RESUMO
OBJECTIVES: Carbapenem resistance in Gram-negative bacteria, mediated by restricted net influx and carbapenem-hydrolysing ß-lactamases, is a growing problem. The monosulfactam antibiotic BAL30072 is stable to most carbapenemases, suggesting that it could be complementary to carbapenems. We have investigated the antimicrobial activity of BAL30072 combined with imipenem, meropenem and doripenem. METHODS: The in vitro activities of the combinations were evaluated using broth microdilution susceptibility and agar disc diffusion tests, broth dilution chequerboard titration and time-kill studies, using strains of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter with carbapenem MICs ≥â2 mg/L. RESULTS: The combinations were effective against 70%-80% of the isolates tested in the presence of 1 mg/L of each antibiotic, whereas the carbapenems were ineffective and BAL30072 alone was effective against 20%-40% of the strains. Synergistic effects were observed with many Enterobacteriaceae and P. aeruginosa, but were less common among the Acinetobacter, although additive effects, where the activity of one partner compensated for lack of activity of the other, were common. None of the combinations exhibited an antagonistic effect in all tests, in contrast to other ß-lactams where negative interactions were frequently observed. Animal models of septicaemia demonstrated that the synergy observed in vitro with BAL30072 and meropenem can translate into greater in vivo efficacy. CONCLUSIONS: BAL30072/carbapenem combinations were effective against a broader range of multidrug-resistant Gram-negative bacteria than either of the single agents. Additive and synergistic effects were observed in Enterobacteriaceae and P. aeruginosa, and this enhanced activity was frequently associated with suppression of resistance development. The in vitro activity translated into improved in vivo efficacy.
Assuntos
Acinetobacter/efeitos dos fármacos , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla , Enterobacteriaceae/efeitos dos fármacos , Monobactamas/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Tiazóis/farmacologia , Doripenem , Sinergismo Farmacológico , Imipenem/farmacologia , Meropeném , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Tienamicinas/farmacologiaRESUMO
BAL30376 is a triple combination comprising a siderophore monobactam, BAL19764; a novel bridged monobactam, BAL29880, which specifically inhibits class C ß-lactamases; and clavulanic acid, which inhibits many class A and some class D ß-lactamases. The MIC(90) was ≤ 4 µg/ml (expressed as the concentration of BAL19764) for most species of the Enterobacteriaceae family, including strains that produced metallo-ß-lactamases and were resistant to all of the other ß-lactams tested. The MIC(90) for Stenotrophomonas maltophilia was 2 µg/ml, for multidrug-resistant (MDR) Pseudomonas aeruginosa it was 8 µg/ml, and for MDR Acinetobacter and Burkholderia spp. it was 16 µg/ml. The presence of the class C ß-lactamase inhibitor BAL29880 contributed significantly to the activity of BAL30376 against strains of Citrobacter freundii, Enterobacter species, Serratia marcescens, and P. aeruginosa. The presence of clavulanic acid contributed significantly to the activity against many strains of Escherichia coli and Klebsiella pneumoniae that produced class A extended-spectrum ß-lactamases. The activity of BAL30376 against strains with metallo-ß-lactamases was largely attributable to the intrinsic stability of the monobactam BAL19764 toward these enzymes. Considering its three components, BAL30376 was unexpectedly refractory toward the development of stable resistance.
