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Harnwegsinfektionen (HWI) gehören mit zu den häufigsten bakteriell bedingten Erkrankungen. Sie treten sporadisch akut, rezidivierend oder chronisch auf. Aufgrund der klinischen Symptome werden Infektionen der unteren und oberen Harnwege unterschieden. Bei strukturellen und funktionellen Veränderungen im Harntrakt, in der Schwangerschaft, bei Diabetes mellitus, bei chronischer Niereninsuffizienz sowie nach einer Nierentransplantation können schwerwiegende Komplikationen auftreten. Für Diagnostik- und Therapieentscheidungen sind diese Faktoren zu beachten. HWI werden vor allem durch gramnegative Erreger, vor allem uropathogene E. coli (UPEC) verursacht, die über entsprechende Virulenzfaktoren verfügen. Die Resistenzzunahme gegenüber vielen Antibiotika erschwert die empirischen Therapieentscheidungen. Aus diesem Grund sollte häufiger eine Urinkultur zur individuellen Therapiekontrolle, aber auch zur Kenntnis der lokalen Resistenzverhältnisse durchgeführt werden. Asymptomatische Bakteriurien sind vorrangig als Kolonisationen der Harnwege durch potenzielle pathogene Keime zu betrachten und sollten nur während der Schwangerschaft, nach einer Organtransplantation und vor traumatisierenden Eingriffen im Harntrakt behandelt werden. Rezidivierende und chronische Infektionsverläufe werden vor allem durch wirtspezifische Faktoren begünstigt. Um Rezidive zu verhindern, werden Antibiotika in reduzierter Dosis, aber auch nichtantibiotische Strategien mit unterschiedlichen Erfolgsraten eingesetzt. Um den Krankheitsverlauf besser zu beeinflussen, sind dringend weitere klinische Studien notwendig.

ABSTRACTThe prospective, multicenter, double-blind study presented in this report evaluated whether or not intravenous (IV) administration of doripenem, a carbapenem with bactericidal activity against gram-negative and gram-positive uropathogens, is inferior to IV administration of levofloxacin in the treatment of complicated urinary tract infection (cUTI). Patients (n= 753) with complicated lower UTI or pyelonephritis were randomly assigned to receive IV doripenem at 500 mg every 8 h (q8h) or IV levofloxacin at 250 mg q24h. Patients in both treatment arms were eligible to switch to oral levofloxacin after 3 days of IV therapy to complete a 10-day treatment course if they demonstrated significant clinical and microbiological improvements. The microbiological cure rate (primary end point) was determined at the test-of-cure (TOC) visit occurring 5 to 11 days after the last dose of antibiotic. For the microbiologically evaluable patients (n= 545), the microbiological cure rates were 82.1% and 83.4% for doripenem and levofloxacin, respectively (95% confidence interval [CI] for the difference, −8.0 to 5.5%); in the microbiological modified intent-to-treat cohort (n= 648), the cure rates were 79.2% and 78.2%, respectively. Clinical cure rates at the TOC visit were 95.1% in the doripenem arm and 90.2% in the levofloxacin arm (95% CI around the difference in cure rates [doripenem cure rate minus levofloxacin cure rate], 0.2% to 9.6%). Both treatment regimens were generally well tolerated. Doripenem was found not to be inferior to levofloxacin in terms of therapeutics and is now approved for use in the United States and Europe for the treatment of adults with cUTI, including pyelonephritis. As fluoroquinolone resistance increases, doripenem may become a more important option for successful treatment of cUTIs, including treatment of pyelonephritis.

Bacterial urinary tract infections (UTI) are frequently found in the outpatient as well as in the nosocomial setting. The bacterial UTI can be stratified into uncomplicated and complicated UTI. Antibiotic resistance is continuously increasing in uncomplicated as well as complicated UTI. In uncomplicated UTI efforts are made to use antibiotic substances exclusively for this indication. In complicated UTI as broad spectrum antibiotics are increasingly used, the higher the antimicrobial resistance rates are reported. There are two predominant aims in the antimicrobial treatment of both uncomplicated and complicated UTI: 1.) rapid and effective response to therapy, prevention of complications and prevention of recurrence in the individual patient treated, and 2.) prevention of emergence of resistance to anti-infective agents in the microbial environment. The use of antibiotics has to keep up with the continuous change in antimicrobial resistance and the tailored needs in the individual patient. Antibiotic substances therefore need to become evaluated for each indication and continuously followed for clinical usage. The knowledge of structure-activity relationships of antimicrobial substances and bacterial resistance mechanisms to antibiotics help to use antibiotics better in daily routine and design new derivatives and substances. The aim of this review is to describe the chemistry and structure-activity relationships of current antibiotics and promising substances in development for the treatment of UTI.

Chronic bacterial prostatitis is the most frequent cause for recurrent urinary tract infection in young and middle-aged men. The selection of an appropriate antimicrobial agent that has optimal pharmacokinetics for urine and prostatic secretion and tissue is important in both entities. Fluoroquinolones possess several pharmacologic characteristics that favor them for treatment of urinary tract infection and prostatitis. The pharmacokinetics of fluoroquinolones and the theoretical background of drug penetration into the prostate is outlined. Analyzing the concentrations of various fluoroquinolones in urine, prostatic and seminal fluid, and in prostatic tissue, it becomes obvious that the fluoroquinolones differ in plasma concentrations and in their concentrations at these sites. Nevertheless, overall, the concentrations at the site of infection of most of the fluoroquinolones should be sufficient for the treatment of chronic bacterial prostatitis and vesiculitis and recurrent urinary tract infection in men caused by susceptible pathogens.Chronic bacterial prostatitis is the most frequent cause for recurrent urinary tract infection in young and middle-aged men. The selection of an appropriate antimicrobial agent that has optimal pharmacokinetics for urine and prostatic secretion and tissue is important in both entities. Fluoroquinolones possess several pharmacologic characteristics that favor them for treatment of urinary tract infection and prostatitis. The pharmacokinetics of fluoroquinolones and the theoretical background of drug penetration into the prostate is outlined. Analyzing the concentrations of various fluoroquinolones in urine, prostatic and seminal fluid, and in prostatic tissue, it becomes obvious that the fluoroquinolones differ in plasma concentrations and in their concentrations at these sites. Nevertheless, overall, the concentrations at the site of infection of most of the fluoroquinolones should be sufficient for the treatment of chronic bacterial prostatitis and vesiculitis and recurrent urinary tract infection in men caused by susceptible pathogens.

