Prospective multicentre randomized double-blind placebo-controlled parallel group study on the efficacy and tolerability of StroVac® in patients with recurrent symptomatic uncomplicated bacterial urinary tract infections.

PURPOSE: To evaluate efficacy and safety of vaccination with StroVac compared to placebo in patients with recurrent urinary tract infections (rUTI). MATERIAL AND METHODS: We performed a prospective, double-blinded, placebo-controlled study in patients with uncomplicated rUTI. Patients received three single intramuscular injections with StroVac every two weeks. Primary endpoint was the number of bacterial urinary tract infections (UTI) over 13.5 months after randomization and adjusted by the respective "baseline" value when comparing verum and placebo group. Secondary endpoints were the number of patients with non-recurrence, time to first recurrence, frequency of recurrences, and patients' self-assessment of quality of life using a validated questionnaire. RESULTS: 376 patients were randomized to both groups between January 2012 and March 2015. Mean age was 44.4 years. Patients were mainly female (98.4%). In the StroVac group (n = 188), the number of UTIs was reduced from 5.5 to 1.2, in the placebo group (n = 188) from 5.4 to 1.3 (p = 0.63). In patients with ≥ 7 UTIs prior to study inclusion, StroVac was statistically significantly superior to placebo (p = 0.048). However, in all other secondary endpoints, no statistical differences between the two groups could be seen (all p > 0.3). CONCLUSION: StroVac reduced the number of clinically relevant UTIs like in former studies but did not show statistically significant better results than the chosen placebo. Most likely, that was due to a, since confirmed, prophylactic effect of the chosen placebo itself. Therefore, placebo-controlled and double-blinded studies using a different ineffective placebo preparation are needed to determine the importance of StroVac in prophylaxis of rUTI.

[Management of multiresistant bacteria in urology]. / Management multiresistenter Erreger in der Urologie.

Contamination and infection with extensive drug resistant (XDR) bacteria are increasing in urology with the exception of methicillin resistant Staphylococcus aureus (MRSA) (stabilization). They often lead to logistic and therapeutical problems. Only 30-50% of XDR cases are of exogenous origin. To slow this trend, screening, hygiene programs, isolation, decontamination, targeted therapy of symptomatic infections, education programs, and success controls should be applied. Furthermore, all regulatory and legal instructions should be followed. Local hygiene networks help to find apt measures for XDR control. It is important to balance hygiene measures against hygiene hysteria. To prepare urological instruments, a local instrument preparation plan that takes into consideration all legal instructions should be followed. The efforts in health system general prophylactic measures should be supported. Only with consistent implementation in all areas of daily life (health care, local environment, animal husbandry, and soil contaminated within the framework of animal husbandry) can a substantial reduction of XDR bacteria be achieved in the long term.

[Bacteriuria after Radical Prostatectomy: Importance of Bacterial Count]. / 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.

In-vitro activity of polyhexanide alone and in combination with antibiotics against Staphylococcus aureus.

BACKGROUND: The resistance of Staphylococcus aureus is increasing, not only to antibiotics but also to antiseptics. AIM: To investigate the activity of the antiseptic polyhexanide and several antibiotics against clinical isolates of meticillin-susceptible and meticillin-resistant Staphylococcus aureus (MSSA and MRSA, respectively). Polyhexanide was tested alone and in combination with oxacillin, penicillin G, ampicillin, cefazolin, cefuroxime, imipenem, gentamicin, erythromycin, doxycycline, levoflocaxin, linezolid and vancomycin. METHODS: Fifty MSSA and 50 MRSA strains, including one vancomycin-intermediate (VISA) strain, were tested. All strains were typed by pulsed-field gel electrophoresis (PFGE) to exclude testing of clonal isolates. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined using the serial broth microdilution technique according to DIN 58940. Combinations of polyhexanide and different antibiotics were investigated using the checkerboard technique. FINDINGS: Polyhexanide MICs and MBCs in the range of 0.5-2mg/L were found for both MSSA and MRSA, and the VISA strain had MIC and MBC values of 2mg/L. All isolates were regarded as susceptible to polyhexanide, and no antagonism was observed between polyhexanide and the tested antibiotics. Synergism between polyhexanide and some bacteriostatic antibiotics (erythromycin, doxycycline and linezolid) was found for some strains. CONCLUSIONS: Polyhexanide appears to be suitable for the topical treatment of S. aureus alone and in combination with antibiotics.