Assuntos
Antibacterianos/farmacologia , Ácido Clavulânico/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Monobactamas/farmacologia , Compostos de Fenilureia/farmacologia , Inibidores de beta-Lactamases , Animais , Citrobacter freundii/efeitos dos fármacos , Enterobacter/efeitos dos fármacos , Bactérias Gram-Negativas/patogenicidade , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Camundongos , Pseudomonas aeruginosa/efeitos dos fármacos , Sepse/tratamento farmacológico , Sepse/microbiologia , Serratia marcescens/efeitos dos fármacosRESUMO
The metabolic profile of BAL4815, an antifungal azole drug, was determined using in vitro rat hepatocyte incubations and subsequent analysis by capillary LC-qTof-MS and MS/MS including accurate mass determination. For the detection of the metabolites, a mixture of the drug and its deuterium-labelled analogue was used for incubations. Metabolic stability of BAL4815 was high in cultured rat hepatocytes. However, several low-abundant metabolites were detected by the use of capillary LC-qTof-MS and manual investigation of the data. The peak intensity of the most abundant metabolite was close to the limit of detection. Except for an apparent oxidation product, the masses of the other detected metabolites could not be assigned to a single and frequently occurring biotransformation. Accurate mass determination and possible elemental compositions suggested that metabolism occurred through a combination of glutathionylation and defluorination. This was verified using accurate mass MS/MS. The use of accurate mass measurements and the derived suggestions for the elemental compositions were essential to elucidate this atypical metabolic pathway. A mass accuracy better than 8 ppm could be achieved for most assigned MS and MS/MS signals with intensities less than 6 cps in the spectra.
Assuntos
Antifúngicos/química , Hepatócitos/metabolismo , Nitrilas/química , Nitrilas/metabolismo , Triazóis/química , Triazóis/metabolismo , Animais , Antifúngicos/isolamento & purificação , Ação Capilar , Cromatografia Líquida/métodos , Deutério , Marcação por Isótopo , Masculino , Espectrometria de Massas/métodos , Modelos Moleculares , Nitrilas/isolamento & purificação , Ratos , Ratos Wistar , Espectrometria de Massas por Ionização por Electrospray/métodos , Triazóis/isolamento & purificaçãoRESUMO
Endosymbiotic bacteria from the genus Bacillus were isolated from different compartments of the gut of various members of insects (Hexapoda) and millipedes (Diplopoda). They were grown in submerged culture and investigated by biological assays and HPLC-diode array analysis regarding their production of bioactive metabolites, which were isolated and determined in structure. Known compounds and yet unknown derivatives from the primary metabolism were detected, as well as antibacterially and antifungally acting peptide antibiotics.
Assuntos
Antibacterianos/isolamento & purificação , Artrópodes/microbiologia , Bacillus/química , Peptídeos , Simbiose , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/classificação , Antifúngicos/isolamento & purificação , Peptídeos Catiônicos Antimicrobianos , Artrópodes/anatomia & histologia , Artrópodes/classificação , Bacillus/isolamento & purificação , Bacitracina/isolamento & purificação , Herbicidas/classificação , Herbicidas/isolamento & purificação , Hipoxantina/isolamento & purificação , Modelos Moleculares , Triptaminas/isolamento & purificação , Uracila/isolamento & purificaçãoRESUMO
A detailed screening of the secondary metabolite pattern produced by different athropod associated strains of the species Streptomyces anulatus resulted in the isolation and structure elucidation of the endophenazines A-D (2, 4-6). The structures were assigned by spectroscopic methods and chemical transformations. 4 represents a chromophoric system based on a phenazin-7-one, 5 and 6 are new 5,10-dihydrophenazine derivatives.
Assuntos
Antibacterianos/química , Artrópodes/microbiologia , Fenazinas/química , Streptomyces/metabolismo , Animais , Espectroscopia de Ressonância MagnéticaRESUMO
Four new members of the phenazine family, endophenazines A-D, and the already known phenazine-1-carboxylic acid (tubermycin B) were detected in the culture broth of various endosymbiotic Streptomyces anulatus strains by chemical screening in a combination of TLC-staining reagents and HPLC-diode array analysis. The endosymbiotic strains were isolated from four different arthropod hosts at various sites. The new phenazine compounds showed antimicrobial activities against Gram-positive bacteria and some filamentous fungi, and herbicidal activity against Lemna minor (duckweed).
