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Featured researches published by H. Grimm.


Infection | 1990

A new plasmidic cefotaximase in a clinical isolate of Escherichia coli

Adolf Bauernfeind; H. Grimm; S. Schweighart

SummaryEscherichia coli GRI was isolated from an ear exudate of a newborn. The strain was highly resistant to cefotaxime (MIC 128 mg/l). Resistance to cefotaxime and the majority of β-lactam antibiotics was readily transferred to anEscherichia coli recipient strain. Both the wild type and the transconjugant strains are different in their resistance phenotype from TEM-3 β-cefotaximase producers by higher MICs to the majority of β-lactams and lower MICs to ceftazidime. The isoelectric point of the cefotaximase ofE. coli GRI was 8.9 in comparison with 6.3 for TEM-3. Thus, the enzyme produced byE. coli GRI represents a new plasmidic (plasmid pMVP-3) broad spectrum β-lactamase (CTX-M) which may not be closely related to either the TEM- oder SHV-family of extended broad spectrum β-lactamases.ZusammenfassungGRI wurde aus dem Ohrexsudat eines Neugeborenen isoliert. Der Stamm war hoch resistent gegenüber Cefotaxim (MHK 128 mg/l). Die Resistenz gegenüber Cefotaxim sowie den meisten übrigen β-Laktamantibiotika war leicht übertragbar auf einen anderenEscherichia coli Stamm. Sowohl derE. coli Wildtypstamm als auch die Transkonjuganten unterscheiden sich in ihrem Resistenzmuster von den TEM-3-cefotaximase produzierenden Stämmen, und zwar durch höhere MHK-Werte gegenüber der Mehrzahl der β-Laktamantibiotika, jedoch niedrigeren MHK-Werten für Ceftazidim. Zudem ist der isoelektrische Punkt der neuen Cefotaximase vonE. coli GRI mit 8,9 gegenüber 6,3 für das TEM-3 Enzym deutlich verschieden. Deshalb liegt mit dem vonE. coli GRI produzierten Enzym eine neue plasmidische (Plasmid pMVP-3) β-Laktamase (CTX-M) mit erweitertem Breitspektrum vor. Sie unterscheidet sich sowohl von den bisher beschriebenen Enzymen der TEM- als auch denen der SHV-Gruppe.


Infection | 1991

Interpretive criteria of antimicrobial disk susceptibility tests with cefpodoxime

H. Grimm

SummaryThe interpretation of disk susceptibility testing with 30 µg cefpodoxime disks was evaluated on the basis of regression line analyses and preliminary MIC breakpoints of 2 and 4 mg/l. Using the DIN-58940 method, zone diameters up to 23 mm are resistant, 24 to 26 mm moderately susceptible, and 27 mm or more susceptible. The respective data for the NCCLS method are: up to 21 mm, 22 to 23 mm, and 24 mm or more.ZusammenfassungDie Interpretation der Testung mit Cefpodoxim-Blättchen (Beladung 30 µg) wurde auf der Basis von Regressionsanalysen und vorläufigen MHK-Grenzwerten von 2 und 4 mg/l untersucht. Bei Benutzung der DIN-58940-Methode bedeuten Hemmhofdurchmesser bis zu 23 mm Resistenz, von 24–26 mm mäßige Empfindlichkeit und von 27 mm oder mehr Empfindlichkeit. Die entsprechenden Werte für die NCCLS-Methode sind: bis zu 21 mm, 22 – 23 mm und 24 mm oder mehr.


Infection | 1979

In vitro investigations with fosfomycin on Mueller-Hinton agar with and without glucose-6-phosphate.