[Prostatitis - diagnostics and therapy]. / Prostatitis: Diagnostik und Therapie.

The prostatitis syndrome is a frequent and complex disease. During the last 40 years the scientific perception has shifted between sometimes success and sometimes disappointment. Whereas acute prostatitis is most frequently considered an infectious disease, in only about 10% of cases with a chronic prostatitis syndrome can pathogens be identified. The bacterial spectrum is similar to that of complicated urinary tract infections with mainly Gram-negative pathogens. In some studies atypical pathogens, such as Chlamydia trachomatis and mycoplasmas, can be found in a considerable proportion. In most cases, however, a multifactorial aetiology is discussed. This has lead to a phenotyping directed multimodal treatment approach, considering the main symptoms. In prostatitis of microbial origin antibiotics, particulary fluorquinolones, are still the therapy of first choice. In the other cases multimodal treatment strategies are used considering evidence-based monotherapeutic studies. The evidence for multimodal combination treatment is still sparse.

Activity of the antiseptic polyhexanide against meticillin-susceptible and meticillin-resistant Staphylococcus aureus.

Staphylococcus aureus is one of the most important pathogens, with increasing emergence of meticillin-resistant S. aureus (MRSA) strains. This is associated not only with multiresistance to antibiotics but also with increasing resistance to topical antibiotics and antiseptics. As the antiseptic polyhexanide has only a low risk of emergence of resistant strains, the aim of the study was to obtain data on the sensitivity of S. aureus towards polyhexanide. The effect of polyhexanide was tested against 80 meticillin-susceptible S. aureus (MSSA) and 80 MRSA strains from sporadic cases as well as against 6 MRSA outbreak strains. The clonal diversity of the 166 strains was proven by pulsed-field gel electrophoresis (PFGE). Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined by the serial broth microdilution technique according to DIN 58940. Time-kill studies were performed for reference strains MSSA ATCC 29213 and MRSA ATCC 33591. MICs and MBCs in the range of 0.5-2mg/L were found. According to a created epidemiological cut-off (ECOFF) value of 4mg/L, all strains were regarded as susceptible to polyhexanide, including MRSA epidemic strains and MSSA and MRSA sporadic strains with various antibiotic susceptibility patterns. Addition of up to 4% albumin to the test medium did not change the MICs and MBCs. Time-kill studies showed reduction rates of 4log10CFU/mL for 200mg/L and 5log10CFU/mL for 400mg/L polyhexanide within 5-30min. It is concluded that polyhexanide is suitable for topical eradication of S. aureus.

Isolation and purification of chiamydospores of Candida albicans.

Two methods were investigated for their efficiency in isolating and purifying chlamydospores of Candida albicans. Chlamydospores were disconnected from pseudomycelial cells either enzymatically using beta-glucuronidase or mechanically by ultrasonic treatment. Free chlamydospores were separated from other cell material by sucrose gradient centrifugation. The resulting preparations were inspected by light-microscopy and electron-microscopy. Both methods yielded preparations with a level of over 90% chlamydospore cells. Ultrasonic treatment caused little change to the ultrastructure of the chlamydospores, whereas the enzyme treatment profoundly affected the cell wall. It is concluded that ultrasonic treatment is an efficient method for obtaining pure preparations of chlamydospores.

[Effectiveness of an improved antiseptic in treatment of contaminated soft tissue wounds]. / Wirksamkeit eines neuartigen Antisepticum in der Behandlung kontaminierter Weichteilwunden.

A novel antiseptic biguanide has been shown to be more bactericidal and tissue compatible in vitro than other antiseptics. In our controlled, prospective and randomized double-blind study on patients with bacteria-contaminated wound types 2-4, one group (n = 45) was treated with humid cotton swab dressings of 0.2% Lavasept solution compared with Ringer solution (n = 35). No deterioration of wound healing was observed in either group. Lavasept treatment resulted in faster and significant reduction of gram-positive germs. The tissue compatibility of Lavasept was evaluated as significantly better than Ringer solution.

Preparation and activity of some novel organo-metallic complexes against Helicobacter pylori.