Assuntos
Antibacterianos/isolamento & purificação , Artrópodes/microbiologia , Fermentação , Fenazinas/isolamento & purificação , Streptomyces/classificação , Simbiose , Animais , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Fenazinas/farmacologia , Streptomyces/metabolismoRESUMO
Aspochalamins A-D, a family of new cytochalasan antibiotics have been isolated from Aspergillus niveus, an endosymbiotic fungus isolated from the gut of a woodlouse belonging to the family Trichoniscidae. Besides aspochalamins, aspochalasin Z, a new member of the aspochalasin family, as well as the known mycotoxins aspochalasin D and citreoviridins A/C and B were isolated from the mycelium. Aspochalamins showed cytostatic effects towards various tumor cell lines and a weak antibacterial activity against Gram-positive bacteria.
Assuntos
Antibacterianos/biossíntese , Antibacterianos/farmacologia , Aspergillus/metabolismo , Citocalasinas/biossíntese , Citocalasinas/farmacologia , Antibacterianos/química , Antibióticos Antineoplásicos/biossíntese , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Aspergillus/classificação , Bactérias/efeitos dos fármacos , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Citocalasinas/química , Ensaios de Seleção de Medicamentos Antitumorais , Fermentação , Humanos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Espectrofotometria UltravioletaRESUMO
The structures of new cytochalasan fungal metabolites aspochalamins A-D have been elucidated by ESI-FTICR-MS, NMR spectroscopy, and chiral amino acid analysis. Aspochalamins A-D consist of different aspochalasin skeletons connected at position C-19 to the N terminus of the tripeptidic moiety amide anthranoyl-L-alanine-E-didehydrotryptamide. Furthermore, the structure of a new aspochalasin analog, aspochalasin Z, was derived from its molecular mass and NMR data as 10-isopropyl-14-methyl[11]-cytochalasa-6Z,13E,19E-triene-1,21-dione.
Assuntos
Antibacterianos/química , Aspergillus/metabolismo , Aminoácidos/química , Aspergillus/química , Citocalasinas/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta , EstereoisomerismoRESUMO
The structures of new lipopeptide antibiotics, arylomycins A and B, were elucidated by a combination of ESI-FTICR-mass spectrometry, NMR spectroscopy, Edman sequencing, and fatty acid and chiral amino acid analyses. The colourless arylomycins A share the peptide sequence of D-N-methylseryl2(D-MeSer2)-D-alanyl3-glycyl4-N-methyl- 4-hydroxyphenylglycyl5(MeHpg5)-L-alanyl6-tyrosine7 cyclised by a [3,3]biaryl bond between MeHpg5 and Tyr7. The yellow arylomycins B differ from arylomycins A by nitro substitution of Tyr7. The N-termini of arylomycins A and B are acylated with saturated C11-C15 fatty acids (fa1) comprising n, iso, and anteiso isomers. Arylomycins A and B represent the first examples of biaryl-bridged lipopeptides.
Assuntos
Antibacterianos/química , Peptídeos Cíclicos/química , Streptomyces/química , Aminoácidos/análise , Antibacterianos/isolamento & purificação , Ácidos Graxos/análise , Cromatografia Gasosa-Espectrometria de Massas , Espectroscopia de Ressonância Magnética , Peptídeos Cíclicos/isolamento & purificação , Análise de Sequência de ProteínaRESUMO
New lipopeptide antibiotics, colourless arylomycins A series and yellow arylomycins B series were detected in the culture filtrate and mycelium extracts of Streptomyces sp. Tü 6075 by HPLC-diode-array and HPLC-electrospray-mass-spectrometry screening. Arylomycins are a family of lipohexapeptide antibiotics, which represent the first examples of biaryl-bridged lipopeptides. They show antibiotic activities against Gram-positive bacteria.