Urinary tract infection (UTI) is classified as uncomplicated if it occurs in a patient with a structurally and functionally normal urinary tract. Acute uncomplicated cystitis is observed chiefly in women. It needs, however, to be differentiated depending on whether it occurs in premenopausal, postmenopausal or pregnant women. Only a small number of 15-50 year old, otherwise healthy men suffer acute uncomplicated cystitis. In premenopausal, non-pregnant women, single-dose antimicrobial therapy is generally less effective than the same antibiotic used for longer duration. However, most antimicrobial agents given for 3 days are as effective as those given for longer duration, and adverse events tend to be found more often with longer treatment. Trimethoprim (or co-trimoxazole) can be recommended as first-line empirical therapy only in communities with resistance rates of uropathogens to trimethoprim of < or =10-20%. Otherwise fluoroquinolones are recommended. Alternatives are fosfomycin trometamol or beta-lactams, such as second- or third-generation oral cephalosporins or pivmecillinam, especially when fluoroquinolones are contraindicated or a high proportion (>10%) of Escherichia coil strains in the community are already resistant to fluoroquinolones, as in Spain, for example. Recurrent UTIs are common among young, healthy women even though they generally have anatomically and physiologically normal urinary tracts. The following prophylactic antimicrobial regimens are recommended: (i) the use of long-term, low-dose prophylactic antimicrobials taken at bedtime; (ii) post-coital prophylaxis for women in whom episodes of infection are associated with sexual intercourse. Other prophylactic methods are not as yet as effective as antimicrobial prophylaxis.

Ninety-two clinical microbiologists, infectious disease clinicians and clinicians with an interest in the management of urinary tract infections (UTIs) participated in an interactive session concerning the management of acute uncomplicated lower UTI. The antibacterials considered most appropriate as first-line agents were trimethoprim, co-trimoxazole, pivmecillinam, nitrofurantoin and fluoroquinolones. The current level of usage of fluoroquinolones for lower UTIs was, however, considered inappropriate by most delegates from a 'societal perspective', in terms of spread of resistance and potential impact on the environment.

Abstract:  Twelve healthy volunteers participated in a randomized crossover study to compare urinary concentrations, serum parameters, and urinary bactericidal activity of ciprofloxacin after single intravenous (i.v.) doses of 200 mg and 400 mg and an oral (p.o.) dose of 500 mg. The median serum concentrations at 1 h after administration were 1 μg/ml, 4.3 μg/ml, and 2.2 μg/ml, respectively. Between the first collection period (0–2 h) and the last collection period (38–48 h), the median urinary concentrations decreased from 394 μg/ml, 675 μg/ml, and 585 μg/ml, respectively, to 0.3 μg/ml, 0.6 μg/ml, and 1 μg/ml, respectively. The urinary concentrations after the 400 mg i.v. and the 500 mg p.o. doses were not statistically different but were significantly higher than those after the 200 mg i.v. dose. The urinary bactericidal titers (UBTs), defined as the highest urinary dilution bactericidal for the organism tested, were determined against Escherichia coli (ATCC 25922) and eight uropathogens up to 48 h after administration of ciprofloxacin. The UBTs after the 400 mg i.v. and the 500 mg p.o. doses were similar and were significantly higher (P<0.05) than those following the 200 mg i.v. dose. After 400 mg i.v. and 500 mg p.o., median UBTs of ≥1 : 4 were present up to 48 h for all strains for which the MIC was ≤0.5 μg/ml, except for one nalidixic-acid resistant Escherichia coli strain for which the MIC was 0.25 μg/ml. Species for which the MIC is ≥1 μg/ml showed median UBTs of ≥1 : 4 for 8–16 h. Median UBTs of ≥1 : 4 were present up to 8 and 12 h for both Pseudomonas strains tested. A once-daily dosage of 400 mg i.v. or 500 mg p.o. might be sufficient for treatment of urinary tract infections caused by highly susceptible pathogens. A twice-daily dosing scheme seems to be preferable for complicated infections caused by pathogens with intermediate susceptibilty (MIC≥1 μg/ml) or for empiric therapy.

Renal function, rate of urine turnover in the renal pelvis, and the role of the renal lymphatics were studied in dogs during total ureteral occlusion lasting from 6 to 34 days with and without induced infection. — Glomerular filtration rate, effective renal plasma flow, concentration ability, and tubular reabsorption of sodium and potassium were followed. The concentrations of 2 radiolabelled clearance substances, iothalamate and o-iodohippurate, as well as those of sodium, potassium, and total protein were determined in hilar and/or subcapsular lymph obtained by cannulization of the lymphatics. — In uninfected hydronephrosis, concentration ability as well as sodium and potassium reabsorption were impaired as compared with control kidneys. In infected hydronephrosis, these partial functions were not maintained. Turnover in the occluded renal pelvis, ranged from 0.04 to 0.16 ml per minute. Following ureteral occlusion of 1 week, pyelolymphatic reabsorption into hilar, but not subcapsular lymph could be demonstrated.

Summary The minimum inhibitory concentrations (MIC) of ciprofloxacin were determined for 441 uropathogens from patients with complicated and/or hospital acquired urinary tract infections (UTI). None of theEnterobacteriaceae was resistant (MIC = 4 mg/l), but 21.7% of enterococci, 28.3% ofPseudomonas spp. and 38.5% of staphylococci were. Subtyping of the strains revealed that with staphylococci there was no clonal spread of resistant strains. In the case of enterococci andPseudomonas spp., however, cross infections played a major role (46% and 40% respectively). In a retrospective analysis of 370 UTI episodes caused byPseudomonas aeruginosa (74), enterococci (185) or staphylococci (111) there was no difference between sensitive and resistant strains with respect to clinical aspects and rates of elimination by appropriate anti-bacterial therapy. The rates of spontaneous disappearance without antibacterial therapy ranged from 28% in the case ofP. aeruginosa up to 63% in the case of coagulase-negative staphylococci. This implies that especially in UTI caused by gram-positive cocci an indication for antibacterial therapy should be weighted thoroughly and fluoroquinolones should only be used in accordance with sensitivity testing.

