The Percentage of Antibiotic Resistance in Uncomplicated Community-Acquired Urinary Tract Infections.

BACKGROUND: Uncomplicated bacterial urinary tract infections(uUTIs) are commonly seen in outpatient practice. They are usuallytreated empirically with antibiotics. The pertinent German ClinicalPractice Guideline contains recommendations on antibiotic selection,with the additional advice that the local resistance situationshould be considered as well. However, up-to-date information onlocal resistance is often unavailable, because microbiological testingis mainly recommended for complicated UTIs. Resistance ratesare often higher in recurrent uUTIs than in single episodes. In thisstudy, we aimed to determine the resistance rates of Escherichiacoli (E. coli) in patients with community-acquired uUTIs and tomake these data available to the treating physicians. METHODS: In a nationwide cross-sectional study in Germany (DRKS00019059), we determined the percentages of resistance to antibioticsrecommended for uUTIs (first choice: fosfomycin, nitro -xoline, mecillinam, nitrofurantoin, trimethoprim; second choice:cefpodoxime, ciprofloxacin, cotrimoxazole, levofloxacin, norfloxacin,ofloxacin) over the period 2019-2021. The data were stratified bysingle episodes vs. recurrent UTIs (rUTIs). RESULTS: Data from 2390 subjects were analyzed. E. coli was foundin 75.4% of the samples with positive urine cultures (1082 out of1435). The resistance rate of E. coli in single episodes (n = 725)was less than 15% for all antibiotics tested. In rUTIs(n = 357), resistance rates were also less than 15%for the most part; the only exceptions were trimethoprim(21.4%) and cotrimoxazole (19.3%). CONCLUSION: For single episodes of uUTI, all of theantibiotics studied can be recommended, at least asfar as their resistance profiles are concerned. Forrecurrent UTI, all but trimethoprim and cotrimoxazolecan be recommended. The second-choice antibioticsexamined do not have a more favorable resistanceprofile than the first-choice antibiotics.

Antibiotic consumption in Germany: first data of a newly implemented web-based tool for local and national surveillance.

Objectives: The features of a newly established, web-based surveillance system for hospital antibiotic consumption are described and data on broad-spectrum antibiotic use in German acute care hospitals are presented. Methods: The watch- and reserve-group antibiotics, two categories of antibiotics derived from the WHO Essential Medicines List comprising key agents for antimicrobial stewardship, were used as a framework for data analysis. The median antibiotic consumption densities (ACDs; DDD/100 patient days) for the years 2015/16 based on data from 137 acute care hospitals have been calculated for whole facilities, ICUs and medical and surgical departments, stratified by type of care. Results: The new web-based system provides real-time surveillance at unit and facility levels, accessible to all relevant stakeholders. User-defined reports are available via an interactive database, various report types support different approaches to analysis, and different complementing quantification measures of antimicrobial consumption are available. Watch- and reserve-group antibiotics accounted for 42% and 2% of total antibiotic use, respectively. Surgical services presented with considerably lower median ACDs of the watch-group antibiotics compared with medical services. Tertiary care hospitals exhibited higher ACDs of the reserve-group antibiotics and carbapenems than primary/secondary care hospitals, while the ACDs of the watch-group antibiotics as a whole did not differ significantly. Comparing the proportional use with other European countries revealed a relatively high use of the watch-group, ranking beyond the 75th percentile. Conclusions: Because of its particular features the new web-based surveillance system is a valuable tool for antimicrobial stewardship. The WHO categories of watch- and reserve-group antibiotics proved to be a useful framework for the analysis of hospital antibiotic consumption data.

Does wastewater treatment plant upgrading with activated carbon result in an improvement of fish health?

