[National S3 guideline on uncomplicated urinary tract infection: recommendations for treatment and management of uncomplicated community-acquired bacterial urinary tract infections in adult patients]. / Nationale S3-Leitlinie "Unkomplizierte Harnwegsinfektionen" : Empfehlungen zu Therapie und Management unkomplizierter bakterieller ambulant erworbener Harnwegsinfektionen bei erwachsenen Patienten.

BACKGROUND: Urinary tract infections (UTI) belong to the most frequent bacterial infections in outpatients. Increasing antibiotic resistance rates and a new appreciation of the epidemiological side effects of antibiotics ("collateral damage") have warranted an update of the guidelines on uncomplicated UTI as an S3 clinical guideline. METHODS: The guideline was developed by the Deutsche Gesellschaft für Urologie (DGU) in collaboration with the Deutsche Gesellschaft für Allgemein- und Familienmedizin (DEGAM), Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG), Deutsche Gesellschaft für Hygiene und Mikrobiologie (DGHM), Deutsche Gesellschaft für Infektiologie (DGI), Deutsche Gesellschaft für Nephrologie (DGfN), Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG) and a patient representative. The systematic review of the literature on the topics of the guideline was performed for the time period of 1 January 1998 to 30 April 2008 in the databases of the Cochrane Library and MEDLINE. International guidelines of the years 1999-2007 were included. RESULTS: Uncomplicated UTI comprise uncomplicated cystitis and uncomplicated pyelonephritis. The leading uropathogen is Escherichia coli. The choice of the antibiotic substance follows the five primary aspects: (1) individual patient risk and antibiotic pretreatment; (2) bacterial spectrum and antibiotic susceptibility; (3) effectivity of the antimicrobial substance demonstrated in clinical studies; (4) epidemiological effects ("collateral damage"); and (5) adverse effects. If antibiotics such as trimethoprim/sulfamethoxazole or fluoroquinolones have previously been given, the risk for pathogens to become resistant against these substances is increased. Because of increasing resistance rates of E. coli against trimethoprim/sulfamethoxazole also in uncomplicated UTI, trimethoprim alone or in combination with sulfamethoxazole is no longer regarded as the first-line agent in the empiric treatment of uncomplicated cystitis, unless the regional resistance rate is below 20%. The antibiotic resistance rates of fluoroquinolones in uncomplicated UTI are still below 10% in Germany, but there is a significant emergence of resistance compared to earlier years. Moreover, fluoroquinolones and group 3 cephalosporins exhibit negative epidemiological effects resulting in selection of multi-resistant pathogens. Because these antibiotic classes are needed in therapy of life-threatening infections, such effects should be taken seriously. For substances like fosfomycin, nitrofurantoin or mecillinam"collateral damage" has not been documented or only to a lesser degree. Therefore, for empiric therapy of frequent uncomplicated cystitis fosfomycin-trometamol, nitrofurantoin or pivmecillinam (not listed in Germany) are recommended as first-line antibiotics. For oral first-line treatment of uncomplicated pyelonephritis, fluoroquinolones are still recommended in sufficiently high dosage due to the resistance rates of E. coli still being below 10% and the superior effectivity compared to other antibiotics. Asymptomatic bacteriuria (ASB) should only be treated in exceptional cases such as pregnant women or prior to expected mucocutaneous traumatising interventions of the urinary tract. CONCLUSION: The S3 guideline on uncomplicated urinary tract infections is a comprehensive set of evidence- and consensus-based recommendations dealing with epidemiology, diagnosis, therapy and management of uncomplicated bacterial UTI of adult outpatients. A broad implementation in all disciplines taking care of patients with UTI is necessary in order to ensure a prudent antibiotic policy in these frequent infections and thus improve patient care.

Prevention of preterm birth is possible by vaginal pH screening, early diagnosis of bacterial vaginosis or abnormal vaginal flora and treatment.

Abnormal vaginal flora as well as bacterial vaginosis have a significant relative risk for miscarriage or preterm birth of 1.4-6.9. In the initial Erfurt trial, 0.3% of the neonates with gestational age <32+0 weeks were seen in an intervention group vs. 3.3% (p < 0.01) in the control group; in the larger Thuringia campaign, the figures were 0.94 vs. 1.36% (p < 0.01). The rate of newborns <1,000 g was reduced to 0.38%, the lowest incidence ever seen in any of the German states. This should count even more, as there was no success in reducing the rate of low-birth-weight children in the decades preceding these prospective studies. However, after discontinuation of the campaign in 2000, the preterm birth rates mounted in 2005 in our hospital and the state to the same rate as prior to the programme.