Summary Twenty-four healthy volunteers and 24 patients undergoing transurethral resection of the prostate received an oral dose of 200 mg of cefpodoxime as proxetil ester in a fasting state. At the same time 3.235 g of iohexol, a renal contrast medium, was injected intravenously to indicate possible urinary contamination of the prostatic fluid. The subjects were divided into three groups each. After 3, 6 and 12 h the cefpodoxime concentrations were measured in plasma, urine, prostatic fluid and ejaculate in volunteers and in plasma, prostatic fluid and prostatic adenoma tissue in patients by a bioassay as well as by an HPLC method. In general, the concentrations measured by bioassay were higher than those by HPLC. The median plasma concentrations (bioassay) in volunteers (patients) after 3, 6 and 12 h were 2.28 (2.34) mg/l, 0.95 (1.17) mg/l and 0.12 (0.28) mg/l, respectively. The median ejaculate concentrations after 6 and 12 h were 0.95 mg/l and 0.19 mg/l, respectively. Only in three volunteers and in one patient prostatic fluid concentration without urinary contamination could be measured after 3 h with a median fluid to plasma ratio of 0.10. The prostatic adenoma tissue concentrations (bioassay) after 3 and 6 h were 0.50 mg/kg and 0.24 mg/kg with tissue to plasma ratios of 0.30 and 0.26, respectively. After 3 h about half of the volunteers and after 12 h about half of the patients showed no detectable concentration in ejaculate (volunteers) and prostatic tissue (patients), respectively. It was concluded that the cefpodoxime should be administered 3 to 6 h prior to surgery if used for perioperative prophylaxis. The concentration in seminal but not in prostatic fluid is high enough for effective treatment.

Summary Chronic bacterial prostatitis is a rare infection but difficult to treat. Usually co-trimoxazole has been used, yet with poor results. Because of their favorable pharmacokinetics and their broad antibacterial spectrum, the newer quinolones may be a good alternative. In contrast to ß-lactam antibiotics their concentrations in prostatic fluid, in prostatic tissue and in seminal fluid are relatively high in comparison to the corresponding plasma concentrations. For prostatic fluid measurements, however, possible urinary contamination has to be considered and identified otherwise falsely high levels are measured. A total of 23 studies with the newer quinolones (norfloxacin, ciprofloxacin, ofloxacin, pefloxacin, enoxacin, temafloxacin and rufloxacin) in the treatment of chronic bacterial prostatitis are available. However, the results of these studies are difficult to compare because not all investigators used the same diagnostic criteria and there was a considerable range of duration of treatment and of follow-up. Since the issue involved in the treatment of prostatitis is that of relapse, patients cannot be considered cured if they have been followed for one week or one month only. There were four studies among the 23 publications, i.e. one with norfloxacin and three with ciprofloxacin, which fulfilled the criteria of standardized prostatic localization and of long-term follow-up of at least six months. The results are promising, but further investigations, especially controlled studies, are needed in order to determine the role of the newer quinolones in the treatment of chronic bacterial prostatitis.

Zusammenfassung Cefixim, ein neues orales Cephalosporin, verfügt über eine höhere Aktivität gegenüber Enterobakterien als die konventionellen oralen Cephalosporine und wird in etwa 20% als aktive Substanz über den Urin ausgeschieden. Die Therapie von Harnwegsinfektionen (HWI) erscheint deshalb erfolgversprechend. In zwei kleineren, unkontrollierten und vier größeren, kontrollierten (Amoxicillin, Co-trimoxazol) „westlichen“ Studien, ebenso wie in acht japanischen Studien, konnte die gute Wirksamkeit von Cefixim bei unkomplizierten HWI nachgewiesen werden. Cefixim kann bei dieser Infektion aufgrund des Erregerspektrums bereits eingesetzt werden, bevor das bakteriologische Ergebnis vorliegt. Für die Behandlung der akuten Pyelonephritis liegen bisher nur wenige Beobachtungsfälle vor, die jedoch gute Ergebnisse (abgesehen von Infektionen, verursacht durchProteus mirabilis) aufwiesen. Bei der Therapie komplizierter HWI zeigten eigene Beobachtungen (im Vergleich mit Norfloxacin) und die Erfahrung aus 13 japanischen, nicht kontrollierten Studien, daß auch bei dieser Infektion gute Ergebnisse bei empfindlichen Erregern zu erzielen sind. Da bei komplizierten HWI häufig auch grampositive Erreger beziehungsweise Nonfermenter vorkommen können, die gegen Cefixim resistent sind, sollte nach Möglichkeit vor Therapiebeginn das bakteriologische Ergebnis vorliegen. Zur Behandlung von HWI im Kindesalter liegen bisher nur wenige, aber erfolgversprechende Fallbeobachtungen vor. Die Verträglichkeit von Cefixim war vergleichbar mit der der Kontrollantibiotika. Da die einmalige Gabe (400 mg) pro Tag offenbar höhere gastrointestinale Nebenwirkungen aufweist, sollte die Tagesdosis besser in zwei Portionen (200 mg) verabreicht werden. Insgesamt kann Cefixim als eine gute Alternative zur Therapie von HWI angesehen werden.

Zusammenfassung In einer vergleichenden Untersuchung an gesunden Probanden wurden die pharmakokinetischen Parameter von Cefixim nach oraler Applikation von 200 mg als Trockensuspension, Fertigsaft und Tablette bestimmt. Alle drei galenischen Formulierungen zeigten eine zuverlässige Resorption. Die maximalen mittleren Plasmakonzentrationen betrugen 2,4–3,4 mg/l und wurden nach 3,3 bis 3,5 h erreicht. Die mittleren Plasmahalbwertszeiten waren 2,9 bis 3,1 h, die Fläche unter der Plasmakonzentrations-Zeit-Kurve 18–26 mg/l·h, die Wiederfindung im Urin 18–24% der applizierten Dosis. Die höchste Bioverfügbarkeit wurde gemessen nach Applikation der Trockensuspension gefolgt von Tablette und Fertigsaft. Vor den Prodrug-Cephalosporinen, Cefuroxim Axetil, Cefetamet Pivoxyl und Cefotiam Hexetil, zeichnet sich Cefixim durch längere Plasmahalbwertszeit und größere, dosiskorrigierte Fläche unter der Plasmakonzentrations-Zeit-Kurve aus. Die im Vergleich zu den genannten anderen Cephalosporinen niedrigere Wiederfindung im Urin bei gleicher absoluter Bioverfügbarkeit läßt auf eine größere extrarenale Clearance schließen.

