[Multi-Resistant Bacteria in Patients in Hospitals and Medical Practices as well as in Residents of Nursing Homes in Saxony - Results of a Prevalence Study 2017/2018]. / Multiresistente Bakterien bei Patienten in Krankenhäusern und Arztpraxen sowie bei Bewohnern von Altenpflegeheimen in Sachsen ­ Ergebnisse einer Prävalenzstudie 2017/2018.

OBJECTIVE: The aim of this study was to determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA), multi-resistant gram-negative bacteria (MRGN) and vancomycin-resistant enterococci (VRE) in three study groups (hospital patients, residents in nursing homes for the elderly and patients in GP practices) and additionally, risk factors for carriage of multidrug-resistant organisms (MDRO). METHODS: Screening for MDRO was performed as a point prevalence study by obtaining nasal, pharyngeal and rectal swabs or stool samples from voluntary participants in 25 hospitals, 14 nursing homes for the elderly as well as 33 medical practices in 12 of 13 districts of Saxony. Suspicious isolates were further examined phenotypically and partially by molecular methods. The participants completed a questionnaire on possible risk factors for MDRO colonisation; the data were statistically evaluated by correlation analyses. RESULTS: In total, 1,718 persons, 629 from hospitals, 498 from nursing homes and 591 from medical practices, were examined. MDRO was detected in 8.4% of all participants; 1.3% persons tested positive for MRSA, 5.2% for 3MRGN, 0.1% for 4MRGN and 2.3% for VRE. Nine persons were colonized with more than one MDRO. The following independent risk factors could be significantly associated with the detection of MDRO: presence of a degree of care (MDRO), male sex (MDRO/VRE), current antibiosis (MDRO/VRE), antibiosis within the last 6 months (MDRO/MRSA/MRGN/VRE), current tumour disease (MDRO/3MRGN), peripheral artery disease (PAD) (MRSA) as well as urinary incontinence (3MRGN). CONCLUSIONS: To our knowledge, this study represents the first survey of prevalence of different multiresistant pathogen groups in 3 study groups including outpatients in Germany. 3MRGN were the pathogens most frequently detected and were also found in patients of younger age groups. VRE were found almost exclusively in specific clinics. In addition to current and past antibiotic therapy, in particular the presence of PAD for MRSA detection, urinary incontinence for 3MRGN detection and a current tumour disease for MDRO and 3MRGN detection were determined as independent risk factors.

Effectiveness of antibiotics given before admission in reducing mortality from meningococcal disease: systematic review.

OBJECTIVE: To review the evidence for effectiveness of treatment with antibiotics before admission in reducing case fatality from meningococcal disease. DESIGN: Systematic review. DATA SOURCES: Cochrane register of trials and systematic reviews, database of abstracts of reviews of effectiveness, health technology assessment, and national research register in England and Wales, Medline, Embase, and CAB Health. INCLUDED STUDIES: Studies describing vital outcome of at least 10 cases of meningococcal disease classified by whether or not antibiotics were given before admission to hospital. RESULTS: 14 observational studies met the review criteria. Oral antibiotic treatment given before admission was associated with reduced mortality among cases (combined risk ratio 0.17, 95% confidence interval 0.07 to 0.44). In seven studies in which all included patients were seen in primary care, the association between parenteral antibiotics before admission and outcome was inconsistent (chi2 for heterogeneity 11.02, P = 0.09). After adjustment for the proportion given parenteral antibiotics before admission, there was no residual heterogeneity. A higher proportion of patients given parenteral antibiotics before admission was associated with reduced mortality after such treatment and vice versa (P = 0.04). CONCLUSION: Confounding by severity is the most likely explanation both for the beneficial effect of oral antibiotics and the harmful effect observed in some studies of parenteral antibiotics. We cannot conclude whether or not antibiotics given before admission have an effect on case fatality. The data are consistent with benefit when a substantial proportion of cases are treated.

Effectiveness of antibiotics in preventing meningococcal disease after a case: systematic review.

OBJECTIVE: To summarise the evidence for the role of antibiotics in preventing further cases of meningococcal disease through chemoprophylaxis given to the index patient, household contacts, and children in day care settings after a single case. DESIGN: Systematic review. METHODS: Studies were identified by searching Embase (1983-2003), Medline (1965-2003), and CAB Health (1973-2003) and by contacting the World Health Organization and the European meningococcal disease surveillance network and examining references of identified papers. The review included all studies with at least 10 cases in which outcomes were compared between treated and untreated groups. MAIN OUTCOME MEASURE: Subsequent cases of meningococcal disease 1-30 days after onset of disease in the index patient. RESULTS: Four observational studies and one small trial met the inclusion criteria. Meta-analysis of studies on chemoprophylaxis given to household contacts showed a significant reduction in risk (risk ratio 0.11, 95% confidence interval 0.02 to 0.58). The number needed to treat to prevent a case was estimated as 218 (121 to 1135). Primary outcome data were not available in studies of chemoprophylaxis given to the index patient: when prophylaxis had not been given, rate of carriage after discharge from hospital was estimated as 3% (0 to 6), probably an underestimate of the true rate. No studies of chemoprophylaxis in day care settings were identified that met the inclusion criteria. CONCLUSION: There have been no high quality experimental trials looking at control policies for meningococcal disease. The best available evidence is from retrospective studies. The risk of meningococcal disease in household contacts of a patient can be reduced by an estimated 89% if they take antibiotics known to eradicate meningococcal carriage. Chemoprophylaxis should be recommended for the index patient and all household contacts.

Description of new mutations in the rpoB gene in rifampicin-resistant Neisseria meningitidis selected in vitro in a stepwise manner.

