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Biomedical subjects

K Kümmerer

Publications and source records attributed to K Kümmerer.

At least 19 recordsLinked to original sources

[Ampicillin and sulbactam concentrations in the irradiated mandible after oral squamous cell cancer].

INTRODUCTION: Radiation therapy of the oral and maxillo-facial region increases the risk of an infected osteoradionecrosis (IORN) which is a severe complication. Therefore, perioperative antibiotics for the prophylaxis of ORN is a standard in clinical oncology. The combination therapy of ampicillin and sulbactam (Unacid) promises a good therapeutic and prophylactic outcome. PATIENTS: We compared the concentration of Unacid in bone and blood specimens of 22 irradiated patients. All patients were irradiated with 39.6 Gy prior to surgery. The specimens were obtained during the operation 3 weeks after the end of the radiation therapy. RESULTS: The concentration of ampicillin/sulbactam in the blood was 124.9/64.5 microg/ml. The bone specimens showed a concentration of ampicillin/sulbactam of 5.54/1.21 microg/g. The concentration of the antibiotic in the bone was three to four times lower than in non-irradiated patients. Nevertheless, this concentration exceeds the minimum inhibitory concentration for bacteria in the oral cavity such as streptcoccae (MHK90<0.25 microg/ml) or staphylococcae (MHK90=0.12-2.0 microg/ml). CONCLUSIONS: The results of this study suggest, that Unacid is an effective antibiotic in the prophylaxis of ORN in irradiated patients with head and neck tumors.

Adult↗

Resistance in the environment.

Antibiotics, disinfectants and bacteria resistant to them have been detected in environmental compartments such as waste water, surface water, ground water, sediments and soils. Antibiotics are released into the environment after their use in medicine, veterinary medicine and their employment as growth promoters in animal husbandry, fish farming and other fields. There is increasing concern about the growing resistance of pathogenic bacteria in the environment, and their ecotoxic effects. Increasingly, antibiotic resistance is seen as an ecological problem. This includes both the ecology of resistance genes and that of the resistant bacteria themselves. Little is known about the effects of subinhibitory concentrations of antibiotics and disinfectants on environmental bacteria, especially with respect to resistance. According to the present state of our knowledge, the impact on the frequency of resistance transfer by antibacterials present in the environment is questionable. The input of resistant bacteria into the environment seems to be an important source of resistance in the environment. The possible impact of resistant bacteria on the environment is not yet known. Further research into these issues is warranted.

Anti-Bacterial Agents↗

Serum bactericidal activity of piperacillin/tazobactam against Staphylococcus aureus, piperacillin-susceptible and piperacillin-resistant Escherichia coli and Pseudomonas aeruginosa.

BACKGROUND: The serum bactericidal test measures the highest level of an antibiotic-containing serum dilution at which 99.9% of bacteria are killed. In this study the serum bactericidal activity of piperacillin/tazobactam was determined for bacteria often involved in severe infections. In earlier studies titres >/=1:8 in the serum bactericidal tests correlated well with clinical success in the treatment of endocarditis and osteomyelitis as well as bacterial eradication. METHODS: Blood samples of 6 healthy volunteers were taken before and 1 and 4 h after piperacillin/tazobactam (4.5 g) administration. Serum concentrations and serum bactericidal activity were determined for 10 strains each of Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, both piperacillin-resistant and piperacillin-susceptible according to NCCLS guidelines. RESULTS: 100% of S. aureus and piperacillin-susceptible E. coli, 90% of piperacillin-resistant E. coli and 80% of P. aeruginosa were killed 1 h after drug administration. 4 h after drug administration serum bactericidal activity decreased to 60% for S. aureus, 90% for piperacillin-susceptible E. coli, 80% for piperacillin-resistant E. coli and 30% for P. aeruginosa. CONCLUSIONS: Excellent serum bactericidal activity of piperacillin/tazobactam was recorded 1 h after drug administration for S. aureus, E. coli and P. aeruginosa. After 4 h limited killing rates for P. aeruginosa could be detected, which supports the idea of a combination therapy.

Adult↗

Promoting resistance by the emission of antibiotics from hospitals and households into effluent.