Summary 20 urologists took part in a single blind, randomized study. Female patients with acute uncomplicated UTI were recruited. The patients received either a single dose of 3 g fosfomycin trometamol versus 200 mg ofloxacin or 1.92 g cotrimoxazole. Follow-up examinations were carried out after one and four weeks. Of 562 patients 446 could be evaluated for efficacy and 496 for tolerance. Patients were analysed according to the amount of bacteriuria: “significant” (= 105/ml), “low count” (102–104 ml) and “no bacteriuria” (= 101/ml), as well as according to the sensitivity of the infecting organisms: sensitive (resistant): fosfomycin trometamol = 16 mg/l (= 128 mg/l), ofloxacin = 1 mg/l (= 8 mg/l), co-trimoxazole = 2/38 mg/l (= 16/304 mg/l). Up to one week the following results could be achieved: clinical improvement was attained in patients with “significant” bacteriuria (fosfomycin trometamol-150, ofloxacin-89, co-trimoxazole -69) in 94.7% for fosfomycin trometamol, in 95.4% for ofloxacin, and in 94% for co-trimoxazole; in patients with “low count” bacteriuria (fosfomycin trometamol-44, ofloxacin-18, co-trimoxazole-30) in 95.2% for fosfomycin trometamol, in 93.7% for ofloxacin, and in 96.4% for co-trimoxazole; and in patients with no bacteriuria (fosfomycin trometamol-11, ofloxacin-6, co-trimoxazole-4) in 81.8% for fosfomycin trometamol, in 100% for ofloxacin and in 100% for co-trimoxazole. Sterile urine or non-significant bacteriuria was achieved in the group with “significant” bacteriuria in 87.4% for fosfomycin trometamol, in 91% for ofloxacin and in 88.4% for co-trimoxazole; and in the group with “low count” bacteriuria in 86.4% for fosfomycin trometamol, in 94.4% for ofloxacin, and in 96.7% for cotrimoxazole. In patients infected by resistant (intermediary sensitive) strains sterile urine or non-significant bacteriuria could be achieved in 7/11 (5/6) patients for fosfomycin trometamol and 2/5 (0/1) for co-trimoxazole. Concerning side effects a total of 6.8% for fosfomycin trometamol, 5.9% for ofloxacin and 7.9% for co-trimoxazole was experienced mostly at the gastrointestinal site (fosfomycin trometamol-6.4%, ofloxacin-5.9%, co-trimoxazole-6.3%). This study demonstrates that fosfomycin trometamol was equally effective and tolerable in single-dose therapy of acute uncomplicated UTI in females when compared to other established drugs such as ofloxacin and co-trimoxazole.

Zusammenfassung Die Bestimmung der minimalen Hemmkonzentrationen (MHK) von Ofloxacin gegenüber 400 Isolaten, angezüchtet aus dem Urin von urologischen Patienten mit komplizierten Harnwegsinfektionen (HWI), ergab bei einer Konzentration von 1 mg/l (2 mg/l) eine Hemmung von 94% (99%) aller grammegativen Erreger und bei einer Konzentration von 1 mg/l (4 mg/l) eine Hemmung von 59% (100%) aller grampositiven Erreger. Entsprechend der MHK 90%-Werte ergibt sich folgende Aktivitätsabstufung: Ciprofloxacin, Ofloxacin, Norfloxacin, Pefloxacin, Enoxacin, Pipemidsäure, Cinoxacin und Nalidixinsäure. Nach oraler Gabe von 400 mg Ofloxacin lag bei zehn Patienten die mittlere Serumspitzenkonzentration bei 5,5 mg/l. Die mittlere renale Ausscheidung betrug 41%. 14,5 bis 19 Stunden nach oraler Gabe von 400 mg betrug bei zehn Patienten, die sich einer transurethralen Resektion der Prostata unterziehen mußten, die mediane Serumkonzentration 1,87 mg/l und die mediane Prostataadenom-Gewebekonzentration 1,20 mg/kg. Aufgrund derIn vitro-Aktivität und der Serum-, Urin- und Gewebekonzentrationen ist zu erwarten, daß Ofloxacin zur Therapie komplizierter HWI sehr gut geeignet ist.

Summary Minimal inhibitory concentrations (MIC) of enoxacin, nalidixic acid, pipemidic acid, norfloxacin, ciprofloxacin, ofloxacin and pefloxacin against isolates from 400 urological in-patients with complicated urinary tract infections (UTI) were determined by means of an agar dilution technique (104 cfu, multipointer). 28 patients (21 male, seven female) aged 36 to 84 years with complicated UTI due to sensitive bacteria were treated orally with 200 mg enoxacin b.i.d. for six to 14 days. Plasma and urine samples were collected from 19 patients, at intervals prior to and following a 400 mg dose of enoxacin, and enoxacin concentrations were determined by a high pressure liquid chromatography (HPLC) method. The MICs of enoxacin against all but one of the gram-negative isolates cultured from 265 urological patients were between 0.03 and 4 mg/l. The MICs against 134 gram-positive isolates were between 0.25 and 16 mg/l except two strains of streptococci. At a concentration of 4 mg/l (8 mg/l), 90.3% (98%) of the total spectrum of isolates were inhibited by enoxacin. Of the quinolones tested, ciprofloxacin appeared to be the most active compoundin vitro and cinoxacin the least active antimicrobial agent. Thein vitro activity of enoxacin was comparable to that of norfloxacin, ofloxacin and pefloxacin. Oral administration of 400 mg enoxacin to elderly patients resulted in peak serum concentrations between 0.7 and 6.3 mg/l (mean 3.6 mg/l) attained between 1.0 and 6.0 h following drug ingestion. The mean urinary recovery of parent drug within 24 h was 31.2% of the administered dose. 25 of 28 patients treated orally with enoxacin could be followed-up for five to 14 days after the end of treatment. Enoxacin therapy in these patients resulted in 18 cures, one failure and six relapses (same species). The drug was well tolerated and there was no evidence of renal, hepatic or haematological toxicity. Enoxacin appears to be well suited for the treatment of complicated UTI.

Zusammenfassung Die minimalen Hemmkonzentrationen (MHK) von Impienem, Ceftazidim, Piperacillin, Tobramycin, Aztreonam und Carumonam wurden für 400 aus dem Urin von urologisch-stationären Patienten mit komplizierten und/oder im Krankenhaus erworbenen Harnwegsinfektionen in Koloniebildnerzahlen von = 105 isolierten Erregern bestimmt. Über 90% der gramnegativen Erreger waren empfindlich gegen alle getesteten Antibiotika. Bei den grampositiven Erregern (etwa zur Hälfte Staphylokokken und Enterokokken) lagen die MHK90-Werte nur für Imipenem und Piperacillin im therapeutischen Bereich. Patienten, bei denen eine Resektion (n=31) bzw. Enukleation (n=1) des Prostataadenoms oder eine Lithotripsie (n=4) durchgeführt wurde, erhielten zu unterschiedlichen Zeiten bis zu sechs Stunden vor der Operation je 0,5 g Imipenem/Cilastatin als perioperative Prophylaxe. Die Plasmaspitzenkonzentrationen von Imipenem (Bioassay) lagen im Durchschnitt bei 49,4 mg/l (zwischen 12,2 und 134,8 mg/l). Bei diesem Patientengut ergab sich eine geschätzte Halbwertszeit von etwa drei Stunden. Die Konzentrationen im Prostataadenomgewebe schwankten sowohl intra- als auch interindividuell erheblich. Bis zu zweieinhalb Stunden waren sie jedoch ausreichend für sensible Erreger (MHK bis 1 mg/l). Die Konzentrationen im Prostatasekret lagen bis zu sechs Stunden zwischen 1 und 2 mg/l. Insgesamt 20 urologische Patienten mit komplizierten Harnwegsinfektionen (15 Männer, 5 Frauen) im Alter von 26 bis 87 Jahren (Median 70 Jahre) erhielten sieben bis 16 Tage lang (Median sieben Tage) täglich 3 × 0,5 g Imipenem/Cilastatin i.v. als Kurzinfusion. Während sowie ein bis zwei Tage nach Therapie wiesen alle 20 Patienten einen sterilen Urin auf. Von den 19 nachuntersuchten (sieben bis zehn Tage nach Therapieende) Patienten blieben zehn Patienten (53%) ohne Infektionen und wurden als Erfolg eingestuft. Sieben Patienten (37%) zeigten Rezidive (gleiche Keimart) und zwei Patienten (10%) Reinfektionen (andere Keimart). Die lokale und systemische Verträglichkeit von Imipenem/Cilastatin war gut.