Assuntos
Antibacterianos/isolamento & purificação , Peptídeos Cíclicos/isolamento & purificação , Streptomyces/metabolismo , Antibacterianos/biossíntese , Antibacterianos/farmacologia , Cromatografia Líquida de Alta Pressão , DNA Bacteriano/química , DNA Bacteriano/genética , Testes de Sensibilidade Microbiana , Peptídeos Cíclicos/biossíntese , Peptídeos Cíclicos/farmacologia , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Microbiologia do Solo , Streptomyces/química , Streptomyces/classificação , Streptomyces/genéticaRESUMO
BACKGROUND: All members of the Statutory Health Insurance are entitled to receive preventive health examinations. The current concept, however, does not take individual risk factors into account systematically. To improve this, the "Bremen Health Examination" was developed. The central component is a screening questionnaire to be completed by the patient, which is stratified by age, i.e., 35 to 69 years and ≥ 70 years. The feasibility and acceptance of this concept have been assessed. METHODS: In a prospective observational study, a selected sample of general practitioners (GPs) was asked to implement the questionnaires during all preventive health examinations within a four-week period. The GPs subsequently answered content-related questions as well as Likert-scaled questions on the relevance of the issues addressed, and the feasibility of the new concept. RESULTS: 17 out of 20 GPs approached for the study included a total of 171 patients. On average, the patients in the two groups were 52 and 75 years of age, respectively, and answered 4.4 prompting questions positively. Age and gender had no significant effect on the frequency of "positively" answered questions. Implementing the questionnaire extended the duration of the health examination, however, GPs overall rated the time required for discussing newly assessed problems as adequate (four-level Likert scale, 1=yes; 4=no; Ø 1.59; SD 0.77). CONCLUSION: The implementation of the Bremen Health Examination appears to be feasible from the GP perspective.
Assuntos
Programas de Rastreamento/normas , Programas Nacionais de Saúde , Exame Físico/normas , Prevenção Primária/normas , Inquéritos e Questionários , Idoso , Diagnóstico Precoce , Estudos de Viabilidade , Feminino , Medicina Geral/organização & administração , Medicina Geral/normas , Alemanha , Implementação de Plano de Saúde/organização & administração , Implementação de Plano de Saúde/normas , Humanos , Masculino , Programas de Rastreamento/organização & administração , Pessoa de Meia-Idade , Exame Físico/métodos , Prevenção Primária/organização & administração , Estudos ProspectivosRESUMO
A systematic comparison between two labeling approaches for the investigation of the in vitro metabolic pattern of pharmaceutical drugs was performed by examining the use of (i) radiolabeled drugs analyzed with LC-MS-offline radiodetection and (ii) stable-isotope labeled drugs, used in a defined mixture with the unlabeled drug and analyzed by LC-MS with recognition of the specific isotopic pattern. (14)C was used for the radioisotope-approach and deuterium for the stable-isotope approach. Olanzapine, diclofenac and ketoconazole were chosen as model drugs, as they are commercially available in their non-, radio- and stable-isotope labeled forms. For all three model drugs, liver microsome- and hepatocyte-incubations (both from rat) were performed with various concentrations and incubation times for both, the radio- and the stable-isotope approaches. The metabolic pattern, including structure elucidation of all detected metabolites, was performed independently for all individual compounds and incubations. Subsequently, the metabolic patterns of the radio-, and the stable-isotope approaches were compared. In conclusion, all metabolites found with the radioisotope approach could also be found with the stable-isotope approach. Although the stable-isotope approach does not provide a quantitative result, it can be considered to be a highly suited analytical alternative for early in vitro metabolism investigations, especially when radiolabeled drug analogues are not yet available and quantitative results are not yet necessary.
Assuntos
Radioisótopos de Carbono , Deutério , Preparações Farmacêuticas/metabolismo , Animais , Benzodiazepinas/metabolismo , Diclofenaco/metabolismo , Hepatócitos/metabolismo , Marcação por Isótopo , Cetoconazol/metabolismo , Masculino , Microssomos Hepáticos/metabolismo , Olanzapina , Ratos , Ratos WistarRESUMO
INTRODUCTION: Because hyperaldosteronism is the most common curable reason for secondary hypertension, screening is recommended. However, prevalence among general practice patients and feasibility of screening is still unclear. A design to assess prevalence in general practice and barriers against screening was created. METHODS: This was an open, observational pilot study and focus group. In 2 general practices, all patients with arterial hypertension were included. Those with resistant hypertension (>140/90 mm Hg and taking ≥3 antihypertensive drugs) were eligible for screening. The design and feasibility of the study were discussed in a focus group of experienced general practitioners. RESULTS: Of 3107 patients visiting the practices, 564 were diagnosed as having arterial hypertension. Seventy-nine fulfilled criteria for resistant hypertension. Aldosterone:renin ratio (ARR) could be measured in 63 of those patients. Withdrawal of ß-blocker was feasible in 34 of the 63 with measurable ARR. ARR was positive in 15, and in 3 of those 15 with positive ARR, it was caused by elevated aldosterone levels. Focus group discussion revealed barriers and concerns regarding organizational, financial, and practical aspects of a systematic screening. CONCLUSIONS: Screening for hyperaldosteronism in general practice seems possible in selected patients, but not in a systematic way. Barriers against systematic screening were a necessity for ß-blocker cessation as well as structural prerequisites for patient identification.
