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This is the thirteenth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2 updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.Bacterial meningitis is a life-threatening infectious disease with high mortality and disability rates requiring prompt initiation of antimicrobial treatment to lower these rates.

A large SO2-rich pollution plume of East Asian origin was detected by aircraft based CIMS (Chemical Ionization Mass Spectrometry) measurements at 3-7.5 km altitude over the North Atlantic. The measurements, which took place on 3 May 2006 aboard of the German research aircraft Falcon, were part of the INTEX-B (Intercontinental Chemical Transport Experiment-B) campaign. Additional trace gases (NO, NOy, CO, H2O) were measured and used for comparison and source identification. The atmospheric SO2 mole fraction was markedly increased inside the plume and reached up to 900 pmol/mol. Accompanying lagrangian FLEXPART particle dispersion model simulations indicate that the probed pollution plume originated at low altitudes from densely populated and industrialized regions of East Asia, primarily China, about 8-12 days prior to the measurements. [ABSTRACT FROM AUTHOR]

Background: Lyme disease is the most frequent tick-borne infectious disease in Europe. The discovery of the causative pathogen Borrelia burgdorferi in 1982 opened the way for the firm diagnosis of diseases in several clinical disciplines and for causal antibiotic therapy. At the same time, speculation regarding links between Borrelia infection and a variety of nonspecific symptoms and disorders resulted in overdiagnosis and overtreatment of suspected Lyme disease.Method: The authors conducted a selective review of the literature, including various national and international guidelines.Results: The spirochete Borrelia burgdorferi sensu lato is present in approximately 5% to 35% of sheep ticks (Ixodes ricinus) in Germany, depending on the region. In contrast to North America, different genospecies are found in Europe. The most frequent clinical manifestation of Borrelia infection is erythema migrans, followed by neuroborreliosis, arthritis, acrodermatitis chronica atrophicans, and lymphocytosis benigna cutis. Diagnosis is made on the basis of the clinical symptoms, and in stages II and III by detection of Borrelia-specific antibodies. In adults erythema migrans is treated with doxycycline, in children with amoxicillin. The standard treatment of neuroborreliosis is third-generation cephalosporins.Conclusions: After appropriate antibiotic therapy, the outcome is favorable. In approximately 95% of cases neuroborreliosis is cured without long-term sequelae. When chronic borreliosis is suspected, other potential causes of the clinical syndrome must be painstakingly excluded. [ABSTRACT FROM AUTHOR]

A large SO2-rich pollution plume of Chinese origin was detected by aircraft based CIMS (Chemical Ionization Mass Spectrometry) measurements at 3-7.5 km altitude over the North Atlantic on 3 May 2006 during the INTEX (Intercontinental Chemical Transport Experiment) campaign. Additional trace gases (NO, NOy, CO, H2O) were measured and used for comparison and source identification. All measurements took place aboard the German research aircraft Falcon. The atmospheric SO2 mole fraction was markedly increased inside the plume and reached up to 900 pmol/mol. The measured ratio SO2/NOy of 1.4 suggests combustion of coal or fuel with a very high sulfur content as a source of the excess SO2. Accompanying FLEXPART particle dispersion model simulations indicate that the probed pollution plume originated at low altitudes over densely populated and industrialized areas in eastern China about 8-12 days prior to the measurements. [ABSTRACT FROM AUTHOR]

Central nervous system tuberculosis remains a clinical diagnostic challenge. The ex vivo Mycobacterium tuberculosis-specific enzyme-linked immunospot assay (ELISPOT) is a novel assay for the rapid detection of M. tuberculosis-specific T-lymphocytes in the peripheral blood. However, when performed on peripheral blood, this assay cannot distinguish between active tuberculosis or latent tuberculosis infection. On the assumption that M. tuberculosis-specific T-lymphocytes migrate to sites of infection, we were able to demonstrate high levels of M. tuberculosis-specific cells by ELISPOT in the cerebrospinal fluid of a patient with tuberculous meningitis and intracerebral tuberculoma four weeks before cerebrospinal fluid culture became positive for M. tuberculosis by culture. [ABSTRACT FROM AUTHOR]

