[Nonviral sexually transmitted infections-epidemiology, clinical manifestations, diagnostic workup, therapy : Part 3: Treponemes, Gardnerella and trichomonads]. / Nichtvirale sexuell übertragene Infektionen ­ Epidemiologie, Klinik, Labordiagnostik und Therapie : Teil 3: Treponemen, Gardnerella und Trichomonaden.

In Germany, the reported syphilis prevalence has increased continuously since 2010, with a total of 6834 syphilis cases being reported in 2015. The largest increase of reported syphilis occurred in men who have sex with men (MSM). The antibiotic agent of choice for treatment of syphilis is still penicillin. There are no penicillin-resistant Treponema pallidum strains. Alternatives are ceftriaxone and doxycycline. In Germany, azithromycin is not approved for treatment of syphilis; however, therapy failures are increasingly reported. Bacterial vaginosis is accompanied by vaginal discharge. The vaginal secretion exhibits an increased pH value higher than 4.5. Clinical symptoms are pruritus, burning, and the characteristic amine odor. The probability for bacterial vaginosis is highest in women with higher numbers of sexual partners, unmarried women, early first sexual intercourse, in commercial female sex workers, and those women who regularly apply vaginal douches. The main pathogen of bacterial vaginosis is Gardnerella vaginalis. For oral therapy metronidazole is given, alternatively clindamycin; the latter should be applied additionally as topical agent. Trichomoniasis is considered as the nonviral sexually transmitted infection with the highest prevalence worldwide. Other than direct microscopic detection of the protozoa (trophozoites) in vaginal secretion or urine, PCR has been approved as the diagnostic method with the highest sensitivity. Oral metronidazole represents the therapy of choice in trichomoniasis.

[Non-viral sexually transmitted infections - Epidemiology, clinical manifestations, diagnostics and therapy : Part 1: Gonococci]. / Nichtvirale sexuell übertragene Infektionen ­ Epidemiologie, Klinik, Labordiagnostik und Therapie : Teil 1: Gonokokken.

Approximately 1 million people are infected per day worldwide by one or more sexually transmitted infections (STI) as estimated by the World Health Organization (WHO). Gonorrhoea represents an almost exclusively sexually transmitted infection, which predominantly affects mucous membranes of the genitourinary tract. Extragenital localization of infections is also possible, e. g. in the anorectal region. Currently, only syphilis and human immunodeficiency virus (HIV) are notifiable diseases according to the Infection Protection Act in Germany. In Saxony, an extended registration ordinance according to the German Infection Protection Act is in force, which means that besides syphilis the laboratory detection of Neisseria gonorrhoeae, Chlamydia trachomatis and genital mycoplasms are also notifiable infections. In particular, beginning in 2009 in Saxony a spectacular increase of registered infections due to N. gonorrhoeae was observed and in 2015 altogether 824 infections due to N. gonorrhoeae were reported. Alarming is the increase in resistance of N. gonorrhoeae against penicillin, doxycycline, ciprofloxacin and recently also against azithromycin and third generation cephalosporins. The so-called superbug of N. gonorrhoeae, which originated in Japan with multidrug resistance against most of the currently available oral antibiotics, has now arrived in Europe. Intramuscular or intravenous injection of ceftriaxone plus oral azithromycin, each given as single dose is the standard therapy for gonorrhoea.

[Non-viral sexually transmitted infections - Epidemiology, clinical manifestations, diagnostics and therapy : Part 2: Chlamydia and mycoplasma]. / Nichtvirale sexuell übertragene Infektionen ­ Epidemiologie, Klinik, Labordiagnostik und Therapie : Teil 2: Chlamydien und Mykoplasmen.

Chlamydia trachomatis is the most common pathogen of sexually transmitted bacterial infections worldwide. Every year in Germany approximately 300,000 new infections are to be expected. Chlamydia infections occur nearly exclusively in the postpubertal period. The peak age group is 15-25 years. The infection usually runs an asymptomatic course and the diagnosis is made by nucleic acid amplification techniques (NAAT) often after chlamydial screening or if complications occur. For treatment of chlamydial infections oral doxycycline 100 mg twice daily over 7 days is initially used or alternatively oral azithromycin 1.5 g as a single dose is recommended. The sexual partner should also be investigated and treated. Genital Mycoplasma infections are caused by Ureaplasma urealyticum (pathogen of urethritis and vaginitis), Ureaplasma parvum (mostly saprophytic and rarely a cause of urethritis) and Mycoplasma hominis (facultative pathogenic). Mycoplasma genitalium represents a relatively new sexually transmitted Mycoplasma species. Doxycycline is effective in Ureaplasma infections or alternatively clarithromycin and azithromycin. Doxycycline can be ineffective in Mycoplasma hominis infections and an alternative is clindamycin. Non-gonococcal and non-chlamydial urethritis due to Mycoplasma genitalium can now be diagnosed by molecular biological techniques using PCR and should be treated by azithromycin.