Intravaginally applied metronidazole is as effective as orally applied in the treatment of bacterial vaginosis, but exhibits significantly less side effects.

OBJECTIVE: Metronidazole is the drug of choice for the treatment of bacterial vaginosis (BV). However, so far the oral administration has not been clinically compared to the intravaginal application regarding efficacy, side effects and patient satisfaction in a scientific sound fashion. STUDY DESIGN: Therefore, this randomized, double-blind, placebo-controlled clinical trial was designed to demonstrate non-inferiority of short-term intravaginal (i.vag.) application of metronidazole (2x 1000 mg pessaries 24h apart) vs. a single oral dose (p.o.) of metronidazole (1 x 2000 mg tablets) in 263 patients with BV (double-dummy design). The follow-up period was 12 weeks. In addition, the number and the type of adverse events induced by the two regimens were compared, assuming better tolerability of the intravaginal application. RESULTS: Following the diagnosis of BV a total of 129 women (mean age 36.2 years) was orally treated with a single dose of 2g metronidazole whereas a total of 134 patients (mean age 35.5 years) was treated intravaginally with 1g metronidazole each day on two consecutive days and included in the per-protocol analysis. Non-inferiority of i.vag. application compared to p.o. administration was statistically significant regarding efficacy: Following intravaginal application the cure rate, assessed on day 8 after starting of the treatment, was 92.5% as compared to 89.9% after oral administration. Nausea was the most common adverse event reported in 10.2% i.vag. vs. 30.4% p.o. of all cases (p<0.001), abdominal pain in 16.8% i.vag. vs. 31.9% p.o. (p<0.01), a "metallic taste" in 8.8% i.vag. vs. 17.9% p.o. (p<0.05). Women treated i.vag. were highly satisfied with the treatment and more content as compared to the women treated p.o. with metronidazole (p<0.05, intent-to-treat analysis). CONCLUSION: In this clinical trial the intravaginal application was as effective as the oral administration of metronidazole in treating BV. However, significantly less adverse events were reported after short-term intravaginal as compared to oral application (p=0.023) and probably led to a better patient compliance.

[Gynaecological and obstetrical aspects of recurrent urinary tract infections]. / Rezidivierende Harnweginfektionen aus der Sicht des Frauenarztes.

The microbial colonization of vulva, vagina and cervix uteri represents the reservoir for recurrent urinary tract infection. All bacterial species of normal cutaneous or gastrointestinal flora can be found in the external genital tract even under physiological conditions. The higher concentration of microbes adds to the predisposition for urinary tract infection in cases of dysbiosis or inflammation, apart from specific infection by Trichomonas vaginalis, Neisseria gonorrhoeae or Chlamydia trachomatis. The specific immunological interaction between bacteria and host, i.e. between virulence factors and intrinsic defense, appears to be the major mechanism paving the way for recurrent infection. The elimination of predisposing factors is the clue for successful therapy as well as for prevention of recurrence.

[Therapy of the acute uncomplicated urinary tract infection]. / Therapie der akuten unkomplizierten Harnweginfektion.

Acute uncomplicated cystitis and acute uncomplicated pyelonephritis are two frequently encountered urinary tract infections (UTI) in premenopausal, healthy females. Recent epidemiological investigations showed that the incidence of these infections is higher than expected. Surveys on healthcare practices in North America revealed a high variability in the therapy of uncomplicated UTI. Standardized criteria for diagnosis and therapy of uncomplicated UTIs therefore are important in order to achieve sufficient sensitivity and specificity in clinical practice. The Infectious Diseases Society of America (IDSA) developed evidence-based guidelines for the treatment of acute uncomplicated cystitis and acute uncomplicated pyelonephritis, which were recently updated by other expert groups.

[Recurrent urinary tract infection in women. Long-term antibiotic prophylaxis]. / Rezidivierende Harnwegsinfektionen der Frau. Antibiotische Langzeitprophylaxe.

Urinary tract infections (UTI) are among the most frequent bacterial infections in women. Mostly young women and, to some extent, postmenopausal women are affected by recurrent UTI (rUTI), defined as >or=3 UTI/year. Modifiable predisposing factors are rare. The differential diagnosis between relapse and reinfection is decisive for therapy. Antibiotic prophylaxis has emerged as one of the most important therapeutic principles in rUTI. Depending on the drug utilized, the various modes of action are described as reducing the number of uropathogens in the gut and vaginal flora and/or in repeatedly eliminating bacteria from the urine. According to the European Association of Urology guidelines, nitrofurantoin, trimethoprim, and cotrimoxazole are available as first-line drugs. Cephalexin and the quinolones should be restricted to specific indications. Depending on the case, long-term antibiotic prophylaxis for 6 months, postcoital single dose prophylaxis, or patient-initiated self-start therapy can all be used successfully. Given the correct indications, the recurrence rate of rUTI can be reduced by 95%.

