Harald Mauch

Publications of Harald Mauch

• Early bactericidal activity of moxifloxacin in treatment of pulmonary tuberculosis: a prospective, randomized study.

  Authors: Mathias W R Pletz, Andres De Roux, Andreas Roth, Karl-Heinz Neumann, Harald Mauch, Hartmut Lode

  Antimicrobial agents and chemotherapy. 04/2004; 48(3):780-2.

  Moxifloxacin is the most active fluoroquinolone against Mycobacterium tuberculosis in vitro. However, data about the efficacy in patients are not available. We enrolled 17 patients with tuberculosisMoxifloxacin is the most active fluoroquinolone against Mycobacterium tuberculosis in vitro. However, data about the efficacy in patients are not available. We enrolled 17 patients with tuberculosis in a prospective, randomized study. After 5 days of monotherapy with either moxifloxacin or isoniazid, we detected significant decreases in mean CFU per milliliter in sputum in both groups. The calculated early bactericidal activities for isoniazid and moxifloxacin were 0.209 and 0.273 log(10) CFU per ml of sputum per day, respectively. According to the data from our study, moxifloxacin exhibits an early bactericidal activity that is comparable to that of isoniazid.

• Optimizing ceftazidime pharmacodynamics in patients with acute exacerbation of severe chronic bronchitis.

  Authors: Annette Lubasch, Stefan Lück, Hartmut Lode, Harald Mauch, Joachim Lorenz, Pal Bölcskei, Tobias Welte

  The Journal of antimicrobial chemotherapy. 03/2003; 51(3):659-64.

  OBJECTIVES: Implementation of current pharmacodynamic knowledge could enhance clinical results, avoid resistance development and reduce treatment costs. In this open, randomized, multicentre study,OBJECTIVES: Implementation of current pharmacodynamic knowledge could enhance clinical results, avoid resistance development and reduce treatment costs. In this open, randomized, multicentre study, we evaluated the clinical and bacteriological outcome and pharmacokinetic as well as pharmacodynamic parameters of two ceftazidime therapy regimens in patients with acute exacerbation of severe chronic bronchitis (AECB). METHODS: Eighty-one patients (56 males, 25 females, age 65.3 +/- 10.1 years) with AECB were included. A subgroup of 21 patients underwent pharmacokinetic and pharmacodynamic examination. The patients received either ceftazidime 2 g every 8 h (C3 x 2) or ceftazidime 2 g as a loading dose, followed by ceftazidime 2 g over 7 h every 12 h (C2 x 2) for 8-14 days. Clinical and bacteriological responses were monitored at day 8 or 9, and 72 h after the end of therapy (EOT). RESULTS: At EOT, clinical success was recorded in 90% and 90.2% of clinically evaluable patients receiving C3 x 2 and C2 x 2, respectively. Bacteriological success at EOT was achieved in 87.5% and 90.2% of evaluable patients treated with C3 x 2 and C2 x 2, respectively. C(max) (mg/L) varied between 168.9 +/- 34.1 and 144.0 +/- 9.8 in the C3 x 2 group, and between 60.1 +/- 34.1 and 54.2 +/- 30.4 at steady-state in the C2 x 2 group. Minimal concentrations were between 9.1 and 13.4 mg/L in the C3 x 2 group, and between 16.6 and 17.7 mg/L in the C2 x 2 group. Concentrations >4-5 x MIC were seen in all pathogens, except Staphylococcus aureus, during 100% of infusion time. CONCLUSION: The 2 x 7 h infusion of ceftazidime 2 g (C2 x 2) was clinically and bacteriologically as effective as the usual 3 x 2 g ceftazidime short-term infusion in the treatment of AECB, and demonstrated advantages in terms of pharmacodynamic parameters compared with the C3 x 2 regimen.

• Phylogeny of the genus Nocardia based on reassessed 16S rRNA gene sequences reveals underspeciation and division of strains classified as Nocardia asteroides into three established species and two unnamed taxons.

  Authors: Andreas Roth, Sebastian Andrees, Reiner M Kroppenstedt, Dag Harmsen, Harald Mauch

  Journal of clinical microbiology. 03/2003; 41(2):851-6.

