Kurt G. Naber

Urinary Concentrations and Antibacterial Activities of Nitroxoline at 250 Milligrams versus Trimethoprim at 200 Milligrams against Uropathogens in Healthy Volunteers

ABSTRACT Because of the increasing bacterial resistance of uropathogens against standard antibiotics, such as trimethoprim (TMP), older antimicrobial drugs, such as nitroxoline (NTX), should be reevaluated. This randomized crossover study investigated the urinary concentrations of parent drugs and their metabolites and their antibacterial activities (urinary inhibitory titers [UITs] and urinary bactericidal titers [UBTs]) against uropathogens at three different urinary pH values within 24 h in six healthy volunteers after a single oral dose of NTX at 250 mg versus TMP at 200 mg. In three additional volunteers, urinary bactericidal kinetics (UBK) were studied after oral administration of NTX at 250 mg three times a day. The mean urinary concentrations of NTX and NTX sulfate in 24 h were 0.012 to 0.507 mg/liter and 0.28 to 27.83 mg/liter, respectively. The mean urinary concentrations of TMP were 18.79 to 41.59 mg/liter. The antibacterial activity of NTX was higher in acidic urine than in alkaline urine, and that of TMP was higher in alkaline urine than in acidic urine. The UITs and UBTs of NTX were generally lower than those of TMP except for a TMP-resistant Escherichia coli strain, for which NTX showed higher UITs/UBTs than did TMP. UBK showed mainly bacteriostatic activity of NTX in urine. NTX exhibits mainly bacteriostatic activity and TMP also shows bactericidal activity in urine against susceptible strains. NTX is a more active antibacterial in acidic urine, and TMP is more active in alkaline urine. The cumulative effects of multiple doses or inhibition of bacterial adherence could not be evaluated. (This study has been registered at EudraCT under registration no. 2009-015631-32.)

Antibiotikaprophylaxe in der Urologie

ZusammenfassungDas Ziel der perioperativen Antibiotikaprophylaxe ist die Vermeidung von postoperativen Gewebeinfektionen sowie bei urologischen Prozeduren auch die Vermeidung von Harnwegsinfektionen. Die Indikation für eine antibiotische Prophylaxe orientiert sich an einer Reihe von Risikofaktoren, wie dem Grad der potenziellen Kontamination des Operationsfelds, einer verlängerten Operationsdauer, Fremdkörperimplantationen oder Komorbiditäten des einzelnen Patienten, und umfasst in der Regel eine einmalige antibiotische Gabe rechtzeitig vor dem operativen Eingriff. Die Antibiotikaprophylaxe trägt zum Gesamtantibiotikaverbrauch und damit zur Antibiotikaresistenzentstehung bei. Sie kann die Hygiene und operative Sorgfalt eines Eingriffs nicht ersetzen.AbstractThe aim of perioperative antibiotic prophylaxis is the prevention of surgical site infections and urinary tract infections during urological procedures. The indication for antibiotic prophylaxis comprises several risk factors such as the degree of contamination of the operative site, duration of surgery, implantation of devices and comorbidities of the individual patient. In general this involves a single antibiotic administration before the operative procedure. The antibiotic prophylaxis is part of the total antibiotic consumption and thus a factor contributing to emergence of antibiotic resistance. It is not a substitute for hygiene measures or operative precision.

German validation of the Acute Cystitis Symptom Score

BACKGROUND The Uzbek version of the Acute Cystitis Symptom Score (ACSS) was developed as a simple self-reporting questionnaire to improve diagnosis and therapy of women with acute cystitis (AC). The purpose of this work was to validate the ACSS in the German language. MATERIALS AND METHODS The ACSS consists of 18 questions in four subscales: (1) typical symptoms, (2) differential diagnosis, (3) quality of life, and (4) additional circumstances. Translation of the ACSS into German was performed according to international guidelines. For the validation process 36 German-speaking women (age: 18-90 years), with and without symptoms of AC, were included in the study. Classification of participants into two groups (patients or controls) was based on the presence or absence of typical symptoms and significant bacteriuria (≥ 10(3) CFU/ml). Statistical evaluations of reliability, validity, and predictive ability were performed. ROC curve analysis was performed to assess sensitivity and specificity of ACSS and its subscales. The Mann-Whitneys U test and t-test were used to compare the scores of the groups. RESULTS Of the 36 German-speaking women (age: 40 ± 19 years), 19 were diagnosed with AC (patient group), while 17 women served as controls. Cronbachs α for the German ACSS total scale was 0.87. A threshold score of ≥ 6 points in category 1 (typical symptoms) significantly predicted AC (sensitivity 94.7%, specificity 82.4%). There were no significant differences in ACSS scores in patients and controls compared to the original Uzbek version of the ACSS. CONCLUSION The German version of the ACSS showed a high reliability and validity. Therefore, the German version of the ACSS can be reliably used in clinical practice and research for diagnosis and therapeutic monitoring of patients suffering from AC.