Efficient prematurity prevention is possible by pH-self measurement and immediate therapy of threatening ascending infection.

In two prospective investigations, the effectiveness of the self care programme for prematurity prevention, developed by Saling, was investigated. Pregnant women in Erfurt have been offered to perform self measurements of their vaginal pH by means of test gloves twice a week in order to screen for any disturbances in the vaginal milieu. The women were instructed to see their physician immediately, if abnormal pH > or = 4.7 or other risk factors were present, in order to get them confirmed and to start lactobacillus acidophilus therapy or in case of bacterial vaginosis to treat with clindamycin cream i. vag. Patients who were not interested in the programme served as a control group. Seventy-three out of 381 women in the intervention group have been identified as risk cases. Fifty-eight of them were treated with a lactobacillus preparation, and 24 with clindamycin cream, three patients refused to have any therapy. In this study, the prematurity rate was 8.1% in the self measurement/intervention group versus 12.3% in the control group (P < 0.05, n = 2341). 0.3% versus 3.3% of the neonates belonged to the group of very early prematures with a gestational age of <32 + 0 (P < 0.01). PROM was registered in 22.8% versus 30.8% (P < 0.001), respectively. Starting 1 March 2000, a similar statewide pH screening programme was initiated in order to reduce prematurity in the State of Thuringia. According to the study design, a significant decrease of prematurity was hypothetically expected for the second half of 2000. In Erfurt, an overall decrease of prematurity from 7.68 to 6.81% and a reduction of cases < or = 32 weeks from 3.22 to 2.39% was observed. Premature rupture of membranes was seen in 19 versus 0 pregnancies with early prematurity (n = 1600). Data from 16,276 women are available for the state of Thuringia. On this basis, a significant reduction of early prematurity from 1.58 to 0.99% was seen, respectively (P < 0.001). Comparing low birthweights a significant reduction of cases was achieved as well in all groups. On the basis of the data obtained we recommend the extension of the campaign in whole of Germany.

[Efficient prevention of prematurity - the Thuringian model]. / Effiziente Frühgeburtenvermeidung - Das Thüringer Modell.

In two prospective projects, the effectiveness of the self-care programme for prematurity prevention developed by Saling was prevented. Pregnant women in Erfurt were shown how to perform self-measurements of their vaginal pH by means of test gloves twice a week in order to screen for any disturbances in the vaginal millieu. The women were instructed to see their physician immediately, if abnormal values (ph > or = 4.7) or other risk factors were present, in order to start Lactobacillus acidophilus therapy or, in cases of bacterial vaginosis, treatment with intravaginal clindamycin cream. Patients who were not interested in the programme, served as a control group. 73 out of 381 women in the intervention group were identified as risk cases. In this study, the prematurity rate was 8.1% in the self-measurement/intervention group versus 12.3% in the control group (p < 0.05, n = 2,341); 0.3 versus 3.3% of the neonates belonged to the group of very early prematures with a gestational age of <32 + 0 weeks (p < 0.01). Starting on March 1, 2000, a similar statewide pH screening programme was initiated in order to reduce prematurity in the State of Thuringia. According to the study design, a significant decrease in prematurity was hypothetically expected for the second half of 2000. Data from 16,276 women are available. On this basis, a significant reduction of early prematurity from 1.58 to 0.99% was seen (p < 0.001). Comparing low birth weights, a significant reduction of cases was also achieved in all groups. On the basis of data obtained, we recommend that the campaign should be extended to the whole of Germany. This recommendation is also supported by the observation that after the campaign had been discontinued the prematurity rates monitored in 2002 were as high as they had been prior to the introduction of the statewide programme.

[Current aspects of the Thuringia prematurity prevention campaign 2000]. / Aktuelle Aspekte der Thüringer Frühgeburtenvermeidungsaktion 2000.