H. Grimm

SummaryDetermination of the minimal inhibitory concentration of fosfomycin in the agar dilution test on Mueller-Hinton agar showed that the addition of glucose-6-phosphate to the nutrient medium potentiates the action of fosfomycin againstEscherichia coli, Klebsiella, Enterobacter, Citrobacter andStaphylococcus aureus, sometimes by as much as 256-fold. Such a potentiation of action was not detectable withSerratia marcescens, the individualProteus species,Pseudomonas aeruginosa or enterococci. Fosfomycin is very effective against most medically important bacterial species on Mueller-Hinton agar containing 25 µg/ml glucose-6-phosphate. Over 90% of the cultures ofE. coli, Citrobacter, Enterobacter, S. marcescens, Proteus mirabilis, Proteus vulgaris, Proteus rettgeri, P. aeruginosa, S. aureus and enterococci examined were inhibited by ≤ 64 µg/ml fosfomycin.ZusammenfassungBestimmungen der minimalen Hemmkonzentration von Fosfomycin im Agardilutionstest auf Mueller-Hinton-Agar zeigen, daß eine Zugabe von Glukose-6-Phosphat zum Nährmedium nur beiEscherichia coli, Klebsiella, Enterobacter, Citrobacter undStaphylococcus aureus die Fosfomycin-Wirkung verstärkt, z. T. bis zu 256fach. So eine potenzierte Wirkung ist bei Serratia marcescens, den einzelnenProteus-Spezies,Pseudomonas aeruginosa oder Enterokokken nicht festzustellen. Auf Mueller-Hinton-Agar mit 25 µg/ml Glukose-6-Phosphat zeigte Fosfomycin eine sehr gute Wirksamkeit gegenüber den meisten medizinisch bedeutsamen Bakterienspezies. Über 90% der untersuchten Kulturen vonE. coli, Citrobacter, Enterobacter, S. marcescens, Proteus mirabilis, Proteus vulgaris, Proteus rettgeri, P. aeruginosa, Staphylococcus aureus und Enterokokken werden durch ≤ 64 µg/ml Fosfomycin gehemmt.


Infection | 1980

Bakteriologische In-vitro-Untersuchungen mit Cefadroxil Korrelation von Hemmhofdurchmesser und minimaler Hemmkonzentration

H. Grimm

ZusammenfassungDie geometrischen Mittelwerte der minimalen Hemmkonzentrationen (MHK) von Cefadroxil ((6R,7R)-7-[(R)-2-Amino-2-(p-hydroxyphenyl)-acetamido]-3-methyl-8-oxo-5-thia-1-azabicyclo-[4.2.0] oct-2-en-2-carbonsäure, Bidocef®) und Cefalexin gegen aus klinischem Material frisch isolierte grampositive und gramnegative Bakterien differieren nur geringfügig; Enterokokken verhalten sich gegen Cefadroxil empfindlicher. Unter Berücksichtigung der unterschiedlichen „Breakpoints“ ist Cefadroxil jedoch meist wirksamer als Cefalexin, besonders beiProteus mirabilis, Enterobacter, Citrobacter undEscherichia coli. Mit der dargestellten Regressionsanalyse ist der Cefadroxil-Agar-Diffusionstest gut interpretierbar.SummaryThere are only slight differences between the geometrical means of minimum inhibitory concentrations of (6R,7R)-7-[(R)-2-amino-2-(p-hydroxyphenyl)-acetamido-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (cefadroxil, Bidocef®) and cefalexin against gram-positive and gramnegative bacteria freshly isolated from clinical material. Enterococci are more susceptible to cefadroxil. Considering the different break points, cefadroxil is on the whole more effective than cefalexin, in particular so againstProteus mirabilis, Enterobacter, Citrobacter andEscherichia coli. With the aid of the described regression analysis a meaningful interpretation of the results of the cefadroxil agar diffusion test is possible.


Infection | 1980

Bakteriologische In-vitro-Untersuchungen mit Cefotaxim im Vergleich zu Cefuroxim und Cefazolin

H. Grimm; R. Rangoonwala

ZusammenfassungDie antibakterielle Wirksamkeit des neuen Antibiotikums Cefotaxim wurde verglichen mit der von Cefazolin und Cefuroxim. Von den 300 aus klinischem Material isolierten Erregern zeigte Cefotaxim eine wesentlich stärkere Aktivität als Cefuroxim, welches eine höhere Wirksamkeit als Cefazolin aufwies. BeiEnterobacter war Cefotaxim 37mal und beiProteus vulgaris sogar über 3000mal wirksamer. Pseudomonaden, die sich gegenüber Cephalosporinen als resistent erwiesen, wurden von Cefotaxim bei einer mittleren minimalen Hemmkonzentration (MHK) von 10,55 mcg/ml an ihrem Wachstum gehindert. Aus den Ergebnissen der Untersuchungen wurden die Regressionsgeraden für Cefotaxim ermittelt. Die Gleichung der Geraden lautet x=−0,40 y+20,00. Daraus folgt für die Empfindlichkeitsgrenze von 4 mcg/ml Cefotaxim ein Hemmhofdurchmesser von ⩾23 mm und für die Resistenzgrenze von 16 mcg/ml ein Hemmhofdurchmesser von ⩽18 mm.SummaryThe antibacterial activity of the new antibiotic cefotaxime was compared with that of cefazolin and cefuroxime. Against 300 pathogens isolated from clinical material, cefotaxime demonstrated considerably more activity than cefuroxime, which in turn was more active than cefazolin. Cefotaxime was 37 times more active againstEnterobacter and as much as 3000 times more active againstProteus vulgaris. The growth of pseudomonads, which are resistant to cephalosporins, was inhibited by an average minimal inhibitory concentration of 10.55 mcg/ml. The regression lines of cefotaxime were derived from the results of the investigation. The equation is x=−0.40y+20.00. We obtained from this an inhibitory zone diameter for cefotaxime of ⩾23 mm at a sensitivity limit of 4 mcg/ml, and an inhibitory zone diameter of ⩽18 mm at a resistance limit of 16 mcg/ml.