Some novel organo-metallic complexes were prepared by complexing the antibiotics erythromycin (CAS 114-07-8), doxycycline (CAS 564-25-0), ciprofloxacin (CAS 85721-33-1) and amoxicillin (CAS 26787-78-0) with bismuth citrate and their antibacterial activity against Helicobacter pylori and other micro-organisms were investigated. Amoxicillin-bismuth citrate had the strongest activity against H. pylori with a lowest minimum inhibitory concentration of 0.007 mg/l. The complexes exhibited moderate activity against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Bacillus subtilis. The findings suggest that the activity of these organo-metallic complexes might be specifically directed against H. pylori.

Antibacterial activity of East African medicinal plants.

In an ethnopharmacological survey, extracts of the six East African medicinal plants Entada abyssinica (stem bark), Terminalia spinosa (young branches), Harrisonia abyssinica (roots), Ximenia caffra (roots), Azadirachta indica (stem bark and leaves), and Spilanthes mauritiana (roots and flowers) were tested against 105 strains of bacteria from seven genera (Staphylococcus, Enterococcus, Pseudomonas, Escherichia, Klebsiella, Salmonella, Mycobacterium). The minimum inhibitory concentration reached by 50% (MIC50%) and 90% (MIC90) of the strains for the extracts of E. abyssinica, T. spinosa, X. caffra, and A. indica (stem bark) ranged from 0.13-8 mg/ml and from 0.5 to > 8 mg/ml, respectively. Their minimum bactericidal concentration by 50% (MBC50%) and MBC90% were all between 0.5 and > 8 mg/ml. H. abyssinica, A. indica (leaves), and S. mauritiana (roots and flowers) had MIC and MBC values > or = 8 mg/ml. Mycobacteria were not inhibited at extract concentrations of 0.5-2 mg/ml. It is concluded that plant extracts with low MIC and MBC values may serve as sources for compounds with therapeutic potency.

Activity of east African medicinal plants against Helicobacter pylori.

The activity of extracts from the East African medicinal plants Entada abyssinica (stem bark), Terminalia spinosa (young branches), Harrisonia abyssinica (roots), Ximenia caffra (roots), Azadirachta indica (leaves and stem bark) and Spilanthes mauritiana (roots and flowers) were evaluated against 12 strains of Helicobacter pylori. The most active extracts were those derived from T. spinosa with an MIC50 of 125 micrograms/ml, an MIC90 of 250 micrograms/ml and an MIC range of 62.5-500 micrograms/ml. An MIC50 of 250 micrograms/ml and an MIC90 of > 4,000 micrograms/ml was reached by H. abyssinica with a range of 125-->4,000 micrograms/ml and by X. caffra with a range of 62.5-->4,000 micrograms/ml, respectively. It is concluded that these plants contain compounds with antimicrobial activity against H. pylori.

Susceptibility of Helicobacter pylori and Candida spp. to the east African plant Terminalia spinosa.

Trees of the genus Terminalia have long been used in the traditional medicine of Kenya (East Africa). In an ethnopharmacological approach, extracts of the stem bark of Terminalia spinosa were investigated for antibacterial and antifungal activity. The extracts were active against Helicobacter pylori, with the following minimum inhibitory concentrations (MIC): MIC50 of 125 mg/l, MIC90 of 250 mg/l, and MIC-range of 62.5-500 mg/l. Yeasts of the genus Candida showed a similar susceptibility. The results indicate that the plant if a source of antimicrobial compounds with therapeutic potential.

Comparison of the E test and a proportion dilution method for susceptibility testing of Mycobacterium avium complex.

The newly developed E test was compared with an extended 1% proportion dilution method for determining the susceptibility of Mycobacterium avium complex (MAC) strains to amikacin, streptomycin, fusidic acid, rifampicin, clarithromycin, ciprofloxacin, ofloxacin and fleroxacin. For all antibiotics tested except clarithromycin and ciprofloxacin, no more than one strain gave a different susceptibility result with the two methods. The discrepant results occurred near the chosen breakpoint concentration of clarithromycin and outside the concentration range of the E test for ciprofloxacin. For the minimum inhibitory concentration (MIC) values obtained within the range of antibiotic concentrations tested, there was good correlation between the two methods; the MICs differed by more than one two-fold dilution in no more than two strains per antibiotic. It is concluded that the E test is suitable for susceptibility testing of MAC.