In the present study, the efficiency of a wastewater treatment plant (WWTP) upgraded with a powdered activated carbon unit for the reduction of micropollutants and the related advantages for fish health have been analyzed by means of different biomarkers, i.e. histopathological investigations, analyses of glycogen content and stress proteins, as well as by chemical analyses in different matrices. Comparative analyses were conducted prior and subsequent to the installation of the additional purification unit. Chemical analyses revealed a significant reduction of several pharmaceuticals, including diclofenac, carbamazepine and metoprolol, in samples of effluent and surface water downstream of the WWTP after its upgrade. In addition, diminished concentrations of diclofenac and PFOS were detected in tissues of analyzed fish. Histopathological investigations of fish liver, gills, and kidney revealed improved tissue integrity in fish after improved wastewater treatment. In parallel, biochemical measurements of glycogen revealed increased energy resources in fish liver and, furthermore, hsp70 levels in livers of exposed rainbow trout and in kidneys of exposed brown trout were lower after than before the WWTP upgrade. In summary, additional treatment with powdered activated carbon led to a reduction of potentially hazardous chemicals in the effluent and the adjacent river and, consequently, to an improvement of fish health in the receiving water course.

Reduction of dioxin-like toxicity in effluents by additional wastewater treatment and related effects in fish.

Efficiency of advanced wastewater treatment technologies to reduce micropollutants which mediate dioxin-like toxicity was investigated. Technologies compared included ozonation, powdered activated carbon and granular activated carbon. In addition to chemical analyses in samples of effluents, surface waters, sediments, and fish, (1) dioxin-like potentials were measured in paired samples of effluents, surface waters, and sediments by use of an in vitro biotest (reporter gene assay) and (2) dioxin-like effects were investigated in exposed fish by use of in vivo activity of the mixed-function, monooxygenase enzyme, ethoxyresorufin O-deethylase (EROD) in liver. All advanced technologies studied, based on degradation or adsorption, significantly reduced dioxin-like potentials in samples and resulted in lesser EROD activity in livers of fish. Results of in vitro and in vivo biological responses were not clearly related to quantification of targeted analytes by use of instrumental analyses.

Occurrence of Antibiotics in Surface and Groundwater of a Drinking Water Catchment Area in Germany.

The contamination of the aquatic environment with organic micropollutants, such as veterinary pharmaceuticals, has become an increasingly serious problem and has aroused attention in the course of the last decades. This study presents a screening for a series of veterinary antibiotics, potentially introduced by the application of liquid manure, in ground- and surface water of a drinking water catchment in Lower Saxony, Germany. Of the 26 compounds analyzed, eight, including sulfadiazine, sulfapyridine, sulfamethoxazole, trimethoprim, dehydrato-erythromycin, sulfadimidine, tylosin, and tetracycline were detected in surface water samples. Trimethoprim was detected in 11 out of 15 shallow groundwater samples, indicating its high environmental relevance. Column sorption experiments conducted on trimethoprim show a comparatively moderate sorption affinity to sandy aquifer material with a retardation coefficient of 5.7.

Biological plausibility as a tool to associate analytical data for micropollutants and effect potentials in wastewater, surface water, and sediments with effects in fishes.

