Antibiotic use by dentists in Germany: a review of prescriptions, pathogens, antimicrobial resistance and antibiotic stewardship strategies.

BACKGROUND: In Germany, 85% of all antibiotics are prescribed in the outpatient care sector, and dentists account for 11% of the total outpatient antibiotic prescriptions. OBJECTIVE AND METHOD: Summarise published literature on antibiotic use, pathogens and antibiotic resistance in odontogenic infections and German clinical guidelines and interventions for antibiotic use in dental care. RESULTS: In contrast to other outpatient physicians, the volume of antibiotics prescribed by dentists in Germany did not decrease over the last decade. Penicillins and aminopenicillins are the most frequently prescribed antibiotics (70% of all prescriptions), followed by clindamycin (26%). Streptococcus spp. and Staphylococcus spp. are frequent pathogens isolated from odontogenic infections. However, the infections are often polybacterial with a mixed growth of anaerobic and aerobic bacteria. While the widespread use of penicillin class antibiotics is compatible with German recommendations on empiric antibiotic therapy, there is evidence that pathogens from odontogenic infections frequently exhibit resistance against them. Moreover, the high prescription volume of clindamycin (⟩25%) appears to be inadequate, since relatively high resistance rates are observed and clindamycin is not recommended as first-line choice in empiric antibiotic therapy. National and international studies show that continuous education of patients and dentists, individual prescription feedback as well as evidence-based guidelines are important measures to improve antibiotic prescription patterns among dentists. CONCLUSION: To promote rational antibiotic use in outpatient dental care, antibiotic stewardship measures are necessary that include prescription guidelines based on AMR surveillance data as well as continuous education of dentists.

Establishing an ICD-10 code based SARI-surveillance in Germany - description of the system and first results from five recent influenza seasons.

BACKGROUND: Syndromic surveillance of severe acute respiratory infections (SARI) is important to assess seriousness of disease as recommended by WHO for influenza. In 2015 the Robert Koch Institute (RKI) started to collaborate with a private hospital network to develop a SARI surveillance system using case-based data on ICD-10 codes. This first-time description of the system shows its application to the analysis of five influenza seasons. METHODS: Since week 40/2015, weekly updated anonymized data on discharged patients overall and on patients with respiratory illness including ICD-10 codes of primary and secondary diagnoses are transferred from the network data center to RKI. Retrospective datasets were also provided. Our descriptive analysis is based on data of 47 sentinel hospitals collected between weeks 1/2012 to 20/2016. We applied three different SARI case definitions (CD) based on ICD-10 codes for discharge diagnoses of respiratory tract infections (J09 - J22): basic CD (BCD), using only primary diagnoses; sensitive CD (SCD), using primary and secondary diagnoses; timely CD (TCD), using only primary diagnoses of patients hospitalized up to one week. We compared the CD with regard to severity, age distribution and timeliness and with results from the national primary care sentinel system. RESULTS: The 47 sentinel hospitals covered 3.6% of patients discharged from all German hospitals in 2013. The SCD comprised 2.2 times patients as the BCD, and 3.6 times as many as the TCD. Time course of SARI cases corresponded well to results from primary care surveillance and influenza virus circulation. The patients fulfilling the TCD had been completely reported after 3 weeks, which was fastest among the CD. The proportion of SARI cases among patients was highest in the youngest age group of below 5-year-olds. However, the age group 60 years and above contributed most SARI cases. This was irrespective of the CD used. CONCLUSIONS: In general, available data and the implemented reporting system are appropriate to provide timely and reliable information on SARI in inpatients in Germany. Our ICD-10-based approach proved to be useful for fulfilling requirements for SARI surveillance. The exploratory approach gave valuable insights in data structure and emphasized the advantages of different CD.

First experience using a novel microsurgical robotic device for free flap surgery in cranio- and maxillofacial surgery.