OBJECTIVE: There is growing concern about bacterial resistance to antimicrobials. The majority of antibiotics used are only partially metabolized after administration, and are released via patient excreta into the municipal sewage system. Data on the use of antibiotics and their emission into hospital effluent are not available. METHODS: Antibiotic consumption in Germany was calculated on the basis of five hospitals of varying size and medical service spectrum and on prescriptions issued by medical practitioners. The predicted environmental concentration (PEC) was calculated for hospital effluent and for municipal sewage. The PECs were compared both with published minimum inhibitory concentrations (MIC50) for sensitive pathogenic bacteria and with the predicted no-effect concentrations (PNECs). RESULTS: The amount of antibiotics emitted into hospital effluent may reach and exceed the MIC50 of susceptible pathogenic bacteria. The PEC/PNEC ratio is highest for hospital effluent (in some cases 10-20 times the MIC50) and frequently > 1 for municipal sewage. PECs are high enough for some compounds to have a PEC/PNEC ratio > 1 even in surface water. CONCLUSION: The volume of antibiotics used in hospitals and private households and released into effluent and municipal sewage indicates a selection pressure on bacteria. Steps should be taken to reduce the risk by proper handling of antibiotics and their residues both in hospitals and by private users.

Anti-Bacterial Agents↗

New and rapid fully automated method for determination of tazobactam and piperacillin in fatty tissue and serum by column-switching liquid chromatography.

A sensitive and rapid HPLC assay for determining tazobactam and piperacillin in fatty tissue and serum is described. While the common methods need liquid-liquid extraction before the injection in a automated column switching HPLC, the new method works by direct injection of the filtered tissue extract or diluted serum in a automated column switching HPLC without any other pre-treatment. This was performed by the use of a NH2-precolumn and enrichment/transfer at different pH-level. During the analyses, the NH2-precolumn was automatically regenerated with acetonitrile-water. The chromatogram peaks for piperacillin and tazobactam were identified by the retention time and quantified by peak area. The calibration curve was linear between 1 and 16 microg/ml. The quantification limit of tazobactam was about 1 microg/ml in fatty tissue extracts and in diluted serum (calculated for pure serum 2 microg/ml), respectively. For piperacillin it was less. The described procedure allows sample clean-up and determination of the antibiotic within 35 min. The chromatograms with this easy sample treatment had the same quantity of matrix peaks and in contrast to liquid-liquid extraction no loss of piperacillin. Because of the automatically rinsing of the NH2-precolumn during the chromatographic separation, more than 50 different biological samples could be measured with one NH2-precolumn without loss of performance.

Adipose Tissue↗

A new and rapid method for monitoring the new oxazolidinone antibiotic linezolid in serum and urine by high performance liquid chromatography-integrated sample preparation.

A sensitive and rapid HPLC-assay for determining the new oxazolidinone antibiotic linezolid in serum and urine is described. HPLC-integrated sample preparation permits the direct injection of serum and urine samples without any pre-treatment. The in-line extraction technique is realized by switching automatically from the extraction column to the analytical column. After the matrix has passed the extraction column the retained analyte will be quantitatively transferred to the analytical column where separation by isocratic HPLC will be performed. Linezolid is detected according to its absorption maximum at 260 nm. The quantification limits are estimated to be 0.3 and 0.5 microg/ml in serum and urine samples, respectively. The described procedure allows sample clean-up and determination of the antibiotic within 20 min, thereby facilitating drug-monitoring in clinical routine.

Acetamides↗

Rapid antibiotic drug monitoring: meropenem and ceftazidime determination in serum and bronchial secretions by high-performance liquid chromatography-integrated sample preparation.

A sensitive and rapid HPLC assay for the determination of the beta-lactam antibiotics ceftazidime and meropenem in serum and bronchial secretions is described. HPLC-integrated sample preparation allows direct injection of serum samples without any pretreatment. Sputum samples need only a simple homogenisation and volume measurement but no liquefying reagents are necessary. The inline extraction technique is realized by automatically switching from the extraction column to the analytical column. After the matrix passed the extraction column, the retained analyte is quantitatively transferred to the analytical column where separation by isocratic HPLC is performed. Ceftazidime and meropenem are detected according to their absorption maxima at 258 and 296 nm, respectively. The detection limit of both antibiotics is estimated to be better than 0.5 microg/ml in serum as well as in sputum samples. The described procedure allows determination of the antibiotics within 30-45 min, thereby facilitating drug monitoring in clinical routine.