Assuntos
Anti-Hipertensivos/uso terapêutico , Resistência a Medicamentos/fisiologia , Hiperaldosteronismo/diagnóstico , Hipertensão/tratamento farmacológico , Atenção Primária à Saúde , Antagonistas Adrenérgicos beta/administração & dosagem , Idoso , Aldosterona/sangue , Estudos de Viabilidade , Feminino , Alemanha/epidemiologia , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/complicações , Hiperaldosteronismo/epidemiologia , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Renina/sangueRESUMO
Four new terpenoglycoside antibiotics, phenalinolactones A-D were isolated from Streptomyces sp. Tü 6071. The structures were elucidated on the basis of detailed NMR and MS analyses. Phenalinolactones combine a diterpenoid tricycle, a 2,3,6-trideoxysugar, a pyrrole-carboxylic acid and an uncommonly oxidized unsaturated γ-lactone in a unique manner. Phenalinolactones show an inhibitory activity against gram-positive bacteria.
Assuntos
Antibacterianos/isolamento & purificação , Diterpenos/isolamento & purificação , Glicosídeos/isolamento & purificação , Streptomyces/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Lactonas/química , Lactonas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Urinary tract infections (UTI) are among the leading reasons for treatment in adult primary care medicine, accounting for a considerable percentage of antibiotic prescriptions. Because this problem is so common and so significant in routine clinical practice, a high level of diagnostic accuracy is essential. Antibiotics should not be prescribed excessively, particularly in view of the increasing prevalence of antibiotic resistance. METHOD: Systematic review of relevant articles that were retrieved by a search of the Medline, Embase, and Cochrane Library databases. The recommendations of selected international guidelines were also taken into account, as were the German national quality standards for microbiological diagnosis. RESULTS: The diagnosis of UTI by clinical criteria alone has an error rate of approximately 33%. The use of refined diagnostic algorithms does not completely eliminate uncertainty. CONCLUSION: With the aid of a small number of additional diagnostic criteria, antibiotic treatment for UTI can be provided more specifically and thus more effectively. Differentiating UTI from asymptomatic bacteriuria, which usually requires no treatment, can lower the frequency of unnecessary antibiotic prescriptions.
Assuntos
Infecções Bacterianas/diagnóstico , Cistite/diagnóstico , Infecções Urinárias/diagnóstico , Adolescente , Adulto , Idoso , Algoritmos , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/etiologia , Bacteriúria/diagnóstico , Bacteriúria/tratamento farmacológico , Bacteriúria/etiologia , Criança , Ensaio de Unidades Formadoras de Colônias , Cistite/tratamento farmacológico , Cistite/etiologia , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Gravidez , Atenção Primária à Saúde , Garantia da Qualidade dos Cuidados de Saúde/normas , Fatores de Risco , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/etiologia , Adulto JovemRESUMO
The in vitro metabolic profile of BAL30630, an antifungal piperazine propanol derivative, which inhibits the 1,3-beta-D-glucansynthase, was investigated by incubation with microsomes of several species and with rat hepatocytes. For the spotting of the metabolites, mixtures of BAL30630 with a stable isotope (deuterium) labeled analogue were incubated. The metabolic pattern comprises several oxidized metabolites. Based on isotope exchange experiments, their structures could be assigned to epoxide- and hydroxylated metabolites. In hepatocyte incubations, several glucuronides formed from these oxidized metabolites could be observed. From the analysis of the metabolic pattern in microsomes, products of carbamate hydrolysis were characterized. This hydrolysis was highly species dependent. In activated incubations and in rat hepatocytes, those metabolites were further oxidized. In incubations without NADPH activation, the resulting hydrolytic metabolites could be enriched without the subsequent oxidation. Final structural elucidation of the metabolites was performed using accurate mass determination and isotope exchange experiments, in which incubations were analyzed by deuterium exchange and capillary HPLC-QTof-MS and MS/MS. The use of non-radioactive, stabile isotope labeled drug analogues in combination with isotope exchange studies was essential in particular for a defined assignment of the functional groups in the structures of the investigated metabolites.