[Prevalence of carbapenemase-producing bacteria in hospitals in Saxony, Germany]. / Prävalenzerhebung zum Vorkommen von Carbapenemase-Bildnern in sächsischen Kliniken.

The presence of pathogenic bacteria with acquired carbapenem resistance constitutes an increasing problem for infection control and infectious disease management. Prompted by an outbreak of infections with Klebsiella pneumoniae producing the carbapenemase KPC-2 at a hospital in Saxony, the Saxon State Ministry of Social Affairs and Consumer Protection (SMS) initiated a point-prevalence survey for carbapenemase-producing gram-negative bacteria. Wards at 53 hospitals in Saxony, mainly intensive care units, were investigated between October 2012 and February 2013. Stool samples and rectal swabs of 1,037 patients were analyzed for the presence of bacteria with resistance against four major groups of antibiotics (4MRGN). Carbapenemase producers were detected in 3 patients [0.3% CI95 (0.0596; 0.843)] and carbapenem-resistant bacteria without carbapenemases were detected in 9 patients [0.9% CI95 (0.397; 1.64)]. Furthermore, antimicrobial susceptibility testing revealed 166 patients [16.0% CI95 (13.82; 18.38)] with extended-spectrum beta-lactamase (ESBL)-producing bacteria. At the time of investigation, K. pneumoniae producing the carbapenemase KPC-2 was diagnosed in 2 patients at one hospital. Moreover, it is necessary to remain vigilant towards other types of carbapenemase producers, as demonstrated by the finding of a Pseudomonas aeruginosa strain harbouring the carbapenemase VIM-1 in another hospital.

Longitudinal study of meningococcal carrier rates in teenagers.

To gain actual information concerning the oropharyngeal carriage of Neisseria meningitidis among teenagers aged 15-18 years in Germany especially in a region with increased incidence of meningococal-related diseases prompted the study. Each teenager was swabbed three times with an interval of 2 months between the examinations. The 901 recovered N. meningitidis strains were characterized using serological (serogrouping, serotyping/serosubtyping) and molecular methods (PCR, PFGE) each. The results of the study demonstrate an overall average carrier rate of 18.8% for the three collection periods. There were, however, significant differences between the carrier rates within a given school and of different towns and counties. Of all isolates, 60.6% were not serogroupable. Serogroup B dominated (12.3%), followed by serogroup Y (9.0%) and serogroup C (3.6%). After PCR-based serogrouping of not serogroupable strains the percentages for serogroups enhanced to 18.8% for B, 10.8% for Y and 4.1% for C. Serotyping led to 305 different phenotypes with the most common being 29E:NT:P1.2,5 followed by Y:14:NST. In the 6 study towns the number of different N. meningitidis clones (PFGE types) isolated, varied between 30 and 87. In Wenden, where a prolonged outbreak had taken place, serogroup C (14.8%) was predominant. Only in this town C:2a isolates were found, all belonging to the ST-11/ET-37 complex and 12/13 matched identically to the ET-15 clone. Of the colonized teenagers, 26.7% were carriers over at least 23 weeks, 22.6% with the same strain, 36.0% were carrier for at least 15 weeks. Over all three collection periods 36.7% of the adolescents acquired a new strain. The highest acquisition rate was related to PFGE type 12.

Applying a case-crossover study design to examine transient exposures in the transmission of N. meningitidis.