In two prospective investigations the effectiveness of the self- care program for prematurity prevention, developed by Saling, was investigated. Pregnant women in Erfurt have been offered to perform self-measurements of their vaginal pH by means of test gloves (Careplan VpH) twice a week. The women were instructed to see their physician immediately, if abnormal values (pH > or = 4.7) or other risk factors were present. 73 out of 381 women in the intervention group have been identified as risk cases. 58 of them were treated with a lactobacillus preparation, and 24 with clindamycin cream for bacterial vaginosis, 3 patients refused to have any therapy. In this study the prematurity rate was 8.1 % in the self-measurement/intervention group vs. 12.3 % in the control group (N=2 341, P < 0.05); 0.3 % vs. 3.3 % of the neonates belonged to the group of early prematures with a gestational age of < 32 + 0 weeks (P < 0.01). PROM was registered in 22.8 % vs. 30.8 % (P < 0.001) respectively. Starting March 1, 2000 a similar statewide pH-screening program was initiated in Thuringia. According to the study design a significant decrease of prematurity was hypothetically expected for the second half of the year 2000. In Erfurt an overall decrease of prematurity from 7.68 to 6.81 % and a reduction of cases < 32 + 0 weeks from 3.22 to 2.39 % was observed (N=1,600). Data from 16,276 women are available for the state of Thuringia. On this basis a significant reduction of early prematurity from 1.58 to 0.99 % was seen respectively (P < 0.001). Comparing low birthweights a significant reduction of cases was achieved as well in all groups. On the basis of the data obtained we recommend the extension of the campaign in the whole of Germany.

Effect of adjuvant imiquimod 5% cream on sustained clearance of anogenital warts following laser treatment.

OBJECTIVES: Imiquimod is an immune response modifier that has demonstrated a good efficacy and relatively low recurrence rates in comparison to other genital wart treatment modalities. The primary objective of this open-label study was to evaluate the effect on sustained clearance of treated lesions and the safety of patient-applied topical imiquimod after laser therapy of external anogenital warts. METHODS: After laser treatment of visible external anogenital warts the ablated region(s) were treated with imiquimod 5% cream three times/week over 12 weeks beginning when the wound healing process was completed, followed by a six-month treatment-free observation period for the assessment of sustained clearance of treated lesions. RESULTS: A total of 211 male and female patients was enrolled in the study. After 12 weeks of treatment, 65.4% of all patients showed sustained clearance. During the treatment period, 15 patients (7.1% of 211 patients) presented with recurrent warts in the treated areas, and 58 (27.5%) patients were excluded for other reasons. During the six-month follow-up period, ten additional patients (7.3% of 138 patients) developed wart recurrences. The application of imiquimod 5% cream was well tolerated. The number of patients with adverse events related to study medication declined from the first month of treatment until the end of the third month. Most frequently, mild to moderate itching, burning, pain and erythema were reported. CONCLUSIONS: After laser therapy and sufficient wound healing, administration of imiquimod 5% cream three times/week appears to be safe and to reduce the incidence of wart recurrences.

Immunotherapy of gynaecological high-risk human papilloma virus infection with human leukocyte ultrafiltrate.

OBJECTIVE: In this preliminary presentation the outcome of women following systemic treatment of cervical human papilloma virus (HPV) with a leukocyte ultrafiltrate is reported. METHODS: Cervical brush specimens of 819 women with low-grade CIN-1 were evaluated for HPV infection. HPV-positive patients were treated either by cone biopsy because of suspicious colposcopy or by antibiotics for symptoms of bacterial cervicitis. The remaining women were considered as asymptomatic carriers of HPV and underwent systemic therapy by a human leukocyte ultrafiltrate in a dosage of 5 IE, 6 times in the first 2 weeks, and additionally as a single dose at weeks 4, 6, 8 and 10. RESULTS: The leukocyte ultrafiltrate was administered to 97 HPV-positive women. In follow-up 88.7% were HPV negative at week 6; the remaining 11 women were tested negative after completion of a second course of therapy. CONCLUSIONS: These preliminary data on the successful treatment of HPV infection by a leukocyte ultrafiltrate are very promising but have to be supported by additional research.

[Initial results of the Erfurt Prevention of Prematurity Campaign]. / Erste Resultate der Erfurter Frühgeburten-Vermeidungs-Aktion.