Discharge of substances like pesticides, pharmaceuticals, flame retardants, and chelating agents in surface waters has increased over the last decades due to the rising numbers of chemicals used by humans and because many WWTPs do not eliminate these substances entirely. The study, results of which are presented here, focused on associations of (1) concentrations of micropollutants in wastewater treatment plant (WWTP) effluents, surface waters, sediments, and tissues of fishes; (2) results of laboratory biotests indicating potentials for effects in these samples and (3) effects either in feral chub (Leuciscus cephalus) from two German rivers (Schussen, Argen) or in brown trout (Salmo trutta f. fario) and rainbow trout (Oncorhynchus mykiss) exposed in bypass systems to streamwater of these rivers or in cages directly in the rivers. The Schussen and Argen Rivers flow into Lake Constance. The Schussen River is polluted by a great number of chemicals, while the Argen River is less influenced by micropollutants. Pesticides, chelating agents, flame retardants, pharmaceuticals, heavy metals, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) were detected in effluents of a WWTP discharging to the Schussen as well as in surface water, and/or fishes from downstream of the WWTP. Results obtained by biotests conducted in the laboratory (genotoxicity, dioxin-like toxicity, and embryotoxicity) were linked to effects in feral fish collected in the vicinity of the WWTP or in fishes exposed in cages or at the bypass systems downstream of the WWTP. Dioxin-like effect potentials detected by reporter gene assays were associated with activation of CYP1A1 enzymes in fishes which are inducible by dioxin-like chemicals. Abundances of several PCBs in tissues of fishes from cages and bypass systems were not associated with these effects but other factors can influence EROD activity. Genotoxic potentials obtained by in vitro tests were associated with the presence of micronuclei in erythrocytes of chub from the river. Chemicals potentially responsible for effects on DNA were identified. Embryotoxic effects on zebrafish (Danio rerio), investigated in the laboratory, were associated with embryotoxic effects in trout exposed in streamwater bypass systems at the two rivers. In general, responses at all levels of organization were more pronounced in samples from the Schussen than in those from the Argen. These results are consistent with the magnitudes of chemical pollution in these two streams. Plausibility chains to establish causality between exposures and effects and to predict effects in biota in the river from studies in the laboratory are discussed.

Are in vitro methods for the detection of endocrine potentials in the aquatic environment predictive for in vivo effects? Outcomes of the Projects SchussenAktiv and SchussenAktivplus in the Lake Constance Area, Germany.

Many studies about endocrine pollution in the aquatic environment reveal changes in the reproduction system of biota. We analysed endocrine activities in two rivers in Southern Germany using three approaches: (1) chemical analyses, (2) in vitro bioassays, and (3) in vivo investigations in fish and snails. Chemical analyses were based on gas chromatography coupled with mass spectrometry. For in vitro analyses of endocrine potentials in water, sediment, and waste water samples, we used the E-screen assay (human breast cancer cells MCF-7) and reporter gene assays (human cell line HeLa-9903 and MDA-kb2). In addition, we performed reproduction tests with the freshwater mudsnail Potamopyrgus antipodarum to analyse water and sediment samples. We exposed juvenile brown trout (Salmo trutta f. fario) to water downstream of a wastewater outfall (Schussen River) or to water from a reference site (Argen River) to investigate the vitellogenin production. Furthermore, two feral fish species, chub (Leuciscus cephalus) and spirlin (Alburnoides bipunctatus), were caught in both rivers to determine their gonadal maturity and the gonadosomatic index. Chemical analyses provided only little information about endocrine active substances, whereas the in vitro assays revealed endocrine potentials in most of the samples. In addition to endocrine potentials, we also observed toxic potentials (E-screen/reproduction test) in waste water samples, which could interfere with and camouflage endocrine effects. The results of our in vivo tests were mostly in line with the results of the in vitro assays and revealed a consistent reproduction-disrupting (reproduction tests) and an occasional endocrine action (vitellogenin levels) in both investigated rivers, with more pronounced effects for the Schussen river (e.g. a lower gonadosomatic index). We were able to show that biological in vitro assays for endocrine potentials in natural stream water reasonably reflect reproduction and endocrine disruption observed in snails and field-exposed fish, respectively.

[MRSA and ESBL in outpatient: development from 2008 up to 2012 and socio demographic differences]. / MRSA und ESBL in der ambulanten Versorgung: Entwicklung in den Jahren 2008 bis 2012 sowie soziodemografische Unterschiede.