Infection | 1979

In-vitro-Vergleich neuer Beta-Laktam-Antibiotika bei Gentamicin-resistenten Erregern und Darstellung der Cefoxitin-Regressionsgeraden

H. Grimm

ZusammenfassungDurch MHK-Bestimmungen im Agar-Dilutionstest wurde gezeigt, daß Gentamicin-resistente Enterobakterien auch weitgehend resistent sind gegenüber Ampicillin, Carbenicillin, Ticarcillin, Mezlocillin und Cephalothin. Cefoxitin, Cefuroxim und z. T. auch Cefamandol erfassen einen hohen Prozentsatz dieser Bakterien. Regressionsanalysen mit Cefoxitin auf Mueller-Hinton-, DST- und Iso-Sensitest-Agar ergaben in allen Fällen eine sehr gute Korrelation von Hemmhofdurchmesser und MHK für das Gesamtkollektiv von 300 Kulturen 15 verschiedener Spezies. Die Regressionslinien der einzelnen Spezies werden, außer beiProteus vulgaris undYersinia enterocolitica, durch die Gesamt-Regressionsgleichung gut beschrieben. Bei Anwendung dieser ungewöhnlich guten Regressionsanalyse werden durch Auswertung der Hemmhofdurchmesser im Intermediärbereich zwischen Sensibilität und Resistenz jedoch immer noch ca. 50% der Kulturen falsch eingestuft. Die Fehlinterpretation der Intermediär-Hemmhöfe führt fast ausschließlich zur Vorhersage einer zu geringen Sensibilität, so daß die therapeutische Sicherheit dadurch nicht beeinträchtigt wird.SummaryThe determination of MIC values by the tube dilution test revealed that gentamicin-resistant enterobacteria are also largely resistant to ampicillin, carbenicillin, ticarcillin, mezlocillin and cephalothin. Cefoxitin, cefuroxime and, to some extent, also cefamandole are effective against a high percentage of these bacteria. Regression analyses with cefoxitin on Mueller Hinton, DST and Iso-Sensitest agar showed a very good correlation of inhibition zone diameter and MIC for all 300 cultures of 15 different species. The regression lines of the individual species, with the exception ofProteus vulgaris andYersinia enterocolitica, are well described by the total regression equation. Using this unusually reliable regression analysis, about 50% of the cultures are still classified wrongly, however, when evaluating the inhibition zone diameters in the intermediate range between sensitivity and resistance. The misinterpretation of the intermediate inhibition zones nearly always leads to the prediction of too low a sensitivity, so that therapeutic efficacy is not impaired.


Infection | 1978

Bakteriologischer In-vitro-Vergleich und Regressionsanalysen mit neuen Cephalosporinen

H. Grimm

ZusammenfassungIn vergleichenden MHK-Bestimmungen für Cefamandol, Cefoxitin, Cefuroxim und Cephalotin an je 50 Stämmen 15 verschiedener Spezies zeigte Cefamandol bei den meisten Spezies die höchste antibakterielle Aktivität. Cefamandol erfaßte auch weitgehend Cefoxitin-resistenteCitrobacter undEnterobacter. Cefamandol-resistente Klebsiellen undSerratia marcescens sind z. T. Cefoxitin-sensibel. Durch jeweils 16 mcg/ml wurden aus dem Gesamtkollektiv von 750 Kulturen durch Cefamandol 76%, durch Cefoxitin 75% und durch Cefuroxim 72% gehemmt. Die Regressionsanalysen auf Mueller-Hinton-, DST- und Iso-Sensitest-Agar ergaben für die vier untersuchten Cephalosporine eine sehr gute Korrelation von Hemmhofdurchmesser und MHK. Die Grenzhemmhofdurchmesser zur Unterscheidung sensibler und resistenter Erreger sind für die einzelnen Antibiotika unterschiedlich, jedoch auf den verschiedenen Nährmedien nahezu identisch.SummaryIn comparative MIC studies for cefamandole, cefoxitin, cefuroxime, and cephalothin with 15 different species (50 strains each) cefamandole showed the highest antibacterial activity against most species including most of theCitrobacter andEnterobacter resistant to cefoxitin. Some of theKlebsiellae andSerratia marcescens resistant to cefamandole are susceptible to cefoxitin. Using 16 mcg/ml of each antibiotic cefamandole inhibited 76%, cefoxitin 75%, and cefuroxime 72% of the total of 750 strains. Regression line analyses on Mueller-Hinton, DST, and Iso-Sensitest agar medium showed excellent correlation of zone size diameter and MIC for all of the four cephalosporines. Cut-off points for the differentiation of susceptible from resistant strains are different for each antibiotic but are almost identical for the three test media investigated.