BACKGROUND: Meningococcal disease is a serious public health problem with a case fatality of about 10%. Recent acquisition of the bacteria is generally regarded as an important risk factor for developing the invasive disease. A case-crossover study to examine the effect of transient exposures on the acute outcome, which is the acquisition of Neisseria meningitidis, was undertaken. METHODS: In the case-crossover design each case serves as its own matched control while case-times are compared to earlier time periods. Data from a longitudinal study was used for a case-crossover analysis. About 1910 students aged 14-19 were tested for meningococcal carriage and interviewed about potential risk factors. About 121 matched pairs of students who were non-carriers in the first survey and became carriers in the second were analysed. Mantel Haenszel Odds Ratios were calculated and a conditional logistic regression analysis was done. RESULTS: Both bivariate and multivariate analysis showed a significant association between meningococcal carriage and the predicting variables rhinitis, visits to cinema, and travelling abroad. While the adjusted results for rhinitis (OR: 0.33; 95% CI: 0.13-0.82) and cinema visits (OR: 0.17; 95% CI: 0.05-0.65) indicate a protective association, travelling abroad (OR: 3.50; 95% CI: 1.45-8.34) turned out as a risk factor. CONCLUSIONS: Transient exposures that trigger the infection with N. meningitidis are generally difficult to study. This case crossover study allows new insights in this process. For the interpretation of the results methodological issues and potential confounding (e.g., seasonal variation) need to be taken into account, especially while comparing the results with those from studies with traditional designs.

[Public health management in invasive meningococcal diseases]. / Public Health Management bei invasiven Meningokokkenerkrankungen.

At the 54(th) Scientific Congress of the German Professional Association of Public Health Service Physicians and Dentists in Marburg on 6th May 2004 the working group on meningococci (Arbeitsgemeinschaft Meningokokken, AGMK) organised the international workshop "Public Health Management of invasive Meningococcal Disease". In recent years significant changes in the epidemiology of meningococcal disease took place in Europe: in some countries and regions the number of disease caused by meningococci serogroup C has increased significantly. In the Netherlands this increase led to the introduction of an immunisation programme with conjugated meningococcal vaccines targeting children aged 1 up to 18 years. In Switzerland a peak in the number of reported meningococcal group C cases could be observed in some regions. Therefore, a regional vaccination programme has been introduced. Nevertheless, compared with Germany, the indications for vaccination against meningococci in Switzerland are more extensive. In the workshop, Professor Ulrich Vogel and Dr. Ingrid Ehrhard presented the epidemiological situation in Germany and the recommended prophylaxis regimen against meningococci.

Continuous infusion of ceftazidime for patients with breast cancer and multiple myeloma receiving high-dose chemotherapy and peripheral blood stem cell transplantation.

This prospective study was performed to examine the safety and efficacy of a continuous infusion of ceftazidime in patients who developed febrile neutropenia after high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (PBSCT) and to determine if the underlying disease represents a risk factor for infectious complications. From September 1995 to May 2000, 55 patients with breast cancer (BC, group I, 54 females, one male) and 32 patients with multiple myeloma (MM, group II, 10 female, 22 male) were included in this study. The febrile patients received a 2 g intravenous bolus of ceftazidime, followed by a 4 g continuous infusion over 24 h using a portable infusion pump. If the fever persisted for 72 h a glycopeptide antibiotic was added. The median age was 42 years (range 22-59) in group I and 52 years (range 35-63) in group II. Thirty-five BC patients (64%) and 20 MM patients (63%) responded to the monotherapy with ceftazidime. After addition of a glycopeptide antibiotic, an additional 11 BC patients vs 10 MM patients became afebrile. The causes of fever in group I were fever of unknown origin (FUO) in 49 patients, microbiologically documented infection (MDI) in five patients, and clinically documented infection (CDI) in one patient. The causes of fever in group II were FUO in 22 patients, MDI in eight patients and CDI in two patients. Forty-one febrile episodes in BC patients (75%) and 22 episodes in the MM patients (69%) were successfully managed by out-patient treatment, resulting in a saving of an average of 20 days of inpatient care. Significantly more episodes of MDI and CDI occurred in patients with MM (P = 0.05). The results indicate that BC and MM patients with febrile neutropenia after HDCT and PBSCT can be treated as outpatients with close monitoring to ensure safety. This approach represents a better use of health care resources.

Efficacy of continuous infusion of ceftazidime for patients with neutropenic fever after high-dose chemotherapy and peripheral blood stem cell transplantation.