OBJECTIVES: Genital infection particularly bacterial vaginosis (BV) increases the relative risk of prematurity. Detection of disturbances of vaginal milieu at an early stage and the use of suitable countermeasures such as intervention with antimicrobial substances, e.g. clindamycin, can reduce the preterm birth rate, provided the diagnosis is made early enough. STUDY DESIGN: Since October 1996 pregnant women being given prenatal care in 16 of the 29 outpatient offices in Erfurt, have been informed about the Prematurity Prevention Programme and have been offered to take part and to perform self-measurements of their vaginal pH twice a week in order to screen for any disturbances in the vaginal milieu. Special CarePlan-VpH gloves (Selfcare, Oberhaching) were used to identify patients a risk (pH > 4.7). The pregnant women taking part in the programme were instructed to see their physician immediately, if abnormal values were present, in order to get them confirmed and to start lactobacillus acidophilus therapy (Gynoflor, Nourypharma, Oberschleissheim) or, in case of BV, to treat with clindamycin cream (Sobelin, Upjohn, Erlangen) i.vag. Patients being given prenatal care in the 13 outpatient offices not participating and other pregnant women in Erfurt who were not interested in the programme served as control group. RESULTS: Up to now 59 out of 314 women in the intervention group have been identified as risk cases (p > or = 4.7). 52 of them were treated with a lactobacillus preparation, and 19 additionally with clindamycin cream, 3 patients refused to have any therapy. In this ongoing study the prematurity rate was 8.3% in the self-measurement/intervention group vs. 13.0% in the control group (n = 1,842); 0.3% vs. 3.3% of the neonates belonged to the group of very early prematures with a gestational age of < 32 + 0 weeks (p < 0.01). PROM was registered in 22.3% vs. 32.1% (p < 0.001) respectively. CONCLUSION: Self-measurement of vaginal pH at close intervals, as recommended by Saling, leads to the early identification of women at risk for prematurity. Earliest possible intervention by the obstetrician appears to result in reducing the rate of prematures and in particular of very early prematures (< 32 + 0 weeks).

[Perioperative antibiotic prophylaxis in breast surgery: cefotiam versus clindamycin]. / Perioperative Antibiotikaprophylaxe in der Mammachirurgie: Cefotiam versus Clindamycin.

97 patients undergoing breast surgery received either 2 g cefotiam or 1200 mg clindamycin as i.v. singleshot application in the course of an open randomised comparison of parallel groups to evaluate the efficacy and tolerability of both antibiotic regimens. Both regimens proved to be well to-lerated and equally suitable for the prophylaxis of postoperative infections in breast surgery.

[Urogenital infections caused by sexually transmitted pathogens from the gynecologic viewpoint]. / Urogenitale Infektionen durch sexuell übertragene Erreger aus gynäkologischer Sicht.

In this review the diagnosis, complications and treatment of female genital tract infections are discussed with special reference to the syndromes of candidiasis and bacterial vaginosis, which are precipitated by sexual intercourse, and to the sexually transmitted diseases gonorrhea, chlamydial infection, trichomoniasis, and HSV and HPV infection.

[Erosion of the uterine artery--an unusual late complication 19 weeks after Cesarean section]. / Arrosion der A. uterina--eine ungewöhnliche Spätkomplikation 19 Wochen nach Sectio caesarea.

In a 30-year old para I, following uncomplicated Caesarean section in late pregnancy, recurrent haemorrhage occurred, which finally peaked as an arterial mass bleeding. The diagnosis of an arrosion of a large branch of the uterine artery was made by clinical and sonographic means. Therapy consisted in operative revision of the uterotomy and the uterus is saved. The possible causes of bleeding in the late puerperium are discussed.

Sexually transmitted diseases in adult, non-pregnant women.

Most of the publications reviewed focus on human papillomavirus (HPV), and a small proportion on herpes simplex virus (HSV), Chlamydia trachomatis, as well as the syndromes of pelvic inflammatory disease and bacterial vaginosis. The present hypothesis associates cervical intraepithelial neoplasia (CIN)-1 with high oncogenic risk HPV types in less than 30% of cases; whereby CIN-2 and CIN-3 are associated with a 90% risk. However, on the basis of HPV types, four categories ['low risk' (HPV 6/11, 42, 43, 44); 'intermediate risk' (HPV 31, 33, 35, 51, 52, 58); 'high risk/HPV 16'; and 'high risk/HPV 18'] for the associated risk for a high-grade lesion or an invasive cancer can also be defined. In practice it appears efficient to re-evaluate patients with oncogenic types in association with low-grade cytology, as well as women with high-grade cytology or suspicious colposcopy in narrow intervals. Several reports have suggested that HPV genital infections are multifocal; however, HPV DNA was also found in the lymph nodes and in the granulocytes of women with cervical cancer, in ovarian and endometrial tissue, in tumours of the urinary bladder, and in mammary ductal carcinoma.