Many surgical fields profit from robotic support devices. After the first case reports about the use of a special microsurgical roboter (Symani Sugrical System, Medical Microinstruments, Pisa, Italy) we evaluated the potential of such a device in cranio- and maxillofacial surgery in a world's first single-center case series. This novel piece of equipment is meant to assist the surgeon anastomosing small vessels, nerves and lymphatic vessels. In total 30 free flaps were performed and compared to another 30 conventionally anastomosed free flaps. In total 127 anastomoses were surveyed. We encountered a lot of potential for robotic supported operations in the field of cranio- and maxillofacial surgery. However, the surgery time for robotic supported anastomosis with an average time of 32.5 min to perform arterial anastomosis was significant longer than the conventional ones, which needed 11.8 min on average. Tremor Filter and Motion Scaling are promising features for future microsurgery but the grip of the microinstruments has to be improved. It remains to be seen if the potential will be validated after the upcoming learning period and if robotic support devices will prevail in cranio- and maxillofacial surgery.

The burden of extrapulmonary and meningitis tuberculosis: an investigation of national surveillance data, Germany, 2002 to 2009.

Tuberculosis (TB) surveillance commonly focuses on pulmonary (PTB) where the main organ affected is the lung. This might lead to underestimate extrapulmonary TB (EPTB) forms, where in addition to the lung other sites are affected by TB. In Germany, TB notification data provide the main site and the secondary site of disease. To gain an overview of all the different EPTB forms, we analysed German TB notification data between 2002 and 2009 using information on both main and secondary disease site to describe all individual EPTB forms. Further, we assessed factors associated with meningitis using multivariable logistic regression. Solely analysing the main site of disease, lead to one third of EPTB manifestations being overlooked. Case characteristics varied substantially across individual extrapulmonary forms. Of 46,349 TB patients, 422 (0.9%) had meningitis as main or secondary site. Of those, 105 (25%) of the 415 with available information had died. Multivariable analysis showed that meningitis was more likely in children younger than five years and between five and nine years-old (odds ratio (OR): 4.90; 95% confidence interval (CI): 3.40­7.07 and OR: 2.65; 95% CI: 1.40­5.00), in females (OR: 1.42; 95% CI: 1.17­1.73), and in those born in the World Health Organization (WHO) regions of south-east Asia (OR: 2.38; 95% CI: 1.66­3.43) and eastern Mediterranean (OR: 1.51; 95% CI: 1.02­2.23). Overall, EPTB manifestations, including meningitis, which is often fatal, were underestimated by routine analysis. We thus recommend using all information on disease manifestation generated by surveillance to monitor severe forms and to transfer the gained knowledge to TB case management where awareness of EPTB is most important.

[Varicella vaccination in Germany. A provisional appraisal in the context of MMR vaccination]. / Die Varizellenimpfung in Deutschland. Eine Zwischenbilanz mit Blick auf die Masern-Mumps-Röteln- (MMR-)Impfung.

In 2004, a general varicella immunization was introduced in Germany for infants from the age of 11 months, followed by the subsequent recommendation in 2009 of a second vaccine dose. The vaccination is carried out at the same time as the immunization against measles, mumps, and rubella (MMR). Results of the nationwide sentinel surveillance of varicella and herpes zoster implemented by the Varicella Working Group (Arbeitsgemeinschaft Varizellen, AGV) show that the defined goals for varicella immunization (reduction of varicella-related morbidity, complications and hospitalizations) have been reached within a few years owing to the advances in vaccine coverage. Although coverage rates for varicella have not yet reached the same levels as for MMR, varicella immunization seems to have benefited from the established MMR immunization schedule. Moreover, there is no evidence for an adverse effect on the use and acceptance of the MMR vaccine. Lessons learnt in measles epidemiology (such as trends in the incidence of the disease in adolescents and infants), as well as in the history of MMR recommendations, may be useful for the evaluation of future epidemiological changes with respect to varicella and herpes zoster. In view of a rapidly waning immunity against the varicella zoster virus after vaccination with one dose and the lifelong persistence of the virus, achieving a robust and sustainable immunity in the general population seems to be an ambitious goal. However, this accomplishment will be indispensable in preventing breakthrough infections and a shift of varicella to older ages and in avoiding an increase in herpes zoster incidence.