Following a single dose of co-trimoxazole or co-tetroxazine, the plasma and urine levels of intact trimethoprim (TMP) and sulphamethoxazole (SMZ) and of tetroxoprim and sulphadiazine (SDZ) were determined in six geriatric patients in a cross-over design by high pressure liquid chromatography. The pharmacokinetic analysis showed a plasma elimination half-life in the terminal phase of 10.39 h for TMP, 11.79 h for SMZ, 6.55 h for TXP and 10.46 h for SDZ. The resulting distribution volumes Vdβ and total plasma clearance values corresponded with the data obtained in young patients or volunteers. Recovery in urine, measured for up to 96 h, was 49.2% (TMP), 19.8% (SMZ), 57.03% (TXP) and 61.1% (SDZ). In contrast to young volunteers, geriatric patients experienced a slight prolongation of renal excretion for both sulphonamides. In this group of patients the renal clearance was 2.42 ml/min for SMZ and 10.7 ml/min for SDZ. Die Plasma- und Harnspiegel von intaktem Trimethoprim (TMP) und Sulphamethoxazol (SMZ) sowie von Tetroxoprim (TXP) und Sulphadiazin (SDZ) wurden nach Einmalgabe von Co-trimoxazol bzw. Co-tetroxazin bei sechs geriatrischen Patienten in cross-over Anordnung hochdruckflüssigkeitschromatographisch bestimmt. Die pharmakokinetische Analyse ergab Plasmaeliminationshalbwertszeiten aus der terminalen Phase von 10,39 (h) für TMP, von 11,79 (h) für SMZ, von 6,55 (h) für TXP und von 10,46 (h) für SDZ. Die resultierenden Verteilungsvolumina Vdβ und Plasmagesamtclearancewerte entsprechen den bei jungen Patienten bzw. Probanden gefundenen Daten. Die bis zu 96 h im Urin gemessenen Wiederfindungsraten betrugen 49,2% (TMP), 19,8% (SMZ), 57,03% (TXP) und 61,1% (SDZ). Im Gegensatz zu jüngeren Versuchspersonen konnte eine leichte Verlängerung der renalen Exkretion beider Sulfonamide bei geriatrischen Patienten festgestellt werden. Die renale Clearance beträgt bei diesem Patientenkollektiv 2,42 ml/min für SMZ und 10,2 ml/min im Falle von SDZ.

Summary Constant infusion experiments were performed on dogs to determine the concentration levels of co-trimazine (a combination of trimethoprim and sulphadiazine) in the dogs' prostatic secretion, prostatic interstitial fluid, prostatic tissue, urine, and other tissues. Trimethoprim concentrations in prostatic secretion, interstitial fluid and tissue were higher than corresponding serum values, whereas the concentrations of sulphadiazine were far below these values. These results were compared to those of a similar study which combined trimethoprim and sulphamethoxazole (co-trimoxazole). The prostatic secretion to serum ratios of sulphadiazine were lower than those for sulphamethoxazole. Urine concentrations of sulphadiazine, however, were much higher than those of sulphamethoxazole. In serum and urine, only co-trimazine had a trimethoprim/sulphonamide ratio approximating the optimal synergy ratio of 1:20. Neither trimethoprim/sulphonamide combination appears to have any theoretical advantage over the other in the treatment of prostatitis. However, co-trimazine may be more effective in the treatment of urinary tract infections in general because of the high concentrations of sulphadiazine in urine.

Zusammenfassung In einer kooperativen, prospektiv offen randomisierten klinischen Studie wurden die Wirksamkeit und Verträglichkeit von Cefaclor (3 × 500 mg) und Amoxicillin (3 × 750 mg) bei der Behandlung des Harnwegsinfektes (HWI) vergleichend geprüft. Insgesamt wurden 110 Patienten (51 Männer und 59 Frauen) im Alter von 10 bis 83 Jahren über einen Zeitraum von fünf bis 14 Tagen (im Mittel 10 Tage) therapiert, von denen 59 Patienten einen komplizierten und 51 Patienten einen unkomplizierten HWI hatten. Bei allen Patienten wurden aus dem Urin Keime angezüchtet, die in vitro gegen beide Antibiotika empfindlich waren. In beiden Therapiegruppen fanden sich je drei Mischinfekte und 35Escherichia coli-Monoinfektionen. Die übrige Verteilung der Keimarten war ebenfalls gut vergleichbar. Die mit Cefaclor behandelten Patienten zeigten einen günstigeren Erfolg, d. h. Reduktion der Keimzahl auf < 104/ml unmittelbar nach Therapieabschluß. Dies beruhte vor allem auf einer statistisch auffälligen, höheren Eliminationsrate beiE. coli-Infektionen. Die Langzeiterfolge waren jedoch bei der Nachuntersuchung 14 bis 60 Tage nach Therapieabschluß in beiden Gruppen mit unkompliziertem Infekt gleich gut und betrafen etwa die Hälfte der Fälle. Bei kompliziertem Infekt lag der Gesamterfolg nur etwa bei einem Viertel der Fälle, wobei das Ergebnis in der Amoxicillin-Gruppe günstiger ausfiel. Dabei muß berücksichtigt werden, daß bei der behandelten Patientenzahl die Gruppen mit kompliziertem HWI nur schwer vergleichbar sind und die Rezidiverkrankung wesentlich vom Grundleiden bestimmt wird. Die Verträglichkeit beider Medikamente war ausgezeichnet.