Neutropenia is an important complication of high-dose chemotherapy (HDCT). Neutropenic patients presenting with fever are routinely hospitalized for treatment with broad-spectrum antibiotics. Neutropenia up to 10 days is associated with a low-risk profile, and antimicrobial therapy administered on an outpatient basis might be an alternative to admission to hospital. This prospective study evaluates the safety of a continuous infusion of ceftazidime in neutropenic patients after HDCT and peripheral blood stem cell transplantation (PBSCT). From September 1995 to October 1999, 81 patients received a 2 g intravenous bolus of ceftazidime, followed by a 4 g continuous infusion per 24 h of ceftazidime using a portable infusion pump. If the fever persisted for 72 h, a glycopeptide antibiotic was added. The median patients' age was 44 years. Fifty-two of 81 patients (64%) responded to the monotherapy with ceftazidime. After addition of a glycopeptide antibiotic, a further 17 patients (21%) became afebrile. The causes of fever were septicaemia in 11 patients, pneumonia in two and fever of unknown origin in 68 patients. Fifty-eight episodes (72%) were successfully managed by outpatient treatment alone. The reason for admission to hospital was the change to imipenem/cilastin, which had to be administered three times per day (12 patients), severe mucositis with parenteral nutrition (eight patients), or a Karnovsky index

Microheterogeneity of serogroup A (subgroup III) Neisseria meningitidis during an outbreak in northern Ghana.

During a meningitis outbreak in the eastern subdistrict of the Kassena-Nankana District of the Upper East Region of Ghana, we analysed cerebrospinal fluid from suspected meningitis cases for the most common causative organisms. In 50 of 92 samples analysed, serogroup A Neisseria meningitidis were detected. The ages of serogroup A N. meningitidis patients ranged from 4 months to 64 years. The case fatality ratio was 20%. Coma or stupor on presentation worsened the prognosis. All serogroup A N. meningitidis isolates recovered revealed the A: 4: P1.9, 20 phenotype characteristic for the subgroup III clonal grouping. No evidence for resistance to penicillin G, chloramphenicol, cefotaxime, ciprofloxacin, rifampicin or tetracycline was found. All strains were resistant to sulphadiazine. Restriction analysis patterns of opa, iga and ingA genes were characteristic for the majority of N. meningitidis serogroup A subgroup III bacteria isolated in Africa after the 1987 epidemic in Mecca. Differences in pulsed-field gel electrophoresis patterns of NheI and SpeI digested DNA revealed microheterogeneity among the Ghanaian isolates.

Serogroup C meningococcal disease outbreak associated with discotheque attendance during carnival.

In the week following a carnival during 19-24 February 1998, an outbreak of meningococcal disease occurred in a rural German county. The available isolates belonged to phenotype C:2a:P1.2,5 and were clonally related by pulsed-field gel electrophoresis. A case-control study was done to identify risk factors for the outbreak and to define possible vaccination target groups. Five persons aged 13-16 years who fell ill during 24-27 February were included in the study. Four of 5 cases and 10 of 32 controls visited local discotheques (OR = 8.8; P = 0.06). Cases also visited discotheques more frequently than controls (chi2 for trend, P = 0.0002). Multiple discotheques during the carnival may have been predominant locations of transmission in this outbreak. Because this risk factor was limited in time, a mass community vaccination campaign was not initiated.

[Meningococcal infections: aspects of microbiology, epidemiology and prevention]. / Meningokokkeninfektionen: Aspekte zur Mikrobiologie, Epidemiologie und Prävention.

Neisseria meningitidis (meningococcus) is responsible for an average of 40% of all cases of bacterial meningitis in Germany. Cerebrospinal fluids, blood cultures, throat swabs and scratches, aspirations and biopsies of the skin rash are appropriate materials for the diagnosis of meningococcal disease. The materials should reach the laboratory without delay. Since 1993, the incidence of meningococcal disease in Germany is less than 1 case per 100,000 inhabitants. The case fatality rate is about 10%. Most cases of meningococcal disease occur in the first quarter of the year. Almost half of all invasive N. meningitidis isolates are from children under five years of age. In the period 1990-1998, in Germany an average of 74% of cases were caused by serogroup B and 21% by serogroup C. In serogroup B disease, isolates of serotype 15, in group C disease strains of serotype 2a are predominating. Chemoprophylaxis should be given to all household members and all contacts living in institutions with household-like character, contacts in institutions for children under six years of age and all persons who had contact with the oropharyngeal secretions of the patient. At present, only capsular polysaccharide vaccines against serogroups A, C, Y and W135 are available for immunoprophylaxis in Germany.

Ceftazidime in combination with glycopeptide antibiotic is an effective first-line therapy for patients undergoing high-dose therapy with autologous peripheral blood stem cell support.