Infection | 1986

Interpretationskriterien der Empfindlichkeitsprüfung von Ofloxacin mit dem Agardiffusionstest

H. Grimm

Regression analyses to determine the correlation of MIC and inhibition zone produced by ofloxacin disks were carried out using 300 freshly isolated cultures of infective organisms (20 strains each from 15 species). It was found in pilot studies that the correlation becomes poorer with increasing disk loads. Disks containing 5 micrograms of ofloxacin were chosen for comparative studies using Mueller-Hinton agar and Kirby-Bauer, as well as DIN-58940 methods. Based on preliminary MIC breakpoints of 1 and 4 mg/l and on calculations from regression equations, the following zone interpretations using the Kirby-Bauer method are recommended: resistant = up to 12 mm, intermediate = 13 to 19 mm, susceptible = 20 mm or more. The respective values for the DIN method are: resistant = up to 14 mm, intermediate = 15 to 21 mm, susceptible = 22 mm or more. The results are similar to those obtained by us in previous studies with norfloxacin, enoxacin and ciprofloxacin.ZusammenfassungAn 300 frisch isolierten Erregern (je 20 Stämme von 15 verschiedenen Spezies) wurden Regressionsanalysen zur Korrelation von minimaler Hemmkonzentration und Hemmhofdurchmesser für Ofloxacin-Disks ausgeführt. In einer Pilot-Studie mit unterschiedlichen Disk-Beladungen wurde festgestellt, daß mit zunehmender Disk-Beladung die Korrelation schlechter wird. Für vergleichende Untersuchungen auf Mueller-Hinton-Agar mit den Methoden nachKirby-Bauer sowie nach DIN 58940 wurden mit 5 µg Ofloxacin beschickte Disks gewählt. Basierend auf vorläufigen MHK-Breakpoints für Ofloxacin von 1 mg/l und 4 mg/l ergeben sich aus den Regressionsgleichungen folgende Interpretationen des mit 5 µg-Disks in derKirby-Bauer-Methode gewonnenen Ofloxacin-Hemmhofs: Resistent bis zu 12 mm, mäßig empfindlich von 13 bis 19 mm und empfindlich ab 20 mm. Die entsprechenden Werte für die Methode nach DIN 58940 lauten: Resistent bis zu 14 mm, mäßig empfindlich von 15 bis 21 mm und empfindlich ab 22 mm. Die Daten sind den von uns in früheren Studien ermittelten Grenzwerten von Norfloxacin, Enoxacin und Ciprofloxacin sehr ähnlich.SummaryRegression analyses to determine the correlation of MIC and inhibition zone produced by ofloxacin disks were carried out using 300 freshly isolated cultures of infective organisms (20 strains each from 15 species). It was found in pilot studies that the correlation becomes poorer with increasing disk loads. Disks containing 5 µg of ofloxacin were chosen for comparative studies using Mueller-Hinton agar and Kirby-Bauer, as well as DIN-58940 methods. Based on preliminary MIC breakpoints of 1 and 4 mg/l and on calculations from regression equations, the following zone interpretations using the Kirby-Bauer method are recommended: resistant = up to 12 mm, intermediate = 13 to 19 mm, susceptible = 20 mm or more. The respective values for the DIN method are: resistant = up to 14 mm, intermediate = 15 to 21 mm, susceptible = 22 mm or more. The results are similar to those obtained by us in previous studies with norfloxacin, enoxacin and ciprofloxacin.