Summary Renal clearance and renal hilar lymph and interstitial fluid concentrations of co-trimazine were investigated in dogs during constant intravenous infusion. The lymph was obtained by direct cannulation of the lymphatics, and the interstitial fluid from small plastic tissue chambers, implanted 4–6 weeks before the experiments. The clearance values for trimethoprim and sulphadiazine, compared to the glomerular filtration rate, as measured by125I-iothalamate clearance, showed a net tubular secretion of trimethoprim and tubular re-absorption of sulphadiazine. Renal lymph and interstitial fluid concentrations were found to be lower than the plasma concentrations, corresponding well with earlier findings for several other antimicrobial agents. We found a statistically significant difference between lymph/plasma and interstitial fluid/plasma ratios, indicating different composition and origin of lymph and interstitial fluid.

Zusammenfassung Serum-Konzentrationen, biologische Halbwertszeit, Verteilungsvolumen und Serum-Clearance von Sisomicin, einem neuen Aminoglykosid-Antibiotikum, wurden bei 23 Patienten untersucht und mit der Pharmakokinetik von125J-markiertem Jothalamat verglichen, das fast ausschließlich durch die Nieren filtriert wird. Die Serum-Kreatinin-Werte von zehn Patienten waren normal oder lagen im Grenzbereich der Norm (= 1,5 mg/100 ml), acht Patienten hatten eine Niereninsuffizienz unterschiedlichen Grades (Serum-Kreatinin 1,7–9,6 mg/100 ml), und sechs Patienten mußten intermittierend dialysiert werden. Nach intravenöser Injektion von 1 mg/kg Sisomicin betrug die Halbwertszeit bei Patienten mit normaler oder an der Grenze der Norm befindlicher Nierenfunktion 3,5 Stunden und war damit der von Jothalamat (3,2 Stunden) ähnlich. Das mittlere Verteilungsvolumen betrug 20,1 % des Körpergewichts (Jothalamat 23,7%). Bei Patienten mit Niereninsuffizienz konnte eine sehr hohe Korrelation zwischen Serum-Kreatinin und Halbwertszeit von Sisomicin und eine noch bessere Korrelation zwischen den Clearances von Jothalamat und Sisomicin festgestellt werden. Bei hämodialyseabhängigen Patienten betrug die mittlere Halbwertszeit zwischen zwei Dialysen 40 Stunden für Sisomicin und annähernd 100 Stunden für Jothalamat, was an eine zusätzliche extrarenale Clearance oder eine tubuläre Sekretion von Sisomicin bei diesen Patienten denken läßt. Die Ergebnisse der pharmakokinetischen Untersuchungen lassen erkennen, daß ein Dosierungsschema, in welchem alle 8 bis 12 Stunden 1 mg/kg Sisomicin injiziert wird, bei Patienten mit normaler Nierenfunktion Serum-und Harnspiegel gewährleistet, die für die Behandlung der meisten Harnwegsinfektionen ausreichend sind. Bei Patienten, deren Nierenfunktion gestört ist, sind die Injektionsintervalle entsprechend den Serum-Kreatinin-Werten zu verlängern. Bei hämodialyseabhängigen Patienten ist je eine übliche Dosis nach Abschluß der Dialyse ausreichend. Neun Patienten mit chronischen Harnwegsinfektionen, die durch ernste Grundkrankheiten kompliziert waren, wurden nach diesem Dosierungsschema behandelt, das befriedigende bakteriologische und klinische Resultate erbrachte. Nebenwirkungen oder Anzeichen einer Kumulation wurden nicht beobachtet.

Zusammenfassung Im Tierexperiment beträgt die Nierenlymphkonzentration von Cephacetril etwa 2/3 der Plasmakonzentration. Dies entspricht cum grano salis auch den Konzentrationen der anderen Cephalosporine. Ein Konzentrationsmechanismus für diese Antibiotika im renalen Interstitium existiert nicht. Cephacetril wird beim Menschen vornehmlich über die Nieren ausgeschieden, und zwar sowohl durch glomeruläre Filtration wie tubuläre Sekretion. Die Halbwertszeit beträgt bei normaler Nierenfunktion 1 bis 1,5 Stunden. Die tubuläre Sekretion kann durch Probenecid blockiert werden. Eine Dosierung von 1 g alle 6 bis 8 Stunden, ja sogar 12 Stunden, ist ausreichend für die Therapie der meisten Harnwegsinfektionen bei Patienten mit normaler Nierenfunktion. Eine randomisierte Studie zeigte bei dieser Dosierung keinen Unterschied zu Gentamicin, wenn die Keime sensibel waren. Bei Niereninsuffizienz richtet sich die Dosierung nach dem Serumkreatinin. Bei schweren Infektionen empfiehlt sich eine Infusionsbehandlung mit 2 g oder bis 4 g drei- bis viermal täglich. Die Antibiotika-Kombinations-Therapie von Cephacetril mit Gentamicin wird in einer Tagesdosierung bis zu 16 g Cephacetril und 160 mg Gentamicin gut vertragen und empfiehlt sich bei komplizierten Harnwegsinfektionen mit septischen Fieberschüben in der Urologie.

Summary The renal clearance, renal lymph concentrations and serum protein binding were determined in the dog for 5 cephalosporine derivatives (cephaloridine, cephalothin, cephazoline, cephacetrile, and cephradine). The protein binding for these cephalosporines was 11%, 50%, 24%, 24%, and 10% respectively. These cephalosporines were either excreted exclusively by glomerular filtration (cephaloridine and cephradine) or in addition by tubular secretion (cephalothin, cephazoline, and cephacetrile). The renal lymph concentrations of all antibiotics were significantly lower than the simultaneous arterial plasma concentrations (mean values between 64% and 84%). There was a significant negative correlation between the renal clearance and the lymph/plasma ratio of the antibiotic. There was also an indirect negative correlation between serum protein binding and the relative renal lymph concentrations. The renal clearance, therefore, but not the protein binding, has a direct effect on the lymph concentration. The renal interstitium is divided into a perivascular and a peritubular interstitium. Since lymph vessels are only present in the perivascular connective tissue, lymph concentrations can only reflect the conditions in the perivascular interstitium. Since the post-glomerular capillaries contain pores offering permeation possibilities for even high molecular substances, good tissue permeability for free as well as protein-bound antibiotics can be assumed. The interstitial concentration depends on the capillary plasma concentration and this in turn on the renal excretion mechanism of the antibiotic.