Bronchi↗

Drugs in the environment: emission of drugs, diagnostic aids and disinfectants into wastewater by hospitals in relation to other sources--a review.

After administration, pharmaceuticals are excreted by the patients into wastewater. Unused medications are sometimes disposed of in drains. The drugs enter the aquatic environment and eventually reach drinking water if they are not biodegraded or eliminated during sewage treatment. Additionally, antibiotics and disinfectants are supposed to disturb the wastewater treatment process and the microbial ecology in surface waters. Furthermore, resistant bacteria may be selected in the aeration tanks of STPs by the antibiotic substances present. Recently, pharmaceuticals have been detected in surface water, ground water and drinking water. However, only little is known about the significance of emissions from households and hospitals. A brief summary of input by different sources, occurrence, and elimination of different pharmaceutical groups such as antibiotics, anti-tumour drugs, anaesthetics and contrast media as well as AOX resulting from hospital effluent input into sewage water and surface water will be presented.

Anesthetics↗

Biodegradation of the antineoplastics vindesine, vincristine, and vinblastine and their toxicity against bacteria in the aquatic environment.

Antineoplastics are excreted into sewage, because patients often poorly metabolize them after administration or they are metabolized into more biologically reactive metabolites. There is little information on their biodegradation and toxicity in aquatic environments. Therefore, the biodegradability of the vinca alkaloids, and their toxicity towards wastewater bacteria were investigated in this study. The biodegradability of vindesine, vincristine, and vinblastine was examined in the closed bottle test (CBT). Additionally, the biodegradability of vinblastine as a model compound of the vinca alkaloids was tested in the Zahn-Wellens test (ZWT). The growth inhibition test with Pseudomonas putida was conducted, and a toxicity control in the CBT and the ZWT was used. The colony-forming units were monitored in the CBT; the test results for the biodegradability after 28 days were: 30% for vincristine, 20% for vindesine, and 10% for vinblastine. Therefore, none of the test compounds met the criteria for being readily biodegradable (> or = 60%). Vinblastine was biodegraded up to 18% in the ZWT after 40 days, and therefore, not inherently. Toxicity towards wastewater bacteria was not found.

Antineoplastic Agents, Phytogenic↗

Biodegradability of some antibiotics, elimination of the genotoxicity and affection of wastewater bacteria in a simple test.

Most antibiotics and their metabolites are excreted by humans after administration and therefore reach the municipal sewage with the excretions. Only little is known about their biodegradability in aquatic environments. It was recognised that genotoxic substances may represent a health hazard to humans but also may affect organisms in the environment. Therefore, the biodegradability of some clinically important antibiotic drugs (ciprofloxacin, ofloxacin, metronidazole) and hereby the elimination of their genotoxicity was investigated as the first step of an environmental risk assessment using the Closed Bottle test (CBT) (OECD 301 D) and the SOS chromotest. Additionally, to assess toxicity of the antibiotics tested against aquatic bacteria (i) a growth inhibition test (GIT) with Pseudomonas putida was conducted, (ii) a toxicity control was used in the CBT and (iii) the colony forming units (CFUs) were monitored in the test vessels. Worst case concentrations of the antibiotics in hospital effluents were estimated and compared with minimum inhibitory concentrations for susceptible pathogenic bacteria and with the genotoxic potency in the SOS chromotest. Both the concentrations calculated for hospital effluents and the adverse effects in bacteria were in the same order of magnitude. None of the test compounds were biodegraded. The genotoxicity was not eliminated.

Anti-Bacterial Agents↗

Biodegradability of antineoplastic compounds in screening tests: influence of glucosidation and of stereochemistry.