  Conventional identification of Nocardia in the routine laboratory remains problematic due to a paucity of reliable phenotypic tests and due to the yet-unresolved taxonomy of strains classified asConventional identification of Nocardia in the routine laboratory remains problematic due to a paucity of reliable phenotypic tests and due to the yet-unresolved taxonomy of strains classified as belonging to the species Nocardia asteroides, which comprises the type strain and isolates with drug pattern types II and VI. The 16S rRNA gene of 74 representative strains of the genus Nocardia, encompassing 25 established species, was sequenced in order to provide a molecular basis for accurate species identification and with the aim of reassessing the phylogeny of taxons assigned to the species N. asteroides. The result of this phylogenetic analysis confirms that the interspecies heterogeneity of closely related nocardial species can be considerably low (a sequence divergence of only 0.5% was found between N. paucivorans and N. brevicatena). We observed a sequence microheterogeneity (sequence divergence of fewer than five bases) in 8 of 11 species of which more than one strain in the species was studied. At least 10 taxons were found that merit description as new species. Strains previously classified as N. asteroides fell into five distinct phylogenetic groups: the type strain cluster (N. asteroides sensu strictu), N. abscessus, N. cyriacigeorgica, and two clusters closely related to N. carnea or N. flavorosea. The strains within the latter two groups probably represent new species, pending further genetic and phenotypic evaluation. Restricted phenotypic data revealed that N. abscessus, N. cyriacigeorgica, and the two Nocardia species taxons are equivalent to drug patterns I, VI, and II, respectively. In the future, these data will help in finding species-specific markers after adoption of a more precise nomenclature for isolates closely related to N. asteroides and unravel confusing phenotypic data obtained in the past for unresolved groups of strains that definitely belong to separate taxons from a phylogenetic point of view.

• Differentiation between Mycobacterium farcinogenes and Mycobacterium senegalense strains based on 16S-23S ribosomal DNA internal transcribed spacer sequences.

  Authors: Mohamed E. Hamid, Andreas Roth, Olfert Landt, Reiner M Kroppenstedt, Michael Goodfellow, Harald Mauch

  Journal of clinical microbiology. 03/2002; 40(2):707-11.

  16S ribosomal DNA (rDNA) and 16S-23S internal transcribed spacer rDNA sequence analyses were performed on Mycobacterium farcinogenes and M. senegalense strains and 26 strains of other rapidly growing16S ribosomal DNA (rDNA) and 16S-23S internal transcribed spacer rDNA sequence analyses were performed on Mycobacterium farcinogenes and M. senegalense strains and 26 strains of other rapidly growing mycobacteria to investigate the phylogenetic structure of bovine farcy mycobacteria within the M. fortuitum complex. M. farcinogenes and M. senegalense were indistinguishable in their 5"-end 16S rDNA but showed both considerable interspecies spacer sequence divergence and a high level of intraspecies sequence stability. A rapid detection assay using PCR and hybridization with species-specific probes was developed. The assay was specific among 46 species other than M. farcinogenes and M. senegalense and correctly identified all M. farcinogenes and M. senegalense strains. PCR- and 16S-23S rDNA sequence-based detection will be a valuable approach for diagnosis of the causal agents of African bovine farcy in cattle.

• Nosocomial pneumonia: epidemiology, pathogenesis, diagnosis, treatment and prevention.

  Authors: Hartmut Lode, Manfred Raffenberg, Reiner Erbes, Hilte Geerdes-Fenge, Harald Mauch

  Current opinion in infectious diseases. 09/2000; 13(4):377-384.

  Nosocomial pneumonia is the second most common nosocomial infection and the leading cause of death from hospital-acquired infection. Supine body position in mechanically ventilated patients, andNosocomial pneumonia is the second most common nosocomial infection and the leading cause of death from hospital-acquired infection. Supine body position in mechanically ventilated patients, and cardiopulmonary resuscitation and continuous sedation are significant risk factors for developing nosocomial pneumonia. During the past 2 years some new therapeutic approaches for nosocomial pneumonia and modifications to established therapies have been described, such as optimal pharmacodynamic evaluations, monotherapy versus combination therapy, computer-assisted management programmes and antibiotic rotations.