Assuntos
1-Propanol/farmacocinética , Antifúngicos/farmacocinética , Cromatografia Líquida/métodos , Deutério/metabolismo , Espectrometria de Massas/métodos , 1-Propanol/química , Animais , Antifúngicos/química , Deutério/química , Cães , Cobaias , Haplorrinos , Hepatócitos/química , Hepatócitos/metabolismo , Humanos , Marcação por Isótopo , Camundongos , Microssomos Hepáticos/química , Microssomos Hepáticos/metabolismo , Coelhos , RatosRESUMO
The in vitro metabolic pattern of BAL19403, a novel macrolide antibiotic, was investigated by capillary liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/QTOF-MS) in incubations with human microsomes. For the elucidation of the metabolic pathway, BAL19403 labeled with four deuterium atoms (D4) was used, and detection of metabolites performed using mixtures of the unlabeled (H4) BAL19403 and its D4 analogue (1:1) as substrate. All metabolites appeared with similar chromatographic behavior. MS/MS spectra of BAL19403 and its metabolites are dominated by non-informative fragment ions. Therefore, the structure of the metabolites was elucidated mainly by accurate mass measurements with subsequent proposals of elemental compositions. Main biotransformations were N-demethylation, lactone ring hydrolysis, and oxidation. Additionally, N-dealkylation of the aromatic moiety was identified. This dealkylation results not only in formation of an aldehyde, according to the classical pathway, but also in formation of the corresponding alcohol and carboxylic acid. Final elucidation of their structures was possible, since this dealkylation takes place vicinal to the deuterium-labeled part of BAL19403 and interferes with D/H exchange. The degree of D/H exchange, determined by analysis of the metabolite isotopic pattern, was used to elucidate the adjacent functional group.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Eletroforese Capilar/métodos , Macrolídeos/química , Macrolídeos/farmacocinética , Microssomos/química , Microssomos/metabolismo , Espectrometria de Massas por Ionização por Electrospray/métodos , Células Cultivadas , Humanos , Marcação por Isótopo/métodos , Taxa de Depuração Metabólica , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Streptocidins, a family of tyrocidine-like cyclic decapeptides, are an ideal demonstration object for the detection and in situ structure analysis of natural compounds directly in microbial cells using whole cell matrix-assisted laser desorption/ionization time-of-flight-mass spectrometry (MALDI-TOFMS), an emerging technique that can be used for rapid sensitive metabolic profiling of microorganisms. Five main members of the streptocidin family (A-E) were detected in Brevibacillus cells picked from agar plates and identified by in situ structure analysis with post-source decay MALDI-TOFMS. This efficient modern method allows the precise detection of metabolites within minutes without the need to isolate and purify the target compounds. The generated mass spectra are of similar quality to those obtained for the purified peptides. In addition, surface extracts were prepared by treating Brevibacillus cells with 70% acetonitrile in the presence of 0.1% trifluoroacetic acid and fractionated by high-resolution reversed-phase high-performance liquid chromatography (HPLC). In this way ten minor streptocidins were detected demonstrating the full biosynthetic variety of streptocidin production on the cellular level. The streptocidins differ from the well-known tyrocidines essentially in position 3 of the decapeptide chain by replacement of the aromatic amino acid (F/W) found in tyrocidines by L-leucine or L-valine.