Data on resistance from ambulatory care are rarely available, since surveillance systems cover mostly isolates come from inpatient care. The outpatient setting is of interest, however, since it is where hospitalized patients with resistant pathogens are also treated as outpatients, and where patients are seen who have resistant pathogens from other sources, such as food. In addition, 85% of the antibiotics used in human medicine, are used in ambulatory care. Using data from the Antibiotic Resistance Surveillance System (ARS), we show the development of resistance of Staphylococcus aureus to oxacillin and of Escherichia coli and Klebsiella pneumoniae to cefotaxime in outpatient care between 2008 and 2012 and corresponding socio-demographic differences in the resistance rate. According to our analyses, the proportion of MRSA in S. aureus since 2009 in the outpatient sector decreased (all materials: 2009 11.5%, 2012 9.8%), which is similar to inpatient care, while the proportion of ESBL in E. coli (2008 2.7%, 2012 5.6%), and K. pneumoniae (2008 2.7%, 2012 6.6%) increased over the total period. At the same time resistance for the three pathogens in both sexes over the age groups continuously increased, women still hold a lower proportion of resistance than men. The resistance levels of S. aureus and K. pneumoniae in ambulatory care are reflected at a lower level than in hospital care. In contrast, the high proportion of resistant E. coli in children suggests another source in ambulatory care.

Metabolic transit of dietary methylglyoxal.

Methylglyoxal (MGO) is responsible for the pronounced antibacterial activity of manuka honey, in which it may reach concentrations up to 800 mg/kg. As MGO formed in vivo is discussed to play a role in diabetic complications, the metabolic transit of dietary MGO was studied within a 3 day dietary recall with four healthy volunteers. Determination of MGO in 24 h urine was performed with GC-MS after derivatization with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine, and D-lactate was quantified enzymatically. Following a diet virtually free from MGO and other glycation compounds, a defined amount of MGO (500 µmol in manuka honey) was administered in the morning of day 2. Renal excretion was between 0.1 and 0.4 µmol/day for MGO and between 50 and 220 µmol/day for D-lactate. No influence on excretion of both compounds was observed following administration of MGO. To investigate the stability of MGO under physiological conditions, a simulated in vitro gastrointestinal digestion was performed with MGO-containing honey. After 8 h of in vitro digestion, only 5-20% of the initial methylglyoxal was recovered. This indicates that dietary MGO is rapidly degraded during the digestion process in the intestine and, therefore, exerts no influence on the MGO level in vivo.

Modelling the removal of p-TSA (para-toluenesulfonamide) during rapid sand filtration used for drinking water treatment.

A finite element model was set-up to determine degradation rate constants for p-TSA during rapid sand filtration (RSF). Data used for the model originated from a column experiment carried out in the filter hall of a drinking water treatment plant in Berlin (Germany). Aerated abstracted groundwater was passed through a 1.6m long column-shaped experimental sand filter applying infiltration rates from 2 to 6mh(-1). Model results were fitted to measured profiles and breakthrough curves of p-TSA for different infiltration rates using both first-order reaction kinetics and Michaelis-Menten kinetics. Both approaches showed that degradation rates varied both in space and time. Higher degradation rates were observed in the upper part of the column, probably related to higher microbial activity in this zone. Measured and simulated breakthrough curves revealed an adaption phase with lower degradation rates after infiltration rates were changed, followed by an adapted phase with more elevated degradation rates. Irrespective of the mathematical approach and the infiltration rate, degradation rates were very high, probably owing to the fact that filter sands have been in operation for decades, receiving high p-TSA concentrations with the raw water.

Investigation of the fate of sulfonamides downgradient of a decommissioned sewage farm near Berlin, Germany.