192 Urinary antibacterial activity of nitroxolin 250 mg versus trimethoprim 200 mg against uropathogens after single oral administration

MATERIAL & METHODS: In this phase 1, monocenter, prospectively randomized study the urinary antibacterial activity of NTX 250mg versus TMP 200mg against uropathogens was investigated after single dose in 6 healthy volunteers in a cross-over design using three different urine pH (native urine, urine adjusted to acid (pH 5.5) and alkaline (pH 8.0) milieu). Urine was collected before and after oral administration of the drugs in intervals: 0,0-4, 4-8, 812, 12-24 h. The urinary inhibitory (UIT) and urinary bactericidal titer (UBT) against 5 uropathogenic bacterial strains (E. coli TMP susceptible, E. coli TMP resistant, K. pneumoniae, P. mirabilis and S. saprophyticus) and a test strain (E. coli ATCC 25922) were determined. In 3 additional volunteers, the urinary bactericidal kinetics (UBK) were studied on the 3rd/4th day after oral administration of NTX 250mg t.i.d.

Mikrobiologische Verfahren und Untersuchungen

Bei den mikroskopischen Untersuchungen unterscheiden wir zwischen der Mikroskopie des Nativmaterials, z.B. mittels Dunkelfeld- oder Phasenkontrastverfahren (Abb. 13), und der mikroskopischen Betrachtung des gefarbten Praparats. Fur eine Ubersichtsfarbung bietet sich Loffler-Methylenblau an, wahrend die Farbung nach Gram bereits eine Differenzierung der verschiedensten Erreger in grampositiv und gramnegative Mikroorganismen gestattet (s. Abb. 11). Abhangig von der Aussage, die man zu erhalten wunscht, ist entweder das eine oder andere Verfahren anzuwenden bzw. die Ubersichtsfarbung durch Spezialfarbungen zu erganzen (s. Abschn. 5.1.2). So ist z.B. eine Trichomoniasis nur anhand der typischen Beweglichkeit unmittelbar nach Probengewinnung durch eine Dunkelfeld- oder Phasenkontrastuntersuchung abzuklaren (s. Kap. 3, Abb. 4). Die Differentialdiagnose zwischen einer gonorrhoischen und nichtgonorrhoischen Urethritis ist durchaus primar mit dem Methylenblaupraparat zu treffen.

Bakteriurie nach radikaler Prostatektomie – Stellenwert der Keimzahl

MATERIAL AND METHODS 100 consecutive cases after radical prostatectomy with a bacterial count of 10(4) CFU/ml in midstream urine were followed during urological inpatient rehabilitation without antibiotic treatment. Before discharge, a follow-up examination with a urine dipstick and a second urine culture were performed. RESULTS No symptomatic urinary tract infections (UTI) occurred during the average follow-up period of 15.2 days. Patients with unremarkable urine dipstick findings at follow-up (no leukocyturia and no haematuria and no nitrituria) had no relevant bacteriuria (≥10(5) CFU/ml).54 of urine culture controls before discharge were negative, 31 showed insignificant bacterial growth (≤10(4) CFU/ml) and 15 had a bacterial count≥10(5) CFU/ml. 4 patients (27%) with > 10(5) CFU/ml were successfully treated with antibiotics for clear signs of infection (fever, chills, leukocytosis); the other 11 patients were just followed further. CONCLUSIONS Even though almost all patients after radical prostatectomy continue to suffer from some discomfort that might be due to UTI, patients with 10(4) CFU/ml in midstream urine samples should not receive antibiotic treatment unless they have clear systemic symptoms of an infection, e. g. fever, chills or leukocytosis. Unremarkable urine dipstick findings during the follow-up period (no leukocyturia and no erythrocyturia and no nitrituria) rule out a relevant bacteriuria (≥10(5) CFU/ml). Clear systemic signs of infection during follow-up only occurred in 4 patients, who were successfully treated with test-adapted antibiotics.