Summary Cefroxadine and cephalexin were compared in a double-blind study in patients with established, complicated urinary tract infections. The patients were treated orally with 1 g t.i.d. for five days. Bacterial counts in the urine were determined one, three and eight hours after the first dose and on the second, third and fifth days of treatment. A significant reduction in the bacterial count was seen one and three hours after the first dose and to a much greater extent eight hours after the dose. Reductions in the bacterial count were more frequent in the group treated with cefroxadine. The results during the first eight hours indicate that cefroxadine kills more rapidly than cephalexin; this is in agreement with the experimental findings. It is still uncertain whether the transient differences observed in the rates of inhibition are of clinical relevance.

Zusammenfassung Sowohl Untersuchungen mit Nierengewebshomogenat bzw. -scheiben als auch autoradiographische Untersuchungen sind bisher nicht in der Lage, die Antibiotikakonzentrationen im Interstitium aufzuzeigen. Die Nierenlymphe ist dazu am besten geeignet, da hierbei die Abtrennung des Urinanteils der Harnwege möglich ist. Die Untersuchungen sollten unter konstanten Plasmaspiegeln und unter Verwendung einer Standardsubstanz, z. B. Jothalamat, durchgeführt werden. Antibiotika mit hoher renaler Clearance, wie z. B. Carbenicillin, Cephacetril, Cephaloridin und Ampicillin haben normalerweise eine deutlich niedrigere Nierenlymph-als arterielle Plasmakonzentration. Bei Harnstauungsnieren mit und ohne Infekt dürften sich die Konzentrationsverhältnisse in beiden Verteilungsräumen annähern.

Studies in vitroshowed that at concentrations of 1 and 4 mg/L ofloxacin inhibited 94 and 99% of the Gramnegative pathogens in isolates cultured from the urine of patients with complicated urinary tract infections (UTI). Against Grampositive bacteria, 60 and 100% were inhibited at the corresponding concentrations. Comparisons of the MIC90values of 8 quinolones showed the decreasing order of in vitroantibacterial activity to be ciprofloxacin, ofloxacin, norfloxacin, pefloxacin, enoxacin, pipemidic acid, nalidixic acid and cinoxacin. After an oral dose of ofloxacin 400mg, the mean peak serum concentration in 10 elderly patients was 5.5 mg/L and mean renal excretion during 24 hours was 41%. In 17 patients undergoing transurethral resection of the prostate, ofloxacin 400mg was given for perioperative prophylaxis. Two to 4.5 hours after administration, the median concentrations in prostatic secretion (5 patients) and prostatic adenoma tissue were 4.0 mg/L and 4.1 mg/kg, respectively. The corresponding serum concentrations of ofloxacin were 3.4 and 3.9 mg/L, respectively. In a group of 10 patients, 14.5 to 19.5 hours after oral administration of ofloxacin 400mg the median serum and prostatic adenoma tissue concentrations of ofloxacin were 1.9 mg/L and 1.2 mg/kg, respectively. The in vitroactivity of ofloxacin concentrations attained in serum, urine, prostatic secretion and adenoma tissue show that it appears to be well suited for the treatment of complicated UTI.

Serum concentration, biological half-life, distribution space and serum clearance of sisomicin, a new aminoglycoside antibiotic, have been studied in twenty-three patients in comparison with the pharmacokinetics of125I-labelled iothalamate, a compound only filtered by the kidney. 10 patients had normal or borderline abnormal serum creatinine (<1,5 mg/100 ml), 8 had various degrees of renal insufficiency (serum creatinine 1.7 – 9.6 mg/100 ml) and 6 were being treated by intermittent haemodialysis. After intravenous injection of sisomicin 1 mg/kg body weight in patients with normal or borderline renal function its half-life was 3.5 h, very similar to that of iothalamate, 3.2 h. The mean distribution space was 20.1 % per cent of body weight; iothalamate, 23.7 %. In patients with renal insufficiency there was a positive correlation between serum creatinine level and the half-life of sisomicin, and an even stronger correlation between the clearances of iothalamate and sisomicin. In patients dependent on haemodialysis, the mean serum half-life between dialysis was 40 h, compared to approximately 100 hours for iothalamate, which implies additional extrarenal clearance or tubular secretion of sisomicin. The results of pharmacokinetic studies indicated that a regime of sisomicin 1 mg/kg every 8 to 12 hours in patients with normal renal function would result in serum and urine levels sufficiently high to treat most urinary tract infections. In patients with impaired renal function the dosage interval should be increased according to the serum creatinine level, and in patients dependent on haemodialysis one standard dose at the end of each dialysis period should suffice. 9 patients with a chronic urinary tract infection severely complicated by an underlying disease were treated according to this dosage regimen with a satisfactory bacteriological and clinical result. No adverse reactions or signs of accumulation were observed.

The distribution kinetics of enoxacin and its main metabolite oxoenoxacin in excretory fluids was investigated in 11 healthy volunteers. A single intravenous dose of 428 mg of enoxacin was given as a 1-h infusion. Serial samples of plasma, urine, saliva, nasal secretions, tears, and sweat were drawn and analyzed for enoxacin and oxoenoxacin by reversed-phase high-pressure liquid chromatography. Large differences in the concentration-time profiles of the excretory fluids analyzed were observed. Nasal secretions exhibited the highest enoxacin exposure, as assessed by the area under the concentration-time curve. Excretory fluid/plasma area under the concentration-time curve ratios were found to be 1.67 +/- 0.36 for nasal secretions, 0.76 +/- 0.28 for saliva, 0.25 +/- 0.07 for sweat, and 0.23 +/- 0.11 for tears. The elimination half-life of enoxacin from sweat (8.27 +/- 2.63 h) was significantly longer than that for plasma (5.10 +/- 0.46 h). Oxoenoxacin was detected in urine and saliva and exhibited a higher renal clearance and a lower saliva exposure than the parent compound. In contrast to that of the metabolite, distribution of enoxacin in saliva was found to be time and pH dependent. In conclusion, our study revealed considerable differences in the distribution kinetics of enoxacin among various excretory sites. Because of distinct acidic and basic properties, the anionic oxometabolite significantly differs from the zwitterionic parent compound in its distribution characteristics.