The drinking water production of a drinking water treatment plant in Berlin is affected by ambient contaminated groundwater. The three organic compounds para-toluenesulfonamide (p-TSA), ortho-toluenesulfonamide (o-TSA) and benzenesulfonamide (BSA) were identified in the catchment area of this plant. The groundwater pollution is a result of former sewage farm irrigation in the area, operating for almost 70 years until the 1980s. The distribution of the sulfonamides in the anoxic groundwater was investigated, and a large number of observation and production wells were sampled for this purpose. The contaminant plume is 25 m3000 m2000 m (depth, length, width) in size. The high concentrations of p-TSA, o-TSA and BSA in the groundwater show that the sulfonamides persist over decades in an anoxic aquifer environment. Groundwater quality assessment revealed that elevated concentrations of the analytes can be expected in the abstraction well galleries in the future. Therefore, sulfonamides should periodically be monitored in the drinking water (maximum allowed concentration of 0.30 microg/L of p-TSA and for o-TSA and BSA, a limit of 0.10 microg/L for unknown substances applies). Because of the widespread application and the persistence of the sulfonamides under anoxic conditions, our local investigations suggest that the substances may generally be present in groundwater under the influence of sewage irrigation. Incubation experiments were conducted under in situ hydrostatic pressure to study the behaviour of these trace organic compounds under different redox conditions (oxic and anoxic). Groundwater sampling equipment was either sterilised or not sterilised in order to distinguish between microbiological processes occurring in the aquifer and those representing sampling and storage artefacts (incubation experiments). Results showed that the addition of oxygen to the anoxic groundwater facilitates p-TSA and o-TSA degradation. Hence, while the substances are persistent under anoxic conditions, they are more degradable in the presence of oxygen. Results also illustrate that maintaining anoxic conditions or applying appropriate preservation techniques is necessary to ensure accurate analysis.

Behaviour and biodegradation of sulfonamides (p-TSA, o-TSA, BSA) during drinking water treatment.

Three sulfonamides -para-toluenesulfonamide (p-TSA), ortho-toluenesulfonamide (o-TSA) and benzenesulfonamide (BSA) - have recently been detected in groundwater within a catchment area of one drinking water treatment plant (DWTP), which is located downstream of a former sewage farm. The degradation pathways of p-TSA, o-TSA and BSA were investigated during drinking water treatment with incubation experiments and an experimental filter. Incubation experiments showed that p-TSA is removed during the treatment by microbiological processes. Removal of p-TSA is performed by adapted microorganisms only present in polluted groundwater. The elimination in an experimental filter of 1.6m length applying filtration velocities from 2 to 6 m h(-1) was approximately 93% of p-TSA. The microbial degradation rates in the incubation experiment were approximately 0.029 microg l(-1) h(-1) (zero order reaction). In the experimental filter, the reaction rate constants were around 0.0063 s(-1) for all filtration velocities (1st order reaction). Drinking water treatment does not reduce the concentration of o-TSA and BSA under conditions encountered in Berlin. p-TSA, o-TSA and BSA were only measured in the low microg l(-1) concentrations range in the purified water.

Identification and significance of sulphonamides (p-TSA, o-TSA, BSA) in an urban water cycle (Berlin, Germany).

Because of the nature of the water cycle in Berlin, a number of persistent wastewater residues are present in the surface water and may potentially reach the groundwater via bank filtration and artificial recharge. The occurrence and behaviour of the wastewater residues para-toluenesulphonamide (p-TSA), ortho-toluenesulphonamide (o-TSA) and benzenesulphonamide (BSA) through wastewater treatment, surface water, bank filtration and drinking water treatment was studied. In addition, groundwater below a former sewage farm was investigated. All three compounds are ubiquitous in the aquatic environment of Berlin. p-TSA concentrations are much higher than those of o-TSA and BSA. p-TSA was found in high concentrations in the wastewater influent (2 to 15microg/L), in the wastewater effluent (<0.15 to 2.34microg/L) and in sewage farm groundwater (<0.05 to 20microg/L) and in lower concentrations in the surface water (<0.05 to 1.15microg/L), bank filtrate (<0.05 to 0.30microg/L) and drinking water (<0.05 to 0.54microg/L). p-TSA is considerably depleted during waste- and drinking water treatment ( approximately 90% reduction each). The concentration ranges for o-TSA and BSA in wastewater influents were 0.11 to 8microg/L and <0.05 to 0.64microg/L, respectively, while the values for wastewater effluents were 0.14 to 4microg/L for o-TSA and 0.25 to 0.49microg/L for BSA. Wastewater treatment and drinking water treatment do not reduce the concentrations of o-TSA and BSA. The behaviour of o-TSA during wastewater treatment varies largely between different wastewater treatment plants where concentrations increase, remain constant or decrease. BSA forms during treatment. The concentrations measured in surface water, sewage farm groundwater, bank filtrate and drinking water were <0.05 to 1.74microg/L for o-TSA and <0.05 to 0.53microg/L for BSA.