Fourteen meningococcal strains were selected towards rifampicin resistance in a stepwise manner in vitro; final MICs were between 8 and >256 microg ml(-1). Sequence analysis of a 295 bp subgenic fragment of the RNA polymerase beta-subunit (rpoB) gene from the original and the fully resistant strains revealed that, with one exception, the strain pairs differed by just one position in the deduced amino acid sequence. Transformation of a PCR-amplified subgenic rpoB fragment harbouring the mutated site into a susceptible strain demonstrated the resistance-conferring mechanism.

Interlaboratory comparison of agar dilution and Etest methods for determining the MICs of antibiotics used in management of Neisseria meningitidis infections.

Previous studies have shown that there is considerable variation in the methods and media used to determine the susceptibility of Neisseria meningitidis to antimicrobial agents in different countries. In this study, national and regional reference laboratories used a standardized methodology to determine the MICs of antibiotics used in the management of meningococcal infection. Fourteen laboratories participated in the study, determining the susceptibility to penicillin G, rifampin, cefotaxime, ceftriaxone, ciprofloxacin, and ofloxacin of a collection of 17 meningococci, of which 11 strains were previously defined as having intermediate resistance to penicillin (Pen(I)) by sequencing and restriction fragment length polymorphism analysis of the penA gene. The MIC was determined by agar dilution and Etest with Mueller-Hinton agar (MH), MH supplemented with sheep blood (MH+B), and MH supplemented with heated (chocolated) blood. Several laboratories encountered problems obtaining confluent growth with unsupplemented MH. MH+B was considered to give the most congruent and reproducible results among the study laboratories. The modal MIC for MH+B for each antibiotic and method was calculated to define the MIC consensus, allowing assessment of each individual laboratory's data in relation to the others. The agreement in each antibiotic/method/medium combination was defined as the percentage of laboratories with a result within one dilution of the modal result. For the whole study, an agreement of 90.6% was observed between agar dilution and Etest methods. The agreement in each laboratory/antibiotic/method combination ranged from 98.2% to 69.7%, with six laboratories demonstrating agreement higher than 90% and 11 more than 80%. The ability of the laboratories to detect the Pen(I) isolates ranged from 18.2% to 100%. The apparent difficulty in interpreting susceptibility to rifampin, particularly with the Etest method, is very interesting.

Immunogenicity of recombinant L7/L12 ribosomal protein of Neisseria meningitidis--high prevalence of specific antibodies in humans but limited immunogenicity for T cells.

The rplL gene, coding for ribosomal protein L7/L12 of Neisseria meningitidis was cloned and expressed as a fusion protein. The recombinant protein was used in Western blots and lymphocyte proliferation assays to study the prevalence of specific antibodies in human sera and the immunogenicity for the cellular immune system. Most of the serum samples studied were found to be positive for L7/L12-specific antibodies. A number of peripheral blood mononuclear cell preparations tested displayed activation in lymphocyte proliferation assays. The magnitude of activation (stimulation index) was moderate, and there was no correlation with a history of meningococcal disease. The high prevalence of specific antibodies is explained by the high carriage rate of meningococci in the normal population or cross-reactivity to ribosomal proteins of other bacteria, thus indicating immunogenicity. However, meningococcal L7/L12 does not seem to be a potential T cell antigen.

Clonal groupings in serogroup X Neisseria meningitidis.

The genetic diversity of 134 serogroup X Neisseria meningitis isolates from Africa, Europe, and North America was analyzed by multilocus sequence typing and pulsed-field gel electrophoresis. Although most European and American isolates were highly diverse, one clonal grouping was identified in sporadic disease and carrier strains isolated over the last 2 decades in the United Kingdom, the Netherlands, Germany, and the United States. In contrast to the diversity in the European and American isolates, most carrier and disease isolates recovered during the last 30 years in countries in the African meningitis belt belonged to a second clonal grouping. During the last decade, these bacteria have caused meningitis outbreaks in Niger and Ghana. These results support the development of a comprehensive conjugate vaccine that would include serogroup X polysaccharide.

A modified ex vivo human whole blood model of infection for studying the pathogenesis of Neisseria meningitidis during septicemia.

For the purpose of establishing a model to study host-bacteria interaction and virulence mechanisms of Neisseria meningitidis during the septic phase of disease a modified human whole blood model of infection is proposed. Compared to published whole blood models the current model was modified with respect to the initial number of viable bacteria (10(4) cfu ml(-1)), the anticoagulant used and the incubation time. The results obtained after incubation of a number of human blood samples from healthy volunteers for 24 h with serogroup B meningococci were in good agreement with findings reported from patients who suffered severe meningococcal disease.

Prospective study of a serogroup X Neisseria meningitidis outbreak in northern Ghana.

After an epidemic of serogroup A meningococcal meningitis in northern Ghana, a gradual disappearance of the epidemic strain was observed in a series of five 6-month carriage surveys of 37 randomly selected households. As serogroup A Neisseria meningitidis carriage decreased, an epidemic of serogroup X meningococcal carriage occurred, which reached 18% (53/298) of the people sampled during the dry season of 2000, coinciding with an outbreak of serogroup X disease. These carriage patterns were unrelated to that of Neisseria lactamica. Multilocus sequence typing and pulsed-field gel electrophoresis of the serogroup X bacteria revealed strong similarity with other strains isolated in Africa during recent decades. Three closely related clusters with distinct patterns of spread were identified among the Ghanian isolates, and further microevolution occurred after they arrived in the district. The occurrence of serogroup X outbreaks argues for the inclusion of this serogroup into a multivalent conjugate vaccine against N. meningitidis.