It was the objective of this study to evaluate the efficacy and toxicity of an empirical antibiotic therapy consisting in ceftazidime and a glycopeptide antibiotic. All patients enrolled in the study had hematological malignancies and underwent high-dose therapy with peripheral blood stem cell (PBSC) support. In this retrospective study, 183 of 207 patients who had received a PBSC-supported high-dose therapy were evaluable. Any patients who had fever higher than 38.5 degrees C received ceftazidime in combination with vancomycin (105 patients) or teicoplanin (69 patients). In 80 of 174 patients with fever (45%) the fever resolved within 72 h as a result of the treatment with ceftazidime and the glycopeptide antibiotic. In nonresponding patients, the changes included the replacement of ceftazidime by imipenem/cilastin (94 patients) and the addition of erythromycin (12 patients) or metronidazole (3 patients). Amphotericin B was administered in 29 patients. Following hematological reconstitution, the fever and clinical signs, including radiographic findings, resolved in 20 primarily nonresponding patients. In blood cultures, a significantly higher incidence of gram-positive than of gram-negative bacteria was observed (26 vs 7). The toxicity of the first-line antibiotic therapy was limited to allergic skin reactions in 12 patients. Ceftazidime in combination with a glycopeptide antibiotic provides an effective and safe first-line therapy for patients with neutropenic fever following PBSC-supported high-dose therapy.

Neisseria meningitidis serogroup B peritonitis associated with continuous ambulatory peritoneal dialysis.

A case of Neisseria meningitidis peritonitis in a 41-year-old female undergoing continuous ambulatory peritoneal dialysis for end-stage renal failure due to insulin-dependent diabetes mellitus is reported. The bacterial strain was serosubtyped as 4:P1.15, a rarely encountered type. Surprisingly, the minimal inhibitory concentration of vancomycin for the isolate was low (16 mg/l). This may have contributed to the complete recovery of the patient.

[Food borne outbreak of a Salmonella enteritidis epidemic in a large pharmaceutical industry]. / Lebensmittelbedingter Ausbruch einer Salmonella-enteritidis-Epidemie in einem pharmazeutischen Grossbetrieb.

In summer 1991 an outbreak of a Salmonella enteritidis epidemic involving about 600 cases of gastroenteritis occurred at one of the leading pharmaceutical companies in southwestern Germany. The main source was a cold fruit soup, in addition Salmonella were isolated from meat strips and a curd cheese which were used for a salad dressing. A total of 2300 contaminated food portions were served resulting in an attack rate of about 25%. The possible origin could have been an asymptomatic Salmonella-positive member of the kitchen personnel who was the only one who was involved with the preparation of all the incriminated foods. A further spread of the epidemic and especially the possible contamination of pharmaceuticals was avoided by the timely and adequate reaction of the company's occupational medical service. This case exemplifies how classical crisis management, "increased initiative on one's own for prevention of infections in all areas of food processing" (Steuer) and finally the cooperation of the company with different institutions of the public health authorities contribute to the control of such a catastrophic scenario.

Presence of quinolone resistance in a strain of Salmonella typhimurium.

A human isolate of Salmonella typhimurium was found to be highly resistant to several antibiotics including quinolones (MIC of ciprofloxacin 16 mg/l). Killing by ciprofloxacin was only achieved after prolonged exposure to drug concentrations above the MIC. The quinolone resistance of this particular strain was not mediated by plasmids which, however, coded for several other resistance properties.

The effect of the carbohydrate moiety upon the size and conformation of human plasma galactoglycoprotein as judged by electron microscopy and circular dichroism. Structural studies of a glycoprotein after stepwise enzymic carbohydrate removal.

Galactoglycoprotein is a unique human plasma protein [76% carbohydrate (23% N-acetylneuraminic acid, 20% galactose, 3% mannose, 1% fucose and 29% N-acetylgalactosamine plus N-acetylglucosamine) and 24% polypeptide, a single polypeptide chain of about 200 amino acid residues that is high in serine and threonine content] [Schmid, Mao, Kimura, Hayashi & Binette (1980) J. Biol. Chem. 255, 3221-3226]. Highly purified exoglycosidases with well-defined specificities were used to prepare five derivatives of galactoglycoprotein in which sequential residues of N-acetylneuraminic acid, galactose, N-acetylglucosamine, a second galactose and N-acetylgalactosamine were removed with 83% of the total carbohydrate cleaved. C.d. shows that native galactoglycoprotein and all derivatives in aqueous buffer are predominantly random coil, suggesting that removal of a large number of electrostatic net charges, as well as the major portion of the carbohydrate moiety, does not alter the secondary structure of the polypeptide chain. Examination of the size and conformation of tungsten-shadowed galactoglycoprotein and asialo and agalacto derivatives by electron microscopy shows the size and conformation of all three preparations to be similar, with only minor differences in particle length and width.