Summary In a multicentre study 163 women with acute lower urinary tract infection were treated orally with either 125 mg cefuroxime axetil or 100 mg ofloxacin twice daily for three days. Both antimicrobial agents were generally well tolerated. Four patients in the group treated with cefuroxime axetil and two in the group treated with ofloxacin experienced adverse events. Clinical cure and improvement were registered in 56 of 66 (84.8%) and 59 of 62 (95.2%) of the evaluable patients treated with cefuroxime axetil and ofloxacin, respectively. Seven to nine days after therapy, bacteriuria (CFU<103/ml) had been eliminated in 53 of 66 (80.3%) and 57 of 64 (89.1%) of the evaluable patients receiving cefuroxime axetil and ofloxacin, respectively. The results were not statistically significantly different (P>0.1). Pathogens present at baseline were eliminated by up to an MIC of 16 mg/l of cefuroxime axetil, independent of susceptibility to this agent. There was no difference with regard to efficacy and tolerance between patients treated with cefuroxime axetil and those treated with ofloxacin. On the basis of the MICs of six antimicrobial agents (cefuroxime, ofloxacin, cefadroxil, ampicillin, trimethoprim with and without sulfamethoxazole) determined for the pathogens isolated prior to therapy, resistance rates were lowest for cefuroxime (2.2%) and ofloxacin (3.4%).

Summary In a multicentric study comparing oral single-dose therapy of fosfomycin trometamol (3 g as fosfomycin) versus co-trimoxazole (1.92 g) or ofloxacin (200 mg) as many as possible of the pathogens were sent to and analysed in a central laboratory. The pathogens were identified and minimal inhibitory concentrations (MIC) of fosfomycin, trimethoprim alone and in combination with sulfamethoxazole, ofloxacin, ampicillin, amoxicillin combined with clavulanic acid, and cephadroxil were determined. The eradication of pathogens (cfu < 103/ml at one week after single-dose therapy) was analysed according to species and MIC of the antibiotic used. Urine cultures of 349 patients were analysed.Escherichia coli was the predominating species followed by staphylococci andProteus mirabilis. Enterococci were mostly found in mixed culture. Baseline pathogens of monoinfections were eradicated in 87.1%, in 88.9% and in 86.4% of 284 patients treated with fosfomycin trometamol, co-trimoxazole and ofloxacin, respectively. The MICs of the five antibacterial agents and the two antibiotic combinations for 253 baseline pathogens showed that of theE. coli strains none was resistant to ofloxacin, three (MIC=128 mg/l) were resistant to fosfomycin, 3.6% to co-trimoxazole, 6.2% to trimethoprim, 8.8% to ampicillin, and 5.7% to amoxicillin/clavulanic acid. The eradication rates according to the MICs of the corresponding drugs showed equally good eradication rates for fosfomycin up to an MIC of 64 mg/l. Above this level two out of three strains were also eradicated by fosfomycin trometamol. For co-trimoxazole and ofloxacin no intermediately sensitive or resistant strains were found. Within the range of MICs found there were equally good eradication rates for both antibacterial agents. It was concluded that fosfomycin trometamol, ofloxacin and trimethoprim plus sulfamethoxazole can be used as first line antibiotics for single-dose therapy of acute uncomplicated UTI in female patients.

Summary According to available studies the experience with cefotaxime in the treatment of urinary tract infections (UTI) is presented. Because of its broad spectrum antibacterial activity cefotaxime is active against most of the causative organisms, including multiresistant strains (except enterococci). Of 400 isolates cultured from 400 urological inpatients with complicated and/or hospital acquired UTI 90.2% of the gramnegatives and 87.7% of the staphylococci were inhibited by concentrations of = 8 mg/l. As with other antibiotics in uncomplicated UTI, high cure rates could be achieved by single dose or short-term treatment. According to six non-comparative and nine comparative studies it could be demonstrated that treatment with cefotaxime achieved favorable results in patients with complicated and hospital acquired UTI even if caused by multiresistant strains. In general, in these studies cefotaxime was superior to gentamicin, cefoxitin, cefazolin and cefuroxime, but as effective as other third generation cephalosporins and aztreonam and as the combination of ampicillin and netilmicin. A good tolerance of cefotaxime was reported in all studies.

Zusammenfassung Bei elf Probanden und 39 Patienten, die sich einer transurethralen Resektion der Prostata oder eines Blasentumors unterziehen mußten, wurden Enoxacinkonzentrationen in der Samenflüssigkeit (Probanden), im Prostatasekret (Probanden, Patienten) und im Prostataadenomgewebe (Patienten) nach oraler Gabe von 400 mg bzw. intravenöser Infusion (60 min) von 428 mg Enoxacin gemessen. Gleichzeitig wurde 2,534 g Ioxitalaminsäure intravenös verabreicht, um mögliche Urinkontaminationen zu identifizieren. Die Enoxacinkonzentrationen in der Samenflüssigkeit nach 2–4 h und im Prostataadenomgewebe nach 1–4 h und nach 14–16 h waren mehr als doppelt so hoch wie die Plasmakonzentrationen. Die Prostatasekretkonzentrationen lagen dagegen nach 1–4 h bei etwa der Hälfte der Plasmakonzentrationen. Nach intravenöser Infusion bei 14 Patienten wurden in Intervallen bis zu 24 h venöse Blutproben entnommen, die Plasmakonzentrationen bestimmt und die pharmakokinetischen Parameter berechnet. Die mittlere maximale Plasmakonzentration von Enoxacin lag am Ende der Infusion bei 6,9 mg/l und sank auf 0,5 mg/l nach 12 h. Eine terminale Halbwertszeit von 6,65 h wurde entsprechend einem offenen Zwei-Kompartiment-Modell errechnet.

Zusammenfassung Die Bedeutung pharmakokinetischer Parameter von antimikrobiellen Substanzen für ihren Einsatz in Klinik und Praxis gilt heute als unumstritten. Pharmakokinetische Untersuchungen sind vielfach von gleicher Bedeutung wie die Bestimmung der antimikrobiellen Aktivität, etwa der minimalen Hemmkonzentration. Die Gyrasehemmer (Chinolone) sind hierfür ein gutes Beispiel. In dem vorliegenden Beitrag werden die pharmakokinetischen Eigenschaften sowie die Gewebepenetration von Enoxacin im Vergleich zu anderen wichtigen Gyrasehemmern dargestellt. Die Resorption von Enoxacin ist auch bei gleichzeitiger Nahrungsaufnahme gut. Die für alle Gyrasehemmer beschriebene Resorptionsbeeinflussung bei gleichzeitiger Antazidagabe ist zu beachten. Bei Verabreichung identischer Mengen Enoxacin, Ciprofloxacin oder Norfloxacin erreicht Enoxacin die höheren Plasmaspiegel. Damit gehen auch höhere Gewebespiegel einher, sowohl was die absolute Konzentration anbetrifft als auch die relative Konzentration von Enoxacin im Gewebe im Vergleich zu Plasma. Die Ausscheidung von Enoxacin erfolgt überwiegend über die Niere, etwa 12–15% der Dosis werden in der Leber verstoffwechselt. Da Enoxacin den Abbau anderer Medikamente hemmen kann, muß auf mögliche Interaktionen Rücksicht genommen werden.