Fungistatic and fungicidal activity of east African medicinal plants.

Extracts of the traditionally used medicinal plants Entada abyssinica (stem bark), Terminalia spinosa (young branches), Harrisonia abyssinica (roots), Ximenia caffra (roots), Azadirachta indica (stem bark), Zanha africana (stem bark) and Spilanthes mauritiana (roots and flowers) were investigated for fungistatic and fungicidal activity against Candida spp. and Aspergillus spp. by a microtitre serial dilution technique. Entada abyssinica, T. spinosa, X. caffra, A. indica, and Z. africana showed activity against various Candida species. The minimum inhibitory concentrations (MICs) ranged from 0.006 to > 8 mg ml-1 and the minimum fungicidal concentrations (MFCs) from 0.06 to > 8 mg ml-1. Extracts from S. mauritiana (both roots and flowers) exhibited no activity against Candida spp., but against Aspergillus spp., the MIC and MFC values ranged from 0.13 to 0.25 mg ml-1 and from 0.13 to 1 mg ml-1 respectively. It is concluded that the extracts contain compounds with high antifungal potency.

Comparison of the E test and a proportion dilution method for susceptibility testing of Mycobacterium tuberculosis.

Minimal inhibitory concentrations (MICs) of amikacin, streptomycin, fusidic acid, rifampicin, clarithromycin, ciprofloxacin, ofloxacin, and fleroxacin were determined by the E test for 20 strains of Mycobacterium tuberculosis. The resulting discrimination in resistant or sensitive strains was compared with the results of an extended proportion dilution method. There were no more than three strains per antibiotic with different ratings with the exception of ciprofloxacin and ofloxacin. In these discrepant cases, the breakpoint concentrations had a position at the top of the test strip, which may be unfavourable for MIC reading. The MICs of streptomycin (1-2 mg/l) and rifampicin (2-4 mg/l) for the control strain M. tuberculosis H37Rv (ATCC 27,294) were close to the reference values according to the German standard DIN 58,943. It is concluded that the E test is suitable for susceptibility testing of slowly growing M. tuberculosis isolates.

Comparison of the E test and a proportion dilution method for susceptibility testing of Mycobacterium kansasii.

The newly developed E test was compared with a conventional proportion dilution method for determining the sensitivity of Mycobacterium kansasii to amikacin, streptomycin, fusidic acid, rifampicin, clarithromycin, ciprofloxacin, ofloxacin, and fleroxacin. There was no more than one strain with different rating, except for ciprofloxacin. In this case, the breakpoint concentration had an unfavourable position at the top of the strip, and susceptible isolates in the dilution test were defined resistant in the E test. It is concluded that the E test is suitable for testing slowly growing mycobacteria other than tubercle bacilli, and may replace the more laborious dilution methods, particularly for testing M. kansasii.

[Amebic liver abscess with hepatobronchial fistula]. / Amöbenabszess der Leber mit hepatobronchialer Fistel.

Four weeks after a holiday in Kenya a 57-year-old woman developed a fever up to 40 degrees C, right upper abdominal pain, icteric sclerae, nausea and vomiting. Laboratory tests revealed leukocytosis (24,400/microliters), markedly accelerated erythrocyte sedimentation rate (123 mm/h) and moderately increased activity of liver enzymes in serum. The liver was unremarkable on ultrasound. Four days after hospitalization the patient complained of dyspnoea and pleuritic pain. Ultrasound examination and computed tomography showed an abscess in the right lobe of the liver. Amoebic abscess of the liver being the most likely diagnosis, although the relevant serological tests were unremarkable and a titre increase occurred only later, treatment was started with metronidazole (four times 500 mg daily intravenously) and paromomycin (three times 10 mg/kg daily). Her condition significantly improved within a day. Two weeks later, however, she developed chest pain, dyspnoea and cough productive of large amounts of white-yellow sputum, even though antibiotic treatment was continuing. A transdiaphragmatic rupture of the abscess with formation of a hepatobronchial fistula proved to be the cause of these symptoms. The patient was treated surgically by drainage and suturing-over of the extensive diaphragmatic defect and after 2 weeks she was discharged symptom-free on a maintenance dose of diloxanide furoate (three times 500 mg/d orally).