• Diagnosis of acute respiratory tract infections: serology and new methods.

  Authors: Harald Mauch

  Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 07/1996; 1 Suppl 2:S16-S19.

  No test is available that can identify all potential pathogens in acute respiratory tract infections. Each diagnostic test is associated with limitations with respect to sensitivity and/orNo test is available that can identify all potential pathogens in acute respiratory tract infections. Each diagnostic test is associated with limitations with respect to sensitivity and/or specificity and/or speed, and thus a combination of tests has to be used. Even so, no etiologic agent is found in 30--60% of cases. The following methods are recommended for use in the routine laboratory for the diagnosis of infections: (1) Legionella --- direct immunofluorescence test, culture, serology and antigen detection (available only in specialized laboratories); (2) Chlamydia pneumoniae --- micro-immunofluorescence test, complement fixation, but not direct antigen detection by immunofluorescence; (3) Mycoplasma pneumoniae - complement fixation and/or particle agglutination or other evaluated methods; (4) Coxiella burnetii --- immunofluorescence test (IgG and IgM) and complement fixation; (5) viruses --- complement fixation or other similar test (ELISAs often lack adequate evaluation). Culture for Chlamydia, Mycoplasma pneumoniae, Coxiella burnetii and viruses should only be performed by very experienced laboratories. Most procedures deliver results only retrospectively or too late. The most promising diagnostic tools for the future are nucleic acid amplification techniques (NAT) or PCR, which could solve many of the problems connected with conventional techniques, but there are enormous contamination problems. Further research and worldwide aid in the development of standardized NAT, especially by industrial companies, is urgently encouraged to improve the laboratory diagnosis of these pneumonias.

• Novel Diagnostic Algorithm for Identification of Mycobacteria Using Genus-Specific Amplification of the 16S-23S rRNA Gene Spacer and Restriction Endonucleases

  Authors: Andreas Roth, Udo Reischl, Anna Streubel, Ludmila Naumann, Reiner M Kroppenstedt, Marion Habicht, Marga Fischer, Harald Mauch

  A novel genus-specific PCR for mycobacteria with simple identification to the species level by restriction fragment length polymorphism (RFLP) was established using the 16S-23S ribosomal RNA geneA novel genus-specific PCR for mycobacteria with simple identification to the species level by restriction fragment length polymorphism (RFLP) was established using the 16S-23S ribosomal RNA gene (rDNA) spacer as a target. Panspecificity of primers was demonstrated on the genus level by testing 811 bacterial strains (122 species in 37 genera from 286 reference strains and 525 clinical isolates). All mycobacterial isolates (678 strains among 48 defined species and 5 indeterminate taxons) were amplified by the new primers. Among nonmycobacterial isolates, only Gordonia terrae was amplified. The RFLP scheme devised involves estimation of variable PCR product sizes together with HaeIII and CfoI restriction analysis. It yielded 58 HaeIII patterns, of which 49 (84%) were unique on the species level. Hence, HaeIII digestion together with CfoI results was sufficient for correct identification of 39 of 54 mycobacterial taxons and one of three or four of seven RFLP genotypes found in Mycobacterium intracellulare and Mycobacterium kansasii, respectively. Following a clearly laid out diagnostic algorithm, the remaining unidentified organisms fell into five clusters of closely related species (i.e., the Mycobacterium avium complex or Mycobacterium chelonae-Mycobacterium abscessus) that were successfully separated using additional enzymes (TaqI, MspI, DdeI, or AvaII). Thus, next to slowly growing mycobacteria, all rapidly growing species studied, including M. abscessus, M. chelonae, Mycobacterium farcinogenes, Mycobacterium fortuitum, Mycobacterium peregrinum, and Mycobacterium senegalense (with a very high 16S rDNA sequence similarity) were correctly identified. A high intraspecies sequence stability and the good discriminative power of patterns indicate that this method is very suitable for rapid and cost-effective identification of a wide variety of mycobacterial species without the need for sequencing. Phylogenetically, spacer sequence data stand in good agreement with 16S rDNA sequencing results, as was shown by including strains with unsettled taxonomy. Since this approach recognized significant subspecific genotypes while identification of a broad spectrum of mycobacteria rested on identification of one specific RFLP pattern within a species, this method can be used by both reference (or research) and routine laboratories.