Some pharmaceuticals such as antineoplastics are carcinogenic, mutagenic, teratogenic and fetotoxic. Antineoplastics and their metabolites are excreted by patients into waste water. In laboratory testing the frequently used isomeric anti-tumour agents cyclophosphamide (CP) and ifosfamide (IF) were shown to be not biodegradable. They are not eliminated in municipal sewage treatment plants and therefore detected in their effluents. Structural related compounds are beta-D-glucosylisophosphoramidmustard (beta-D-Glc-IPM; INN = glufosfamide) and beta-L-glucosylisophosphoramidmustard (beta-L-Glc-IPM). beta-L-Glc-IPM has no antineoplastic effects whereas beta-D-Glc-IPM is active against tumours. In contrast to IF and CP and almost all other investigated antineoplastics beta-D-Glc-IPM is inherently biodegradable. Improved biodegradability of beta-D-Glc-IPM compared to IF shows that reducing the impact of pharmaceuticals on the aquatic environment is feasible by changing the chemical structure of a given compound exerting a similar mode of action and therapeutic activity. Stereochemistry may be crucial for pharmaceutical activity of the compounds as well as for its biodegradability in the environment.

Antineoplastic Agents↗

Drugs, diagnostic agents and disinfectants in wastewater and water--a review.

After administration pharmaceuticals are excreted by the patients into the aquatic environment via wastewater. Unused medications are sometimes disposed of in drains. The drugs may enter the aquatic environment and eventually reach drinking water, if they are not biodegraded or eliminated during sewage treatment. Additionally, antibiotics and disinfectants are assumed to disturb the wastewater treatment process and the microbial ecology in surface waters. Furthermore, resistant bacteria may be selected in the aeration tanks of sewage treatment plants by the antibiotic substances present. Since the 1980s, data on the occurrence of pharmaceuticals in natural surface waters and the effluents of sewage treatment plants have been reported. More recently, pharmaceuticals have been detected in ground and drinking water. However, only little is known about the risk imposed on humans by pharmaceuticals and their metabolites in surface and drinking water. An overview of input, occurrence, elimination (e.g. biodegradability) and possible effects of different pharmaceutical groups such as anti-tumour drugs, antibiotics and contrast media as well as AOX resulting from hospitals effluent input into sewage water and surface water is presented.

Anti-Bacterial Agents↗

European hospitals as a source for platinum in the environment in comparison with other sources.

The concentration of platinum in the sewage of five European hospitals originating from excreted antineoplastic drugs, cisplatin and carboplatin, was analyzed in a short term study to provide an order of magnitude of Pt emissions from hospitals into aquatic environments. These emissions were compared with a rough estimation of emissions by cars. The average daily concentrations in the hospital effluents were approximately < 10-601 ng l-1 Pt (20-3580 ng l-1 in 2-h mixed samples). As expected from consumption data, the daily average concentrations should range from < 10-710 ng l-1 Pt. Platinum emitted by hospitals is 3.3-12.3% (1.3-14.3 kg per year) the estimated amount emitted by cars equipped with catalytic converters in the different European countries. Compared to platinum emissions from other sources, the effluents of hospitals are a minor source of platinum in municipal sewage, but they should not to be disregarded. Other possible sources for the emission of platinum into the environment should be considered in further investigations.

Antineoplastic Agents↗

AOX-emissions from hospitals into municipal waste water.

Adsorbable organically bound halogens (AOX) are mostly persistent in the environment, and accumulate in the food web. Some of them are toxic to humans and other organisms. AOX were measured in the effluents from six German hospitals of different size and departments like internal medicine and ear-nose and throat (ENT) as well as from laundry, kitchen and laboratory. The concentrations in the day time mixed samples of the total effluent were 0.13 mg l(-1)-0.94 mg l-1 (phi = 0.43 mg l-1). For the separately investigated departments the lowest concentrations were found in the effluent from laundry and kitchen (0.015 mg l-1), and the highest ones in the effluents from the medical departments (0.12-1.71 mg l-1, phi 0.95 mg l-1 during the week and 0.06-0.10 mg l-1 at the week-end) and the laboratories (0.05-14.2 mg l-1, phi 2.73 mg l-1). The AOX concentration in night time mixed samples were 0.07-0.41 mg l-1 (phi = 0.41 mg l-1) for the total effluents and 0.25-2.64 mg l-1 (phi = 1.11 mg l-1) for medical departments. Concentrations expected by computing the input of AOX attributable to pharmaceuticals were between 11% and 16% for two hospitals and 7.7% for an ENT department. One additional important source of AOX in hospital effluents may be x-ray contrast media containing a iodine carbon bond.

Adsorption↗