International Journal of Antimicrobial Agents | 1996

The influence of sulbactam on the in vitro activity of mezlocillin, piperacillin and cefotaxime

Adolf Bauernfeind; H. Grimm; W. Klietmann; Wolfgang Opferkuch; H. Werner

In a multicentre study, the in-vitro activity of mezlocillin (MEZ, Chemical Abstract Service [CAS] 51481-65-3), piperacillin (PIP, CAS 61477-96-1) and cefotaxime (CTX, CAS 63527-52-6) against mezlocillin-resistant organisms was determined alone and in combination with the beta-lactamase inhibitor sulbactam (SBT, CAS 68373-14-8). A total of 870 strains were investigated (481 Enterobacteriaceae, 57 Pseudomonas aeruginosa, 41 Acinetobacter spp., 194 Bacteroides fragilis and 97 Staphylococcus spp.). MIC values were determined using the agar dilution test (aerobic organisms) or the microbroth dilution test (Bacteroides spp.) in accordance with Deutsche Industrie für Normung 58 940. SBT was added in fixed concentrations of 5 mg/l and 10 mg/l. For all combinations with SBT investigated, the geometric mean of the MIC and the MIC(50) and MIC(90) values were reduced as compared with the antibiotic alone (without SBT). Consequently, the proportion of sensitive strains was appreciably increased, for example in the Enterobacteriaceae: MEZ 1%, MEZ + 10 mg/l SBT 53%; PIP 4%, PIP + 10 mg/l SBT 54%; CTX 52%, CTX + 10 mg/l SBT 68%. The effect of SBT was especially pronounced on Bacteroides spp. For this organism, the proportion of sensitive strain rose from 2% to 97% (MEZ), 6% to 95% (PIP) and from 7% to 98% (CTX). The results show that adding SBT appreciably enhances the activity of MEZ, PIP and CTX against resistant strains of microorganism, and extends the activity spectrum to include anaerobic organisms. Thus the availability of SBT as a single-agent preparation for use in combination with various beta-lacta antibiotics represents a worthwhile enlargement of the therapeutic armamentarium for treating bacterial infections.


Infection | 1996

Re: A. Bauernfeind et al.: Comparative pharmacodynamics of clarithromycin and azithromycin against respiratory pathogens (Infection 23 [1995] 316-321)

D. Adam; H. Grimm; H. Lode

The publication of the above by Bauernfeind et al. elicits criticism with regard to scientific and methodological principles and especially regarding the resulting therapeutic conclusions. To substantiate this we would like to refer to the following points: 1) Experimental models comparing macrolide antibiotics on the basis of their serum concentrations are of no significance. It is well known that for this class of antibiotics, tissue concentrations in particular in phagocytizing cells are of greater importance for therapeutic success than serum concentrations. 2) The serum kinetics selected in the study by Bauernfeind et al. are not representative. For clarithromycin, a steady state concentration has been chosen as maximum level, for azithromycin on the other hand, the concentration chosen is from a study using a single application in only six subjects. The data available for azithromycin from the international literature are nearly twice as high. This makes the entire experimental kinetic approach in this study very problematic. 3) The selection and very low number of test organisms is also highly questionable. Many studies show a mean MIC of 4-8 mg/1 for Haemophilus influenzae versus clarithromycin, whereas concentrations for azithromycin range between 0.5 and I rag/1. The selection of test strains is accordingly by no means representative, and combined with the low number of organisms tested do not allow for a conclusive comparison. 4) The hypothesis regarding the development of resistant mutants has no clinical correlation. This is the case especially with regard to the fact that in this study highly susceptible organisms show an unfavorable change of their MIC values during the course of exposure to the antibiotic, whereas organisms with primarily high MIC values do not show such a development, The possibility of selection of resistant mutants is highly dependent on the inoculum. Therefore, choosing an initial inoculum with a load suitable for measuring bactericidal kinetics (106 CFU/ml) rather than an inoculum featuring a load equivalent to that which one could expect to find in the blood of patients with bacteremic respiratory tract infections appears to be unrealistic. In addition, a difference in resistance development between various macrolide antibiotics has never been observed clinically. 5) Even in bacteremic pneumococcal pneumonias, highest therapeutic importance must be accorded to the bactericidal reduction of organisms primarily at the infection site. Furthermore, organisms circulating in the intravascular space are phagocytized by granulocytes, or by the macrophages in organs with a high content of reticulo-endothelial cells. Macrolides, and in particular azithromycin, are highly concentrated in these cells and the factor of this concentration is approximately 10 to 20 for clarithromycin and approximately 50 to 100 for azithromycin. The clinical results available to date concerning azithromycin in bacteremic pneumococcal pneumonias show the same success or failure rates as seen with other groups of substances. D. Adam, H. Grimm, H. Lode

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Helmut Hahn

Free University of Berlin

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H. Flamm

University of Vienna

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