• Mycobacterium heckeshornense sp. nov., a New Pathogenic Slowly Growing Mycobacterium sp. Causing Cavitary Lung Disease in an Immunocompetent Patient

  Authors: Andreas Roth, Udo Reischl, Nicolas Schönfeld, Ludmila Naumann, Stefan Emler, Marga Fischer, Harald Mauch, Robert Loddenkemper, Reiner M Kroppenstedt

  A pathogenic scotochromogenic Mycobacterium xenopi-like organism was isolated from the lung of an immunocompetent young woman. This pathogen caused severe bilateral cavitary lung disease, making twoA pathogenic scotochromogenic Mycobacterium xenopi-like organism was isolated from the lung of an immunocompetent young woman. This pathogen caused severe bilateral cavitary lung disease, making two surgical interventions necessary after years of chronic disease. This case prompted us to characterize this mycobacterium by a polyphasic taxonomic approach. The isolate contained chemotaxonomic markers which were typical for the genus Mycobacterium, i.e., the meso isomer of 2,6-diaminopimelic acid, arabinose, and galactose as diagnostic whole-cell sugars, MK-9(H2) as the principal isoprenoid quinone, a mycolic acid pattern of α-mycolates, ketomycolates, and wax ester mycolates, unbranched saturated and unsaturated fatty acids plus a significant amount of tuberculostearic acid, and small amounts of a C20:0 secondary alcohol. On the basis of its unique 16S rRNA and 16S-23S spacer gene sequences, we propose that the isolate should be assigned to a new species, Mycobacterium heckeshornense. This novel species is phylogenetically closely related to M. xenopi. The type strain of M. heckeshornense is strain S369 (DSM 44428T). The GenBank accession number of the 16S rRNA gene of M. heckeshornense is AF174290.

• Differentiation of Phylogenetically Related Slowly Growing Mycobacteria Based on 16S-23S rRNA Gene Internal Transcribed Spacer Sequences

  Authors: Andreas Roth, Marga Fischer, Mohamed E. Hamid, Sabine Michalke, Wolfgang Ludwig, Harald Mauch

  Interspecific polymorphisms of the 16S rRNA gene (rDNA) are widely used for species identification of mycobacteria. 16S rDNA sequences, however, do not vary greatly within a species, and they areInterspecific polymorphisms of the 16S rRNA gene (rDNA) are widely used for species identification of mycobacteria. 16S rDNA sequences, however, do not vary greatly within a species, and they are either indistinguishable in some species, for example, in Mycobacterium kansasii and M. gastri, or highly similar, for example, in M. malmoense and M. szulgai. We determined 16S-23S rDNA internal transcribed spacer (ITS) sequences of 60 strains in the genus Mycobacterium representing 13 species (M. avium, M. conspicuum, M. gastri, M. genavense, M. kansasii, M. malmoense, M. marinum, M. shimoidei, M. simiae, M. szulgai, M. triplex, M. ulcerans, and M. xenopi). An alignment of these sequences together with additional sequences available in the EMBL database (for M. intracellulare, M. phlei, M. smegmatis, and M. tuberculosis) was established according to primary- and secondary-structure similarities. Comparative sequence analysis applying different treeing methods grouped the strains into species-specific clusters with low sequence divergence between strains belonging to the same species (0 to 2%). The ITS-based tree topology only partially correlated to that based on 16S rDNA, but the main branching orders were preserved, notably, the division of fast-growing from slowly growing mycobacteria, separate branching for M. simiae, M. genavense, and M. triplex, and distinct branches for M. xenopi and M. shimoidei. Comparisons of M. gastri with M. kansasii and M. malmoense with M. szulgai revealed ITS sequence similarities of 93 and 88%, respectively. M. marinum and M. ulcerans possessed identical ITS sequences. Our results show that ITS sequencing represents a supplement to 16S rRNA gene sequences for the differentiation of closely related species. Slowly growing mycobacteria show a high sequence variation in the ITS; this variation has the potential to be used for the development of probes as a rapid approach to mycobacterial identification.