Deutsche Validierung des „Acute Cystitis Symptom Score“@@@German validation of the Acute Cystitis Symptom Score

BACKGROUND The Uzbek version of the Acute Cystitis Symptom Score (ACSS) was developed as a simple self-reporting questionnaire to improve diagnosis and therapy of women with acute cystitis (AC). The purpose of this work was to validate the ACSS in the German language. MATERIALS AND METHODS The ACSS consists of 18 questions in four subscales: (1) typical symptoms, (2) differential diagnosis, (3) quality of life, and (4) additional circumstances. Translation of the ACSS into German was performed according to international guidelines. For the validation process 36 German-speaking women (age: 18-90 years), with and without symptoms of AC, were included in the study. Classification of participants into two groups (patients or controls) was based on the presence or absence of typical symptoms and significant bacteriuria (≥ 10(3) CFU/ml). Statistical evaluations of reliability, validity, and predictive ability were performed. ROC curve analysis was performed to assess sensitivity and specificity of ACSS and its subscales. The Mann-Whitneys U test and t-test were used to compare the scores of the groups. RESULTS Of the 36 German-speaking women (age: 40 ± 19 years), 19 were diagnosed with AC (patient group), while 17 women served as controls. Cronbachs α for the German ACSS total scale was 0.87. A threshold score of ≥ 6 points in category 1 (typical symptoms) significantly predicted AC (sensitivity 94.7%, specificity 82.4%). There were no significant differences in ACSS scores in patients and controls compared to the original Uzbek version of the ACSS. CONCLUSION The German version of the ACSS showed a high reliability and validity. Therefore, the German version of the ACSS can be reliably used in clinical practice and research for diagnosis and therapeutic monitoring of patients suffering from AC.

Antibiotikaprophylaxe in der Urologie@@@Antibiotic prophylaxis in urology

ZusammenfassungDas Ziel der perioperativen Antibiotikaprophylaxe ist die Vermeidung von postoperativen Gewebeinfektionen sowie bei urologischen Prozeduren auch die Vermeidung von Harnwegsinfektionen. Die Indikation für eine antibiotische Prophylaxe orientiert sich an einer Reihe von Risikofaktoren, wie dem Grad der potenziellen Kontamination des Operationsfelds, einer verlängerten Operationsdauer, Fremdkörperimplantationen oder Komorbiditäten des einzelnen Patienten, und umfasst in der Regel eine einmalige antibiotische Gabe rechtzeitig vor dem operativen Eingriff. Die Antibiotikaprophylaxe trägt zum Gesamtantibiotikaverbrauch und damit zur Antibiotikaresistenzentstehung bei. Sie kann die Hygiene und operative Sorgfalt eines Eingriffs nicht ersetzen.AbstractThe aim of perioperative antibiotic prophylaxis is the prevention of surgical site infections and urinary tract infections during urological procedures. The indication for antibiotic prophylaxis comprises several risk factors such as the degree of contamination of the operative site, duration of surgery, implantation of devices and comorbidities of the individual patient. In general this involves a single antibiotic administration before the operative procedure. The antibiotic prophylaxis is part of the total antibiotic consumption and thus a factor contributing to emergence of antibiotic resistance. It is not a substitute for hygiene measures or operative precision.

O35 Empiric antibiotic prescription: does it always hit susceptible microorganisms?

the slope of the regression line between corrected AUC0 24 and ABW was 0.0271. Conclusions: This study reveals that AUC0 24 acts independently of body weight, as our simulations were able to achieve the same AUC0 24 for each patient regardless weight. This is not the case for V, which demonstrated a positive relationship with weight. Unlike dosing based on V, AUC0 24 based dosing would eliminate the need to stratify patients based on weight as well as the need to choose an appropriate correction factor.

Interne und externe Qualitätskontrolle

Zur Uberprufung der eigenen Arbeit sind regelmasig typisierte Stamme (z.B. Staphylococcus aureus ATCC 29213, E. coli ATCC 25922, E. faecalis ATCC 29212 und P. aeruginosa ATCC 27853) zur Erregerdifferenzierung und Resistenzprufung mitzufuhren.