concentrations measured at the same time, being proportionate to the administered dose, while there was no dose dependence for the relative distribution volume. The elimination half-life was about 55 min. In 25 children of different age who had to undergo bronchoscopy for diagnositic and therapeutic reasons, the azlocillin concentrations in the bronchial secretions were measured 1 h and 4 h after the administration of 75 mg/kg quantity of bronchial secretion was obtained, azlocillin concentrations of 30 - 240 microgram/g were found. Measurements of azlocillin concentration in the bronchial secretion and in the serum, which were made at the same time, did not show any correlation.

[Clinical and pharmacokinetic researches of doxycyclin vibravenös in childhood (author's transl)]. / Klinische und pharmakokinetische Untersuchungen von Doxycyclin (Vibravenös) im Kindesalter

Doxycyclin is one of the first efficacious depot antibiotics. It is used in two applications as Vibramycin (R) (peroral and Vibravenös (R) (parenteral). Doxycyclin has a favourable effect not only on different gram-positive and gram-negative bacteria but also on a lot of other germs as mycoplasms, rickettsias, protozoons and large viruses. The tissue invasions is a good one, because there is only a low fraction of free Doxycyclin and further a high lipid activity. Pharmacokinetic investigations of different age-groups show that good serum-levels can be reached because of the sensitivity of numerous germs. The levels are higher, as our experiences demonstrate, if the dose of 4 mg/kilo/weight is injected in two single doses. Our investigations are reported on 49 patients with diseases of the respiratory tract and on 25 patients with diseases of the urogenital tract. Doxycyclin was very useful especially in different forms of pneumonias. The results in infects of the urogenital tract are not so good ones. The compatibility of Doxycyclin can be characterised as very good for children.

[Amoxicillin and its excretion into bronchial secretion (author's transl)]. / Uber das Amoxicillin and seine Ausscheidung im Bronchialsekret.

Various dates on amoxicillin (resorption, distribution, elimination, tissue passage, urinary excretion) are presented. The bacterial spectrum is more fully discussed. Amoxicillin is compared with ampicillin. Dosage and therapeutical results are presented. Within repeated bronchoscopic examinations necessary on account of bronchopulmonary affections determination of germs were done in 88 children. At the same time examination of ampicillin levels in bronchial secretions were performed after amoxicillin therapy with different high doses (3 x 125 mg to 3 x 750 mg) for 7 days. It could be shown that good antibiotic levels could be found in secretion specimens above all obtained 2 to 4 hours after the last amoxicillin administration. They could be found too, if there did not exist any purulent secretion or stronger inflammation. There are relations between the amount of dosage, the level in secretion as well as the influence on germs.