Electron microscopy in myofibrillar myopathies reveals clues to the mutated gene.

We studied the ultrastructural characteristics in patients with myofibrillar myopathy (MFM) and differentiated between MFM-subtypes using electron microscopic (EM) findings. The ultrastructural findings in 19 patients with different genetically proven MFMs (9 desmin, 5 alphaB-crystallin, 3 ZASP, 2 myotilin) were analyzed. In one ZASPopathy, we additionally performed an immunoEM study, using antibodies against desmin, alphaB-crystallin, ZASP and myotilin. The ultrastructural findings in desminopathies and alphaB-crystallinopathies were very similar and consisted of electrondense granulofilamentous accumulations and sandwich formations. They differed in the obvious presence of early apoptotic nuclear changes in alphaB-crystallinopathies. ZASPopathies were characterized by filamentous bundles (labeled with the myotilin antibody on immunoEM), and floccular accumulations of thin filamentous material. Tubulofilamentous inclusions in sarcoplasm and myonuclei in combination with filamentous bundles were characteristic for myotilinopathies. We conclude that MFMs ultrastructural findings can direct diagnostic efforts towards the causal gene mutated, and that EM should be included in the diagnostic workup of MFMs.

An autosomal-recessive congenital myasthenic syndrome with tubular aggregates in a Libyan family.

We studied a Libyan family in which five out of seven siblings have had slowly progressive limb-girdle weakness accentuated by exercise since childhood. Ptosis or ophthalmoplegia were not observed. Pronounced decremental electromyographic responses on 3 Hz stimulation indicated the presence of a defect of neuromuscular transmission. Repeated testing for acetylcholine receptor antibodies was negative. Muscle biopsy revealed tubular aggregates in 34% of the type 2 muscle fibers. Our observation illustrates the wide clinical spectrum of congenital myasthenic syndromes.

Sporadic adult-onset distal myopathy with rimmed vacuoles, 15-18 nm tubulofilaments and extensive rod formation.

Starting after the age of 35 years this German man had a slowly progressive distal myopathy greater in the legs than in the arms. First he realized gait difficulties with reduced ankle dorsiflexion. Serum creatine kinase activity was normal. Muscle biopsy studies showed myopathic changes, rimmed vacuoles and the presence of rods in 66% of the type 1 muscle fibers. Ultrastructural examination revealed cytoplasmatic aggregates of tubulofilaments measuring 15-18 nm in diameter, myeloid bodies and rod formation. The nosological situation of this distal myopathy with tubulofilamentous inclusions is discussed.

Smad-interacting protein 1 affects acute and tonic, but not chronic pain.

BACKGROUND: Smad-interacting protein 1 (also named Zeb2 and Zfhx1b) is a transcription factor that plays an important role in neuronal development and, when mutated, causes Mowat-Wilson syndrome (MWS). A corresponding mouse model carrying a heterozygous Zeb2 deletion was comprehensively analysed in the German Mouse Clinic. The most prominent phenotype was the reduced pain sensitivity. In this study, we investigated the role of Zeb2 in inflammatory and neuropathic pain. METHODS: For this, we tested mutant Zeb2 animals in different models of inflammatory pain like abdominal constriction, formalin and carrageenan test. Furthermore, we studied the pain reactivity of the mice after peripheral nerve ligation. To examine the nociceptive transmission of primary sensory dorsal root ganglia (DRG) neurons, we determined the neuronal activity in the spinal dorsal horn after the formalin test using staining of c-Fos. Next, we characterized the neuronal cell population in the DRGs and in the sciatic nerve to study the effect of the Zeb2 mutation on peripheral nerve morphology. RESULTS: The present data show that Zeb2 is involved in the development of primary sensory DRG neurons, especially of C- and Aδ fibres. These alterations contribute to a hypoalgesic phenotype in inflammatory but not in neuropathic pain in these Zeb2(+/-) mice. CONCLUSION: Our data suggest that the under-reaction to pain observed in MWS patients results from a reduced responsivity to nociceptive stimulation rather than an inability to communicate discomfort.