Quantitative determination of three sulfonamides in environmental water samples using liquid chromatography coupled to electrospray tandem mass spectrometry.

An analytical method was developed to detect the three sulfonamides para-toluenesulfonamide (p-TSA), ortho-toluenesulfonamide (o-TSA) and benzenesulfonamide (BSA) in environmental water samples at concentrations down to 0.02 microg/L using liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Wastewater, surface water, groundwater and drinking water samples from Berlin (Germany) were analysed for all three compounds which appear to be ubiquitously present in the aquatic environment. p-TSA was found in high concentrations in the wastewater (<0.02-50.8 microg/L) and in groundwater below a former sewage farm (<0.02-41 microg/L), and in lower concentrations in the surface water (<0.02 to 1.15 microg/L) and drinking water (<0.02-0.27 microg/L). o-TSA and BSA were detected in considerably lower concentrations. The study makes clear that p-TSA should be monitored because of its comparatively high concentration in Berlin's drinking water.

Pathogenicity of entomopathogenic fungi on hibernating pupae of Cameraria ohridella Deschka & Dimic 1986 (Lepidoptera, Gracillariidae). Part 2: Efficacy of entomopathogenic fungi against pupa in her pupal cell.

The naked pupae of chestnut leafminer Cameraria ohridella are susceptible for entomopathogenic fungi Paecilomyces fumosoroseus strain P6; Lecanicillium muscarium strain V24; Metarhizium anisopliae strain M72 and Beauveria bassiana strain B412. Their activity at low temperature is advantageous especially for the use in the winter season. (Richter et al., 2007a). Therefore the possibility of infection should be examined in biotest for pupae in their pupal cells on leaf of chestnut at conditions Like in winter. Efficacy of entomopathogenic fungi is decreased, if pupae are in their pupal cells. But fungi, especially L. muscarium, proved the ability to infect pupae of C. ohridella in their pupal cells. Infected pupae moulded in their pupal cells after application. Infection doesn't come from spores. In semi field trials with L. muscarium 60% of pupae were infected in their pupal cells and died after incubation with mouldiness.

Pathogenicity of entomopathogenic fungi on hibernating pupae of Cameraria ohridella Deschka & Dimic 1986 (Lepidoptera, Gracillariidae). Part 1: Pathogenicity against the naked pupa.

Strains from Paecilomyces fumosoroseus, Lecanicillium muscarium, Metarhizium anisopliae and Beauveria bassiana were examined in standardized Biotest to control the horse-chestnut leaf miner (Cameraria ohridella) in her pupal stage in winter. The fungi were pathogenic against the hibernating pupae of Cameraria ohridella at dose of 1.9 x 10(7) conidia/ml. They were aggressive, led to infection, death and mouldiness of naked pupae. Even at low temperature of 5 degrees C and 12 degrees C. L. muscarium strain V24 showed the highest pathogenicity after 4 weeks against this host, close followed by P. fumosoroseus strain P6. M. anisopliae strain 72 and 8. bassiana strain B412 were also pathogen but after a long-time period. Experiments gave information for general susceptibility of naked pupae of C. ohridella under low temperatures against entomopathogenic fungi. In further examinations it has to be tested, whether fungi can infected, when the pupae stay in their natural surroundings, the pupal cell in the leaf.