The course of bacterial titers, meningeal inflammation, behavioral abnormalities, and neuronal damage was studied in a mouse model of Streptococcus pneumoniae meningitis. At 24 h after injection of 104 colony-forming units (CFU) S. pneumoniae into the right forebrain, infected mice became severely lethargic. Bacterial titers in cerebrospinal fluid and cerebellum rose to 109 CFU/ml, with strong granulocyte invasion into the meninges and neuronal necroses in the neocortex, striatum and hippocampal formation. Meningeal inflammation and neuronal damage in intercellular cell adhesion molecule-1- and macrophage colony-stimulating factor-deficient mice was similar to that in wild-type littermates. Untreated, the infection was fatal. Wild-type mice treated earlier than 24 h after infection with ceftriaxone (2 mg every 12 h for 3 days) survived without apparent behavioral abnormalities. Delay of treatment beyond 30 h led to the death of more than 50% of the infected mice. This mouse model is suitable for therapeutic studies and for the investigation of inflammation in knockout mice. The neuronal damage resembles morphological abnormalities observed in humans. [ABSTRACT FROM AUTHOR]

Apoptosis followed by macrophage phagocytosis is the principal mechanism by which neutrophil granulocytes (PMN) are removed from the site of inflammation. To investigate whether Streptococcus pneumoniae causes apoptosis of PMN, we exposed PMN to viable and heat-killed pneumococci and purified pneumococcal cell walls (PCW). The occurrence of PMN cell death was quantified by flow cytometry using annexin V/propidium iodide labelling of the cells. Intracellular histone-associated DNA fragments were quantified by ELISA. The presence of apoptosis was confirmed by in situ tailing. Exposure of PMN to viable pneumococci caused necrosis of the cells. The pneumococcal cytotoxin pneumolysin, the bacterial production of hydrogen peroxide, and PCW contributed to necrosis. Heat-killed pneumococci accelerated the process of apoptosis observed in cultivated non-stimulated PMN in vitro. These results demonstrated that pneumococci induce PMN cell death. Depending on the intensity of the stimulus, PMN necrosis and apoptosis were observed. [ABSTRACT FROM AUTHOR]

The release of teichoic acids (TA) and lipoteichoic acids (LTA) from 30 different strains of Streptococcus pneumoniae during exposure to ceftriaxone, meropenem, quinupristin/dalfopristin, rifampicin and trovafloxacin at concentrations of 10 μg/mI and of the respective MIC was determinded by an enzyme immunoassay. At 10 μg/mI the most rapid and intense release was detected during treatment with the β-lactam antibiotics ceftriaxone and meropenem,the lowest release was seen with rifampicin and quinupristin/dalfopristin. Trovafloxacin delayed the release of TA/LTA. The maximum concentrations of TA/LTA, however, during trovafloxacin treatment were almost as high as those during exposure to ceftriaxone and meropenem. During exposure to the MIC, ceftriaxone, meropenem, rifampicin and trovafloxacin released significantly higher amounts of TA/LTA than during exposure to 10 μg/mI (p < 0.01). Only quinupristin/dalfopristin released small amounts of TA/LTA at the low and high concentration. In conclusion, at high concentrations antibiotics that do not affect the bacterial cell wall released less pro-inflammatory compounds from S. pneumoniae than ceftriaxone and meropenem. This may be of value in the treatment of meningitis and sepsis. [ABSTRACT FROM AUTHOR]

The administration of osmotic agents is one of the principal strategies to lower elevated intracranial pressure (ICP) and to increase cerebral perfusion pressure. Of the 3 osmotic agents frequently used (mannitol, glycerol and sorbitol), each has characteristic advantages and disadvantages. In addition to renal filtration, sorbitol [elimination half-life (t1/2beta) approximately 1h] and glycerol (t1/2beta 0.2 to 1h) are metabolised, mainly by the liver. The risk of these compounds accumulating in patients with renal insufficiency is low. However, both compounds frequently affect glucose metabolism, leading to an increase in the serum glucose concentration. Mannitol is almost exclusively renally filtered and possesses the slowest elimination from serum (t1/2beta 2 to 4h). The t1/2beta of mannitol is markedly increased in patients with renal insufficiency, but it does not interfere with glucose metabolism. Entry into the cerebrospinal fluid (CSF) is highest with glycerol [CSF: serum ratio of the areas under the concentration-time curves (AUC(CSF): AUCs) approximately 0.25], intermediate with mannitol (AUC(CSF): AUCs approximately 0.15) and lowest with sorbitol (AUC(CSF): AUCs approximately 0.10). The elimination of all osmotic agents from the CSF compartment is substantially slower than from serum. During the elimination phase, the CSF-to-serum osmotic gradient is temporarily reversed. This is one cause of the paradoxical rise of ICP above the pretreatment level sometimes observed with osmotherapeutics. The ability of mannitol, glycerol and sorbitol to lower elevated ICP has been extensively documented. However, whether the use of osmotic agents, particularly with repeated application, improves outcome remains unproven. Therefore, these agents should only be used to treat manifest elevations of ICP, not for prophylaxis of brain oedema. [ABSTRACT FROM AUTHOR]